INTRODUCTION — Topical therapy is the primary mode of treatment for plaque psoriasis in patients with limited skin involvement but is often insufficient for patients with moderate to severe plaque psoriasis (psoriasis involving more than 5 to 10 percent of the body surface area). (See "Treatment of psoriasis in adults", section on 'Choice of therapy'.)
The major treatment options for moderate to severe psoriasis include phototherapy and systemic medications. Selection among these treatments must involve consideration of the patient's comorbidities (table 1).
The approach to the treatment of plaque psoriasis in adult patients with hepatitis B virus infection, hepatitis C virus infection, HIV infection, latent tuberculosis, and internal malignancy will be reviewed here. General reviews of plaque psoriasis therapy are provided separately. (See "Treatment of psoriasis in adults" and "Psoriasis in children: Management of chronic plaque psoriasis".)
OVERVIEW — The major categories of treatments for moderate to severe plaque psoriasis are listed below. Topical agents are often used in conjunction with these therapies (see "Treatment of psoriasis in adults"):
●Ultraviolet light phototherapy (see "Treatment of psoriasis in adults", section on 'Ultraviolet light'):
•Narrowband ultraviolet B (UVB) phototherapy
•Broadband UVB phototherapy
•Psoralen plus ultraviolet A (PUVA) phototherapy
●Oral agents (see "Treatment of psoriasis in adults", section on 'Systemic therapies'):
•Apremilast (phosphodiesterase-4 inhibitor)
●Biologic agents (see "Treatment of psoriasis in adults", section on 'Biologic agents'):
•Etanercept (tumor necrosis factor [TNF]-alpha inhibitor)
•Adalimumab (TNF-alpha inhibitor)
•Infliximab (TNF-alpha inhibitor)
•Ustekinumab (interleukin [IL] 12 and IL-23 inhibitor)
•Secukinumab (IL-17A inhibitor)
•Ixekizumab (IL-17A inhibitor)
•Brodalumab (IL-17RA inhibitor)
•Guselkumab (IL-23 inhibitor)
•Tildrakizumab (IL-23 inhibitor)
•Risankizumab (IL-23 inhibitor)
These therapies have side effects that can be detrimental in patients with certain underlying diseases. For example, the safety of a potentially hepatotoxic drug, such as methotrexate, is a concern when treating patients with hepatitic disorders. In addition, the potential adverse effects of immunosuppressive therapy on patients with chronic infections or malignancies must be considered.
Selection of the optimal approach to treatment in patients with comorbidities, such as hepatitis B virus infection, hepatitis C virus infection, HIV infection, latent tuberculosis, and malignancy, is hampered by limited data on the safety of these treatments in the psoriasis population. Proposed guidelines have been based upon a combination of published data from patients with psoriasis, data from studies of similar treatment regimens for other diseases, and expert consensus (table 1) [1-7].
CHRONIC HEPATITIS B VIRUS INFECTION — Hepatitis B virus (HBV) infection is one of the most common chronic viral infections in humans [8,9].
HBV infection is divided into phases that reflect the interplay between virus replication and the host immune response (figure 1). Laboratory studies are useful for determining the phase of the disease (table 2A-B). In patients with chronic HBV infection, hepatitis B surface antigen (HBsAg) and immunoglobulin G (IgG) hepatitis B core antibodies (IgG anti-HBc) persist in serum. Hepatitis e antigen (HBeAg), a marker of viral replication and infectivity that is usually associated with high levels of HBV DNA in serum and active liver disease, also may be detected. Upon recovery from HBV infection, HBsAg is no longer detectable in serum. However, patients with prior infection remain positive for IgG anti-HBc and are at risk for reactivation of disease during immunosuppressive therapy, particularly when hepatitis surface antibody (anti-HBs) negative. (See "Hepatitis B virus: Clinical manifestations and natural history" and "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
Our approach — Overall, data on the safety of psoriasis therapies in patients with HBV infection are limited. Consideration of two factors is necessary for selection of a therapeutic agent:
●Does the therapy have direct hepatotoxic effects that can compound the existing viral liver disease?
●Does the therapy have immunomodulatory effects that may promote viral replication and reactivation of HBV infection? (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
In patients with moderate to severe plaque psoriasis and HBV infection, we use ultraviolet B (UVB) phototherapy (preferably narrowband UVB) supplemented with topical therapy as first-line treatment when it is available and convenient for the patient [2]. Narrowband UVB phototherapy is effective for psoriasis and has negligible risk for hepatotoxicity, systemic immunosuppression, or other systemic side effects. (See 'Phototherapy' below.)
