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Psoriasis in the Patient With Human Immunodeficiency Virus, Part 2: Review of Treatment

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Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)–infected population. Psoriasis appears in patients with HIV either as the first clinical manifestation of the disease or, less commonly, during the advanced stages of HIV when it has progressed to AIDS.
This 2-part series reviews the pathogenesis of HIV-associated psoriasis as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV. These therapies address the profound immune dysregulation that defines psoriasis. The second part of the series focuses on the treatment of HIV-associated psoriasis.



The stepwise approach to the treatment of psoriasis, from topical to systemic treatment depending upon the severity of the condition, applies to the management of immunocompetent patients with psoriasis. Treatment of psoriasis associated with human immunodeficiency virus (HIV) infection is challenging because most of the available modalities currently marketed for treatment involve immunosuppression; additionally, the symptomatology in patients with HIV often is more severe and refractory to conventional treatment.1 The second part of this series serves to complement the review of the pathogenesis of psoriasis in patients with HIV2 by delineating currently available therapeutic options while also reviewing landmark studies that have evaluated the efficacy and safety of these measures in immunocompromised patients with psoriasis (Table).

Topical Therapy
Treatment options for psoriasis in HIV-infected individuals include conventional topical therapies, such as corticosteroids, tar, calcipotriene, or anthralin, for mild localized disease.15 Calcipotriol, a topical vitamin D3 analog, is a biologically active form of vitamin D capable of inhibiting cell proliferation in cultures of human keratinocytes and has been an effective local treatment of HIV-associated psoriasis.16 Gray et al3 reported the use of topical calcipotriol daily in conjunction with oral etretinate to markedly improve erythrodermic psoriasis that had been refractory to etretinate monotherapy, psoralen plus UVA (PUVA), and topical steroids in a patient with advanced HIV disease (CD4 lymphocyte count, 70X106 cells/L).

In more advanced cases in which psoriasis is refractory to topical therapy, UV radiation (either UVB or PUVA) can be utilized.17-20 Increased risk for skin cancer and reduced resistance to infection are possible consequences of the immunomodulatory effects of these UV therapies.21 In an immunocompromised patient, such as one with HIV infection, even modest changes in the immune system can be clinically relevant.22 Concerns about the use of UV therapy in HIV-infected individuals arose from in vivo and transgenic animal experiments in which HIV markers were induced or up-regulated, and HIV transcription and replication were activated.23-25 The effects of UVB and PUVA treatment on the clinical course of HIV infection have shown increases in p24 antibodies and viral load after phototherapy; overall, UV radiation does not appear to have a deleterious effect on the CD4 lymphocyte count or clinical status in treated patients.26 UV radiation is generally considered to be a safe treatment modality in HIV-infected individuals, and Adams et al27 have proposed clinical guidelines for its use as follows:

  • "Is the skin disease UV responsive? If the answer is yes, consider phototherapy.
  • Do alternative therapies offer less risk to the patient? If yes, it may be judicious to try alternative treatments first.
  • Is anticipated improvement in morbidity after phototherapy enough to justify potential risks? If yes, proceed with phototherapy. If no, consider other treatments.
  • Are there other contraindications to phototherapy (eg, medication that confers photosensitivity)? If yes, weigh the risk-benefit ratio."

Oracion et al28 recommend HIV serology in patients who are candidates for phototherapy and monitoring of viral load and CD4 lymphocyte count before treatment, at monthly intervals during treatment, and 3 months after treatment. Despite the lack of definitive clinical evidence of deleterious effects of phototherapy in HIV-infected individuals, the risk-benefit ratio of phototherapy should be examined on a case-by-case basis, taking into account the patient's stage of HIV disease; the degree of discomfort, disfigurement, and disability caused by the dermatologic condition; and the availability of other possible treatment modalities.26 The impact of the immunosuppression or HIV activation during phototherapy on the progression of HIV disease is poorly understood. Phototherapy has been reported to have no apparent adverse effects in studies measuring CD4 T-cell counts as an immunologic parameter.17,29-31 A prospective study conducted by Breuer-McHam et al4 followed patients with documented HIV infection referred by their dermatologists for phototherapy of psoriasis or pruritus by measuring T-cell subsets, levels of p24 antigen, and HIV RNA values. For comparison, HIV-positive individuals without skin disease, with quiescent psoriasis or pruritus or with Kaposi sarcoma, were studied as a control group. Human immunodeficiency virus–negative controls included those with psoriasis undergoing UVB or PUVA phototherapy. All patients were treated with UVB for 1 minute up to 3 times weekly, with the dosage increasing over time for 6 weeks. The light box emitted 1.01 mW/cm2 or 1.01 mJ/s. The data showed that although phototherapy clinically benefits HIV-positive patients with skin disease, phototherapy can increase both p24 and viral load in patients who are not receiving suppressive antiviral therapy. When patients' viral load levels were suppressed at baseline by antivirals, they also were protected from any increase in HIV RNA levels at the end of the 6-week phototherapy period. Dramatic changes occurred in the serum HIV RNA of black patients who were found to have greater increases at week 6 than white patients. Therefore, the skin pigmentation type (Fitzpatrick skin types IV and V) must be taken into account because, in general, more UV light is given to more darkly pigmented individuals with consequently greater increases in circulating virus. Low-dose UV light may be safely used to decrease HIV expression at appropriate doses in conjunction with suppressive antiviral therapy.4 The reliance of clinicians on phototherapy in HIV-infected individuals varies tremendously among treatment centers, and a survey revealed almost no agreement as to which type of UV therapy is optimal among these patients.22 One survey found that phototherapy is widely used for HIV-infected patients: 80% (249/311) received UVB, 9% (28/311) received PUVA, and the remaining 11% (34/311) received a variety of combinations.32 A case has been made that PUVA may be preferable to UVB therapy because of its increased efficacy, especially with thick plaques and palmoplantar involvement, as is frequently encountered in the setting of HIV-associated psoriasis.33 However, it should be noted that psoralens are commonly associated with gastrointestinal side effects and concomitant use of medications that can photosensitize the skin, such as trimethoprim-sulfamethoxazole, may be a contraindication to phototherapy.34,35

