Infectious dx, Systemic diseases Flashcards
a
Regarding HIV, discuss:
1. What type of virus is it?
2. Pathophysiology of HIV?
3. What is AIDS?
4. What are the risk factors of infection?
5. Diagnosis
6. Treatment
HIV VIRUS:
- Human Immunodeficiency Virus
- Family retrovirus, lentivirus
- HIV is a spherical, enveloped, single stranded RNA virus containing two copies of its genome
- Strong disease correlation with CD4 counts
PATHOPHYSIOLOGY:
- Infection results from inoculation of infected body fluid (e.g. blood, semen, saliva, etc.)
- Retrovirus that attaches to CD4+ cell marker of T-helper cells, macrophages, and other immunologic cells
- Once attaches –> becomes internalized –> proviral DNA gets synthesized from reverse transcriptase –> proviral DNA integrates into host DNA
- Results in decreased number of T-helper cells and impaired function of macrophages, neutrophils, B-lymphocytes, and complement activation also associated with abnormal immune regulation, atopy, and autoimmune disease
AIDS = ACQUIRED IMMUNE DEFICIENCY SYNDROME:
- Defined when an HIV patient:
1. Develops an “AIDS-defining illness”, OR
2. CD4 counts < 200cells/µL, OR
3. CD4 percentage < 14% prior to effective antiretroviral therapy, OR
4. CD4/CD8 ratio < 1.5
- AIDS-defining illness examples: Esophageal or tracheal candidiasis, CMV disease, Kaposi’s sarcoma, pneumocystic pneumonia
- Cause of death for most AIDS patients is sepsis or disseminated neoplasms
RISK FACTORS:
1. Multiple sex partners
2. Unprotected intercourse
3. IV drug use
4. Racial/ethnic minority status
5. Blood transfusions (rare in US with current screening methods)
6. Health care workers (rare)
7. Most common methods of acquisition vary depending on region
- Male homosexual intercourse + IV drug use in US
- Heterosexual intercourse in the developing world
- IV drug use in eastern europe
DIAGNOSIS:
1. First diagnosed by screening with ELISA (enzyme-linked immunosorbent assay) to detect anti-HIV antibodies (rule out test) - diagnosed with 2 or more reactive screenings
2. Then confirmed with Western Blot or recombinant ELISA (rule in test) or immunofluorescence assays that detect specific Antibodies against HIV antigen
3. Also confirm with CD4+ count, and CD4+/CD8+ ratio
TREATMENT:
1. Combination antiviral medications
2. Prophylaxis against opportunistic infections
Describe the categories or stratification of HIV illness based on CD4 counts
CLINICAL CATEGORIES (3):
- Type A = CD4 > 500 cells / µL
- Asymptomatic
- Progressive generalized Lymphadenopathy (PGL)
- Acute HIV infection - Type B = CD4 between 200-499 cells/µL
- Symptomatic condition attributed to HIV infection and associated defects in cell-mediated immunity
- Mild weight loss
- Recurrent URTIs
- Skin/fungal/oral infections (e.g. dermatitis, angular cheilitis)
- VZV reacftivation - Type C = CD4 < 200 cells/µL = AIDS (Defined above)
- Severe weight loss
- Oral opportunistic infections (e.g. candida, HSV)
- Pulmonary TB
- Anemia, neutropenia, thrombocytopenia
- Treatment: consider prophylactic Septra - CD4 < 50 cells/µL
- Wasting
- Esophageal candida
- Extrapulmonary TB
- CMV
- Defining manifestations: Pneumocystis pneumonia (PCP) - caused by the opportunistic fungus Pneumocystis jiroveci, MAC (Mycobacterium avium complex), Cryptococcus-meningitis
- Malignancies: Kaposi’s sarcoma, CNS-lymphoma, other (skin, cervix, etc.)
What are the pathologies associated with low CD4 counts and what prophylaxis can be given if possible?
- < 400 cells/uL = TB
- < 200 cells/uL = Non-Hodgkin’s lymphoma (including sinonasal), pneumocystic jirovecci (PCP fungal pneumonia)
- < 150 cells/uL = Fungal sinusitis
- < 100 cells/uL = Kaposi sarcoma, Cryptococcal meningitis, toxoplasmosis
- < 50 cells/uL = Aspergillus, Cryptosporidiosis, CMV, MAC Mycobacterium avium complex - treated with Azithromycin prophylaxis
Note: Hodgkin’s lymphoma is associated with a wide range of CD4
What are 5 dermatologic manifestations of HIV? How can they be managed?
- Molluscum Contagiosum - excise
- Herpes Zoster Virus
- Seborrheic dermatitis - steroids
- Kaposi sarcoma - low dose XRT, palliative ± chemo
- Bacillary angiomatosis (neovascular proliferation in the skin or the internal organs (peliosis) due to an infection with Bartonella henselae or Bartonella quintana) - Erythromycin
Molluscum: https://en.wikipedia.org/wiki/Molluscum_contagiosum
What are all the Otolaryngologic manifestations of HIV?
OTOLOGY:
1. EAC: Kaposi sarcoma, seborrheic dermatitis, otitis externa or necrotizing OE
2. Serous and AOM - bacterial (staph, pseudomonal, candida, p. carinii)
3. Mild-moderate SNHL (30%) - cryptococcal or mycobacterial meningitis, otosyphillis, toxoplasmosis, autoimmune demyelination of the cochlear nerve, CPA tumors
4. Mastoiditis (invasive aspergillosis, pneumocystic, mycobacterium)
5. TM perforations
6. Aural polyps
7. Facial nerve paralysis (herpes zoster, CMV, EBV, autoimmune demyelination, meningitis, encephalitis, necrotizing OE)
8. Temporal bone neoplasms (Hodgkins and NHL, Kaposi’s sarcoma)
SINONASAL:
1. CRS: Pseudomonas, mucor, aspergillosis
2. Kaposi sarcoma
3. Non-hodgkin’s lymphoma
4. Acute invasive fungal sinusitis (mucor)
OROPHARYNGEAL:
1. Thrush / candidiasis
2. Recurrent aphthous ulcers
3. Hairy leukoplakia (anterior/lateral border of tongue)
4. Kaposi sarcoma - often ulcerated
5. Non-Hodgkin’s lymphoma (Waldeyer’s ring)
6. Necrotizing ulcerating gingivitis/periodontal disease/stomatitis
7. Herpes stomatitis
8. Thrombocytopenic purpura
9. Bone loss caused by bacillary angiomatosis
LARYNGEAL:
1. Laryngitis (viral, fungal, myobacterial, CMV, EBV)
2. Non-Hodgkin’s lymphoma
3. Kaposi sarcoma
4. Epiglottitis
NECK:
1. Deep neck space abscess
2. Infectious lymphadenopathy (e.g. mycobacterium, pneumocystis, CMV, EBV, Toxoplasmosis, cat-scratch disease, bacterial)
3. Neoplastic lymphadenopathy (e.g. HOdgkin’s and NHL, metastatic disease, thyroid tumors)
4. Persistent generalized adenopathy
PAROTID:
1. Xerostomia
2. Enlargment/hypertrophy
3. Benign lymphoepithelial lesions
4. Malignancies and neoplasms
5. Parotitis
What is the differential diagnosis of cervical disease in HIV? (5)
- Progressive generalized lymphadenopathy (PGL, 12-45%)
- Mycobacterium tuberculosis
- Pneumocystis carinii
- Lymphoma
- Kaposi sarcoma
What are 8 indications for open biopsy of lymphadenopathy in HIV?
- FNA suggestive of malignancy
FNA negative for malignancy with any of:
1. Enlarging node
2. Node > 2cm
3. Asymmetric, localized, unilateral adenopathy
4. Significant mediastinal or abdominal lymphadenopathy
5. Failed antibiotic trial
6. Low CD4 with new lymphadenopathy
7. B symptoms - fever, night sweats, weight loss
How many types of Human Herpes Virus are there, and what are their names?
9 (HHV 1-8 with 6A + 6B)
HHV1: Herpes simplex virus -1 (HSV-1)
HHV2: Herpes simplex virus-2 (HSV-2)
HHV3: Varicella zoster virus (VZV)
HHV4: Epstein-barr virus (EBV), lymphocryptovirus
HHV5: Cytomegalovirus
HHV6a: Roseolovirus
HHV6b: Herpes Lymphotropic virus
HHV7: Pityriasis Rosea
HHV8: Kaposi’s sarcoma-associated herpesvirus
Regarding Kaposi’s sarcoma, discuss:
1. Cause
2. Clinical Presentation
3. What are the types?
4. What is the general treatment?
5. Indications for treatment of localized Kaposi (4)
4. Treatment for small localized Kaposi (6)
5. Indications for treatment of systemic Kaposi (4)
6. Treatment optiosn for systemic Kaposi (6)
CAUSE:
- Tumor caused by infection with HHV-8 (95%)
- Exacerbated by immunosuppression
CLINICAL PRESENTATION:
- Purple patches or nodules on the skin and/or mucous membranes
- Can be ulcerated
- May have visceral lesions as well
TYPES: “CIAA”
1. Classic (seen in Mediterranean and European middle aged men; cutaneous lesions)
2. Iatrogenically immunocompromised
3. African endemic
4. AIDS-related
Treatment:
- Overall, correct underlying immunosuppression
- Generally palliative
INDICATIONS FOR LOCALIZED TREATMENT:
1. Symptomatic lesions
2. Improve local control
3. Cosmetically disfiguring lesions
4. Functional impairment
TREATMENT OPTIONS FOR SMALL LOCALIZED KAPOSI SARCOMAS:
1. Alitretinoin topical gel
2. XRT (for localized obstructing lesions)
3. Laser excision
4. Surgical excision
5. Intralesional chemotherapy - vinblastine, or interferon
6. Cryotherapy
INDICATIONS FOR SYSTEMIC TREATMENT:
1. Visceral disease
2. Pulmonary disease
3. Extensive mucocutaneous involvement (>10 new in 1 month)
4. Pain or edema associated with lymphadenopathy
TREATMENT OPTIONS FOR SYSTEMIC KAPOSI SARCOMA:
1. Liposomal anthracyclines (Doxo/Daunorubicin)
2. Paclitaxel (taxane chemotherapy)
3. Interferon-a (antiviral, antineoplastic)
4. Vinca alkaloids (vinblastine, vincristine)
5. Bleomycin
6. HAART if AIDS+ (Highly active antiretroviral therapy)
Regarding oral hairy leukoplakia, discuss:
1. What is the cause?
2. What is the chance of developing this with HIV/AIDS?
3. Clinical presentation
4. Differential diagnosis
5. Treatment
CAUSE: EBV infection
AIDS with HIV positivity, chance of oral hair leukoplakia:
- 50% chance of developing this at 16 months
- 80% at 30 months
- 100% at 60 months
CLINICAL PRESENTATION:
1. White, vertically corrugated asymptomatic lesion
2. Usually located on anterolateral tongue
DIFFERENTIAL:
1. Oral candidiasis
2. Kaposi’s sarcoma
3. HSV
4. CMV infections
5. SCC
TREATMENT:
1. Acyclovir if symptomatic
2. Usually recurs
Vancouver Page 14
What are the risks of developing HBV, HCV, and HIV with a known infected needle source?
