Abby S. Van Voorhees

Guidelines of care for the management of psoriasis and psoriatic arthritis Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis.

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with an emphasis on the biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

TSLP Elicits IL-33–Independent Innate Lymphoid Cell Responses to Promote Skin Inflammation

Group 2 innate lymphoid cells are essential to the pathogenesis of atopic dermatitis–like disease in a TSLP-dependent, IL-33–independent manner. Immune Cell Activity at the Skin Barrier The skin acts like soft armor, protecting the body from disease and environmental insults. In atopic dermatitis (AD), this barrier is disrupted, leading to inflammation. The role of various immune cells in this chronic disease has not been clear. Now, Kim and colleagues identify a subset of innate lymphoid cells (ILCs) in both human and mouse skin that contribute to disease pathogenesis. ILCs have been reported in inflamed nasal polyps in people, as well as in inflamed lungs in mice. Hypothesizing that they also play a role in skin inflammation, Kim et al. analyzed cells isolated from the skin tissue of healthy control subjects and from the lesions of AD patients. There were more Lin− CD25+ IL-33R+ RORγt− group 2 ILCs (ILC2s) in the lesions of AD patients. In healthy mouse skin, the authors identified a similar ILC2 population. AD in humans is linked to cytokines interleukin-33 (IL-33), IL-25, and thymic stromal lymphopoietin (TSLP) in the skin. To this end, the authors investigated in mice whether the ILC2s played a role in inflammation at the skin barrier and if they were dependent on these cytokines. In a mouse model of AD, Kim et al. noted that ILC2s were increased and that AD pathogenesis was initiated independently of adaptive immunity and RORγt+ cells (a marker of group 3 ILCs). The mechanism was also independent of IL-25 and IL-33—which are normally implicated in group 2 ILC responses—yet dependent on TSLP. Depletion of the ILCs attenuated AD-like dermatitis in mice. Group 2 ILCs have not yet been described in skin barrier function in humans. In these studies, Kim and colleagues show that ILC2s are always present in healthy skin, but accumulate in AD lesions and function by a mechanism that contrasts what has been reported in lungs and intestine. Future functional studies will be needed for human ILC2s in skin inflammation, but these preliminary data in mice and humans suggest that targeting group 2 ILCs will be a viable target for treating AD and other allergic diseases. Innate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines interleukin-5 (IL-5) and IL-13 and promote type 2 inflammation in the lung and intestine. However, whether group 2 ILCs reside in the skin and contribute to skin inflammation has not been characterized. We identify a population of skin-resident group 2 ILCs present in healthy human skin that are enriched in lesional human skin from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin and were critical for the development of inflammation in a murine model of AD-like disease. Remarkably, in contrast to group 2 ILC responses in the intestine and lung, which are critically regulated by IL-33 and IL-25, group 2 ILC responses in the skin and skin-draining lymph nodes were independent of these canonical cytokines but were critically dependent on thymic stromal lymphopoietin (TSLP). Collectively, these results demonstrate an essential role for IL-33– and IL-25–independent group 2 ILCs in promoting skin inflammation.

Systemic and Vascular Inflammation in Patients With Moderate to Severe Psoriasis as Measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography –Computed Tomography (FDG-PET/CT): A Pilot Study

OBJECTIVE To evaluate the feasibility of using [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) to detect and quantify systemic inflammation in patients with psoriasis. DESIGN Case series with a nested case-control study. SETTING Referral dermatology and preventive cardiology practices. PARTICIPANTS Six patients with psoriasis affecting more than 10% of their body surface area and 4 controls age and sex matched to 4 of the patients with psoriasis for a nested case-control study. MAIN OUTCOME MEASURES The FDG uptake in the liver, musculoskeletal structures, and aorta measured by mean standardized uptake value, a measure of FDG tracer uptake by macrophages and other inflammatory cells. RESULTS FDG-PET/CT identified numerous foci of inflammation in 6 patients with psoriasis within the skin, liver, joints, tendons, and aorta. Inflammation in the joints was observed in a patient with psoriatic arthritis as well as in 1 patient with no history of joint disease or joint symptoms. In a nested case-control study, FDG-PET/CT imaging demonstrated increased vascular inflammation in multiple segments of the aorta compared with controls. These findings persisted after adjustment for traditional cardiovascular risk factors in multivariate analysis (mean β = 0.33; P < .001). Patients with psoriasis further demonstrated increased hepatic inflammation after adjusting for cardiovascular risk factors (β = 0.18; P < .001), but the association was no longer significant when adjusted for alcohol intake (β = -0.25; P = .07). CONCLUSION FDG-PET/CT is a sensitive tool for identifying inflammation and can be used to identify clinically observed inflammation in the skin and subclinical inflammation in the blood vessels, joints, and liver of patients with psoriasis.

National Psoriasis Foundation consensus statement on screening for latent tuberculosis infection in patients with psoriasis treated with systemic and biologic agents

BACKGROUND Chronic immunosuppression is a known risk factor for allowing latent tuberculosis (TB) infection to transform into active TB. Immunosuppressive/immunomodulatory therapies, while highly efficacious in the treatment of psoriasis and psoriatic arthritis, may be associated with an increased rate of active TB in patients receiving some of these therapies. OBJECTIVE Our aim was to arrive at a consensus on screening for latent TB infection in psoriasis patient treated with systemic and biologic agents. METHODS Reports in the literature were reviewed regarding immunosuppressive therapies and risk of TB. RESULTS Screening patients for latent TB infection before commencement of treatment is of utmost importance when beginning treatment with the tumor necrosis factor-alpha inhibitors, T-cell blockers, cyclosporine, or methotrexate. The currently recommended method for screening is the tuberculin skin test. It is preferable that positively screened patients be treated with a full course of latent TB infection prophylaxis before immunosuppressive/immunomodulatory therapy is initiated. However, in the opinion of many experts, patients may be started on the immunosuppressive/immunomodulatory therapy after 1 to 2 months, if their clinical condition requires, as long as they are strictly adhering to and tolerating their prophylactic regimen. LIMITATIONS There are few evidence-based studies on screening for latent TB infection in psoriasis patients treated with systemic and biologic agents. CONCLUSIONS The biologic TNF-alpha inhibitors are very promising in the treatment of psoriasis. However, because TNF-alpha is also an important cytokine in preventing TB infection and in keeping latent TB infection from becoming active disease, the use of TNF-alpha inhibitors has been associated with an increased risk of developing active TB. A higher incidence of TB has also been reported with other immunosuppressive/immunomodulatory treatments for psoriasis. It is, therefore, of utmost importance to appropriately screen all patients for latent TB infection prior to initiating any immunologic therapy. Delaying immunologic therapy until latent TB infection prophylaxis is completed is preferable. However, if the patient is adhering to his prophylactic regimen and is appropriately tolerating the regimen, therapy may be started after 1 to 2 months if the clinical condition requires.

Consensus Guidelines for the Management of Plaque Psoriasis

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies

BACKGROUND Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD. OBJECTIVE We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes. RESULTS Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain. LIMITATIONS Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor. CONCLUSION Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies.

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 patients underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration.

Psoriasis and comorbid diseases: Epidemiology

Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psoriasis remains unknown; however, shared inflammatory pathways, cellular mediators, genetic susceptibility, and common risk factors are hypothesized to be contributing elements. As additional psoriasis comorbidities continue to emerge, education of health care providers is essential to ensuring comprehensive medical care for patients with 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 patients 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 patients 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.