3 Rhinology, Allergy, and Immunology

Question 1

1 What cells contribute to the formation of the nose during the 4th week of embryogenesis?

Answer 1

Neural crest cells

Question 2

2 Before closure during embryogenesis, what are the following spaces called?
● Between the frontal and nasal bones
● Between the frontal and ethmoid bones
● Between the nasal bones and nasal capsule

Answer 2

Fronticulus nasofrontalis
Foramen cecum
Prenasal space

Question 3

3 What embryologic structures form within the thickened ectoderm of the nasal placodes of the frontonasal process and after dividing each placode into medial and lateral nasal processes become the early nasal cavities?

Answer 3

Nasal pits

Question 4

4 Into what structures do the (1) medial and (2) lateral processes of the nasal pits and the (3) maxillary process of the maxilla develop?

Answer 4

● Medial: Nasal septum (from the globular processes of His), philtrum, premaxilla
● Lateral: Nasal alae
● Maxillary process: Lateral nasal wall

Question 5

5 What embryologic membrane separates the nasal and oral cavities, and normally degenerates to allow open passages as the choanae are formed by the deepening olfactory pits during development?

Answer 5

Nasobuccal membrane

Question 6

6 The nasal bones attach to what structures within the facial skeleton?

Answer 6

Frontal bone, nasal process of the maxilla, upper lateral cartilages, contralateral nasal bone, perpendicular plate of the ethmoid, and cartilaginous septum

Question 7

7 What are the three different regions of the paired lower lateral cartilages of the nose?

Answer 7

● Medial crus ● Intermediate crus ● Lateral crus

Question 8

8 What is the name of the area that connects the lower lateral cartilages with the upper lateral cartilages?

Answer 8

Scroll region

Question 9

9 What are the boundaries of the internal nasal valve? (▶ Fig. 3.1)

Answer 9

● Caudal septum ● Head of the inferior turbinate ● Remainder of tissues around the piriform aperture ● Upper lateral cartilage, distal end Note: Also called the valve area, nasal valve region

Question 10

10 What structure does the frontal process of the maxilla, nasal floor, and lateral fibrofatty tissue form?

Answer 10

Piriform aperture

Question 11

11 What are the boundaries of the external nasal valve?

Answer 11

● Caudal septum ● Lower lateral cartilage (caudal edge of the lateral crus, junction with the upper lateral cartilage) ● Piriform aperture

Question 12

12 Name the components of the nasal septum. (▶ Fig. 3.2)

Answer 12

● Perpendicular plate of the ethmoid bone ● Quadrangular cartilage ● Vomer ● Maxillary crest ● Palatine bone

Question 13

13 What is the blood supply of the nasal septum?

Answer 13

● Anterior and posterior ethmoid arteries (superior septum) ● Sphenopalatine artery branches/posterior septal branch (posterior/inferior septum)

Question 14

14 Most cases of epistaxis arise in what area?

Answer 14

Kiesselbach plexus (Little area), anterior septum

Question 15

15 The uncinate process is an extension of what bone?

Answer 15

Ethmoid bone

Question 16

16 What are the three most common superior attachment points for the uncinate? (▶ Fig. 3.3)

Answer 16

● Lamina papyracea ● Skull base ● Middle turbinate

Question 17

17 How does the superior attachment of the uncinate process relate to the drainage of the frontal sinus outflow tract?

Answer 17

When attached to the lamina papyracea, the frontal sinus usually drains medial to the uncinate, and when it is attached to the skull base or middle turbinate, it often drains lateral to the uncinate.

Question 18

18 What is the opening to the space between the uncinate process and the ethmoid bulla called?

Answer 18

Semilunar hiatus

Question 19

19 The uncinate process covers the medial aspect of which space that provides a common drainage pathway for some of the anterior sinuses?

Answer 19

(Ethmoidal) Infundibulum

Question 20

20 True or False. The uncinate attaches to the ethmoid crest of the maxilla, the lacrimal bone, the ethmoidal process of the inferior turbinate bone, and the palatine bone via the lamina perpendicularis.

Answer 20

True

Question 21

21 The lamina papyracea is formed by which bone?

Answer 21

Ethmoid bone

Question 22

22 The nasolacrimal duct empties under what structure in the nose?

Answer 22

Inferior turbinate (via the Hasner valve)

Question 23

23 What is the name for a pneumatized middle turbinate, which is an extension of the ethmoid bone?

Answer 23

Concha bullosa

Question 24

24 The middle turbinate attaches superiorly to the lateral aspect of the cribriform plate, laterally to the lamina papyracea/maxillary sinus, posteriorly to the lateral wall just anterior to the crista ethmoidalis of the palatine bone, and anteriorly near the agger nasi to what structure, which is a part of the frontal process of the maxilla?

Answer 24

Cristal ethmoidalis of the maxilla

Question 25

25 What structure separates the anterior and posterior ethmoid sinuses?

Answer 25

Ground or basal lamella

Question 26

26 What are the five ethmoturbinals, and what do they become?

Answer 26

First → Agger nasi (ascending portion) and uncinate process (descending portion) Second → Middle turbinate Third → Superior turbinate Fourth and fifth fuse → supreme turbinate

Question 27

27 List the first four ethmoid lamellae. (▶ Fig. 3.4)

Answer 27

● Uncinate process ● Ethmoid bulla ● Basal lamella of the middle turbinate ● Lamella of the superior turbinate

Question 28

28 What is the horizontal plate of the ethmoid bone that forms the roof of the ethmoid sinus and separates the ethmoid air cells from the anterior cranial fossa called?

Answer 28

Fovea ethmoidalis

Question 29

29 What are the three infundibular cells that are anterior ethmoid air cells?

Answer 29

● Agger nasi cells ● Terminal cell (recessus terminalis) ● Suprainfundibular cell

Question 30

30 Which cell type is the most anterior of the ethmoid cells and forms near the attachment of the middle turbinate to the lateral nasal wall?

Answer 30

Agger nasi cell(s)

Question 31

31 After removing the uncinate process, the ethmoid bulla typically sets just anterior to the basal lamella. Where does this sinus drain?

Answer 31

Suprabullar or retrobullar recess (sinus lateralis)

Question 32

32 What arterial structure typically runs through the roof of the ethmoid bulla?

Answer 32

Anterior ethmoid artery

Question 33

33 The middle meatus, uncinate, infundibulum, anterior ethmoid cells, and ostia (frontal, ethmoid, maxillary) collectively are referred to as what? (▶ Fig. 3.5)

Answer 33

Ostiomeatal complex

Question 34

34 What is the name of the infraorbital ethmoid air cells that pneumatize into the maxillary sinus and can narrow the maxillary sinus ostium?

Answer 34

Haller cells

Question 35

35 In the adult, the posterior ethmoidal complex consists of one to five cells, which typically drain into which space?

Answer 35

Superior or supreme meatus

Question 36

36 Air cells that pneumatize lateral or posterior to the anterior wall of the sphenoid sinus are called what?

Answer 36

Onodi cells (sphenoethmoidal cell)

Question 37

37 What is the first sinus to develop embryologically?

Answer 37

Maxillary sinus

Question 38

38 What structure must be removed to visualize the natural ostium of the maxillary sinus?

Answer 38

Uncinate process

Question 39

39 Where is the most common location for the maxillary ostium within the infundibulum?

Answer 39

Inferior third (65%)

Question 40

40 Where are the anterior and posterior nasal fontanelles located?

Answer 40

Located anterior and posterior to the inferior aspect of the uncinate process

Question 41

41 What structure runs through the roof of the maxillary sinus?

Answer 41

Infraorbital nerve

Question 42

42 A series of three or four frontal furrows arise out of the ventral middle meatus and give rise to what?

Answer 42

● First frontal furrow = agger nasi cell ● Second frontal furrow = frontal sinus ● Third and fourth furrow = anterior ethmoid cells

Question 43

43 What is the last sinus to fully develop, and at what age has it typically reached full size?

Answer 43

Frontal sinus. Late teens

Question 44

44 The frontal sinus drains via the frontal sinus outflow tract or frontal recess into which space?

Answer 44

Ethmoid infundibulum (most common)

Question 45

45 The frontal or frontoethmoidal cells are located superior to the agger nasi cell and can have quite variable pneumatization. Describe the four Kuhn types of pneumatization.

Answer 45

● Type I: Single cell superior to the agger nasi but not extending into the frontal sinus ● Type II: Tier of two or more cells above the agger nasi but below the orbital roof ● Type III: Single cell extending from the agger nasi into the frontal sinus ● Type IV: Isolated cell within the frontal sinus

Question 46

46 What type of cell can be found posterior to the frontal sinus and superior to the orbit? (▶ Fig. 3.6)

Answer 46

Supraorbital ethmoid cells

Question 47

47 The spread of frontal sinus infections intracranially is commonly thought to pass through what structures?

Answer 47

Foramina of Breschet (small venules that drain the frontal sinus mucosa to the dural veins)

Question 48

48 How is the sphenoid sinus formed during development?

Answer 48

Nasal mucosa invaginates into the cartilaginous nasal capsule, which forms the cupolar recess. The wall of this recess becomes ossified later in development into the ossiculum Bertini. The cartilage is resorbed in the 2nd and 3rd years of life, and the ossiculum attaches to the sphenoid bone. Pneumatization then progresses and is complete in the 9th to the 12th years.

Question 49

49 What is the most posterior paranasal sinus, and where does its natural ostium drain?

Answer 49

Sphenoid sinus; sphenoethmoidal recess (between the superior turbinate and the anterior wall of the sphenoid sinus)

Question 50

50 Describe four surgical landmarks to help safely identify the natural ostium of the sphenoid sinus.

Answer 50

● 6.2 to 8.0 cm from the anterior nasal spine ● 30 to 40 degrees from the nasal floor ● Medial to the posterior end of the superior turbinate (85%) ● ~ Halfway up the anterior sphenoid wall

Question 51

51 The carotid artery is reported to be dehiscent in the sphenoid sinus in what percent of patients?

Answer 51

~ 15%

Question 52

52 What are the main types of sphenoid pneumatization in the Hamberger classification?

Answer 52

● Conchal type: No pneumatization ● Presellar type: Pneumatization restricted anterior to a vertical plane passing through the anterior clinoid process ● Sellar type: Well-pneumatized, most common (90%); can be complete or incomplete depending on whether the pneumatization extends to the clivus

Question 53

53 When removing the intersinus septum within a sphenoid sinus, attachment of this septation to what critical structure must be considered? (▶ Fig. 3.7)

Answer 53

Internal carotid artery

Question 54

54 What is the space between the internal carotid artery and the optic nerve within the sphenoid sinus called?

Answer 54

Opticocarotid recess

Question 55

55 What portion of the internal carotid artery can be seen within the sphenoid sinus?

Answer 55

(Inter)cavernous portion: ● Presellar: Anterior vertical segment and anterior bend ● Infrasellar: Short horizontal segment ● Retrosellar: Posterior bend and posterior vertical segment

Question 56

56 What neurovascular structures set within the parasellar cavernous sinus?

Answer 56

● Internal carotid artery ● Cranial nerves III, IV, and VI ● Cranial nerves V1 and V2

Question 57

57 What anatomical structures pass through the optic canal?

Answer 57

● Optic nerve ● Ophthalmic artery ● Ophthalmic vein

Question 58

58 The vidian nerve is formed by which two nerves before it runs through the vidian canal and exits into the pterygopalatine fossa? (▶ Fig. 3.8)

Answer 58

1. Greater superficial petrosal nerve from the geniculate ganglion of the facial nerve (parasympathetic fibers from the superior salivary nucleus)
2. Deep petrosal nerve from the sympathetic plexus of the internal carotid artery (sympathetic fibers)

Question 59

59 What is the lateral craniopharyngeal canal that may persist in the adult patient anad lead to encephalocele formation and cerebrospinal fluid (CSF) leak and most commonly is noted in patients with significant lateral pneumatization of the sphenoid sinus?

Answer 59

Sternberg canal

Question 60

60 The cribriform plate lies medially within the anterior skull base, surrounded laterally by what structure?

Answer 60

Fovea ethmoidalis (roof of the ethmoid sinuses): Joins the cribriform plate via the lateral lamella of the cribriform plate, which is often quite thin

Question 61

61 According to Keros et al (Laryngol Rhinol Otol, 1965), the anterior skull base can be described based on the depth of the cribriform plate in relation to the fovea ethmoidalis according to which three classifications? (▶ Fig. 3.9)

Answer 61

● Type I: 1 to 3 mm ● Type II: 4 to 7 mm ● Type III: 8 to 16 mm (highest risk for iatrogenic injury)

Question 62

62 Describe the slope of the anterior skull base from anterior to posterior.

Answer 62

Highest anteriorly, lowest posteriorly

Question 63

63 What major branches of the internal maxillary artery provide arterial blood supply to the nose?

Answer 63

● Sphenopalatine artery ● Descending palatine artery → greater and lesser palatine arteries

Question 64

64 The sphenopalatine foramen is located posterior to the attachment of the middle turbinate to the lateral nasal wall, may have several foramina, and almost always is demarcated by what small, raised, bony crest just anterior or anteroinferior to the foramen?

Answer 64

Crista ethmoidalis of the palatine bone

Question 65

65 The sphenopalatine artery can exit the foramen in up to 10 separate branches, what are the most common branches and their distribution?

Answer 65

● Lateral nasal artery: Lateral nasal wall including the turbinates ● Posterior septal artery: Posterior/inferior septum

Question 66

66 When ligating the anterior ethmoid artery via an external approach, the vessel can be found running in what suture line?

Answer 66

Frontoethmoid suture

Question 67

67 What is the distance between the anterior lacrimal crest of the maxilla’s frontal process to the anterior ethmoid artery?

Answer 67

20 to 25 mm

Question 68

68 What is the average distance between the anterior and posterior ethmoid arteries?

Answer 68

10 to 19 mm

Question 69

69 What is the average distance from the posterior ethmoid artery to the optic nerve?

Answer 69

3 to 7 mm

Question 70

70 What intranasal vessels are branches of the internal carotid artery?

Answer 70

Anterior and posterior ethmoid arteries

Question 71

71 What is the blood supply to the nasal septum?

Answer 71

● Superior labial artery (anteriorly) ● Greater palatine artery (posteriorly) ● Anterior and posterior ethmoid arteries (superiorly) ● Posterior septal artery (posterior and inferiorly)

Question 72

72 What arterial plexus is formed along the posterior lateral nasal wall just under the inferior turbinate by branches from the ascending pharyngeal, posterior ethmoid, sphenopalatine, and lateral nasal arteries?

Answer 72

Woodruff plexus

Question 73

73 True or False. Venules within the respiratory mucosa of the nasal and paranasal cavities do not have valves.

Answer 73

True

Question 74

74 Where do the (1) sphenopalatine, (2) ethmoid, (3) angular, and (4) anterior facial veins drain?

Answer 74

● Pterygoid plexus ● Superior ophthalmic vein ● Ophthalmic vein → cavernous sinus ● Common facial vein → internal jugular vein

Question 75

75 What is the primary blood supply to the external nose?

Answer 75

● Angular artery (facial artery) ● Superior labial artery (facial artery)

Question 76

76 What arterial supply contributes to the formation of the Kiesselbach plexus (the Little area)?

Answer 76

● Posterior septal artery (sphenopalatine artery, external carotid artery) ● Anterior ethmoid artery (ophthalmic artery, internal carotid artery) ● Greater palatine artery (internal maxillary artery, external carotid artery) ● Septal branches of the superior labial artery (facial artery, external carotid artery)

Question 77

77 What major nerve branches arise from the nasociliary nerve (V1), and what regions of the nose do they supply?

Answer 77

● Infratrochlear nerve → medial eyelid skin ● Anterior ethmoid nerve → anterior/superior nasal cavity, lateral nasal wall, and septum, external skin of nasal tip

Question 78

78 After exiting the foramen rotundum, the maxillary nerve (V2) contributes fibers to the pterygopalatine (sphenopalatine) ganglion, which then supplies innervation to the nose via which branches?

Answer 78

• Infraorbital nerve → anterior area of inferior meatus, anterior nasal floor, nasal vestibule
• Superior nasal branches (medial/lateral posterior) → posterior superior/middle turbinates, posterior ethmoid sinuses, face of the sphenoid, nasal vault, posterior septum
• Nasopalatine nerve → anterior hard palate
• Greater palatine nerve → middle/inferior meatus, posterior aspect of inferior turbinate

Question 79

79 Where do the parasympathetic fibers that provide vasodilation and secretomotor stimulation to mucous glands synapse?

Answer 79

• Pterygopalatine (sphenopalatine) ganglion
• Superior salivatory nucleus → nervus intermedius → geniculate ganglion → vidian nerve → pterygopalatine ganglion → sphenopalatine nerve branches → vasodilation/secretomotor function

Question 80

80 Postganglionic sympathetic fibers that ultimately control vasoconstriction in the nose arise from what ganglion?

Answer 80

• Superior cervical ganglion
• T1–T3 → superior cervical ganglion → internal carotid artery plexus → join greater superficial petrosal nerve → vidian nerve → pterygopalatine ganglion → sphenopalatine nerve branches → vasoconstriction

Question 81

81 Where do olfactory neurons synapse?

Answer 81

• Olfactory bulb
• Olfactory receptor neurons → unmyelinated axons → myelinated fascicles → olfactory fila/cribriform plate/→ olfactory bulb → olfactory tract

Question 82

82 Name the bones of the orbit. (▶ Fig. 3.10)

Answer 82

● Lacrimal bone ● Ethmoid bone ● Frontal bone ● Maxillary bone ● Sphenoid bone ● Zygomatic bone ● Palatine bone

Question 83

83 What extraocular muscle is at highest risk during medial orbital decompression for Graves ophthalmopathy?

Answer 83

Medial rectus muscle

Question 84

84 What epithelium covers the cribriform plate bilaterally, extending to the superior and middle turbinates?

Answer 84

Olfactory neurepithelium: Pseudostratified columnar epi thelium containing bipolar spindle-shaped olfactory recep tor cells (cranial nerves I and V), columnar sustentacular cells, microvillar cells, and basal cells. Note: This sets on a vascular lamina propria containing Bowman (olfactory) glands and no submucosa.

Question 85

85 What part of the nasal cavity is composed of stratified keratinizing squamous epithelium, hair follicles, sebaceous glands, and sweat glands?

Answer 85

Nasal vestibule

Question 86

86 What ectodermally derived epithelium lines most of the nasal and paranasal cavities?

Answer 86

Ciliated pseudostratified columnar (respiratory) epithelium with ciliated and nonciliated columnar cells, mucoserous (minor salivary) glands within the submucosa, goblet cells, and basal cells Note: Anterior third → squamous and transitional cell epithelium, posterior two-thirds → pseudostratified col umnar epithelium

Question 87

87 Ciliated columnar cells may contain 50 to 200 cilia per cell with each cilia arranged in a specific pattern. On electron microscopy, what do you expect to see for a normal ciliary structure?

Answer 87

“9 + 2” microtubules in doublets (dynein arms)

Question 88

88 What is another name for the ciliated pseudostratified columnar epithelium that lines the nasal and paranasal cavities?

Answer 88

Schneiderian membrane (ectodermally derived)

Question 89

89 In normal individuals, the mucosa of one nasal passageway will be congested compared with the contralateral side owing to cyclic engorgement of the nasal turbinates. What is this normal physiologic phenomenon, which may function to optimize humidification and warming of the air, called?

Answer 89

Nasal cycle

Question 90

90 What is the length of the average nasal cycle? What factors can cause an increase or decrease in “congestion” on a given side?

Answer 90

● Average cycle: 2 to 4 hours ● Decreased exercise, increased heart rate ● Increased: on “down” side when lying on one’s side

Question 91

91 True or False. The nasal mucosal microvasculature is under parasympathetic tone.

Answer 91

False. Sympathetic tone → vasoconstriction → when tone decreases → increased vasodilation. Changes in tone result in the normal nasal cycle.

Question 92

92 What is typically the narrowest area inside the nose, which creates the area of greatest resistance to airflow?

Answer 92

Internal nasal valve

Question 93

93 Without changing nasal resistance, injecting lidocaine into the nose can result in the sensation of nasal obstruction, whereas inhaling menthol, camphor or eucalyptol can result in the sensation of a more “open” nasal passageway. Why?

Answer 93

Change in the level of activity of cold receptors, located predominantly in the nasal vestibule

Question 94

94 On what is airflow through the nose dependent?

Answer 94

● Cross-sectional area of the nasal passageway ● Pressure differential across the nose ● Laminar vs. turbulent airflow

Question 95

95 Describe the Bernoulli principle with respect to the nasal valve.

Answer 95

The speed of a fluid through a tubular structure is greatest at the point of smallest diameter. At the point of maximum velocity, the pressure reaches a nadir. The difference between intranasal pressure at the nasal valve and atmospheric pressure leads to potential for collapse.

Question 96

96 As air moves from the nasal vestibule to the nasopharynx, the relative humidity increases by approximately what percent?

Answer 96

95%

Question 97

97 What nasal structure filters out large particles (20 to 30 μm) from the air?

Answer 97

Nasal vibrissae ● Nasal septum and turbinates filter particles 10 to 30 μm. ● Bronchial tree mucosa filters out particles 2 μm in diameter. ● Particles 0.2 to 0.5 μm in diameter tend to remain suspended and are exhaled.

