Amyloidosis and Sarcoidosis – exam 1 – Flashcards
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Amyloidosis
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Generic term describing the deposition of amyloid
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Amyloid
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Extracellular deposition of fibrous protein which is resistant to proteolytic digestion (due to protein folding; β-pleated sheets). Amorphous, eosinophilic material. + Congo Red, bi-refringent (apple-green)*
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Two major forms of acquired systemic amyloidosis:
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AL (primary amyloidosis) AA (secondary amyloidosis
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AL (primary amyloidosis)
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Source of amyloid protein is a population of monoclonal plasma cells in the bone marrow. 90% Immunoglobulin light chain identifiable* Accompanies about 15% of multiple myeloma May affect kidneys, heart, liver, intestines, skin, peripheral sensory nervous system, spleen, and lungs.
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AA (secondary amyloidosis)
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Associated with chronic inflammatory diseases Rheumatoid arthritis IBD Chronic infection Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) Amyloid deposits in kidneys, liver, and spleen.
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Other Types of amyloidosis
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Hemodialysis amyloidosis (β2-microglobulin) Heredofamilial (familial amyloid polyneuropathy) Rare - Autosomal Dominant Organ-limited (Alzheimer's disease)
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Amyloidosis - Epidemiology (US)/incidence
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Most common type: Immunoglobulin light chain related (AL) ♂>♀ (2:1) Usually >40 with peak 60-70 years.
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Amyloidosis - Clinical Presentation
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Variable with organ system involvement (local or systemic) joint renal pulmonary GI cardiac/vascular opthalmic
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amyloidosis presentation - joints
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Symmetric polyarthritis, peripheral neuropathy, and carpal tunnel syndrome.
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amyloidosis presentation - renal
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Nephrotic syndrome (proteinuria, ↓ albumin, edema)
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amyloidosis presentation - pulmonary
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Fatigue and dyspnea. Hoarseness (vocal cords)
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amyloidosis presentation - GI
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Macroglossia (20% of patients), malabsorption, diarrhea, hepatomegaly.
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amyloidosis presentation - cardiac
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Infiltrative or restrictive cardiomyopathy (common) right-sided CHF, JVD, peripheral edema.
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amyloidosis presentation - vascular
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Easy bleeding, periorbital purpura ("raccoon eyes").
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amyloidosis presentation - opthalmic
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visual disturbance.
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Amyloidosis - Diagnoisis
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Demonstration of amyloid deposits in tissues. Abdominal fat pad biopsy (primary*) Rectal biopsy (positive in >60% of cases) Biopsy of other affected areas GI, renal, cardiac
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Abdominal fat pad biopsy Not positive in
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hemodialysis amyloidosis
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Amyloidosis - Lab Tests
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Urine: proteinuria (found in >70% of cases) CBC: anemia BUN/Creatinine: renal insufficiency ALT/AST: liver function abnormalities TSH: hypothyroidism (10% to 20% of patients) SPEP/UPEP: elevated monoclonal proteins. The finding of a monoclonal light chain in the serum or urine is very useful for diagnosis. SAA: prognostic value in AA amyloidosis. DNA studies: diagnosis of hereditary amyloidosis
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Amyloidosis - Imaging
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CXR may reveal hilar and mediastinal adenopathy. Echocardiogram and Nuclear Imaging Serum amyloid P component (SAP) scintigraphy
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Echocardiogram and Nuclear Imaging
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useful to identify and evaluate cardiac involvement
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Serum amyloid P component (SAP) scintigraphy
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high sensitivity for the detection of amyloid deposits in liver, spleen, kidneys, adrenal glands, and bones.
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Amyloidosis - Treatment
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Variable Amyloidosis associated with plasma cell disorders: chemo stem cell transplant Renal transplantation Peritoneal dialysis In secondary (AA) amyloidosis, treat underlying disorder
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Chemotherapy
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may use melphalan (alkylating agent) and prednisone, along with colchicine
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Peritoneal dialysis
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in place of hemodialysis in renal failure. May improve amyloidosis by clearing β-2 microglobulin Renal transplantation may also be done in renal amyloidosis
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Amyloidosis - Prognosis Determined primarily by:
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presence or absence of cardiac involvement the form of amyloidosis
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AL prognosis
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Median survival 1-2 years Immunocytic processes carries the worst prognosis. (life expectancy < 1 yr). Median survival in patients with overt CHF is approximately 6 mo. (30 mo without CHF).
