Infectious dx, Systemic diseases Flashcards

Question

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

Answer 1

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

Answer 2

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 ## Footnote Koplik: https://en.wikipedia.org/wiki/Koplik%27s_spots

Answer 3

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 2. 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 3. Latent - Asymptomatic (may return to mucocutaneous lesions) - 1/3 progress to tertiary - 1/3 latent - 1/3 resolve 4. 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 ## Footnote Gumma: https://escholarship.org/content/qt5gs4q6wz/1.jpg Vancouver notes Page 18

Answer 4

Cogan's Syndrome - Should look for congenital syphillis in a patient presenting with Cogan's syndrome

Answer 5

Secondary syphillis

Answer 6

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

Answer 7

1. Suppurative pharyngitis - Group A strep 2. Acute otitis media - Strep pneumo, H. flu, M. Catarrhalis 3. Acute sinusitis - Strep pneumo, H. flu, M. Catarrhalis 4. Mastoiditis - Strep pneumo, Strep viridans, pseudomonas 5. Otitis externa - Pseudomonas, staph aureus

Answer 8

1. 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 2. 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) ## Footnote Jones: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734099/#:~:text=The%20five%20cardinal%20manifestations%20of,with%20little%20amendment%20over%20time.

Answer 9

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

Answer 10

1. Elevated WBC 2. >50% lymphocytes 3. Atypical lymphocytes >10% 4. Monospot = Serum heterophile antibodies to horse or sheep erythrocyte - 10% false negative

Answer 11

1. < 10 years old 2. CMV mono 3. Early disease

Answer 12

1. IgM: Viral capsid antigen (current and recent disease) 2. 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 3. 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

Answer 13

1. Brucella 2. Rheumatoid arthritis 3. Serum sickness 4. Hodgkin's lymphoma 5. Hepatitis BRoS He's a Heterophile Brucella Rheumatoid arthritis Serum sickness Hodgkin's lymphoma Hepatitis

Answer 14

ORGANISM: 1. Bordetella pertussis PHASES: 1. Catarrhal - Lasts 1-2 weeks, highly contagious - Runny nose, low grade/no fever - Mild, occasional cough 2. Paroxysmal - Lasts 1-6 weeks, up to 10 weeks - Contagious - Fits of rapid coughing that may be followed by "whoop" sound or vomiting 3. 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)

Answer 15

1. Chronic sore throat 2. Halitosis 3. Tonsilliths 4. Peritonsillar erythema 5. Persistent tender cervical adenopathy

Answer 16

1. Purulent rhinorrhea 2. Nasal obstruction 3. Fever 4. Otitis media

Answer 17

Greater than 4 episodes in a 6 month period Treatment: INCS ± reflux management for 6-8 weeks minimum

Answer 18

1. Persistent nasal discharge 2. Chronic congestiion 3. Postnasal drip 4. Halitosis 5. Adenoid facies - open mouth, elongated face, dark circles under the eyes 6. Middle ear effusion - obstructs the ET orifice and allows for bacterial colonization of the area

Answer 19

1. Nystagmus 2. Scanning speech (words are as if measured or scanned; there is a pause after every syllable, and the syllables themselves are pronounced slowly) 3. Intention tremor Associated with multiple sclerosis

Answer 20

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 ## Footnote 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

Answer 21

1. Vertigo - presenting symptom in 7-10% 2. Nystagmus - mainly horizontal 3. Deafness - rare 4. Diplopia - can be intermittent, paralyzed medial rectus (in INO) 5. Bilateral internuclear ophthalmoplegia (INO) - diplopia on one side and unilateral nystagmus, lesion in the medial longitudinal fasciculum (MLF), but convergence is normal

Answer 22

1. MS 2. ALS (EOMs preserved) 3. Basilar artery thrombosis 4. Lambert-eaton (antibodies against presynaptic calcium channels releasing ACh - muscle weakness - can be associated with paraneoplastic small cell lung cancer) 5. Thyroid disease

Answer 23

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

Answer 24

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

Answer 25

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)

Answer 26

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) 2. "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 2. Bronchoscopy: Rule out multiple airway lesions 3. Biopsy Bone Marrow; high number of plasma cells = multiple myeloma 4. Urinalysis = Bence-Jones proteins TREATMENT: 1. Conservative removal of deposits 2. Steroids 3. Antimetabolites not helpful 4. Supportive treatment of involved organs ## Footnote https://www.stainsfile.com/theory/methods/staining-amyloid-proteins-for-histology/#:~:text=It%20stains%20metachromatically%20with%20crystal,be%20stained%20with%20trypan%20blue.