Question 98

98 The nose filters out particles from the air larger than what size? Particles smaller than this size are able to reach the alveoli of the lungs.

Answer 98

5 μm

Question 99

99 What are the two mucous layers associated with the nasal mucociliary system? (▶ Fig. 3.11)

Answer 99

• Upper gel layer:
  
  • Trap inhaled particle
  • Formed by goblet cells and submucosal glands
• Lower sol layer:
  
  • Surround cilia of epithelium
  • Formed by microvilli

Question 100

100 What cells are responsible for producing the airway mucus?

Answer 100

1. Goblet cells: Secrete mucins
2. Submucosal seromucous glands: Secrete mucins
3. Epithelial cells: Hydration of the mucus via active transepithelial transport systems
4. Venules: Plasma proteins

Question 101

101 What factors can contribute to decreased mucociliary clearance?

Answer 101

• Dysfunction of cilia: Trauma, environmental damage, genetic disorder (i.e., primary ciliary dyskinesia, Karta gener syndrome, cystic fibrosis, etc.)
• Altered mucus production or viscosity: Cystic fibrosis

Question 102

102 What test can be used to measure mucociliary transport time in the nose?

Answer 102

Saccharin test : A saccharin pellet is placed in the anterior nasal cavity and dissolves, passing toward the oropharynx via the mucociliary system and resulting in the sensation of a sweet taste. Time for placement to sensation: < 20 minutes.

Question 103

103 What nasal reflex results in congestion/swelling of the nasal mucosa when lying in a dependent position?

Answer 103

Postural reflex

Question 104

104 Which nerves contribute to the overall experience of an odor?

Answer 104

● Olfactory nerve ● Trigeminal nerve ● Vagus nerve ● Glossopharyngeal nerve

Question 105

105 What produces the nasal mucus, a key component of olfaction?

Answer 105

Bowman glands found within the lamina propria beneath the olfactory epithelium and goblet cells and submucous glands found within the adjacent respiratory epithelium produce mucus

Question 106

106 What type of cell is responsible for olfaction?

Answer 106

Olfactory receptor cells are bipolar ciliated neurons.

Question 107

107 What layer(s) must odorants penetrate to reach the olfactory receptor neurons?

Answer 107

Olfactory mucus

Question 108

108 What organ is often noted in the anteroinferior nasal septum as a small pit whose function in humans is unknown but in many other mammals is thought to be related to the detection of pheromones?

Answer 108

Vomeronasal organ (Jacobson organ)

Question 109

109 What characteristics of particles are important for their recognition by the olfactory nerves?

Answer 109

For particles to be recognized by the olfactory nerves, the particles must be volatile substances that are lipid soluble.

Question 110

110 What terms are associated with each of the following?

Answer 110

● Normal olfaction ● Complete loss of smell ● Decreased sense of smell ● Altered perception of smell ● Perception of odor without stimulus present ● Altered perception of an odor in the presence of an odorant stimulus ● Normosmia ● Anosmia ● Hyposmia ● Dysosmia ● Phantosmia ● Parosmia or troposmia

Question 111

111 Describe the two main types of olfactory dysfunction.

Answer 111

● Conductive olfactory loss: Occurs secondary to obstruc tion of the nasal airflow to the olfactory cleft ● Sensorineural or nonconductive olfactory loss: Occurs secondary to damage or dysfunction of the olfactory neurons anywhere along the olfactory system

Question 112

112 What are common causes of conductive olfactory loss?

Answer 112

● Chronic rhinosinusitis (CRS), allergic rhinitis, polyps, septal deflection, tumors ● Also occurs with diverted airway (tracheostomy or laryngectomy) from diminished or absent airflow through the nose

Question 113

113 What are common causes of sensorineural olfactory loss?

Answer 113

1. Post-upper respiratory tract infection (UTI; viral) loss
2. CRS (certain patients)
3. Head trauma, toxin exposure
4. Congenital disorders
5. Dementia, Alzheimer disease, Parkinson disease
6. Multiple sclerosis

Question 114

114 How often does olfactory loss occur after head trauma, and when does it occur?

Answer 114

5% to 10% The amount of loss usually correlates with the severity of trauma. Onset is often immediate but can be delayed for months.

Question 115

115 What is the mechanism thought to be associated with olfactory dysfunction resulting from head trauma?

Answer 115

Shearing of the olfactory nerve axons, contusion/hemor rhage within the olfactory regions of the brain, or structural alteration of the sinonasal tract The most common trauma type is impact to the frontal region, followed by trauma to the occiput.

Question 116

116 How does post-traumatic olfactory dysfunction differ in the pediatric population compared with that in adults?

Answer 116

Olfactory dysfunction is less common: 3.2% transient dysfunction and 1.2% with permanent dysfunction.

Question 117

117 What percentage of adults will recover their sense of smell after experiencing anosmia from a head trauma?

Answer 117

5 to 10%

Question 118

118 What is the most common cause of olfactory loss?

Answer 118

Persistent olfactory dysfunction after URI. This type of olfactory loss is more common in women, typically women older than 50 years (70 to 80% of cases).

Question 119

119 What proportion of patients will likely recover their sense of smell following a postviral URI, regardless of treatment?

Answer 119

~ One-third

Question 120

120 Olfaction is dependent on the health of the olfactory neural elements, which are slowly lost over time, resulting in an age-dependent decline in olfaction, most noticeable after what decade(s)?

Answer 120

Sixth and seventh

Question 121

121 Olfactory function can be lost after exposure to specific toxins, such as formalin or cigarette smoke. What factors most strongly influence the olfactory dysfunction?

Answer 121

● Type of toxin ● Concentration and duration of exposure

Question 122

122 In what two neurologic diseases is olfactory loss thought to be one of the earliest signs?

Answer 122

Parkinson disease and Alzheimer disease

Question 123

123 What disorder is associated with anosmia and hypogonadism?

Answer 123

Kallmann syndrome (hypogonadotropic hypogonadism); can be X-linked (KAL 1 gene) or autosomal dominant (KAL 2 gene)

Question 124

124 Describe Kallmann syndrome and its relation to congenital olfactory dysfunction.

Answer 124

Gonadotropin-releasing hormone neurons fail to migrate from the olfactory placode to the hypothalamus. Magnetic resonance imaging (MRI) may demonstrate the absence of olfactory bulbs.

Question 125

125 In what familial autosomal dominant condition do patients develop anosmia, early baldness, and bilateral vascular headaches?

Answer 125

Familial anosmia

Question 126

126 What advice is critical to relay to patients with significantly impaired olfaction?

Answer 126

It is critical to review the risks of inability to smell “warning” odors, such as smoke, natural gas, and spoiled foods, and to recommend the use of smoke alarms and natural gas detectors.

Question 127

127 Describe the principle of olfactory threshold testing and one method of performing it.

Answer 127

Absolute threshold of detection is identified, which is the lowest concentration of an odorant that can be detected reliably. An odorant in one sniff bottle and water in another bottle are presented at varying concentrations from weak to strong (based on distance).

Question 128

128 Describe the principle of odor identification tests.

Answer 128

This is a quantitative test (number of odorants identified). Odorants are presented at suprathreshold concentrations to a patient who is asked to identify the odorants.

Question 129

129 Describe the University of Pennsylvania Identification Test (UPSIT).

Answer 129

The UPSIT is a self-administered test with four ‘‘scratch and sniff’’ booklets, each containing 10 odorants. Each odorant has a question with four answers. The patient is required to answer even if he or she does not recognize the odorant. Random-chance performance would be 10 of 40, so scores lower than 5 are concerning for malingering. The UPSIT has been studied extensively, and the reliability of the test is high.

Question 130

130 Describe the Cross-Cultural Smell Identification Test (CC-SIT).

Answer 130

This test is a variant of the UPSIT. It comprises 12 items (banana, chocolate, cinnamon, gasoline, lemon, onion, paint thinner, pineapple, soap, smoke, and turpentine) and is based on odorants most consistently identified by subjects representing various countries (China, France, Germany, Italy, Japan, Russia, and Sweden).

Question 131

131 What are the most common side effects of second-generation histamine type 1 (H1) blockers?

Answer 131

Headache, urinary retention, dry mouth, blurry vision, and GI upset

Question 132

132 What is the most common side effect of intranasal steroid sprays?

Answer 132

Epistaxis resulting from incorrect technique

Question 133

133 What are the most common side effects of pseudoephedrine?

Answer 133

Nervousness, hypertension, and urinary retention

Question 134

134 What is the onset of action of cocaine?

Answer 134

5 to 10 minutes

Question 135

135 What is the duration of action of cocaine?

Answer 135

6 hours

Question 136

136 What is the maximum recommended dose of cocaine?

Answer 136

Varies between 1 and 3 mg/kg; 3 mg/kg is most common. Commonly comes in a 4% solution, and it is estimated that < 40% is truly absorbed

Question 137

137 What are the two general forms of nasal valve obstruction?

Answer 137

● Static = does not change with respiration (i.e. caudal septal deviation) ● Dynamic = changes with respiration, causes collapse of the structures of the nasal valve (i.e. internal nasal valve collapse)

Question 138

138 While examining a patient, you use lateral distraction on the cheek while asking the patient to breathe in and out and tell you whether this maneuver increases airflow. What is the name of this test, and what is it most useful for?

Answer 138

Cottle maneuver. Nonspecific. Almost all nasal obstruction improves with this maneuver. It can point to internal nasal valve collapse, which can also be demonstrated with Breathe Right strips.

Question 139

139 How does the modified Cottle maneuver differ from the Cottle maneuver?

Answer 139

The modified Cottle maneuver is performed by placing an ear curette or end of a Q-tip inside the nose with gentle support of the internal and/or the external nasal valve while the patient breathes to determine whether his or her breathing improves. The modified test is a better test than the Cottle maneuver.

Question 140

140 What test can be used to determine whether the inferior turbinates are a significant contributor of nasal airway obstruction?

Answer 140

Spray the patient’s nasal cavities with phenylephrine spray
to decongest the patient’s inferior turbinates and determine
whether nasal obstruction improves.

Question 141

141 What is the point of highest resistance in the adult airway?

Answer 141

Internal nasal valve

Question 142

142 What structure visualized on anterior rhinoscopy is responsible for two-thirds of upper airway resist ance at the internal nasal valve?

Answer 142

Inferior turbinate

Question 143

143 On anterior rhinoscopy you note a normal, but enlarged, middle turbinate. On CT scan, there is an air-filled sinus within the head of the middle turbinate. What is the most likely cause?

Answer 143

Concha bullosa : Pneumatized middle turbinate

Question 144

144 What percentage of the population will have a concha bullosa?

Answer 144

25%

Question 145

145 What is the approximate angle between the septum and upper lateral cartilage within the internal nasal valve?

Answer 145

10 to 15 degrees

Question 146

146 Identify treatment options for both internal and external nasal valve collapse.

Answer 146

Septoplasty, batten grafts, spreader grafts, lateral crural strut grafts, lower lateral cartilage suture suspension

Question 147

147 List the possible causes of nasal septal perforation.

Answer 147

• Iatrogenic: Prior septal surgery, prior cauterization, nasogastric tube placement, nasotracheal intubation, etc.
• Trauma: Nose picking (i.e., digital trauma), septal hematoma
• Inhalants: Cocaine abuse, intranasal corticosteroids, chronic vasoconstrictor use, glass dust, etc.
• Autoimmune: Wegener granulomatosis, sarcoidosis, sys temic lupus erythematosus, Crohn disease, etc.
• Infectious: Syphilis, leishmaniasis, tuberculosis, acquired immunodeficiency syndrome (AIDS), etc.
• Neoplastic: T-cell lymphomas, etc.
• Miscellaneous: Lime dust, cryoglobulinemia, renal failure
• Idiopathic

Question 148

148 What common symptoms are associated with septal perforation?

Answer 148

● Asymptomatic (vast majority) ● Nasal crusting ● Epistaxis ● Nasal obstruction ● Postnasal drip ● Whistling

Question 149

149 Where are septal perforations most commonly found in the septum, and how large are they usually?

Answer 149

Anterior septum. Most commonly 1 to 2 cm

Question 150

150 When should you take a biopsy of a septal perforation?

Answer 150

When there is concern for malignancy, a biopsy should be taken, although this is controversial and not recommended routinely; yield is low when biopsy is done for vasculitic disease, etc.

Question 151

151 What size septal perforation has a high risk of failed surgical closure?

Answer 151

Large perforation (> 2 cm)

Question 152

152 What perforations should you treat with conservative management, and what does this involve?

Answer 152

Asymptomatic perforations. The goal is to keep the perforation moist (i.e., nasal saline sprays, Vaseline, saline irrigations, etc.).

Question 153

153 For large septal perforations not amenable to surgical closure or smaller symptomatic perforations, what nonsurgical option can be offered that can decrease epistaxis, nasal crusting, obstruction, and whistling?

Answer 153

Septal button placement. Prefabricated or custom buttons are available. Custom prostheses for large or irregular perforations can be optimally sized using a maxillofacial CT scan.

Question 154

154 Identify complications associated with septal button placement.

Answer 154

● Intranasal pain (particularly if displaced) ● Erosion of perforation edges (rare, usually protects) ● Intranasal crusting ● Bacterial colonization/biofilm Note: All are relatively low risk but should be discussed.

Question 155

155 Describe the surgical approaches and techniques available for nasal septal perforation repair.

Answer 155

Endonasal versus open techniques:

• Primary closure
• Interposition grafts: Bone, cartilage, periosteum, temporalis fascia, acellular dermis
• Flaps: Bipedicaled mucoperichondrial flap, rotational mucoperichondrial flap
• Alternative flaps (large perforations > 2 cm): Inferior turbinate pedicled flap, tunneled sublabial mucosal flap, facial artery musculomucosal flap, radial forearm free flap, pericranial/glabellar flap

Question 156

156 Describe the process and potential danger of septal hematoma.

Answer 156

Blood collection causes elevation of the mucoperichon drium/mucoperiosteum off the septal cartilage causing devascularization of underlying cartilage and potential for avascular necrosis and reabsorption.

Question 157

157 Identify complications associated with septal hematoma.

Answer 157

Septal perforation, subperichondrial fibrosis, septal abscess, intracranial infection (spread to cavernous sinus through emissary veins, extremely rare)

Question 158

158 What factor places children at increased risk for developing nasal septal hematoma?

Answer 158

Loose adherence of the mucoperichondrium and muco periosteum to the underlying bone and cartilage

Question 159

159 What is the treatment for septal hematoma?

Answer 159

Incision and drainage with application of nasal stent or packing to keep the potential space reduced. The patient should be receiving prophylactic antibiotics while packing is in place.

Question 160

160 What is defined as a collection of purulent material between the nasal septal mucoperiosteum/ mucoperichondrium and the bony and/or cartilaginous septum?

Answer 160

Nasal septal abscess

Question 161

161 What are the risk factors for developing a nasal septal abscess?

Answer 161

● Septal hematoma resulting from trauma or prior surgery ● Nasal vestibule furuncle ● Sinusitis ● Dental infection

Question 162

162 What is the recommended management for nasal septal abscesses?

Answer 162

● Anti-staphylococal antibiotics ● Incision and drainage

Question 163

163 What complications are associated with nasal septal abscesses?

Answer 163

• Intracranial complications (abscess, cavernous sinus thrombosis)
• Orbital cellulitis
• Septal perforation or weakening or loss of the nasal framework resulting in saddle nose deformity

Question 164

164 A patient with pain and itching of the nasal vestibule is examined, and you note small pustular lesions with an erythematous base, pierced by a single hair follicle. What is the diagnosis?

Answer 164

Nasal folliculitis

Question 165

165 Facial or nasal folliculitis can be superficial or deep and is often associated with what pathogen?

Answer 165

S. aureus

Question 166

166 What pathologic condition generally follows folliculitis, or hair follicle infection, and develops as a small abscess with extension of purulent material from the dermis to subcutaneous tissue?

Answer 166

Furuncle (boil)

Question 167

167 Why are incision and drainage of nasal furuncles, if necessary, deferred for at least 24 hours after initiating antistaphylococcal antibiotics?

Answer 167

Risk of cavernous sinus thrombosis

Question 168

168 Inflammatory nasal masses can form around a foreign body, blood clot, or secretion and grow as a result of accumulation of salts (calcium, magnesium, phosphate, carbonate) over time, potentially resulting in pressure injury to adjacent structures and causing nasal obstruction, pain, headache, infection, or recurrent epistaxis. This process is referred to as what?

Answer 168

Rhinolith

Question 169

169 A previously healthy 3-year-old patient has had 2 days of unilateral rhinorrhea associated with a foul odor, intermittent ipsilateral epistaxis, and general ized irritability. Examination reveals a mass in the right nasal cavity. What is the most likely diagnosis?

Answer 169

Nasal foreign body

Question 170

170 What proportion of epistaxis arises from an anterior source?

Answer 170

Approximately 90% to 95%

Question 171

171 What are the common local causes of epistaxis?

Answer 171

● Trauma: Digital, fracture, nasotracheal intubation, feed ing tube placement, foreign body, recent surgery ● Drug related: Nasal steroid sprays, cocaine inhalation ● Desiccation: Nasal oxygen, continuous positive airway pressure (CPAP) ● Inflammatory or infectious ● Neoplastic

Question 172

172 What systemic processes can result in epistaxis?

Answer 172

Coagulopathy: ● Genetic: Hemophilia, hereditary hemorrhagic telangiec tasis (HHT), von Willebrand disease ● Drug related: Coumadin, heparin, aspirin ● Hypertension ● Neoplastic: Pancytopenia, thrombocytopenia, etc.

Question 173

173 List nonsurgical methods of epistaxis management.

Answer 173

ABCs (airway, breathing, and circulation): Epistaxis can be life threatening! ● Direct pressure ● Vasoconstrictive agents ● Cautery under direct visualization ● Nasal packing ● Absorbable packing ● Nonabsorbable packing ● Control hypertension and correct coagulopathy if possible ● Nasal hygiene ● Saline sprays, humidity, emollients (petroleum jelly, etc.)

Question 174

174 What are the surgical methods available for epistaxis control if bleeding continues despite maximum nonoperative intervention?

Answer 174

● Surgical ligation ● Sphenopalatine artery (transnasal endoscopic, identify crista ethmoidalis, may use large maxillary antrostomy) ● Internal maxillary artery (transmaxillary endoscopic, either via the Caldwell-Luc procedure, mega-antrostomy, or partial medial maxillectomy) ● Anterior ethmoid artery (Lynch incision, identify fron toethmoid suture line) ● External carotid artery (transcervical) ● Endovascular embolization (most commonly internal maxillary artery; risk of stroke)

Question 175

175 External ligation of the anterior ethmoid artery is obtained through what approach?

Answer 175

Accessed via Lynch incision, located approximately 24 mm posterior to the anterior lacrimal crest, along the frontoethmoid suture line

(The Lynch incision is commonly used during external ethmoidectomy and is classically described as a 2- to 3-cm curvilinear skin incision in a vertical direction centered halfway between the nasal dorsum and inner canthus of the eye.)

Question 176

176 Describe the location of the sphenopalatine artery for endoscopic ligation.

Answer 176

Posterior to the inferior attachment of the middle turbinate, submucosal on the lateral nasal sidewall

Question 177

177 Why are antibiotics prescribed while a patient has nasal packing in place?

Answer 177

To prevent toxic shock syndrome

Question 178

178 What autosomal dominant disorder results in punctate hemangiomas or vascular sinuses that are irregularly shaped, associated with thin epithe lium, and have no muscular or elastic layers resulting in easy bleeding?

Answer 178

Osler-Weber-Rendu disease (HHT)

Question 179

179 What are the organs most commonly associated with HHT?

Answer 179

Nasal cavity, oral cavity, GI tract, lungs, liver

Question 180

180 Which genetic mutations are most commonly seen with HHT?

Answer 180

Endoglin gene (ENG, HHT1) and activin A receptor type II like 1 gene (ACVRL1, HHT2). Mutation detection rates are as high as 75% with sequence analysis of these two genes. SMAD4 is less common (3%) and is associated with HHT and juvenile intestinal polyposis.

Question 181

181 What are the most common sign and symptom associated with HHT?

Answer 181

Mucocutaneous telangiectasias and recurrent epistaxis

Question 182

182 What are the nonsurgical treatment options available for HHT patients with recurrent epistaxis?

Answer 182

● Anemia: Iron supplementation, blood transfusions ● Nasal hygiene: Oil of sesame with rose-geranium, nasal saline spray; tolerated in some patients ● Intranasal bevacizumab

Question 183

183 What are the surgical treatment options available for HHT patients with recurrent epistaxis?

Answer 183

Surgical management: ● Potassium-titanyl-phosphate (KTP) laser ablation of le sions ● Injection of bevacizumab ● Septodermoplasty ● Young’s procedure

Question 184

184 Describe Saunder’s septodermoplasty.

Answer 184

Denuding of nasal mucosa affected by telangiectasias and coverage of denuded area with a split-thickness skin grafts

Question 185

185 In what surgical procedure are the nasal cavities closed by creating two layered flaps (nasal mucosa and skin), thus eliminating airflow through the nasal cavities?

Answer 185

Young’s procedure

Question 186

186 A patient with irritation and inflammation of the nasal mucous membranes complains of rhinorrhea, nasal congestion, and postnasal drip. What is the most likely general diagnosis based on this information?

