IMMUNOLOGY Flashcards
What is the underlying pathology in patients who die from anaphylaxis without antecedent respiratory insufficiency? (HPIM 20th ed. C346 P2506)
a. Visceral congestion leading to loss of intravascular volume
b. Mechanical laryngeal obstruction
c. Bronchospasm and peribronchial congestion
d. Volume depletion due to profuse vomiting
The correct answer is: Visceral congestion leading to loss of intravascular volume
A 30/F slumped on a sidewalk was brought to ER by a bystander. On physical exam, she was hypotensive, tachycardic and desaturated. There was audible stridor and tight air entry on chest auscultation. Her extremities showed multiple erythematous wheals, and larger plaques. With her belongings was a budesonide + formoterol inhaler. Which of the following inciting factors is LEAST likely for this patient? (HPIM 20th ed. C346 P2506)
a. Peanuts
b. Latex
c. Exercise
d. Bee sting
The correct answer is: Bee sting
A 45/F was sent to the ER due to difficulty of breathing. The patient was undergoing her 2nd cycle of chemotherapy when a few minutes into the infusion, she suddenly developed pruritus, nausea and difficulty breathing. BP was 110/80 HR 110 RR 24 T 37º C, O2 sats 92%. Bilateral wheezing and generalized erythematous maculopapular rash was noted on physical examination. What is the first line treatment for this patient? (HPIM 20th ed. C346 P2507)
a. Diphenhydramine 25mg IM
b. Epinephrine 0.3-0.5 ml of 1:1000 concentration IM
c. Hydrocortisone 100mg IV q8
d. Nebulization with beta agonist
The correct answer is: Epinephrine 0.3-0.5 ml of 1:1000 concentration IM
More favorable outcomes are seen in patients with anaphylaxis who are given epinephrine within the first: (HPIM 20th ed. C346 P2507)
a. 30 minutes
b. 20 minutes
c. 2 hours
d. 1 hour
The correct answer is: 20 minutes
What is the key effector cell in asthma and allergic rhinitis? (HPIM 20th ed. C345 P2498)
a. Mast cells
b. B lymphocytes
c. Eosinophils
d. Basophils
The correct answer is: Mast cells
A 20/F presented in the OPD due to recurrent urticaria. On probing, you note that the wheals often show up on her bilateral shoulders after a long day of carrying her backpack around. Which of the following is NOT an appropriate treatment for this patient? (HPIM 20th ed. C345 P2502)
a. H1 antagonist
b. H2 antagonist
c. CysLT1 receptor antagonist
d. Topical steroid
The correct answer is: Topical steroid
What immunodeficiency is associated with recurrent viral infections? (HPIM 20th ed C344 P2488)
a. Complement deficiency
b. Impaired T cell immunity
c. Defective antibody response
d. Innate immune defects
The correct answer is: Impaired T cell immunity
Which of the following conditions involve deficiency in the innate immune system? (HPIM 20th ed. C344 P2489)
a. IgA deficiency
b. DiGeorge’s syndrome
c. Leukocyte adhesion deficiency
d. Severe-combined immune deficiency
The correct answer is: Leukocyte adhesion deficiency
Which of the following vasculitides involves mainly the large vessels? (HPIM 20th ed. C356 P2585)
a. Takayasu’s arteritis
b. Polyarteritis nodosa
c. Churg-strauss syndrome
d. Henoch-schonlein purpura
The correct answer is: Takayasu’s arteritis
What is the most common arterial thrombosis in patients with antiphospholipid syndrome? (HPIM 20th ed. C350 P2527 T350-2)
a. Digital gangrene
b. Myocardial ischemia
c. Renal artery thrombosis
d. Stroke
The correct answer is: Stroke
Which of the following is a risk factor for developing allergic rhinitis?
a. Male sex
b. Younger age
c. Maternal smoking
d. Being underweight
The correct answer is: Maternal smoking
A patient experiencing sneezing and ocular itching around 2 days a week with no impairment in sleep or daily activities can be classified as?
a. Intermittent mild
b. Intermittent moderate
c. Persistent mild
d. Persistent severe
The correct answer is: Intermittent mild
Which of the following responses is associated with biopsy findings of infiltrating and activated TH2 cells and various leukocytes?
a. Skin erythema with swelling
b. Wheal-and-flare response with pruritus
c. Bronchospasm and mucus secretion
d. Nasal pruritus and watery discharge
ALLERGIC INFLAMMATION
Immediate phase
• Pruritus and watery discharge in the nose
• Bronchospasm and mucus secretion in the lung
• Wheal-and-flare response with pruritus in the skin
Late phase (6-8 hrs)
• Reduced nasal patency
• Reduced pulmonary function
• Erythema with swelling at the skin site
• Biopsy findings: Infiltrating and activated TH2 cells, eosinophils, basophils, and some neutrophils
The correct answer is: Skin erythema with swelling
Which of the following aspects is the basic differentiating feature between urticaria and angioedema?
a. Skin layers involved
b. Duration of episodes
c. Area of the body affected
d. Presence of systemic symptoms
URTICARIA AND ANGIOEDEMA
same pathophysiologic process occurring at different levels of the skin
- Urticaria – dilation of vascular structures in the superficial dermis
- Angioedema – originates from the deeper dermis and subcutaneous tissues
The correct answer is: Skin layers involved
How many weeks is the cutoff point for differentiating acute vs. chronic urticaria/angioedema?
a. 6
b. 8
c. 10
d. 12
- Acute – <6 weeks
- Chronic – >6 weeks
The correct answer is: 6
During which decades are chronic urticaria/angioedema the most common?
a. Second to fourth
b. Third to fifth
c. Fourth to sixth
d. Fifth to sevenths
CHRONIC URTICARIA/ANGIOEDEMA
- Can occur at any time, with the third to fifth decade being the most common
- Women > men
- Slight predominance for those with a history of atopy
The correct answer is: Third to fifth
What is the most common type of chronic urticaria/angiodema?
a. Hereditary
b. Idiopathic
c. Physical
d. Vasculitic
Acute urticaria – most often from food/environmental/drug allergen exposure or viral infection
Chronic urticaria – most often idiopathic
The correct answer is: Idiopathic
Which of the following types of physical urticaria is not influenced by atopy?
a. Cholinergic
b. Cold
c. Dermatographic
d. Solar
DERMOGRAPHISM/DERMATOGRAPHISM • Appearance of a linear wheal with surrounding erythema at the site of a brisk stroke with a firm object • Peaks in the second to third decades • Duration generally <5 years • Not influenced by atopy
The correct answer is: Dermatographic
Who among the following could be the most at risk for ACE inhibitor related angioedema?
a. White male
b. Elderly smoker
c. Young asthmatic
d. Female cancer patient
RISK FACTORS FOR ACE-INHIBITOR RELATED ANGIOEDEMA • Black race • Organ transplant • Female gender • Smoking • Increasing age
The correct answer is: Elderly smoker
Which of the following is the best evidence for IgE and mast cell involvement in urticaria and angioedema?
a. Cholinergic urticaria
b. Cold urticaria
c. Pressure urticaria
d. Urticaria pigmentosa
COLD URTICARIA
• Cryoglobulins or cold agglutinins are present in up to 5%
• Histology: Marked mast cell degranulation with associated edema of the dermis and subcutaneous tissues
• Elevated histamine levels
The correct answer is: Cold urticaria
Which of the following is the most likely diagnosis in a patient presenting with isolated angioedema and abdominal colic, nausea, and vomiting?
a. C1 inhibitor deficiency
b. Gleich syndrome
c. Mastocytosis
d. Urticarial vasculitis
BRADYKININ-MEDIATED ANGIOEDEMA (ACE INHIBITORS/C1INH DEFICIENCY)
• Absence of concomitant urticaria or pruritus
• Frequent involvement of the GI tract
• Duration of symptoms >24 hrs
• *Gleich syndrome = episodic angioedema with eosinophilia
The correct answer is: C1 inhibitor deficiency
Which of the following histologic features is most likely to be found in a patient complaining of prolonged episodes of painful and nonpruritic urticaria with resultant scarring?
