Patel RV

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).

Phototherapy
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,

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).

Phototherapy
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,

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).

Phototherapy
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,

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)–infected population, an incidence equal to the general population.1 The presentation of psoriasis in patients with HIV varies. Psoriasis may present as the first clinical manifestation of HIV or, less commonly, may appear in the advanced stages of HIV when it has progressed to AIDS.2-4 A substantial proportion of patients with HIV-associated psoriasis have a pattern of acral involvement, often with pustules and sometimes with severe destructive nail changes.1 Patients with AIDS and a severe exacerbation of psoriasis are more prone to developing systemic infections, such as a superinfection of Staphylococcus aureus, whereas systemic infections are uncommon in the immunocompetent psoriatic patient.5,6 In patients with preexisting psoriasis, the severity of the condition is closely correlated with the progression of HIV and correspondingly low CD4 lymphocyte counts, making the prognosis of the patient with HIV-associated psoriasis overwhelmingly poor.4,7,8 The pathogenesis of psoriasis in patients with HIV is considered a medical paradox that revolves around 3 main quandaries. First, this T-cell–mediated disease manages to flourish in an environment of decreasing T-cell counts.9 Second, although various therapies targeting T lymphocytes are effective in psoriasis, the condition worsens with decreasing CD4 T-cell counts in patients with HIV.10,11 Third, HIV is characterized by a strong helper T cells type 2 (TH2) cytokine profile and psoriasis is characterized by a strong helper T cells type 1 (TH1) secretion pattern.12-15 This 2-part series discusses these quandaries as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV by addressing the profound immune dysregulation that defines psoriasis. 

