Diseases Exam 5 Flashcards
(44 cards)
Systemic Lupus Erythrmatosis
Pathophysiology: Type III hypersensitivity autoimmune diesease which involves multiple organs. Onset may be acute or chornic (typically chronic - relapsing/remitting course). Environmental trigger leads to apoptosis –> increased nuclear antigens in genetically susceptible individual.
Tests: ANA (sensitive but not specific); dsDNA (specific, poor prognosis) and anti-Smith (specific, not prognostic), antihistone (drug-induced lupus)
Prevalence: 1 in 2500 (90% female ages 14-45)
Can have anti-phospholipid antibodies (30-40%). These cause false positive syphilis test, and are associated with hypercoaguable state (even though they prolong partial thromboplastin time) –> can cause anti-phospholiped antibody syndrome.
Symptoms: I'M DAMN SHARP Immunoglobulins - anti-dsDNA, anti-Smith, anti-phospholipid Malar rash Discoid rash Antinuclear antibody Mucositis Neurologic disorders Serositis Hematologic disorders Arthritis Renal disorders, reynauds Photosensitivity
Most common COD = immunosuppression.
Chronic discoid lupus erythematosis
A form of SLE predominately limited to the skin. (no systemic manifestations)
Subacute cutaneous lupus erythematosis
Another form of SLE. Predominantly linked to the skin, but mild systemic lesions may be present.
Drug induced lupus erythematosis
Diagnosed by anti-histone antibodies.
Rheumatoid Arthritis
Pathophysiology: Type III hypersensitivity which primarily attacks the joints, producing a nonsupprative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis.
Activation of CD4+ and B cells form a pannus (mass of inflamed synovium) which grows over the joint cartilage –> inflammatory destruction.
Genetic susceptibility is a major contributor - HLA DRB1, PTPN22
Labs - rhematoid factor (sensitive), Anti-CCP (specific)
Common sites- PIP joints, MP joints, elbow
Sjorgren Syndrome
Chronic disease characterized by dry eyes (keratoconjucitivitis sicca) and dry mouth (xerostomia) resulting from autoimmune, immunologically mediated destruction of the lacrimal and salivary glands.
It can be isolated (primary sjogren) or w/ another autoimmune disorder (secondary sjogren)
Typically occurs in middle aged women.
Pathology demonstrates lymphocytic inflammation involving lacrimal and salivary glands followed by fibrosis and atrophy. May also see parotid gland enlargement due to inflammation (Mikulicz disease)
Labs: Antibodies to SS-A and SS-B (sensitive), lip biopsy
Increased risk for the development of lymphoma
Systemic Sclerosis (Scleroderma)
Chronic inflammation, presumably autoimmune, with widespread damage to small blood vessels and progressive interstitial and perivascular fibrosis of the skin (most common) and mutliple organs (GI, kidneys, heart, muscles, and lungs)
Adults with 3:1 = F:M ratio.
The pathologic findings are secondary to ischemic damage and fibrosis in the affected organs.
Labs: antibodies to Scl-70 (DNA topo I); patients with CREST may have anti-centromere antibodies
Sx: Raynaud’s (most common initial complaint), skin - sclerotic atrophy and sclerosis (sclerodactyly) that begins in the distal fingers and moves proximal, esophageal fibrosis, interstistial fibrosis of lungs, non-destructive arthritis, kidney problems
Diffuse scleroderma
Widespread skin involvement at onset, with rapid progression and early visceral involvement
Limited scleroderma
Skin involvement is confined to fingers, forearms, and face with late visceral involvement (more indolent form).
Some patients develop the CREST syndrome (Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactyly, and telangiectasia)
CREST syndrome
Calcinosis, Raynaud’s, esophageal dysmotility, sclerodactlyly, and telangiectasia
Associated w/ limited scleroderma.
May have anti-centromere antibodies
Raynaud’s phenomenon
Exaggerated vasospastic response to cold or emotional stress, causing discoloration of the fingers, toes, and occasionally other areas.