Answer 186

Rhinitis

Question 187

187 What are the main forms of rhinitis?

Answer 187

● Allergic rhinitis ● Nonallergic rhinitis

Question 188

188 Allergic rhinitis reflects what type of Gell and Coombs hypersensitivity?

Answer 188

Type I (anaphylactic/immediate) hypersensitivity with both early and late-phase reactions occurring after re-exposure to the antigen (see section on Allergy)

Question 189

189 What are the primary subtypes of allergic rhinitis?

Answer 189

● Seasonal allergic rhinitis ● Perennial allergic rhinitis ● Mixed allergic rhinitis

Question 190

190 What are the classic symptoms of allergic rhinitis?

Answer 190

● Sneezing ● Rhinorrhea ● Nasal congestion ● Pruritus (nasal, palatal, ocular) ● Watery eyes ● Postnasal drainage ● Anosmia/hyposmia

Question 191

191 Diagnosis of allergic rhinitis hinges most heavily on what factor?

Answer 191

Clinical history

Question 192

192 What comorbidities are commonly associated with allergic rhinitis?

Answer 192

Asthma, acute rhinosinusitis, otitis media with effusion, sleep disordered breathing, and obstructive sleep apnea

Question 193

193 What treatments exist for allergic rhinitis?

Answer 193

Intranasal/oral corticosteroids, intranasal/oral antihist amines, leukotriene inhibitors, cromolyn sodium, immune therapy (sublingual and injection) (see section on Allergy)

Question 194

194 A patient presents with nasal congestion, rhinorrhea, and postnasal drip but has a history of negative allergy testing. What type of rhinitis does this most likely represent? What are the major subtypes associated with this condition?

Answer 194

Nonallergic rhinitis:

• Infectious rhinitis
• Vasomotor rhinitis (60%)
• Nonallergic rhinitis of eosinophilia syndrome (NARES)
• Gustatory rhinitis
• Occupational
• Hormonally induced
• Medication induced
• Atrophic
• Inflammatory/immune-related disorders

Question 195

195 What are the key symptoms associated with non allergic rhinitis?

Answer 195

● Sneezing ● Rhinorrhea ● Nasal congestion ● Postnasal drainage

Question 196

196 True or False. Negative allergy testing is required for the diagnosis of nonallergic rhinitis.

Answer 196

False

Question 197

197 Viral infections (rhinovirus, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus, and enterovirus) can result in URI symptoms, including congestion, rhinorrhea, and postnasal drip, but often they do not cause pruritic symptoms. The infection typically resolves within 7 to 10 days. What diagnosis does this describe?

Answer 197

Infectious rhinitis

Question 198

198 In what type of nonallergic rhinitis is there excess parasympathetic tone resulting in vasodilation, which can be triggered by cold temperatures and strong smells?

Answer 198

Vasomotor rhinitis

Question 199

199 What are the characteristics of vasomotor rhinitis?

Answer 199

It is a diagnosis of exclusion. Patients usually manifest this condition in older age, with copious clear rhinorrhea that is triggered by alcohol, temperature, or humidity changes or exposure to odors.

Question 200

200 What are the common triggers for vasomotor rhinitis?

Answer 200

Changes in temperature, change in relative humidity, odors (e.g., perfumes, cleaning agents), second-hand tobacco smoke, alcohol, sexual arousal, and emotional changes can be triggers.

Question 201

201 What is the underlying pathophysiology associated with vasomotor rhinitis?

Answer 201

This condition is poorly understood. It may be related to the increased neural efferent input to mucosal vasculature.

Question 202

202 Though controversial, what surgical interventions can be considered in patients with vasomotor rhinitis?

Answer 202

Vidian neurectomy

Question 203

203 What type of nonallergic rhinitis manifests with perennial symptoms including sneezing, watery rhinorrhea, nasal pruritus, and intermittent hyposmia/anosmia; demonstrates ~10 to 20% eosinophils on nasal smear, and is associated with negative in vivo and in vitro allergy testing?

Answer 203

NARES

Question 204

204 A 33-year-old man has profuse watery rhinorrhea whenever he eats his favorite hot and spicy meals. What is the likely diagnosis?

Answer 204

Gustatory rhinitis

Question 205

205 What is the underlying pathophysiology of gustatory rhinitis?

Answer 205

Vagally (cholinergically) mediated vasodilation after eating (especially with hot or spicy foods)

Question 206

206 What type of rhinitis is can be associated with (1) inhaled protein or chemical antigens that result in an IgE mediated response (allergic rhinitis), (2) inhaled chemical respiratory sensitizers that cause an unknown immune response, or (3) exacerbation of rhinitis and is often associated with concurrent asthma?

Answer 206

Occupational rhinitis

Question 207

207 Pregnancy, puberty, menstruation, and hypothyroidism can all be associated with what type of rhinitis?

Answer 207

Hormonally induced rhinitis

Question 208

208 During pregnancy, hormone-induced vasodilation, vascular pooling, and increased blood volume can contribute to congestion and rhinitis. Is it more common for this to occur as a new diagnosis of rhinitis or as an exacerbation of preexisting rhinitis?

Answer 208

1/3 of women = exacerbation

2/3 of women = de novo = typically resolves ~2 weeks after delivery

Question 209

209 What are some common medications that can cause rhinitis?

Answer 209

Angiotensin-converting enzyme (ACE) inhibitors, β-blockers and other antihypertensives, erectile dysfunction or pul monary hypertension medications (i.e., sildenafil), oral contraceptives and aspirin in sensitive individuals. Ethanol in wine, beer, and other alcoholic beverages can result in vasodilation and rhinitis.

Question 210

210 What condition is associated with rebound nasal congestion secondary to using topical nasal decon gestants (α-adrenergic) for more than 5 to 7 days?

Answer 210

Rhinitis medicamentosa

Question 211

211 What condition is associated with degeneration of sinonasal sensory and autonomic nerve fibers leading to mucosal gland involution, squamous metaplasia of the sinonasal epithelium, and signifi cant alteration of mucociliary transport and can be either primary or secondary (after surgery or trauma)?

Answer 211

Atrophic rhinitis (also called rhinitis sicca or ozena)

Question 212

212 What organism commonly colonizes the nasal mucosa in patients suffering from atrophic rhinitis?

Answer 212

Klebsiella ozaenae

Question 213

213 What are the clinical examination findings associated with atrophic rhinitis?

Answer 213

● Foul odor ● Yellow/green crusting ● Atrophic/fibrotic mucosa

Question 214

214 In addition to the categories of rhinitis included above, what important inflammatory-immune diseases are also associated with nonallergic rhinitis?

Answer 214

● Granulomatous infections (rhinoscleroma, rhinosporidiosis) ● Wegener granulomatosis ● Sarcoidosis ● Midline granuloma ● Churg-Strauss syndrome ● Relapsing polychondritis ● Amyloidosis (Covered in the section on inflammatory/infectious nasal masses and Systemic Disease sections of this chapter)

Question 215

215 What management options have demonstrated utility in the management of nonallergic rhinitis?

Answer 215

● Intranasal glucocorticoids* ● Intranasal antihistamine (azelastine [Astelin, Astepro], olapatadine [Patanase])* ● Intranasal ipratropium bromide (Atrovent) ● Nasal irrigation ● Adjunctive oral medications (antihistamines, decongest ants) *Primary management: Use full dose daily, often in combination (results are better with intranasal steroid and antihistamine than with either alone).

Question 216

216 What specific feature of nonallergic rhinitis is the target of ipratropium bromide intranasal spray?

Answer 216

Watery rhinorrhea

Question 217

217 What is the proposed reason an intranasal antihistamine nasal spray would offer a benefit to patients with nonallergic rhinitis?

Answer 217

Anti-inflammatory: Decreased eosinophil activation, ex pression of adhesion molecules, and cytokine production. Potentially decreases neurogenic excitation from olfactory stimuli.

Question 218

218 In the past decade, the term rhinosinusitis has been commonly used to describe what condition?

Answer 218

Inflammation of the nose and paranasal sinuses. This term is preferred over sinusitis because sinusitis almost always involves the nasal cavity.

Question 219

219 According to the European Position Paper on Rhinosinusitis and Nasal Polyposis (2007), what are the criteria for diagnosing rhinosinusitis?

Answer 219

Inflammation of the paranasal sinuses, with two or more of the following: ● Nasal blockage, obstruction, congestion, or nasal dis charge (anterior and/or posterior) ● ± Facial pain or pressure ● ± Hyposmia or anosmia

Question 220

220 Describe the five major classifications of rhinosinusitis based on symptom time course.

Answer 220

• Acute: < 4 weeks with complete resolution
• Recurrent Acute: 4+ episodes per year lasting ≥ 7 to 10 days; complete resolution between episodes
• Subacute: 4 to 12 weeks; controversial designation (considered as a “filler term”)
• Chronic (± NP): > 12 weeks, without complete resolution
• Acute exacerbations of CRS: Worsening from baseline chronic symptoms, followed by return to baseline

Question 221

221 What is one of the tools used to assess the severity of rhinosinusitis symptoms?

Answer 221

● 10-cm visual analog scale: “How troublesome are your symptoms of rhinosinusitis?” ● Range: 0 = Not troublesome, 10 = Worst thinkable ● 0 to 3 = Mild ● 3 to 7 = Moderate ● 7 to 10 = Severe

Question 222

222 Define double worsening/sickening.

Answer 222

Symptoms that worsen following initial improvement

Question 223

223 What type of acute rhinosinusitis occurs two to five times per year in the average adult, has a symptom peak at 2 to 3 days, progressively improves after day 5, and has symptom resolution by day 10 to 14?

Answer 223

Acute viral rhinosinusitis

Question 224

224 What are the two most common pathogens asso ciated with acute viral rhinosinusitis?

Answer 224

Rhinovirus and Influenza virus

Question 225

225 What percentage of viral rhinosinusitis is estimated to progress to bacterial sinusitis?

Answer 225

0.5 to 2%

Question 226

226 What type of acute rhinosinusitis lasts for > 10 days or manifests with worsening of symptoms after day 5?

Answer 226

Acute bacterial rhinosinusitis (ABRS)

Question 227

227 In addition to the diagnostic symptoms associated with rhinosinusitis, what secondary symptoms may suggest ABRS?

Answer 227

Fever, aural fullness, cough, myalgias, or headache

Question 228

228 What pathogens are most commonly involved in ABRS?

Answer 228

● Streptococcus pneumoniae (30%) ● Haemophilus influenzae (20 to 30%) ● Moraxella catarrhalis (10 to 20%)

Question 229

229 What workup is recommended for acute rhinosinusitis?

Answer 229

● Not recommended: CT or X-ray ● CT may be considered for severe disease, immunocom promised patients, clinically suspicious complications, preoperative evaluation, or evaluation of recurrent acute rhinosinusitis. Optional ● Anterior rhinoscopy ● Nasal endoscopy: Consider for initial workup, if disease is refractory to empiric treatment, for unilateral disease, when symptoms are severe or disabling ● Nasal culture: Treatment failure, complications

Question 230

230 When should you consider a sinus puncture using a large-bore needle through the canine fossa or inferior meatus for workup of acute rhinosinusitis?

Answer 230

● Clinical trials: Standard for identifying bacterial pathogens in the maxillary sinuses ● Potentially useful if episodes are refractory to treatment or when rapid diagnosis and identification of pathogens are required (e.g., in an immunocompromised patient)

Question 231

231 According to the European Position (EPOS) Paper on Rhinosinusitis and Nasal Polyposis (2007) and supported by data in EPOS 2012, what treatment strategy should be used for mild acute rhinosinusitis with symptoms lasting < 5 days or improving after 5 days?

Answer 231

Symptomatic treatment ● Decongestant ● Saline irrigation ● Analgesics

Question 232

232 Why do some guidelines on acute rhinosinusitis recommend against using mucus color to dictate antibiotic use?

Answer 232

Mucus color is driven by neutrophils, not bacteria.

Question 233

233 If a patient has moderate to severe symptoms of acute rhinosinusitis that persist or worsen after 5 days, what is the recommended treatment according to the European Position Paper on Rhinosinusitis and Nasal Polyposis (2007) and supported by data in EPOS 2012?

Answer 233

Initiate intranasal corticosteroids. If no improvement is seen after 14 days → reconsider diagnosis, perform nasal endoscopy, consider an intranasal culture, and consider imaging. Also consider antibiotics, if indicated, if no improvement has occurred after 14 days.

Question 234

234 For a patient with acute rhinosinusitis with a temperature > 38ºC or in severe pain, what treatment is recommended?

Answer 234

● Intranasal corticosteroids ● Antibiotics ● May consider an oral steroid to decrease pain ● Symptomatic management (i.e., analgesia) Note: Improvement is expected within 48 to 72 hours.

Question 235

235 When should an antihistamine be used in the treatment of patients with acute rhinosinusitis?

Answer 235

Use antihistamines only in patients with a history of allergic rhinitis or allergic disease.

Question 236

236 Although decongestants can benefit patients with rhinosinusitis by decreasing mucosal swelling and potentially relieving paranasal sinus outflow obstruction, there is no conclusive published evi dence for their use in this disease. What is the maximum amount of time they should be used for?

Answer 236

5 days

Question 237

237 The Infectious Disease Society of America’s (IDSA) 2012 Guidelines for ABRS in children and adults recommends initiating antibiotic therapy for what signs and symptoms?

Answer 237

● Persistent signs or symptoms of ABRS for ≥ 10 days ● Severe signs or symptoms for ≥ 3 to 4 days (temper ature ≥ 39ºC, 102ºF; purulent nasal discharge, facial pain at the beginning of illness, or other concerning findings suggestive of complicated ABRS) ● Worsening or double sickening at ≥ 3 to 4 days

Question 238

238 In the IDSA’s algorithm, once a patient meets the criteria to receive an antibiotic, the risk for resistance must be assessed. What makes a patient high risk?

Answer 238

● Age < 2 years or > 65 years ● Attends daycare ● Antibiotics taken within the past month ● Hospitalization within the past 5 days ● Immunocompromised status ● Other comorbidities such as asthma, cystic fibrosis, etc. ● Geographic region with high endemic rates of penicillin resistant Streptococcus pneumoniae (> 10%)

Question 239

239 If a patient meets the criteria for an antibiotic and is not considered at high risk for resistance, what is the first-line antibiotic recommended by the IDSA?

Answer 239

Standard-dose Augmentin for 5 to 7 days (adults)

These guidelines recommend against the use of amoxicillin because of concern about an increasing number of patients developing ABRS from Haemophilus influenza since the introduction of pneumococcal conjugate vaccines as well as increasing β-lactamase production in these strains. However, previous guidelines published in the otolaryngology literature suggest amoxicillin as first line.

Question 240

240 If a patient meets the criteria for an antibiotic and is considered at high risk for resistance, what is the second-line antibiotic recommended by the IDSA?

Answer 240

• High-dose amoxicillin-clavulanate (amoxicillin dosed at 2 g twice daily or 90 mg/kg daily given twice daily) for 7 to 10 days
• Doxycycline
• Levofloxacin/moxifloxacin

Question 241

241 In penicillin allergic patients, what antibiotics are recommended by the IDSA for adults?

Answer 241

• Doxycycline
• Levofloxacin
• Moxifloxacin
• Cefixime/cefpodoxime and Clindamycin

Not macrolides or trimethoprim-sulfamethoxazole because of concern for resistance

Question 242

242 According to the IDSA, for a patient being treated with either a first- or second-line antibiotic for acute bacterial rhinosinusitis (who does not demonstrate symptomatic improvement or presents with worsening symptoms after 3 to 5 days of treatment), is switched to a different class of antibiotic or broader coverage, and again demon strates no improvement or worsening after 3 to 5 days, what additional steps should be considered?

Answer 242

● CT and/or MRI (CT preferred) to look for anatomical problems and suppurative complications ● Sinus culture to help direct pathogen specific antimicro bials ● Consider referral to infectious disease or allergy specialist (and ear, nose, and throat [ENT] specialist).

Question 243

243 When should surgical intervention be considered for patients with acute rhinosinusitis?

Answer 243

Only if complications are present that would benefit from surgical intervention or for recurrent acute rhinosinusitis thought to be caused by an anatomical abnormality

Question 244

244 What criteria are required for diagnosis of CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyposis (2007 and 2012) and the Clinical Practice Guidelines: Adult Sinusitis (2007)?

Answer 244

Two or more of the following symptoms for ≥ 12 weeks: ● At least one of (1) nasal blockage/obstruction/congestion or (2) nasal discharge (anterior or posterior, mucopur ulent) ● Facial pain/pressure or fullness (less common in patients with NP) ● Decreased or loss of smell (more common in patients with NP) ● Objective evidence of inflammation ● Purulent mucous or edema in the middle meatus or ethmoid region ● NP ● CT without contrast demonstrating inflammation in the paranasal sinuses (more commonly recommended for endonasal tumors)

Question 245

245 During the workup for CRS or recurrent acute rhinosinusitis, what comorbidities should be investigated that might modify management?

Answer 245

● Allergic rhinitis ● Cystic fibrosis ● Immunocompromise ● Ciliary dyskinesia ● Anatomical abnormality

Question 246

246 What is the classic triad associated with Kartagener syndrome?

Answer 246

● Situs inversus ● Bronchiectasis ● CRS Note: Caused by a dynein arm defect; autosomal recessive

Question 247

247 What percentage of patients with CRS will also have asthma?

Answer 247

50%

Question 248

248 If patients with CRS do not improve with standard therapy, allergy testing may be considered because 60% of these patients have significant allergies. What are the most common allergens implicated?

Answer 248

Perennial allergens: Dust mites, cockroaches, pet dander, fungi

Question 249

249 What diagnosis is given to patients who have aspirin sensitivity, NP, and asthma?

Answer 249

Samter triad

Question 250

250 What cytokine, or proinflammatory mediator, is thought to be primarily involved in Samter triad patients?

Answer 250

Leukotrienes

Question 251

251 What bacterial antigen is thought to be associated with nonspecific T-cell activation and cytokine release via cross linking of T-cell receptors with major histocompatibility class (MHC) II receptors on antigen presenting cells, and has been hypothesized to be involved in the pathogenesis of CRS with NP?

Answer 251

Staphylococcal superantigen

Question 252

252 What term defines the organized, three dimensional bacterial structures encased in an extracelluar matrix, which protects it from conven tional treatment modalities and may contribute to some cases of CRS?

Answer 252

Bacterial biofilms

Question 253

253 In patients with refractory rhinosinusitis, according to Chee et al (Laryngoscope 2001), what underlying immunodeficiencies may be identified?

Answer 253

● Combined variable immunodeficiency (10%) ● Selective IgA deficiency (6%) ● Low titers of IgG (18%), IgA (17%), or IgM (5%)

Question 254

254 What is the prevalence of rhinosinusitis in the HIV population?

Answer 254

20 to 70%.

Patients with HIV are at increased risk because of:

• Lymphocyte dysfunction
• Increased mucociliary transport time.

Question 255

255 What laboratory tests should be considered for a patient with refractory CRS or recurrent acute rhinosinusitis to evaluate for an underlying immunodeficiency?

Answer 255

• Quantitative immunoglobulin assays (IgG, IgA, IgM)
• Antibody response to tetanus toxoid and pneumococcal vaccines (before and after vaccination)
• T-cell number and function

Question 256

256 What is the genetic inheritance and cause of CRS in cystic fibrosis?

Answer 256

Autosomal recessive disorder causes abnormally tenacious exocrine gland secretions involving multiple organ systems. Patients with cystic fibrosis universally develop chronic sinusitis as a result of tenacious sinonasal secretions.

Question 257

257 Describe the management of CRS in patients with cystic fibrosis.

Answer 257

Conservative management is with mucolytics, topical anti biotic irrigations, and saline irrigations. The patient may need aggressive endoscopic surgical management followed by nasal saline irrigations and antipseudomonal antibiotic irrigations (tobramycin, especially if he or she is undergoing lung transplant.

Question 258

258 What findings on CT scan should be specifically evaluated for when evaluating a patient with CRS or recurrent acute rhinosinusitis?

Answer 258

● Mucosal inflammation ● Osseous destruction, extrasinus extension, or local invasion suggestive of aggressive disease or a malignant process ● Anatomical abnormalities: Septal deviation, concha bul losa, Haller cell, maxillary sinus hypoplasia, and/or obstruction of the osteomeatal complex

Question 259

259 What staging system grades the amount of mucosal disease present in the left and right frontal, anterior/posterior ethmoid, maxillary and sphenoid sinuses (0 = clear, 1 = partial opacification, 2 = complete opacification) and ostiomeatal complex (0 = clear, 2 = occluded)?

Answer 259

Lund-Mackay system (Annals of Otology, Rhinology, and Laryngology, 1995)

Question 260

260 Although bacterial infection in CRS is often related to more common pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumo niae, and Proteus mirabilis, over time, more rare anaerobic infections can occur. Name three such pathogens.

Answer 260

● Fusobacterium spp. ● Peptostreptococcus spp. ● Prevotella spp.