Pathogenesis of HIV-Associated Psoriasis
Although the etiology of HIV-associated psoriasis has yet to be clearly identified, it is postulated that both genetics and environmental factors play dynamic roles in its pathogenesis.16 Mallon et al17 provided the first evidence of a possible immunogenetic association between psoriasis and its expression in patients with HIV. The study compared the genomic DNA isolated from the lymphocytes of 14 men with HIV and psoriasis versus lymphocytic DNA extracted from a control group of HIV-1 seropositive men without psoriasis (n=147). The HLA-Cw6 antigen (HLA-Cw*0602 allele) was detected in 79% (11/14) of the HIV-1–positive psoriatics, while the allele, which codes for proteins capable of presenting antigens to lymphocytes, was present in only 24.5% (36/147) of HIV-1–positive controls (95% CI, 2.73–65.36; P=.0001).17 While there is a possibility that the association of psoriasis with the HLA-Cw*0602 allele is due to linkage disequilibrium with other recognized psoriasis susceptibility genes, it also can be inferred that the allele may be directly involved in the pathogenesis of the disease. Genetic evaluation has shown evidence for the linkage of psoriasis to the HLA-C locus and indicates that one or more genes located within this major histocompatiblity complex (MHC) may represent the key determinant of the genetic basis of psoriasis.18 The functional role of HLA-C is less well-defined than other HLA class I antigens. However, the identification of T-lymphocyte epitopes that are presented by certain HLA-C alleles supports the theory that HLA-C molecules are capable of presenting viral proteins such as the Epstein-Barr virus antigen and, more pertinently, HIV-1 proteins to cytotoxic CD8 T lymphocytes.19-21 The recognition of HIV-1 proteins and subsequent activation of T lymphocytes could trigger or maintain psoriatic lesions, as this locus has been proven to play an important role in susceptibility by increasing relative risk of developing psoriasis by 14 to 24 times.22 While there is consensus that T cells are integral in the pathogenesis of psoriasis, it is still debatable which cells mediate the disease, either CD4 helper T cells or CD8 cytotoxic T cells. Evaluation of these various cell types has shown that there is a substantial disruption in their balance in the HIV infection.9 Historically, it was believed that CD4 T cells were responsible for creating the immune process that characterized psoriasis and CD8 T cells were designated as having a suppressive role.13 However, recent studies have established CD8 lymphocytes as having a more independent role in the pathogenesis of the disease. Genetically, the strong association of psoriasis with class I MHC antigens, such as the aforementioned HLA-Cw*0602, which interact exclusively with CD8 T cells, bolsters the importance of this particular cell in creating psoriatic lesions.17,22,23 Histologically, various studies have shown that CD8 T cells, especially the memory T-cell subset, increased in concentration in the epidermis and papillary dermis of plaques as compared to uninvolved skin.24-28 Additionally, CD8 T cells have been shown to express proinflammatory cytokines such as interferon-γ(IFN-γ) and tumor necrosis factor α (TNF-α) more frequently than the CD4 subpopulation, which further defends the significance of this particular cell type in the pathogenesis of psoriasis.13,15 Recent theories on the effects of the HIV virus on T-cell populations have begun to explain how an imbalance in the CD4:CD8 ratio can be responsible for the immune dysregulation of HIV-associated psoriasis. The majority of studies have shown that the virus preferentially infects memory CD4 T cells and naive CD8 T cells.29-35 As HIV progresses and naive CD8 T cells become depleted, there is a disproportional relative expansion of the CD8 memory T-cell population that comprises more than 85% of the total CD8 T-cell count in patients with HIV versus 50% in healthy controls.32 The overall decrease in naive CD8 T cells not only diminishes the ability of patients to fight off new infections but also allows autoimmune diseases such as psoriasis to become established.9 The disproportional expansion of memory CD8 T cells also explains the unique cytokine profile that permits psoriasis to present in patients with HIV. A key feature of these cytokine profiles is that they are mutually antagonistic, with TH1 cytokines inhibiting the release of TH2 cytokines, and vice versa.36,37 Psoriatic lesions are associated with a TH1 cytokine pattern (ie, high levels of IL-2, IFN-γ, and TNF-α) without a substantial component of TH2 cytokines (ie, IL-2, IL-5, and IL-10).13,14,26,38,39 Evidence suggests that IFN-γ is the key contributor to the hyperproliferation of psoriasis.14,40-42 In patients with HIV without psoriasis, the cytokine profile is characterized by a strong propensity of TH2 cytokines, especially IL-4 to IL-6 and IL-10, with a decreased production of TH1 cytokines as the HIV infection progresses.42,43 This shift from a TH1 profile to a TH2 profile has been correlated with overall prognosis, as the cell-mediated immunity of the TH1 response permits lower rates of seroconversion and progression to AIDS. However, the cytokine pattern found in psoriatic patients with HIV is not characterized by a clean shift in cytokines to a complete TH2 profile. Instead, due to the increased subpopulation of memory T cells, there is a distinctive increase in the production of IFN-γ, the cytokine most responsible for creating and maintaining psoriatic phenotype (Figure).30,44-47

The link between IFN-γ and psoriatic HIV is further supported by the unique expression of the class II MHC antigen HLA-DR during inflammatory dermatoses such as psoriasis. While normally limited in expression to Langerhans cells and acrosyringial epithelium, HLA-DR is synthesized by keratinocytes in actively inflamed psoriatic lesions when exposed to IFN-γ, promoting further accumulation of leukocytes.48-53 The overexpression of HLA-DR in keratinocytes has been postulated to allow for the increased frequency of exacerbations associated with bacterial infection. The ability of streptococcal pyrogenic exotoxins and staphylococcal enterotoxins to act as superantigens that stimulate production of TNF-α by HLA-DR keratinocytes permits the vicious inflammatory cycle of psoriasis in patients with HIV to continue, even in the absence of T cells.54-57

Conclusion
The exacerbation of psoriasis in patients with HIV is largely mediated by memory CD8 T cells, a population of cells that are relatively and absolutely expanded in HIV infection. The IFN-γ produced by the memory CD8 T cells is capable of inducing keratinocytes to abnormally express HLA-DR, which predisposes these cells to become activated by bacterial superantigens that are more likely to be in excess in the immunocompromised patient. Once activated, these keratinocytes perpetuate the psoriatic phenotype by producing the proinflammatory cytokine, TNF-α. This tumultuous cycle is important because targeting specific disease mediators has proved to be therapeutic and clinically applicable in patients with HIV and psoriasis. This article is the first of a 2-part series. The second part, providing a comprehensive, in-depth appraisal of current treatment regimens available to patients with both HIV and psoriasis, will appear in a future issue of Cutis®.

