Comment
Currently, all of the systemic immunosuppressive therapies approved for psoriatic disease have a warning by the US Food and Drug Administration for increased risk of serious infection. Given such labels, these therapies are not routinely prescribed for HIV-positive patients who are already immunocompromised; however, many HIV-positive patients have severe psoriatic disease that cannot be adequately treated with first- and second-line therapies including topical agents, phototherapy, or oral retinoids.
Our comprehensive review yielded a total of 25 reported cases of systemic immunosuppressive therapies used to treat psoriatic disease in HIV-positive patients including methotrexate, cyclosporine, etanercept, adalimumab, in-fliximab, and ustekinumab. Although data are limited to case reports and case series, some trends were observed.
Efficacy
In most of the cases reviewed, the patients had inadequate improvement of psoriatic disease with first- and second-line therapies, which included antiretrovirals alone, topical agents, phototherapy, and oral retinoids. Some cases reported poor response to methotrexate and cyclosporine.4-8 Biologic agents were effective in many such cases.
Safety
Overall, there were 11 cases in which the patient was not on adequate HAART while being treated with systemic immunosuppressive therapy for psoriatic disease.4-8,15 Of them, 3 were associated with serious infection while on methotrexate.5,6 There was only 1 report of serious infection13 of 14 cases in which the patient was on concomitant HAART. In this case, which reported polymicrobial infections and subsequent death of the patient, the infections continued after discontinuing etanercept; thus, the association is unclear. Interestingly, despite multiple infections, the CD4 and viral counts were stable throughout treatment with etanercept.13
From reviewing the 4 total cases5,6,13 of serious infection, HAART appears to be a valuable concomitant treatment during systemic immunosuppressive therapy for HIV-positive patients; however, it does not necessarily prevent serious infections from occurring, and thus the clinician’s diligence in monitoring for signs and symptoms of infection remains important.
CD4 and Viral Counts
Although reports of CD4 and viral counts were not available in earlier studies,4-8 there were 15 cases that reported consistent pretreatment and posttreatment CD4 and viral counts during treatment with etanercept, adalimumab, infliximab, and ustekinumab.9-20 In all cases, the CD4 count was stable or increased. Similarly, the viral count was stable or decreased. All patients, except 1 by Cepeda et al,15 were on concomitant HAART.9-14,16-20
Although data are limited, treatment of psoriatic disease with biologic agents when used in combination with HAART may have beneficial effects on CD4 and viral counts. Tumor necrosis factor has a role in HIV expression through the action of nuclear factor κβ.21 An increase in TNF levels is shown to be associated with increased viral count, decreased CD4 count, and increased symptoms of HIV progression, such as fever, fatigue, cachexia, and dementia.22 Although more studies are necessary, TNF-α inhibitors may have a positive effect on HIV while simultaneously treating psoriatic disease. Other cytokines (eg, IL-12, IL-23, IL-17) involved in the mechanism of action of other biologic agents (ustekinumab and secukinumab) have not been shown to be directly associated with HIV activity; however, studies have shown that IL-10 has a role in inhibiting HIV-1 replication and inhibits secretion of proinflammatory cytokines such as IL-12 and TNF-α.21 It may be speculated that the inhibition of IL-12 and TNF-α may create a positive feedback effect to increase IL-10, which in turn inhibits HIV replication.
Conclusion
Although there are limited data on the efficacy and safety of systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive patients, a review of 25 individual cases suggest that these treatments are not only required but also are sufficient to treat some of the most resistant cases. It is possible that with adequate concomitant HAART and monitoring for signs and symptoms of infection, the likelihood of serious infection may be low. Furthermore, biologic agents may have a positive effect over other systemic immunosuppressive agents, such as methotrexate and cyclosporine, in improving CD4 and viral counts when used in combination with HAART. Although randomized controlled trials are necessary, current biologic therapies such as etanercept, adalimumab, infliximab, and ustekinumab may be safe viable options as third-line treatment of severe psoriasis in the HIV-positive population.
