Pathways to cures for multiple sclerosis: A research roadmap.

BACKGROUND: Multiple Sclerosis (MS) is a growing global health challenge affecting nearly 3 million people. Progress has been made in the understanding and treatment of MS over the last several decades, but cures remain elusive. The National MS Society is focused on achieving cures for MS. OBJECTIVES: Cures for MS will be hastened by having a roadmap that describes knowledge gaps, milestones, and research priorities. In this report, we share the Pathways to Cures Research Roadmap and recommendations for strategies to accelerate the development of MS cures. METHODS: The Roadmap was developed through engagement of scientific thought leaders and people affected by MS from North America and the United Kingdom. It also included the perspectives of over 300 people living with MS and was endorsed by many leading MS organizations. RESULTS: The Roadmap consist of three distinct but overlapping cure pathways: (1) stopping the MS disease process, (2) restoring lost function by reversing damage and symptoms, and (3) ending MS through prevention. Better alignment and focus of global resources on high priority research questions are also recommended. CONCLUSIONS: We hope the Roadmap will inspire greater collaboration and alignment of global resources that accelerate scientific breakthroughs leading to cures for MS.

COVID-19 in people with multiple sclerosis: A global data sharing initiative.

BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.

Landscape of MS patient cohorts and registries: Recommendations for maximizing impact.

BACKGROUND: There is a growing number of cohorts and registries collecting phenotypic and genotypic data from groups of multiple sclerosis patients. Improved awareness and better coordination of these efforts is needed. OBJECTIVE: The purpose of this report is to provide a global landscape of the major longitudinal MS patient data collection efforts and share recommendations for increasing their impact. METHODS: A workshop that included over 50 MS research and clinical experts from both academia and industry was convened to evaluate how current and future MS cohorts could be better used to provide answers to urgent questions about progressive MS. RESULTS: The landscape analysis revealed a significant number of largely uncoordinated parallel studies. Strategic oversight and direction is needed to streamline and leverage existing and future efforts. A number of recommendations for enhancing these efforts were developed. CONCLUSIONS: Better coordination, increased leverage of evolving technology, cohort designs that focus on the most important unanswered questions, improved access, and more sustained funding will be needed to close the gaps in our understanding of progressive MS and accelerate the development of effective therapies.

Hyaluronan anchored to activated CD44 on central nervous system vascular endothelial cells promotes lymphocyte extravasation in experimental autoimmune encephalomyelitis.

The extravasation of lymphocytes across central nervous system (CNS) vascular endothelium is a key step in inflammatory demyelinating diseases including multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). The glycosaminoglycan hyaluronan (HA) and its receptor, CD44, have been implicated in this process but their precise roles are unclear. We find that CD44(-/-) mice have a delayed onset of EAE compared with wild type animals. Using an in vitro lymphocyte rolling assay, we find that fewer slow rolling (<1 µm/s) wild type (WT) activated lymphocytes interact with CD44(-/-) brain vascular endothelial cells (ECs) than with WT ECs. We also find that CD44(-/-) ECs fail to anchor HA to their surfaces, and that slow rolling lymphocyte interactions with WT ECs are inhibited when the ECs are treated with a pegylated form of the PH20 hyaluronidase (PEG-PH20). Subcutaneous injection of PEG-PH20 delays the onset of EAE symptoms by ~1 day and transiently ameliorates symptoms for 2 days following disease onset. These improved symptoms correspond histologically to degradation of HA in the lumen of CNS blood vessels, decreased demyelination, and impaired CD4(+) T-cell extravasation. Collectively these data suggest that HA tethered to CD44 on CNS ECs is critical for the extravasation of activated T cells into the CNS providing new insight into the mechanisms promoting inflammatory demyelinating disease.

Patients' educational needs about topical treatments for psoriasis.

BACKGROUND: Topical medications are a mainstay of psoriasis treatment. Many patients lack education about topicals. This may contribute to low adherence with long-term disease management. OBJECTIVE: We sought to describe educational needs concerning topical treatment for patients with psoriasis. METHODS: Patients' questions regarding topical therapy were collected from a National Psoriasis Foundation webcast on topical medications. The prebroadcast question responses and the postwebcast survey responses were categorized into common themes and ranked by frequency. RESULTS: Thirty percent asked about side effects, with a major emphasis on topical steroids; 16% asked about proper use; and 11% asked about efficacy. Popular new and useful education concerned specific medication facts and information on medication (especially steroid) safety, the need for treatment adherence, and the variety of options available in topical form. LIMITATIONS: The study population consisted of online users expressing interest in the National Psoriasis Foundation educational material, not the general population of patients with psoriasis. CONCLUSIONS: Patient needs can be better met by providing information regarding side effects, proper use, and efficacy of topical medications. Communication regarding treatment changes and adherence to the treatment regimen should also occur.