a. Adventitial and medial fibrosis
b. Fibrinoid necrosis of the venules
c. Perivascular lymphocytic infiltrate
d. Necrotizing granulomatous inflammation of vessel walls
URTICARIAL VASCULITIS
• Painful, nonpruritic urticarial lesions that last >36 hrs with subsequent scarring
• Warrants biopsy
o Cellular infiltration and nuclear debris (leukocytoclastic vasculitis)
o Fibrinoid necrosis of the venules
The correct answer is: Fibrinoid necrosis of the venules
Which of the following medications are the treatment of choice for most forms of urticaria?
a. CysLT1 receptor antagonists
b. H1 antihistamines
c. H2 antagonists
d. Topical glucocorticoids
FIRST-LINE TREATMENT OF URTICARIA
• Preferred: Long-acting, non-sedating H1 antihistamines (loratadine, desloratadine, fexofenadine) or low-sedating agents (cetirizine, levocetirizine) given QID
• Add-on therapies:
o H2 antagonists (cimetidine, ranitidine, famotidine) in conventional dosages
o CysLT1 receptor antagonists (montelukast, zafirlukast)
The correct answer is: H1 antihistamines
Which of the following is the next line of therapy for a patient with recurrent episodes of hives and wheezing upon exposure to low ambient temperatures that does not adequately respond to first-line treatments?
a. Cyclosporine
b. Hydroxychloroquine
c. Methylprednisolone
d. Omalizumab
COLD URTICARIA
- IgE and mast cell involvement
- Omalizumab (monoclonal anti-IgE antibody) – next line of therapy for chronic urticaria which has failed to respond to a combination of long-acting H1 antihistamines QID and a CysLT1 receptor antagonist or cold urticaria
The correct answer is: Omalizumab
For which of the following types of urticaria should the addition of systemic glucocorticoids be considered in the presence of severe disease that is poorly responsive to conventional therapies?
a. Allergen-induced
b. Cold
c. Cholinergic
d. Pressure
SYSTEMIC GLUCOCORTICOIDS
Useful in patients with debilitating disease that responds poorly to conventional treatment:
• Pressure urticaria
• Vasculitic urticaria (esp. with eosinophil prominence)
• Idiopathic angioedema ± urticaria
• Chronic urticaria
Generally avoided due to long-term toxicity:
• Idiopathic urticaria
• Allergen-induced urticaria
• Physical urticarias
The correct answer is: Pressure
Which of the following is a risk factor for developing allergic rhinitis?
a. Male sex
b. Younger age
c. Maternal smoking
d. Being underweight
RISK FACTORS • Atopy o Up to 50% of patients with allergic rhinitis manifest asthma o 70–80% of individuals with asthma and 80% of individuals with chronic bilateral sinusitis experience allergic rhinitis • Female sex • Particulate air pollution exposure • Maternal tobacco smoking The correct answer is: Maternal smoking
How many weeks is the cutoff point for differentiating acute vs. chronic rhinitis?
a. 4
b. 6
c. 8
d. 12
The correct answer is: 4
Oral long-acting H1 antihistamines are less effective for which of the following symptoms?
a. Tearing
b. Sneezing
c. Nasal congestion
d. Watery rhinorrhea
Oral long-acting H1 antihistamines are more effective for: • Nasopharyngeal itching • Sneezing • Watery rhinorrhea • Ocular itching/erythema • Tearing
The correct answer is: Nasal congestion
. Immunotherapy for allergic rhinitis is contraindicated in which of the following situations?
a. Advanced age
b. Breastfeeding
c. Significant cardiovascular disease
d. Concomitant antihypertensive therapy
IMMUNOTHERAPY CONTRAINDICATIONS
- Significant cardiovascular disease
- Unstable asthma
- Should be conducted with caution in any patient requiring β-adrenergic blocking therapy because of the difficulty in managing an anaphylactic complication
The correct answer is: Significant cardiovascular disease
Which of the following medications is an appropriate option for a patient experiencing sneezing and ocular itching around 2 days a week with no impairment in sleep or daily activities?
a. Intranasal glucocorticoid
b. Intranasal ipratropium bromide
c. Oral corticosteroid
d. Oral antihistamine
MILD INTERMITTENT AR
• <4 days/week or
• <4 weeks
• No troublesome symptoms or impairment in sleep/daily activities
ARIA 2008
The correct answer is: Oral antihistamine
Which of the following medications is the best option for a patient suffering from daytime somnolence and fatigue due to allergic rhinitis symptoms occurring around 4 days a week for 2 weeks?
a. CysLT1 receptor antagonist
b. Intranasal glucocorticoid
c. Intranasal ipratropium bromide
d. Oral corticosteroid
MODERATE-SEVERE INTERMITTENT AR
• <4 days/week, or
• <4 weeks
• (+) Troublesome symptoms or impairment in sleep/daily activities
ARIA 2008
The correct answer is: Intranasal glucocorticoid
Which of the following clinical manifestations is the least consistent with allergic rhinitis?
a. Nasal and ocular itching
b. Paroxysmal sneezing with tearing
c. Posterior rhinorrhea with anosmia
d. Eye swelling with nasal congestion
The correct answer is: Posterior rhinorrhea with anosmia
Intranasal decongestants should be given for less than how many days to prevent rhinitis medicamentosa?
a. 10
b. 14
c. 21
d. 30
RHINITIS MEDICAMENTOSA
Rebound nasal congestion that occurs with prolonged use (more than 10 days) of topical decongestants such as oxymetazoline and phenylephrine
The correct answer is: 10
Which of the following is not an indication for initiating subcutaneous immunotherapy?
a. Undesirable side effects from pharmacotherapy
b. Concomitant bronchial asthma that is poorly controlled
c. Refusal of patient to be on constant or long-term pharmacotherapy
d. Inadequate relief of rhinitis symptoms with antihistamines and moderate-dose topical glucocorticoids
The correct answer is: Concomitant bronchial asthma that is poorly controlled
Based on the ARIA 2016 update, what is the preferred treatment for perennial allergic rhinitis (PAR) in addition to an intranasal corticosteroid (INCS)?
a. CysLT1 receptor antagonist
b. Intranasal antihistamine
c. Oral antihistamine
d. No additional agent
In patients with PAR, there is no additional benefit from a combination therapy compared with INCS alone
The correct answer is: No additional agent
In patients with seasonal allergic rhinitis, which of the following concomitant conditions might make them benefit more from a CysLT1 receptor antagonist vs. an oral antihistamine?
a. Allergic conjunctivitis
b. Brittle asthma
c. Exercise-induced bronchoconstriction
d. Postnasal drip
The correct answer is: Exercise-induced bronchoconstriction
Which of the following vasculitis syndromes is associated with pathogenic immune-complex formation?
a. Churg-Strauss syndrome
b. Henoch-Schönlein purpura
c. Microscopic polyangiitis
d. Takayasu arteritis
The correct answer is: Henoch-Schönlein purpura
Which of the following vasculitis syndromes is associated with both antineutrophilic cytoplasmic antibody (ANCA) production and granuloma formation?
a. Churg-Strauss syndrome
b. Henoch-Schönlein purpura
c. Polyarteritis nodosa
d. Takayasu arteritis
The correct answer is: Churg-Strauss syndrome
What is the major cytoplasmic ANCA (cANCA) antigen?
a. Cathepsin G
b. Elastase
c. Myeloperoxidase
d. Proteinase-3
cANCA • Proteinase-3 (>90%) pANCA • Myeloperoxidase (major) • Elastase • Cathepsin G • Lactoferrin • Lysozyme • Bactericidal/permeability- increasing protein
The correct answer is: Proteinase-3
What is the major perinuclear ANCA (pANCA) antigen?