If UVB phototherapy is not feasible, we consider systemic therapy (table 1). Preferred systemic therapies are apremilast and ustekinumab, based upon the mechanism of action of apremilast and the availability of long-term safety data for ustekinumab (see 'Ustekinumab' below). Secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab may also be well tolerated based upon their mechanisms of action, although cautious use of these drugs is indicated because of a paucity of safety data in this population. Selection amongst these systemic therapies is also based upon consideration of factors such as other comorbidities, clinician familiarity with specific agents, patient preference, treatment history, and treatment availability. (See 'Biologic agents' below and 'Oral agents' below and "Treatment of psoriasis in adults".)
Phototherapy — UVB phototherapy is generally considered safe in patients with HBV infection (table 1). Although the immunosuppressive effects of ultraviolet light are believed to contribute to the efficacy of UVB phototherapy in psoriasis and the risk for reactivation of HBV infection due to phototherapy has not been evaluated, the systemic effects of treatment are likely minimal [2,10]. (See "Treatment of psoriasis in adults", section on 'Ultraviolet light'.)
The lack of need for topical or systemic administration of psoralens has led to a preference for UVB phototherapy (particularly narrowband UVB phototherapy) as the preferred mode of phototherapy for psoriasis. Although two one-year studies of patients without hepatitis failed to find statistically significant histologic differences in pre-psoralen plus ultraviolet A (PUVA) and post-PUVA liver biopsy specimens [11,12], there have been several reports of liver injury after PUVA therapy [13-17]. In addition, severe liver disease is a relative contraindication for treatment with PUVA (table 3). (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)
Oral agents — Treatment with methotrexate or acitretin is generally avoided in patients with HBV infection. Limited data suggest apremilast is well tolerated. Cyclosporine should be used with caution (table 1):
●Methotrexate – Reactivation of HBV infection resulting in fulminant hepatic failure has been documented in case reports of patients treated with methotrexate for rheumatologic diseases [18-21]. This finding and the potential for methotrexate-induced hepatotoxicity raise concern about the safety of methotrexate therapy in patients with HBV infection, particularly given the existence of other therapeutic options. A 2012 consensus statement from the Medical Board of the National Psoriasis Foundation advised that methotrexate should not be prescribed in this population [1,22]. (See "Major side effects of low-dose methotrexate" and "Treatment of psoriasis in adults", section on 'Methotrexate'.)
●Acitretin – Acitretin is not an immunosuppressant [23,24]. Therefore, despite a lack of data on the safety of acitretin use in HBV-infected patients, acitretin is not thought to increase the risk for reactivation of HBV infection.
However, elevation of liver enzymes is a common side effect of acitretin [25], though severe hepatotoxic reactions are rare [24,26]. A two-year study of pretreatment and post-treatment liver biopsies in patients treated with acitretin for psoriasis failed to find clinically significant toxic effects on the liver, suggesting that hepatic tolerance of the drug may be good in healthy patients [25]. However, patients with chronic HBV infection may be more susceptible to hepatotoxic effects from acitretin; therefore, its use is not recommended. Patients treated with acitretin should be followed closely for laboratory evidence of liver toxicity and comanaged with a hepatologist. (See "Treatment of psoriasis in adults", section on 'Acitretin'.)
●Apremilast – There are no known direct hepatotoxic effects of apremilast. Although data on the effect of apremilast on HBV infection are lacking, the mechanism of action of apremilast suggests risk for reactivation of HBV infection may be low. Apremilast is considered one of the preferred treatment options in this patient population. (See "Treatment of psoriasis in adults", section on 'Apremilast'.)
●Cyclosporine – The safety of cyclosporine in patients with psoriasis and hepatitis B has not been specifically evaluated. Immunosuppressive properties of cyclosporine raise concern for the possibility of reactivation of HBV infection [27,28]. Caution is indicated for use of cyclosporine in patients with psoriasis and HBV infection. Patients should be managed in conjunction with a hepatologist, and initiation of antiviral therapy is recommended prior to treatment in HBsAg-positive patients. Close laboratory monitoring for signs of reactivation of infection should be performed during treatment; liver function tests and viral load should be routinely monitored. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
Cyclosporine is generally used as a short-term treatment (eg, up to 12 weeks); long-term use is avoided due to drug side effects. (See "Treatment of psoriasis in adults", section on 'Cyclosporine'.)
Biologic agents — The use of tumor necrosis factor (TNF)-alpha inhibitors (eg, etanercept, adalimumab, infliximab) in patients with HBV infection is not recommended due to risk for reactivation of infection. Risk for reactivation of HBV infection appears to be low for ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab, which makes these biologics preferred over TNF inhibitors in patients with HBV infection (table 1).