Answer 27

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

Answer 28

1. Biopsy: Fluroescence of immunoglobulins/complement at the dermal-epidermal junction 2. Blood: Positive ANA, APA, anti-ENA, anti-Sm, and anti-dsDNA

Answer 29

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%)

Answer 30

1. Skin eruptions 2. Serositis (Pericarditis, myocarditis) 3. Pneumonitis 4. Nephritis 5. Hypercoagulability/anemia 6. CNS: headaches, seizures, psychosis NYD 7. Oral ulcers (25% - may reseemble lichen planus, leukoplakia, SCC) 8. Arthritis 9. Photosensitiviity 10. Pulmonary fibrosis 11. Cytopenias 12. Renal dysfunction 13. Raynauds 14. Malar rash, discoid rash

Answer 31

1. NSAIDs 2. Antimalarials 3. Glucocorticoids 4. Azathioprine & Cyclophosphamide for resistant cases 5. Oral ulcers - topical cortisone, nystatin

Answer 32

- 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 ## Footnote 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

Answer 33

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

Answer 34

1987 criteria: A. Need 4/7 criteria B. Criteria 1-4 must be > 6 weeks and must be observed by a physician 1. Morning stiffness ~1 hour 2. Swelling in 3 or more joints 3. Swelling in hands joints 4. Symmetrical joint swelling 5. Subcutaneous rheumatoid nodules 6. Serum RF 7. 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

Answer 35

1. Neck - cervical pain, decreased neck ROM 2. TMJ dysfunction - pain/tender joint or muscles (due to erosion of condylar heads) 3. Ossicular arthritis - CHL or SNHL 4. Larynx: Cricoarytenoid joint involvement (86%) - see next card for details 5. Xerostomia (often associated with Sjogren's)

Answer 36

1. Rheumatoid nodule deposition into folds (bamboo nodules) - 30% hoarseness 2. RLN neuropathy (etiology unknown) 3. Acute inflammation/edema over arytenoids 4. Arytenoid process tenderness on palpation 5. Decreased mobility and fixed fold in adducted position 6. Subluxed cricoarytenoid joint on CT scan can be seen

Answer 37

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)

Answer 38

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 ## Footnote https://www.pathologyoutlines.com/topic/skinnontumorsarcoidosis.html

Answer 39

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) ## Footnote Vancouver Pg 24

Answer 40

- 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 ## Footnote Vancouver pg 24

Answer 41

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) ## Footnote Vancouver page 39

Answer 42

1. Finding of a Gallium-67 citrate scan 2. 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 ## Footnote Vancouver Page 39

Answer 43

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 44

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 45

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 46

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 47

1. Small and medium vessel vasculitis (angiocentric) 2. Fibrinous "geographic" necrosis 3. Necrotizing granulomas 4. Mixed plasma cell, lymphocyte, histiocyte, and macrophage infiltration, with isolated multinucleated giant cells 5. Angioinvasion, better identified on elastic stain Hallmark = Necrotizing granulomatous vasculitis (found all together in < 20% of single cases) ## Footnote https://www.pathologyoutlines.com/topic/kidneyGPA.html

Answer 48

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 2. 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 3. Bloodwork for Secondary Sjogren's - HLA-DW4 4. 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!) 5. Salivary scintigraphy (reduced uptake, concentration, or excretion of tracer) - Assessing the uptake and excretion characteristics of radiotracer by salivary glands following secretive stimulation. 6. IgM levels (low = risk of progression to NHL) 7. Schirmer's test - Total tear secretion/reflex tearing 8. Sialometry (amount of saliva produced) 9. Rose Bengal Score (fluorescein staining score) 10. 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 ## Footnote https://www.pathologyoutlines.com/topic/salivaryglandssjogren.html Kevan Gen #109