a. Cathepsin G
b. Elastase
c. Myeloperoxidase
d. Proteinase-3
cANCA • Proteinase-3 (>90%) pANCA • Myeloperoxidase (major) • Elastase • Cathepsin G • Lactoferrin • Lysozyme • Bactericidal/permeability- increasing protein
The correct answer is: Myeloperoxidase
Arteriogram of organs with suspected involvement should be performed in which of the following vasculitis syndromes?
a. Churg-Strauss syndrome
b. Cryoglobulinemic vasculitis
c. Henoch-Schönlein purpura
d. Polyarteritis nodosa
ARTERIOGRAM INDICATIONS
• Polyarteritis nodosa
• Takayasu arteritis
• Primary CNS vasculitis
The correct answer is: Polyarteritis nodosa
What is the histopathologic hallmark of Wegener’s granulomatosis?
a. Necrotizing inflammation of small- and medium-sized muscular arteries
b. Necrotizing vasculitis of small arteries and veins with granuloma formation
c. Inflammatory mononuclear cell infiltration of medium- and large-sized arteries
d. Eosinophilic infiltration of small- and medium-sized muscular arteries, capillaries, veins, and venules
HISTOPATHOLOGIC HALLMARKS OF GRANULOMATOSIS WITH POLYANGIITIS (WEGENER’S)
• Necrotizing vasculitis of small arteries and veins
• Granuloma formation (may be either intravascular or extravascular)
• Classically found in the respiratory tract and kidneys
The correct answer is: Necrotizing vasculitis of small arteries and veins with granuloma formation
In a patient with bloody nasal discharge, nodular cavitary lung infiltrates, palpable purpura, and glomerulonephritis, which tissue should be obtained for the highest diagnostic yield?
a. Upper airway
b. Lung
c. Kidney
d. Skin
TISSUE DIAGNOSIS OF WEGENER’S GRANULOMATOSIS
• Pulmonary tissue – highest diagnostic yield; almost invariably reveals granulomatous vasculitis
• Upper airway tissue – usually reveals granulomatous inflammation with necrosis but may not show vasculitis
• Renal tissue – pauci-immune glomerulonephritis
The correct answer is: Lung
What is the most frequent cause of mortality among patients with Wegener’s granulomatosis?
a. Stroke
b. Cardiomyopathy
c. Pulmonary hemorrhage
d. Renal failure
RENAL DISEASE IN WEGENER’S GRANULOMATOSIS
• Generally dominates the clinical picture (77%)
• Once clinically detectable renal functional impair- ment occurs, rapidly progressive renal failure usually ensues unless appropriate treatment is instituted
• Accounts for most of the mortality rate if left untreated
The correct answer is: Renal failure
On top of glucocorticoids, what is the treatment of choice for granulomatosis with polyangiitis?
a. Azathioprine
b. Cyclophosphamide
c. Methotrexate
d. Rituximab
CYCLOPHOSPHAMIDE
• Marked improvement in >90% of patients
• Complete remission in 75% of patients
• 5-year patient survival in >80%
The correct answer is: Cyclophosphamide
Which of the following clinical manifestations is the least consistent with microscopic polyangiitis?
a. Cutaneous vasculitis
b. Endobronchial disease
c. Mononeuritis multiplex
d. Pauci-immune glomerulonephritis
CLINICAL FEATURES OF MICROSCOPIC POLYANGIITIS
• Fever, weight loss, and musculoskeletal pain
• Pauci-immune glomerulonephritis
• Mononeuritis multiplex
• GI tract vasculitis
• Cutaneous vasculitis
• Elevated ESR, anemia, leukocytosis, and thrombocytosis
The correct answer is: Endobronchial disease
Which of the following laboratory findings is most likely to be seen in a patient presenting with severe asthmatic attacks, pulmonary infiltrates, mononeuritis multiplex, and cutaneous vasculitis?
a. Circulating ANCA
b. Marked eosinophilia
c. Elevated γ-globulin level
d. Elevated C-reactive protein
LABORATORY FINDINGS IN CHURG-STRAUSS DISEASE
• Striking eosinophilia (>80%)
• Elevated ESR, fibrinogen, or α-globulins (81%)
• Circulating ANCA (48%)
The correct answer is: Marked eosinophilia
What is the most frequent cause of death among patients with eosinophilic granulomatosis with polyangiitis?
a. Renal failure
b. Status asthmaticus
c. Pulmonary hemorrhage
d. Myocardial involvement
CARDIAC INVOLVEMENT IN CHURG-STRAUSS SYNDROME
- Clinically recognizable heart disease occurs in ~14% of patients
- Myocardial involvement – most frequent cause of death (39%)
- Echocardiography – should be performed in all newly diagnosed patients
- Treatment of choice: Daily cyclophosphamide + prednisone, followed by azathioprine or methotrexate
The correct answer is: Myocardial involvement
Which of the following arteries are not involved in polyarteritis nodosa?
a. Cerebral
b. Coronary
c. Pulmonary
d. Renal
Polyarteritis nodosa – necrotizing inflammation of small- and medium-sized muscular arteries
• Pulmonary arteries are not involved
• Bronchial artery involvement is uncommon
HPIM 20e, Ch. 356, p. 2583 (Table 356-6)
The correct answer is: Pulmonary
Which of the following is the main differentiating histologic feature between polyarteritis nodosa and microscopic polyangiitis?
a. Involvement of venules
b. Obliteration of vasa vasorum
c. Perivascular collagen deposition
d. Fibrinoid necrosis of vessel walls
HISTOLOGIC FINDINGS IN POLYARTERITIS NODOSA
• Acute stages: Polymorphonuclear neutrophils infiltrate all layers of the vessel wall and perivascular areas -> intimal proliferation and degeneration of the vessel wall
• Subacute and chronic stages: Mononuclear cells infiltrate the area -> fibrinoid necrosis of the vessels -> luminal narrowing -> thrombosis, tissue infarction, hemorrhage -> collagen deposition as the lesions heal -> further luminal occlusion
• Involvement of venules is not seen
The correct answer is: Involvement of venules
Which of the following vasculitides is more common in females?
a. Giant cell arteritis
b. Kawasaki disease
c. Polyarteritis nodosa
d. Wegener’s granulomatosis
VASCULITIDES THAT ARE MORE COMMON IN WOMEN
• Giant cell arteritis
• Takayasu arteritis
The correct answer is: Giant cell arteritis
Which of the following is the most likely diagnosis in a 60-year-old patient presenting with fever, arthralgias, and recurrent headaches associated with anemia and an elevated ESR?
a. Giant cell arteritis
b. Polyarteritis nodosa
c. Primary CNS vasculitis
d. Takayasu arteritis
DIAGNOSIS OF GIANT CELL ARTERITIS
• Can often be suggested clinically by the complex of fever, anemia, and high ESR ± symptoms of polymyalgia rheumatica in a patient >50 years
• Can be confirmed by biopsy of the temporal artery but may not be positive in all patients due to patchy histologic findings
The correct answer is: Giant cell arteritis
Patients with giant cell arteritis are 18-fold more likely to develop which of the following vascular abnormalities compared to the general population?
a. Cerebral artery aneurysm
b. Subclavian artery stenosis
c. Thoracic aortic aneurysm
d. Renal artery stenosis
GIANT CELL ARTERITIS COMPLICATIONS
• Acute disease-related mortality directly from giant cell arteritis is uncommon
o Cerebrovascular events or myocardial infarction – most common causes of mortality
• However, patients are at risk of late mortality from aortic aneurysm rupture or dissection
o Patients are 18x more likely to develop thoracic aortic aneurysms than the general population
The correct answer is: Thoracic aortic aneurysm
What is the most commonly involved artery in Takayasu arteritis?
a. Common carotid
b. Subclavian
c. Aortic arch
d. Abdominal aorta
The correct answer is: Subclavian
Which of the following should be suspected in a 23-year-old female presenting with weight loss, anorexia, and arthralgias, accompanied by weak peripheral pulses and Raynaud’s phenomenon?