Patients requiring biologic therapies should be managed in conjunction with a hepatologist. Initiation of antiviral therapy is recommended prior to the start of biologic agents in HBsAg-positive patients [1,29-31]. In addition, close laboratory monitoring for signs of reactivation of infection is indicated during treatment; liver function tests and viral load should be routinely monitored [1,4].
Tumor necrosis factor-alpha inhibitors — TNF-alpha inhibitors usually do not induce direct hepatotoxic effects [32]. Transaminase elevations develop only occasionally [33]. However, reactivation of HBV infection is the major concern with the use of TNF inhibitors, and their use is generally not recommended in patients with HBV infection.
Reactivation of HBV infection in patients treated with TNF-alpha inhibitors may be related to a suppressive role of endogenous TNF-alpha on replication of HBV [4]. HBsAg-positive patients have the greatest risk for disease reactivation. Reactivation occurs less frequently in HBsAg-negative patients who have a prior history of HBV infection and is rare in HBsAg-negative patients who have achieved full immunologic recovery (anti-HBs-positive and anti-HBc-positive (table 2B)) [4,32,34].
The lack of clarity on the level of risk for HBV reactivation due to TNF-alpha inhibitor therapy for psoriasis reflects the consistent exclusion of patients with HBV infection from trials evaluating the efficacy and safety of these therapies. Reactivation of HBV infection in HBsAg-positive patients treated with TNF-alpha inhibitors for psoriasis has been reported [35]. As an example, in one series of seven HBsAg-positive patients with psoriasis or psoriatic arthritis who were treated with etanercept or adalimumab for an average of 29 months, three patients, including one who had undetectable HBV DNA levels prior to treatment, developed reactivation of HBV infection [36]. Antiviral prophylaxis was given to only one patient; reactivation of HBV infection did not occur in this patient.
As a result of the paucity of treatment data in patients with moderate to severe psoriasis and HBV infection, much of the knowledge of the use of these agents in the setting of HBV infection stems from literature published in patients with conditions other than psoriasis. Most reported cases of HBV reactivation have occurred in patients who were taking infliximab for rheumatologic conditions [37,38], suggesting that infliximab may be the TNF-alpha inhibitor that is most likely to cause HBV reactivation. It is unclear whether the disproportionate number of reports for infliximab compared with other TNF-alpha inhibitors is related to its longer half-life or greater drug potency [4]. (See "Treatment of psoriasis in adults", section on 'Etanercept' and "Treatment of psoriasis in adults", section on 'Infliximab' and "Treatment of psoriasis in adults", section on 'Adalimumab'.)
Ustekinumab — Long-term data on ustekinumab have not shown an increase in HBV reactivation rates [35]. Antiviral prophylaxis may be important in HBsAg-positive patients [30,31]. In a retrospective study of patients treated with ustekinumab for psoriasis, reactivation of HBV infection occurred in two of seven HBsAg-positive patients who did not receive antiviral prophylaxis, whereas none of four HBsAg-positive patients given antiviral prophylaxis developed reactivation [31]. Of note, reactivation of HBV infection also has been documented in a patient who was HBsAg-negative, anti-HBc-positive, and anti-HBs-positive prior to ustekinumab therapy [39]. (See "Treatment of psoriasis in adults", section on 'Ustekinumab'.)
Secukinumab, ixekizumab, and brodalumab — Clinical data on the effect of interleukin (IL) 17 inhibitors on reactivation of HBV infection are limited to case reports [40]. For example, based on case reports, secukinumab has been used in patients with HBV and hepatitis C virus (HCV) infection without viral reactivation or significant elevations in liver enzymes [40]. The mechanism of effect of IL-17 inhibitors in patients with viral hepatitis is unknown. Thus, the benefit/risk assessment needs to be carefully considered when using IL-17 inhibitors in patients with viral hepatitis. (See "Treatment of psoriasis in adults", section on 'Secukinumab' and "Treatment of psoriasis in adults", section on 'Ixekizumab' and "Treatment of psoriasis in adults", section on 'Brodalumab'.)
Guselkumab, tildrakizumab, and risankizumab — The effects of guselkumab, tildrakizumab, and risankizumab on psoriasis patients with HBV infection are unknown due to excluding patients with active hepatitis B from phase II and III studies. The use of IL-23 inhibitors must be carefully monitored in patients with viral hepatitis. (See "Treatment of psoriasis in adults", section on 'Guselkumab' and "Treatment of psoriasis in adults", section on 'Tildrakizumab'.)