Answer 49

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 50

1. Lymphocyte and histiocyte infiltration 2. Acinar atrophy 3. Prominence of myoepithelial components as ductal lumens disappear 4. Ductal epithelial hyperplasia and metaplasia 5. Germinal Centres LAPD ## Footnote https://www.pathologyoutlines.com/topic/salivaryglandssjogren.html

Answer 51

- 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) 1. Ocular symptoms: dry eyes, sensation of gravel in eyes > 3 months, or use of tear substitutes >3x/day 2. Oral symptoms: Dry mouth > 3 months, recurrent or persistent swelling of salivary glands 3. Ocular signs: Schirmer test < 5mm in 5 min; or Rose-bengal score > 4 (scores eye dryness) 4. 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) 5. Histopathology: Focus score ≥ 1 = ≥50 lymphocytes in 4mm2 of glandular tissue 6. Serology: Presence of Anti-Ro/SS-A or Anti-La/SS-B antibodies (sensitivity 85 + 94%, specificity 93 + 94%)

Answer 52

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 2. OTOLOGIC - Eosinophilic otitis media - OME - SNHL - CN VII paresis - Vertigo - Recurrent mastoiditis 3. ORBITAL PSEUDOTUMOR - Eye lid edema - Chemosis - Diplopia - Vision loss (20%) - Pain with movement, EOM myositis - Proptosis/diplopia (EOM tendons involved on imaging) 4. LACRIMAL - Swelling with at least 1 major salivary gland 5. LYMPHADENOPATHY - 2/3 submandibular region - Can be diffuse - < 2-3 cm, non-tender, rubbery 6. THYROID - RIEDEL'S - Riedel fibrosing thyroiditis is a rare disease characterized by chronic inflammation and fibrosis of the thyroid gland 7. AIRWAY - Hoarseness - Airway stenosis 8. NON-HEAD/NECK - Pancreas - Kidney - Gallbladder - Aorta

Answer 53

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) ## Footnote Kevan Gen #156 - Obliterative pheblitis

Answer 54

1. IgG4 plasma cells trigger B-cells to secrete cytokines & toxic enzymes 2. CD4 T-cells are attracted to the tissue with an inflammatory response, then causes fibrosis 3. Response is proportional to IgG4 level

Answer 55

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 ## Footnote https://www.pathologyoutlines.com/topic/kidneyigg4related.html

Answer 56

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 57

1. Refer to Rheumatology and hematology 2. Conservative symptomatic management 3. Medical Management 4. 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 58

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 59

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) ## Footnote Vancouver notes Page 28

Answer 60

PAN = A small-medium vessel vasculitis 1. Bilateral SNHL or CHL or vestibular dysfunction 2. CN palsy (FN CNVII most common) 3. Septal perforation

Answer 61

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 62

1. Intubation granuloma - Vocal process of arytenoids - Contact ulcer --> granuloma --> pedunculated ulcer 2. Teflon granuloma (2-3% in VC injection) 3. Reparative granuloma anterior to 1st molar - lytic, expansive, unilocular cavity - Peripheral: blue/red mass on gingiva of anterior mandible - Central: Endosteal 4. Pyogenic granuloma (lobular capillary hemangioma) - Not a true granuloma, but included for completion

Answer 63

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

Answer 64

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 65

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 2. 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 3. 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 4. 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 ## Footnote Vancouver Notes Page 30

Answer 66

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 67

Limited cutaneous scleroderma with the following features ("CREST"): 1. C: Calcinosis (deposition of calcium in the skin/tissue/muscles/organs) 2. R: Raynaud's phenomenon (90%) 3. E: Esophageal stenosis/dysmotility 4. S: Sclerodactyly (thickening and tightening of the skin of the fingers or toes) 5. T: Telangiectasias

Answer 68

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 69

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

Answer 70

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 71

Giant cell / Temporal Arteritis (see Headache section under GenOTOHNS)

Answer 72

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).

Infectious dx, Systemic diseases Flashcards

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