Systemic Therapy
In the past, dermatologists have opted for systemic immunosuppressive therapy in severe refractory cases in which neither topical nor UV therapy had yielded benefit to patients with HIV-associated psoriasis. Cyclosporine A (CyA) has been used to successfully treat intractable psoriasis in immunocompetent patients, often showing results after conventional therapy has failed.36,37 Cyclosporine A is known to inhibit T-cell activation, thereby reducing the number of CD4 cells while also inhibiting HIV replication by removing the host cell target.38 A case study conducted by Allen,5 which involved an HIV-positive patient (CD4 lymphocyte count, 0.04X109 cells/L) with psoriasis who had failed to improve with multiple treatments including zidovudine, methotrexate sodium, and etretinate combined with topical steroids, disputed the theory that the added immunosuppression associated with CyA would only aggravate the already present immune dysfunction in patients with HIV infection. An immediate benefit was seen with the administration of CyA at 5 mg/kg, as shown by the rapid clearing of psoriatic lesions and a dramatic improvement in overall well-being, though the CD4 lymphocyte count remained low. No clear signs of acute deterioration or opportunistic infections were reported, except for a brief episode of oral thrush that responded to treatment with nystatin.5 While it is theorized that CyA, by inhibiting T cells and other antigen-presenting cells, could slow the overall course of HIV infection, further clinical trials are required to identify HIV-positive patients who will reap the overall benefits of treatment with CyA.6 Methotrexate sodium has been reported to cause profound leukopenia and death in some psoriatic patients with HIV infection and is therefore used with great trepidation.39 Additionally, because of the known interaction with trimethoprim-sulfamethoxazole, methotrexate sodium is contraindicated in patients being treated prophylactically for Pneumocystis carinii pneumonia.35

Tumor Necrosis Factor Blockers
The pathogenesis of psoriatic HIV infection revolves around cytokines that are involved in chronic inflammation. Tumor necrosis factor α (TNF-α) represents one such cytokine that is important in mediating immune responses in healthy patients; however, in patients with HIV infection, TNF-α has been shown to stimulate viral replication in vitro and also may contribute to the development of aphthous ulcers, fatigue, lipodystrophy, fever, and dementia.40-44 In patients with psoriasis, TNF-α, along with other mediators, induces keratinocytes to produce chemotactic factors for T cells and neutrophils and is strongly up-regulated in the psoriatic epidermis.45 Some biologic agents are known to inhibit the effects of TNF-α in skin and attenuate its destructive process on bone and joints.46 These biologic agents (ie, adalimumab, alefacept, efalizumab, etanercept, infliximab) have been employed as treatment of psoriasis.47-50 Various controlled trials have been conducted on the efficacy and safety of TNF blockers in psoriasis. This therapy has been proven to be a valuable option for controlling psoriasis versus placebo because it has a more rapid time to response, gives a better clearing rate of plaques, and most importantly, is well-tolerated by all study participants.51,52 While TNF blockers have been demonstrated to be effective and safe in clinical trials of healthy patients treated for inflammatory conditions, its use in patients with HIV infection has not yet been examined in detail because it is thought that cytokine-suppressive medications may increase the risk of opportunistic infections, sepsis, and progression to AIDS.46 Aboulafia et al7 described the use of etanercept in an HIV-positive patient (CD4 lymphocyte count,

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