a. Churg-Strauss syndrome
b. Giant cell arteritis
c. Microscopic polyangiitis
d. Takayasu arteritis
DIAGNOSIS OF TAKAYASU ARTERITIS
• Should be suspected strongly in a young woman who develops a decrease or absence of peripheral pulses, discrepancies in blood pressure, and arterial bruit
• Confirmed by the characteristic pattern on arteriography, which includes irregular vessel walls, stenosis, poststenotic dilation, aneurysm formation, occlusion, and evidence of increased collateral circulation
The correct answer is: Takayasu arteritis
Which of the following vasculitis syndromes is not associated with the development of palpable purpura?
a. Churg-Strauss syndrome
b. IgA vasculitis
c. Microscopic polyangiitis
d. Takayasu arteritis
• Palpable purpura – reflect involvement of postcapillary venules; not seen in large-vessel vasculitides such as Takayasu arteritis and giant cell arteritis
The correct answer is: Takayasu arteritis
Which of the following clinical manifestations are less frequent in adults vs. children with Henoch-Schönlein purpura?
a. Cardiac
b. Cutaneous
c. Gastrointestinal
d. Musculoskeletal
IgA VASCULITIS/HENOCH-SCHONLEIN PURPURA IN ADULTS
• Presenting symptoms are most frequently related to the skin and joints
• Initial complaints related to the gut are less common
• Myocardial involvement can occur in adults but is rare in children
• Renal disease may be more frequent and more severe in adults, but this has not been a consistent finding
The correct answer is: Gastrointestinal
A skin biopsy specimen showing leukocytoclastic vasculitis with IgA and C3 deposition by immunofluorescence is most consistent with which of the following diseases?
a. Henoch-Schönlein purpura
b. Idiopathic cutaneous vasculitis
c. Lupus vasculitis
d. Polyarteritis nodosa
IMMUNE COMPLEX DEPOSITION IN HENOCH-SCHONLEIN PURPURA • IgA – most common • Possible inciting antigens: o Upper respiratory tract infections o Drugs o Food o Insect bites o Immunizations
The correct answer is: Henoch-Schönlein purpura
What is the most common type of renal pathology seen in patients with hepatitis C virus-associated vasculitis?
a. Focal segmental glomerulosclerosis
b. Membranoproliferative glomerulonephritis
c. Minimal change disease
d. Thrombotic microangiopathy
CRYOGLOBULINEMIC VASCULITIS
• Renal disease develops in 10–30% of patients
o Poor prognostic factor
• Membranoproliferative glomerulonephritis – 80% of all renal lesions
• 15% progress to end-stage renal disease
• Life-threatening rapidly progressive glomerulonephritis occurs infrequently
The correct answer is: Membranoproliferative glomerulonephritis
What are the most commonly involved vessels in cutaneous vasculitides?
a. Capillaries
b. Vasa vasorum
c. Terminal arterioles
d. Postcapillary venules
HISTOLOGIC FINDINGS IN CUTANEOUS VASCULITIDES
• Postcapillary venules – most commonly involved vessels
• Acute: Leukocytoclasis (nuclear debris remaining from the neutrophils that have infiltrated in and around the vessels)
• Subacute/chronic: Mononuclear cell infiltration
The correct answer is: Postcapillary venules
A patient who develops cutaneous lesions and glomerulonephritis after taking propylthiouracil will most likely have which of the following antibodies?
a. Anti-histone
b. Anti-myeloperoxidase
c. Anti-proteinase 3
d. Anti-Ro/SSA
ANTI-MYELOPEROXIDASE ANCA-POSITIVE DRUG-INDUCED VASCULITIS
• Best evidence:
o Hydralazine
o PTU
• Clinical manifestations can range from cutaneous lesions to glomerulonephritis and pulmonary hemorrhage
The correct answer is: Anti-myeloperoxidase
. Which of the following malignancies is classically associated with polyarteritis nodosa?
a. Hairy cell leukemia
b. Hepatocellular carcinoma
c. Mantle cell lymphoma
d. Renal cell carcinoma
MALIGNANCIES ASSOCIATED WITH VASCULITIS
• Vasculitis can be associated with certain malignancies, particularly lymphoid or reticuloendothelial neoplasms
o Hairy cell leukemia – associated with polyarteritis nodosa
• Leukocytoclastic venulitis confined to the skin – most common finding
• However, widespread systemic vasculitis may also occur
The correct answer is: Hairy cell leukemia
Which of the following is a risk factor for increased mortality from anaphylaxis?
a. Asian ethnicity
b. History of beta agonist use
c. Preexisting bronchial asthma
d. Young age
RISK FACTORS FOR RAPID DECOMPENSATION FROM ANAPHYLAXIS
(a) Underlying cardiovascular disease
• one of the most dangerous manifestations of anaphylaxis is involvement of the cardiovascular system
(b) Underlying bronchial asthma
• predisposed to having severe involvement of the lower airways –> leading to increased mortality
The correct answer is: Preexisting bronchial asthma
History of atopy increases the risk for which type of anaphylactic reaction?
a. Exercise-induced anaphylaxis
b. Severe hymenoptera sting
c. Anaphylaxis from insulin
d. Anaphylaxis from penicillin
ATOPY • Increases risk of: (a) exercise-induced anaphylaxis (b) Idiopathic anaphylaxis (c) Latex-induced anaphylaxis (d) Radiocontrast allergy (e) Food allergy
• Not associated with:
(a) Drug allergies (insulin, penicillin, muscle relaxants
(b) Hymenoptera stings
The correct answer is: Exercise-induced anaphylaxis
Which is the expected histologic finding in the bronchi of fatal anaphylaxis from bronchial obstruction?
a. Increased intraluminal secretions
b. Neutrophilic infiltration
c. Submucosal hemorrhage
d. Vascular congestion
BRONCHIAL MICROSCOPIC CHANGES IN FATAL ANAPHYLAXIS IN OBSTRUCTION • Increased luminal secretions • Eosinophilic infiltration • Peribronchial congestion • Submucosal edema
The correct answer is: Increased intraluminal secretions
Which gastrointestinal finding in anaphylaxis may contribute to possible cardiovascular collapse?
a. Angioedema of intestinal wall
b. Bowel ischemia
c. Bowel ulceration
d. Ileus
ANGIOEDEMA OF BOWEL WALL
• causes intravascular volume depletion leading to possible cardiovascular collapse
The correct answer is: Angioedema of intestinal wall
Which case exhibits an IgE-mediated hypersensitivity reaction?
a. A 60/F with ovarian cancer, developing urticarial lesions during her first carboplatin infusion
b. A 24/F developed auricular wheals 3 days after she had new ear piercings
c. A 45/M, post kidney transplant with antibody-mediated rejection, developed arthalgias, fever, and maculopapular eruptions on the face and torso 5 days after infusion of Anti-thymocyte globulin
d. A 7/M with wheals 4 days after accidental contact with poison ivy plant
TYPES OF HYPERSENSITIVITY REACTIONS (A) Type 1: Immediate hypersensitivity IgE-mediated drug allergies are most common with antibiotics and certain chemotherapeutic agents (notably platinum-based) (B) Type II: Antibody-dependent reaction Hemolytic anemia (C) Type III: Immune complex reaction Serum sickness, SLE (D) Type IV: Delayed type hypersensitivity Contact dermatitis, PPD test
The correct answer is: A 60/F with ovarian cancer, developing urticarial lesions during her first carboplatin infusion
Serum levels of this arachidonic-acid derived product directly correlates with anaphylaxis severity
a. Leukotrienes
b. Platelet activating factor (PAF)
c. Prostagladin D2
d. Prostagladin E2
SERUM PAF LEVELS
Directly correlate with severity of anaphylaxis
The correct answer is: Platelet activating factor (PAF)
Which of the following mediators of anaphylaxis causes hypotension and tachycardia when released in high concentrations?
a. Chondroitin sulfate
b. Histamine
c. Leukotrienes
d. Prostaglandin D2
HISTAMINE
• Causes flushing, urticaria, pruritus
• High concentrations result in hypotension
The correct answer is: Histamine
Which is true regarding the use of serum biomarkers in anaphylaxis?
a. Serum histamine is a practical biomarker to determine severity of anaphylaxis.
b. An elevated baseline serum histamine level should prompt the clinician to investigate possible mastocytosis.
c. Serum tryptase level can remain elevated as long as 5 hours after the episode of anaphylaxis.
d. A second serum tryptase determination after an elevated initial test is not recommended.