CHRONIC HEPATITIS C VIRUS INFECTION — Hepatitis C is a common blood-borne infection [41]. Similar to hepatitis B virus (HBV) infection, the primary concerns for the treatment of moderate to severe psoriasis in hepatitis C virus (HCV)-infected patients are exacerbation of the infection and drug-induced hepatotoxicity. Of note, interferon, a treatment for HCV infection, may exacerbate psoriasis [42]. (See "Clinical manifestations and natural history of chronic hepatitis C virus infection" and "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Introduction'.)
Our approach — Patients with HCV infection should be referred to a hepatologist for evaluation, particularly given the existence of treatments that can eradicate the infection. (See "Overview of the management of chronic hepatitis C virus infection".)
The paucity of data on the treatment of psoriasis in patients with HCV infection makes the identification of the best approach to the treatment difficult. Ultraviolet B (UVB) phototherapy in combination with topical therapy is considered safe and a preferred treatment for patients with moderate to severe psoriasis and HCV infection [3]. Other treatment options that are likely to be well tolerated include tumor necrosis factor (TNF)-alpha inhibitors, ustekinumab, and apremilast based on the mechanisms of action of these drugs or evidence that suggests low risk for hepatotoxicity or exacerbation of HCV infection. Use of newer biologic agents, including secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab, may also be well tolerated, though a cautious approach is indicated because of limited experience with these agents in patients with HCV infection. Selection amongst the systemic therapies is also based upon consideration of factors such as other comorbidities, clinician familiarity with specific agents, patient preference, treatment history, and treatment availability (table 1). (See 'Phototherapy' below and 'Biologic agents' below.)
Phototherapy — Although the safety of phototherapy in patients with HCV infection has not been specifically studied, UVB phototherapy generally is considered safe in these patients (table 1) [3]. Psoralen plus ultraviolet A (PUVA) is an additional therapeutic option; however, there have been several reports of liver injury after PUVA therapy [13-17], and severe liver disease is considered a relative contraindication for PUVA (table 3). (See 'Phototherapy' above and "Treatment of psoriasis in adults", section on 'Ultraviolet light' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)
Oral agents — Methotrexate and acitretin are generally avoided in patients with HCV infection due to safety concerns. Limited data suggest that apremilast is well tolerated. Caution is necessary for the use of cyclosporine (table 1):
●Methotrexate – Methotrexate is contraindicated for the treatment of psoriasis in patients with HCV infection due to an increased risk for hepatotoxicity [3]. (See "Major side effects of low-dose methotrexate" and "Treatment of psoriasis in adults", section on 'Methotrexate'.)
●Acitretin – The safety of acitretin in patients with HCV infection has not been studied. Liver function test abnormalities, and occasionally long-term hepatotoxic effects, can occur during treatment [25]. A two-year study of pretreatment and post-treatment liver biopsies in patients without hepatitis who were treated with acitretin for psoriasis failed to find clinically significant toxic effects on the liver [25]. Nevertheless, due to the potential for hepatotoxicity, we do not use acitretin unless other therapeutic options are not feasible. (See "Treatment of psoriasis in adults", section on 'Acitretin'.)
●Apremilast – There are no known direct hepatotoxic effects of apremilast. A case report describes successful use in a patient with HCV and HIV infections [43]. (See "Treatment of psoriasis in adults", section on 'Apremilast'.)
●Cyclosporine – Traditionally, cyclosporine has been avoided in the treatment of psoriasis in patients with HCV infection due to concerns that the drug's immunosuppressive effects might exacerbate the infection [3]. However, in vitro studies have found that cyclosporine has suppressive effects on HCV replication [44-46]. In addition, case reports have documented improvements in both transaminase levels and psoriasis during treatment with cyclosporine in patients with HCV infection [47-50]. These findings suggest that cyclosporine therapy may be tolerated in patients with psoriasis and HCV infection. Consultation with a hepatologist should be performed prior to starting treatment with cyclosporine. In addition, periodic laboratory assessment for signs of reactivating disease is warranted. (See "Treatment of psoriasis in adults", section on 'Cyclosporine'.)
Biologic agents — Consultation with a hepatologist should be performed prior to starting treatment with a biologic agent in patients with moderate to severe psoriasis and HCV infection. In addition, biologic therapy should be accompanied by regular monitoring of viral hepatitis activity [1,32]. TNF inhibitors and ustekinumab appear to be well tolerated provided liver function enzymes and viral load are monitored.
Data on interleukin (IL) 17 and IL-23 inhibitors are lacking in patients with HCV infection. While the mechanisms of these drugs do not suggest substantial adverse effects, due to the lack of data in this population, clinicians should use them with caution. Liver function enzymes and viral activity should be monitored (table 1).