Variation in dermatologist beliefs about the safety and effectiveness of treatments for moderate to severe psoriasis.

BACKGROUND: Multiple systemic treatments are available for moderate to severe psoriasis, but dermatologists' perceptions of these treatments are unknown. Physician perceptions can influence prescribing patterns and patient outcomes, and may help to explain variations in clinical practice. OBJECTIVE: We sought to describe the variation in dermatologist's beliefs about the safety and effectiveness of psoriasis treatments and evaluate how these relate to dermatologist characteristics and treatment preferences. METHODS: We conducted a cross-sectional mail survey of a random sample of 500 National Psoriasis Foundation (NPF) members and 500 American Academy of Dermatology (AAD) members who treat psoriasis. RESULTS: Of 989 clinicians who could be contacted, 246 NPF members and 141 AAD members returned the survey (39% response rate). Respondents perceived infliximab, ustekinumab, cyclosporine, and adalimumab to have the highest likelihood of skin clearance in 3 months (67%-75%). Etanercept, adalimumab, ultraviolet B, and ustekinumab had the lowest perceived likelihood of side effects requiring treatment discontinuation (9%-11%). Up to 49% of respondents "didn't know" the effectiveness or likelihood of side effects; calculated coefficients of variation were higher for perceived likelihood of side effects than perceived effectiveness. There were few significant associations between safety and effectiveness perceptions and respondent characteristics, and treatment preferences were not consistently predictive of perceptions. LIMITATIONS: Only dermatologists with interest in treating psoriasis were surveyed and general perceptions were elicited via survey format. Perceptions may differ between survey respondents and nonrespondents. CONCLUSIONS: Psoriasis providers demonstrate wide variation in their perception of the effectiveness and especially safety of systemic treatments.

Patient-reported reasons for the discontinuation of commonly used treatments for moderate to severe psoriasis.

BACKGROUND: Despite widespread dissatisfaction and low treatment persistence in moderate to severe psoriasis, patients' reasons behind treatment discontinuation remain poorly understood. OBJECTIVES: We sought to characterize patient-reported reasons for discontinuing commonly used treatments for moderate to severe psoriasis in real-world clinical practice. METHODS: A total of 1095 patients with moderate to severe plaque psoriasis from 10 dermatology practices who received systemic treatments completed a structured interview. Eleven reasons for treatment discontinuation were assessed for all past treatments. RESULTS: A total of 2231 past treatments were reported. Median treatment duration varied by treatment, ranging from 6.0 to 20.5 months (P < .001). The frequency of each cited discontinuation reasons differed by treatment (all P < .01). Patients who received etanercept (odds ratio [OR] 5.19; 95% confidence interval [CI] 3.23-8.33) and adalimumab (OR 2.10; 95% CI 1.20-3.67) were more likely to cite a loss of efficacy than those who received methotrexate. Patients who received etanercept (OR 0.34; 95% CI 0.23-0.49), adalimumab (OR 0.48; 95% CI 0.30-0.75), and ultraviolet B phototherapy (OR 0.21; 95% CI 0.14-0.31) were less likely to cite side effects than those who received methotrexate, whereas those who received acitretin (OR 1.56; 95% CI 1.08-2.25) were more likely to do so. Patients who underwent ultraviolet B phototherapy were more likely to cite an inability to afford treatment (OR 7.03; 95% CI 3.14-15.72). LIMITATIONS: The study is limited by its reliance on patient recall. CONCLUSIONS: Different patterns of treatment discontinuation reasons are important to consider when developing public policy and evidence-based treatment approaches to improve successful long-term psoriasis control.

Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for pustular psoriasis. Meetings were held by teleconference. Consensus on treatment of pustular psoriasis was achieved. Pustular psoriasis has been classified into localized and generalized forms. There are a number of treatment modalities, but there is little evidence-based information to guide the management of this type of psoriasis. OBJECTIVES: The purpose of this article was to present treatment recommendations to aid in the treatment of patients with pustular psoriasis. METHODS: A literature review was conducted to examine treatment options for pustular psoriasis and assess the strength of the literature for each option. RESULTS: Overall the quality of the literature about the treatment of pustular psoriasis is weak. Treatment should be governed by the extent of involvement and severity of disease. Acitretin, cyclosporine, methotrexate, and infliximab are considered to be first-line therapies for those with generalized pustular psoriasis. Adalimumab, etanercept, and psoralen plus ultraviolet A are second-line modalities in this setting. Pustular psoriasis in children, in pregnant women, and in localized forms alter which agents are first-line modalities as concerns such as teratogenicity need to be factored into the decisionmaking for the individual patient. LIMITATIONS: There are few high-quality studies examining treatment options for pustular psoriasis. CONCLUSIONS: Treatment of patients with pustular psoriasis depends on the severity of presentation and patient's underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration.

Dermatologist preferences for first-line therapy of moderate to severe psoriasis in healthy adult patients.

BACKGROUND: Despite increasing therapies for moderate to severe psoriasis, dermatologists' treatment preferences are unknown. OBJECTIVE: We sought to assess dermatologists' preferences for first-line treatments and their selection determinants. METHODS: We surveyed 1000 US dermatologists (500 National Psoriasis Foundation and 500 American Academy of Dermatology members who treat psoriasis) about their preferences for first-line treatment of moderate to severe psoriasis in healthy adults of childbearing age using standardized patient vignettes. RESULTS: The response rate was 39% (N = 387). Preferred therapies for male and female patients were: ultraviolet (UV) B (40% and 56%, respectively), etanercept (15% and 19%), methotrexate (16% and 4%), and adalimumab (12% and 10%). Of respondents, 66% administered phototherapy in their practice. After adjusting for all physician characteristics, those preferring first-line UVB for male or female patients were significantly more likely to have phototherapy in their practice (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.8-6.6 and OR 2.8, 95% CI 1.5-5.3, respectively) and to have used UVB in more than 10 patients in the last 3 months (OR 8.0, 95% CI 3.9-16.4; OR 9.6, 95% CI 4.3-21.6). Dermatologists in the Midwest were more likely than those in the Northeast to prefer adalimumab first line for male and female patients. LIMITATIONS: We surveyed only dermatologists with interest in treating psoriasis and elicited their treatment preferences for a single base case scenario. Treatment preferences may differ between survey respondents and nonrespondents. CONCLUSION: UVB is most commonly preferred as a first-line treatment for moderate to severe psoriasis in healthy adults, and preferences vary based on region, phototherapy availability, and prior treatment use.

Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation.

Demyelination is the hallmark of numerous neurodegenerative conditions, including multiple sclerosis. Oligodendrocyte progenitors (OPCs), which normally mature into myelin-forming oligodendrocytes, are typically present around demyelinated lesions but do not remyelinate affected axons. Here, we find that the glycosaminoglycan hyaluronan accumulates in demyelinated lesions from individuals with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis. A high molecular weight (HMW) form of hyaluronan synthesized by astrocytes accumulates in chronic demyelinated lesions. This form of hyaluronan inhibits remyelination after lysolecithin-induced white matter demyelination. OPCs accrue and do not mature into myelin-forming cells in demyelinating lesions where HMW hyaluronan is present. Furthermore, the addition of HMW hyaluronan to OPC cultures reversibly inhibits progenitor-cell maturation, whereas degrading hyaluronan in astrocyte-OPC cocultures promotes oligodendrocyte maturation. HMW hyaluronan may therefore contribute substantially to remyelination failure by preventing the maturation of OPCs that are recruited to demyelinating lesions.

COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: The continuous increase in the US population older than 65 years and the chronic course of psoriasis make management of psoriasis in the elderly an important health care problem. OBJECTIVE: We sought to develop a treatment algorithm for patients with psoriasis who are older than 65 years. METHODS: A systematic literature search for studies on elderly patients with psoriasis was performed using MEDLINE. RESULTS: We summarize the available published data on therapeutic modalities used in the elderly. We suggest a treatment algorithm including topical medications as first-line treatment for limited disease, with phototherapy, systemic retinoids, methotrexate, and biologics as the first-line systemic treatments for patients with more extensive disease. Cyclosporine should only rarely be used as a second-line systemic treatment for extensive disease in elderly patients with psoriasis. LIMITATIONS: Limited data are available regarding treatment modalities specifically for elderly patients with psoriasis. CONCLUSION: Appropriate treatment for elderly patients with limited psoriasis includes topical corticosteroids, topical vitamin D analogues, and topical tazarotene. For appropriately monitored elderly patients who have psoriasis with extensive disease, phototherapy, acitretin, methotrexate, alefacept, etanercept, adalimumab, infliximab, and ustekinumab are first-line therapies that can generally be safely used. There remains a need for further research on the management of psoriasis in elderly patients with psoriasis.

Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation.

An association between obesity and psoriasis has been reported. For a variety of reasons, obese persons with psoriasis are often more difficult to treat. We sought to review the literature on obesity and psoriasis and to discuss efficacy and safety data that could be utilized by clinicians who are making treatment decisions for obese persons with psoriasis. We performed a literature review using the terms "obesity and psoriasis" and "metabolic syndrome and psoriasis." Evidence from relevant literature was evaluated and categorized according to the criteria of Shekelle et al (published 1999). Numerous reports cite an association between obesity and psoriasis. When compared with non-obese patients with psoriasis, obese patients with psoriasis are more likely to experience certain adverse effects to medications and are less likely to respond favorably to systemic therapies. The amount of category I evidence for objectively determining the best treatment choices for obese patients with psoriasis was scarce and thus did not allow for the development of a treatment algorithm that could be generally applied for all psoriasis patients who are obese. Efficacy and safety concerns affected by obesity are important considerations for clinicians who are making decisions on proper treatment of psoriasis.

Treatment of erythrodermic psoriasis: from the medical board of the National Psoriasis Foundation.

BACKGROUND: Erythrodermic psoriasis is a severe form of psoriasis that can arise acutely or follow a chronic course. There are a number of treatment options, but overall there are few evidence-based data to guide clinicians in managing these challenging cases. OBJECTIVE: Our aim was to create treatment recommendations to help dermatologists treat patients with erythrodermic psoriasis. METHODS: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for erythrodermic or exfoliative psoriasis. Meetings were held by teleconference and were coordinated and funded by the National Psoriasis Foundation. Consensus on treatment of erythrodermic psoriasis was achieved. A literature review was conducted to examine treatment options for erythrodermic psoriasis and the strength of the evidence for each option. RESULTS: There is no high-quality scientific evidence on which to base treatment recommendations. Treatment should be dictated by the severity of disease at time of presentation and the patient's comorbidities. Cyclosporine and infliximab appear to be the most rapidly acting agents for the treatment of erythrodermic psoriasis. Acitretin and methotrexate are also appropriate first-line choices, although they usually work more slowly. Treating physicians can consider a number of second-line agents, including etanercept or combination therapy, in the treatment of patients with erythrodermic psoriasis. Combination therapy may be more effective than a single-agent approach; there is a paucity of scientific data in this area. All patients should be evaluated for underlying infection. Supportive care can help control disease and patient symptoms if instituted appropriately. Physicians should avoid potential exacerbating agents when managing this challenging disease. LIMITATIONS: There are few high-quality studies examining treatment options for erythrodermic psoriasis. CONCLUSION: Treatment of patients with erythrodermic psoriasis demands a thorough understanding of the treatment options available. Therapy should be based on acuity of disease and the patient's underlying comorbidities. There are limited data available to compare treatment options for erythrodermic psoriasis. Further studies are necessary to explore the optimal treatment algorithm for these patients.

Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation.

BACKGROUND: Patients with psoriasis and HIV infection often present with more severe and treatment-refractory cutaneous disease. In addition, many of these patients have significant psoriatic arthritis. Many effective drugs for psoriasis and psoriatic arthritis are immunosuppressive. Therefore, therapy for the HIV-infected patient is more challenging, requiring both careful consideration of the potential risks and benefits of treatment and more fastidious monitoring for potential adverse events. OBJECTIVE: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to arrive at a consensus on therapy for psoriasis in patients with HIV. METHODS: A MEDLINE search of the terms "psoriasis," "psoriatic arthritis," "human immunodeficiency virus (HIV)," and "HIV skin diseases" was performed and literature relevant to HIV-associated psoriasis and the treatment of HIV-associated psoriasis were reviewed. RESULTS: Based on a review of the literature, 29 reports were included as evidence in this review. Topical therapy is the first-line recommended treatment for mild to moderate disease. For moderate to severe disease, phototherapy and antiretrovirals are the recommended first-line therapeutic agents. Oral retinoids may be used as second-line treatment. For more refractory, severe disease, cautious use of cyclosporine, methotrexate, hydroxyurea, and tumor necrosis factor-alpha inhibitors may also be considered. LIMITATIONS: There are no randomized, placebo-controlled trials evaluating the therapeutic efficacy or safety of treatments for patients with HIV-associated psoriasis; consequently, the evidence supporting this review consists mainly of case reports or case series. CONCLUSIONS: HIV-associated psoriasis is often refractory to traditional treatments. Treatment is challenging and requires careful consideration and should be tailored to patients based on disease severity and the input from an infectious disease specialist. Close monitoring for potential adverse events is necessary.

