Paradoxical Exacerbation of Psoriasis in AIDS: Proposed Explanations Including the Potential Roles of Substance P and Gram-negative Bacteria

Abstract

Psoriasis, a TH1-induced disorder, is not more common in human immunodeficiency virus (HIV) infection than in the general population. However, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. The paradoxical exacerbation of psoriasis in AIDS has not been fully explained. Various explanations have been proposed including (a) the reduction of Langerhans' cells (LCs) in HIV disease, (b) the direct epidermal proliferative effect of HIV, (c) the altered cytokine profile in HIV disease, (d) HIV-induced macrophage nitric oxide (NO) production, (e) the increased CD8/CD4 T-cell ratio in HIV infection and (f) the increased colonization of skin by Staphylococcus aureus. However, the observations that (a) LCs cells play an important role in the pathogenesis of psoriasis and a variety of topical and systemic psoriasis treatments cause a reversible decrease in LC function, (b) psoriasis may improve in end-stage HIV infection, (c) overproduction of some TH2 cytokines and underproduction of IL-2 in HIV infection, and (d) the presence of NO favors a TH2 response over a TH1 response make the first four explanations difficult to interpret. Since psoriasis is exacerbated in HIV infection possibly due to the increased staphylococcal colonization, and psoriatic keratinocytes could aggravate HIV infection through production of TNF-alpha, it could be reasoned that in HIV-positive psoriatics a strong vicious cycle is present between the degree of immune deficiency and the staphylococcal colonization, explaining the poor prognosis of both AIDS and psoriasis in these patients. With reference to the studies which indicate significant involvement of substance P (SP) in the pathogenesis of psoriasis and on the other hand increased release of this agent by HIV-infected immune cells it is proposed that SP plays an important role in creating the paradox. Since in HIV-positive psoriatics the source of SP is largely immune cells not neurons, capsaicin, which exerts its action selectively on a subpopulation of neurons, could not be of significant therapeutic value. As SP significantly enhances HIV-1 replication in latently infected immune cells, psoriatic lesions, being heavily infiltrated with immune cells and having high concentrations of SP, could serve as high HIV-replication foci, with the resultant rapid progression of the infection towards AIDS. Additionally, given that lipopolysaccharide is supposed to exacerbate psoriasis, increase of gram-negative infections or cutaneous colonization with these organisms in AIDS may partly explain the paradox. Understanding the HIV-induced immunodysregulation that is associated with psoriasis in some HIV-seropositive patients may assist in the delineation of the immunopathogenesis of the disease in HIV-seronegative psoriatics.

Neuronal Control of Skin Function: The Skin as a Neuroimmunoendocrine Organ

“…Moreover, several immune cells are capable of generating SP induced by stress, inflammation, or infection (569,570,596). For example, SP appears to be involved in keratinocyte/antigen-presenting cell interactions during chronic stress (569), T-cell regulation (607), natural killer cell activation (485), innate host defense (116), human immunodeficiency virus (HIV)-associated psoriasis (338,570), wound healing (189), murine hair follicle apoptosis (636), genital herpes infection (836), and immunosurveillance during experimentally induced tumor growth (murine melanoma) (509). SP may be also involved in inflammation and host responses of the CNS (511) as well as transmitting sensory signals (neurogenic inflammation, pain, pruritus) to the CNS (reviewed in Refs.…”

The Role of Immune Response and the Impact of Biological Drugs in Psoriasis Patients

“…Another evidence against the fundamental role of T cells in psoriasis arise from the observation that HIV + patients (which usually have reduced number of CD4 + T cells) develop psoriasis with similar frequency as the rest of the population (Namazi, 2004 (Zenz et al, 2005); They knocked out JunB and c-Jun, two components of the AP-1 transcription factor, which control cell proliferation and differentiation , cytokine production, and stress responses in the skin. The importance of this animal model lies in the fact that JunB is located in the PSORS6 locus, which has been shown to be a psoriasis susceptibility region (Hensen et al, 2003).…”

Chronic Plaque Psoriasis

“…7 Chronic human immunodeficiency virus infection is associated with severe psoriasis exacerbations. 8 …”