HBV = 2-40%
- Increased risk if HBeAg in serum
- Chronic active infection - high risk of infectivity
HCV = 3-10%
HIV = 0.2-0.5% (mucosal or broken skin contact - 0.1%)
- Hollow bore needles (3%) have increased risk over suture needles (0.3%)
- Mucous membranes - 0.09%
“30, 3, 0.3” for HBV, HCV, HIV
What are the 3 main types of oral aphthous ulcers? Briefly describe them
- HERPETIFORM: Least common
- < 2mm, self-limited
- Shallow craterform, widespread distribution
- Diferentiate from HSV: Absence of vesicular phase before adult formation, adult onset, pain levels disproportionately greater than the extent of lesion development
- Most affect non-keratinized surface tissue - MINOR: 85% of aphthous ulcers
- < 1cm
- Erythematous halo
- Nonkeratinized mucosa, usually anterior oral cavity
- 7-10 days, healing without scarring - MAJOR (Sutton Disease): 10% of aphthous ulcers
- Size usually more than 1cm
- Posterior aspect of oral cavity and oropharynx
- Odynophagia, deeply cratered, sharply marginated, painful
- Can last up to 6 weeks
- May be a marker for HIV
Compared and contrast Human Herpesvirus lesions with recurrent aphthous stomatitis (minor), with respect to:
1. Etiology
2. Location
3. Vesicle phase
4. Duration
5. Management
6. Prodrome
7. Triggers
8. Biopsy findings
- Etiology
- HHV: Herpes simplex 1+2
- AS: Varied, immune dysfunction - Location
- HHV: Keratinized tissue, mucosa
- AS: movable, non-keratinized - Vesicle phase
- HHV: Yes
- AS: No - Duration
- HHV: 7-14 days
- AS: Varies, usually 7-10 days - Management
- HHV: Topical (docosanol, penciclovir), oral antivirals
- AS: Severity related, usually topical steroids - Prodrome
- HHV: Often
- AS: Uncommonly - Triggers
- HHV: Stress, trauma
- AS: Stress, UV light, foods - Biopsy findings
- HHV: Viral cytopathic effect
- AS: Nonspecific
List all the different head and neck manifestations of tuberculosis
NECK:
1. Cervical lymphadenopathy - most common H/N involvement, usually posterior triangle/supraclavicular, matted
2. Cervical sinus fistula (“Scrofula” - may develop spontaneous via necrosis to skin, or necrosis from biopsy) - pull skin so puncture is not over the mass is a way to alleviate this
OTOLOGIC:
1. Thickened TM
2. Multiple small TM perforations (TB until proven otherwise) - perforations may coalesce into total TM destruction
3. Middle ear granulation
4. Seropurulent drainage, serous otitis media
5. Facial palsy
NOSE:
1. Septal perforation (cartilaginous perforation)
- vs. Tertiary syphillis - bony septal perforation
OROPHARYNX:
1. Tonsillitis
2. Painful, deep tongue ulcers (can affect any oral surface)
LARYNX: - most common location = posterior glottis
1. Granulation
2. Nodular/exophytic/Ulcerative lesions on any mucosal surface of glottis/supraglottis (may resemble SCC)
3. Turban epiglottis (distorted and thickened epiglottis)
4. Polypoid changes
SALIVARY:
1. Parotid enlargement/salivary enlargement
Regarding tuberculosis of the head and neck, discuss:
1. What are the options for diagnosis?
2. What are the imaging findings?
3. What are the treatment options?
4. What are the stages?
DIAGNOSIS:
1. FNA
2. Sputum C+S
3. DNA or RNA nucleic acid amplification (better sensitivity and specificity)
4. Quantiferon-TB, T-Spot.TB - in-vitro assays
5. Tuberculin (PPD) test + 3-9 weeks post-infection
- >15mm induration in normal hosts
- ≥10mm in high risk populations (inmates, homeless, recent immigrants, etc.)
- ≥5mm in HIV positive individuals, organ transplant recipients, or other patients with defects of cell mediated immunity
IMAGING:
- Chest and neck CT - multiloculated low-density nodal mass with enhancing rims and normal fascial planes
TREATMENT:
1. Intensive phase: Four drug daily regimen for the first two months of - Isoniazid (inhibit Mycolic acid; neurotoxic + hepatotoxic - need to give B6), Rifampin (inhibit RNA polymerase; side effect red-orange color body fluids), Pyrazinamide, and Ethambutol (RIPE)
2. Contintuation phase: 4-9 months of daily Isoniazid and rifampin (based on smear C&S at end of intensive phase)
STAGES:
1. Primary (resp) - lung lesions/pulmonary complex, GI, tonsillar, iliac fossa, lymphadenopathy and caseating granulomas
2. Re-activation stage
3. Systemic
4. Miliary - terminal (disseminated disease)
Regarding Leprosy, discuss:
1. What is the cause?
2. What is the clinical presentation? 8
3. What is the treatment? 3
= Hansen’s disease
CAUSE:
- Mycobacterium Leprae (slow-growing bacteria)
PRESENTATION:
Skin - hypopigmented or erythematous macules
Eyes - Keratitis
Nose - Anterior nasal spine atrophy and maxillary alveolar atrophy; hyposmia
Mouth - mucosal nodules
Neck - lymphadenopathy
Larynx - Laryngeal ulcerations
Face - Facial nerve paralysis
- Keratitis
- Hypopigmented or erythematous macules
- Mucosal nodules
- Hyposmia
- Atrophy of the anterior nasal spine and maxillary alveolar process (fish-mouth deformity)
- Lymphadenopathy
- Laryngeal ulcerations
- Facial nerve paralysis
TREATMENT:
1. Multi-drug therapy x 1 year
- Rifampicin
- Dapsone
- Clofazimine
Regarding Anthrax, discuss:
1. What is the cause?
2. What is the clinical presentation?
3. What is the treatment?
CAUSE: Bacillus anthracis (gram +ve bacteria)
PRESENTATION:
1. 95% - small papule, painless necrotic ulcer (looks like an eschar)
2. ± adenopathy
TREATMENT:
1. Penicillin G
https://en.wikipedia.org/wiki/Anthrax
Regarding Tularemia, discuss:
1. What is the cause?
2. What are the symptoms?
3. How is it diagnosed?
4. What is the treatment?
= “Rabbit fever”
CAUSE:
1. Francisella Tularensis (gram negative coccobacillus)
SYMPTOMS: (vision symptoms, blind like a rabbit)
1. Photophobia
2. Decreased visual acuity
3. Cervical lymphadenopathy
4. Ulceroglandular form: Patients have a skin ulcer(s) and swollen tender glands.
DIAGNOSIS:
1. Serum agglutination test (tests for smooth lipopolysaccharide antibodies) - also used for brucellosis
TREATMENT:
1. Streptomycin
Regarding Brucellosis, discuss:
1. What is the cause?
2. What are the symptoms? 3
3. How is it transmitted?
4. How is it diagnosed?
5. What is the treatment?
CAUSE:
1. Brucella Meltenesis (aerobic gram negative)
SYMPTOMS:
1. Granuloma formation
2. Arthalgias
3. Neuropsychiatric manifestations
TRANSMISSION:
1. Transmitted by livestock - goats, sheep, camels
DIAGNOSIS:
1. Serum agglutination test for antibodies against S-LPA (smooth lipopolysaccharide)
TREATMENT:
1. Tetracycline
Regarding Cat Scratch Disease, discuss:
1. What is the cause?
2. What it the clinical presentation? 4
3. What is the diagnostic criteria?
4. What are the investigations?
5. What is the treatment?
6. Complications? 6
CAT-SCRATCH DISEASE
- One of the most common causes of chronic lympahdenopathy in children (vs. atypical mycobacterium)
- Suppurative and necrotic granulomatous lymphadenitis caused by an intracellular pleomorphic gram negative bacilus
CAUSE:
1. Bartonella Henselae (gram negative rod/bacillus)
CLINICAL PRESENTATION:
1. Cutaneous papules at primary sites
2. Tender lymphadenpathy that is later painless and lasts for months - can become suppurative (so don’t I+D)
3. Mild fever/malaise
4. Pustulous lesion tend to ulcerate/fistulize (self-limited)
DIAGNOSTIC CRITERIA:
At least 1 Node ≥ 10mm for ≥ 3 weeks, AND 3/4 of the following
1. Contact with cat
2. Laboratory and radiology findings (PCR showing Bartonella, CT with liver or spleen abscesses)
3. ELISA positive for serum antibody to bartonella henselae or indirect immunofluorescent antibody (IFA) test of >1:64
4. Biopsy of node/skin/liver/bone/eye granuloma showing granulomatous inflammation/stellate pattern in keeping with cat scratch disease & Warthin-Starry silver stain positive
INVESTIGATIONS:
1. Excisional biopsy with Warthin-Starry (silver) staining
2. Cat scratch antigen testing not useful
3. Serum antibody to Bartonella (or ELISA/PCR/IFA as above)
4. CT (liver or spleen abscesses)
TREATMENT:
1. Most sources recommend Macrolides, Fluoroquinolones, or Rifampin x 4-6 weeks - especially if immunocompromised
2. Self-limited
3. Excision (NOT I+D)
COMPLICATIONS:
1. Fistula formation (avoid I&D)
2. Parinaud Oculo-glandular syndrome: Unilateral granulomatous conjunctivitis and regional lymphadenitis
3. Bacillary angiomatosis - skin lesions (also caused by B. Quinatana, in immunocompromised patients)
4. Vertebral osteomyelitis encephalitis
5. Optic neuritis
6. Granulomatous hepatitis
Appearance of nodules: https://www.cancertherapyadvisor.com/wp-content/uploads/sites/12/2019/01/ch6567.fig1_.jpg
Pathology: https://www.pathologyoutlines.com/topic/lymphnodescatscratch.html
Kevan Gen #138
A patient has a first neck mass after dental surgery, FNA shows sulfur granules. What is the diagnosis?
Actinomycosis (acid fast negative)
Note: Nocardia can also produce sulfur granules, but these are differentiated from actinomyces by positive acid-fast staining
Regarding actinomycosis of the head/neck, discuss:
1. What is it
2. What is the cause
3. What is the differential
4. How is it diagnosed? What is the histopathology?
5. Clinical presentation?
6. Treatment
WHAT IS IT?
- Chronic granulomatous and suppurative disease
CAUSE:
1. Actinomyces Israelii (most common) - BACTERIA (despite sounding like a fungus)
2. Non-spore forming anaerobes
3. Normal constituent of the oral flora
4. Dental infection or oromaxillofacial trauma are common antecedent events
DIFFERENTIAL:
1. Nocardia
2. TB
DIAGNOSIS/HISTOLOGY: “The great masquerader of head/neck disease”
- Culture (difficult, takes 14 days)
- Multifilament, branching, anaerobic gram-positive rods
- Sulfur granules (collections of Actinomyces organisms)
- Granuloma formation
- Stains: H&E, Gomorri silver stain
- Note - Gomorri silver stain detects fungus but Actinomyces is a bacteria. It was named like this because of fungal-LIKE fillaments (which is what Actinomyces looks like)
Actino-mycic = “ray-fungus”
CLINICAL PRESENTATION:
- Palpable purple mass - most common H&N manifestation (looks like atypical mycobacteria)
- 61% have visible sinus tracts, CRS symptoms
- 40% have lymphadenopathy
- Often have concurrent dental, sinus or perimandibular disease - infetion typically occurs when mucosa/dental cavity is breached, forming granuloma (as it lives endogenous to oral cavity) - can spread to sinus or larynx
TREATMENT:
1. Longterm antibiotics: Penicillin G IV x 2-6 weeks, then 6 months of PO penicillin
2. Tetracycline or Erythromycin if Pen allergic
3. Surgical debridement possible
Vancouver page 17 pathology slide (gomorri silver stain looks quite blue, like a blue round crystal)
List 5 non-infectious, non-neoplastic causes of lymphadenopathy
3 K’s
1. Kawasaki disease
2. Kikuchi disease (lymphocytosis, fever, splenomegaly - like lymphoma, usually posterior chain adenopathy)
3. Kimora (idiopathic unilateral, usually submandibular adenopathy in asians, high IgE, eosinophilia)
Lipid storage diseases:
1. Gaucher
2. Niemann-Pick
Autoimmune:
1. Sarcoid
2. Sjogren’s
3. Juvenile RA
Granulomatous:
1. Sarcoid
2. Wegener
3. Langerhans Histiocytosis
4. Lupus
Other:
1. Drug reaction
2. Castleman’s disease - HHV8, IL-6, VEGF mediated
Regarding Atypical mycobacterial infection, discuss:
1. Cause
2. Clinical presentation
3. Diagnosis
4. Treatment
ATYPICAL MYCOBACTERIUM:
- Acid fast gram positive obligate aerobes found in the environment: soil, water, vegetables, domestic animals, and dairy products
ORGANISMS:
- M. Avium Intracellulare
- M. Scrofulaceum
- M. Kansasii
“ASK if you want to go to Kansas”
CLINICAL PRESENTATION:
- Ages 1-5
- Submandibular region > pre-auricular > parotid region
- Nontender, slowly enlarging, skin fixation with a violaceous hue
- Corneal ulceration is most common H/N manifestation
- Few systemic effects, rare pulmonary involvement
DIAGNOSIS:
1. PPD (5 units) intradermally - negative or weakly positive; if strongly positive may suggest typical TB (do CXR!)
2. Ziehl-Neelson stain shows AFB & Lowenstein-Jensen medium for culture/sensitivity (2-8 weeks incubation period)
TREATMENT:
1. Antibiotics
- Less cure rate compared to excision, used as an adjunct, if severe adenopathy, residual/recurrent disease, immunocompromised, disseminated disease
- Mono, dual, or triple therapy: Clarithromycin or Azithromycin ± Ethambutol ± Rifampin for disseminated disease
- Used for 6-12 months
- Avoid I&D - fistulization
- Treatment of choice: Curretage or excision (caution in regard to marginal mandibular nerve) - at review course, the optimal answer was surgical excision
- Observation (self-resolving)
Regarding Kawasaki disease, discuss:
1. What is it?
2. Clinical presentation, 4 complications
3. AHA Diagnostic criteria
4. Investigations/workup
5. Treatment
KAWASAKI DISEASE:
- Acute febrile illness of childhood
- Small vessel vasculitis
- Most common cause of acquired heart disease in children
CLINICAL PRESENTATION:
- Usually presents < 5 years of age
- Fever
- Non-suppurative conjunctivitis
- Red dry lips
- Oral ulcers & erythema
- Erythematous desquamative rash of fingers and toes
- Polymorphous truncal rash
- Nonsuppurative cervical adenopathy (1.5cm)
AHA DIAGNOSTIC CRITERIA:
- Fever lasting longer than 5 days and 4/5 of the following main clinical features:
1. CONJUNCTIVITIS: Bilateral, nonexudative, painless bulbar conjunctival injection
2. RASH: Polymorphous generalized rash
3. ADENOPATHY: Acute non-purulent cervical lymphadenopathy with LN diameter >1.5cm, usually unilateral
4. STRAWBERRY TONGUE: Oropharyngeal changes - erythema, fissuring, and crusting of the lips, strawberry tongue
5. HANDS/FEET: Erythema or edema of the palms and soles, followed by membranous desquamation of the finger and toe tips
“CRASH and Burn”
INVESTIGATIONS/WORKUP:
1. Echocardiography to evaluate for coronary artery aneurysms
2. ESR + CRP
3. Abdominal U/S (acalculous cholecystitis)
TREATMENT:
1. IVIg
2. Aspirin (high-dose)
3. Steroids
4. Methotrexate
5. Cyclophosphamide
6. Anticoagulants in aneurysm patients
Regarding Measles, discuss:
1. Causative organisms
2. Clinical presentation
3. Management
4. Systemic complications 5
MEASLES = RUBEOLA
CAUSE:
1. Paramyxoviridae family (same as mumps)
CLINICAL PRESENTATION:
1. Prodrome of fever, cough, coryza, and conjunctivitis
2. During prodrome: Koplik’s spots on mucosal membranes
3. 14 days after exposure: Morbilliform rash (maculopapular rash)
4. Otologic complications (0.1% cases)
- AOM/mastoiditis (superinfection)
- Profound bilateral SNHL (50%)
- Thought to lead to otosclerosis
5C’s: cutaneous rash, cough, coryza, conjunctivitis, Koplik spots
MANAGEMENT:
1. Supportive care
SYSTEMIC COMPLICATIONS:
1. Diarrhea
2. Superinfections
3. Laryngotracheobronchitis
4. Acute encephalitis
5. Subacute sclerosing panencephalitis
Koplik: https://en.wikipedia.org/wiki/Koplik%27s_spots
Regarding Syphillis, discuss:
1. What are the stages and manifestations?
2. What is congenital syphillis?
3. What is the cause?
4. How is it diagnosed?
5. What is the treatment?
CAUSE:
- Treponema Pallidum (spirochete bacteria) - transmitted sexually or vertically
STAGES:
1. Primary
- Oral/genital painless chancre at inoculation site
- Reactive LN
- Incubation 3 weeks asymptomatic
- Secondary (highly contagious)
- General malaise, fever, arthralgia
- Maculopapular rash
- Nephrotic syndrome, hepatosplenomegaly
- Mucocutaneous lesions “mucous patches”, serpiginous ulcers, nodules / genital condyloma lata, fissures of nasal vestibule
- Painless “snail-track” ulcers of the tonsils and soft palate
- Nose, oral cavity, pharynx, larynx - pharyngitis
- 3-12 weeks - Latent
- Asymptomatic (may return to mucocutaneous lesions)
- 1/3 progress to tertiary
- 1/3 latent
- 1/3 resolve - Tertiary (may occur years after initial infection, slowly progressive)
- Gumma - rubbery-like lesion with a centre of necrotic tissue and punched out edges
- Septal perforations (bony)/saddle nose deformity
- TM perforations
- VC paralysis
- Dysphagia
- SNHL neurosyphillis
- Tullio phenomenon (sound-induced vertigo, nystagmus, or both)
- Hennebert’s sign (Pressure-induced vertigo, nystagmus, or both, elicited by insufflation of the external auditory canal)
- Meniere’s like symptoms
- Aortic aneurysms
- CNS complications
- Argyll-Robertson pupil - constricts with accomodation but not to light
- Osseous and cartilaginous destruction
CONGENITAL SYPHILLIS (often fatal)
- Early like secondary, late like tertiary
- Frontal bossing
- Mental retardation
- Mulberry molars
- Sabre shins (bent), Clutton’s joints (bilateral knee effusions)
- Septal perforation + saddle nose
- Hepatosplenomegaly
- Lymphadenopathy
- Labyrinthitis
- Epiphysitis (ends of the longer bones become swollen and painful)
- Hutchinson’s Triad: Notched incisors, SNHL, interstitial keratitis (NOTE: Cogan Syndrome - has SNHL + Interstitial keratitis - need to rule out Syphillis if you see Cogan syndrome)
DIAGNOSIS:
1. Screen: VDRL test (Gram negative spirochete), RPR - rapid plasma reagin screening test
2. If negative, repeat
3. If positive –> fluorescent treponemal antibody-absorption (FTA-TP) or Microhemoagglutination test (MHA-TP), using Warthin-Starry stain
TREATMENT:
1. Penicillin G (alternative: Ceftriaxone, Doxycyclin, Azithromycin)
2. Steroids for SNHL or vestibular symptoms
3. Treat until serologic markers are negative
Gumma: https://escholarship.org/content/qt5gs4q6wz/1.jpg
Vancouver notes Page 18
What disease can look like congenital syphillis with interstitial keratitis but negative VDRL?
Cogan’s Syndrome
- Should look for congenital syphillis in a patient presenting with Cogan’s syndrome
What is the likely cause of superficial “snail track” ulcers of the tonsils and soft palate?
Secondary syphillis
What are viral causes of pharyngitis?
Viral is the most common in adults and children
Common causes:
1. EBV
2. Adenovirus
3. Rhinovirus (most common cause of common cold)
4. Respiratory Syncytial virus (30-60%)
Other:
1. HSV 1+2
2. CMV
3. Parainfluenza
4. HIV
5. Measles
What are the most common bacterial causes of:
1. Suppurative pharyngitis
2. Acute otitis media
3. Acute sinusitis
4. Mastoiditis
5. Otitis externa
- Suppurative pharyngitis - Group A strep
- Acute otitis media - Strep pneumo, H. flu, M. Catarrhalis
- Acute sinusitis - Strep pneumo, H. flu, M. Catarrhalis
- Mastoiditis - Strep pneumo, Strep viridans, pseudomonas
- Otitis externa - Pseudomonas, staph aureus
How is rheumatic fever diagnosed at the first episode vs. subsequent episodes?
- Diagnosis at first episode: evidence of antecedent group A beta-hemolytic streptococcal infection of two major criteria or one major and two minor Jones criteria
- Diagnosis of subsequent episodes require a confirmation of two major criteria or one major and two minor or three minor criteria
JONES CRITERIA (stratified into low vs. mod/high risk based on epidemiological location)
Major Criteria:
Carditis
Chorea
Arthritis
Polyarthralgia
Erythema marginatum
Subcutaneous nodules
Minor criteria:
Fevers
ESR or CRP elevated
Arthralgias
Prolonged PR intervals
MAJOR CRITERIA: LOW RISK
1. Carditis (clinical or subclinical)
2. Arthritis - only polyarthritis
3. Chorea
4. Erythema marginatum
5. Subcutaneous nodules
MAJOR CRITERIA: HIGH RISK
1. Carditis (clinical or subclinical)
2. Arthritis - monoarthritis or polyarthritis
3. Polyarthralgia
4. Chorea
5. Erythema marginatum
6. Subcutaneous nodules
MINOR CRITERIA: LOW RISK
1. Polyarthralgia
2. Hyperpyrexia (≥ 38.5 degrees)
3. ESR ≥ 60mm/h and/or CRP ≥ 3.0mg/dl
4. Prolonged PR interval (after taking into account the differences related to age, if there is no carditis as major criterion)
MINOR CRITERIA: HIGH RISK
1. Monoarthralgia
2. Hyperpyrexia (≥ 38 degrees)
3. ESR ≥ 30mm/h and/or CRP ≥ 3.0mg/dl
4. Prolonged PR interval (after taking into account the differences related to age, if there is no carditis as major criterion)
Jones: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734099/#:~:text=The%20five%20cardinal%20manifestations%20of,with%20little%20amendment%20over%20time.
Regarding Scarlet Fever, discuss:
1. What is the organism cause?
2. Clinical features 4
3. How is it diagnosed?
4. What is the treatment?
CAUSE:
1. Strep Pyogenes (Group A Strep) which release pyrogenic exotoxins
CLINICAL FEATURES:
1. Pharyngitis
2. High fever
3. Erythematous rash that blanches with pressure, sandpaper quality, worse in flexor creases “Pastia’s lines”, begins on trunk and spreads laterally, spares palms/soles/face
4. Strawberry tongue
DIAGNOSIS:
1. Rapid antigen detection test
2. GAS culture (gold standard)
TREATMENT:
1. Penicillin x 10 days
What are the diagnostic laboratory findings of EBV?
What is the false negative rate?
- Elevated WBC
- > 50% lymphocytes
- Atypical lymphocytes >10%
- Monospot = Serum heterophile antibodies to horse or sheep erythrocyte
- 10% false negative
What are 3 reasons for false negative monospot tests (heterophil antibody test)
- < 10 years old
- CMV mono
- Early disease
What are the most sensitive tests for mononucleosis?
- IgM: Viral capsid antigen (current and recent disease)
- IgG: current and past disease; antibodies against the following last:
- EBV-Viral capsid antigen (lasts 4-6 weeks)
- EBV-Nuclear antigen (NA) (present at 1 week - for life)
- Early antigen - 3-6 months - Monospot/Heterophile Antibody test is negative in early disease (for 2-3 weeks)
- False negative in < 3 years old
- 60% at 2 weeks
- 90% at 4 weeks
What are five causes of false positive heterophil antibody test for infectious mononucleosis?
- Brucella
- Rheumatoid arthritis
- Serum sickness
- Hodgkin’s lymphoma
- Hepatitis
BRoS He’s a Heterophile
Brucella
Rheumatoid arthritis
Serum sickness
Hodgkin’s lymphoma
Hepatitis
Regarding Pertussis, discuss:
1. What are the causative organisms?
2. What are the phases/clinical presentation?
3. What is the treatment?
ORGANISM:
1. Bordetella pertussis
PHASES:
1. Catarrhal
- Lasts 1-2 weeks, highly contagious
- Runny nose, low grade/no fever
- Mild, occasional cough
- Paroxysmal
- Lasts 1-6 weeks, up to 10 weeks
- Contagious
- Fits of rapid coughing that may be followed by “whoop” sound or vomiting - Convalescent:
- Lasts 2-3 weeks
- Cough may return with other respiratory infections for many months
- Recovery is gradual, cough lessens but may return
TREATMENT:
1. Macrolides (e.g. Erythromycin, Clarithromycin, and Azithromycin)
What are 5 symptoms/signs of chronic tonsillitis?
- Chronic sore throat
- Halitosis
- Tonsilliths
- Peritonsillar erythema
- Persistent tender cervical adenopathy
What are 4 symptoms of acute adenoiditis?