Tumor necrosis factor-alpha inhibitors — Although data on biologic therapy in patients with HCV infection are limited, the available data from studies in patients with psoriasis and other diseases suggest that patients with chronic HCV infection may tolerate TNF-alpha inhibitor therapy [35]. Interestingly, a small randomized trial found that patients who were given etanercept as an adjunct to interferon and ribavirin for the treatment of HCV infection were more likely to achieve clearance of HCV RNA than patients who received interferon, ribavirin, and a placebo [51]. (See "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections", section on 'Hepatitis C'.)
Data on the use of etanercept, the biologic agent most studied in patients with psoriasis and HCV infection, primarily consist of case reports and small retrospective studies. A systematic review of published reports between 1990 and 2010 identified 22 case reports of patients treated with etanercept for psoriasis or psoriatic arthritis [52]. The review found that viral loads or transaminase levels remained stable in 17 of these patients and decreased in 4 patients during treatment with etanercept. Only one patient developed an increase in viral load.
Additional case reports and small retrospective studies have documented successful use of etanercept, adalimumab, and infliximab for psoriasis in patients with HCV infection [35,52-60]. As an example, a retrospective study of 20 adults with psoriasis and HCV infection who were treated with etanercept (18 patients), adalimumab (4 patients), ustekinumab (3 patients), and/or infliximab (1 patient), found that these biologic agents were well tolerated by most patients [30]. (See "Treatment of psoriasis in adults", section on 'Etanercept' and "Treatment of psoriasis in adults", section on 'Infliximab' and "Treatment of psoriasis in adults", section on 'Adalimumab'.)
Ustekinumab — Data on the use of ustekinumab in patients with HCV infection and psoriasis are limited [30,31]. Long-term studies have not shown an increase in HCV reactivation rates in patients treated with ustekinumab [31,61]. However, close monitoring and collaboration with a hepatologist are indicated during treatment with ustekinumab for following HCV disease progression.
Secukinumab, ixekizumab, and brodalumab — Safety data on the use of IL-17 inhibitors in HCV-infected patients are lacking because the phase II and III trials excluded patients with active hepatitis C. However, there are no biologic mechanisms or postmarketing data suggesting increased risk associated with use of IL-17 inhibitors in this population. Patients treated with IL-17 inhibitors should be routinely monitored for viral hepatitis activity. (See "Treatment of psoriasis in adults", section on 'Secukinumab' and "Treatment of psoriasis in adults", section on 'Ixekizumab' and "Treatment of psoriasis in adults", section on 'Brodalumab'.)
Guselkumab, tildrakizumab, and risankizumab — Safety data on the use of the IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab in hepatitis C patients are lacking. However, there are no biologic mechanisms or postmarketing data suggesting increased risk associated with use of these drugs in the setting of HCV infection. Patients treated with guselkumab, tildrakizumab, or risankizumab should be routinely monitored for viral hepatitis activity. (See "Treatment of psoriasis in adults", section on 'Guselkumab' and "Treatment of psoriasis in adults", section on 'Tildrakizumab'.)
HIV INFECTION — HIV infection is a risk factor for severe psoriasis [6]. In some patients, psoriasis is the initial presenting sign of HIV infection [5]. The immunosuppressive effects of psoriasis therapies are the major concern in this population.
Our approach — Patients with HIV infection and moderate to severe psoriasis are best managed by coordinated care with a dermatologist and infectious disease specialist. The Medical Board of the National Psoriasis Foundation recommends phototherapy and antiretrovirals as first-line therapies for patients with HIV infection and moderate to severe psoriasis, and acitretin is an appropriate second-line treatment [6]. Recommendations in a 2015 update to the European S3-Guidelines are fairly similar, supporting antiretroviral therapy plus skin-directed treatments, such as phototherapy and topical agents, as first-line treatments and acitretin plus antiretroviral therapy as second-line treatment [62].
Our typical first-line therapeutic approach to moderate to severe psoriasis in patients with HIV infection consists of antiretroviral treatment along with phototherapy supplemented with topical therapy. However, multiple phototherapy visits are inconvenient for many patients. Acitretin supplemented with topical medication or apremilast supplemented with topical medication are well-tolerated alternatives to phototherapy (table 1).
Therapies such as cyclosporine, methotrexate, and biologic drugs (tumor necrosis factor [TNF]-alpha inhibitors, ustekinumab, secukinumab, ixekizumab, brodalumab, and guselkumab) should be reserved for refractory cases and should be used cautiously; the status of the HIV infection should be monitored closely during treatment.
Antiretroviral drugs — Psoriasis in HIV-infected patients may improve with antiretroviral therapy [5,63-68]. As an example, in an open-label study in which 24 patients with HIV-associated psoriasis were treated with zidovudine, 90 percent of the 19 patients who were followed for at least eight weeks achieved either partial or complete improvement of psoriasis [63].
