Infectious dx, Systemic diseases Flashcards

Question 1

Q

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

Answer

A

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

Question 2

Q

Describe the categories or stratification of HIV illness based on CD4 counts

Answer

A

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.)

Question 3

Q

What are the pathologies associated with low CD4 counts and what prophylaxis can be given if possible?

Answer

A

< 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

Question 4

Q

What are 5 dermatologic manifestations of HIV? How can they be managed?

Answer

A

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

Question 5

Q

What are all the Otolaryngologic manifestations of HIV?

Answer

A

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

Question 6

Q

What is the differential diagnosis of cervical disease in HIV? (5)

Answer

A

Progressive generalized lymphadenopathy (PGL, 12-45%)
Mycobacterium tuberculosis
Pneumocystis carinii
Lymphoma
Kaposi sarcoma

Question 7

Q

What are 8 indications for open biopsy of lymphadenopathy in HIV?

Answer

A

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

Question 8

Q

How many types of Human Herpes Virus are there, and what are their names?

Answer

A

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

Question 9

Q

Regarding Kaposi’s sarcoma, discuss:
1. Cause
2. What are the types?
3. Clinical Presentation
4. 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)

Answer

A

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:
1. Classic (seen in Mediterranean and European middle aged men; cutaneous lesions)
2. African endemic
3. Iatrogenically immunocompromised
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)

Question 10

Q

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

Answer

A

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

Question 11

Q

What are the risks of developing HBV, HCV, and HIV with a known infected needle source?

Answer

A

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

Question 12

Q

What are the 3 main types of oral aphthous ulcers? Briefly describe them

Answer

A

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

Question 13

Q

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

Answer

A

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

Question 14

Q

List all the different head and neck manifestations of tuberculosis

Answer

A

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

Question 15

Q

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?

Answer

A

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)

Question 16

Q

Regarding Leprosy, discuss:
1. What is the cause?
2. What is the clinical presentation?
3. What is the treatment?

Answer

A

= Hansen’s disease

CAUSE:
- Mycobacterium Leprae (slow-growing bacteria)

PRESENTATION:
1. Keratitis
2. Hypopigmented or erythematous macules
3. Mucosal nodules
4. Hyposmia
5. Atrophy of the anterior nasal spine and maxillary alveolar process (fish-mouth deformity)
6. Lymphadenopathy
7. Laryngeal ulcerations
8. Facial nerve paralysis

TREATMENT:
1. Multi-drug therapy x 1 year
- Rifampicin
- Dapsone
- Lofazimine

Question 17

Q

Regarding Anthrax, discuss:
1. What is the cause?
2. What is the clinical presentation?
3. What is the treatment?

Answer

A

CAUSE: Bacillus anthracis (gram +ve bacteria)

PRESENTATION:
1. 95% - small papule, painless necrotic ulcer ± adenopathy

TREATMENT:
1. Penicillin G

https://en.wikipedia.org/wiki/Anthrax

Question 18

Q

Regarding Tularemia, discuss:
1. What is the cause?
2. What are the symptoms?
3. How is it diagnosed?
4. What is the treatment?

Answer

A

= “Rabbit fever”

CAUSE:
1. Francisella Tularensis (gram negative coccobacillus)

SYMPTOMS:
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

Question 19

Q

Regarding Brucellosis, discuss:
1. What is the cause?
2. What are the symptoms?
3. How is it transmitted?
4. How is it diagnosed?
5. What is the treatment?

Answer

A

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

Question 20

Q

Regarding Cat Scratch Disease, discuss:
1. What is the cause?
2. What it the clinical presentation?
3. What is the diagnostic criteria?
4. What are the investigations?
5. What is the treatment?
6. Complications?

Answer

A

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 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)

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

Question 21

Q

A patient has a first neck mass after dental surgery, FNA shows sulfur granules. What is the diagnosis?