- Purulent rhinorrhea
- Nasal obstruction
- Fever
- Otitis media
What is the definition of recurrent acute adenoiditis? What is the treatment?
Greater than 4 episodes in a 6 month period
Treatment: INCS ± reflux management for 6-8 weeks minimum
What are the symptoms of chronic adenoiditis?
- Persistent nasal discharge
- Chronic congestiion
- Postnasal drip
- Halitosis
- Adenoid facies - open mouth, elongated face, dark circles under the eyes
- Middle ear effusion - obstructs the ET orifice and allows for bacterial colonization of the area
Define Charcot’s triad
- Nystagmus
- Scanning speech (words are as if measured or scanned; there is a pause after every syllable, and the syllables themselves are pronounced slowly)
- Intention tremor
Associated with multiple sclerosis
Regarding multiple sclerosis, discuss:
1. What is it?
2. What are the causes/risk factors?
3. What is the differential?
4. Clinical presentation and complications?
5. Investigations?
6. How is it diagnosed?
7. What are the types?
8. Treatment?
MS = Demyelinating disease of young adults
CAUSES/RISKS:
1. Unknown cause
2. ?Genetic
3. Caucasian
4. Living in higher latitudes are more at risk
DIFFERENTIAL:
1. ALS
2. MG
3. HIV encephalopathy
4. Lyme disease
5. TIA/CVA
CLINICAL PRESENTATION:
1. Vertigo, nystagmus
2. Deafness
3. Dysphagia
3. Diplopia
4. Bilateral INO (internuclear ophthalmoplegia)
5. Charcot’s triad: nystagmus, scanning speech, intention tremor
6. Lhermitte’s sign is a sudden, uncomfortable sensation that travels from your neck down your spine when you flex your neck.
COMPLICATIONS:
1. Seizures
2. Falls
3. Pressure ulcers
4. Aspiration
5. Pneumonia
INVESTIGATIONS:
1. MRI Brain
2. CSF cytology and chemistry (glucose, high protein, IgG, oligoclonal bands)
3. Evoked potentials
DIAGNOSIS:
- MRI findings of demyelinated foci in white matter
- Abnormal auditory and visual evoked responses
- Elevated CSF protein content (oligoclonal bands)
- Dissemination in time and space. Multiple areas and must have multiple bouts
TYPES:
1. Primary progressive
2. Secondary progressive
3. Relapsing progressive
4. Relapsing remitting
TREATMENT:
1. Interferon beta-1a/b (cytokine)
2. Steroids
Types: https://www.researchgate.net/profile/Daniel-Garcia-Lorenzo/publication/43978711/figure/fig5/AS:669534138675210@1536640786399/Evolution-of-the-four-dierent-clinical-types-of-multiple-sclerosis-Source.png
List the head and neck manifestations of multiple sclerosis
- Vertigo - presenting symptom in 7-10%
- Nystagmus - mainly horizontal
- Deafness - rare
- Diplopia - can be intermittent, paralyzed medial rectus (in INO)
- Bilateral internuclear ophthalmoplegia (INO) - diplopia on one side and unilateral nystagmus, lesion in the medial longitudinal fasciculum (MLF), but convergence is normal
List a differential diagnosis of conditions resembling Myasthenia Gravis 5
- MS
- ALS (EOMs preserved)
- Basilar artery thrombosis
- Lambert-eaton (antibodies against presynaptic calcium channels releasing ACh - muscle weakness - can be associated with paraneoplastic small cell lung cancer)
- Thyroid disease
Regarding myasthenia gravis, discuss:
1. What is it
2. Cause
3. Types
4. Clinical presentation
5. Diagnosis
6. Complications
7. Treatment
MYASTHENIA GRAVIS
- Acquired autoimmune disease with autoantibodies targeting the nicotinic ACh receptor at the motor end plate
CAUSES:
1. Idiopathic (most common)
2. Drugs (penicillamine, antibiotics, beta blockers, lithium)
TYPES:
- Class I: Involves any ocular muscle weakness, including weakness of eye closure. All other muscle groups are normal.
- Class II: Involves mild weakness of muscles other than ocular muscles. Ocular muscle weakness of any severity may be present.
- Class IIa: Involves predominant weakness of the limb, axial muscles, or both. It may also involve the oropharyngeal muscles to a lesser extent.
- Class IIb: Involves mostly oropharyngeal, respiratory muscles, or both. It can have the involvement of limb, axial muscles, or both to a lesser extent.
- Class III: Involves muscles other than ocular muscles moderately. Ocular muscle weakness of any severity can be present.
- Class IIIa: involves the limb, axial muscles, or both predominantly. Oropharyngeal muscles can be involved to a lesser degree.
- Class IIIb: Involves oropharyngeal, respiratory muscles, or both predominantly. The limb, axial muscles, or both can have lesser or equal involvement.
- Class IV: Involves severe weakness of affected muscles. Ocular muscle weakness of any severity can be present.
- Class IVa: Involves limb, axial muscles, or both predominantly. Oropharyngeal muscles can be involved to a lesser degree.
- Class IVb: Involves oropharyngeal, respiratory muscles, or both predominantly. The limb, axial muscles, or both can have lesser or equal involvement. It also includes patients requiring feeding tubes without intubation.
- Class V: Involves intubation with or without mechanical ventilation, except when employed during routine postoperative management.
Overall:
1 = Eyes
2 = Mild other (a = limb, axial, both; b = oropharyngeal, respiratory, both)
3 = Moderate other (a = limb, axial, both; b = oropharyngeal, respiratory, both)
4 = Severe other (a = limb, axial, both; b = oropharyngeal, respiratory, both)
5 = Intubated ± ventilation
CLINICAL PRESENTATION
1. Weakness and fatigue of striated muscles (ptosis, diplopia, dysphonia, dysarthria, dysphagia, VPI, aspiration), especially with repetitive movements
DIAGNOSIS:
1. Tensilon test (Edrophonium) prevents the breaking down of acetylcholine (anti-cholinesterase) –> stimulates muscles –> stronger = positive test
2. 85% positive anti-AchR antibodies
COMPLICATIONS:
1. Myasthenic crisis (with intercurrent illness or medications) and rapid respiratory collapse
TREATMENT:
1. Thymectomy (thymus main production of Anti-AchR antibodies; abnormal thymus = abnormal antibodies)
2. Acetylcholinesterase inhibitors - Edrophonium (Tensilon), Neostygmine, Pryidostigmine (Mestinon) = increases concentration of Ach at the junction
Regarding Carcinoid syndrome, discuss:
1. What is it?
2. Clinical presentation
3. Diagnosis
4. Associations
5. Treatment
CARCINOID SYNDROME:
- Occurs when a rare cancerous tumor called a carcinoid tumor secretes certain chemicals into your bloodstream
- Most common APUDoma (Amine precursor uptake decarboxylase tumor)
- Found usually in ileum & bronchi
- High synchronous (occurs at the same time) and metachronous (occurs at a result of) rate
-Secretes Serotonin
CLINICAL PRESENTATION:
1. Flushing
2. Diarrhea
3. Cardiac valve disease
4. Wheezing
5. Right sided heart failure
DIAGNOSIS:
1. 24 hour urine collection for 5-HIAA (breakdown product of serotonin)
TREATMENT:
1. Surgery
2. Pharmacotherapy
ASSOCIATIONS:
1. MEN1
2. MEN2 (less common than MEN1)
3. NF1
4. Von Hippel Lindau
5. Tuberous sclerosis
Regarding eosinophilic granulomatosis with polyangitis (Churg-Strauss syndrome), discuss:
1. What is it?
2. Differential
3. Clinical presentation
4. Diagnostic criteria
5. Types/stages
6. Investigations
7. Treatment
EGPA:
- Aka. Allergic granulomatous vasculitis; Allergic granulomatous angiitis
- Characterized by fibrinoid, necrotizing epithelioid eosinophilic extravascular granulomas
- Can be fatal if untreated!
DIFFERENTIAL:
- GPA (Wegener’s)
- PAN (Polyarteritis nodosa)
- Goodpasture’s Syndrome
- Hypereosinophilic syndrome
CLINICAL PRESENTATION:
1. Triad: Asthma/allergic rhinitis, eosinophilia, systemic vasculitis of small-medium vessels
2. 70% have nasal involvement (allergic rhinitiis, polyps, obstruction, rhinorrhea, crusting)
3. Asthma
4. Other H/N involvement: Serous otitis media, SNHL in phase 3
DIAGNOSIS: 4/6 CRITERIA NEEDED (85% sensitive, 95% specific)
1. Paranasal sinusitis / polyps
2. Eosinophilia > 10% of WBC in peripheral blood smear
3. Pulmonary infiltrates (non-fixed)
4. Asthma
5. Histology showing vasculitis with eosinophilic infiltrates
6. Mononeuritis complex (ie. mono or polyneuropathy): Painful, asymmetrical asynchronous sensory and motor peripheral neuropathy with isolated damage to at least two separate nerve areas
P-SHAME
Pulmonary infiltrates
Sinusitis
Histology proof of vasculitis
Asthma
Mononeuritis complex
Eosinophilia > 10% peripheral smear
TYPES/STAGES OF EGPA:
1. Allergic (allergic rhinitis, nasal polyps, asthma)
2. Eosinophilic stage (chronic eosinophilic pneumonia or gastritis)
3. Systemic necrotizing vasculitis & infiltrative stage: neuropathies, life-threatening vasculitis (GI ulceration/perforation, peritonitis, myocarditis, pericarditis, CHF)
INVESTIGATIONS:
1. CBC, ESR, CRP
2. **pANCA (+ve in 70%) **
3. cANCA (50% positive)
4. CXR
5. Creatinine and eGFR
6. Biopsy: (note nasal biopsy is rarely helpful)
- Necrotizing extravascular granulomas
- Vasculitis
- Extravascular eosinophilia
TREATMENT:
1. High dose corticosteroids
2. Can try adding cyclophosphamide but does not respond as well as GPA
3. Rapid polyp recurrence after FESS, therefore surgery NOT recommended (only in severe cases to help gain control)
Regarding amyloidosis, discuss:
1. What is it?
2. Where is the most common site in the head and neck?
2. What are the causes?
3. What are the different types and where are their typical deposition locations?
3. Symptoms?
4. How is it diagnosed?
5. Investigations?
6. Pathology and stains?
6. Treatment?
AMYLOIDOSIS:
- A disease that is characterized by the extracellular deposition of fibrillar proteins (build-up of amyloid in structures) - all forms are identical under microscope
COMMON SITE:
1. Glottic involvement (usually vocal cords) - thickening, lumpy cord, rarely yellowing
CAUSES:
1. Idiopathic (2/3)
2. Multiple myeloma (1/4)
3. TB
4. RA
5. Osteomyelitis (1/10)
TYPES:
1. “AL amyloidosis” - previously known as Primary systemic (56%)
- Composed of LIGHT-chain immunoglobulin
- Plasma cell dyscrasia
- Deposition of protein fragments generated by aberrant proteolytic cleavage of normal Ig
- Predominantly affects mesenchymal tissues (heart, tongue, GI)
- 18-24 months survival
- Treatment: Melphalan (chemo) and autologous stem cell transplant (extends survival to 40 months)
Subtypes:
1. Myeloma associated (26%)
2. Primary localized (9% - limited to one site. ofbody and can occur in several neurodegenerative diseases)
- “AA Amyloidosis” - previously known as Secondary systemic (8%)
- Composed of amyloid PROTEIN A
- Overproduction and deposition of serum amyloid A protein
- Associated with chronic inflammatory destructive diseases such as tuberculosis, spondyloarthritis, RA, osteomyelitis
- Primarily affects kidney, adrenals, liver, spleen
- Occurs 10-20 years after inflammatory disease
Subtypes:
1. Secondary localized (limited to one site of body and can occur in several neurodegenerative diseases - Alzheimer’s, Parkinson’s, Huntington’s)
2. Familial amyloidosis (deposition of transthyretin TTR variants)
SYMPTOMS:
1. Nephrotic syndrome (most common systemic amyloidosis)
2. Restrictive myocarditis
3. Hepatomegaly
4. Peripheral neuropathy
5. Macroglossia
6. Ecchymosis (capillary wall infiltration)
7. Bleeding (factor X deficiency)
8. Carpal tunnel syndrome
9. Arthropathy
10. Lymphadenopathy
11. GI dysmotility
DIAGNOSIS:
1. Biopsy, light microscopy - amyloid exhibits an acellular, amorphous, homogeneous, eosinophilic appearance after hematoxylin and eosin staining
2. Primary & myeloma = light chain immunoglobulin (Amyloid is tissue deposits of fibrils composed of monoclonal light chain fragments)
3. Secondary = Amyloid associated protein, confirmed by electron microscopy
INVESTIGATIONS:
1. Biopsy - can biopsy FNA abdominal fat, tongue, minor salivary glands, buccal mucosa
- Shows apple green birefringence (double refraction of light) with Congo Red staining
- When using Potassium Permanganate on the Congo stain, reversal of the apple green birefringence suggests secondary amyloid (e.g. rheumatoid arthritis)
- Metachromatically stains with crystal violet
- Bronchoscopy: Rule out multiple airway lesions
- Biopsy Bone Marrow; high number of plasma cells = multiple myeloma
- Urinalysis = Bence-Jones proteins
TREATMENT:
1. Conservative removal of deposits
2. Steroids
3. Antimetabolites not helpful
4. Supportive treatment of involved organs
https://www.stainsfile.com/theory/methods/staining-amyloid-proteins-for-histology/#:~:text=It%20stains%20metachromatically%20with%20crystal,be%20stained%20with%20trypan%20blue.
