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The manifestations are protean, and there is no characteristic or pathognomonic finding. Instead, this disease is diagnosed by finding suggestive serologic and clinical findings. Findings may include:
Skin rash - malar or discoid Sensitivity to light (photodermatitis) Serositis - inflammation of serosal surfaces along with effusions Glomerulonephritis - the worst problem with SLE Cytopenias - anemia, leukopenia, thrombocytopenia Antinuclear antibody - rim pattern, anti double stranded-DNA and anti-Smith autoantibodies are most specific for SLE Arthralgias, myalgias Vasculitis - anywhere: CNS, skin, kidney, etc Decreased serum complement - especially C1q Thrombosis - in arteries or veins
Genetic factors: tends to run in families; association with HLA Dr-2 and Dr-3; more common in young women (especially African-American). Drugs can produce "drug-induced" SLE: list includes procainamide, hydralazine, isoniazid, d-penicillamine. Discoid lupus erythematosus (DLE): a benign disease with skin involvement; ANA positive in only a third (but some of these go on to SLE).
C = Calcinosis in skin and elsewhere R = Raynaud's phenomenon, sensitivity to cold E = Esophageal dysmotility from submucosal fibrosis S = Sclerodactyly from dermal fibrosis T = Telangiectasias
Diffuse scleroderma: the worst form of PSS; Scl-70 (anti-DNA topoisomerase I) antibody shows specificity for this form. It may include all of the findings with CREST, but additionally has renal findings: arterial intimal thickening and proliferation (hyperplastic arteriolosclerosis) leading to malignant hypertension with arterial fibrinoid necrosis, thrombosis, and renal infarction. Half of diffuse PSS patients die from renal disease. The lungs in this form of scleroderma may have diffuse alveolar fibrosis leading to honeycomb fibrosis
Polymyositis-Dermatomyositis
Characterized by inflammation of skeletal muscle with weakness. Sometimes it is associated with a skin rash (hence, dermatomyositis). It is seen in ages 40-60, but also in ages 5-15, mostly in women. Some of these patients have Jo-1 antibody. Inflammation in polymyositis is mainly mediated by cytotoxic CD8 cells. In dermatomyositis, mainly antigen-antibody complexes produce a vasculitis in muscle and skin. Some adults (1020%) develop cancer.
Sjogren's Syndrome
Characterized by dry eyes and dry mouth as a result of lacrimal and salivary gland involvement by lymphocytic infiltration, fibrosis, and destruction mediated by CD4+ cells helping antibody production, of which anti-SS-A and anti-SS-B are the most specific. Most patients are middle to older age women. Lacrimal and salivary gland inflammation of any cause (including Sjogren's) is called Mikulicz's syndrome.
There is an increased incidence of autoimmune diseases, particularly hemolytic anemia, thrombocytopenia, and pernicious anemia. In about two thirds of cases, normal numbers of circulating B lymphocytes are present. There is a decrease in immunoglobulins, generally in all classes, more often IgG and IgA, but sometimes only of IgG.
DiGeorge Syndrome
The DiGeorge syndrome (or sequence) is a field defect of third and fourth pharyngeal pouch development in utero during organogenesis in the first trimester of pregnancy. A specific deletion on the long arm of chromosome 22 has been implicated. Anatomic structures that may be aplastic or hypoplastic include the thymus, parathyroid glands, great vessels, and esophagus. DiGeorge syndrome may be further subclassified as complete, in which there is almost total absence of thymic tissue, or as partial, in which there is only a decrease in thymic tissue Complete DiGeorge syndrome is characterized by normal levels of circulating immunoglobulin, though in some cases serum IgE is increased and IgA is decreased. However, affected children have markedly decreased numbers of circulating T lymphocytes, making them susceptible to fungal and viral infections. Children with partial DiGeorge syndrome have only a slight decrease in peripheral T lymphocytes and have increased infections, but with less frequency and with less severity than children with the complete form. Accompanying aplasia of parathyroid glands can lead to lifethreatening hypocalcemia that may appear soon after birth.
An X-linked form is due to a mutation on the long arm of the X chromosome which produces a defective gamma chain of the interleukin-2 receptor (cytokine receptor). Lacking an intact interleukin receptor renders early lymphocytes incapable of normal differentiation and development to functional T and B cells in response to growth factors. This form accounts for about 60% of cases. Autosomal recessive inheritance linked to a lack of the enzyme adenosine deaminase (ADA) leads to about 35 to 40% of cases. The ADA enzyme is involved in purine metabolism, and its deficiency results in production of metabolites toxic to lymphocytes
There tends to be a greater decrease in cell mediated immunity than in humoral immunity. Normal or increased numbers of B lymphocytes may be present with the X-linked form, but these cells still do not function properly. There is very little serum IgG and virtually no IgM or IgA. Infants develop Candida skin rashes and thrush, persistent diarrhea, severe respiratory tract infections with Pneumocystis carinii and Pseudomonas soon after birth, and failure to thrive after 3 months of age. Severe viral can occur. Maternal T lymphocytes crossing the placenta may produce graft versus host disease
Wiskott-Aldrich Syndrome
An X-linked recessive pattern is seen because the defective gene is located on the short arm of the X chromosome (Xp11.23). The immunodeficiency is accompanied by thrombocytopenia and eczema. Circulating platelets are markedly decreased. T lymphocytes exhibit cytoskeletal disorganization and loss of microvilli by electron microscopy, and they express little CD43 by immunohistochemical staining. There is usually a normal level of serum IgG, along with a decrease in IgM, but often an increase in both IgA and IgE. The initial onset of disease in early childhood is accompanied by recurrent bacterial infections, particularly to encapsulated bacteria such as Streptococcus pneumoniae, with development of pneumonia, meningitis, and septicemia. Later, failure of T lymphocyte function may predispose to recurrent herpetic infections and to Pneumocystis carinii pneumonia. A bleeding problem may result from the severe thrombocytopenia.
Ataxia-Telangiectasia
A genetic defect is present on the long arm of chromosome 11 which predisposes to chromosome breakage and rearrangement, particularly on chromosomes 7 and 14, leading to a high risk for neoplasia and a marked sensitivity to radiation. This disorder is quite rare and has an autosomal recessive pattern of inheritance. There is a triad of progressive cerebellar ataxia, mucocutaneous telangiectasias, and recurrent respiratory tract infections with a variety of bacterial and fungal organisms. Immunoglobulin deficiencies, particularly IgA and/or IgE, may be present, though serum IgM is usually elevated. The symptoms usually begin between 9 months and 2 years of age.
Complement component deficiencies: C2 deficiency carries a risk for development of autoimmune disease. C3 deficiency is associated with recurrent bacterial infections. Chediak-Higashi syndrome: A rare autosomal recessive disorder in which peripheral blood neutrophils, monocytes, and lymphocytes contain giant cytoplasmic granules and patients have leukopenia, making them susceptible to bacterial and fungal infections of skin, mucous membranes, and respiratory tract Chronic granulomatous disease: neutrophils and monocytes lack the enzyme NADPH oxidase which is needed to generate intracellular oxidants that destroy phagocytosed infectious organisms, particularly catalase-positive agents such as Staphylococcus aureus, Candida, and Aspergillus, so that chronic infections are common