Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Antihistamines in Psoriasis.

Psoriasis is polygenic, interleukin (IL)-17 and IL-23 driven chronic relapsing inflammatory multisystem disease caused by a complex interplay of endogenous and environmental factors. The most common and distressing symptom in psoriasis is itch, adding significantly to the burden of disease. Although histamine has historically not been considered a key itch mediator in psoriasis, there is some evidence from the literature that antihistamines may be effective to reduce itch in psoriasis. This review focuses on the role of antihistamines in the management of itch in psoriasis. The literature search included peer-reviewed articles published in English language (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) until January 2021 and by reference lists of respective articles. J Drugs Dermatol. 2021;20(8):844-847. doi:10.36849/JDD.5966.

Interleukin 23p19 inhibitors in chronic plaque psoriasis with focus on mirikizumab: A narrative review.

Psoriasis, a T-cell mediated chronic dermatosis, has a complex etiopathogenesis. There has been extensive research into the aberrant immune response, which leads to the formation of clinical lesions, and the need for developing better and safer drugs has been unrelenting. The past two decades of research has opened up new areas of the immune pathway that can be targeted in order to control the disease. Therefore, we have seen the emergence of biologics which either target T-cell receptors or inhibit Tumor Necrosis Factor-alpha (TNF-α) or inhibit interleukins (IL) like IL-12, IL-17, IL-17 receptor, and more recently IL-23. Drugs specifically targeting the p19 subunit of IL-23 have shown promising results in the management of chronic plaque psoriasis. This has given way to the development of a new class of biologics, that is, the IL-23p19 inhibitors that have a better safety profile as compared to its predecessors. In this review, we shall scrutinize the role of IL-23 and Th17 cell signaling in the evolution of the psoriatic lesions and summarize the clinical experience with IL-23p19 inhibitors especially mirikizumab in the treatment of chronic plaque psoriasis.

Necrobiosis Lipoidica Mimicking Cutaneous Sarcoidosis Finally Treated With an Intralesional Injection of Corticosteroid: A Case Report

BACKGROUND: Necrobiosis lipoidica (NL) and sarcoidosis are granulomatous disorders with an unknown pathogenesis. They may coexist in the same patient, which suggests a possible overlap between these diseases among shared granulomatous inflammatory pathways. Case Presentation: This study presents the case of a non-diabetic 52-year-old woman who presented with red-yellowish border plaques on the face and upper extremities previously diagnosed as sarcoidosis. After 13 years of inappropriate treatment, histopathological findings consistent with the clinical and para-clinical examination suggested the diagnosis of NL. After treatment with an intralesional injection of steroids, significant improvement was observed, and no recurrent lesions were found. CONCLUSION: Necrobiosis lipoidica may mimic cutaneous sarcoidosis. Prompt recognition and treatment of NL can be helpful for managing the disease. J Drugs Dermatol. 2020;19(1):92-94. doi:10.36849/JDD.2020.4675

Pityriasis Lichenoides Chronica in a Patient With Ankylosing Spondylitis Treated With Etanercept.

BACKGROUND: Pityriasis lichenoides chronica, a papulosquamous disorder often considered a subtype of pityriasis lichenoides. It is considered a clonal T-cell disorder, which may be associated with cutaneous T-cell lymphoma that may develops in response to foreign antigens. CASE PRESENTATION: We present a 38-year-old male patient with ankylosing spondylitis who was on treatment with etanercept. After 8 weeks of treatment, the patient presented with scaly erythematous papules, on the back and arms. He was diagnosed clinically with pityriasis lichenoides chronica. CONCLUSION: Pityriasis lichenoides chronica should be included among the broad clinical spectrum of chronic inflammatory skin diseases which may occur during treatment with TNF-alpha antagonists. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.2191.

Pityriasis Lichenoides Chronica in a Patient With Ankylosing Spondylitis Treated With Etanercept.

Pityriasis lichenoides is a scarce cutaneous disorder with unknown etiology. It contains a range of clinical manifestations including acute papular lesions that quickly grow into pseudo vesicles and central necrosis to small, scaling, benign-appearing papules.1,2.