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)–infected population, an incidence equal to the general population.1 The presentation of psoriasis in patients with HIV varies. Psoriasis may present as the first clinical manifestation of HIV or, less commonly, may appear in the advanced stages of HIV when it has progressed to AIDS.2-4 A substantial proportion of patients with HIV-associated psoriasis have a pattern of acral involvement, often with pustules and sometimes with severe destructive nail changes.1 Patients with AIDS and a severe exacerbation of psoriasis are more prone to developing systemic infections, such as a superinfection of Staphylococcus aureus, whereas systemic infections are uncommon in the immunocompetent psoriatic patient.5,6 In patients with preexisting psoriasis, the severity of the condition is closely correlated with the progression of HIV and correspondingly low CD4 lymphocyte counts, making the prognosis of the patient with HIV-associated psoriasis overwhelmingly poor.4,7,8 The pathogenesis of psoriasis in patients with HIV is considered a medical paradox that revolves around 3 main quandaries. First, this T-cell–mediated disease manages to flourish in an environment of decreasing T-cell counts.9 Second, although various therapies targeting T lymphocytes are effective in psoriasis, the condition worsens with decreasing CD4 T-cell counts in patients with HIV.10,11 Third, HIV is characterized by a strong helper T cells type 2 (TH2) cytokine profile and psoriasis is characterized by a strong helper T cells type 1 (TH1) secretion pattern.12-15 This 2-part series discusses these quandaries as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV by addressing the profound immune dysregulation that defines psoriasis. 

Pathogenesis of HIV-Associated Psoriasis
Although the etiology of HIV-associated psoriasis has yet to be clearly identified, it is postulated that both genetics and environmental factors play dynamic roles in its pathogenesis.16 Mallon et al17 provided the first evidence of a possible immunogenetic association between psoriasis and its expression in patients with HIV. The study compared the genomic DNA isolated from the lymphocytes of 14 men with HIV and psoriasis versus lymphocytic DNA extracted from a control group of HIV-1 seropositive men without psoriasis (n=147). The HLA-Cw6 antigen (HLA-Cw*0602 allele) was detected in 79% (11/14) of the HIV-1–positive psoriatics, while the allele, which codes for proteins capable of presenting antigens to lymphocytes, was present in only 24.5% (36/147) of HIV-1–positive controls (95% CI, 2.73–65.36; P=.0001).17 While there is a possibility that the association of psoriasis with the HLA-Cw*0602 allele is due to linkage disequilibrium with other recognized psoriasis susceptibility genes, it also can be inferred that the allele may be directly involved in the pathogenesis of the disease. Genetic evaluation has shown evidence for the linkage of psoriasis to the HLA-C locus and indicates that one or more genes located within this major histocompatiblity complex (MHC) may represent the key determinant of the genetic basis of psoriasis.18 The functional role of HLA-C is less well-defined than other HLA class I antigens. However, the identification of T-lymphocyte epitopes that are presented by certain HLA-C alleles supports the theory that HLA-C molecules are capable of presenting viral proteins such as the Epstein-Barr virus antigen and, more pertinently, HIV-1 proteins to cytotoxic CD8 T lymphocytes.19-21 The recognition of HIV-1 proteins and subsequent activation of T lymphocytes could trigger or maintain psoriatic lesions, as this locus has been proven to play an important role in susceptibility by increasing relative risk of developing psoriasis by 14 to 24 times.22 While there is consensus that T cells are integral in the pathogenesis of psoriasis, it is still debatable which cells mediate the disease, either CD4 helper T cells or CD8 cytotoxic T cells. Evaluation of these various cell types has shown that there is a substantial disruption in their balance in the HIV infection.9 Historically, it was believed that CD4 T cells were responsible for creating the immune process that characterized psoriasis and CD8 T cells were designated as having a suppressive role.13 However, recent studies have established CD8 lymphocytes as having a more independent role in the pathogenesis of the disease. Genetically, the strong association of psoriasis with class I MHC antigens, such as the aforementioned HLA-Cw*0602, which interact exclusively with CD8 T cells, bolsters the importance of this particular cell in creating psoriatic lesions.17,22,23 Histologically, various studies have shown that CD8 T cells, especially the memory T-cell subset, increased in concentration in the epidermis and papillary dermis of plaques as compared to uninvolved skin.24-28 Additionally, CD8 T cells have been shown to express proinflammatory cytokines such as interferon-γ(IFN-γ) and tumor necrosis factor α (TNF-α) more frequently than the CD4 subpopulation, which further defends the significance of this particular cell type in the pathogenesis of psoriasis.13,15 Recent theories on the effects of the HIV virus on T-cell populations have begun to explain how an imbalance in the CD4:CD8 ratio can be responsible for the immune dysregulation of HIV-associated psoriasis. The majority of studies have shown that the virus preferentially infects memory CD4 T cells and naive CD8 T cells.29-35 As HIV progresses and naive CD8 T cells become depleted, there is a disproportional relative expansion of the CD8 memory T-cell population that comprises more than 85% of the total CD8 T-cell count in patients with HIV versus 50% in healthy controls.32 The overall decrease in naive CD8 T cells not only diminishes the ability of patients to fight off new infections but also allows autoimmune diseases such as psoriasis to become established.9 The disproportional expansion of memory CD8 T cells also explains the unique cytokine profile that permits psoriasis to present in patients with HIV. A key feature of these cytokine profiles is that they are mutually antagonistic, with TH1 cytokines inhibiting the release of TH2 cytokines, and vice versa.36,37 Psoriatic lesions are associated with a TH1 cytokine pattern (ie, high levels of IL-2, IFN-γ, and TNF-α) without a substantial component of TH2 cytokines (ie, IL-2, IL-5, and IL-10).13,14,26,38,39 Evidence suggests that IFN-γ is the key contributor to the hyperproliferation of psoriasis.14,40-42 In patients with HIV without psoriasis, the cytokine profile is characterized by a strong propensity of TH2 cytokines, especially IL-4 to IL-6 and IL-10, with a decreased production of TH1 cytokines as the HIV infection progresses.42,43 This shift from a TH1 profile to a TH2 profile has been correlated with overall prognosis, as the cell-mediated immunity of the TH1 response permits lower rates of seroconversion and progression to AIDS. However, the cytokine pattern found in psoriatic patients with HIV is not characterized by a clean shift in cytokines to a complete TH2 profile. Instead, due to the increased subpopulation of memory T cells, there is a distinctive increase in the production of IFN-γ, the cytokine most responsible for creating and maintaining psoriatic phenotype (Figure).30,44-47

