Tropical regions, including sub-Saharan Africa, the Caribbean, Latin America, India, and Southeast Asia, account for more than 80% of human immunodeficiency (HIV) infections around the globe. The intersection of the HIV pandemic and tropical infectious diseases is inevitable; however, the lack of sophisticated medical infrastructure and diagnostic techniques, along with underreporting from these regions, has limited the understanding of how the epidemiology and clinical course of tropical infections is affected by coinfection with HIV, and much of the existing literature describes cases noted in immigrants to the developed world. As access to highly active antiretroviral therapy (HAART) in tropical regions increases, so does the understanding of its effect on persons coinfected with HIV and tropical infections.

The immune reconstitution inflammatory syndrome (IRIS), also known as immune restoration disease or immune reconstitution syndrome, is a well-documented but poorly understood phenomenon. IRIS occurs in the setting of HAART-induced immune restoration and is best described as a deregulated immunologic response to a previously existing pathogen or antigen, which then causes new or worsening clinical disease. In other words, as the HIV patient’s immune system improves under HAART, it reacts to existing but clinically quiescent pathogens and immunologically ignored antigens in unexpected ways. IRIS typically occurs in the initial weeks or months after starting HAART and subsequent immune reconstitution. There are 2 principal types of IRIS that occur: unmasking IRIS, in which a previously unrecognized infection becomes clinically apparent as immune reconstitution occurs, and paradoxical IRIS, which causes clinical deterioration of a previously recognized and sometimes treated infection. IRIS lacks a clear case definition, and diagnostic biomarkers have remained elusive. The only reliable predictors of IRIS risk are a low CD4 ⁺ nadir and preexisting opportunistic infection. Shelburne and colleagues proposed the following clinical criteria for IRIS: “(1) HIV infection, (2) receiving HAART, (3) decrease in HIV-1 RNA viral load, (4) increase in the level of CD4 ⁺ cells from baseline, and (5) clinical symptoms consistent with an inflammatory process whose clinical course is not consistent with the expected progression of a previously diagnosed opportunistic infection, expected progression of a newly diagnosed opportunistic infection, or drug toxicity.” ^(p168) In reality, IRIS probably represents a collection of unique disorders, each with a distinct immunopathogenesis driven by the interaction of pathogen-specific immune responses and host characteristics (eg, degree of HIV-induced immunosuppression and immunodysregulation, host genetics, and possibly the inflammatory milieu created by coinfection with other pathogens). IRIS may be simply a symptomatic inconvenience for a patient or may cause significant morbidity and mortality, affecting vital organs with excessive inflammation (eg, cytomegalovirus retinitis or cryptococcal meningitis). Distinguishing IRIS from opportunistic disease caused by persistent immunodeficiency, treatment failure, or adverse drug reaction presents significant diagnostic and therapeutic challenges.

The emergence of the HIV/AIDS pandemic in the tropical developing world and the subsequent rollout of HAART in these regions have led to numerous reports of IRIS occurring in association with tropical infections. The factors known to predispose to IRIS, such as very low CD4 ⁺ cell count before initiation of antiretroviral therapy and preexisting opportunistic infection, are far more likely to be encountered in these regions. Although most articles focus on IRIS caused by leprosy and leishmaniasis, IRIS has also been reported with helminthic infections (eg, schistosomiasis, strongyloidiasis) and fungal infections (eg, histoplasmosis, sporotrichosis, and penicilliosis), and many of these infections have cutaneous manifestations. With the massive burden of HIV infection in the tropical world, it is reasonable to anticipate that the range of reported tropical dermatoses with associated IRIS will continue to expand.

Relatively few IRIS events have been reported in association with parasitic helminthic infections endemic to much of the tropical world. This underreporting may reflect underdiagnosis or result from the helper T cell (T _H ) 2 immunologic shift caused by advancing HIV, because T _H 2-type cytokines are made during an appropriate response to many parasitic infections.

This article focuses on dermatoses endemic to tropical regions that have been reported to precipitate cutaneous IRIS events, including leprosy, leishmaniasis, penicilliosis, sporotrichosis, and strongyloidiasis.