What are all the head and neck manifestations of amyloidosis?
EYE:
- Painless mass in the superior orbit
EAR: (extremely rare)
- EAC and concha involvement
NOSE:
- Paranasal sinuses
- Nasopharynx
ORAL:
- Tongue: most common involved area (~50%)
- Macroglossia (5%)
- Oral and pharyngeal mucosa
- Minor salivary glands
LARYNX:
- True vocal folds - most common site of deposition in the respiratory tract, typical firm gray, red, or yellow deposits are usually localized
- Supraglottis, subglottis, trachea, and bronchial tree may also be involved
- Subglottis: diffuse nodules
HEAD/NECK:
- Parotid gland
- Cervical lymph nodes
- Skin
How is Systemic lupus erythematosus (SLE) typically diagnosed?
- Biopsy: Fluroescence of immunoglobulins/complement at the dermal-epidermal junction
- Blood: Positive ANA, APA, anti-ENA, anti-Sm, and anti-dsDNA
List 10 head and neck manifestations of Systemic Lupus Erythematosus (SLE)
SKIN:
1. Malar rash (50%)
2. Telangiectasias
NOSE:
1. Painless septal ulceration/perforation (3-5%)
ORAL/SALIVARY:
1. Acute parotid enlargement (10%)
2. Chronic xerostomia
3. Painless oral mucosal ulcers
LARYNX:
1. True vocal fold thickening/paralysis
2. Cricoarytenoid arthritis
3. Subglottic stenosis
NECK:
1. Parotid swelling
NEURO:
1. Cranial neuropathy (15%)
What are the different systemic manifestations of SLE?
- Skin eruptions
- Serositis (Pericarditis, myocarditis)
- Pneumonitis
- Nephritis
- Hypercoagulability/anemia
- CNS: headaches, seizures, psychosis NYD
- Oral ulcers (25% - may reseemble lichen planus, leukoplakia, SCC)
- Arthritis
- Photosensitiviity
- Pulmonary fibrosis
- Cytopenias
- Renal dysfunction
- Raynauds
- Malar rash, discoid rash
What are the treatment options for SLE?
- NSAIDs
- Antimalarials
- Glucocorticoids
- Azathioprine & Cyclophosphamide for resistant cases
- Oral ulcers - topical cortisone, nystatin
What is discoid lupus? What is the typical clinical presentation?
- Cutaneous lesions (round, coin shaped, demarcated) with scarring, without visceral involvement
- Well demarcated, erythematous, depigmentation and scar on resolution
- Cutaneous lesions with scarring on the face involvement in 85%, scalp and ears less often
- Leukoplakia of tongue and oral cavity
https://www.google.com/search?sca_esv=a5d739ec3717dc50&sxsrf=ACQVn09BwdaoJGJs-BbaoDBBetlkuWLw1g:1706579478621&q=discoid+lupus&tbm=isch&source=lnms&sa=X&ved=2ahUKEwj3pOr8_4OEAxULADQIHT93CigQ0pQJegQIChAB&biw=1440&bih=760&dpr=2
Regarding Rheumatoid arthritis, discuss:
1. What is it?
2. What is the F:M predilection?
3. How is it typically diagnosed?
4. Treatment?
RHEUMATOID ARTHRITIS:
- Autoimmune inflammation of synovial (joint) tissue)
EPIDEMIOLOGY:
- 3F : 1M
DIAGNOSIS:
1. Clinical (see diagnostic criteria below)
2. Labs: ESR, CRP, RF, ANA, ACPA (Anti-Citrullinated Peptide Antibody - suggestive, not diagnostic)
3. X-ray: joint space narrowing and erosions
TREATMENT:
1. NSAIDs
2. Immunosuppressants (e.g. steroids)
3. DMARDs (Disease-modifying antirheumatic drugs) or Biologics - e.g. methotrexate, anti-TNF
What are the diagnostic criteria of rheumatoid arthritis?
1987 criteria:
A. Need 4/7 criteria
B. Criteria 1-4 must be > 6 weeks and must be observed by a physician
- Morning stiffness ~1 hour
- Swelling in 3 or more joints
- Swelling in hands joints
- Symmetrical joint swelling
- Subcutaneous rheumatoid nodules
- Serum RF
- Radiologic evidence of erosions or osteopenia in hand joints
2010 Criteria: Score of ≥ 6 is DEFINITE RA
A. Joints distribution (0–5)
- 1 large joint - 0
- 2–10 large joints - 1
- 1–3 small joints (large joints not counted) - 2
- 4–10 small joints (large joints not counted) - 3
- >10 joints (at least 1 small joint) - 5
B. Serology (0–3)
- Negative RF AND negative ACPA - 0
- Low positive RF OR low positive ACPA - 2
- High positive RF OR high positive ACPA - 3
C. Symptom duration (0–1)
- < 6 weeks - 0
- ≥6 weeks - 1
D. Acute phase reactants (0–1)
- Normal CRP AND normal ESR - 0
- Abnormal CRP OR abnormal ESR - 1
What are 5 head/neck manifestations of rheumatoid arthritis?
- Neck - cervical pain, decreased neck ROM
- TMJ dysfunction - pain/tender joint or muscles (due to erosion of condylar heads)
- Ossicular arthritis - CHL or SNHL
- Larynx: Cricoarytenoid joint involvement (86%) - see next card for details
- Xerostomia (often associated with Sjogren’s)
What are 6 features of cricoarytenoid joint involvement of rheumatoid arthritis?
- Rheumatoid nodule deposition into folds (bamboo nodules) - 30% hoarseness
- RLN neuropathy (etiology unknown)
- Acute inflammation/edema over arytenoids
- Arytenoid process tenderness on palpation
- Decreased mobility and fixed fold in adducted position
- Subluxed cricoarytenoid joint on CT scan can be seen
Regarding Behcet’s syndrome, discuss:
1. What is it?
2. Risk factors
3. Possible etiology
3. Clinical presentation
4. Differential diagnosis
5. Complications
6. Diagnostic criteria
7. Treatment
BEHCET’S SYNDROME:
- Relapsing and remitting Auto-inflammatory systemic vasculitis (can affect all sizes)
- Unknown etiology
RISK FACTORS:
1. Japanese + Korean populations
2. Mediterranean region - Turkey, Iran
3. 3rd decade of life
ETIOLOGY:
1. Idiopathic
2. HLA B51 associated with susceptibility
3. Relationship between streptococcal infections?
CLINICAL PRESENTATION
1. Ulcerations of oro-genital mucous membranes (painful punched out lesions, typically first symptom) - can extend to hypopharynx and oropharynx, resulting in stenosis
2. Iritis/uveitis (60%, loss of sight 25%)
3. Progressive SNHL
Triad:
1. Recurrent aphthous ulcers of mouth (> 3 pisodes in 12 months, persistinig up to 6 weeks)
2. Recurrent painful ulcers of genitals
3. Uveitis or conjunctivitis
DIFFERENTIAL:
1. IBD
2. Reiter’s (reactive arthritis)
3. Pemphigus
4. Infectious (HSV, EBV, HIV, Cox)
5. Major aphthous ulcers
6. Trauma
7. SCC
COMPLICATIONS:
1. Uveitis (50%) –> blindness 25%
2. Cardiac and vascular aneurysms
DIAGNOSTIC CRITERIA
- Mouth sores (oral ulcers) at least 3 times in 12 months
- Any two of the following:
1. Recurring genital sores/ulcers
2. Eye inflammation with loss of vision (iritis, uveitis)
3. Characteristic skin lesions (punched out lesions)
4. Positive pathergy (skin prick test, papule >2mm)
- Pathergy phenomenon = state of altered tissue reactivity in response to minor trauma
- Pathergy test = nonspecific hypersensitivity skin reaction induced by needle prick that is performed to look for evidence of this phenomenon
TREATMENT:
1. Corticosteroid cream for ulcers, or PO steroids for systemic disease
2. Colchicine or dapsone PO (for mucocutaneous manifestations)
3. Mydriatics and corticosteroid drops for eyes
4. Azathioprine
5. Interferon-alfa
6. Cyclophosphamide
7. Methotrexate
8. Tumor necrosis fator-alpha blockers (Infliximab)
9. Conservative - hydration, sialogogues, oral lubrication, eye drops, etc.
“O2PEGS”
Oral, and 2 of:
Positive pathergy test
Eye inflammation
Genital ulcers
Skin lesions (characteristic)
Regarding Sarcoidosis, discuss:
1. What is it?
2. What are the risk factors?
3. Clinical presentation?
4. Systemic features?
5. Complications?
6. Types and variants?
7. Investigations that should be done? What labs should be done?
8. Diagnostic findings? Biopsy findings?
9. Treatment?
SARCOIDOSIS:
- Idiopathic systemic noncaseating (no necrosis) granulomatous disease
- Chronic systemic granulomatous disease
- Rarely affects H/N - < 10%, but nose is the most common
RISK FACTORS: Unknown etiology
1. African-American - 10-20x higher
2. M = F (some say slightly higher in females?)?
CLINICAL PRESENTATION:
1. 40% cervical LN (most common HN presentation)
2. Uveoparotid fever (Heerford’s syndrome)
3. Supraglottic mass (“turban-shaped” epiglottis)
4. Vocal cord paralysis
5. Nasal or orbital mass
6. Septal perforation
7. Incidental hilar pulmonary LN (most common presentation overall)
8. Darier-Roussey (subcutaneous) nodules
9. Hepatic, renal, splenic, cardiac, bone, or nerve involvement
10. Salivary gland involvement
Systemic features:
1. Non-caseating granulomas
2. Lupus pernio
3. Perihilar adenopathy, pulmonary infiltrates (90%)
4. Extrapulmonary granulomas (40%)
COMPLICATIONS:
1. SNHL
2. Facial palsy
3. VF paralysis
4. Blindness
5. Lung disease
6. Airway obstruction
TYPES/VARIANTS:
1. Heerfordt’s syndrome: Uveoparotid fever (chronic inflammatory disease of the uveal tract of the eye with enlargement of the parotid glands, febrile, often facial nerve paralysis)
2. Lupus Pernio (purple skin lesion) - associated with Melkersson-Rosenthal Syndrome
3. Loffgren syndrome - acute sarcoidosis characterized by erythema nodosum, hilar adenopathy, and polyarthralgia
INVESTIGATIONS
1. Biopsy
2. ACE (angiotensin converting enzyme) elevated in 85% - serum biomarker
3. Elevated calcium levels (hypercalcemia)
4. SPEP (hypergammaglobulinemia)
5. CXR
6. Positive Kveim-Siltzbach skin test (involves development of sarcoidal granulomas at the site of an intradermal injection of a 10% suspension of human sarcoidal tissue) - no longer used or approved by FDA
7. Gallium-67 scan: “Panda sign” - focal uptake in nasopharynx, lacrimal glands, parotid glands (NP is normal uptake, and the glands are from sarcoid)
8. CT - Pulmonary and sinus involvement
DIAGNOSTIC FINDINGS:
1. BIOPSY
- Noncaseating granulomas composed of langerhans giant cells
- Containing Schaumann bodies (laminated basophilic calcifications)
- Containing Asteroid bodies (stellate inclusions - intracytoplasmic star-shaped inclusions)
2. Must rule out infectious etiology
TREATMENT:
1. Steroids for acute exacerbations
2. Conservative surgery for obstructing laryngeal lesions
3. Hydroxychloroquine
4. Methotrexate
5. Azathioprine
6. Tracheostomy
https://www.pathologyoutlines.com/topic/skinnontumorsarcoidosis.html
What are all the head and neck manifestations of sarcoidosis? (16)
EYE:
1. Episcleritis
2. Uveitis
3. Orbital mass
4. Lacrimal gland involvement
SALIVARY GLANDS:
1. Parotid swelling
NECK:
1. Cervical lymphadenopathy (often posterior triangle)
2. Heerfordt’s syndrome (Uveoparotid fever” = fever, parotitis, uveitis, bilateral FN paralysis (self resolves)
OROPHARYNX:
1. Tonsillar hypertrophy
NOSE:
1. Yellow, submucosal nodules (characteristic)
2. Lupus pernio
3. Inflammation
4. Septal perforation (adhesions)
5. Nasal mass
6. Oronasal fistula
LARYNX: Usually SUPRAGLOTTIC involvement
1. Epiglottic swelling “turban-shaped”
2. Subglottic stenosis
NEUROPATHIES:
1. CNVIII (sudden SNHL)
2. CNVII (unilateral or bilateral facial palsy)
3. CNX (VF paralysis)
Vancouver Pg 24
What is Lupus Pernio?
