The prevalence of psoriasis among human immunodeficiency virus (HIV)–positive patients in the United States is reported to be approximately 1% to 3%, which is similar to the rates reported for the general population.1 Recalcitrant cases of psoriasis in patients with no history of the condition can be the initial manifestation of HIV infection. In patients with preexisting psoriasis, a flare of their disease can be seen following infection, and progression of HIV correlates with worsening psoriasis.2 Psoriatic arthropathy also affects 23% to 50% of HIV-positive patients with psoriasis worldwide, which may be higher than the general population,1 with more severe joint disease.
The management of psoriatic disease in the HIV-positive population is challenging. The current first-line recommendations for treatment include topical therapies, phototherapy, and highly active antiretroviral therapy (HAART), followed by oral retinoids as second-line agents.3 However, the clinical course of psoriasis in HIV-positive patients often is progressive and refractory2; therefore, these therapies often are inadequate to control both skin and joint manifestations. Most other currently available systemic therapies for psoriatic disease are immunosuppressive, which poses a distinct clinical challenge because HIV-positive patients are already immunocompromised.
There currently are many systemic immunosuppressive agents used for the treatment of psoriatic disease, including oral agents (eg, methotrexate, hydroxyurea, cyclosporine), as well as newer biologic medications, including tumor necrosis factor (TNF) α inhibitors etanercept, adalimumab, infliximab, golimumab, and certolizumab pegol. Golimumab and certolizumab pegol currently are indicated for psoriatic arthritis only. Other newer biologic therapies include ustekinumab, which inhibits IL-12 and IL-23, and secukinumab, which inhibits IL-17A. The purpose of this systematic review is to evaluate the most current literature to explore the efficacy and safety data as they pertain to systemic immunosuppressive therapies for the treatment of psoriatic disease in HIV-positive individuals.
Methods
To investigate the efficacy and safety of systemic immunosuppressive therapies for psoriatic disease in HIV-positive individuals, a PubMed search of articles indexed for MEDLINE (1985-2015) was conducted using the terms psoriasis and HIV and psoriatic arthritis and HIV combined with each of the following systemic immunosuppressive agents: methotrexate, hydroxyurea, cyclosporine, etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab, and secukinumab. Pediatric cases and articles that were not available in the English language were excluded.
For each case, patient demographic information (ie, age, sex), prior failed psoriasis treatments, and history of HAART were documented. The dosing regimen of the systemic agent was noted when different from the US Food and Drug administration–approved dosage for psoriasis or psoriatic arthritis. The duration of immunosuppressive therapy as well as pretreatment and posttreatment CD4 and viral counts (when available) were collected. The response to treatment and adverse effects were summarized.
Results
Our review of the literature 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 (Table). There were no reports of the use of hydroxyurea, golimumab, certolizumab pegol, or secukinumab to treat psoriatic disease in this patient population.
Methotrexate
Eight individual cases of methotrexate used to treat psoriasis and/or psoriatic arthritis in HIV-positive patients were reported.4-6 Duvic et al6 described 4 patients with psoriatic disease that was treated with methotrexate with varying efficacy. One patient developed toxic encephalopathy, which improved after discontinuation of methotrexate; however, he died 5 months later from pneumocystis pneumonia. In this early study, none of the 4 patients were on antiretroviral therapy for HIV.6
In the cases reported by Masson et al4 and Maurer et al,5 4 patients were treated with a single antiretroviral agent and received appropriate prophylaxis against opportunistic infections. In 1 case, methotrexate was given at a chemotherapeutic dose of 525 mg once weekly for Kaposi sarcoma.4 In 2 of 4 cases, the patients developed pneumocystis pneumonia.4,5
Cyclosporine
There were 2 case reports of successful treatment of psoriatic disease with cyclosporine in HIV-positive patients.7,8 Skin and joint manifestations improved rapidly without reports of infection for 27 and 8 years.8 Both patients were treated with one antiretroviral agent.7,8
Etanercept
There were 5 case reports of successful treatment of psoriatic disease with etanercept. In all 5 cases the patients were on HAART, and the CD4 count increased or remained stable and viral count became undetectable or remained stable following treatment.9-13 In 2 cases, the patient also had hepatitis C virus, which remained stable throughout the treatment period.9,12 The maximum duration of treatment was 6 years, with only 1 reported adverse event.13 In this case reported by Aboulafia et al,13 the patient experienced recurrent polymicrobial infections, including enterococcal cellulitis, cystitis, and bacteremia, as well as pseudomonas pneumonia and septic arthritis. Therapy was discontinued at 6 months. Four months after discontinuation of etanercept, the patient died from infectious causes.13
Adalimumab
There was 1 case of successful treatment of psoriatic disease with adalimumab in an HIV-positive patient. In this case, the patient was on HAART, and CD4 and viral counts improved substantially after 30 months of treatment.14
Infliximab
Six individual cases of successful treatment of psoriatic disease with infliximab were reported.15-17 In a report by Cepeda et al,15 HIV-positive patients with various rheumatologic diseases were chosen to receive etanercept followed by adalimumab and/or infliximab if clinical improvement was not observed on etanercept. In 3 patients with psoriasis and psoriatic arthritis, inadequate response was observed on etanercept. Two of these 3 patients received adalimumab with only partial response. All 3 were treated with infliximab in the end and showed excellent response. One of the patients experienced facial abscess responsive to antibiotics and was continued on infliximab therapy without further complications. In all 6 cases of infliximab therapy, the patients were on HAART, and CD4 and viral counts improved or remained stable.15
Ustekinumab
There were 3 case reports of successful treatment of psoriatic disease with ustekinumab in HIV-positive patients on HAART. CD4 and viral counts improved or remained stable.18-20