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AA prognosis
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Median survival after diagnosis is 133 months. Renal dysfunction is the predominant disease manifestation of AA amyloidosis. More favorable outcome in patients with blood samples showing SAA concentrations that remain in the low to normal range ( < 4 mg/L).
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Sarcoidosis
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A chronic systemic granulomatous disease which predominantly affects the lungs
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sarcoidosis etiology
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Unknown. May result from the interaction of multiple genes with environmental exposures or infection (mycobacterial?). A complete occupational and environmental exposure history is recommended.
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Sarcoidosis - Epidemiology (US)
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AAs, northern europeans ♀>♂ (slight) Age: Most frequent 20 - 29 (usually < 40) *Presents most commonly in winter and early spring
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sarcoidosis typical presentation
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Up to 50% of patients are asymptomatic and are diagnosed on routine chest radiographs. ~1/3 patients have nonspecific symptoms of fever, fatigue, weight loss, and malaise. Symptoms related to organ-specific involvement
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sarcoidosis presentation - pulmonary
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: dry cough, dyspnea, chest pain
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sarcoidosis presentation - constitutional
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fatigue, wt. loss, anorexia, malaise
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sarcoidosis presentation - Visual disturbances
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blurred vision, ocular discomfort, conjunctivitis, iritis, uveitis
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sarcoidosis presentation -Dermatologic manifestations
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erythema nodosum, macules, papules, subcutaneous nodules, hyperpigmentation
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sarcoidosis presentation - Rheumatologic/hematologic manifestations
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arthralgias hepato/splenomegaly
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sarcoidosis presentation - Neurologic, Cardiac, and other manifestations
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cranial nerve palsies, diabetes insipidus, meningeal involvement, parotid enlargement, hypothalamic and pituitary lesions, peripheral adenopathy
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Sarcoidosis - Lab Tests
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Hypergammaglobulinemia (Polyclonal) Anemia of chronic disease, leukopenia LFT abnormalities Hypercalcemia, hypercalciuria Cutaneous anergy Angiotensin-converting enzyme (ACE) -Elevated in approximately 60% -May be useful as a marker of disease activity.
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Hypercalcemia, hypercalciuria with sarcoidosis
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Secondary to increased GI absorption, abnormal vitamin D metabolism, and increased calcitriol production by sarcoid granuloma
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Cutaneous anergy
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Candida, Trichophyton and tuberculin
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Sarcoidosis - Imaging*
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Chest x-ray (Abnormal in 90%) Adenopathy of the hilar and paratracheal nodes is a frequent finding Gallium-67 scan
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Gallium-67 scan
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Localizes in areas of granulomatous infiltrates; however, it is not specific. The "panda" sign (localization in the lacrimal and salivary glands, giving a "panda" appearance to the face) is suggestive of sarcoidosis.
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Sarcoidosis - Diagnosis
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Biopsy Should be done on accessible tissues suspected of sarcoid involvement. Bronchoscopy with transbronchial biopsy is the procedure of choice in patients without any readily accessible site.
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Sarcoidosis - Treatment
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Corticosteroids considered in patients with: Severe symptoms (dyspnea, chest pain) Hypercalcemia Ocular CNS Cardiac involvement Progressive pulmonary disease (prednisone or alternative: methotrexate)
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Sarcoidosis - Prognosis
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Majority have spontaneous remission within 2 yr and do not require treatment. (50-80%). Followed by: periodic clinical evaluation chest x-ray PFTs
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African Americans with sarcoidosis have
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increased rates of pulmonary involvement, a worse long-term prognosis, and more frequent relapses.
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15 - 20% of sarcoidosis patients with lung involvement
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advance to irreversible lung impairment bronchiectasis cavitation progressive fibrosis pneumothorax respiratory failure Death from pulmonary failure occurs in 5-7% of patients.
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Sarcoidosis - referal
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Ophthalmologic examination is indicated in all patients with suspected sarcoidosis, because ocular involvement found in > 25%