Clinical and Molecular Effects of Interleukin-17 Pathway Blockade in Psoriasis

The interleukin-17 (IL-17) pathway plays a crucial role in the development of psoriasis. Briefly, naive T cells differentiate into helper T (Th17) cells through interaction with activated dendritic cells in the presence of IL-23, Th17 cells produce IL-17 cytokines, and keratinocytes stimulated by IL-17 ligands lead to aberrant differentiation and proliferation that promote production of proinflammatory chemokines and further recruitment of inflammatory cells, setting up a positive feedback loop. Currently, 3 US Food and Drug Administration­approved agents to treat psoriasis affect the IL-17 pathway: brodalumab, secukinumab, and ixekizumab. Brodalumab is a fully human IL-17 receptor A antagonist that blocks signaling of multiple downstream inflammatory cytokines involved in psoriasis. Secukinumab and ixekizumab selectively bind to and neutralize only IL-17A. Pharmacologic effects in patients with psoriasis include decreased keratinocyte hyperproliferation, reduced epidermal thickening, decreased inflammatory markers, and resolution of histologic and genomic features of psoriasis. In clinical trials, therapeutic doses of brodalumab, secukinumab, and ixekizumab have demonstrated skin clearance efficacy by psoriasis area and severity index and static physician's global assessment scores at 12 weeks. The immunomodulation of these agents is associated with a favorable safety profile. Overall, the clinical improvement and normalization of genetic hallmarks of psoriasis provide a strong case for the unique role of IL-17 receptor blocking as a therapeutic mechanism of action to treat psoriasis. Understanding the unique mechanisms by which treatments interact with the IL-17 pathway to inhibit downstream proinflammatory signal cascade can help physicians make informed treatment decisions when selecting the appropriate medication for patients. J Drugs Dermatol. 2020;19(2)138-143. doi:10.36849/JDD.2020.4645

Successful Treatment of Refractory Plaque-Type Psoriasis and Psoriatic Arthritis With Guselkumab and Adalimumab Combination Therapy: A Case Report

Copy: A number of biologics have been approved for use in plaque-type psoriasis. They act by either blocking the action of a specific type of cell or protein in the immune system. Case presentation: Herein, we report a case of a 46-year-old woman with a 12-year history of severe plaque psoriasis and psoriatic arthritis who was treated successfully with guselkumab and adalimumab after failure of prior topical corticosteroids, cyclosporine and narrow-band ultraviolet B (NBUVB) phototherapy. Conclusion: There is limited data supporting the combination of biological agents in the management of psoriasis and psoriatic arthritis. This is the first case report of plaque psoriasis with arthritis, successfully treated with guselkumab and adalimumab combination therapy, without concurrent use of other systemic agents during the treatment. However, further studies need to be carried out to evaluate the efficacy and safety of this biologic combination therapy. J Drugs Dermatol. 2019;18(4):394-396.

Management of psoriasis in patients with inflammatory bowel disease: From the Medical Board of the National Psoriasis Foundation.

BACKGROUND: There is a significant association between psoriasis and inflammatory bowel disease (IBD). Many treatments for psoriasis and psoriatic arthritis are also used for IBD. OBJECTIVE: To assess therapeutic options for patients with psoriasis and concurrent IBD. METHODS: A systematic literature search was performed for clinical studies of biologic and systemic psoriasis medications in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease, for the period from January 1, 1947, to February 14, 2017. Randomized, controlled, double-blinded studies were selected if available. If not, the next highest level of available evidence was selected. RESULTS: Of the 2282 articles identified, 132 were selected. Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative; colitis, and Crohn's disease. Ustekinumab has demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn's disease. Certolizumab has demonstrated efficacy in psoriatic arthritis and Crohn's disease. Etanercept, secukinumab, brodalumab, and ixekizumab have demonstrated efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD. Guselkumab has demonstrated efficacy in psoriasis. LIMITATIONS: There are no known clinical trials of treatment specifically for concurrent psoriasis and IBD. CONCLUSIONS: Infliximab and adalimumab have demonstrated efficacy in psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease; other agents have demonstrated efficacy for some, but not all, of these indications.