Phototherapy — Phototherapy can be effective for HIV-associated psoriasis [2,69-71]. Although ultraviolet radiation has been linked to activation of HIV in some in vitro and animal studies [72-74], small case series and uncontrolled studies suggest that phototherapy administered to HIV-positive patients is well tolerated and not associated with significant changes in viral load, CD4+, and CD8+ T cells during or after therapy [69,71,75,76]. (See "Treatment of psoriasis in adults", section on 'Ultraviolet light'.)
Oral agents — Patients with HIV infection typically tolerate acitretin and apremilast. Methotrexate and cyclosporine must be used with caution (table 1):
●Acitretin – Acitretin is an attractive therapeutic option for psoriasis in patients with HIV infection because it is not an immunosuppressant. In a 20-week uncontrolled study in which 11 HIV-positive men with moderate to severe psoriasis (including seven men with plaque-type psoriasis) were treated with acitretin (up to 100 mg per day), four patients achieved at least 75 percent reduction in the Psoriasis Area and Severity Index (PASI) score, and an additional two patients achieved at least 51 to 75 percent improvement. Two of the three patients who discontinued treatment stopped treatment due to worsening psoriasis. The third patient stopped treatment due to a myocardial infarction that was presumed to be unrelated to acitretin therapy [77]. Of note, typical doses of acitretin for the treatment of psoriasis range from 25 to 50 mg per day; higher doses are often poorly tolerated due to side effects. (See "Treatment of psoriasis in adults", section on 'Acitretin'.)
●Methotrexate – Methotrexate is not commonly used for psoriasis in HIV-infected patients due to concern about the drug's immunosuppressive effects [5,69,78]. Although case reports have documented successful treatment in the setting of HIV infection [78], the risks and benefits of therapy must be weighed carefully prior to treatment [5]. Treatment with methotrexate is usually reserved for refractory cases. (See "Major side effects of low-dose methotrexate" and "Treatment of psoriasis in adults", section on 'Methotrexate'.)
●Apremilast – Apremilast is considered a treatment option for HIV-infected patients because it does not appear to have significant immunosuppressive effects [79]. Treatment was well tolerated in a patient with HIV and hepatitis C virus (HCV) infections [43]. (See "Treatment of psoriasis in adults", section on 'Apremilast'.)
●Cyclosporine – Case reports have documented the successful use of cyclosporine for psoriasis in patients with HIV infection [80,81]. However, as with methotrexate, the immunosuppressive effects are a concern. Treatment with cyclosporine is primarily reserved for short courses (up to 12 weeks) of treatment in patients with refractory disease. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects' and "Treatment of psoriasis in adults", section on 'Cyclosporine'.)
Some authors have suggested an initial starting dose of 2.5 mg/kg per day of cyclosporine if the drug is used in this population [5]. Trough levels of cyclosporine should be monitored carefully in patients taking protease inhibitors, since these agents may increase the bioavailability of cyclosporine [82].
Biologic agents — Data are limited on the safety of biologic therapies in patients with HIV infection. Several cases of successful use of biologic TNF-alpha inhibitors for psoriasis or rheumatologic conditions in patients with HIV infection have been reported [83-87]. Viral counts and immune status remained stable in these patients. However, one report documented the eventual discontinuation of etanercept due to the occurrence of multiple infections [87].
An additional case report has described successful treatment of psoriasis with ustekinumab [88]. The patient achieved great improvement in psoriasis, and treatment was well tolerated.
Tolerance of secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab in the setting of HIV infection has not been evaluated. The mechanisms of action of these drugs suggest risk for exacerbation of HIV infection would be low.
Further studies are necessary to determine the role biologic therapy should play in the management of psoriasis in patients with HIV infection (table 1). In general, these agents should be used with caution and reserved for HIV-infected patients who cannot be adequately treated with preferred therapies, are receiving antiretroviral therapy, and can be regularly monitored. Concomitant antiretroviral therapy is suggested to decrease the likelihood of opportunistic infections during biologic treatment [5,6,83,89]. (See "Treatment of psoriasis in adults", section on 'Biologic agents'.)
Other therapies — Other drugs that have been reported to be useful in individual patients with HIV infection and psoriasis include cimetidine, ranitidine, carbamazepine, antibiotics, nicotinamide, and mycophenolate mofetil [5]. Ranitidine has been withdrawn from the United States market.