SERUM BIOMARKERS
(a) Serum histamine
• Can only remain elevated up to 1 hour from onset of anaphylaxis
(b) Serum tryptase: more practical
• Peaks at 60-90 minutes after onset of symptoms
• Elevated up to 5 hours after episode of anaphylaxis
• Elevated baseline level may warrant work-up for mastocytosis
• Another determination is helpful (after resolution of symptoms) to establish baseline
• May not be elevated in food allergy
The correct answer is: Serum tryptase level can remain elevated as long as 5 hours after the episode of anaphylaxis.
In cases of anaphylactic shock, failure to administer epinephrine within this time frame increases risk of poor clinical outcomes
a. 5 minutes
b. 10 minutes
c. 20 minutes
d. 30 minutes
The correct answer is: 20 minutes
Which of the following leads to ‘empty heart syndrome’ in cases of anaphylaxis?
a. Patient in the supine position
b. Epinephrine use
c. Administration of vasopressor agents
d. Vigorous fluid resuscitation
EMPTY HEART SYNDROME
• Insufficient venous return to the heart from sudden onset hypotension secondary to intravascular volume depletion
• Epinephrine accelerates empty heart syndrome (chronotropic effect of drug)
• In the acute setting, patients should be placed in supine position when receiving epinephrine
• Vasopressor support and IV fluids should be given to patients with refractory hypotension
The correct answer is: Epinephrine use
A 24/M was brought to the ER due to sudden onset of difficulty of breathing and generalized flushing after intake of amoxicillin for Helicobacter pylori infection. On physical examination, he was encephalopathic, hypotensive, tachycardic, and tachypneic. Chest exam revealed tight air entry with bilateral wheezing. Wheals were noted on his face and anterior chest. What is the appropriate initial management for this patient?
a. 0.3 – 0.5 ml of 1:1000 epinephrine delivered intramuscularly
b. 0.3 – 0.5 ml of 1:1000 epinephrine delivered subcutaneously
c. 0.3 – 0.5 ml of 1:10000 epinephrine delivered intramuscularly
d. 0.3 – 0.5 ml of 1:10000 epinephrine delivered subcutaneously
MANAGEMENT FOR ANAPHYLAXIS
• First line: Epinephrine 1:1000 (1 mg/ml), 0.3 to 0.5 ml intramuscularly
• Others: fluid resuscitation, oxygen support
The correct answer is: 0.3 – 0.5 ml of 1:1000 epinephrine delivered intramuscularly
Which of the following childhood food allergies tend to persist later in life?
a. Egg
b. Peanut
c. Soy
d. Wheat
FOOD ALLERGY
• Allergies that usually resolve spontaneously during childhood:
o Eggs, soy, wheat, milk
• 80% remain sensitive to peanuts for life
The correct answer is: Peanut
Which is true of desensitization?
a. It entails the administration of incremental increases in doses of the drug to induce permanent tolerance.
b. It is effective for penicillin and platinum-based chemotherapy allergies.
c. It works best for non IgE-mediated reactions.
d. Hypersensitivity to the drug does not recur when the medication is discontinued or treatment is interrupted.
DRUG DESENSITIZATION
• Elicits temporary state of tolerance to the drug in sensitized patients
• Established technique in penicillin allergy
• Also effective for platinum-based chemotherapeutic agents
• Shown to work best in IgE-mediated reactions
• If patient is receiving drug in regular intervals, a desensitized state can be maintained
The correct answer is: It is effective for penicillin and platinum-based chemotherapy allergies.
A 60-kg male will undergo abdominal CT scan with triphasic contrast for surveillance of treated liver cancer. On review of systems, he recalled appearance pruritic rashes during last year’s CT scan. What is the correct dose and frequency of his premedication regimen prior to contrast?
a. Prednisone 30 mg tablet, 6- and 1 hour prior to CT scan + Diphenhydramine 25 mg
b. Prednisone 60 mg tablet, 6- and 1 hour prior to CT scan + Diphenhydramine 25 mg
c. Prednisone 30 mg tablet, 13-, 6-, and 1 hour prior to CT scan + Diphenhydramine 25 mg
d. Prednisone 60 mg tablet, 13-, 6-, and 1 hour prior to CT scan + Diphenhydramine 25 mg
PREMEDICATION REGIMEN PRIOR TO RADIOCONTRAST
(a) Prednisone 0.5 mg/kg, 13-, 6-, and 1 hour prior
(b) Diphenhydramine 25 mg
The correct answer is: Prednisone 30 mg tablet, 13-, 6-, and 1 hour prior to CT scan + Diphenhydramine 25 mg
Which is true regarding biphasic anaphylaxis?
a. This is a clinical entity wherein signs and symptoms do not fully respond to initial treatment.
b. It is more common than uniphasic anaphylaxis.
c. Signs and symptoms recur less than an hour after onset of initial anaphylactic reaction.
d. Signs and symptoms may recur as late as 72 hours after resolution of initial reaction.
BIPHASIC ANAPHYLAXIS
• Less common than uniphasic reactions (80-90% of anaphylactic reactions are uniphasic)
• Biphasic anaphylaxis: defined as recurrent anaphylaxis after complete improvement
• Must be clinically differentiated from an episode that does not fully respond to treatment
• Reported to occur between 1 to 72 hours after resolution of initial reaction
The correct answer is: Signs and symptoms may recur as late as 72 hours after resolution of initial reaction.
What is the mechanism of death in patients with anaphylactic reaction from respiratory failure without antecedent hypoxia?
a. Mast cell-mediated cardiac event
b. Laryngeal obstruction
c. Intractable bronchospasm
d. Visceral congestion
VISCERAL CONGESTION
• Noted in patients dying of vascular collapse without antecedent hypoxia from respiratory insufficiency
The correct answer is: Visceral congestion
Which of the following is true regarding the diagnostic criteria of anaphylaxis (NIAID/FAAN*, 2006)?
a. Hypotension after exposure to a known allergen is enough to suggest anaphylaxis.
b. Sudden appearance of cutaneous manifestations (generalized hives, swollen lips-tongue-uvula) after exposure to a likely allergen is a requisite in the diagnosis of anaphylaxis.
c. When occurring after exposure to likely allergen, gastrointestinal symptoms (crampy abdominal pain, vomiting) should be associated with two other system involvement (sudden respiratory symptoms, mucosal signs, or cardiovascular collapse).
d. Respiratory symptoms in the context of anaphylaxis should include the presence of hypoxemia.
NIAID/FAAN, National Institutes of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network
AAAAI Guidelines 2020 (https://doi.org/10.1016/J.JACI.2020.01.017)
The correct answer is: Hypotension after exposure to a known allergen is enough to suggest anaphylaxis.