The link between IFN-γ and psoriatic HIV is further supported by the unique expression of the class II MHC antigen HLA-DR during inflammatory dermatoses such as psoriasis. While normally limited in expression to Langerhans cells and acrosyringial epithelium, HLA-DR is synthesized by keratinocytes in actively inflamed psoriatic lesions when exposed to IFN-γ, promoting further accumulation of leukocytes.48-53 The overexpression of HLA-DR in keratinocytes has been postulated to allow for the increased frequency of exacerbations associated with bacterial infection. The ability of streptococcal pyrogenic exotoxins and staphylococcal enterotoxins to act as superantigens that stimulate production of TNF-α by HLA-DR keratinocytes permits the vicious inflammatory cycle of psoriasis in patients with HIV to continue, even in the absence of T cells.54-57

Conclusion
The exacerbation of psoriasis in patients with HIV is largely mediated by memory CD8 T cells, a population of cells that are relatively and absolutely expanded in HIV infection. The IFN-γ produced by the memory CD8 T cells is capable of inducing keratinocytes to abnormally express HLA-DR, which predisposes these cells to become activated by bacterial superantigens that are more likely to be in excess in the immunocompromised patient. Once activated, these keratinocytes perpetuate the psoriatic phenotype by producing the proinflammatory cytokine, TNF-α. This tumultuous cycle is important because targeting specific disease mediators has proved to be therapeutic and clinically applicable in patients with HIV and psoriasis. This article is the first of a 2-part series. The second part, providing a comprehensive, in-depth appraisal of current treatment regimens available to patients with both HIV and psoriasis, will appear in a future issue of Cutis®.

Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)–infected population, an incidence equal to the general population.1 The presentation of psoriasis in patients with HIV varies. Psoriasis may present as the first clinical manifestation of HIV or, less commonly, may appear in the advanced stages of HIV when it has progressed to AIDS.2-4 A substantial proportion of patients with HIV-associated psoriasis have a pattern of acral involvement, often with pustules and sometimes with severe destructive nail changes.1 Patients with AIDS and a severe exacerbation of psoriasis are more prone to developing systemic infections, such as a superinfection of Staphylococcus aureus, whereas systemic infections are uncommon in the immunocompetent psoriatic patient.5,6 In patients with preexisting psoriasis, the severity of the condition is closely correlated with the progression of HIV and correspondingly low CD4 lymphocyte counts, making the prognosis of the patient with HIV-associated psoriasis overwhelmingly poor.4,7,8 The pathogenesis of psoriasis in patients with HIV is considered a medical paradox that revolves around 3 main quandaries. First, this T-cell–mediated disease manages to flourish in an environment of decreasing T-cell counts.9 Second, although various therapies targeting T lymphocytes are effective in psoriasis, the condition worsens with decreasing CD4 T-cell counts in patients with HIV.10,11 Third, HIV is characterized by a strong helper T cells type 2 (TH2) cytokine profile and psoriasis is characterized by a strong helper T cells type 1 (TH1) secretion pattern.12-15 This 2-part series discusses these quandaries as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV by addressing the profound immune dysregulation that defines psoriasis. 

Pathogenesis of HIV-Associated Psoriasis
Although the etiology of HIV-associated psoriasis has yet to be clearly identified, it is postulated that both genetics and environmental factors play dynamic roles in its pathogenesis.16 Mallon et al17 provided the first evidence of a possible immunogenetic association between psoriasis and its expression in patients with HIV. The study compared the genomic DNA isolated from the lymphocytes of 14 men with HIV and psoriasis versus lymphocytic DNA extracted from a control group of HIV-1 seropositive men without psoriasis (n=147). The HLA-Cw6 antigen (HLA-Cw*0602 allele) was detected in 79% (11/14) of the HIV-1–positive psoriatics, while the allele, which codes for proteins capable of presenting antigens to lymphocytes, was present in only 24.5% (36/147) of HIV-1–positive controls (95% CI, 2.73–65.36; P=.0001).17 While there is a possibility that the association of psoriasis with the HLA-Cw*0602 allele is due to linkage disequilibrium with other recognized psoriasis susceptibility genes, it also can be inferred that the allele may be directly involved in the pathogenesis of the disease. Genetic evaluation has shown evidence for the linkage of psoriasis to the HLA-C locus and indicates that one or more genes located within this major histocompatiblity complex (MHC) may represent the key determinant of the genetic basis of psoriasis.18 The functional role of HLA-C is less well-defined than other HLA class I antigens. However, the identification of T-lymphocyte epitopes that are presented by certain HLA-C alleles supports the theory that HLA-C molecules are capable of presenting viral proteins such as the Epstein-Barr virus antigen and, more pertinently, HIV-1 proteins to cytotoxic CD8 T lymphocytes.19-21 The recognition of HIV-1 proteins and subsequent activation of T lymphocytes could trigger or maintain psoriatic lesions, as this locus has been proven to play an important role in susceptibility by increasing relative risk of developing psoriasis by 14 to 24 times.22 While there is consensus that T cells are integral in the pathogenesis of psoriasis, it is still debatable which cells mediate the disease, either CD4 helper T cells or CD8 cytotoxic T cells. Evaluation of these various cell types has shown that there is a substantial disruption in their balance in the HIV infection.9 Historically, it was believed that CD4 T cells were responsible for creating the immune process that characterized psoriasis and CD8 T cells were designated as having a suppressive role.13 However, recent studies have established CD8 lymphocytes as having a more independent role in the pathogenesis of the disease. Genetically, the strong association of psoriasis with class I MHC antigens, such as the aforementioned HLA-Cw*0602, which interact exclusively with CD8 T cells, bolsters the importance of this particular cell in creating psoriatic lesions.17,22,23 Histologically, various studies have shown that CD8 T cells, especially the memory T-cell subset, increased in concentration in the epidermis and papillary dermis of plaques as compared to uninvolved skin.24-28 Additionally, CD8 T cells have been shown to express proinflammatory cytokines such as interferon-γ(IFN-γ) and tumor necrosis factor α (TNF-α) more frequently than the CD4 subpopulation, which further defends the significance of this particular cell type in the pathogenesis of psoriasis.13,15 Recent theories on the effects of the HIV virus on T-cell populations have begun to explain how an imbalance in the CD4:CD8 ratio can be responsible for the immune dysregulation of HIV-associated psoriasis. The majority of studies have shown that the virus preferentially infects memory CD4 T cells and naive CD8 T cells.29-35 As HIV progresses and naive CD8 T cells become depleted, there is a disproportional relative expansion of the CD8 memory T-cell population that comprises more than 85% of the total CD8 T-cell count in patients with HIV versus 50% in healthy controls.32 The overall decrease in naive CD8 T cells not only diminishes the ability of patients to fight off new infections but also allows autoimmune diseases such as psoriasis to become established.9 The disproportional expansion of memory CD8 T cells also explains the unique cytokine profile that permits psoriasis to present in patients with HIV. A key feature of these cytokine profiles is that they are mutually antagonistic, with TH1 cytokines inhibiting the release of TH2 cytokines, and vice versa.36,37 Psoriatic lesions are associated with a TH1 cytokine pattern (ie, high levels of IL-2, IFN-γ, and TNF-α) without a substantial component of TH2 cytokines (ie, IL-2, IL-5, and IL-10).13,14,26,38,39 Evidence suggests that IFN-γ is the key contributor to the hyperproliferation of psoriasis.14,40-42 In patients with HIV without psoriasis, the cytokine profile is characterized by a strong propensity of TH2 cytokines, especially IL-4 to IL-6 and IL-10, with a decreased production of TH1 cytokines as the HIV infection progresses.42,43 This shift from a TH1 profile to a TH2 profile has been correlated with overall prognosis, as the cell-mediated immunity of the TH1 response permits lower rates of seroconversion and progression to AIDS. However, the cytokine pattern found in psoriatic patients with HIV is not characterized by a clean shift in cytokines to a complete TH2 profile. Instead, due to the increased subpopulation of memory T cells, there is a distinctive increase in the production of IFN-γ, the cytokine most responsible for creating and maintaining psoriatic phenotype (Figure).30,44-47

