Long-term management of HIV/hepatitis C virus associated psoriasis with etanercept
2 Infectious Diseases, Department of Medicine and Medical Specialities, Arcispedale Santa Maria NuovaIRCCS, 42100 Reggio Emilia, Italy
Vito Di Lernia
Unit of Dermatology, Arcispedale Santa Maria Nuova-IRCCS, Viale Risorgimento 80, 42123 Reggio, Emilia
|How to cite this article:
Di Lernia V, Zoboli G, Ficarelli E. Long-term management of HIV/hepatitis C virus associated psoriasis with etanercept. Indian J Dermatol Venereol Leprol 2013;79:444
Psoriasis is a chronic inflammatory skin disease that, due to its prevalence, can be observed in HIV patients. In such patients, the disease course can be critical and recalcitrant to therapy.  A concurrent chronic hepatitis C virus (HCV) infection is a further challenging clinical situation to manage.
A 51-year-old psoriatic erythroderma patient, co-infected with HIV and HCV came to us for consultation of his skin lesions. After failure of conventional treatments, continuous, uninterrupted etanercept therapy was followed by long-term clinical remission without significant infectious episodes.
The patient had a 30-year history of moderate to severe plaque psoriasis without arthritis. He smoked 20 cigarettes/day and his records noted moderate alcoholism and was positive for hepatitis C genotype 2a/2c. Some years before his psoriasis had been treated with intermittent courses of cyclosporine 3 mg/kg/day for 5 years. The patient was "lost to follow-up" for about 5 years. Then the patient was again admitted to hospital because of an erythrodermic psoriasis (PASI score 30) and intermittent fever with leukocytosis of 3 weeks′ duration. Patient at presentation showed widespread erythema affecting nearly 100% of his body surface. The patient was treated with prednisolone 20 mg/day intramuscularly for a week. After tapering of steroids and administration of acitretin 0.3 mg/kg/day, the patient experienced a relapse of his psoriasis (PASI score 27.9). At this time HIV seropositivity was discovered, stage (Centers for Disease Control and Prevention) CDC B2 (CD4 cell count 200-499 cells/μL). Antiretroviral therapy was started with fosamprenavir, tenofovir disoproxil fumarate/emtricitabine, and ritonavir with clinical follow-up in the infectious diseases department. Narrow band ultraviolet B phototherapy (starting dose 1000 mJ/cm 2 with increment 10% pre treatment) plus acitretin at a dose of 0.3 mg/kg/day was administered. The latter had to be suspended due to elevated liver enzymes (AST 198 U/l, ALT 655 U/l) after 6 weeks. PASI score was 21. Cyclosporine 3 mg/kg/day provided effective control of psoriasis, but an increase in serum creatinine level (1.41 mg/dL, normal values 0.70-1.20 mg/dL) was noted after 8 weeks. Dose reduction was followed by rapid worsening of psoriasis. PASI score was 13.4 [Figure - 1] with persistent elevated creatinine. In view of the lack of response to systemic treatments, a tumor necrosis factor-alfa blocker was considered. The investigations like chest radiograph was normal; the Mantoux test and the Quantiferon TB Gold were negative. The HIV-RNA load was 7,930 copies/mL. Etanercept was given at a dose of 50 mg twice weekly for the 1 st 12 weeks, thereafter 50 mg/weekly. At 12 weeks, skin lesions showed marked improvement (PASI score 6.2). The patient continued to take this dose with good clinical remission of psoriasis [Figure - 2]. As of his most recent follow-up visit, 132 weeks after the initiation of therapy, the patient remained partially free of psoriasis. Sporadic relapses were controlled increasing the frequency of topical treatment with betametasone/calcipotriol without modifying the schedule of etanercept injections. Lymphocyte count remained stable throughout treatments. The HIV-RNA gradually declined and was negative 18 months after the diagnosis of HIV infection. A decrease of HCV-RNA titres was also recorded. No significant infectious episodes occurred.
|Figure 1: Plaque psoriasis involving extensively the dorsum|
|Figure 2: Significant clinical remission (120 week follow-up after treatment with etanercept)|
HIV/AIDS is listed among the relative contraindication for anti-TNF-α treatment  and HIV infection is usually ruled out prior to initiation TNF-α therapy. However, high levels of TNF-α are associated with all stages of HIV infection.  TNF-α stimulates HIV transcription in vitro and is thought to be involved in the pathogenesis of fatigue, fever, and cachexia in HIV.  Hence, Ting and Koo suggested that etanercept could be used safely in the management of HIV-associated psoriasis.  Etanercept or other TNF-α inhibitors have been administered effectively in patients with plaque or pustular psoriasis or psoriatic arthritis refractory to conventional treatments in the setting of HIV infection. 
The long-term safety or efficacy of anti-TNF-α agents in patients with chronic HCV is not established at present, but the presence of HCV is not considered a contraindication to therapy with TNF-α inhibitors.  High levels of TNF-α are associated also with HCV infection, hence TNF-α inhibitors may be beneficial in moderate to severe psoriasis associated to HCV infection. In particular, etanercept and possibly, other TNF-α blockers have been suggested as second line drugs for patients with psoriasis and HCV infection. 
The safety of TNF-α antagonists in the context of HIV infection is unknown. TNF-α-mediated immune responses are of crucial importance in opportunistic infections. Toxoplasmosis is the most common opportunistic encephalitis in HIV-infected patients. A crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis has been shown.  Etanercept has no activity on p55 receptor, and therefore may have some theoretic advantage in minimizing the potential risk of toxoplasmosis. Since the conceivable risk of opportunistic infections, a firm alliance between dermatologists and infectious diseases specialists remains mandatory in the managing of psoriatic patients with HIV/HCV co-infection.
Morar N, Willis-Owen SA, Maurer T, Bunker CB. HIV-associated psoriasis: Pathogenesis, clinical features, and management. Lancet Infect Dis 2010;10:470-8.[Google Scholar]
Domm S, Cinatl J, Mrowietz U. The impact of treatment with tumour necrosis factor-alpha antagonists on the course of chronic viral infections: A review of the literature. Br J Dermatol 2008;159:1217-28.[Google Scholar]
Ting PT, Koo JY. Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients. Int J Dermatol 2006;45:689-92.[Google Scholar]
Barco T, Puig L, Alomar A. Treatment of moderate-severe psoriasis with etanercept in patients with chronic human immunodeficiency virus infection. Actas Dermosifiliogr 2012;101:77-81.[Google Scholar]
Frankel AJ, Van Voorhees AS, Hsu S, Korman NJ, Lebwohl MG, Bebo BF Jr, et al. Treatment of psoriasis in patients with hepatitis C: From the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2009;61:1044-55.[Google Scholar]
Deckert-Schlüter M, Bluethmann H, Rang A, Hof H, Schlüter D. Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis. J Immunol 1998;160:3427-36.[Google Scholar]