Amyloidosis
Amylodiosis
Amyloid:
-a group of substances with B-pleeted sheet configuration.
-eosnophilic appearance, located extracellularly proximate to basement membranes
-stain with Congo red, has apple green birefringence
Clinical Patterns
-Primary amylodisos (immuncytic dyscrasia): AL protein (derived from immuglobulin light chains) à deposits in heart, muscle, tongue, kidney
- associated with plasma cell disorders (multiple myeloma, waldenstrom macroglobulinemia)
-Secondary amyloidosis (ractive systemic): AA protein. Chronic tissue destruction à increase in SAA (serum amyloid-associated protein)à deposition of fibrils consisting of amyloid protein (called AA protein) in parenchymous organs.
-“saga spleen”: perifollicular involvement resulting in a spleen that looks like tapioca granules.
Other forms
-Portugeues type of polyneuropathy: derived from Transthyretin (a protein that transports thyroxine and retinol). Characterized by peripheral nerve involvment.
-Alzheimer disease: A4 amyloid (or AB-portein). Chromosome 21
-Familial medicteranean fever: AA amyloid. Autosomal recessive disease.
-Medullary carcinoma of thyroid: Amyloid protein from calcitonin deposits within the tumor
-Diabetes mellitus: amylin deposits in islet cells
-Senile amyloidosis : found during autopsy in brain, heart. Transthyretin
-Dialysis-associated : amyloid depsoits in joints. derived from B-microglobulin
Connective Tissue Diseases
Mixed Connective Tissue Disease
Mixed Connective tissue Disease
-women, 35-40
-No renal involvement
-arthralgias, Raynaud phenomoneon, esophageal hypomotility, myositis
-anti-nRNP, speckled nuclear appearance
Polyarteritis Nodosa
Polyarteritis Nodosa
-more common in men
-affects small and medium vessels
-segmental, fibrinoid, necrosis
-an immune complex vasculitis
-the antigen (which causes the formation of antibodies) could be Hepatitis B or drugs (sulfonamides and penicillin)
-if lung involved à chest pain, cough, dyspnea, eosinophilia
Polymyositis
Polymyositis
-pregnant women
-proximal muscles of extremities
-skin can get involved (red-purple rash) à dermatomyositis
-increased serum creatine kinase
-muscle biopsy à necrotic muscle cells, lymphocytic infiltrate
Progressive Systemic Sclerosis
Progressive systemic sclerosis
-widespread fibrosis and degenerative changes involving many organs
-fixed facial appearance, sclerodactyly (claw-like hand), Raynaud phenomenon, visceral organs involvement (esophagus-dysphagia, lung-internsitial pulmonary fibrosis, hypertension).
-anti-Scl-70, ANAs with anticentromere activity (in CREST syndrome)
-CREST syndrome: caclinosis, raynaud phenomenon, esophageal dysfunction, sclerodactyly, telangiectasia
Sjogren Syndrome
Sjogren syndrome
-women
-Triad: dry mouth, dry eyes, rheumatoid arthritis
-Sicca syndrome: only dry mouth and dry eyes
-infiltration by lymphocytes and plasma cells of the Parotids à obscure parenchyma of parotid gland à malignant lymphoma
-hypergammaglobulinemia, anit-SS-B, anti-SS-A
Systemic Lupus Erythematosus
Systemic Lupus erythematosus
-women of childbearing age
-join problems
-butterfly rash
-Raynaud
-serosal: pericarditis, pleuritis
-diffuse interstitial pulmonary fibrosis: interstitial pneumonitis, diffuse fibrosing alveolitis
-verrucous endocarditis – affects mitral valves on both sides
-vasculitis – onion skin appearnce (concentric rings of collagen)
-Glomerular changes
-immune complex deposition: subendothelial (wireloop), mesangial
-endothelial proliferation
-thickening basement memberane
-Diagnosis: LE cells, dsDNA, Sm antigen, decreased serum complement, immun complexes at dermal-epidermal junction, false-positive test for syphilis (due to cardiolipin)