Question 261

261 What are the three primary subtypes of CRS?

Answer 261

● CRS with NP ● CRS without NP ● Allergic fungal rhinosinusitis

Question 262

262 What is a key difference between the inflammation seen in CRS with and without NP?

Answer 262

• Without NP: Neutrophils
• With NP: Eosinophils; interleukin-5 (IL-5) also increased

Question 263

263 What is the treatment recommended for CRS without NP (European Position Paper on RS and NP, 2007, supported 2012)?

Answer 263

Mild disease (visual analog scale: 0 to 3)

• Topical corticosteroids, nasal saline irrigation
• If no improvement in 3 months, treat as moderate/severe

Moderate/severe disease (visual analog scale: 4–10)

• Topical corticosteroids, nasal saline irrigation
• Long-term macrolide (~3 months) (if IgE is not elevated)
• Culture
• If no improvement: Consider CT and surgical candidacy
• If improvement noted:
  
  • Continue close follow-up, nasal irrigation, and topical corticosteroids.
  • Consider continuation of long-term macrolide Tx
  • Note: Evidence for the 3-month duration cutoff is lacking

Question 264

264 Name the four macrolides that can be considered for long-term antibiotic therapy in CRS without NP?

Answer 264

• Azithromycin
• Clarithromycin
• Roxithromycin
• Erythromycin

Question 265

265 What is the treatment recommended for CRS with NP (European Position Paper on RS and NP, 2007)?

Answer 265

Mild disease (visual analog scale: 0 to 3) Mod disease (4 to 7)

• Topical corticosteroids for 3 months
• Benefit noted → cont Tx, review every 6 months
• No benefit → 1 month of oral corticosteroid
  
  • Benefit noted → continue or switch back to topical corticosteroid drops; review after 3 months
  • No benefit → CT, consider surgical candidacy

Severe disease (visual analog scale: 8 to 10)

• 1-month course of PO + topical corticosteroid
• Benefit → continue topical corticosteroid drops only and review every 3 months
• No benefit → CT; consider surgical candidacy

Note: Antibiotics are not recommended by these guidelines. Evidence for the 3-month duration cutoff, topical corticosteroid drop vs. spray, and 1 month of steroid therapy is controversial.

Question 266

266 What is the only Food and Drug Administration (FDA)-approved topical corticosteroid spray for NP?

Answer 266

Mometasone furoate

Question 267

267 What are indications for ESS in patients with CRS

Answer 267

• Allergic fungal rhinosinusitis
• Failed medical therapy
• Anatomical abnormalities that hinder sinus drainage or medication application
• Significant NP
• Complications of rhinosinusitis or previous therapy (e.g., mucoceles, synechiae, etc.)

Question 268

268 After surgical intervention with polypectomy for CRS with NP, what medical management is recommended?

Answer 268

Maintenance therapy with topical corticosteroids and nasal irrigation

Question 269

269 What are the most common sites for extrasinus complications associated with rhinosinusitis (generally acute or acute-on-chronic)?

Answer 269

• Orbit 60%
• Intracranial 20%
• Bone 10%

Question 270

270 Name the valveless veins that allow retrograde spread of thrombophlebitis from mucosal veins to emissary veins, which pass through the diploe between the anterior and posterior tables of cranial cancellous bone to subdural veins and ultimately to cerebral veins.

Answer 270

Veins of Breschet (also known as diploic veins)

Question 271

271 What term refers to the paralysis or paresis of one or more of the extraocular muscles?

Answer 271

Ophthalmoplegia

Question 272

272 Describe the classification system used for orbital complications associated with rhinosinusitis. (▶ Fig. 3.12)

Answer 272

Chandler classification groups

• Preseptal cellulitis
• Orbital cellulitis
• Subperiosteal abscess
• Orbital abscess
• Cavernous sinus thrombosis

Question 273

273 You are evaluating a patient with acute rhinosinusitis who has unilateral eyelid edema, periorbital erythema, and tenderness with no evidence of proptosis, visual change, or restriction of ocular muscle movement. Imaging suggests rhinosinusitis and inflammation/infection of the periorbital soft tissues anterior to the orbital septum. What is the most likely diagnosis?

Answer 273

Preseptal cellulitis (Chandler group 1)

Question 274

274 What is the treatment for preseptal cellulitis?

Answer 274

Medical therapy: IV antibiotics (may consider oral), warm compresses, elevation of the head of the bed, decongest ants, mucolytics, and sinus irrigation. Close follow-up

Question 275

275 You are evaluating a patient with acute rhinosinusitis who has unilateral eyelid edema and erythema, proptosis, chemosis, normal vision, decreased extraoccular motility, and pain. CT scan shows an area of low attenuation adjacent to the lamina papyracea but no discrete abscess. What is the likely diagnosis?

Answer 275

Orbital cellulitis (Chandler group 2)

Question 276

276 Although most patients with orbital cellulitis should be treated with medical management (similar to preseptal cellulitis), what are two indica tions that a patient will need surgical drainage?

Answer 276

● Visual acuity ≤ 20/60 ● Worsening or lack of improvement after 48 hours of medical therapy

Question 277

277 You are evaluating a patient with acute rhinosinusitis who has unilateral proptosis, chemosis, and ophthalmoplegia with decreased visual acuity and significant orbital pain. CT scan demonstrated a rim-enhancing hypodensity with mass effect adjacent to the lamina propria. What is the likely diagnosis?

Answer 277

Subperiosteal abscess (Chandler group 3)

Question 278

278 Although medical cure is possible in patients with subperiosteal abscesses with the use of IV antibiotics, warm compresses, and nasal decongestants/irrigation/mucolytics, surgical intervention is recommended for worsening visual acuity, increased restriction of range of motion, or lack of improvement after 48 hours. What approaches can be used?

Answer 278

● Endonasal endoscopic drainage: medial abscess ● External ethmoidectomy via a Lynch incision ● Transcaruncular transconjunctival approach

Question 279

279 You are evaluating a patient with acute rhinosinusitis who has unilateral severe ophthalmo plegia, chemosis, proptosis, severe vision loss, and pain. CT scan demonstrates fluid collection within the orbital tissue. What is the likely diagnosis?

Answer 279

Orbital abscess (Chandler group 4)

Question 280

280 What syndrome, which can result from an orbital abscess, is associated with ptosis, proptosis, oph thalmoplegia, a fixed and dilated pupil, and V1 anesthesia?

Answer 280

Superior orbital fissure syndrome

Question 281

281 What syndrome, which can result from an orbital abscess, is associated with ptosis, proptosis, oph thalmoplegia, a fixed and dilated pupil, V1 anesthesia, and vision loss?

Answer 281

Orbital apex syndrome

Question 282

282 True or False. Orbital abscesses associated with rhinosinusitis can be managed with outpatient antibiotics, decongestants, and an ophthalmology consultation with close follow-up.

Answer 282

False. Inpatient admission, IV antibiotics, decongestants, and a low threshold for surgical drainage

Question 283

283 You are evaluating a patient with acute rhinosinusitis who has bilateral orbital pain, proptosis, chemosis, ophthalmoplegia, V2 sensory loss, sepsis, and meningismus. CT is suggestive of a process within the cavernous sinus, and MRI demonstrates heterogeneity and increased size of the sinus. What is the likely diagnosis?

Answer 283

Cavernous sinus thrombosis (Chandler group 5)

Question 284

284 What imaging modality is best to diagnose a cerebral venous sinus thrombosis?

Answer 284

MRI (T1, T2, T2 echo, and MR venography)

Question 285

285 The primary treatment for cavernous sinus throm bosis associated with rhinosinusitis includes IV antibiotics, management of increased intracranial pressure, management of predisposing factors, surgical drainage of associated abscesses, and/or sinuses. When should anticoagulation be used?

Answer 285

This topic is controversial! Although anticoagulation may decrease the propagation of thrombosis, it also increases the risk of intracranial bleeding.

Question 286

286 Describe the symptoms of cavernous sinus thrombosis.

Answer 286

• Orbital pain, photophobia
• Proptosis/Exophthalmos
• Conjunctival and lid edema
• Cranial nerves II, III, IV, V1, and VI involvement
  
  • Vision loss

Question 287

287 Name the five intracranial complications associated with rhinosinusitis.

Answer 287

● Meningitis ● Epidural abscess ● Subdural abscess ● Intracerebral abscess ● Cavernous sinus or venous sinus thrombosis

Question 288

288 What symptoms are frequently seen in patients with intracranial complications associated with rhinosinusitis?

Answer 288

Fever, headache, nausea or vomiting, altered mental status, focal neurologic signs, seizures, visual changes, and meningismus

Question 289

289 What management strategies are frequently used in patients with intracranial complications of rhinosinusitis?

Answer 289

IV antibiotics, often 4 to 8 weeks. Management of elevated intracranial pressure. (Note: Lumbar puncture is often contraindicated). Possible surgical drainage: endonasal and intracranial (bur hole vs. craniotomy, needle aspiration vs. resection)

Question 290

290 Why are steroids considered controversial in the management of intracerebral abscesses?

Answer 290

Steroids can result in decreased encapsulation of the abscess, increased necrosis, increased risk of rupture into the ventricular system, decreased antibiotic penetration into the abscess, and possible rebound edema after discontinuation.

Question 291

291 Thrombophlebitic spread of infectious material from acute bacterial rhinosinusitis into the adjacent bone with resulting osteomyelitis can occur via which vascular structures?

Answer 291

Diplopic veins (veins of Breschet)

Question 292

292 A patient with a history of CRS has a recent exacerbation and new-onset headache, fever, nasal congestion, and rhinorrhea. On examination, you note an area of swelling, erythema, and fluctuance over the frontal bone. On CT, you note a frontocutaneous fistula through the anterior table. What is the diagnosis?

Answer 292

Pott puffy tumor

Question 293

293 What are the cornerstones for management of Pott puffy tumor?

Answer 293

● Surgical drainage and removal of infected bone ● IV antibiotic therapy continued for 6 weeks

Question 294

294 What percentage of Pott puffy tumors can be associated with additional periorbital, pericranial, or intracranial abscesses?

Answer 294

60%

Question 295

295 Describe the origin of a sinonasal mucocele.

Answer 295

Sinus ostial obstruction leading to mucus accumulation. Origins include mucus retention cyst, trauma, inflammation (chronic sinusitis, allergy), iatrogenic surgical injury, pol yposis, and osteoma.

Question 296

296 Which paranasal sinuses are most frequently involved by mucoceles?

Answer 296

• Frontal (most common)
• Ethmoid sinus (second MC)
• Maxillary and sphenoid sinuses are less frequently involved.

Question 297

297 Why might a patient have an enlarged sinus or dehiscent area of bone associated with a known mucocele?

Answer 297

Mucocele growth is expansile and can result in bony remodeling.

Question 298

298 Describe the cause of allergic fungal sinusitis.

Answer 298

A noninvasive fungal sinusitis arising from an allergic response (type I hypersensitivity) to sinonasal fungal exposure

Question 299

299 Describe the criteria presented by Bent and Kuhn (Otolaryngology HNS, 1994) for the diagnosis of allergic fungal rhinosinusitis.

Answer 299

• Type I hypersensitivity to mold allergens (history or formal allergy testing)
• Eosinophilic mucin with Charcot-Leyden crystals
• Fungal hyphae without invasion into soft tissue
• NP

Characteristic imaging

• CT: Hyperdense central mucin surrounded by a rim of hypointensity with speckled areas of increased attenu ation resulting from ferromagnetic fungal elements. Unilateral > bilateral. May have bony expansion of the paranasal sinuses
• MRI: T1 and T2 show central hypointensity surrounded by hyperintensity and T2 may show a central void.

Question 300

300 What are the characteristics of eosinophilic mucin?

Answer 300

• Necrotic inflammatory cells
• Eosinophils
• Charcot-Leyden crystals
• Fungal hyphae

Question 301

301 What fungi are commonly implicated in allergic fungal rhinosinusitis?

Answer 301

• Alternaria
• Aspergillus
• Bipolaris
• Curvularia
• Cladosporium
• Dreschlera

Question 302

302 When evaluating a patient with NP, eosinophilic mucin on examination, and a history of atopy to inhaled mold allergens, what comorbid condition must also be investigated?

Answer 302

Asthma

Question 303

303 During the workup for allergic fungal rhinosinusitis, what procedures and/or diagnostic tests are recommended?

Answer 303

• Allergy testing for fungi-specific IgE (skin or blood tests)
• May consider total serum IgE
• Endoscopy for assessment and procurement of mucin specimen
• Pathologic analysis of eosinophilic mucin for fungal stains and possible culture
• Strongly consider CT without contrast

Question 304

304 What term was proposed by Ponikau (Mayo Clinic Proceedings, 1999) to describe patients with CRS and fungal hyphae in eosinophilic mucin but no evidence of type I hypersensitivity reactions on allergy testing?

Answer 304

Eosinophilic fungal rhinosinusitis

Question 305

305 What is the recommended treatment for allergic fungal rhinosinusitis?

Answer 305

• Nasal saline irrigations
• Consider systemic or topical steroids
• Endoscopic surgery
• Possibly systemic or topical antifungals

Question 306

306 What are the two categories of fungal rhinosinusitis?

Answer 306

• Invasive
• Noninvasive

Question 307

307 Name the subtypes of noninvasive fungal rhinosinusitis.

Answer 307

• Fungus ball (old terms no longer recommended: mycetoma, aspergilloma)
• Allergic fungal rhinosinusitis (see preceding)
• Saprophytic fungal infestation

Question 308

308 Fungus balls most frequently form in an isolated paranasal sinus as a mass of fungal hyphae with associated inflammatory debris and no evidence of mucosal invasion in immunocompetent patients and are found incidentally or manifest with associated symptoms. What is the most common fungus that is isolated?

Answer 308

Aspergillus fumigatus

Question 309

309 Define the distribution of paranasal sinus fungus balls.

Answer 309

Maxillary > sphenoid > ethmoid > frontal sinuses

Question 310

310 Paranasal fungus balls exhibit what imaging characteristics?

Answer 310

• Complete or subtotal opacification, usually of a single sinus
• Osteal thickening or sclerosis
• Noncontrast CT shows hyperattenuating lesion with punctate calcifications. The fungus ball is hypointense on T1-weighted and T2-weighted images owing to the absence of free water.
• Calcifications and paramagnetic metals generate areas of signal void on T2-weighted images.

Question 311

311 How are paranasal sinus fungus balls treated?

Answer 311

Surgical debridement and postoperative irrigations

Question 312

312 What type of noninvasive fungal rhinosinusitis often has an asymptomatic or foul-smelling fungal colonization of mucous crusts after previous sinus surgery?

Answer 312

Saprophytic fungal colonization

Question 313

313 What are the three types of invasive fungal rhinosinusitis?

Answer 313

• Acute invasive
• Chronic invasive
• Chronic granulomatous

Question 314

314 An immunocompromised patient has sudden-onset and rapidly progressive periorbital or facial swelling and/or ophthalmoplegia, neutropenic fever, and a nonpainful intranasal ulcer or eschar most likely has developed what disease process?

Answer 314

Acute invasive fungal rhinosinusitis (old terms that are no longer recommended: fulminant, necrotizing)

Question 315

315 True or false. Acute invasive fungal rhinosinusitis is defined as an invasive fungal infection that can take up to 4 weeks to develop.

Answer 315

True

Question 316

316 What patient populations are at highest risk for development of acute invasive fungal rhinosinusitis?

Answer 316

Immunocompromised:

• Hematologic malignancy
• Hematopoietic stem cell transplant
• Solid-organ transplant
• Diabetes mellitus
• Advanced HIV
• Immunodeficiency
• Chemotherapy induced neutropenia
• Corticosteroids

Question 317

317 What are the most common initial symptoms associated with acute invasive fungal rhinosinusitis?

Answer 317

• Fever
• Facial pain*
• Nasal congestion
• Decreased sensation over malar regions*
• Epistaxis
• Change in vision and mentation

*Important complaint that warrants attention.

Question 318

318 What are the most common physical examination findings suggestive of acute invasive fungal sinusitis?

Answer 318

Early: Pale, boggy mucosa, petechiae, or areas of ischemia

Late: Black eschar, sloughing mucosa, gross hyphae, decreased sensation. Mucosa does not bleed.

Question 319

319 What areas of the sinonasal cavities most commonly manifest acute invasive fungal rhinosinusitis?

Answer 319

The middle turbinate is reported to be the most common, followed by the septum and inferior turbinate. The palate and oral cavity must also be evaluated.

Question 320

320 What findings on CT scan would be suggestive of invasive fungal sinusitis?

Answer 320

• Unilateral sinus involvement (more common than bilateral)
• Paranasal sinus mucoperiosteal thickening
• Severe soft tissue edema of the nasal cavity mucosa (turbinates, lateral nasal wall and floor, septum)
• Facial soft tissue swelling
• Bone erosion
• Retroantral fat pad thickening (CT or MRI)
• Orbital/intracranial invasion

Question 321

321 When should an MRI be ordered during the workup for invasive fungal sinusitis?

Answer 321

If a patient is symptomatic but the CT and/or examination are equivocal or to evaluate the extent of intracranial or intraorbital invasion as suggested by CT or examination

Question 322

322 What two fungal organisms are most commonly involved in acute invasive fungal rhinosinusitis?

Answer 322

• Mucorales
• Aspergillus

Question 323

323 Which fungal organisms have nonseptate (aseptate) twisted hyphae that branch at 90-degree angles, are seen in a necrotic background, and often demonstrate angioinvasion, which most commonly occurs in diabetic ketoacidosis?

Answer 323

Mucormycoses (order: Mucorales)

Question 324

324 What are the most common Mucorales species associated with acute invasive fungal rhinosinusitis, and where are they found in the environment?

Answer 324

• Mucor
• Rhizopus
• Absidia
• Cunninghamella
• Rhizomucor
• Mortierella
• Saksenaea
• Apophysomycoses
• Zygomycoses

Found in the soil or associated with decaying organic matter such as leaves, wood, or compost

Question 325

325 What fungal organisms are known to have septate hyphae that branch at 45-degree angles and are best seen by using methenamine silver stain?

Answer 325

Aspergillus spp.

Question 326

326 What are the keys to effective management of acute invasive fungal rhinosinusitis, which carries a very poor overall prognosis?

Answer 326

• Rapid diagnosis and intervention!
• IV antifungal medications
• Aggressive surgical resection
• Reverse underlying immune dysfunction

If a patient is cured and lifelong immunosuppression is required, then lifelong oral suppressive antifungal therapy can be used.

Question 327

327 What IV antifungal medications should be considered empirically in the early management of acute invasive fungal rhinosinusitis?

Answer 327

IV amphotericin B (drug of choice for mucormycosis) +/- voriconazole (drug of choice for Aspergillus)

Question 328

328 What type of rhinosinusitis results from invasion by fungal elements and tissue destruction over a period of > 12 weeks?

Answer 328

Chronic invasive fungal rhinosinusitis

Question 329

329 What is the most common initial manifestation in patients with chronic invasive fungal rhinosinusitis?

Answer 329

Symptoms suggestive of CRS with few, if any, systemic complaints

Question 330

330 What patient populations are most at risk for development of chronic invasive fungal rhinosinusitis?

Answer 330

• Mildly immunocompromised
• Elderly
• Diabetes mellitus
• Glucocorticoid use
• AIDS

Question 331

331 True or False. Patients with chronic invasive fungal rhinosinusitis do not develop the severe complications associated with acute infection.

Answer 331

False. They can develop orbital and intracranial invasion. Prognosis is poor.

Question 332

332 What are the most common CT findings associated with chronic invasive fungal rhinosinusitis?

Answer 332

Thickened mucosa associated with bony erosions and a mass lesion in a single paranasal sinus (most common in the sphenoid or ethmoid)

Question 333

333 What are the findings on histopathology that suggest chronic invasive fungal rhinosinusitis?

Answer 333

• Dense accumulation of hyphae
• • /- Vascular invasion
• Little to no inflammatory reaction to invasion and destruction of local structures

Question 334

334 What is the most common fungal species associated with chronic invasive fungal rhinosinusitis?

Answer 334

Aspergillus fumigatus

Question 335

335 What is the recommended treatment for chronic invasive fungal rhinosinusitis?

Answer 335

• Rapid diagnosis and intervention
• IV antifungal medications
• Aggressive surgical resection
• Reverse underlying immune dysfunction

Question 336

336 What form of invasive fungal rhinosinusitis is diagnosed after 12 weeks’ duration, most commonly in immunocompetent patients from Sudan, India, Pakistan, or Saudi Arabia?

Answer 336

Chronic granulomatous invasive fungal rhinosinusitis

Question 337

337 What is the most common manifestation seen in patients with chronic granulomatous invasive fungal rhinosinusitis?

Answer 337

• Enlarging mass (cheek, orbit, nose, paranasal sinus)
• Gradual onset of symptoms

Question 338

338 What are the histopathologic findings most commonly seen in chronic granulomatous invasive fungal rhinosinusitis?

Answer 338

• Significant fibrosis
• Noncaseating granulomas
• Foreign body–type reaction
• Langherhans type multinucleated giant cells
• Possible vasculitis, vascular proliferation, perivascular fibrosis

Question 339

339 What fungal species is most often implicated in chronic granulomatous invasive fungal rhinosinusitis?

Answer 339

Aspergillus flavus

Question 340

340 What is the recommended treatment for chronic granulomatous invasive fungal rhinosinusitis?

Answer 340

• Surgical biopsy and debridement
• Systemic antifungals

Question 341

341 What type of papilloma arises within the nasal vestibule and nostril from stratified squamous epithelium, is more common in males, and can be treated by simple excision or cauterization?