Treatment with selective estrogen receptor modulators regulates myelin specific T-cells and suppresses experimental autoimmune encephalomyelitis.

Steroidal estrogens can regulate inflammatory immune responses and may be involved in the suppression of multiple sclerosis (MS) during pregnancy. However, the risks and side effects associated with steroidal estrogens may limit their usefulness for long-term MS therapy. Selective estrogen receptor modulators (SERMs) could provide an alternative therapeutic strategy, because they behave as estrogen agonists in some tissues, but are either inert or behave like estrogen antagonists in other tissues. In this study, we investigated the ability of two commercially available SERMs (tamoxifen and raloxifene) to regulate myelin specific immunity and experimental autoimmune encephalomyelitis (EAE) in mice. Both tamoxifen and raloxifene suppressed myelin antigen specific T-cell proliferation. However, tamoxifen was more effective in this regard. Tamoxifen treatment reduced the induction of major histocompatibility complex II by lipopolysaccharide stimulated dendritic cells and decreased their ability to activate myelin specific T-cells. At lower doses, tamoxifen was found to increase the levels of Th2 transcription factors and induce a Th2 bias in cultures of myelin-specific splenocytes. EAE symptoms and the degree of demyelination were less severe in mice treated with tamoxifen than in control mice. These findings support the notion that tamoxifen or related SERMs are potential agents that could be used in the treatment of inflammatory autoimmune disorders that affect the central nervous system.

Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: The scalp is the most commonly affected part of the body in patients with psoriasis. Signs and symptoms of scalp psoriasis vary significantly for individual patients. OBJECTIVE: A task force of the National Psoriasis Foundation was convened to evaluate treatment options. Our aim was to achieve a consensus for scalp psoriasis therapy. METHODS: Reports in the medical literature were reviewed regarding scalp psoriasis therapy. LIMITATIONS: There is a paucity of evidence-based and double-blind studies in the treatment of scalp psoriasis particularly for long-term therapy. Many of the studies in scalp psoriasis were designed to attain Food and Drug Administration approval for a medication and not to provide treatment guidance. CONCLUSIONS: The recommended short-term or intermittent therapy for scalp psoriasis is topical corticosteroids. The primary alternatives are topical retinoids, vitamin D analogues, and salicylic acid. Combination therapy has many advantages. The choice of an appropriate vehicle is crucial to increase patient compliance. While scalp psoriasis can often be adequately treated with topical therapy, recalcitrant disease may require more aggressive approaches, including systemic agents.

Treatment of psoriasis in patients with hepatitis C: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: Treating psoriasis in patients with concomitant hepatitis C virus (HCV) infection presents a special challenge. Not only is psoriasis exacerbated by interferon therapy, the standard of care for HCV, but many psoriasis therapies are potentially hepatotoxic, immunosuppressive, or both, which has been generally thought to be a contraindication in chronic infections such as HCV. OBJECTIVE: Our aim was to arrive at a consensus on treating psoriasis in patients with concomitant HCV infection. METHODS: Reports in the literature were reviewed regarding common psoriasis therapies and liver toxicity. RESULTS: Topical therapies are first-line therapy for patients with limited psoriasis and HCV. Ultraviolet B phototherapy may be considered as a second-line treatment when needed. Ultraviolet B phototherapies in combination with topical therapies are first line for patients with moderate to severe psoriasis, and are considered safe in those patients with concomitant HCV infection. Other systemic therapies, such as acitretin, etanercept, and, possibly, other tumor necrosis factor inhibitors, are considered second line. Psoralen plus ultraviolet A should also be considered a second-line therapy. LIMITATIONS: There are few evidence-based studies on treating psoriasis with systemic therapy in patients with pre-existing liver disease. CONCLUSIONS: There are no large double-blind clinical trials addressing the treatment of psoriasis in patients with HCV infection and more studies are needed.