Answer

A

Actinomycosis (acid fast negative)

Note: Nocardia can also produce sulfur granules, but these are differentiated from actinomyces by positive acid-fast staining

Question 22

Q

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

Answer

A

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

Question 23

Q

List 5 non-infectious, non-neoplastic causes of lymphadenopathy

Answer

A

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

Question 24

Q

Regarding Atypical mycobacterial infection, discuss:
1. Cause
2. Clinical presentation
3. Diagnosis
4. Treatment

Answer

A

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)
Observation (self-resolving)

Question 25

Q

Regarding Kawasaki disease, discuss:
1. What is it?
2. Clinical presentation
3. AHA Diagnostic criteria
4. Investigations/workup
5. Treatment

Answer

A

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

Question 26

Q

Regarding Measles, discuss:
1. Causative organisms
2. Clinical presentation
3. Management
4. Systemic complications

Answer

A

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

Question 27

Q

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?

Answer

A

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 of the foal 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

Question 28

Q

What disease can look like congenital syphillis with interstitial keratitis but negative VDRL?

Answer

A

Cogan’s Syndrome

Should look for congenital syphillis in a patient presenting with Cogan’s syndrome

Question 29

Q

What is the likely cause of superficial “snail track” ulcers of the tonsils and soft palate?

Answer

A

Secondary syphillis

Question 30

Q

What are viral causes of pharyngitis?

Answer

A

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

Question 31

Q

What are the most common bacterial causes of:
1. Suppurative pharyngitis
2. Acute otitis media
3. Acute sinusitis
4. Mastoiditis
5. Otitis externa

Answer

A

Suppurative pharyngitis - Group A strep
Acute otitis media - Strep pneumo
Acute sinusitis - Strep pneumo, H. flu, M. Catarrhalis
Mastoiditis - Strep pneumo, Strep viridans, pseudomonas
Otitis externa - Pseudomonas, staph aureus

Question 32

Q

How is rheumatic fever diagnosed at the first episode vs. subsequent episodes?

Answer

A

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: 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.

Question 33

Q

Regarding Scarlet Fever, discuss:
1. What is the organism cause?
2. Clinical features
3. How is it diagnosed?
4. What is the treatment?

Answer

A

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

Question 34

Q

What are the diagnostic laboratory findings of EBV?
What is the false negative rate? What are possible reasons for false negatives?

Answer

A

Elevated WBC
> 50% lymphocytes
Atypical lymphocytes >10%
Monospot = Serum heterophile antibodies to horse or sheep erythrocyte
- 10% false negative

Question 35

Q

What are 3 reasons for false negative monospot tests (heterophil antibody test)

Answer

A

< 10 years old
CMV mono
Early disease

Question 36

Q

What are the most sensitive tests for mononucleosis?

Answer

A

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

Question 37

Q

What are five causes of false positive heterophil antibody test for infectious mononucleosis?

Answer

A

Brucella
Rheumatoid arthritis
Serum sickness
Hodgkin’s lymphoma
Hepatitis

Question 38

Q

Regarding Pertussis, discuss:
1. What are the causative organisms?
2. What are the phases/clinical presentation?
3. What is the treatment?

Answer

A

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)

Question 39

Q

What are 5 symptoms/signs of chronic tonsillitis?

Answer

A

Chronic sore throat
Halitosis
Tonsilliths
Peritonsillar erythema
Persistent tender cervical adenopathy

Question 40

Q

What are 4 symptoms of acute adenoiditis?

Answer

A

Purulent rhinorrhea
Nasal obstruction
Fever
Otitis media

Question 41

Q

What is the definition of recurrent acute adenoiditis? What is the treatment?

Answer

A

Greater than 4 episodes in a 6 month period

Treatment: INCS ± reflux management for 6-8 weeks minimum

Question 42

Q

What are the symptoms of chronic adenoiditis?

Answer

A

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

Question 43

Q

Define Charcot’s triad

Answer

A

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

Question 44

Q

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?

Answer

A

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. Diplopia
4. Bilateral INO (internuclear ophthalmoplegia)
5. Charcot’s triad: nystagmus, scanning speech, intention tremor

COMPLICATIONS:
1. Seizures
2. Falls
3. Pressure ulcers
4. Aspiration
5. Pneumonia

INVESTIGATIONS:
1. MRI Brain
2. CSF cytology and chemistry (glucose, protein, IgG)
3. Evoked potentials

DIAGNOSIS:
- MRI findings of demyelinated foci in white matter
- Abnormal auditory and visual evoked responses
- Elevated CSF protein content (oligoclonal bands)

