The link between IFN-γ and psoriatic HIV is further supported by the unique expression of the class II MHC antigen HLA-DR during inflammatory dermatoses such as psoriasis. While normally limited in expression to Langerhans cells and acrosyringial epithelium, HLA-DR is synthesized by keratinocytes in actively inflamed psoriatic lesions when exposed to IFN-γ, promoting further accumulation of leukocytes.48-53 The overexpression of HLA-DR in keratinocytes has been postulated to allow for the increased frequency of exacerbations associated with bacterial infection. The ability of streptococcal pyrogenic exotoxins and staphylococcal enterotoxins to act as superantigens that stimulate production of TNF-α by HLA-DR keratinocytes permits the vicious inflammatory cycle of psoriasis in patients with HIV to continue, even in the absence of T cells.54-57
Conclusion
The exacerbation of psoriasis in patients with HIV is largely mediated by memory CD8 T cells, a population of cells that are relatively and absolutely expanded in HIV infection. The IFN-γ produced by the memory CD8 T cells is capable of inducing keratinocytes to abnormally express HLA-DR, which predisposes these cells to become activated by bacterial superantigens that are more likely to be in excess in the immunocompromised patient. Once activated, these keratinocytes perpetuate the psoriatic phenotype by producing the proinflammatory cytokine, TNF-α. This tumultuous cycle is important because targeting specific disease mediators has proved to be therapeutic and clinically applicable in patients with HIV and psoriasis. This article is the first of a 2-part series. The second part, providing a comprehensive, in-depth appraisal of current treatment regimens available to patients with both HIV and psoriasis, will appear in a future issue of Cutis®.