The link between IFN-γ and psoriatic HIV is further supported by the unique expression of the class II MHC antigen HLA-DR during inflammatory dermatoses such as psoriasis. While normally limited in expression to Langerhans cells and acrosyringial epithelium, HLA-DR is synthesized by keratinocytes in actively inflamed psoriatic lesions when exposed to IFN-γ, promoting further accumulation of leukocytes.48-53 The overexpression of HLA-DR in keratinocytes has been postulated to allow for the increased frequency of exacerbations associated with bacterial infection. The ability of streptococcal pyrogenic exotoxins and staphylococcal enterotoxins to act as superantigens that stimulate production of TNF-α by HLA-DR keratinocytes permits the vicious inflammatory cycle of psoriasis in patients with HIV to continue, even in the absence of T cells.54-57

Conclusion
The exacerbation of psoriasis in patients with HIV is largely mediated by memory CD8 T cells, a population of cells that are relatively and absolutely expanded in HIV infection. The IFN-γ produced by the memory CD8 T cells is capable of inducing keratinocytes to abnormally express HLA-DR, which predisposes these cells to become activated by bacterial superantigens that are more likely to be in excess in the immunocompromised patient. Once activated, these keratinocytes perpetuate the psoriatic phenotype by producing the proinflammatory cytokine, TNF-α. This tumultuous cycle is important because targeting specific disease mediators has proved to be therapeutic and clinically applicable in patients with HIV and psoriasis. This article is the first of a 2-part series. The second part, providing a comprehensive, in-depth appraisal of current treatment regimens available to patients with both HIV and psoriasis, will appear in a future issue of Cutis®.