- A form of sarcoidosis characterized by chronic, violaceous, cutaneous lesions with a predilection for cold-sensitive areas such as the nose, cheeks, ears, and fingers
- Intranasal involvement is characterized by diffuse nasal crusting, or a vasomotor-like appearance to the nasal mucosa, causing diffuse mucosal swelling
Vancouver pg 24
XxRegarding Heerfordt’s disease, discuss:
1. What is it?
2. What is the cause?
3. Clinical presentation
4. Diagnostic findings/investigations
5. Treatment
6. Complications
HEERFORDT’S DISEASE: UVEOPAROTID FEVER
- A variant of sarcoidosis characterized by parotitis, uveitis, CNVII paralysis
CAUSE: Idiopathic
CLINICAL PRESENTATION:
1. Prodrome: fever, malaise, weakness, nausea, night sweats
2. Parotitis
3. Uveitis
4. CN paralysis in 5% patients (CNVII 50%)
5. SNHL
6. Facial swelling
7. Commonly seen in 3-4th decades
DIAGNOSIS:
1. Presentation often clinical/classic findings, no biopsy required
2. CXR to check for hilar lymphadenopathy
3. If dx uncertain - biopsy looking for non-caseating granulomas
4. Rule out other conditions: Serum IgG levels, Lyme testing, HIV testing, TB skin test
5. ACE level has been suggested as a serologic marker utility for diagnosis and monitoring (no clear evidence of utility)
COMPLICATIONS:
1. Facial nerve paralysis
2. SNHL
3. Blindness
TREATMENT:
1. Self-limiting
2. Corticosteroids
3. If nonresponsive, use methotrexate or azathioprine (DMARD); ocular care (artificial tears, ointment, night patch)
Vancouver page 39
What is the Panda sign of sarcoidosis?
What lights up on a technitium perchlorate scan?
- Finding of a Gallium-67 citrate scan
- Due to bilateral involvement of parotid and lacrimal glands in sarcoidosis, superimpose the normal uptake in the nasopharyngeal mucosa –> looks like a panda
Note: With radionucleotide imaging: Technitium perchlorate lights up in Warthins & Oncocytoma
- Secondary to oncocyte uptake
Vancouver Page 39
Regarding Granulomatosis with polyangitis (Wegener’s Granulomatosis), discuss:
1. What is it?
2. Clinical presentation and Triad
3. Differential
4. Diagnosis
5. Types
6. Investigations
7. Treatment
GPA:
- Idiopathic autoimmune vasculitis
TRIAD: (Nose, Lung, Kidney)
1. Upper airway necrotizing granulomas - Nose & sinuses most common site
2. Lower airway/ Lung granulomas
3. Focal glomerulonephritis
Systemic vasculitis
CLINICAL PRESENTATION: (Nose, Lung, Kidney)
Granulomas of the upper and lower respiratory tract:
1. Pulmonary involvement > 95%
2. Nasal involvement > 90%
3. Renal involvement >85%
4. Head and Neck manifestations (See separate card)
DIFFERENTIAL:
1. Churg-Strauss (eGPA)
2. NK/T cell or Diffuse large B cell lymphoma
3. Goodpasture’s
DIAGNOSIS:
1. Clinical, lab findings
2. cANCA positive (anti-PR3) - 85% (high sens and spec, but negative doesn’t rule out)
2. pANCA positive in 25% (anti-MPO)
3. Pathologic findings (nasal biopsy - see separate card on histologic findings)
TYPES (3):
1. Limited (e.g. ENT)
2. Systemic (e.g. Lung)
3. Widely disseminated (e.g. Kidney)
INVESTIGATIONS:
1. CBC (anemia)
2. Elevated ESR, CRP
3. c ANCA positive (90% in systemic vasculitis stage; 65% in granulomatous phase, 30% in remission patients)
4. Urine sediment
5. CXR or CT lungs
6. Nasal biopsy
TREATMENT:
1. Prednisone (1mg/kg/day x 4 weeks, then taper)
2. Cyclophosphamide (2mg/kg/day for 6-12 months)
3. If hemorrhagic cystitis occurs may use Methotrexate or Azathioprine
4. IVIg in immunosuppression non-responders
5. Rituximab (CD20 monoclonal antibody inhibitor)
6. Plasma exchange (for patients with severe disease)
Maintenance = Chronic low-dose septra for limited/early disease (mechanism unknown)
What are the head and neck symptoms of Granulomatosis with Polyangitis (GPA?) List 18
NASAL (90%):
1. Crusting, ulceration
2. Epistaxis
3. Obstruction
4. Septal perforation
5. Saddle nose deformity
6. Serosang rhinorrhea
EAR (25%):
1. CHL
2. Eustachian tube Granulomas - Suppurative otitis media
3. SNHL (can be bilateral and profound)
4. TM perforation (can have multiple TM perforations - may mimic TB - differentiate with biopsy)
5. CN VII palsy
6. Middle ear granulation tissue (may mimic TB - differentiate with biopsy)
OROPHARYNX:
1. Gingival hyperplasia
2. Gingivitis
3. Oral granulomas - red/purple hyperplastic gingival ulcerations with petechiea
4. Loose teeth
LARYNX: - usually SUBGLOTTIC involvement
1. Laryngeal ulceration and edema (25%)
2. Subglottic stenosis (8.5%)
Upper airway involvement frequency at presentation = 73%
Frequency of upper airway involvement throughout disease course = 92%
Describe ANCA testing:
1. How does it work?
2. How do you interpret the results?
3. What are the likely diagnoses?
ANCA testing process:
- Get a bunch of neutrophils and stain them with ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) for immunofluorescence
- ANCA is an IgG antibody
RESULTS:
1. Cytoplasm lights up = cANCA + = likely GPA
- cANCA binds to proteinase-3 (PR3)
2. Perinuclear area lights up = pANCA + = likely eGPA
- pANCA binds to myeloperoxidase (MPO)
MEASURED BY:
1) The staining needs to be confirmed with ELISA testing (Detect actual antibodies causing the staining)
- Sensitivity 65-90%
- Specificity 90%
2) Indirect immunofluorescence
cANCA = anti-PR3 antibody = GPA
Other associations:
- Polyarteritis
- eGPA (50%)
- Kawasaki
pANCA = anti-MPO Antibody = eGPA (70%)
Other associations:
- Glomerulonephritis
- Polyarteritis
- Kawasaki
Describe the diagnostic criteria from the American College of Rheumatology for GPA
At least two of the following:
1. Oral or nasal inflammation (E.g. oral ulcers or purulent/bloody nasal discharge)
2. Abnormal chest radiograph showing nodules, fixed infiltrates, or cavities
3. Abnormal urinary sediment (microscopic hematuria ± red cell casts; or more than 5 RBC per hpf)
4. Granulomatous inflammation on biopsy of an artery or perivascular area
The presence of two or more of these four criteria was associated with an 88% sensitivity and 92% specificity.
What are five histologic findings of GPA?
- Small and medium vessel vasculitis (angiocentric)
- Fibrinous “geographic” necrosis
- Necrotizing granulomas
- Mixed plasma cell, lymphocyte, histiocyte, and macrophage infiltration, with isolated multinucleated giant cells
- Angioinvasion, better identified on elastic stain
Hallmark = Necrotizing granulomatous vasculitis (found all together in < 20% of single cases)
https://www.pathologyoutlines.com/topic/kidneyGPA.html
Regarding Sjogren’s syndrome, discuss:
1. What is it?
2. Cause or risk factors?
3. Clinical presentation
4. Complications
5. Types of Sjogren’s
6. Investigations
7. Treatment
SJOGREN’S DISEASE:
- Chronic autoimmune disease, characterized by lymphocytic infiltration of exocrine glands and epithelial in multiple organs
- Exocrine glands are glands that secrete substances on to an epithelial surface by way of a duct (e.g. salivary, lacrimal glands)
CAUSE/RISK FACTORS:
- Unknown
- ?HLA typing
- Risk factors: 90% women, onset 40-60 years old
CLINICAL PRESENTATION:
1. Triad (“sicca complex”): (1) Xeropthalmia (2) Keratoconjunctivitis (3) Xerostomia
2. Association with other autoimmune diseases
3. Altered taste
4. Intermittent unilateral/bilateral submandibular gland enlargment
Symptoms:
- Dry eyes, dry mouth
- Fatigue
- Arthritis
- Interstitial pneumonitis
- Rash or dry skin
- Achlorhydria (lack of HCl produced from stomach)
- Hepatosplenomegaly
- Genital dryness
- Myositis
- Pancreatitis
COMPLICATIONS:
1. Dental caries
2. Oral candidiasis
3. Angular cheilitis
4. Epistaxis
5. Hyposmia
6. Chronic sinusitis
7. 40-fold increase in lymphoma (NHL, greatest with Primary Sjogren’s, constant parotid swallinw, lymphadenopathy, splenomegaly, and decreased IgM) - MALT type (B-cell)
8. Systemic involvement - nephritis, vasculitis, peripheral neuropathy
TYPES:
1. Primary (Exocrine glands only)
2. Secondary (associated with another defined disease)
- Most common = Rheumatoid arthritis
- SLE
- Scleroderma
- PBC (Primary biliary cholangitis)
- Polymyositis
INVESTIGATIONS:
1. Minor Salivary gland biopsy (lip, septum, hard palate)
- Focus score ≥ 1 in a 4mm^2 field - ie. >50/hpf
- Focus score definition = the number of mononuclear cell infiltrates containing at least 50 inflammatory cells in a 4 mm^2 glandular section (e.g. Focus score 1 = 1 focus of 50 lymphocytes per 4 mm^2)
- Recommended at least 4-5 MSG biopsies separated by connective tissue with a surface area of at least 8 mm2 to allow for adequate assessment and focus scoring
- Bloodwork for Primary Sjogren’s
- Elevated Anti-SS-A/Ro (60%)
- Elevated Anti-SS-B/La (30%)
- RF +ve (non-specific)
- Antinuclear antibody (ANA) +ve (non-specific)
- ANCA
- HLA-DW3
- HLA-B8
- CD4+ T cells predominate with B cells accounting for ~20% of cells - Bloodwork for Secondary Sjogren’s
- HLA-DW4 - Sialography (introduction of contrast into duct, then x-ray)
- Punctate (≤1mm) to globular (1-2mm) contrast collections, progresses to cavitary or destructive when superinfected (ie. no tissue!) - Salivary scintigraphy (reduced uptake, concentration, or excretion of tracer)
- Assessing the uptake and excretion characteristics of radiotracer by salivary glands following secretive stimulation. - IgM levels (low = risk of progression to NHL)
- Schirmer’s test
- Total tear secretion/reflex tearing - Sialometry (amount of saliva produced)
- Rose Bengal Score (fluorescein staining score)
- IMAGING: Early normal, Late finding - “Honeycomb” or “Speckled” calcification appearance of parotids on CT/MRI
TREATMENT:
1. Symptomatic for xerostomia, prevention of ocular or dental damage
2. Hydration
3. Sugarless or sour candies, fruit slices
4. Artificial saliva/tears or lubricants
5. Pilocarpine (muscarinic-cholinergic agonist salivary stimulant); side effect = sweating, flushing, increased urination
6. Antifungals
7. Fluoride treatments to reduce dental caries
8. Cevimeline (acetylcholine derivative)
9. Dental and eye care diligent
10. Sialendoscopy to irrigate salivary ductal system ± steroid application
11. Rituximab for systemic involvement
https://www.pathologyoutlines.com/topic/salivaryglandssjogren.html
Kevan Gen #109
What are five risk factors for lymphoma in patients with Sjogren’s disease?