LATENT TUBERCULOSIS — Immunosuppressive treatment may result in reactivation of latent tuberculosis (TB) infection. Thus, screening for TB infection is recommended prior to the administration of immunosuppressive therapies for psoriasis (eg, biologic agents, methotrexate, and cyclosporine) [7,62,90]. These drugs should be used with caution (table 1). Tumor necrosis factor (TNF)-alpha plays a particularly important role in the immune defense against TB infection, raising particular concern about the use of TNF-alpha inhibitor therapy. Use of therapies without systemic immunosuppressive effects, such as phototherapy, acitretin, and apremilast, are not considered to increase risk for TB reactivation (table 1). (See "Risk of mycobacterial infection associated with biologic agents and JAK inhibitors".)
Screening for TB is performed through a patient interview and testing via a tuberculin skin test or interferon-gamma release assay. A chest radiograph should be performed if the screening test is positive. Screening for TB infection is not necessary prior to treatment with topical agents, phototherapy, acitretin, or apremilast since these therapies do not appear to increase the risk for reactivation of TB infection. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)
Patients who have latent TB should be given treatment for this condition to reduce the risk for TB [91,92]. Opinions vary on how long patients must be on treatment for latent TB before TNF-alpha inhibitor therapy can be initiated. While some authors recommend completing the full course of prophylactic TB therapy prior to biologic therapy [93], other sources, including the Medical Board of the National Psoriasis Foundation, suggest initiation of immunologic therapies after the first one to two months of prophylactic TB treatment if it is required by the clinical condition [2,7,94,95].
We agree with the National Psoriasis Foundation's approach. While the full course of prophylactic TB treatment can be completed before initiating a biologic agent, we consider acceptable the initiation of biologic therapy following at least one month of TB treatment, such that the patient will then continue TB treatment concurrently with biologic therapy. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection".)
The risk for TB reactivation among patients who are treated with prophylactic therapy prior to the start of biologic therapy appears to be low [91,96-100]. As an example, in an analysis of data from five phase III trials of ustekinumab therapy for moderate to severe plaque psoriasis, none of the 167 patients with newly diagnosed latent TB infection who began TB prophylaxis before or at the time of the first dose of ustekinumab developed active TB during a 28-week follow-up period [97]. The risk for mycobacterial infections in patients treated with TNF-alpha inhibitors is reviewed in greater detail separately. (See "Risk of mycobacterial infection associated with biologic agents and JAK inhibitors".)
MALIGNANCY — The immunosuppressive effects of systemic agents for psoriasis are the primary safety concerns for systemic psoriasis therapy in patients with a history of internal malignancy. The best approach to the treatment varies based upon the severity of psoriasis and the type of malignancy (table 1). Consultation with the patient's oncologist and a thorough discussion with the patient about the risk-benefit ratios of the therapeutic options should take place prior to deciding on a treatment.
Methotrexate and cyclosporine may increase the risk for lymphoproliferative disorders. In long-term studies in the psoriasis population, tumor necrosis factor inhibitors and ustekinumab do not appear to increase risk for internal malignancies. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Risk of malignancy' and "Tumor necrosis factor-alpha inhibitors: Risk of malignancy" and "Comorbid disease in psoriasis", section on 'Malignancy' and "Major side effects of low-dose methotrexate", section on 'Risk of lymphoproliferative disorders' and "Treatment of psoriasis in adults", section on 'Ustekinumab'.)
Data have not shown an association between internal malignancies and the use of interleukin (IL) 17 inhibitors, such as secukinumab [101,102], ixekizumab [103], or brodalumab [104]. Similarly, short-term data have not shown an association between internal malignancies and IL-23 inhibitors, such as guselkumab [105], tildrakizumab [106], and risankizumab [107].
Nonimmunosuppressive therapies, such as phototherapy and acitretin, are generally considered safe treatment options for patients with current or prior hematologic or solid tumor malignancies [2,62]. Patients with a history of melanoma or multiple nonmelanoma skin cancers are an exception since these conditions are relative contraindications for phototherapy [10]. Of note, patients with a history of multiple squamous cell skin cancers may benefit from the suppressive effect of acitretin on the development of these lesions. (See "Cutaneous squamous cell carcinoma: Primary and secondary prevention", section on 'Oral retinoids'.)
Long-term data on the risk of malignancy and apremilast are not available. Short-term data do not suggest a link between internal malignancy and apremilast [79].
PREGNANCY — The management of psoriasis in pregnant women is reviewed separately. (See "Management of psoriasis in pregnancy".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriasis".)
SUMMARY AND RECOMMENDATIONS
●Patients with moderate to severe psoriasis (psoriasis involving more than 5 to 10 percent of the body surface area) generally require phototherapy, oral medications (eg, acitretin, methotrexate, apremilast, cyclosporine), or biologics (eg, tumor necrosis factor [TNF]-alpha inhibitors, ustekinumab, interleukin [IL] 17 inhibitors, guselkumab, tildrakizumab) for optimal management of the disease. The potential adverse effects of these therapies must be considered carefully in patients with comorbidities. (See 'Overview' above and "Treatment of psoriasis in adults", section on 'Choice of therapy'.)
