MIXED CONNECTIVE-TISSUE DISEASE - A CLINICAL, HISTOLOGIC, AND IMMUNOFLUORESCENCE STUDY OF 8 CASES

A study of the cutaneous eruptions of eight patients with mixed connec tive tissue disease (MCTD) was performed to better characterize its de rmatopathology and to explore a role for the membrane attack complex o f complement C5b-9 in lesional pathogenesis. Nine lesional skin biopsi es were obtained from eight patients with MCTD and analyzed by convent ional light microscopy. Direct immunofluorescence (IF) and indirect IF using a monoclonal antibody to C5b-9 were applied in six and five cas es respectively, The biopsied cutaneous eruptions were characterized c linically as photo-distributed erythematous annular and/or papulosquam ous lesions mimicking subacute cutaneous lupus erythematosus (SCLE) in five of eight patients as an ill-defined, telangiectatic, scaly patch on the face in one patient,palpable purpura in one patient, and dorsa l hand blisters resembling porphyria cutanea tarda (PCT) in another. W ith the exception of the latter two patients. the histology appeared s imilar, comprising a cell poor and/or lichenoid interface dermatitis w ith suprabasilar exocytosis around necrotic keratinocytes in the absen ce of deep periadnexal or perivascular extension or conspicuous follic ular plugging, a pattern similar to that of SCLE. However, the lesions differed from SCLE by virtue of vasculopathic alterations comprising vascular ectasia, hypovascularity, and/or luminal thrombosis confined to the superficial vascular plexus and a sclerodermoid tissue reaction , the latter seen in two cases. One biopsy showed a pustular leukocyto clastic vasculitis (LCV). In another case, a biopsied hand blister dem onstrated a PCT-like appearance histologically, namely, pauci-inflamma tory subepithelial blister formation with hyalinization of dermal papi llae capillaries accompanied by an LCV. There was nuclear keratinocyte decoration with IgG and C5b-9 in all cases studied, accompanied by a positive lupus band test in two cases and homogenous deposition of imm unoreactants along the dermoepidermal junction and within vessels in t he PCT-Iike eruption. Granular vascular decoration with immunoreactant s including C5b-9 was seen in two LCV cases and in two biopsies from r ashes clinically mimicking SCLE, Although the epidermal pathology of M CTD mimicks that of SCLE, a concomitant vasculopathy paralleling that seen in skin lesions of dermatomyositis distinguishes the dermatopatho logy of MCTD from that of SCLE, Corroborating the role of microangiopa thy in the pathogenesis of the skin lesions of MCTD was the demonstrat ion of C5b-9 in blood vessels, The deposition of C5b-9 in keratinocyte s may explain the pattern of IgG decoration of keratinocytes; the form ation of plasmalemmal pores may permit binding of immunoglobulin to an tigens in the nucleus and/or cytosol. The C5b-9 complex may be the eff ector mechanism of epithelial and/or endothelial cell injury in MCTD o r may serve to augment the effects of antibody-dependent cellular cyto toxicity.