A 76 year-old diabetic professor was brought to the ER due to recurrent vomiting, crampy abdominal pain and sudden loss of consciousness a few minutes after taking Enalapril 5 mg tablet. Review of past medical history revealed previous PCI for 2-vessel disease. On examination, he was hypotensive and tachycardic. Hypoxemia was noted on ABG. Which of the following does not predispose this patient to severe or fatal anaphylaxis?
a. Older age
b. Preexisting diabetes mellitus
c. Use of ACE inhibitors
d. History of coronary artery disease
AAAAI Guidelines 2020, p 1090 (https://doi.org/10.1016/J.JACI.2020.01.017) RISK FACTORS FOR SEVERE ANAPHYLAXIS 1. Preexisting asthma 2. Cardiovascular disease 3. Use of beta blockers 4. Use of ACE inhibitors 5. Mast cell disorders 6. Older age
The correct answer is: Preexisting diabetes mellitus
Which of the following primary immunodeficiencies is secondary to impaired development of T lymphocytes?
a. Ataxia telangiectasia
b. Common variable immune deficiency (CVID)
c. Severe combined immune deficiencies (SCID)
d. Wiskott—Aldrich Syndrome
The correct answer is: Severe combined immune deficiencies (SCID)
What is the hallmark of severe congenital neutropenia (SCN)?
a. Absence of pus
b. Florid mycobacterial infections
c. Localized fungal soft tissue infections
d. Refractory to GCSF
SEVERE CONGENITAL NEUTROPENIA (SCN)
• A PID of the innate immune system
• Characterized by severely impaired neutrophil counts
• Bacterial and fungal infections rapidly disseminate through bloodstream
• Absence of pus is the hallmark of SCN
• In most cases, neutrophil counts improve with injection of GCSF
o Exception: + ELANE mutation (refractory to GCSF); same subset of patients are at increased risk of AML
The correct answer is: Absence of pus
A 12/F was diagnosed with Ivemark Syndrome after presenting with recurrent streptococcal infections, and most recently, meningitis from N. meningitides. Aside from up to date vaccinations, which of the following is an effective prophylactic measure to prevent fatal infections?
a. GCSF injections
b. Oral penicillin
c. Special oral and dental care
d. Trimetoprim-sulfamethoxazole
ASPLENIA • A feature of Ivemark Syndrome • Predisposes individuals to encapsulated bacterial infections • Prophylactic measures: o (a) Vaccination o (b) Oral penicillin twice daily
The correct answer is: Oral penicillin
Which is true of infections arising from chronic granulomatous diseases (CGD)?
a. Fungal elements are rarely isolated from deep tissue abscesses in the lungs and lymph nodes.
b. Recurrent skin infections are uncommon.
c. Macrophage-rich granulomas seen in the liver and spleen are often sterile.
d. Granulomatous lesions are mostly steroid-refractory.
CHRONIC GRANULOMATOUS DISEASES
• Bacterial and fungal abscesses are usually seen; in fact, prophylactic regimen includes azole derivatives
• Recurrent skin infections, such as folliculitis, are common– that these prompt early diagnosis of disease
• Granulomas are often sterile and steroid-responsive
The correct answer is: Macrophage-rich granulomas seen in the liver and spleen are often sterile.
Patients with deficiencies in the alternative complement pathway are predisposed to systemic infections from which organism?
a. Neisseria spp
b. Haemophilus spp
c. Klebsiella spp
d. Streptococcus spp
COMMON INFECTIONS IN COMPLEMENT DEFICIENCY
• Bacterial infections: deficiencies in any component of the classical pathway
• Invasive Neisseria infections: deficiencies in components of the alternative pathway
The correct answer is: Neisseria spp
Which of the following T cells activate and recruit eosinophils and other cells required to fight helminthic infections?
a. CD4+ TH1 cells
b. CD4+ TH2 cells
c. CD4+ TH17 cells
d. Cytotoxic CD8+ T cells
T CELL EFFECTORS
• CD4+ TH1 cells: help in intracellular killing of Salmonella and mycobacterial infections
• CD4+ TH2 cells: activate eosinophils, among others, to help fight helminthic infections
• CD4+ TH17 cells: recruit neutrophils to skin and lungs to fight bacterial and fungal infections
• Cytotoxic CD8+ T cells: kill infected cells (viral infections)
The correct answer is: CD4+ TH2 cells
Which is true of severe combined immune deficiencies (SCID)?
a. Failure to thrive and recurrent oral fungal infections are frequent manifestations of the disease.
b. Bacille Calmette-Guarin (BCG) vaccine can be safely given to infants with SCID.
c. Pneumocystis jiroveci pneumonia is exclusively seen in children afflicted with this T cell immunedeficiency.
d. Severe infections and other clinical consequences occur after the first year of life.
SCID
• Most common manifestations: protracted diarrhea, recurrent oral candidiasis, and failure to thrive
• P. jiroveci pneumonia may also be seen during the first year of life in patients with B cell immunedeficiencies
• Administration of BCG vaccine may lead to complications, such as local and disseminated fatal infections
• These severe clinical consequences occur early in life (within 3 to 6 months of birth)
The correct answer is: Failure to thrive and recurrent oral fungal infections are frequent manifestations of the disease.
Which is the most frequent underlying mechanism of SCID?
a. Adenosine deaminase (ADA) deficiency
b. Adenylate kinase 2 deficiency
c. γ chain cytokine receptor deficiency
d. Selective deficiency of both T and B lymphocytes
Feedback
CAUSATIVE MECHANISMS OF SCID
(a) Gamma chain cytokine receptor deficiency – most common phenotype
(b) ADA deficiency – causes bone dysplasia and abnormal costochondral junctions
(c) Adenylate kinase 2 deficiency – causes sensorineural deafness and severe neutropenia
(d) Selective deficiency of both T and B lymphocytes
(e) Defective pre-T cell receptor signaling in the thymus
The correct answer is: γ chain cytokine receptor deficiency
A newborn infant was note to have micrognathia, cleft palate, severe hypocalcemia, absence of thymic shadow on chest x-ray, and Tetralogy of Fallot on further work-up. On repair of cardiac defect, no thymic tissue was noted. Which of the following chromosomal abnormality is expected in this patient?
a. Chromosome 5 deletion
b. Chromosome 22 deletion
c. Trisomy 13
d. Trisomy 18
DiGEORGE SYNDROME
- Multiple developmental defects (dysmorphic facial features, cardiac defects)
- Thymic hypoplasia is expected; in some cases: thymus is completely absent, with no mature T cells
- Diagnosis: deletion in long arm of chromosome 22
The correct answer is: Chromosome 22 deletion
Which of the T cell immunodeficiencies places the affected individual at very high risk for development of hematopoietic and solid organ malignancies in his lifetime?
a. Ataxia-telangiectasia
b. Dyskeratosis congenita
c. Omenn Syndrome
d. SCID
IMMUNODEFICIENCY WITH ATAXIA-TELANGIECTASIA
• T cell primary immunodeficiency associated with DNA repair defects
• Progressive disease
• Hallmark features: cerebellar ataxia and telangiectasia
• Affected individuals are at very high risk for lymphomas, leukemia, and carcinomas in adulthood
The correct answer is: Ataxia-telangiectasia
Which of the following is a common clinical manifestation of Wiskott-Aldrich Syndrome?
a. Alopecia
b. Cerebellar ataxia
c. Eczema
d. Pneumatoceles from complicated respiratory infections
WISKOTT-ALDRICH SYNDROME • Results from mutations in the WASP gene (which affect T cells, dendritic cells, and lymphocytes, and platelets) • Common clinical manifestations: (a) Bleeding from thrombocytopenia (b) Eczema (c) Recurrent bacterial infections
The correct answer is: Eczema
Which of the following is the most frequent primary immunodeficiency?
a. Deficiencies of the innate immune system
b. T cell immunodeficiencies
c. B cell immunodeficiencies
d. Regulatory defects of the innate immunity (i.e. HLH)
PRIMARY IMMUNODEFICIENCIES
• B cell immunodeficiencies: account for 70% of PIDs
• Deficiencies of the innate immune system are rare (10%)
The correct answer is: B cell immunodeficiencies
Which is true of infections in B lymphocyte immunodeficiencies?
a. Infections occur commonly in the first 6 months of life.
b. Recurrent respiratory infections are frequently caused by gram-negative bacteria.
c. The gastrointestinal tract is virtually spared from infections in B cell immunodeficiencies.
d. Individuals with agammaglobulinemia are at increased risk of viral meningoencephalitis and hepatitis.