Answer 341

Vestibular (keratotic) papilloma

Question 342

342 What three types of papillomas arise in the nasal cavity?

Answer 342

• Fungiform papilloma (also called exophytic, septal, or everted papilloma)
• Inverted papilloma (also called Schneiderian, epithelial, transitional cell, or Ringertz papilloma)
• Oncocytic papilloma (also called cylindrical)

Question 343

343 Where do everted papillomas of the nasal cavity most commonly arise?

Answer 343

Nasal septum (rarely: inferior turbinate, nasal vestibule, nostril)

Question 344

344 Describe the gross and microscopic characteristics of everted papillomas of the nasal cavity.

Answer 344

• Gross: Raised, verrucous, 1 to 15 mm in diameter, single, unilateral, attached to mucosa via a broad base
• Micro: Branching fronds of mucosa with a connective tissue core with stratified squamous epithelium; koilocy tosis is common

Question 345

345 What human papillomavirus (HPV) subtypes are commonly associated with everted nasal papillomas?

Answer 345

HPV 6 and 11.

Question 346

346 What is the treatment for everted papillomas of the nasal cavity?

Answer 346

Simple excision or cauterization. Rare recurrence or transformation

Question 347

347 Where do inverted papillomas most commonly arise within the nasal cavity, and from what epithelial subtype do they originate? Unit vs bilat?

Answer 347

Lateral nasal wall. May also arise from ethmoid air cells or maxillary sinus.

Unilateral > > > bilateral.

Schneiderian epithelium.

Question 348

348 What patient demographic most commonly has inverted papillomas?

Answer 348

White men (0.75F:1M) in their 60 s and 70s

Question 349

349 Describe the gross and microscopic characteristics of inverted papilloma.

Answer 349

• Gross: Unilateral, pale pink to reddish gray, polypoid (“mulberry”) mass arising from a stalk (can be broad or narrow), irregular, friable, often firmer than inflammatory polyps, although may be difficult to differentiate
• Microscopic: Hyperplastic ribbons of basement mem brane and epithelium invaginating into the underlying stroma. Stroma demonstrates inflammatory changes containing fibrosis and edema. Multilayered squamous, columnar, or transitional cell epithelium (or a combina tion) containing mucocytes and intraepithelial mucous cysts

Question 350

350 Which HPV subtypes are most commonly associated with inverted papilloma?

Answer 350

HPV 16 and 18 although 6 and 11 have been seen as well

Question 351

351 What is the incidence of malignant degeneration of inverted papillomas to squamous cell carcinoma?

Answer 351

5 to 10%

Note: Adenocarcinoma and small cell carcinoma have also been identified.

Question 352

352 Although the risk of recurrence for inverted papilloma is high, what might increase the risk of recurrence?

Answer 352

Surgical approach and multicentricity of the tumor

Question 353

353 What two imaging modalities are used most commonly during the workup for inverted papillomas?

Answer 353

• CT w con: Demonstrates bony destruction, including erosion, remodeling, and sclerosis; may demonstrate areas of calcification within the lesion
• MRI w con: Can differentiate inspissated secretions, mucoperiosteal thickening, and inflammatory changes. T1 lesion is ~ hyperintense to muscle; T2 inspissated secretions and inflammatory polyps are hyperintense.

Question 354

354 What are the treatment options available for sinonasal inverted papilloma?

Answer 354

• Complete surgical excision: Endoscopic or open
• Radiation therapy
• Observation

Question 355

355 What are the surgical approaches used for endoscopic and open surgical resection of inverted papillomas?

Answer 355

• Endoscopic: En bloc wide local excision, medial maxillectomy, Sturman-Canfield operation (Denker opera tion), Draf procedure
• Open: Lateral rhinotomy, midfacial degloving, osteoplastic flap, frontal sinus trephination

Note: The key is subperiosteal dissection, removal of all involved mucosa, and drilling down the bone in contact or attached to the papilloma.

Question 356

356 When is radiation therapy recommended for inverted papilloma?

Answer 356

• For aggressive, multifocal disease
• For squamous cell carcinoma
• If patient cannot tolerate surgery or if the functional or cosmetic results of surgical resection are not acceptable

Note: The risks of radiation include potential for malignant conversion.

Question 357

357 How long should patients be followed up for surveillance of inverted papilloma, and when should CT scans be ordered?

Answer 357

Minimum of 5 years. Recurrence most often occurs between 2 and 10 years. CT scans should be ordered if scarring limits full visualization of the resection cavity, if the patient is symptomatic, or there is evidence of recurrence.

Question 358

358 What is the least common unilateral Schneiderian nasal papilloma?

Answer 358

Oncocytic (cylindrical) papilloma, 3 to 5% of all sinonasal papillomas

Question 359

359 You are evaluating the pathology report on a patient with a lateral nasal papilloma; biopsy was performed at an outside hospital. The report describes endophytic invaginations of tall columnar, multilayered epithelium composed of oncocytes and containing microcysts laden with mucin and neutrophils. What is the most likely diagnosis?

Answer 359

Oncocytic (cylindrical) papilloma

Question 360

360 What is the reported malignant potential of oncocytic papillomas, and what histologic findings have been reported?

Answer 360

10 to 17% (although controversial); squamous cell carcinoma (most common), mucoepidermoid carcinoma, small cell carcinoma, and undifferentiated carcinoma

Question 361

361 Similar to inverted papillomas, oncocytic papillomas can be locally aggressive and have a relatively high rate of recurrence. What is the best management strategy for these tumors?

Answer 361

Complete surgical excision, as for inverted papillomas

Question 362

362 What is the most common benign nasopharyngeal tumor that most commonly affects prepubescent males at an average age of 14 to 15 years (range: 10 to 25)?

Answer 362

Juvenile nasopharyngeal angiofibroma

Question 363

363 Describe the major hypotheses put forth to explain the development of juvenile nasopharyngeal angiofibromas.

Answer 363

• Incomplete regression of the first branchial arch artery
• Development from embryologic chondrocartilage of the skull base at the junction of the palatine bone, horizontal ala of the vomer, and root of the pterygoid process.
• Abnormality of the pituitary androgen-estrogen axis

Question 364

364 What is the most common blood supply to juvenile nasopharyngeal angiofibromas?

Answer 364

Internal maxillary artery

Note: May also arise from ascending pharyngeal, external/ internal/carotid artery, and occasionally from contralateral supply

Question 365

365 What are the two most common symptoms described by patients with juvenile nasopharyngeal angiofibromas?

Answer 365

Epistaxis and unilateral nasal obstruction.

More progressive symptoms can include middle ear effusion, facial deformity, headache, dacryocystitis, rhinolalia, palatal deformity, hyposmia/anosmia, cranial neuropathies, and massive hemorrhage.

Question 366

366 Describe the characteristic gross appearance of a juvenile nasopharyngeal angiofibroma.

Answer 366

Well-circumscribed, smooth, lobulated, purple to reddish hue, compressible

Question 367

367 Describe the characteristic routes of spread or patterns of growth associated with juvenile nasopharyngeal angiofibromas.

Answer 367

• Pterygopalatine (sphenopalatine) fossa →
  
  • Orbit → middle cranial fossa
  • Masticator space → intracranial cavity
  • Infratemporal fossa → cheek or intracranial cavity
• Nasal cavity →
  
  • Paranasal sinus (i.e., sphenoid sinus → intracranial cavity)
  • Nasopharynx

Note: Dural invasion is rare.

Question 368

368 CT, MRI, and magnetic resonance angiography can each be used during the workup of patients with suspected juvenile nasopharyngeal angiofibromas. What characteristics are common?

Answer 368

• Epicenter located adjacent to the sphenopalatine fora men within the posterior nasal cavity
• Hypervascularity after contrast enhancement
• Distinct pattern of growth
• No regional or distant metastases

Question 369

369 What specific findings can be seen on CT and MRI that help distinguish a juvenile nasopharyngeal angiofibroma?

Answer 369

• CT: Bony remodeling without frank bony destruction
• MRI: Flow voids on both T1- and T2-weighted imaging

Question 370

370 Describe the Holman-Miller sign. (▶ Fig. 3.13)

Answer 370

Anterior bowing of the posterior maxillary sinus associated with juvenile nasopharyngeal angiofibroma

Question 371

371 True or False. Because angiography can be used to identify a source vessel, perform carotid balloon occlusion studies if necessary, and perform preoperative embolization in patients with juvenile nasopharyngeal angiofibromas, it is considered a required step in the workup and intervention.

Answer 371

False.

Angiography, when used 24 to 72 hours preoperatively, can provide all of this information and result in decreased intraoperative bleeding and need for transfusions and can result in shrinkage of the tumor. However, it is not required and is considered controversial.

Question 372

372 What arguments have been made against the use of preoperative embolization in patients undergoing resection for a juvenile nasopharyngeal angiofibroma?

Answer 372

• It can potentially obscure the tumor boundaries, resulting in a higher rate of recurrence
• Complications associated with embolization are not benign: cerebrovascular accident, blindness, facial para lysis, skin or soft tissue necrosis.
• Some argue that tumor hypoxia can decrease the radiosensitivity of these tumors.

Question 373

373 What is the most common staging system used to classify juvenile nasopharyngeal angiofibromas?

Answer 373

The most recent is the Radkowski system (1996).

• IA: Limited to nasal cavity and nasopharynx
• IB: Involvement of at least one paranasal sinus
• IIA: Minimal extension through the sphenopalatine foramen to involve the medial portion of the pterygopalatine fossa
• IIB: Extensive involvement of the pterygopalatine fossa with a positive Holman-Miller sign and anterolateral displacement of the maxillary artery branches. Possible superior extension with orbital bone erosion
• IIC: Extension through the pterygopalatine fossa to involve the cheek, infratemporal fossa, or posterior to the pterygoids
• IIIA: Skull base erosion with minimal intracranial exten sion
• IIIB: Skull base erosion with significant intracranial extension and possible cavernous sinus involvement

Question 374

374 What treatment options are available for patients with juvenile nasopharyngeal angiofibromas?

Answer 374

• Surgery (gold standard; open vs. endoscopic vs. combined)
• XRT (30 to 36 Gy, 20 fractions; has been shown to have similar efficacy to surgery in some situations)
• Hormonal therapy (controversial and not commonly used)
• Chemotherapy (potentially used for recurrences, rarely used)

Question 375

375 What is the risk of recurrence for juvenile nasopharyngeal angiofibromas, and what increases this risk?

Answer 375

Up to 40%. Large tumors; intracranial extension; involvement of the sphenoid, base of the pterygoids, or clivus; failure to remove all the tumor; or primary radiation treatment. Most are diagnosed within the first year either based on symptoms or with MRI.

Question 376

376 Sinonasal hemangiomas can arise from bone, mucosa, or submucosa within the nasal cavity and sinonasal cavities. Both cavernous and capillary subtypes can be seen. Which is more common in adults?

Answer 376

Cavernous hemangiomas

Question 377

377 Where do sinonasal hemangiomas most commonly arise within the nasal cavity and/or paranasal sinuses?

Answer 377

• Cavernous hemangioma → lateral nasal wall or medial maxillary wall
• Capillary hemangioma → septum

Question 378

378 What are the most common symptoms associated with sinonasal hemangiomas?

Answer 378

Epistaxis and nasal obstruction.

For patients with hemangiomas restricted to the bone, symptoms may include a firm, painless swelling associated with a pulsatile sensation.

Question 379

379 Describe the imaging characteristics of sinonasal hemangiomas on CT and MRI.

Answer 379

• CT w con: enhancement. It is often indistinct from turbinates and can be associated with bony destruction.
• MRI w con: enhancement, intermediate signal intensity, ± flow voids. If intraosseous, it may have a soap-bubble, sun-ray, or honeycomb appearance.

Question 380

380 What is the management of choice for sinonasal hemangiomas?

Answer 380

Surgical resection. Can consider preoperative embolization, especially for intraosseous lesions.

Question 381

381 What pathologic lesion can be seen in the sinonasal or oral cavity as a rapidly growing mass resulting in nasal obstruction and epistaxis and is composed of proliferating capillaries separated into lobules by loose connective stroma?

Answer 381

Lobular capillary hemangiomas (previously known as pyogenic granulomas)

Question 382

382 What theories have been presented as explanations for the formation of lobular capillary hemangiomas?

Answer 382

• Local trauma (e.g., nose picking, nasal packing)
• Hormonal fluctuations (e.g., pregnancy)
• Infection (e.g., influence of viral oncogenes)
• AVM
• Local production of angiogenic growth factors

Question 383

383 What are the clinical examination findings associated with a sinonasal lobular capillary hemangioma?

Answer 383

• Purplish/red mass
• Generally < 1 cm, but can be larger

Question 384

384 What is the treatment of choice for lobular capillary hemangiomas?

Answer 384

Complete surgical excision, although recurrence has been reported in up to 40%

Question 385

385 What benign neoplasm can develop from Zimmerman pericytes (contractile cells surrounding small vessels) and can be seen in the sinonasal tract, retroperitoneum, lower extremities, and pelvis?

Answer 385

Hemangiopericytoma

Question 386

386 What is the typical clinical presentation and gross appearance of a sinonasal hemangiopericytoma?

Answer 386

Epistaxis and nasal obstruction. Gray/tan mass that is spongy, vascular, and polypoid in appearance and involving the sinonasal cavity and often one or more paranasal sinus

Question 387

387 True or False. Sinonasal hemangiopericytomas can demonstrate malignant potential.

Answer 387

True. The risk is low, but regional metastases and death from disease progression have been reported.

Question 388

388 What are the typical imaging characteristics associated with sinonasal hemangiopericytomas?

Answer 388

• CT: Homogeneous, enhancing lesions; expansile, resulting in bony remodeling
• MRI: Enhance on T2-weighted imaging, intermediate enhancement on T1-weighted imaging

Question 389

389 What are the management options available for sinonasal hemangiopericytomas?

Answer 389

Complete surgical resection. Adjuvant radiation and chemotherapy may play a role, especially in patients with positive surgical margins. Recurrence rates of up to 19% have been reported.

Question 390

390 What is the most common benign tumor of the sinonasal tract that occurs as an expansile proliferation of mature bone within the membranous bones of the skull and face?

Answer 390

Osteoma

Question 391

391 Which sinuses are most commonly involved with osteomas?

Answer 391

Frontal > ethmoid > > maxillary > > > sphenoid

Question 392

392 What is the most likely diagnosis for a patient with multiple osteomas (often seen in the mandible), intestinal polyps, and epidermoid inclusion cysts and desmoids tumors?

Answer 392

Gardner syndrome (autosomal dominant)

Question 393

393 What theories have been described to explain the development of osteomas?

Answer 393

• Embryologic theory (development from the junction of the frontal bone, which is membranous, and the ethmoid bone, which is cartilaginous)
• Inflammation/infection theory
• Traumatic theory
• Slow growing osseous hamartomas

Question 394

394 Describe the three subtypes of osteomas.

Answer 394

• Ivory (eburnated): Compact, dense bone, minimal fibrous tissue
• Mature (spongiosum): Spongy, mature bony, trabeculum composed of fibrous tissue
• Mixed: Components of both ivory and mature osteomas

Question 395

395 What is the average growth rate of an osteoma?

Answer 395

1.6 mm/year (range: 0.44 to 6.0 mm/year)

Question 396

396 Although most osteomas are asymptomatic, they can result in a mass effect such as sinus outflow obstruction and resultant pain, sinusitis, and mucocele formation or orbital symptoms, such as proptosis, diplopia, etc. Less commonly, osteomas can grow intracranially. In these situations, what complications can arise?

Answer 396

CSF leak, meningitis, pneumocephalus, abscess formation

Question 397

397 What imaging characteristics are associated with osteomas?

Answer 397

• CT: Range from a high-density lesion to a less dense ground-glass appearing lesion based on the amount of mineralized bone
• MRI: Necessary only to evaluate adjacent soft tissue, trapped secretions, or mucoceles.

Question 398

398 How are osteomas best managed?

Answer 398

• Observation: For lesions that are asymptomatic and present a low risk for intracranial or orbital complications
• Surgical resection: Endoscopic vs. open vs. combined

Question 399

399 Name the following disorders associated with sinonasal exostoses:

• Hyperostosis of the inner table of the skull, thickened cancellous bone, and intact cortex sparing the midline and frequently seen in post menopausal women
• Hyperostosis in postmenopausal women in the presence of obesity and hirsutism
• Hyperostosis associated with thickened dura in adolescent males

Answer 399

• Hyperostosis frontalis interna
• Morgagni syndrome (metabolic craniopathy)
• Acromegaly

Question 400

400 What characteristics can be used to differentiate an ossifying fibroma from fibrous dysplasia?

Answer 400

An ossifying fibroma typically has a capsule and more mature bone and is more common in black women in their 30s and 40s.

Question 401

401 What are the imaging characteristics common to ossifying fibromas?

Answer 401

• CT: Well-defined, multiloculated lesion, surrounded by a bony capsule
• MRI: Hyperintense T2-signal; T1-signal is intermediately intense centrally and hyperintense peripherally.

Question 402

402 What is the treatment of choice for ossifying fibromas?

Answer 402

Radical surgical resection (44% recurrence rate)

Question 403

403 What bony disorder is due to the replacement of normal bone with fibro-osseous tissue (woven ossified tissue, increased bony matrix, abnormal mineralization, marrow fibrosis) that can occur in monostotic, polyostotic, or syndromic (McCune Albright) forms?

Answer 403

Fibrous dysplasia

Question 404

404 Describe the radiographic and histologic appearance of fibrous dysplasia.

Answer 404

• Radiographic pattern: Expansile lesion with relatively homogeneous smooth ground-glass appearance
• Histologic pattern: Irregularly shaped, patternless woven trabecular bone within a vascularized fibrous stroma; the irregular shaped spicules can occur as (1) Chinese writing type, (2) pagetoid type, and (3) hypercellular type.

Question 405

405 When should intervention, the gold standard of which is surgical resection, for fibrous dysplasia be considered?

Answer 405

• Aesthetic concerns
• Compression of neurovasculature resulting in symptomatic or functional sequelae
• Functional impairment, such as malocclusion
• To rule out malignancy

Question 406

406 Although rare (< 4%), malignant transformation of fibrous dysplasia can occur. What is the most common cancer associated with this transformation?

Answer 406

Osteosarcoma

Question 407

407 What is the rate of CSF production?

Answer 407

~ 500 mL/day or ~ 20 mL/hour

Question 408

408 What is the most common cause of anterior cranial fossa CSF leaks?

Answer 408

Noniatrogenic trauma > > iatrogenic trauma > nontraumatic (neoplastic process, spontaneous, congenital)

Question 409

409 What is the most common location for sinonasal CSF leaks to occur?

Answer 409

Ethmoid region (cribriform > lateral lamella) > sphenoid sinus (lateral > midline) > > frontal sinus

Question 410

410 What is the name given to the congenital dehiscence seen in some patients in the lateral sphenoid roof and is thought to be due to persistence of the lateral craniopharyngeal canal?

Answer 410

Sternberg canal

Question 411

411 Describe the reservoir sign.

Answer 411

A change in head position, generally leaning forward that results in a gush of fluid (CSF) collected in an anatomical depression or open sinus

Question 412

412 How much CSF is required to test for β-2 transferrin, a protein that is highly specific to CSF?

Answer 412

0.4 mL

Question 413

413 What imaging modality can demonstrate the site of a CSF leak in the absence of an obvious bony abnormality based on fine cut CT scanning?

Answer 413

CT cisternography (requires intrathecal contrast) Note: MRI cisternography using highly weighted T2 images does not require intrathecal contrast but does not demonstrate the bony anatomy.

Question 414

414 In a patient with an anterior skull base defect resulting in CSF rhinorrhea after blunt head trauma, what is the best first course of action?

Answer 414

Conservative management: stool softeners, bed rest, lumbar drain, and prophylactic antibiotics

Question 415

415 What are the potential side effects or complications associated with the use of low-dose intrathecal fluorescein?

Answer 415

In order of frequency (most to least):

• Fever, malaise
• Headache, back pain, neck pain
• Dizziness, nausea, vomiting
• Lower-extremity weakness

At higher doses, seizures and cranial neuropathies have been reported.

Question 416

416 What two grafting techniques can be used to repair skull base defects?

Answer 416

• Overlay: Graft material is placed over the defect on the sinonasal side.
• Underlay: Graft material is placed over the defect on the intracranial side.

The two techniques are often used in combination. Grafts may include mucosa, mucoperiosteum, bone, cartilage, synthetic material, vascularized local flaps, or free flaps.

Question 417

417 Which patient demographic is at highest risk for developing idiopathic intracranial hypertension, which is thought to be due to chronically elevated intracranial pressure?

Answer 417

Obese women of childbearing age. Recurrent disease is associated with the number of pregnancies. Note: This condition was reviously referred to as benign intracranial hypertension and pseudotumor cerebri.

Question 418

418 Describe the head and neck symptoms associated with idiopathic intracranial hypertension.

Answer 418

Headache, transient visual obscurations, papilledema, pulsatile tinnitus; no localizing signs with the exception of abducens nerve palsy

Question 419

419 In patients with known idiopathic intracranial hypertension and a history of recurrent CSF leak, what additional interventions can decrease the risk of recurrence?

