IMMUNOHISTOLOGICAL ASSESSMENT OF CUTANEOUS DRUG HYPERSENSITIVITY IN PATIENTS WITH HIV-INFECTION

The pathogenesis of drug hypersensitivity in patients with HIV infecti on is unknown. To study further the nature of hypersensitivity, the hi stopathological features of morbilliform drug hypersensitivity reactio ns were examined in a group of HIV-infected patients. Skin sections fr om 23 HIV-infected subjects with morbilliform drug hypersensitivity re actions were examined by light microscopy, direct immunofluorescence a nd immunohistochemistry, to determine the nature of the inflammatory i nfiltrate and the role of immunoglobulin, complement and cytokines. Th e principal light microscopic findings were spongiosis, hydropic gener ation of the basal layer, civatte bodies, an epidermal lymphocytic inf iltrate (48%), and a perivascular dermal infiltrate of lymphocytes (87 %) and macrophages (52%). Two patients had findings consistent with to xic epidermal necrolysis. Immunohistochemistry demonstrated that the l ymphocytic infiltrate consisted of CD8(+), HLA-DR(+) T lymphocytes (so me of which also stained for CD38), a marked depletion of epidermal La ngerhans cells (90%), and strong cytoplasmic staining of keratinocytes for IL-6 (60%), IL-1 beta (50%), tumour necrosis factor-alpha (TNF-al pha) (45%) and to a lesser degree, interferon-gamma (IFN-gamma) (35%). Immunofluorescence did not demonstrate any significant deposition of immunoglobulin or complement. The histological findings were independe nt of the responsible drug, the duration of either therapy or the rash , and of peripheral blood CD4(+) and CD8(+) cell counts. These finding s suggest that activated CD8(+) lymphocytes and perhaps epidermal prod uction of cytokines are involved in the pathogenesis of cutaneous drug hypersensitivity in HIV-infected patients. The common histological fe atures, regardless of the causative drug, suggest a common pathogenesi s.