B LYMPHOCYTE DEFICIENCIES
• Defective antibody production predisposes one to recurrent pyogenic sinus and respiratory infections
o Causative agents: S. pneumoniae, H. influenzae, M. catarrhalis; RARELY gram-negative bacteria
• Campylobacter and Helicobacter infections (of the gut) are common
• Those with agammaglobulinemia: increased risk of disseminated enteroviral infections (meningoencephalititis, hepatitis)
The correct answer is: Individuals with agammaglobulinemia are at increased risk of viral meningoencephalitis and hepatitis.
Which is true regarding immunoglobulin replacement in patients with B cell immunodeficiencies?
a. IgG levels dictate frequency of immunoglobulin infusion.
b. Immunoglobulin replacement via subcutaneous route is preferred by patients since injections are done less frequently compared to intravenous injections.
c. The subcutaneous route is safer and more efficacious.
d. The clinician should monitor occurrence of sinus and respiratory infections to determine frequency of immunoglobulin replacement.
PRINCIPLES OF IMMUNOGLOBULIN REPLACEMENT
• Should not be based on IgG levels alone
• Guided by occurrence of infections
• Intravenous and subcutaneous routes are equally safe and efficacious
• IV injections are done every 3-4 weeks
• Subcutaneous injections are usually done weekly
The correct answer is: The clinician should monitor occurrence of sinus and respiratory infections to determine frequency of immunoglobulin replacement.
Which is the most frequent trigger of Hemophagocytic lymphohistiocytosis (HLH)?
a. CMV infections
b. EBV infections
c. Streptococcal infections
d. Enteroviral infections
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)
• Characterized by unremitting activation of CD8+ T cells and macrophages that lead to organ damage
o Often induced by viral infections
• Most frequent: EBV infections
The correct answer is: EBV infections
Recurrent viral, Candida, and opportunistic infections are suggestive of impairment in which line of immune defense?
a. B cells
b. Complement system
c. T cells
d. Innate immune system
CLINICAL FINDINGS IN PIDs
- Respiratory tract infections: reflect impaired antibody response
- Invasive bacterial infections: complement deficiencies
- Recurrent Candida, viral, and opportunistic infection: impaired T cell immunity
- Deep-seated abscesses: innate immune defects
The correct answer is: T cells
Which is true regarding Mendelian susceptibility to Mycobacterial disease?
a. This is the most common PID of the innate immune system.
b. Patients are only susceptible to tuberculous mycobacterial infections.
c. Prognosis is good in complete IFN-gamma receptor deficiency once anti-mycobacterial medications are administered.
d. Those with IL-12 deficiency are also at risk for Salmonella infections.
Feedback
MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE
- It is a rare PID of the innate immune system
- Patients are susceptible to BOTH tuberculous and non-tuberculous mycobacterial infections
- Complete IFN-gamma receptor deficiency may lead to fatal mycobacterial infections despite aggressive treatment
- Patients with IL-12 deficiency are also at risk for Salmonella infections
The correct answer is: Those with IL-12 deficiency are also at risk for Salmonella infections.
Howell-Jolly bodies are seen in peripheral blood smear of patients with:
a. Leukocyte adhesion deficiency
b. Severe congenital neutropenia
c. Asplenia
d. Wiskott-Aldrich syndrome
The correct answer is: Asplenia
Which organism is commonly associated in biliary, hepatic, and chronic gut infections of patients with certain T cell immunodeficiencies?
a. Klebsiella pneumoniae
b. Cryptosporidium
c. Non-tuberculous mycobacteria
d. Escherichia coli
PREDISPOSITION TO INFECTIONS OF CERTAIN T CELL DEFICIENCIES
Early in life:
• P. jiroveci pneumonia
Late in life:
• Cryptosporidium colitis, biliary, and hepatic infections
The correct answer is: Cryptosporidium
Which is true regarding management of SCID?
a. Hematopoietic stem cell transplantation (HSCT) is often not curative.
b. SCID does not respond to immunoglobulin replacement.
c. Gene therapy is effective in all phenotypes of SCID.
d. Aggressive antimicrobial prophylaxis/treatment should be instituted.
TREATMENT OF SCID • Anti-infective therapies • Nutritional support • Immunoglobulin replacement • HSCT: high curative potential
The correct answer is: Aggressive antimicrobial prophylaxis/treatment should be instituted.
Which primary immunodeficiency of the innate immune system is characterized by delayed loss of the umbilical cord, impaired wound healing, and massive hyperleukocytosis?
a. Asplenia
b. Chronic granulomatous diseases
c. Leukocyte adhesion deficiency (LAD)
d. Severe congenital neutropenia (SCN)
LEUKOCYTE ADHESION DEFICIENCY (LAD)
• Mutation in ß2 integrin gene
• Affected individuals are susceptible to bacterial and fungal infections
• Other features include:
(a) Impaired wound healing
(b) Hyperleukocytosis (> 30,000, predominantly granulocytes)
(c) Delayed loss of the umbilical cord
The correct answer is: Leukocyte adhesion deficiency (LAD)
A 16/F with history of clipping of ruptured basilar artery aneurysm (histopathology: hyphal elements), was referred to the immunology clinic for further evaluation. On review of past medical history, she had repeated admissions for bronchiectasis. Examination revealed oral thrush and dysmorphic nail beds. What is the most likely PID of this patient?
a. Chronic mucocutaneous candidiasis (CMC)
b. IgA deficiency
c. Chronic granulomatous diseases
d. Wiskott-Aldrich Syndrome
CHRONIC MUCOCUTANEOUS CANDIDIASIS Abnormality: failure of T cells to produce cytokines, which are essential for expression of cell-mediated immunity to Candida Characterized by: • Recurrent noninvasive thrush • Dystrophic nails • Enamel hypoplasia • Recurrent bronchiectasis • Brain aneuryms
The correct answer is: Chronic mucocutaneous candidiasis (CMC)
Which is true regarding common variable immunodeficiency (CVID)?
a. This disease is usually diagnosed in childhood.
b. Family history of CVID is noted in most cases.
c. Asplenia is a common finding.
d. Aside from infections, patients are also prone to develop granulomatous lesions.
COMMON VARIABLE IMMUNODEFICIENCY (CVID)
• Characterized by low serum levels of one or more subtypes of Ig
• Disease is usually recognized in adulthood
• Only 10% of cases have family history of disease
• Aside from infections, patients tend to develop granulomatous lesions, lymphomas, and lymphoproliferation (splenomegaly).
The correct answer is: Aside from infections, patients are also prone to develop granulomatous lesions.
Which of the following is a laboratory feature of Hemaphagocytic lymphohistiocytosis (HLH)?
a. High natural killer (NK) cell activity
b. Hypertriglyceridemia
c. Hyperleukocytosis
d. Normal fibrinogen
LABORATORY FEATURES OF HLH • Cytopenias • Hypertriglyceridemia • Hypofibrinogenemia • Reduced or absent NK activity • Elevated liver enzymes • Hemophagocytic features on bone marrow or CSF
The correct answer is: Hypertriglyceridemia
A 22/F medical student presented with enlarged lymph nodes, splenomegaly, jaundice, elevated liver enzymes, and an anti-smooth muscle antibodies (ASMA) titer of 1:40. After further work-up, she was told that she has a FAS mutation and a defect in lymphocyte apoptosis. What are other autoimmune diseases she is at risk of developing?
a. Anti-phospholipid syndrome
b. Hashimoto’s thyroiditis
c. SLE
d. Uveitis
AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME (ALPS)
• Nonmalignant T and B cell proliferation
• Clinical manifestations: splenomegaly and enlarged lymph nodes
• Associated autoimmune diseases:
o Uveitis
o Autoimmune hepatitis
o Guillain-Barre Syndrome
o Autoimmine hemolytic anemia
The correct answer is: Uveitis
Which of the following is true regarding Ataxia-telangiectasia (AT)?
a. Cerebellar ataxia may not be detected before the age of 3.
b. This disorder should be considered in children with elevated levels of IgE.
c. Associated sinus and respiratory infections are mild and resolve with antibiotic therapy.
d. Except for cerebellar ataxia, an otherwise unremarkable course in adulthood is expected.