Answer 419

• Weight loss
• Daily acetazolamide
• Ventriculoperitoneal shunt

Question 420

420 What are the three primary granulomatous diseases that can involve the nasal airway?

Answer 420

• Sarcoidosis
• Wegener granulomatosis (granulomatosis with polyangitis)
• Churg-Strauss syndrome

Question 421

421 What is the classic clinical triad seen in Wegener granulomatosis?

Answer 421

• Necrotizing granulomas of the respiratory tract (lung effected most commonly)
• Vasculitis
• Glomerulonephritis

Question 422

422 Describe the otolaryngologic manifestations of Wegener disease.

Answer 422

• Sinonasal: Obstruction, rhinorrhea, crusting, sinusitis, epistaxis, septal perforation, saddle-nose deformity
• Otologic: CHL with serous otitis media; less commonly, SNHL and vertigo
• Subglottic: Stridor, dyspnea, subglottic stenosis, crusting

Question 423

423 What are the nasal manifestations of Wegener granulomatosis?

Answer 423

Nasal inflammation, rhinorrhea, nasal crusting and purulence, CRS, septal perforation

Question 424

424 The antibodies used for diagnosis of Wegener granulomatosis are directed at what protein?

Answer 424

PR3

Question 425

425 What blood tests are highly sensitive for Wegener granulomatosis but if negative do not completely exclude the diagnosis?

Answer 425

c-ANCA, PR3 (most typical for Wegener, granulomatosis with polyangitis (GPA) Anti-myeloperoxidase (AMO); possibly more common with microscopic polyangiitis (MPA)

Question 426

426 What pathologic findings are seen on biopsies of a patient with Wegener granulomatosis?

Answer 426

• Necrotizing, noncaseating multinucleated giant cell granulomas
• Small and medium vessel vasculitis
• Microabscesses

Note: Biopsies are often nondiagnostic.

Question 427

427 What are the three systemic medications used to treat Wegener granulomatosis?

Answer 427

• Cyclophosphamide (used in severe cases)
• Methotrexate (used in limited Wegener granulomatosis)
• Glucocorticoids

Question 428

428 What is the cause of sarcoidosis?

Answer 428

Unknown. There is the potential for a genetic susceptibility that is triggered by exposure to an antigen (bacteria, virus, dust, etc). African Americans are 10 to 20 times more likely to be affected than are whites.

Question 429

429 What is the most common nasal symptom associated with sarcoidosis?

Answer 429

Nasal obstruction

Other symptoms include epistaxis, epiphora, nasal pain, and dyspnea. Nasal symptoms are present in < 5%.

Question 430

430 Where does sarcoidosis most commonly manifest in the nose?

Answer 430

Septum and inferior turbinates and commonly involved with thick crusting. At later stages, yellow subcutaneous nodules can be seen.

Question 431

431 What is the typical disease course of sarcoidosis?

Answer 431

• Spontaneous resolution within 2 years of disease onset
• ~ 10% → Progressive disease and pulmonary fibrosis

Question 432

432 What is the key histopathologic characteristic seen on nasal biopsy in a patient with sarcoidosis?

Answer 432

Noncaseating granulomas

Question 433

433 What laboratory test can be used in the diagnosis of sarcoidosis?

Answer 433

Serum angiotensin-converting enzyme (SACE)

Question 434

434 What percentage of patients with active sarcoidosis will have a positive SACE test?

Answer 434

~ 80%

Question 435

435 How is sarcoidosis most commonly systemically managed?

Answer 435

Medically with one or more of the following:

• Corticosteroids
• Antirejection medications
• Antimalarial medications
• Tumor necrosis factor (TNF)-α inhibitors

Rarely organ transplant can be considered.

Question 436

436 What is the treatment for sinonasal sarcoidosis?

Answer 436

Nasal saline irrigations and topical nasal steroids. Some advocate intralesional steroid injections. In acute exacer bations of aggressive disease, systemic corticosteroids should be administered.

Question 437

437 What is the clinical triad associated with Churg-Strauss syndrome?

Answer 437

• Asthma
• Systemic vasculitis
• Eosinophilia

Question 438

438 What are the three phases of Churg-Strauss syndrome?

Answer 438

• Prodromal or allergic phase: Adult onset asthma and allergic rhinitis
• Eosinophilic phase: Peripheral eosinophilia with variable organ involvement
• Vasculitic phase: Systemic vasculitis

Question 439

439 What are the criteria for the diagnosis for Churg-Strauss Syndrome?

Answer 439

Four of the following must be present in a patient with known vasculitis:

• Asthma
• More than 10% eosinophils in peripheral blood
• Neuropathy
• Pulmonary opacities on chest X-ray
• Sinonasal disease
• Biopsy of blood vessel showing eosinophil accumulation

Question 440

440 What is the management of sinonasal Churg-Strauss disease?

Answer 440

Nasal saline irrigations and topical nasal steroids, antibiotics as needed

Question 441

441 What are the two most common causes of midline granuloma syndrome?

Answer 441

• Wegener granulomatosis
• T-cell lymphoma

Improved diagnostic techniques have largely proven that these two are the only true diagnostic entities. Other older terms, such as malignant midline granuloma, lethal midline granuloma, and others, generally should not be used.

Question 442

442 Describe the typical clinical presentation of T-cell lymphoma as a midline granuloma.

Answer 442

• Most common in Asian men
• Associated with EBV
• Initial symptoms include nasal obstruction, drainage, pain, epistaxis, fatigue, weight loss, and potentially night sweats. May demonstrate external midface destructuring with advanced disease.

Question 443

443 What criteria are needed to make a diagnosis of relapsing polychondritis?

Answer 443

Michet et al criteria:

• Chondritis of two of three sites (auricular, nasal, or laryngotracheal) OR
• Chondritis of one of the above-listed sites, with two other features (ocular inflammation, seronegative inflammatory arthritis or vestibular dysfunction, hearing loss)

Question 444

444 What are the nasal symptoms commonly seen in 48 to 72% of patients with relapsing polychondritis?

Answer 444

• Acute and painful chondritis
• Sensation of fullness over the nasal bridge
• Mild epistaxis
• Long-standing disease → saddle-nose deformity

Question 445

445 What are the treatment options available for relapsing polychondritis?

Answer 445

● Immune-suppressing medications: Corticosteroids, dap sone, azathioprine, cyclophosphamide, cyclosporine, penicillamine ● Plasma exchange ● Airway surgery: Tracheostomy, tracheal stent placement, etc. ● Reconstructive surgery: Rhinoplasty for saddle nose can be considered if disease is well controlled.

Question 446

446 What are the clinical manifestations of anhidrotic ectodermal dysplasia?

Answer 446

Abnormal development of the skin, hair, nails, teeth, and sweat glands

Question 447

447 What is the method of inheritance associated with the most common form of anhidrotic ectodermal hypoplasia?

Answer 447

X-Linked recessive

Question 448

448 What triad is associated with anhidrotic ectodermal hypoplasia?

Answer 448

Anhydrosis, hypotrichosis, and anodontia Patients often have hypotrichosis, hypodontia, eczema, and atrophic rhinitis.

Question 449

449 What percentage of patients with primary ciliary dyskinesia will have situs inversus?

Answer 449

50%. May also have recurrent sinopulmonary infections and infertility

Question 450

450 Nasal biopsy followed by electron microscopy looking at the ultrastructure of the cilia is a useful test when looking for what disorder?

Answer 450

Ciliary dyskinesia. Looking at the number of inner and outer dynein arms and evaluating ciliary orientation can assist in differentiating primary from secondary causes.

Question 451

451 What nasal disorder results from hypertrophy of the sebaceous glands in both the nasal skin and fibrosis?

Answer 451

Rhinophyma

Question 452

452 Describe two early signs of rhinophyma.

Answer 452

● Dilated (patulous) pores ● Telangiectatic vessels on the distal nose

Question 453

453 Rhinophyma may manifest as the final stage of what other skin disease?

Answer 453

Acne rosacea, although not all patients with rhinophyma have a history of rosacea

Question 454

454 What malignant condition can be associated with rhinophyma?

Answer 454

Basal cell carcinoma

Question 455

455 What patient populations are affected by rhinophyma?

Answer 455

Although acne rosacea is more common in women (3:1) compared with men, rhinophyma almost always affects men (30:1). The disease typically afflicts white males in their 50s to 70s.

Question 456

456 How is rhinophyma managed?

Answer 456

Inflammation can be managed conservatively, similar to rosacea. For significant hypertrophy, deformity, and nasal obstruction, surgical recontouring can be performed using most commonly a carbon dioxide laser with or without dermabrasion.

Question 457

457 Rosacea is a chronic skin disorder that can appear with erythematotelangiectatic, papulopustular, phymatous, or ocular characteristics and is thought to be related to what underlying cause?

Answer 457

● Immune disorder ● Inflammatory reaction to infection (e.g., Demodex folli culorum, Bacillus olenorium, Helicobacter pylori) ● Other: UV radiation, vascular hyperreactivity, family history

Question 458

458 What is the infectious cause of rhinoscleroma, an infectious granulomatous disease that is endemic to Africa, southeast Asia, and Central America and affects the nasal cavity and occasionally the larynx, paranasal sinuses, and nasopharynx?

Answer 458

Klebsiella rhinoscleromatis (Frisch bacillus)

Question 459

459 What are the clinical stages associated with rhinoscleroma?

Answer 459

• Catarrhal (atrophic): Purulent rhinorrhea, rhinitis, honey nasal crusting
• Granulomatous (hypertrophic): Painless granulomatous nodules in the upper respiratory tract
• Sclerotic: Healing with extensive scar tissue formation and nasal stenosis

Question 460

460 Describe the histologic findings associated with rhinoscleroma.

Answer 460

Mikulicz cells (foamy histiocytes), and Russel bodies (intra cellular inclusions associated with excessive immunoglobu lin synthesis)

Question 461

461 What is the management of choice for treating rhinoscleroma?

Answer 461

Long-term culture-specific antibiotics and surgical debride ment

Question 462

462 What granulomatous infection is endemic to Africa, Pakistan, Sri Lanka, and India and manifests with strawberry-red, friable, polypoid lesions of the nose and eye causing nasal obstruction and epistaxis?

Answer 462

Rhinosporidiosis

Question 463

463 What is the agent responsible for rhinosporidiosis, and what is the primary means of transmission?

Answer 463

● Rhinosporidium seeberi ● Contaminated water

Question 464

464 What is the classic histopathologic finding(s) associated with rhinosporidiosis?

Answer 464

Fungal sporangia with chitinous elements in the setting of pseudoepitheliomatous hyperplasia and submucosal cystic structures

Question 465

465 How is rhinosporidiosis managed?

Answer 465

Surgical excision with close follow-up for recurrent lesions Note: Long-term treatment with dapsone has been effec tive. Other treatments that can be tried are local steroid injection, and antifungal agents

Question 466

466 What hypothesis postulates that the increase in allergic and atopic diseases in the world is secondary to reductions in infectious disease as well as cleaner environments that limit our exposure to common allergens when we are young and more likely to become tolerant to them rather than allergic?

Answer 466

Hygiene hypothesis

Question 467

467 What are the two phases of an allergic reaction?

Answer 467

Early and late responses

Question 468

468 What is the clinical term used to refer to patients who have a genetic predisposition toward developing an allergic response after exposure to an antigen?

Answer 468

Atopy

Question 469

469 What are the types of hypersensitivity reactions? (▶ Fig. 3.14; ▶ Fig. 3.15; ▶ Fig. 3.16; ▶ Fig. 3.17)

Answer 469

● Type I: Immediate/anaphylactic or antibody mediated ● Type II: Cytotoxic T-cell mediated ● Type III: Immune complex mediated ● Type IV: Delayed hypersensitivity

Question 470

470 What is another name for the hypersensitivity reactions?

Answer 470

Gell and Coombs classes

Question 471

471 Anaphylaxis is a form of what type of hypersensitivity reaction?

Answer 471

Type I, immediate or antibody-mediated

Question 472

472 What is the most important cytokine in the early or acute phase of a type I hypersensitivity reaction?

Answer 472

Histamine

Question 473

473 What is the predominant cell type during an early or acute phase type I hypersensitivity reaction?

Answer 473

Mast cells

Question 474

474 What is the predominant cell type during the late phase of a type I hypersensitivity reaction?

Answer 474

Eosinophils

Question 475

475 In what type of hypersensitivity reaction might you see a systemic hypersensitivity induced by an unknown factor that results in IgG- or IgM mediated cytotoxic action against an antigen located on the surface of a cell (or complement mediated lysis of the cell)?

Answer 475

Type II (cytotoxic) hypersensitivity

Question 476

476 In what hypersensitivity reaction are immune com plexes formed (IgG) as a result of the presence of drugs/bacterial products, which result in complement activation and a delayed (days) acute inflammatory reaction?

Answer 476

Type III (immune complex mediated) hypersensitivity

Question 477

477 In what hypersensitivity reaction do antigens directly stimulate T-cell activation and cell mediated inflammation resulting in dermatitis, granulomatous disease and some fungal disease?

Answer 477

Type IV (delayed) hypersensitivity

Question 478

478 What three cell types are required during the primary antigen exposure for the formation of antigen specific IgE antibody formation?

Answer 478

● Mast cells ● T cells (T-helper cells type 2 [TH2] pathway) ● B Cells

Question 479

479 After reexposure to an antigen, what is the result of antigen-specific IgE crosslinking on mast cell surfaces followed by release of preformed mediators (histamine, tryptase, chymase) and syn thesis of newly formed mediators (leukotrienes, prostaglandins, platelet activating factor, interleukins, etc) that results in allergic symptoms within minutes?

Answer 479

Early phase allergic response

Question 480

480 After reexposure to an antigen, what occurs after the release of newly generated inflammatory mediators that cause eosinophil, basophil, monocyte, and lymphocyte migration, infiltration, and cell-mediated inflammation, which can take hours (i.e., 3 to 12 hours) to occur and can last for up to or more than 24 hours?

Answer 480

Late-phase allergic response

Question 481

481 What is the definition of anaphylaxis?

Answer 481

A severe life-threatening generalized or systemic hyper sensitivity reaction that may involve urticaria, angioedema, bronchospasm, hypotension, and shock

Question 482

482 What are the criteria for diagnosing anaphylaxis?

Answer 482

● Criterion 1: Acute onset (minutes) of illness with involvement of skin, mucosa, or both with either respiratory compromise or hypotension ● Criterion 2: At least two of the following occurring within minutes of an exposure to a likely allergen: ○ Involvement of skin-mucosa tissue ○ Respiratory compromise ○ Hypotension ○ Persistent gastrointestinal symptoms ● Criterion 3: Hypotension after exposure to a known allergen for the patient

Question 483

483 What are the two most common causes of anaphylaxis?

Answer 483

● Foods ● Drug reactions

Question 484

484 What medication, not including antibiotics, most commonly causes drug-induced anaphylaxis?

Answer 484

ACE inhibitors

Question 485

485 A patient has multiple recurrent episodes of anaphylaxis with an unidentified cause. The patient states his allergist asked him to have a laboratory test in the emergency department the next time he had an episode of angioedema in an effort to confirm the diagnosis. What test does the allergist want, and when should it be drawn?

Answer 485

Serum tryptase. Serum tryptase peaks in 30 minutes and should be drawn within 3 hours of the start of the episode.

Question 486

486 What percentage of patients with anaphylaxis initially have cutaneous findings?

Answer 486

Greater than 90%

Question 487

487 What is the most common condition to be mistaken for anaphylaxis?

Answer 487

Vasodepressor reaction, usually triggered by trauma or stress and manifesting as flushing, pallor, weakness, diaphoresis, hypotension, and at times loss of conscious ness

Question 488

488 What is the initial treatment of a patient with anaphylaxis?

Answer 488

● Advanced cardiovascular life support (ACLS) protocol, and secure the airway if necessary ● Elevate lower extremities in recumbent position if possible ● Supplemental O2 (100%, 8 to 10 L by open face mask) ● Gain peripheral IV access (two large-bore IVs) → fluid resuscitation ● First-line medications: ○ Vasopressors (i.e., intramuscular epinephrine) if hypo tension is not responding ○ Second-line medications ○ IV H1- or H2-antihistamine (e.g., diphenhydramine 50 mg IV) ○ Nebulized ß2-adrenergic agonist ○ Administer corticosteroids (e.g., dexamethasone 8 to 10 mg IV) Remember, death can occur in minutes!

Question 489

489 What dose of epinephrine should be given during anaphylaxis to adults and children?

Answer 489

Intramuscular administration is preferred to subcutaneous: 1 mg/1 ml (1:1000), mid-outer thigh ● Adult: 0.3 to 0.5 mg ● Child: 0.01 mg/kg, maximum 0.5 mg Can repeat at 5- to 15-minute intervals Note: Autoinjectors generally have 0.3-mg doses for adults and 0.15-mg doses for children who weigh < 25 kg.

Question 490

490 What is the primary reason for administering an antihistamine to patients with anaphylaxis?

Answer 490

Resolution of cutaneous manifestations of anaphylaxis

Question 491

491 A patient taking what kind of class of drugs might be refractory to the treatment of anaphylaxis?

Answer 491

β-blockers

Question 492

492 What type of anaphylaxis results in recurrence of symptoms after the initial resolution of associated symptoms without any additional allergen exposure?

Answer 492

Biphasic anaphylaxis (23% of adults, 11% of children; generally 8 to 10 hours after initial reaction)

Question 493

493 What is the definition of angioedema?

Answer 493

Significant swelling of deep dermal or subcutaneous tissues; less often associated with pruritus and more commonly associated with burning or pain

Question 494

494 What is the most common cause of angioedema presenting to emergency departments today?

Answer 494

ACE inhibitors

Question 495

495 What is the cause of hereditary angioedema?

Answer 495

The condition is caused by high levels of activated C1 in the bloodstream secondary to deficiency of C1 inhibitor.

Question 496

496 What is the mechanism of inheritance of hereditary angioedema?

Answer 496

Autosomal dominant

Question 497

497 What is the treatment for hereditary angioedema?

Answer 497

Attacks usually spontaneously abate in 3 to 4 days. Many patients respond to androgen derivatives, such as danazol, that stimulate the production of C1 inhibitor and C4 but help even at levels that do not stimulate the production of these proteins. Purified C1 inhibitor is now starting to be used in Europe for acute attacks or monthly preventative therapy. Laryngeal involvement may not respond to subcutaneous epinephrine, and a tracheostomy may be needed.

Question 498

498 Inhalant allergens include proteins such as pollens, animal dander, and molds. How is an inhalant allergy classified in the United States, and based on the World Health Organization (WHO) ARAI (allergic rhinitis and its impact on asthma) guidelines?

Answer 498

U.S. Classification

• Seasonal allergy (outdoor allergen): Seasonal occurrence, winter/spring = tree, summer = grass, fall = mold
• Perennial allergy (indoor allergen): No consistent seasonal pattern, dust mites, animal dander, etc

WHO ARAI Guidelines

• Intermittent allergic rhinitis: Present < 4 d/wk, < 4 wks/yr
• Persistent allergic rhinitis: Present > 4 d/wk, > 4 wks/yr
• Mild: Does not impact quality of life or function
• Moderate/severe: Does impact quality of life or function

Question 499

499 During which seasons would you expect to see seasonal allergic rhinitis in response to the following inhalant allergens?

• Elm, birch, ash, oak, aspen, maple, box elder, hickory, sycamore, cedar, etc.
• Bermuda grass, Johnson grass, sweet vernal grass, Timothy grass, Orchard grass, etc.
• Ragweed, nettle, mugwort, sage, lamb’s quarter, goosefoot, sorrel, etc.

Answer 499

• Winter/spring (February-May)
• Late spring/summer (April-August)
• Late summer/fall (July to first hard frost)

Question 500

500 What are some measures to decrease exposure to house dust mite antigen?

Answer 500

● Wash bedding weekly at > 130°F ● Use impermeable covers over pillows and bedding ● Use hardwood flooring or laminates instead of carpet ● Keep humidity levels at less than 45%

Question 501

501 How long after removing a pet from a home can it take for the amount of allergen to decrease below clinically significant levels?

Answer 501

4 months

Question 502

502 What is the definition of urticaria?

Answer 502

Pruritic, erythematous cutaneous elevations that blanch with pressure

Question 503

503 What percentage of the general population will develop urticaria at some point in their lives?

Answer 503

10 to 20%

Question 504

504 A patient with aspirin-sensitive asthma and urticaria. In addition to NSAIDs, what chemical, used in foods, would you recommend they avoid as well?

Answer 504

Tartrazine (Yellow #5); as many as 15% of affected individuals also react to this.

Question 505

505 Infection with what pathogenic organism is most commonly associated with eosinophilia and urticaria?

Answer 505

Helminth infections such as Ascaris lumbricoides

Question 506

506 What is cold urticaria, and what should patients be warned to avoid?

Answer 506

Rapid swelling, erythema, and pruritus after exposure to cold objects or weather. It affects only the areas exposed to the cold. There have been reported deaths, secondary to hypotension, of people who swam in cold water.

Question 507

507 What clinical test might be used to determine whether a patient suffers from cold (temperature) urticaria?

Answer 507

Clinical history is most important. However, the ice cube test can be used to confirm the diagnosis. Place an ice cube on the forearm for 4 minutes, and then observe the area for 10 minutes. Symptoms should develop in 2 minutes.

Question 508

508 Stroking of the skin with a fingernail or tongue blade causes a wheal and flare reaction where the skin was touched. What is the diagnosis?

Answer 508

Dermatographism

Question 509

509 What form of allergy testing must be used in patients with dermatographism?

Answer 509

Radioallergosorbent test (RAST) or enzyme-linked immu nosorbent assay (ELISA)-based blood assays

Question 510

510 What is the treatment for dermatographism?

Answer 510

Patients are typically treated with diphenhydramine or hydroxyzine 25 to 50 mg daily. Use of second-generation antihistamines works for mild symptoms. Doses needed are typically two or three times the advised doses.