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

Question 45

Q

List the head and neck manifestations of multiple sclerosis

Answer

A

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

Question 46

Q

List a differential diagnosis of conditions resembling Myasthenia Gravis

Answer

A

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

Question 47

Q

Regarding myasthenia gravis, discuss:
1. What is it
2. Cause
3. Types
4. Clinical presentation
5. Diagnosis
6. Complications
7. Treatment

Answer

A

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

Question 48

Q

Regarding Carcinoid syndrome, discuss:
1. What is it?
2. Clinical presentation
3. Diagnosis
4. Associations
5. Treatment

Answer

A

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

Question 49

Q

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

Answer

A

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)

Question 50

Q

Regarding amyloidosis, discuss:
1. What is it? Where is the most common site in the head and neck?
2. What are the causes? What are the different types and where are their typical deposition locations?
3. Symptoms?
4. How is it diagnosed?
5. Investigations? Pathology and stains?
6. Treatment?

Answer

A

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.

Question 51

Q

What are all the head and neck manifestations of amyloidosis?

Answer

A

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

Question 52

Q

How id Systemic lupus erythematosus (SLE) typically diagnosed?

Answer

A

Biopsy: Fluroescence of immunoglobulins/complement at the dermal-epidermal junction
Blood: Positive ANA, APA, anti-ENA, anti-Sm, and anti-dsDNA

Question 53

Q

List 10 head and neck manifestations of Systemic Lupus Erythematosus (SLE)

Answer

A

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%)

Question 54

Q

What are the different systemic manifestations of SLE?

Answer

A

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

Question 55

Q

What are the treatment options for SLE?

Answer

A

NSAIDs
Antimalarials
Glucocorticoids
Azathioprine & Cyclophosphamide for resistant cases
Oral ulcers - topical cortisone, nystatin

Question 56

Q

What is discoid lupus? What is the typical clinical presentation?

Answer

A

Cutaneous lesions 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

Question 57

Q

Regarding Rheumatoid arthritis, discuss:
1. What is it?
2. What is the F:M predilection?
3. How is it typically diagnosed?
4. Treatment?

Answer

A

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

Question 58

Q

What are the diagnostic criteria of rheumatoid arthritis?

Answer

A

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

Question 59

Q

What are 5 head/neck manifestations of rheumatoid arthritis?

Answer

A

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)

Question 60

Q

What are 6 features of cricoarytenoid joint involvement of rheumatoid arthritis?

Answer

A

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

Question 61

Q

Regarding Behcet’s syndrome, discuss:
1. What is it?
2. Risk factors and possible etiology
3. Clinical presentation
4. Differential diagnosis
5. Complications
6. Diagnostic criteria
7. Treatment

Answer

A

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)

Question 62

Q

Regarding Sarcoidosis, discuss:
1. What is it?
2. What are the risk factors?
3. What is the diagnostic findings?
4. Clinical presentation?
5. Complications?
6. Types/variants of sarcoidosis?
7. Investigations and biopsy findings?
8. Treatment?

Answer

A

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

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

Question 63

Q

What are all the head and neck manifestations of sarcoidosis? (16)

Answer

A

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

Question 64

Q

What is Lupus Pernio?

Answer

A

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

Answer 65

A

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

Answer 66

A

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

Answer 67

A

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)

Answer 68

A

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%

Answer 69

A

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

Answer 70

A

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.

Answer 71

A

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

Answer 72

A

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

Answer 73

A

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

Answer 74

A

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

Answer 75

A

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%)

Answer 76

A

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

Answer 77

A

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

Answer 78

A

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

Answer 79

A

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

Answer 80

A

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

Answer 81

A

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

Answer 82

A

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

Answer 83

A

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

Answer 84

A

PAN = A small-medium vessel vasculitis

Bilateral SNHL or CHL or vestibular dysfunction
CN palsy (FN CNVII most common)
Septal perforation

Answer 85

A

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

Answer 86

A

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

Answer 87

A

Macrophage/dendritic cell (APC) that normally resides in the epidermis of skin
Antigen presenting cell

Answer 88

A

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

Answer 89

A

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

Answer 90

A

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

Answer 91

A

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

Answer 92

A

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

Answer 93

A

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

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

Answer 94

A

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

Answer 95

A

Giant cell / Temporal Arteritis

(see Headache section under GenOTOHNS)

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