Cocaine-Associated Retiform Purpura

Abstract

Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex.

Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene activation mediated by p300-dependent IRF-1 acetylation

“…It has been reported that sublytic C5b-9 is able to induce cell apoptosis in many types of cells; 20, 44, 45 however, sublytic C5b-9 can protect oligodendrocytes from apoptosis and lead to survival, 46 suggesting that the different response to C5b-9 in these cells may be because of different cell types and different biochemical reactions upon sublytic C5b-9 attack. It is worth mentioning that sublytic C5b-9 was also found to be able to induce GMC proliferation at 36 and 54 h after sublytic C5b-9 stimulation in our previous studies.…”

Retrospective Case Series of Cocaine-Associated Plasma Cell Orificial Mucositis

“…Other antibodies that may be observed are antiphospholipid, antinuclear, and anti-DNA antibodies . Finally, cocaine metabolites have been demonstrated to enhance the synthesis and deposition of complement C5b-9, leading to thrombotic microangiopathy phenomena, even without the presence of vasculitis …”

“…leading to thrombotic microangiopathy phenomena, even without the presence of vasculitis. 6 Accordingly, the classic differential diagnoses of cocaine-related skin diseases include various neutrophilic disorders, such as cocaine-induced midline destructive lesions, ANCA-associated vasculitis-retiform purpura/ cocaine-levamisole-associated autoimmune syndrome (CLAAS), pyoderma gangrenosum, pyostomatitis vegetans and neutrophilic dermatosis of the dorsal hands (eFigure 1 in Supplement 1). 2,4,7,8 For all of them, neutrophils, vasculitis, and intravascular thrombotic phenomena in the results of biopsy are diagnostic hallmarks.…”

The potential role of complements in cocaine-induced thrombotic microangiopathy

“…Tanhehco et al showed that cocaine increased the gene expression of several complement components and the protein expression of the terminal complement complex C5b-9 in the rabbit heart [ 2 ]. Magro et al reported extensive vascular C5b-9 deposition in cocaine-induced retiform purpura that is characterized by skin necrosis secondary to cutaneous TMA [ 3 ]. Durán et al reported a 28-year-old man with complement factor H deficiency who developed TMA (aHUS) triggered by cocaine use [ 11 ].…”