Question 511

511 A patient has a history of developing itchy red skin on any sun-exposed skin and intense hives if he or she spends any significant time in the sun. The patient does not report a similar reaction when exposed to heat not associated with sunlight. How is this type of reaction classified?

Answer 511

Solar urticaria is classified by the wavelength of light that causes immediate hypersensitivity.

Question 512

512 What immunoglobulin mediates most food allergies?

Answer 512

IgE

Question 513

513 Although it is no longer regularly used in the United States, what test can be used to look for eosinophils versus neutrophils in the nasal mucus in an effort to distinguish eosinophilic rhinitis from other rhinitis?

Answer 513

Nasal cytology

Question 514

514 Allergy testing to specific allergens can be done via which two broad techniques?

Answer 514

● In vivo (skin testing) ● In vitro (serum testing)

Question 515

515 What immunoglobulin is being tested for with in vivo skin testing?

Answer 515

Antigen-specific IgE

Question 516

516 What are the two most common locations for performing skin testing?

Answer 516

● Volar surface of the forearm ● Back

Question 517

517 What type of in vivo allergy test is performed using scratch, prick/puncture, or patch to challenge a patient by introducing allergen into the epidermis only?

Answer 517

Epicutaneous testing

Question 518

518 What type of in vivo allergy test is performed using intradermal techniques to place antigen into the superficial dermis?

Answer 518

Percutaneous testing

Question 519

519 What variables impact both epicutaneous and percutaneous skin testing?

Answer 519

● Age of the skin (very young and very old may be less sensitive) ● Area of the body being tested (sensitivity: upper back > lower back > upper arm > lower arm) ● Skin pigmentation (darker skin colors may be less sensitive) ● Concurrent medications ● Potency and biologic stability of the allergen test extract ● Dermatopathology: Dermatographism, eczema → con traindications, including degree of sensitization, recent anaphylaxis, recent exposure, prior immunotherapy

Question 520

520 During skin testing, what controls are commonly used

Answer 520

● Negative control: Glycerin-saline, saline, allergen diluent ● Positive control: Histamine (10 mg/mL)

Question 521

521 During skin testing, what term is used to describe the white (blanched) raised area at the site of the allergen application?

Answer 521

The area of erythema that extends beyond this raised region? Wheal Flare

Question 522

522 Why is scratch testing (small superficial lacerations made in the skin, a drop of concentrated antigen then applied) not recom mended for skin testing?

Answer 522

Poor reproducibility, variable sensitivity, poor specificity, frequent false-positives, painful, and reaction may be due to trauma to skin instead of reaction to allergen

Question 523

523 During an in vivo epicutaneous allergy test, a drop of antigen is placed on the patient’s skin. The tester then uses a needle, lancet, or prick device (single or multiple tines) to puncture or prick the skin through the drop of antigen and deliver the antigen to the epidermis. What is this called?

Answer 523

Skin-prick or puncture testing. It is the most commonly used test.

Question 524

524 What instrument(s) can be used to perform a skin prick or puncture test?

Answer 524

Hypodermic needle, solid-bore needle, lancet ± bifurcated tip, multiple-head devices (more commonly used because of OSHA concerns regarding inadvertent health care worker needle sticks) Pass through the droplet, then the skin at a 45- to 60- degree angle to the skin, lift and break the skin without causing bleeding for the prick test; or the skin device can be passed through the drop at a 90-degree angle to the skin for puncture test.

Question 525

525 After performing a skin prick or puncture, how long should you wait before assessing the response?

Answer 525

15 to 20 minutes

Question 526

526 How can you assess the allergic response to a skin test (epicutaneous or percutaneous)?

Answer 526

Direct measurement: Recommended scoring system ● Longest diameter or longest diameter and orthogonal diameter (perpendicular) of wheal in millimeters ● Presence or absence of flare and size in millimeters as in preceding ● Presence or absence of pseudopods Classically based on a 0 to 4 + system: Based on wheal and flare compared with the negative control and the presence or absence of pseudopods Subjective analysis is no longer recommended by the American Academy of Allergy, Asthma and Immunology because of interphysician variability in scoring and inter pretation.

Question 527

527 The American Academy of Allergy, Asthma, and Immunology guidelines for skin testing recommend that wheals < 3 mm should not be considered positive. Why?

Answer 527

Trauma can affect wheal size.

Question 528

528 What are the major disadvantages to skin-prick tests?

Answer 528

• Semiqualitative (less objective than intradermal testing).
• Low degrees of sensitivity may be missed → false-negative results.

Question 529

529 When should you use an intradermal/ percutaneous allergy test?

Answer 529

When the primary goal of testing is increased sensitivity, or for evaluating drug or venom anaphylactic reactions

Question 530

530 Describe the technique used for single dilutional intradermal (percutaneous) allergy testing.

Answer 530

1. Using a small needle (generally 26- or 27-gauge needle at 45-degree angle), inject 0.02 to 0.05 mL of antigen diluted to 1:500 to 1:1000 weight/volume intradermally (create a 2- to 3-mm bleb in dermis). 2. Positive control: Histamine (0.001 mg/mL) if needed; can be excluded if reaction was proven by prick testing. Negative control also performed. 3. Wait 10 to 15 minutes, and then assess response.

Question 531

531 What is the major risk in using intradermal allergy testing, and how can this risk be decreased?

Answer 531

Significant systemic reaction (anaphylaxis). Patients should be screened with prick/puncture testing initially. They can also be screened with very dilute concentrations adminis tered intradermally.

Question 532

532 What part of the body is commonly used for intradermal testing and why?

Answer 532

Volar surface of the forearm. To allow a tourniquet to be placed in case of systemic symptoms

Question 533

533 True or False. Single-dilution intradermal skin testing is more specific than it is sensitive.

Answer 533

False. High sensitivity, less specificity. It has a higher false positive rate than skin prick testing.

Question 534

534 What type of allergy test requires the sequential administration of fivefold-diluted antigens intradermally, beginning with dilute concentrations?

Answer 534

Intradermal dilutional testing, also called skin endpoint titration

Question 535

535 What does the American Academy of Allergy, Asthma and Immunology recommend as a starting dose of intracutaneous extract solution in patients with a preceding negative prick test?

Answer 535

100- to 1000-fold dilutions of the concentrated extracts used for prick/puncture tests.

Question 536

536 What size needle/syringe is recommended during intradermal dilutional testing?

Answer 536

0.5- or 1.0-mL syringe with a 26- to 30-gauge needle (can come as a single unit)

Question 537

537 What volume of antigen concentrate should be injected during intradermal dilutional testing?

Answer 537

0.01 mL (Goal is to create a 4-mm round wheal.)

Question 538

538 After injection of 0.01 mL and creation of a 4-mm wheal, you appropriately wait 10 minutes to measure the final wheal. If the injected solution was inert diluent, what diameter do you expect based on passive physical diffusion in the skin?

Answer 538

5 mm

Question 539

539 What is required for a whealing response to be considered positive during intradermal dilutional testing?

Answer 539

A final wheal size of 7 mm, which is 2 mm larger than the expected size at 10 minutes from physical diffusion alone. Flare is not measured during this type of testing. This topic is somewhat controversial, as many practitioners use 3 mm.

Question 540

540 During intradermal dilutional testing, you note that the no. 6 dilution produces a 5-mm wheal after 10 minutes. You then inject the no. 5 dilution and again note a 5-mm wheal after 10 minutes. You therefore inject the no. 4 dilution and note a 7-mm wheal. What should you do?

Answer 540

The no. 4 dilution demonstrated progressive whealing, so you must perform a confirmatory wheal by injecting the no. 3 dilution. If this is > 7 mm, it would suggest progressive whealing, and the no. 4 dilution would be considered the end point of the examination. A confirmatory wheal must grow by at least 2 mm.

Question 541

541 Describe the technique used for intradermal dilutional testing.

Answer 541

● Dilutions created and labeled as no. 1 to no. 6, with no. 6 representing the weakest concentration and the least likely to induce a response ● Inject a negative control: 4 mm wheal → 5 mm or less. ● Inject a positive control (histamine: 0.0004 mg/mL): 4- mm wheal → 7 mm or more ● 0.01 mL of the no. 6 dilution is injection intradermally to create a 4-mm wheal ● Wait 10 minutes. ● If the wheal is 5 mm, it is considered negative. If it is 7 mm or larger, it is considered positive. Continue with dilution no. 5. ● If at any dilution you note growth of the wheal > 2 mm over the negative wheal (so 7 mm or more), continue with the next dilution. ● It the next dilution demonstrates progressive growth (an additional 2 mm), stop the test. The first wheal to demonstrate growth is the endpoint dilution, and the second dilution to demonstrate progressive whealing is the confirmatory wheal.

Question 542

542 After a positive fivefold sequential intradermal dilutional testing, what dilution should be used as a safe starting point for immunotherapy?

Answer 542

The endpoint dilution (the wheal that initiated progressive whealing)

Question 543

543 What test uses skin-prick/puncture testing to determine the approximate degree of allergic sensitization, followed by specific sequential intradermal dilutional tests to assess further the prick/puncture results and to determine an endpoint dilution that can be used for initiating immunotherapy?

Answer 543

Modified quantitative testing (MQT)

MQT is Frequently used by otolaryngologists practicing in the allergy field. It is used for its reproducibility, decreased cost, high sensitivity and specificity, and excellent correla tion with full intradermal dilutional testing batteries.

Question 544

544 Describe the technique used when performing a modified quantitative test for allergic disease?

Answer 544

• Use mutlitest (a device with multiple skin prick/puncture device).
• Wait 20 minutes.
• Wheal < 3 mm → Place no. 2 dilution in upper arm. → Wait 10 minutes → assess wheal
  
  • ≤ 6 mm = Negative
  • ≥ 7 mm = Endpoint: no. 3 dilution
  • Wheal 3 to 8 mm → place no. 5 dilution in upper arm.
• → Wait 10 minutes → assess wheal:
  
  • ≤ 5 mm = Endpoint: no. 4 dilution
  • 7 to 8 mm = Endpoint: no. 5 dilution
  • ≥ 8 mm = Endpoint: no. 6 dilution
  • Wheal ≥ 9 mm = Endpoint: no. 6 dilution

Question 545

545 What medications can suppress the wheal and flare response for 48 to 72 hours?

Answer 545

First-generation antihistamines (i.e., brompheniramine, chlor pheniramine, clemastine, diphenhydramine, hydroxyzine)

Question 546

546 Which medications should be avoided for 7 days because of suppression of the wheal and flair response?

Answer 546

Second-generation antihistamines and tricyclic antidepres sants

Question 547

547 What are the second-generation antihistamines that should be avoided at least 7 days before skin testing?

Answer 547

Cetirizine, loratidine, fexofenadine, levocetirizine. Note: Desloratidine should be avoided for > 14 days.

Question 548

548 True or False. Leukotriene receptor antagonists should always be stopped at least 7 days before to skin testing.

Answer 548

False. They have not been shown to routinely inhibit wheal and flare response. They can be stopped in individual patients in whom the wheal and flare response is thought to be impacted by the medication.

Question 549

549 What impact do intranasal or systemic corticosteroids have on the wheal and flare response during skin testing?

Answer 549

Little to none

Question 550

550 To resuscitate a patient adequately in the unlikely event he or she develops anaphylaxis after skin testing in your office, what medication(s) should be stopped?

Answer 550

β-blockers (both topical and systemic)

Question 551

551 What test measures serum concentrations of allergen-specific IgE antibodies?

Answer 551

RAST and modified RAST (has better sensitivity and more consistent scoring but is based on the original RAST immunoassay)

Question 552

552 Describe the steps involved in the original RAST immunoassay?

Answer 552

● Allergen-bound paper disk is placed in test tube. ● Patient’s serum is added and antigen-specific IgE binds the antigen. ● Excess serum and IgE are washed away. ● Radiolabeled anti-IgE antibodies are added to the test tube and bind the antigen-specific IgE already bound to antigen on the paper disk. ● Excess is washed away. ● Gamma counter is used to determine the amount of bound IgE.

Question 553

553 What are the benefits of immunoassay testing for allergic disease over skin testing?

Answer 553

Condition of skin does not matter, the results are not affected by drugs, no risk of anaphylaxis, greater patient convenience, quality control is easier, allows for quantitative assessment in preparation for immunotherapy, greater specificity. It may be less sensitive and is more expensive.

Question 554

554 What are the benefits of skin testing over immunoassay for allergic disease?

Answer 554

Less time and expense to perform, increased sensitivity, wider variety of antigens to test, faster results

Question 555

555 What level of total IgE in a patient’s serum is suggestive of allergy?

Answer 555

> 200 IU. However, lower concentrations do not rule out allergy.

Question 556

556 When should in vitro studies be recommended?

Answer 556

Patient is uncomfortable undergoing skin testing. Patient is not responding to medical therapy or doing poorly on immunotherapy. Patient is unable or unwilling to stop taking antihistamines, tricyclic antidepressants, or β-blockers. Patient has eczema or dermatographism. Patient has venom sensitivity Patient has possible IgE-mediated food sensitivity.

Question 557

557 During a nasal provocation test, a patient is exposed to an allergen to determine whether exposure to a clinically significant allergen results in symptoms. The outcome can be measured based on symptoms and what other diagnostic tool?

Answer 557

Rhinomanometry

Question 558

558 What are the three main strategies used to manage allergy?

Answer 558

● Environmental modification ● Pharmacotherapy ● Immunotherapy

Question 559

559 What drug class works on H1 receptors as antago nists, is most effective in treating early phase allergic response related symptoms and can cause sedation as a major side effect?

Answer 559

Antihistamines

Question 560

560 Why do first-generation antihistamines result in sedation, psychomotor impairment, and central nervous system suppression?

Answer 560

They are highly lipophilic and cross the blood brain barrier.

Question 561

561 In addition to sedation, what two side effects should be considered when prescribing first generation antihistamines?

Answer 561

● Anticholinergic side effects (i.e., urinary retention, dry mucous membranes, constipation, etc.) ● Tachyphylaxis

Question 562

562 Why are second-generation antihistamines currently preferred?

Answer 562

● Lipophobic → Do not cross the blood-brain barrier ● Fewer or no anticholinergic side effects ● Less or no tachyphylaxis

Question 563

563 Provide examples of systemic first-generation antihistamines.

Answer 563

● Diphenhydramine ● Chlorpheniramine ● Azatadine ● Hydroxyzine ● Tiprolidine ● Brompheniramine. ● Clemastine (Tavist)

Question 564

564 Provide examples of systemic second-generation antihistamines.

Answer 564

● Desloratidine* (Clarinex) ● Loratidine (Claritin) ● Fexofenadine* (Allegra) ● Cetirizine (Zyrtec) ● Levocetirizine* (Xyzal) * Can be considered third-generation antihistamines.

Question 565

565 Name two second-generation topical antihistamines that have relatively rapid onset and effectiveness in treating congestion.

Answer 565

● Azelastine ● Olopatadine

Question 566

566 What drug class works primarily as α1-receptor agonists resulting in vasoconstriction?

Answer 566

Decongestants

Question 567

567 What are the primary side effects associated with systemic decongestants such as phenylephrine and pseudoephedrine?

Answer 567

● α-Adrenergic side effects: Hypertension, increased ap petite, tachycardia, arrhythmia ● Tachyphylaxis (rebound rhinitis)

Question 568

568 Name four medications that function as topical decongestants.

Answer 568

● Tetrahydrozoline ● Naphazoline ● Oxymetazoline ● Phenylephrine

Question 569

569 What condition can occur as a result of tachyphylaxis associated with topical decongestants when used for as little as 3 days?

Answer 569

Rhinitis medicamentosa

Question 570

570 What are the three most commonly used oral corticosteroids for allergic rhinitis, which function to decrease the inflammatory reaction in as little as 12 to 24 hours?

Answer 570

● Prednisone ● Methylpredisolone ● Dexamethasone

Question 571

571 What is the only topical corticosteroid nasal spray that is pregnancy class B?

Answer 571

Budesonide (Rhinocort Aqua)

Question 572

572 What intranasal topical corticosteroids are commonly used?

Answer 572

● Budesonide (Rhinocort Aqua) ● Triamcinolone acetate (Nasacort) ● Fluticasone propionate/furoate (Flonase/Veramyst)* ● Mometasone furoate (Nasonex)* ● Ciclesonide (Omnaris) ● Flunisolide (Nasarel) *Onset of action within 12 hours

Question 573

573 Which intranasal corticosteroids are approved for patients as young as 2 years of age?

Answer 573

Mometasone furoate and fluticasone furoate

Question 574

574 What side effect of intranasal corticosteroids has been related to drying and thinning of the nasal mucosa and can be related to improper intranasal application?

Answer 574

Epistaxis

Question 575

575 What intranasal topical medication can be used prophylactically to stabilize mast cell degranulation, is well tolerated due to low systemic absorption (lipophobic), but must be redosed multiple times per day (short half-life)?

Answer 575

Cromolyn sodium

Question 576

576 Name the leukotriene receptor antagonist that is approved for allergic rhinitis and can be used in children as young as 6 months.

Answer 576

Montelukast

Question 577

577 What conditions have been shown to benefit from immunotherapy?

Answer 577

Allergic rhinitis, allergic conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Potential uses include preven tion of asthma in patients with allergic rhinitis and manage ment of atopic dermatitis and aeroallergen sensitization.

Question 578

578 For a patient to be considered for immunotherapy, what conditions must be met?

Answer 578

The allergen must cause clinically significant symptoms, and allergen-specific IgE must be demonstrated through in vivo or in vitro testing. Environmental avoidance and medical management should have been optimized.

Question 579

579 What are the contraindications for immunotherapy?

Answer 579

● Non-IgE mediated symptoms ● Symptoms controlled with maximal medical treatment and environmental avoidance ● Atopic dermatitis (small studies suggest some benefit if induced by aeroallergens) ● Food allergy ● Allergies related to very short seasonal allergen exposure ● Poorly controlled asthma ● Use of β-blockers

Question 580

580 Describe the major impact(s) immunotherapy has on the immune system resulting in allergic tolerance and decreased associated symptoms over time.

Answer 580

● Increase in the number of TH2 cells and increased numbers of T reg cells. ● Increase in IL-10 and IL-12, decrease in IL-4 and IL-5 ● Decreased release of early and late phase inflammatory mediators. ● Decreased migration of inflammatory cells ● Suppression of antigen-specific IgE over time following initial rise ● Increased levels of IgG4 (blocking antibody vs. T-helper regulatory cell)

Question 581

581 What is the length of time normally required for immunotherapy to achieve good effect?

Answer 581

3 to 5 years

Question 582

582 What technique is used to administer gradually increasing concentrations of allergy-provoking antigen over time to the patient in an effort to modulate allergen-specific immune reactions and symptoms via subcutaneous injection?

Answer 582

Subcutaneous immunotherapy (SCIT)

Question 583

583 When choosing a starting dose for SCIT, what two goals should be achieved?

Answer 583

● Strong enough concentration to induce rapidly an antigen-specific response ● Not strong enough to induce a significant local or systemic reaction

Question 584

584 What dose is considered the maximum dose that can be delivered without inducing significant local or systemic effects?

Answer 584

Maintenance dose (delivers a goal cumulative amount of antigen over 3 to 5 years; should control symptoms for 1 week)

Question 585

585 Describe the process of dose escalation from a starting dose (generally chosen based on modified quantitative testing) to a maintenance dose.

Answer 585

● Increase antigen load by 0.05 to 0.10 mL weekly (safe). ● Increase antigen load by 0.05 to 0.10 mL twice weekly in healthy patients (no significant asthma or history of anaphylaxis). ● Once maintenance dose is achieved, space injections from weekly or biweekly to every 2 to 3 weeks, then every 6 to 12 months (assuming symptoms are con trolled) for 3 to 5 years. ● Treatment can be discontinued after 3 to 5 years, with careful observation for recurrent symptoms.

Question 586

586 What might result in an unexpected systemic or significant local reaction during immunotherapy?

Answer 586

● Wrong patient ● Wrong concentration ● Administering the immunotherapy during a time of year with increased environmental allergen load ● Upper or lower respiratory tract infection ● Asthma, poorly controlled ● Drug allergy

Question 587

587 True or False. Successful immunotherapy will elimi nate the need for any adjuvant medical therapy and should stop any breakthrough symptoms.

Answer 587

False. Some breakthrough symptoms are expected, and medications may be necessary to augment the immuno therapy effect even when successful.

Question 588

588 Describe the grading system used by the World Allergy Organization for systemic complications related to SCIT.

Answer 588

World Allergy Organization Grade I: One organ system ● Cutaneous ○ General pruritis, urticaria, flushing, sensation of heat or warmth ○ Angioedema (not laryngeal, tongue, or uvular) ● Upper respiratory ○ Rhinitis (sneezing, rhinorrhea, nasal pruritis, and/or congestion) ○ Throat clearing (itchy throat) ○ Cough (not lower airway) ● Conjunctival ○ Erythema ○ Pruritis ○ Tearing ● Other ○ Nausea ○ Metallic taste ○ Headache Grade II: More than one organ system ● Lower respiratory ○ Asthma (cough, wheeze, shortness of breath) ○ A drop of < 40% in peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) ○ Responsive to bronchodilators ● Gastrointestinal ○ Abdominal cramps, vomiting, diarrhea ● Other ○ Uterine cramps Grade III: More than one organ system ● Lower respiratory ○ Asthma ○ A drop of 40% or more in PEF or FEV1 ○ Not responsive to bronchodilators ● Upper respiratory ○ Laryngeal, uvular, or tongue edema with or without stridor Grade IV: More than one organ system ● Lower or upper respiratory ○ Respiratory failure with or without loss of conscious ness ● Cardiovascular ○ Hypotension with or without loss of consciousness Grade V: Death Note: Many patients report a sense of impending doom with worsening complications.

