Ref Harrison 16/e p2423,9/e p242_243 Patient with AT present in the first decade of life with progressive telangiectasia lesions associated with deficit in cerebellar function and nystagmus It is caused due to defect in DNA repair genes Thymic hypoplsia with cellular and humoral immunoglbulin deficiency , premature ageing, and endocrine disorders such as insulin resistance Skin. The skin is involved in a majority of patients; a characteristic erythematous or maculopapular eruption over the malar eminences and bridge of the nose ("butterfly pattern") is observed in approximately half of the cases. Exposure to sunlight (UV light) exacerbates the erythema (so-called photosensitivity), and a similar rash may be present elsewhere on the extremities and trunk, frequently in sun-exposed areas. Histopathologic findings include lique- factive degeneration of the basal layer of the epidermis, edema at the dermoepidermal junction, and mononuclear infiltrates around blood vessels and skin appendages (Fig. 4-19, A). Immunofluorescence microscopy reveals deposi- tion of immunoglobulin and complement at the dermoepi- dermal junction (Fig. 4-19, B); similar immunoglobulin and complement deposits may also be present in apparently unin- volved skin. Joints. Joint involvement is frequent but usually is not associ- ated with striking anatomic changes or with joint deformity. When present, it consists of swelling and a nonspecific mono- nuclear cell infiltration in the synol membranes. Erosion of the membranes and destruction of aicular cailage, such as in RA, are exceedingly rare. CNS. Central nervous system (CNS) involvement also is very common, with focal neurologic deficits and/or neuropsychiatric symptoms. CNS disease often is ascribed to vascular lesions causing ischemia or multifocal cerebral microinfarcts. Small vessel angiopathy with noninflammatory intimal proliferation is the most frequent pathological lesion; frank vasculitis is uncommon. The angiopathy may result from thrombosis caused by antiphospholipid antibodies. Premature atherosclerosis occurs and may contribute to CNS ischemia. Another postulated mechanism for CNS disease is injury from antineuronal antibodies with conse- quent neurologic dysfunction, but this hypothesis remains unproved. Other Organs. The spleen may be moderately enlarged. Capsular fibrous thickening is common, as is follicular hyper- plasia with numerous plasma cells in the red pulp. Central penicilliary aeries characteristically show thickening and perivascular fibrosis, producing onion-skin lesions. Pericardium and pleura, in paicular, are serosal mem- branes that show a variety of inflammatory changes in SLE ranging (in the acute phase) from serous effusions to fibrinous exudates that may progress to fibrous opacification in the chronic stage. Involvement of the hea is manifested primarily in the form of pericarditis. Myocarditis, in the form of a nonspecific mononuclear cell infiltrate, and valvular lesions, called Libman-Sacks endocarditis, also occur but are less common in the current era of aggressive coicosteroid therapy. This nonbacterial verrucous endocarditis takes the form of irregular, 1- to 3-mm way deposits, seen as distinctive lesions on either surface of the leaflets (i.e., on the surface exposed to the forward flow of the blood or on the underside of the leaflet) (see Chapter 10). An increasing number of patients also show clinical and anatomic manifes- tations of coronary aery disease. The basis of accelerated atherosclerosis is not fully understood, but the process seems to be multifactorial; ceainly, immune complexes can deposit in the coronary vasculature, leading to endothelial damage by that pathway. Moreover, glucocoicoid treatment causes alterations in lipid metabolism, and renal disease (common in SLE) causes hypeension; both of these are risk factors for atherosclerosis (Chapter 9). Many other organs and tissues may be involved. The changes consist essentially of acute vasculitis of the small vessels, foci of mononuclear infiltrations, and fibrinoid deposit Absence of IgG The serum electrophoretic pattern of the patient showed absence of immunoglobulin G and an increase of the IgA and IgM precipitation bands