M-CLIPS
M: Mixed monoclonal cryoglobulinemia
C: Constant parotid enlargment
L: Lymphadenopathy, leg ulcers, Low C4 level
I: Decreased IgM, cross-reactive Idiotypes of monoclonal RFs
P: Primary Sjogren’s, palpable purpura
S: Splenomegaly
Describe the histopathology of Sjogren’s syndrome
- Lymphocyte and histiocyte infiltration
- Acinar atrophy
- Prominence of myoepithelial components as ductal lumens disappear
- Ductal epithelial hyperplasia and metaplasia
- Germinal Centres
LAPD
https://www.pathologyoutlines.com/topic/salivaryglandssjogren.html
Describe the diagnostic criteria of Sjogren’s
- 4 of 6 criteria, one must be histology or serology
- 3 of those 4 must be objective tests (either oral/ocular signs, histology, or serology)
- Ocular symptoms: dry eyes, sensation of gravel in eyes > 3 months, or use of tear substitutes >3x/day
- Oral symptoms: Dry mouth > 3 months, recurrent or persistent swelling of salivary glands
- Ocular signs: Schirmer test < 5mm in 5 min; or Rose-bengal score > 4 (scores eye dryness)
- Oral signs: Salivary gland involvement - either (1) unstimulated flow of < 1.5mL in 14 min, (2) Abnormal parotid sialography (Diffuse sialectasia), (3) abnormal salivary scintigraphy (reduced uptake, concentration, or excretion of tracer)
- Histopathology: Focus score ≥ 1 = ≥50 lymphocytes in 4mm2 of glandular tissue
- Serology: Presence of Anti-Ro/SS-A or Anti-La/SS-B antibodies (sensitivity 85 + 94%, specificity 93 + 94%)
Regarding IgG4 disease, discuss:
1. What is it?
2. Epidemiology
3. Natural course
4. Clinical presentation including all the head and neck manifestations
IgG4 DISEASE:
- Chronic immune-mediated fibroinflammatory disorder that often manifests with tumor-like masses and/or painless enlargement of multiple organs.
- “Multi-organ autoimmune fibrosis”
EPIDEMIOLOGY:
- 6-7 decades
- Asian predominant
- Any organ (majority >1)
NATURAL COURSE:
- Slow growing mass over years, lymphadenopathy
- Sicca symptoms: (1) Xeropthalmia (2) Keratoconjunctivitis (3) Xerostomia
- Natural history not well described
CLINICAL PRESENTATION:
1. SALIVARY (Formerly Mikulicz disease or Kutner’s tumor)
- Unilateral or bilateral submandibular gland enlargment (sialosis)
- Elastic, firm, recurrent parotid swallowing
- SMG > Parotid > SLG
- OTOLOGIC
- Eosinophilic otitis media
- OME
- SNHL
- CN VII paresis
- Vertigo
- Recurrent mastoiditis - ORBITAL PSEUDOTUMOR
- Eye lid edema
- Chemosis
- Diplopia
- Vision loss (20%)
- Pain with movement, EOM myositis
- Proptosis/diplopia (EOM tendons involved on imaging) - LACRIMAL
- Swelling with at least 1 major salivary gland - LYMPHADENOPATHY
- 2/3 submandibular region
- Can be diffuse
- < 2-3 cm, non-tender, rubbery - THYROID - RIEDEL’S
- Riedel fibrosing thyroiditis is a rare disease characterized by chronic inflammation and fibrosis of the thyroid gland - AIRWAY
- Hoarseness
- Airway stenosis - NON-HEAD/NECK
- Pancreas
- Kidney
- Gallbladder
- Aorta
Regarding IgG4 disease of the salivary glands, discuss:
1. What is Mikulicz disease?
2. What is Kuttner’s tumor?
3. Clinical features?
4. Diagnosis features?
5. Treatment
MIKULICZ DISEASE:
- Persistent (>3 months) symemtrical enlargement of at least 2 glands
- Lacrimal, parotid, or submandibular glands
- Exclusion of secondary causes (e.g. lymphoma, sarcoidosis, etc.)
- Secondary causes are previously referred to as “Mikulicz syndrome” - whereby inflammation/enlargement of lacrimal/salivary glands were secondary to identifiable underlying diseases - Sjogren, Lupus, sarcoid, HIV, TB, Lymphoma, Leukemia, Malnutrition
KUTTNER TUMOR:
- Chronic sclerosing sialadenitis
- “Hard” swelling of one or both submandibular glands
Most cases of Mikulicz and Kuttner now thought to be IgG-4 related sialadenitis, therefore these terms are discouraged
CLINICAL FEATURES:
1. Elderly men (mean age 55)
2. Symmetrical enlargement of the lacrimal, parotid and/or submandibular salivary glands
DIAGNOSIS FEATURES:
1. Labs: elevated IgG4 serum, elevated serum IgG4/IgG ratio (but don’t correlate well)
2. Exclusion of Sjogrens (low SS-A, SS-B)
3. Histology: Lymphoplasmacytic infiltrate with IgG-4 positive cells and obliterative phlebitis and fibrosis (>15/hpf), storiform fibrosis
4. Stains: IgG4, Elastin (highlights obliterative phlebitis - organized obstruction of veins with wall destruction due to dense lymphoplasmacytic infiltration)
TREATMENT:
1. Steroids
2. Rituximab (B-cell depletion)
Kevan Gen #156 - Obliterative pheblitis
Describe the pathophysiology of IgG4 disease
- IgG4 plasma cells trigger B-cells to secrete cytokines & toxic enzymes
- CD4 T-cells are attracted to the tissue with an inflammatory response, then causes fibrosis
- Response is proportional to IgG4 level
Describe the workup and diagnostic criteria of IgG4 disease, including histology, labs, and diagnostic criteria
LABS:
1. Elevated serum IgG4
2. Elevated serum IgG4/IgG ratio
3. Exclusion of Sjogren’s (low SS-A, SS-B)
4. Exclusion of lymphoma, sarcoidosis, etc.
HISTOLOGY:
1. Dense lymphoplasmacytic infiltrate - T-cells, plasma cells, scattered B-cells, eosinophils, obliterative phlebitis
2. “Storiform fibrosis” (on silver stain)
3. IgG4:IgG ratio >40% /hpf
DIAGNOSTIC CRITERIA: Japanese Comprehensive Clinical Diagnostic (CCD) Criteria
1. Exam showing characteristic diffuse/localized swelling or masses in a single or multiple organs
2. Hematological exam showing elevated IgG4 >135mg/dL
3. Histopathological examination showing: (1) marked lymphocyte and plasmacyte infiltration, (2) fibrosis or infiltration of IgG4 plasma cells, (3) Ratio IgG4/IgG > 40% and greater than 10 IgG4 cells per HPF
Definite: 1 + 2 + 3
Probable: 1 + 3
Possible: 1 + 2
There is a second validated diagnostic criteria (ARC2019), however this is intended for research purposes only
NOTE:
- Asians have elevated IgG4 levels
- Serum levels can be higher with more organs involved
- IgG4 levels lower in females
- No current threshold exists for patient variability
https://www.pathologyoutlines.com/topic/kidneyigg4related.html
What are the imaging findings in IgG4 disease?
CT:
- Lesions show well defined homogeneous attenuation with non-contrast
- Enhancement with contrast
MRI:
- Low signal intensity on T1/T2
- Enhance with contrast
PET:
- Lesions are PET avid
US:
- Most sensitive, classic pattern
- Relatively uniform hypoechoic nodules superficially
- Hyperechoic reticulated septi
- Increased vascularity on doppler
What is the management for IgG4-related disease?
- Refer to Rheumatology and hematology
- Conservative symptomatic management
- Medical Management
- Surgery: used for indefinite diagnosis, rule out malignancy, no convincing data to support in definitive IgG4-RD
Medical Management Options:
- Glucocorticoids: Mainstay, induction dose (0.6-1mg/kg/day) then maintenance (2.5-10mg/day). Overall response 90%, complete remission 66%, 85% maintained remission over 60 months
- Immunomodulators - no role in induction or maintenace as single therapy (Azathioprine, MMF Mycophenolate mofetil, methotrexate, etc.)
- Rituximab - Monoclonal antibody - causes B-cell depletion. Response rate >90%, poor maintenace
- Combination therapy: Rituximab and steroid maintence best for reduction of relapse, immunomodulators and steroids possibly best for induction
Discuss the management plan for patients with Xerostomia
A. LIFESTYLE INSTRUCTIONS: self-care to stimulate oral secretions and prevent oral dryness and dental caries
1. Good hydration with regular sipping
2. Avoid sucrose, carbonated beverages, juices, and water with additives
3. Sugar free salivary stimulants
4. Meticulous dental care
5. Regular dental follow up
B. MEDICAL
1. Artificial saliva
2. Muscarinic/cholinergic agonists (e.g. pilocarpine or cevimeline)
C. OTHER
1. Maintain high level of suspicion for candida
Regarding Relapsing Polychondritis, discuss:
1. What is it?
2. Risk factors?
2. What is the diagnostic criteria?
3. Clinical features
4. Complications
5. Investigations
6. Treatment
RELAPSING POLYCHONDRITIS:
- Episodic recurrent inflammation of cartilage/perichondrium and tissues high in glycosaminoglycans, eventually replaced by granulation and fibrosis
- Destruction of collagen (ie. predilection for cartilaginous, valvular structures)
- Predilection for whites
DIAGNOSTIC CRITERIA: DAMIANI & LEVINE CRITERIA
1. 3 of the clinical features below (McAdam’s criteria) in the absence of histologic confirmation; OR
2. 2 of the clinical features below (McAdam’s criteria) with response to steroids or dapsone (antibiotic); OR
3. 1 of the clinical features (McAdam’s criteria) with histologic confirmation
MCADAM’S CRITERIA = 6 CLINICAL FEATURES: 5-10 days then resolves with lasting deformity
1. Nasal chondritis - e.g. saddle nose deformity, septal perforation (15%)
2. Recurrent bilateral Auricular chondritis (with sparing of the lobule) - 50% bilateral
3. Respiratory tract chondritis - e.g. loss of tracheal rings, tracheomalacia, subglottis stenosis (50%)
4. Cochlear (SNHL or tinnitus) or vestibular damage (vertigo)
5. Ocular inflammation - e.g. uveitis (15%)
6. Non-erosive Seronegative inflammatory polyarthritis
COMPLICATIONS:
1. Nasal deformity
2. Serous otitis media
3. Death may result from tracheal collapse or CV disease
4. Perform tracheotomy for severe glottic/subglottic edema, or laryngeal collapse
INVESTIGATIONS:
1. CRP and ESR (elevated)
2. Biopsy: demonstrates inflammation
TREATMENTS:
1. Steroids
2. NSAIDs (arthritis)
3. Colchicine (auricular chondritis)
4. Dapsone (type of antibiotic)
5. Methotrexate or Azathioprine (for recalcitrant)
Vancouver notes Page 28
What are 3 head and neck features of polyarteritis nodosa (PAN)?