Question 589

589 What form of immunotherapy relies on fixed or escalating-dose schedules for antigen administered sublingually or orally with the goal of decreasing allergic symptoms, modulating the immune system, and providing a safe and easy method for immunotherapy?

Answer 589

Sublingual immunotherapy (SLIT). Used in Europe. Currently, SLIT is used off-label in the United States as a physician-prepared serum (similar to that given subcutaneously) and is not covered by third-party payers.

Question 590

590 True or False. Sublingual immunotherapy has pre dominantly been used for single antigen therapy.

Answer 590

True

Question 591

591 What are the two major types of immunity? (▶ Fig. 3.18)

Answer 591

● Innate (nonspecific): First line of defense; antigen independent, immediate maximal response, no immu nologic memory ● Adaptive (specific immunity): Antigen dependent, delayed maximal response, immunologic memory, lymphocytes and lymphocyte-derived immunity

Question 592

592 What are the three major components of innate (nonspecific) immunity?

Answer 592

● Anatomical boundaries: Epithelium; mechanical move ment and trapping from cilia, tears, saliva, and mucus; competition from normal flora ● Humoral barrier: Cytokine system, complement system, coagulation; fatty acids, lysozyme, lactoferrin, transferrin, phospholipase, defensins, surfactants, IL-1, TNF-α, inter ferons (IFNs) ● Cellular barrier: Polymorphonuclear cells, macrophages, NK cells, and eosinophils

Question 593

593 In what type of immunity do toll-like receptors coordinate the responses of cytokine-complement phagocytic responses?

Answer 593

Innate (nonspecific) immunity

Question 594

594 How do NK cells differ from NK T cells?

Answer 594

They are part of the innate immune system but can participate in the adaptive immune response. They arise from the lymphoid progenitor cell, which gives rise to T and B cells, do not have common T cell–specific markers (CD3, TCR, MHC, etc), they express CD-16, CD-56, and often CD8. They can be activated by IFN to target virally infected or tumor formation within 3 days based on the absence of “self” markers.

Question 595

595 The anti-tumor effect of NK cells is thought to be due to their unique ability to recognize what?

Answer 595

The absence of self. Although T cells and many other immune effector cells are programmed to recognize nonself proteins produced by viruses or bacteria, NK cells have the ability to recognize when self peptides and proteins have been downregulated as a result of tumor transformation or what might be seen with viral infections. The most commonly encountered down regulated self molecule that might be “recognized” by NK cells are MHC molecules.

Question 596

596 The adaptive immune system reacts specifically to individual antigens (proteins, polysaccharides, or macromolecules). What is the region of the antigen that is recognized by antigen-specifc receptors (T and B cells) and immunoglobulins within the adaptive immune system called?

Answer 596

Epitope (determinant)

Question 597

597 What is the term that defines the ability of a host to ignore self and demonstrate immunologic unre sponsiveness to self for both innate and adaptive immune responses?

Answer 597

Tolerance

Question 598

598 Name the two subtypes of adaptive immunity.

Answer 598

. ● Humoral immunity → B cells, antibodies ● Cell-mediated → T cells, cytokines

Question 599

599 Describe the three basic steps of adaptive immunity.

Answer 599

● Recognition of antigen ● Lymphocyte activation → production of cytokines, cytokine receptors, and other proteins; clonal expansion of lymphocytes; cellular differentiation (i.e., B cell into plasma cell) ● Removal of the offending antigen (clearance)

Question 600

600 What are the primary lymphoid organs?

Answer 600

● Thymus ● Bone marrow

Question 601

601 What are the secondary lymphoid organs, and what is their purpose?

Answer 601

● Systemic (spleen and lymph nodes) ● Mucosal immune system (tonsils, Peyer patches, intra epithelial lymphocytes, lamina propria of mucosal tissues) ● Cutaneous immune system

Question 602

602 Where do myeloid (erythrocytes, neutrophils, platelets, basophils, eosinophils, monocytes/macro phages, and dendritic cells) and lymphoid cells (T cells, B cells, NK cells, plasma cells) arise from?

Answer 602

Bone marrow

Question 603

603 Name the immature dendritic cell found in the skin and mucosa that contains Birbeck granules, is most prominent in the stratum spinosum of the skin, and is involved in antigen processing.

Answer 603

Langerhans cells

Question 604

604 Name the specialized mucosal immune cell that is responsible for transocytosis (pinocytosis) of antigens across the follicular epithelium to germinal centers within Peyer patches within tonsillar tissue.

Answer 604

M (microfold) cells

Question 605

605 Immune responses to hematogenous antigens and encapsulated organisms occur predominantly in the spleen, where lymphoid follicles surround small arterioles forming what structure?

Answer 605

Periarteriolar lymphoid sheaths

Question 606

606 Lymphocytes can be identified by what specialized molecules on their surface that can help other cells (and researchers/clinicians) recognize their level of maturity, lineage, and extent of immune activation?

Answer 606

Cluster of differentiation (CD) markers

Question 607

607 Name the cell associated with the following CD markers: ● CD2 ● CD3 ● CD4 ● CD8 ● CD25

Answer 607

● All T cells ● All T cells ● TH1 or TH2 cells ● T-suppressor cells (cytotoxic T cells) ● + CD4 = TH17 or T regulatory cells

Question 608

608 What cell is required to undergo maturation in the thymus, and what are the possible outcomes of differentiation?

Answer 608

T cells differentiate in the thymus via both positive and negative differentiation:

• Apoptosis
• CD4 + helper T cell
• CD8 + precytotoxic T cell

Question 609

609 What percentage of CD4 + and CD8 + T cells survive selection in the thymus?

Answer 609

Less than 5%; most say 2% or less

Question 610

610 Where does negative selection of developing T cells occur?

Answer 610

Thymic medulla

Question 611

611 The process by which developing T cells that react too strongly with self peptides are deleted is called what?

Answer 611

Negative selection

Question 612

612 What is the process called by which developing T cells that react appropriately with self peptides are signaled to survive and continue to develop?

Answer 612

Positive selection

Question 613

613 What cell type is stimulated to develop from naïve CD4 cells (TH0) by intracellular pathogens and IL12 and subsequently inhibits B cells, produces INF-γ and IL2, and stimulates cell-mediated immunity (activates cytotoxic CD8 cells, etc)?

Answer 613

TH1 cells

Question 614

614 What cell type is stimulated to develop from naïve CD4 cells (TH0) by allergens and IL-4 and subse quently recruits/activates eosinophils, activates B cells; produces IL-4, IL-5, IL-6, IL-10, and IL-13; and is involved in both allergic disease and humoral immunity?

Answer 614

TH2 cells

Question 615

615 How does the immunologic T-cell response to oral antigens differ compared with more systemic responses?

Answer 615

Oral antigens are more likely to induce T-cell anergy or T cell tolerance than T-cell activation.

Question 616

616 What are the two types of MHC molecules?

Answer 616

• MHC Class I: Display self and nonself antigens (8–10 amino acids), membrane associated glycoprotein.
• MHC Class II: Display extracellular proteins (various length, generally longer, 18 to 20 amino acids) that are phagocytosed and processed intracellularly before presentation

Question 617

617 What type of MHC molecules are expressed by almost all nucleated cells and when downregulated can result in targeted destruction by NK cells and present endogenous antigen?

Answer 617

MHC class I

Question 618

618 What type of MHC molecules are expressed primarily on antigen-presenting cells and lymphocytes (B cells, macrophages, endothelial cells, or dendritic cells primarily) and present processed exogenous antigen?

Answer 618

MHC class II

Question 619

619 What type of T cell recognizes antigen presented by MHC class II molecules?

Answer 619

TH cells (CD4 +)

Question 620

620 What type of T cell recognizes antigen presented by MHC class I molecules and kills cells presenting that antigen?

Answer 620

Cytotoxic T cells (CD8 +)

Question 621

621 What are the components of MHC molecules?

Answer 621

• Extracellular peptide binding region
• Pair of Ig-like domains (bind CD4 and CD8)
• Transmembrane region
• Cytoplasmic tail

Question 622

622 To activate TH cells, antigen-presenting cells must present antigen via an MHC class II molecule, as well as secrete which important cell signal?

Answer 622

IL-1

Question 623

623 Which cells secrete antibodies, and how are they activated?

Answer 623

B cells phagocytose antigen and present it to TH cells via MHC class II molecules. T-cell then stimulates the B cell via IL-2 and IL-4 to mature into an Ig-producing plasma cell. Alternatively, large antigens can crosslink enough B-cell receptors to lead to direct activation of the cells and antibody production.

Question 624

624 What cell type can be identified by the CD markers 19 and 21?

Answer 624

B cells

Question 625

625 How is antibody isotype switching induced in B cells?

Answer 625

B cells encounter antigen and migrate out of follicles to a B cell-T cell interface, where they encounter activated TH cells. The B cells present their processed antigen in the context of MHC class II recognized by the T-cell receptors. The costimulatory molecule CD40 L interacts with the CD40 receptor, providing survival signals and isotype switching. The type of cytokine environment encountered at the time this is happening helps determine which isotype is then secreted.

Question 626

626 What glycoprotein molecules are produced by plasma cells in response to humoral immune stimulation?

Answer 626

Immunoglobulins

Question 627

627 What are the basic functions of immunoglobulins?

Answer 627

1. Antigen binding
2. Effector functions: complement fixation, neutralization, or antibody-dependent cellular cytotoxicity via opsonization (“tagging” an antigen for ingestion and destruction by a phagocyte), stimulation of phagocytosis, etc.

Question 628

628 What is the basic structure of an immunoglobulin?

Answer 628

Four chains (two heavy, two light), variable regions (bind antigen), constant regions, and hinge regions

Question 629

629 What component of an immunoglobulin molecule is responsible for most of the effector functions of an antibody?

Answer 629

Fc domain of the antibody

Question 630

630 What component of an immunoglobulin molecule is responsible for the specificity of antibodies?

Answer 630

Variable region of the antibody

Question 631

631 Cleavage at the hinge region of an immunoglobulin results in production of what three fragments?

Answer 631

• 1–2. Fab fragments: Two identical fragments that contain the light chain and the variable and first constant domain of the heavy chains; binds antigen
• 3. Fc fragments: One fragment containing the remaining heavy chains and their constant regions; may stimulate complement

Question 632

632 What are the five classes of immunoglobulins produced in the body, which vary based on the amino acid sequences in the constant region of the heavy chain?

Answer 632

• IgA (serum, monomer; secretions, dimer)
• IgD (monomer)
• IgE (monomer)
• IgG (monomer)
• IgM (pentamer)

Question 633

633 Which immunoglobulin makes up more than 70% of the total body immunoglobulin (only 15% of serum immunoglobulin), is found in mucosal secretions (nasal, pulmonary, lacrimal, salivary, colostrum, sweat, GI tract, and genitourinary), and is important in preventing microrganisms from invading the body?

Answer 633

IgA

Question 634

634 How do IgA molecules primarily mediate mucosal immunity?

Answer 634

They are weak activators of complement and mediate their affects primarily via neutralization of antigen and prevention of systemic access.

Question 635

635 What are the two subclasses of IgA?

Answer 635

• IgA1 (~85% serum): Strong immune response to protein antigens. Some response to polysaccharide and lipopolysaccharides
• IgA2 (~15% serum): Key player in defense against mucosal invasion via immune response to polysaccharide and lipopolysaccharide antigens

Question 636

636 What are the two forms of IgA found in the body?

Answer 636

• Monomeric serum IgA: Fc portion binds phagocytic cells, stimulating ingestion and destruction.
• Dimeric secretory IgA: Two IgA molecules + J (joining) chain and a secretory piece; secreted by plasma cells located below the basement membrane of the basement epithelial surfaces

Question 637

637 How does IgA gain access to extravascular secretions and tissues?

Answer 637

IgA is produced in a monomeric form and is joined with a J chain to form a dimer that is too large to diffuse across cellular membranes. The IgA dimer binds to polymeric IgA receptors on cells, which results in endocytosis and passes through the cell. The immunoglobulin is secreted on the luminal side of the cell still attached to the receptor. The receptor is then degraded, and the IgA molecule is free to diffuse throughout the lumen.

Question 638

638 Which immunoglobulin deficiency is largely asymptomatic, correlating with the poorly under stood function of its associated monomeric glycoprotein?

Answer 638

IgD

Question 639

639 What is the structure of IgM?

Answer 639

IgM is a pentamer made up of five immunoglobulin subunits linked by a J chain.

Question 640

640 What immunoglobulin is produced first in a humoral immune response and is excellent at binding complement?

Answer 640

IgM

Question 641

641 What monomeric immunoglobulin is implicated in allergic responses to environmental allergens?

Answer 641

IgE

Question 642

642 What conditions can lead to high levels of IgE antibodies?

Answer 642

Allergic diseases, lymphoma, IgE myeloma, systemic parasitosis, tuberculosis, HIV infection, Churg-Strauss, among others

Question 643

643 Which monomeric immunoglobulin class is the most prevalent both in the serum and in extravascular spaces, is the only immunoglobulin to cross the placenta; play an important role in immunologic memory; and function to fix complement and activate macrophages, monocytes, polymorphonuclear cells, and some lymphocytes via opsonization?

Answer 643

IgG

Question 644

644 Describe the function of the four IgG subclasses, which are divided based on structural variation of the Fc and hinge region, as well as the difference in number of disulfide bonds.

Answer 644

• IgG1 (60 to 70%): Opsonization, strong C1q binding, and classic complement cascade activation, response to protein and viral antigens
• IgG2 (20 to 30%): Opsonization, weak C1q binding and classic complement cascade activation, response to bacterial polysaccharide antigens (i.e., Pneumococcus)
• IgG3 (5 to 8%): Opsonization, strong C1q binding and classic complement cascade activation, response to protein and viral antigens
• IgG4 (1 to 4%): Minimal opsonization, no complement activation, may be involved in immune response to parasites (Schistosoma and Filaria spp.)

Question 645

645 What component of the nonspecific immune system functions to opsonize bacteria, recruit and activate polymorphonuclear cells and macrophages, participate in antibody regulation, clear immune complexes, clear apoptotic cells, and can result in inflammation and anaphylaxis?

Answer 645

Complement system

Question 646

646 What are the four pathways involved in complement activation?

Answer 646

1. Classic pathway (C1qrs, C2, C3, C4; C1-INH, C4-BP); antibody dependent
2. Lectin pathway (mannan binding protein, mannan associated serine protease); antibody independent
3. Alternative pathway (C3, Factors B and D, properdin; decay accelerating factor, CR1, etc); antibody independent
4. Lytic (membrane attack) pathway (C5–9; protein S)

Note: The classic, lectin, and alternative pathways can all result in the cleavage of C3 and activation of C5 convertase. C5 convertase is required for activation of C5 and the lytic (membrane attack) pathway.

Question 647

647 How is the mannose-binding lectin pathway of complement activated?

Answer 647

Microbes containing mannan are recognized by mannan binding lectins, which in turn activate serine proteases (MASPs) which mediate cleavage of C1, C4, and C2, leading to the C3 convertase

Question 648

648 How is the alternative pathway of the complement system activated?

Answer 648

Microbial structures neutralize inhibitors of spontaneous complement activation leading to unimpeded complement activation.

Question 649

649 What are considered the anaphylatoxins produced by the complement cascade?

Answer 649

C3a, C4a, and C5a

Question 650

650 What nonantibody proteins act as mediators between cells, result in signaling cascades, and can be produced both by immune (innate and cell mediated) and nonimmune system cells?

Answer 650

Cytokines

Question 651

651 Name the general cytokine subtype associated with the following:

• Results in an antiviral response
• Produced by lymphocyte
• Produced by leukocytes and effect the function of other leukocytes
• Result in an acute inflammatory response to Gram-negative bacteria
• Influence maturation and release of bone marrow cell populations

Answer 651

• INF
• Lymphokine
• Interleukin
• TNF
• Colony stimulating factor

Question 652

652 Name the cytokine associated with adaptive immunity system described by the following:

• Produced by TH cells, major growth factor for T cells, B cells, and NK cells
• Stimulated bone marrow immune cells to expand, especially mast cells and eosinophils
• Produced by macrophages, mast cells, and T cells; stimulates development of TH cells, stim ulates B-cell immunoglobulin class switch to IgE
• Produces by TH cells, promotes maturation of B cells, and eosinophils
• Produced by T cells, among others, and inhibits proliferation of T cells and macrophages and inhibits the effect of proinflammatory cytokines on polymorphonuclear cells and endothelial cells

Answer 652

• IL-2
• IL-3
• IL-4
• IL-5
• Transforming growth factor (TGF)-β

Question 653

653 Which cytokine functions to regulate both the innate and adaptive immune system by inhibiting macrophages, cytokine synthesis, and antigen-presenting cells and is produced by macrophages and CD4 + T cells?

Answer 653

IL-10

Question 654

654 Name the cytokine associated with the innate immunity described by the following:

• Produced by activated macrophages (response to lipopolysaccharide of Gram-negative bacteria), mediates acute inflammation, stimulates thalamus to produce a fever
• Produced by activated macrophages, mediates acute inflammation, stimulates T cells
• Produced by many different cells (i.e., lymphocytes, macrophages, endothelium, and keratinocytes) to inhibit viral replication, increase MHC class I expression in cells making them more susceptible to cytotoxic T cells, activate NK cells
• Produced by TH1 cells, produces a myriad of direct cytotoxic effects

Answer 654

• TNF-α
• IL-1
• Type I interferons (INF-α and INF-β)
• INF-γ

Question 655

655 What is the clinical impact of IgG1 deficiency?

Answer 655

Generalized hypogammaglobulinemia. Often associated with IgG3 deficiency.

Question 656

656 When patients have significant IgG1 deficiency in combination with IgA and/or IgM deficiency. What is the diagnosis?

Answer 656

Common variable immunodeficiency

Question 657

657 Although rare, selective IgG1 deficiencies (i.e., no other detectable immunoglobulin abnormality) can occur and can result in frequent and/or repeated infections of what two organs?

Answer 657

Upper (i.e., sinuses) and lower respiratory tracts.

Question 658

658 You are evaluating a child with recurrent sinusitis, otitis media, and bronchitis. Immunologic workup suggests deficiency in the IgG subclass, which is important in the defense against polysaccharide capsular antigens. What is the likely diagnosis and to which bacteria is this child most susceptible?

Answer 658

IgG2 deficiency. Streptococcus pneumoniae, Haemophilus influenza type b, Neisseria meningitidis

Question 659

659 IgG3 deficiency can result in increased susceptibility to viral infections, as well as Moraxella catarrhalis and Streptococcus pyogenes, resulting in recurrent sinopulmonary and GI infections, as well as recurrent lymphocytic meningitis. What additional IgG subtype is often deficient in these patients?

Answer 659

IgG1

Question 660

660 You are evaluating a patient with sialadenitis and salivary gland enlargement. Biopsy reveals lymphoplasmacytic infiltrate IgG + plasma cells and fibrosis. The condition seems to respond to glucocorticoids. Which IgG subclass is likely involved?

Answer 660

IgG4 (IgG4-related systemic disease). May also result in autoimmune pancreatitis

Question 661

661 What is the clinical impact of IgA deficiency?

Answer 661

Patients are often asymptomatic, although the deficiency may be one of the most common primary immunodeficiency syndromes. May have recurrent sinopulmonary or GI infections, skin infections, anaphylaxis with transfusions, or autoimmune disorders

Question 662

662 A patient has eczema, thrombocytopenia, and recurrent otitis media, pneumonia, and sinusitis. What immunodeficiency syndrome do you suspect, and how is it inherited?

Answer 662

Wiskott-Aldrich syndrome (X-linked)

Question 663

663 A 6-month-old patient has severe and recurrent otitis media, sinopulmonary infections, pneumonia, and associated autoimmune disorders and is found to have an underlying immunodeficiency affecting B cells, but not T cells. What are the most likely diagnosis, inheritance pattern, and genetic defect?

Answer 663

Bruton agammaglobulinemia: X-linked, defect in tyrosine kinase (Bruton tyrosine kinase), resulting in inability of pro B cells to mature

Question 664

664 Patients with Bruton agammaglobulinemia develop masses in what organ?

Answer 664

Thymus (thymoma)

Question 665

665 Patients with X-linked agammaglobulinemia have recurrent infections secondary to a low level of which antibody isotype(s)?

Answer 665

All antibody isotypes

Question 666

666 Abnormality of the third and fourth branchial arches leading to thymic hypoplasia or agenesis, hypoplastic parathyroids with resultant hypocalcemia, and abnormalities of the face and aortic arch results in what syndrome?

Answer 666

DeGeorge syndrome (22q11.2 deletion)

Question 667

667 What form of immune responses are impaired in DeGeorge syndrome?

Answer 667

T-cell–mediated immune responses are impaired or absent secondary to thymic agenesis.