Dermatomyositis
Autoimmune disease w/ immunologic injury and damage to small blood vessels and capillaries in the skeletal muscle, along with skin involvement and characteristic skin rash (violaceous discoloration of upper eyelids associated w/ periorbital edema accompanied by red patches over knuckles, elbows, and knees (Gottron papules) “mechanic’s hands”.
Muscle weakness typically affects proximal first accompanied by myalgias.
15-25% have an underlying malignancy.
Labs:elevated CK and aldolase. Positive ANA and anti-Jo-1.
Treatment = steroids
Polymyositis
Muscle and systemic involvement is similar to that seen in dermatomyosistis except lack of skin involvement. Most often involves shoulders.
Labs: Biopsy with perifascicular inflammation is diagnositc. elevated CK and aldolase. Positive ANA and anti-Jo-1.
Treatment = steroids
Mixed connective dissue disease
Patient’s w/ overlap autoimmune disease that has features that are a mixture of SLE, scleroderma, and polymyositis.
antibodies to ribonucleoprotein containing U1 (anti-U1-RNP)
X-linked Agammaglulinemia (Bruton’s Agammaglobulinemia)
Failure of B-cell precursors to develop into mature B cells. Due to defect in X linked gene (XLA) which codes for Bruton’s tyrosine kinase (Btk).
Present w/ decreased or absent B cells, Ig, plasma cells, and underdeveloped germinal centers.
Recurrent sinopulmonary bacterial infections, certian viral infections, giardia lablia.
No decreased susceptiblity to viral, fungal, or protozoal infections.
At risk for arthirtis and dermatomyositis.
Rx: prophylactic IVIG
Combined Variable Immunodeficiency
Heterogenous disorders characterized by a failure of B cells to differentiate into plasma cells.
Decreased Ig, but normal B cells. Germinal centers are hyperplastic.
Sporadic and inheritied and affects both sexes equally.
DiGeorge Syndrome
Thymic hypoplasia
T cell deficiency due to failure of develoment of the theird and fourth pharyngeal pouches.
Sx: CATCH 22 Cardiac abnormalities Abnormal facies Thymus aplasia Cleft palate Hypercalcemia 22q11 deletion
Hyper IgM syndrome
Patient’s are able to make IgM but are deficient in their ability to make IgG, IgA, and IgE.
Approximately 70% have X-linked recessive mutation in gene for CD40L.
SCID
A group of syndromes all having profound defects in both humoral and cell mediated immunity. Without hematopoetic cell transplantation, death occurs within a year.
Many different genetic mutations can give rise to SCID. Most common (50-60%) is X-linked mutation in the gene encoding the common gamma-chain subunit of cytokine receptors. –> deficient T and NK cells. B cells are normal, but can’t activate properly.
Also deficiency in enzyme Adenosine Deaminase (ADA) causes a toxic accumulation of deoxyadenosine.
Rx: ematopoetic cell transplantation, gene therapy (x-linked)
Wiskott-Aldrich Syndrome
Immunodeficiency with thrombocytopenia and eczema.
X-linked recessive disorder.
The disease is due to mutation is in WASP protein on the short arm of the X chromosome. Causes defects in cell migration and signal conduction and subsquent T cell deficiencies.
X linked lymphoproliferative syndrome
Inability to eliminate EBV leading to severe and sometimes fatal mononucleosis and B cell lymphomas.
Chediak-Higashi
Mutation in CHS1/LYST. Rare autosomal recessive.
Sx: recurrent pyogenic infections, partial oculocutaneous albinism, progressive neuro abnormalities.
Caused by defect in fusion of phagosomes and lysosomes.
Pathognomonic giant cytoplasmic granules in leukocytes.
Deficiencyies in terminal complement
Increased susceptibility to Neisseria infections due to mutated MAC. (Neisseria have thin walls –> especially sensitive to complement)
Cellular rejection
T cell-mediated graft rejection.
Involves destruction of donated graft cells by recipient CD8 and delayed hypersensitivity reactions by recipient CD4.
The major differences are in the highly pleomorphic HLA alleles.