●The determination of the best approach to the management of psoriasis in patients with hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, HIV infection, latent tuberculosis (TB), and internal malignancy is challenging because data on psoriasis therapy in these populations are limited. Recommendations for the management of these patients are based upon data from patients with psoriasis, patients with other disorders treated with similar therapies, and expert opinion (table 1) (see 'Overview' above and 'Chronic hepatitis B virus infection' above and 'Chronic hepatitis C virus infection' above and 'HIV infection' above and 'Latent tuberculosis' above and 'Malignancy' above):
•Narrowband ultraviolet B (UVB) phototherapy – Narrowband UVB phototherapy has negligible effects on hepatic tissue and systemic immunity. Narrowband UVB phototherapy is a safe treatment for psoriasis in patients with HBV infection, HCV infection, HIV infection, latent TB, and internal malignancy. (See "Treatment of psoriasis in adults", section on 'Ultraviolet light'.)
•Acitretin – Acitretin lacks immunosuppressive effects and is typically well tolerated by patients with HIV infection, latent TB, or malignancy. However, acitretin may have adverse hepatic effects and is generally avoided in the setting of HBV or HCV infection. (See "Treatment of psoriasis in adults", section on 'Acitretin'.)
•Methotrexate – Methotrexate has hepatotoxic and immunosuppressive effects and is not recommended for the treatment of psoriasis in patients with HBV or HCV infection. In patients with HIV infection or latent TB, methotrexate should be used with caution. Methotrexate may increase risk for lymphoproliferative disorders. (See "Treatment of psoriasis in adults", section on 'Methotrexate'.)
•Cyclosporine – Cyclosporine has immunosuppressive effects. The drug should be used with caution; consultation with disease specialists and close monitoring are indicated for patients with viral hepatitis, HIV, latent TB, or malignancy. Long-term use of cyclosporine is generally not recommended due to renal toxicity. (See "Treatment of psoriasis in adults", section on 'Cyclosporine'.)
•Apremilast – Apremilast appears to have minimal immunosuppressive effects. Apremilast is one of the preferred therapies for psoriasis in patients with HBV infection, HCV infection, HIV infection, and latent tuberculosis. Short-term data do not suggest an increased risk of malignancy with apremilast. (See "Treatment of psoriasis in adults", section on 'Apremilast'.)
•TNF-alpha inhibitors – TNF-alpha inhibitors are generally avoided in patients with HBV infection due to concerns for disease reactivation. In contrast, TNF-alpha inhibitor therapy is one of the preferred biologic therapies for patients with HCV infection provided consultation with a hepatologist and close monitoring are feasible. TNF-alpha inhibitors should be used with caution and in conjunction with antiviral therapy and anti-TB therapy in patients with HIV infection and latent TB, respectively. TNF-alpha inhibitors do not increase risk for malignancy in the psoriasis population. (See "Treatment of psoriasis in adults", section on 'Etanercept' and "Treatment of psoriasis in adults", section on 'Infliximab' and "Treatment of psoriasis in adults", section on 'Adalimumab'.)
•Ustekinumab – Ustekinumab is a preferred biologic therapy in patients with HBV or HCV infection provided consultation with a hepatologist and close monitoring are feasible. Among patients with HIV infection, ustekinumab is primarily reserved for refractory psoriasis in patients who can be closely monitored for HIV activity. Ustekinumab is a preferred biologic agent for patients with latent TB provided patients also receive anti-TB therapy. Ustekinumab does not increase risk of internal malignancy in the psoriasis population. (See "Treatment of psoriasis in adults", section on 'Ustekinumab'.)
•IL-17 inhibitors, guselkumab, and tildrakizumab – Caution is indicated for use of IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab), guselkumab, and tildrakizumab in patients with HBV, HCV, or HIV infection because of a lack of long-term data. Consultation with disease specialists and close monitoring are indicated. IL-17 inhibitors, guselkumab, and tildrakizumab are considered preferred biologic therapies in patients with latent TB provided patients also receive anti-TB therapy. Short-term studies have not found increased risk of internal malignancy in psoriasis patients treated with IL-17 inhibitors, guselkumab, or tildrakizumab. (See "Treatment of psoriasis in adults", section on 'Secukinumab' and "Treatment of psoriasis in adults", section on 'Ixekizumab' and "Treatment of psoriasis in adults", section on 'Brodalumab' and "Treatment of psoriasis in adults", section on 'Guselkumab' and "Treatment of psoriasis in adults", section on 'Tildrakizumab'.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