PAN = A small-medium vessel vasculitis
- Bilateral SNHL or CHL or vestibular dysfunction
- CN palsy (FN CNVII most common)
- Septal perforation
List the complete differential diagnosis of granulomatous diseases of the head/neck
INFECTIOUS - BACTERIAL:
1. Cat scratch disease/ bacillary angiomatosis (bartonella henselae)
2. Rhinoscleroma (Klebsiella)
3. TB
4. Non-tuberculous mycobacterium
5. Leprosy
6. Syphillis (treponema pallidum)
7. Actinomycosis
INFECTIOUS - FUNGAL:
1. Histoplasmosis (Mississippi & Ohio river valleys, rarely can cause Fibrosing mediastinitis, and mediastinal granulomatosis)
2. Blastomycosis (east of mississippi and central america)
3. Coccidiomycosis (San Joaquin valley, california)
4. Rhinosporidiosis
5. Candidiasis
6. Aspergillus/Mucorales
INFECTIOUS - PARASITES:
1. Leishmaniasis (Sand fly bite)
2. Toxoplasmosis (cat feces)
3. Myiasis (maggots)
TRAUMA:
1. Intubation
2. Teflon granuloma
NEOPLASTIC:
1. Histiocytosis X (Langerhans Cell granulomatous, Hand-Schuller-Christian)
2. Pyogenic granuloma (Lobular capillary hemangioma)
3. Foreign body granuloma
4. NK T-cell lymphoma
IDIOPATHIC:
1. Sarcoidosis
2. Necrotizing Sialometaplasia
AUTOIMMUNE/VASCULITIS:
1. Wegener’s granulomatous (GPA)
2. Churg-Strauss syndrome (eGPA)
3. Relapsing polychondritis
4. Systemic lupus erythematous
5. Sjogren’s syndrome
What trauma induced disorders can cause granulomas? (4)
- Intubation granuloma
- Vocal process of arytenoids
- Contact ulcer –> granuloma –> pedunculated ulcer - Teflon granuloma (2-3% in VC injection)
- Reparative granuloma anterior to 1st molar - lytic, expansive, unilocular cavity
- Peripheral: blue/red mass on gingiva of anterior mandible
- Central: Endosteal - Pyogenic granuloma (lobular capillary hemangioma)
- Not a true granuloma, but included for completion
What are Langerhan’s cells?
- Macrophage/dendritic cell (APC) that normally resides in the epidermis of skin
- Antigen presenting cell
What type of infection may resemble granulomatous disease?
Mycosis (Histoplasmosis, blastomycosis, cryptococcus, coccidiomycosis)
- All similar manifestations: pulmonary involvement, hoarseness (may resemble SCC, TB, WG)
- All diagnosed with fungal stains
- All treated with IV Amphotericin B
Granulomatous Bacterial infections:
- Leprosy
- Actinomycosis
- Bartonella
- Rhinoscleroma
- Atypical TB
- TB
- Brucellosis
- Anthrax
- Tularemia
- Syphillis
Regarding Histiocytosis X, discuss:
1. What is it?
2. What is the clinical presentation?
3. What are the types?
4. How is it diagnosed? Histological findings?
5. What are the investigations?
6. Treatment?
HISTIOCYTOSIS X:
- Aka. Langerhans Cell Histiocytosis (LCH)
- Group of rare disorders involving abnormal increase of langerhans cells
CLINICAL PRESENTATION:
- Temporal bone involvement 20-60% cases (25% present with initial otologic symptoms)
- Fever, anemia, thrombocytopenia, pulmonary infiltrates, skin lesions, and enlargement of lymph nodes, spleen, and liver
TYPES:
1. Eosinophilic Granuloma
- Benign, localized form of Histiocytosis X with a chronic course
- Monoostotic or polyostotic
- Favours frontal and temporal bones; other sites include femur, pelvis, vertebrae, ribs
- Treatment: Surgical excision; radiation for recurrence/inoperable/high risk patients
- Hand-Schuller-Christian
- More severe, chronic disseminated form of Histiocytosis X
- 30% overall mortality
- Presents in children and young adults
- Classic triad in 10%: Diabetes insipidus, exophthalmos, skull lesions
- Treatment: Radiation, surgery, chemotherapy, or combination, medical oncology consult - Letterer-Siwe disease
- Acute disseminated and rapidly progressive form of Histiocytosis X
- Affects patients under 3 years of age, uniformly fatal
- Fever, proptosis, adenopathy, hepatosplenomegaly, multiple bone lesions, anemia, thrombocytopenia, exfoliative dermatitis
- Treatment: Chemo-radiation - Rosai-Dorfman disease (rare)
- Sinus histiocytosis
- Massive lymphadenopathy
DIAGNOSIS/HISTOLOGY:
1. Birbeck granules (laminar rod-shaped, or “tennis-racket” organelles with nuclear cytoplasm, central linear density, and a striated appearance
2. X-bodies (cytoplasmic inclusions) within the histiocyte are pathognomonic
3. CD1 antigen present
4. Bilobed cells
INVESTIGATIONS:
1. BIopsy
2. If biopsy positive, then work-up includes skeletal survey, CT or MRI skull/orbit/chest and Abdomen PETCT to look for other lesions
TREATMENT:
1. Consult medical oncology
2. Radiation
3. Surgery
4. Chemotherapy
5. Comnbination, depending on the type
Vancouver Notes Page 30
Regarding Scleroderma, discuss:
1. What is it?
2. Pathophysiology
3. Epidemiology
4. Symptoms and ENT manifestations
5. Diagnosis
6. Types of Scleroderma and their associated antibody?
7. Treatment
SCLERODERMA:
- Chronic Autoimmune small vessel vasculitis and fibrosis
- Widespread collagen deposition and smooth muscle atrophy
- Sclerotic skin changes often with multisystem disease and progressive fibrosis
- Can be limited or systemic
PATHOPHYSIOLOGY:
- Widespread collagen deposition and smooth muscle atrophy
- Esophageal dysmotility is thus limited to the lower 2/3 of the esophagus
- Benign cutaneous involvement, extremities distal to elbow, knees, face and neck
EPIDEMIOLOGY:
- M:F 1:3
- ~50 years old
SYMPTOMS:
1. Raynaud’s
2. Finger skin thickening
3. Muscle weakness (common)
4. Arthralgias
5. Visceral: Fatal, GI, lung, heart, kidneys
6. H/N manifestations
ENT MANIFESTATIONS:
1. Oral
- Wide periodontal ligament spaces (most common)
- Thin lips, vertical furrows of lips
- Trismus from fibrosis of masticatory muscles
- Reduced tongue mobility
- Mucosal atrophy, xerostomia
- Gingivitis
- Dysarthria
2. Swallowing
- Dysphagia
- Hiatal hernia
- Esophageal dysmotility
3. Larynx
- Hoarseness
4. Nose
- Nasal telangiectasis - epistaxis
5. Ears
- Immune complex deposition in stria vascularitis of basal turn of cochlea –> mild-mod high frequency SNHL
6. Head/neck
- Facial nerve palsy
- Trigeminal neuralgia
- Facial tightness
- Telangiectasis
- Calcinosis of scalp
DIAGNOSIS (1 major; or ≥2 minor)
1. Major criteria: Proximal scleroderma (symmetrical thickening, tightening and induration of the skin to MCP joints)
2. Minor:
- Sclerodactyly (induration and tightening of skin of fingers)
- Digital ischemia (digital pitting scars or atrophy of finger pads)
- Bibasilar pulmonary infiltrates on CXR (reticular or reticulonodular densities in the basilar areas of the lungs - “honeycomb lung”) - must NOT be due to primary lung pathology
INVESTIGATIONS:
1. Labs: ANA, Scl-70, Anti-centromere
2. Barium swallow (dilated flaccid esophagus, similar to achalasia, patent LES)
3. Manometry (normal UES pressure, loss of LES tone, aperistalsis)
TYPES:
1. CREST syndrome: Anti-centromere antibody
2. Diffuse/systemic scleroderma (organ involvement including kidneys, heart, lungs/pHTN): Anti-Scl-70 (anti-DNA topoisomerase-I antibody) and anti-RNA polymerase III
TREATMENT:
1. Supportive care (e.g. NSAIDs)
2. Calcium channel blocker for Raynaud’s (vasodilators - nifedipine, nicardipine)
3. PPI
4. Diet modification
5. ACE inhibitor
6. Consider corticosteroids and NSAIDs
7. No clear benefit to immunosuppression - MTX, cyclophosphamide, azathioprine
What are the clinical findings in CREST syndrome?
Limited cutaneous scleroderma with the following features (“CREST”):
- C: Calcinosis (deposition of calcium in the skin/tissue/muscles/organs)
- R: Raynaud’s phenomenon (90%)
- E: Esophageal stenosis/dysmotility
- S: Sclerodactyly (thickening and tightening of the skin of the fingers or toes)
- T: Telangiectasias
XxRegarding Lyme disease, discuss:
1. Etiology? How is it transmitted?
2. Diagnosis
3. Stages
4. ENT manifestations
5. Treatment
ETIOLOGY:
- Borrelia Burgdorferi (spirochete)
- Transmitted by Ixodes ticks on mice and deer
DIAGNOSIS:
1. ELISA (for antibody)
2. Western blot
STAGES:
1. Stage I: Early local infection (< 30 days): Erythema migrans occur at bite site, “target” lesions, influenzae-like prodrome, lymphadenopathy, and malaise
2. Stage II: Early disseminated infection (weeks to months): Hematogenous spread mimics viral illness (e.g. rash, fever, malaise, joinit pain), leads to sequestration and inflammation (e.g. arthritis, cranial nerve palsies including CNVII, carditis, meningitis, neuropathies)
3. Stage III: Late/persistent infection (> 1 year): Chronic inflammation (e.g. arthritis, scleroderma, polyneuropathies, encephalitis, recurrent meningitis, keratitis, carditis), neurologic deficits, mental disorders
ENT MANIFESTATIONS:
1. Facial nerve paralysis - 5-10% of patients have ipsilateral involvement after 1-4 weeks incubation period; can also be bilateral; typically self-resolves in 6-12 months
2. Lymphocytoma (red-purple nodules on earlobe) = pathognomonic
TREATMENT
1. Ceftriaxone x 2 weeks for neurologic symptoms; otherwise
2. Doxycycline, Amoxicillin, or Cefuroxime x 2 weeks
3. Steroids for disseminated involvement or facial nerve paralysis
Regarding Multiple Myeloma in the head/neck, discuss:
1. What is it?
2. What are the clinical features?
3. How is it diagnosed?
4. What is the treatment
MULTIPLE MYELOMA:
- Proliferation of monoclonal plasma cells, producing abnormal M-paraprotein (myeloma protein)
- Leads to abnormal protein accumulation and deposition
CLINICAL FEATURES:
1. Bone marrow deposition –> cytopenias, fragility fractures, bone pain
2. Especially skull desposition can affect otic capsule –> Hearing loss, vertigo, FN paralysis
3. Kidney basement membrane deposition –> renal failure
4. Can also be associated with extramedullary plasmacytoma
“CRAB”
Calcium elevated
Renal failure
Anemia
Bone lytic lesions
DIAGNOSIS:
1. UPEP/SPEP - M-protein spike
2. Hypercalcemia
3. Cytopenias
4. X-ray: lytic “punched out” bony lesions (especially pepper pot skull)
5. Bone marrow biopsy: plasma cell infiltration
TREATMENT:
1. Steroids
2. Induction chemotherapy
3. Stem cell transplant
4. Bisphosphonates
5. EPO (Erythropoietin) - stimulates RBC production
What bugs are usually implicated in the following bites:
1. Human
2. Cat
3. Dog
HUMAN:
1. Eikenella
2. Staph
3. Strep
4. Fusobacteria
5. Prevotella
6. Corynebacterium
7. Bacteroides
8. Peptostreptococcus
CAT:
1. Pasteurella
DOG:
1. Staph
2. Pasteurella
What is the most common type of vasculitis?
Giant cell / Temporal Arteritis
(see Headache section under GenOTOHNS)
What is the difference between Pemphigus and Pemphigoid?
Pemphigus is autoimmune to the epidermis layer.
Pemphigoid is autoimmune to the subepidermal layer between the dermis and epidermis, ie. basement membrane (lower down - can be basement membrane or even the dermis).