ATAXIA-TELANGIECTASIA (AT)
• Disorder should be considered in children with IgA deficiency and problematic/recurrent infections
• Cerebellar ataxia may not be detectable before the age of 3.
• Telangiectasias are seen over the sclerae.
• Affected individuals are at increased risk of lymphomas, leukemias, and carcinomas in adulthood.
The correct answer is: Cerebellar ataxia may not be detected before the age of 3.
Which is true of IgA deficiency?
a. Affected individuals are less likely to develop drug allergies and atopic disorders.
b. Most individuals with IgA deficiency are symptomatic.
c. Symptomatic cases are usually related to CVID.
d. Indications for immunoglobulin replacement is limited for this disorder.
IgA DEFICIENCY
• Most common PID
• Affected individuals are at increased risk
• Most cases are asymptomatic
• Symptomatic IgA deficiency is usually related to CVID
• Recurrent sinus and pulmonary infections – should prompt immunoglobulin replacement
The correct answer is: Symptomatic cases are usually related to CVID.
Which of the following is a feature of autosomal dominant-hyper IgE syndrome?
a. Coarse facial features
b. Supernumerary teeth
c. Uncomplicated lung infections
d. Non-responsive to immunoglobin replacement
AUTOSOMAL DOMINANT-HYPER IgE SYNDROME • Elevated IgE level is typical • Features include: o Facial dysmorphy o Defective loss of primary teeth o Recurrent lung infections complicated by pneumatocoeles o Recurrent skin infections • To prevent bacterial infections, immunoglobulin replacement be used
The correct answer is: Coarse facial features
Which of the following strongly suggests SCID?
a. Eosinophilia
b. Lymphocytopenia
c. Neutropenia
d. Platelet clumping
DIAGNOSIS OF SCID
• Lymphocytopenia – strongly suggests SCID (seen in at least 90% of cases)
• Caveat: this may be masked by presence of maternal T cells (derived by maternal-fetal blood transfers)
The correct answer is: Lymphocytopenia
Which PID is characterized by short-limb dwarfism, sparse hair, and metaphyseal dysostosis?
a. Autosomal dominant hyper IgE Syndrome
b. Cartilage Hair Hypoplasia Disease
c. DiGeorge Syndrome
d. Wiskott-Aldrich Syndrome
CARTILAGE HAIR HYPOPLASIA (CHH) DISEASE
• Mode of inheritance: autosomal recessive
• Features:
o (a)Short-limb dwarfism
o (b)Fine, sparse hair
o (c)hyperextensible joints of hand and feet
• Affected individuals are at risk for autoimmunity, tumors, and erythroblastopenia
The correct answer is: Cartilage Hair Hypoplasia Disease
Which underlying mechanism of SCID causes bone dysplasia with abnormalities noted in costochondral junction on X-ray?
a. Adenosine deaminase (ADA) deficiency
b. Adenylate kinase 2 deficiency
c. Cytokine signaling deficiency
d. Rearrangement in T and B cell receptors
ADENOSINE DEAMINASE (ADA) DEFICIENCY
• Induces premature cell death of lymphocyte progenitors
• Causes:
o (a) Bone dysplasia with abnormal costochondral junctions
o (b) Neurologic defects
The correct answer is: Adenosine deaminase (ADA) deficiency
Which B cell immunodeficiency can be a manifestation of myelodysplastic syndrome?
a. Agammaglobulinemia
b. Common variable immunodeficiency (CVID)
c. Hyper IgM syndrome
d. IgA deficiency
AGAMMAGLOBULINEMIA
• Mutation in the BTK gene (located in X chromosome)
• Types:
o (a)X-linked agammaglobulinemia
o (b)Autosomal recessive agammaglobulinemia
• Enteroviral infections are common
• It can be a manifestation of MDS
• Some cases in adulthood are associated with thymoma
• Treatment: immunoglobulin replacement
The correct answer is: Agammaglobulinemia
In patients with persistent severe rhinitis, what is the first recommended step for management?
a. Immunotherapy
b. Subcutaneous omalizumab
c. ENT evaluation
d. Short course oral steroids
The correct answer is: Short course oral steroids
Which of the following factors portend a poor outcome in anaphylaxis?
a. Recurrent idiopathic anaphylaxis
b. Childhood anaphylaxis
c. Anaphylaxis in an asthmatic
d. Drug triggers like allopurinol
The correct answer is: Anaphylaxis in an asthmatic
A 20 year old female who has allergies consults in your late afternoon clinic frequent nasal congestion with pruritus and watery nasal discharge. She notes that there is with improvement when she takes decongestant. What is the appropriate question to ask to ascertain the possible allergen?
a. What did you eat for breakfast?
b. What time of the day do the symptoms develop?
c. Where did you last travel?
d. Did you apply a new perfume lately?
The correct answer is: What time of the day do the symptoms develop?
A school teacher consults for acute edema and pruritus around the eyes after cleaning the classroom for start of classes. Which level of the skin is affected by this manifestation?
a. Dermis
b. Epidermis
c. Dermo-epidemal junction
d. All levels of the skin
The correct answer is: Dermis
Which of the following histologic features is most likely to be found in a patient complaining of prolonged episodes of painful and nonpruritic urticaria with resultant scarring?
a. Adventitial and medial fibrosis
b. Fibrinoid necrosis of the venules
c. Perivascular lymphocytic infiltrate
d. Necrotizing granulomatous inflammation of vessel walls
The correct answer is: Fibrinoid necrosis of the venules
Which of the following is the next line of therapy for a patient with recurrent episodes of hives and wheezing upon exposure to low ambient temperatures that does not adequately respond to first-line treatments?
a. Cyclosporine
b. Hydroxychloroquine
c. Methylprednisolone
d. Omalizumab
The correct answer is: Omalizumab
What is rhinitis medicamentosa?
a. Intermittent nasal congestion after chronic exposure to oral decongestants
b. Rebound nasal congestion usually noted after 3 weeks of oral decongestants
c. Chronic nasal congestion after a week’s use of a newly prescribed intranasal decongestant
d. Nasal congestion developing after more than 10 days use of topical intranasal decongestant
The correct answer is: Nasal congestion developing after more than 10 days use of topical intranasal decongestant
Which of the following primary immunodeficiencies is secondary to impaired development of T lymphocytes?
a. Ataxia telangiectasia
b. Common variable immune deficiency (CVID)
c. Severe combined immune deficiencies (SCID)
d. Wiskott—Aldrich Syndrome
The correct answer is: Severe combined immune deficiencies (SCID)
Which statement corresponds to congenital asplenia?
a. Recurrent encapsulated bacterial infections from childhood
b. History of gram negative sepsis in a young non-diabetic
c. Overwhelming pulmonary and extrapulmonary tuberculosis
d. Recurrent fungal infections
The correct answer is: Recurrent encapsulated bacterial infections from childhood
A 26-year old patient diagnosed with SLE has recurrent infections. Which infections is usually seen in her case?
a. Invasive Neisserial infections
b. Recurrent furunculosis and folliculitis
c. Frequent fungal infection
d. Extrapulmonary TB
The correct answer is: Recurrent furunculosis and folliculitis
Which of the T cell immunodeficiencies places the affected individual at very high risk for development of hematopoietic and solid organ malignancies in his lifetime?
a. Ataxia-telangiectasia
b. Dyskeratosis congenita
c. Omenn Syndrome
d. SCID
The correct answer is: Ataxia-telangiectasia
Serum levels of this arachidonic-acid derived product directly correlates with anaphylaxis severity of anaphylaxis
a. Leukotrienes
b. Platelet activating factor (PAF)
c. Prostagladin D2
d. Prostagladin E2
The correct answer is: Platelet activating factor (PAF)
