# HIV-Associated Systemic Sclerosis: Literature Review and a Rare Case Report
## 3 Discussion
Compensatory stimulation of B-Cell proliferation with the increased production of immunoglobulins (mostly abnormal) occurs, and this dysregulated immune mechanism may increase the likelihood of autoimmune disease development ([PERSON] et al., 2016). HIV infection may evoke autoantibody production as there is structural antigen simulation between HIV proteins and self-antigens. This molecular simulation between the viral protein and self-antigens causes the antibodies to cross-react and eventually leads to the onset of autoimmune diseases. HIV infection may also result in T-lymphocytes disparity, typified by decreased CD4+ T cells and a proportionate increase in CD8+ T cells. This HIV-evoked T lymphocyte disparity may also attribute to the onset of autoimmune diseases ([PERSON] et al., 2016). Published literature has revealed the sequence congruity between viral proteins and self-antigens ([PERSON] et al., 2016; [PERSON] et al., 2016) (Table 3). \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**S. No** & **Author(s) and Year** & **Age/Sex** & **HIV Status** & **Systemic Sclerosis Features** & **Other Associated** \\ \hline \multirow{6}{*}{6.} & [PERSON], et al., & & & & \\  & 2008 ([PERSON] et al., 2016) & & & & \\  & Retrospective & & & & \\  & study; out of & & & & \\  & 888 HIV diagnosed & & & & \\  & cases, only 1 case & & & & \\  & of SSc was seen & & & & \\ \hline \multirow{3}{*}{7.} & [PERSON] et al., 2016 ([PERSON] et al., 2016) & \multirow{3}{*}{45/F} & 1 patient on HAART & \multirow{3}{*}{-} & \\  & Only 4 cases of SSc & & & & \\  & out of & 1 female & & & \\ \cline{1-1}  & 20,444 HIV cases & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: _Cont._Recent national recommendations in the USA advocate a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) with an integrase strand transfer inhibitor (INSTI) as initial therapy for ART-naive individuals [31]. However, lifelong ART therapy is mandatory, with no definitive cure. Once the therapy is discontinued, there is a resurgence of the infection. The literature has reported that a combination of immune activators, therapeutic vaccines, and neutralizing antibodies have provided cures in some nonhuman primates, thus posing a hope for future treatment strategies in humans. In vivo delivery of gene-editing tools to either target the virus, boost immunity, or protect cells from infection may also serve as future HIV treatment strategies [32]. SSc is a multisystemic autoimmune disorder characterized by microvascular and immune abnormalities, resulting in cutaneous and internal organ fibrosis. Thick, hardened skin is the distinctive disease manifestation; hence, it has also been termed a \"hidebound disease\" [8;33]. The disease is categorized into two major forms--(a) a diffuse form, with extensive skin involvement and rapid advanced internal organ involvement, and (b) a localized form, with limited skin involvement (distal of the elbows, knees, fingers, and face). The extent of disease progression, internal organ involvement, and production of specific antibodies form the differentiation basis of these forms [8]. Environmental factors may also induce the development of autoimmune disorders. Exposure to infections (_H. pylori_, cytomegalovirusovirus, Ebstein-Barr virus), chemicals (silica, organic solvents, xylene), heavy metals (mercury, palladium), and drugs (bleomycin, antiretrovirals) have been proposed as potential triggers for SSc development [34]. The published literature has revealed that scleroderma-like cutaneous lesions have been observed with the injectable fusion inhibitor antiretroviral drug enfuvirtide [35]. Another antiretroviral integrase inhibitor drug, raltegravir, has also been associated with the flares of an autoimmune episode [5]. However, our patient did not report any exposure to these environmental factors, nor was she on any medication known to produce scleroderma-like lesions. The skin over the extremities, face, and trunk may exhibit hyperpigmentation, with distinct depignmented regions.