Herpes zoster in psoriasis patients treated with tofacitinib.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models. RESULTS: One hundred thirty (3.6%) patients on tofacitinib (IR 2.55), no patients on placebo, and 2 using etanercept (IR 2.68) developed HZ. Nine patients (7%) were hospitalized, and 8 (6%) had multidermatomal HZ; no encephalitis, visceral involvement, or deaths occurred. In total, 121 (93%) patients on tofacitinib continued or resumed use after HZ. HZ risk factors included Asian descent (hazard ratio [HR] 2.92), using tofacitinib 10 mg twice daily (vs 5 mg twice daily; HR 1.72), prior use of biologics (HR 1.72), and older age (HR 1.30). LIMITATIONS: Generalizability to other psoriasis populations might be limited. The effect of HZ vaccination was not studied. CONCLUSION: Tofacitinib is associated with increased HZ risk relative to placebo. Asian race, increasing age, higher dose, and prior biologic exposure are associated with heightened risk.

From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

BACKGROUND: An urgent need exists in the United States to establish treatment goals in psoriasis. OBJECTIVE: We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. METHODS: The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. RESULTS: A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. LIMITATIONS: Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. CONCLUSION: With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.

From the Medical Board of the National Psoriasis Foundation: Perioperative management of systemic immunomodulatory agents in patients with psoriasis and psoriatic arthritis.

Treatment with systemic immunomodulatory agents is indicated for patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these patients, surgery may confer an increased risk of infectious or surgical complications. We conducted a literature review to examine studies addressing the use of methotrexate, cyclosporine, and targeted immunomodulatory agents (tumor necrosis factor-alfa inhibitors, interleukin [IL]-12/23 inhibitors, IL-17 inhibitors) in patients undergoing surgery. We examined 46 total studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. One study in patients with psoriasis and psoriatic arthritis reviewed 77 procedures and did not find an elevated risk of postoperative complications with tumor necrosis factor-alfa and IL-12/23 inhibitors even with major surgeries. Based on level III evidence, infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.

Novel psoriasis therapies and patient outcomes, Part 3: Systemic medications.

The therapeutic armamentarium for patients with psoriasis and psoriatic arthritis (PsA) has been strengthened by research affording more individualized treatment regimens with new therapeutic targets. In this article, new systemic therapies for psoriasis are discussed, including a review of the relevant clinical trials for novel therapeutics and their respective mechanisms of action, patient outcomes, and safety profiles. This article is the final installment in a 3-part series on agents in the pipeline for the management of psoriasis and PsA including topical agents, biologic treatments, and systemic therapies in phase 2 through phase 4 clinical trials. These systemic agents offer patients more targeted treatment regimens with the prospect of enhanced therapeutic efficacy and more favorable side-effect profiles with better tolerability.

Novel psoriasis therapies and patient outcomes, part 1: topical medications.

In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on potential therapeutic targets, which has led to the development of several new promising treatments. In this article, key clinical trials, mechanisms of action, patient outcomes, and relevant safety information for these novel topical medications will be evaluated. This article is the first in a 3-part series on treatments presently in the pipeline for the management of psoriasis and psoriatic arthritis including topical agents, biologic treatments, and systemic therapies in phase 2 and phase 3 clinical trials. With novel approaches to the disease process, these therapies may afford more targeted individualized treatment regimens and offer hope to patients with psoriasis and psoriatic arthritis who have reported a suboptimal therapeutic response to conventional therapies.

Novel psoriasis therapies and patient outcomes, part 2: biologic treatments.

Biologic treatments have revolutionized the management of psoriasis and psoriatic arthritis (PsA). Anti-tumor necrosis factor (TNF) α monoclonal antibodies presently are approved by the US Food and Drug Administration (FDA) for treatment of these conditions. In this article, new therapies that target this pathway and other steps in the pathogenesis of psoriasis and PsA are discussed, including IL-12/IL-23, IL-17, T-cell activation in antigen-presenting cells, regulatory T cells, toll-like receptors, and granulocyte-macrophage colony-stimulating factor. This article is the second in a 3-part series on treatments presently in the pipeline for the management of psoriasis and PsA including topical agents, biologic treatments, and systemic therapies in phase 2 through phase 4 clinical trials as well as agents that are recently FDA approved. Pivotal clinical trials, mechanisms of action, patient outcomes, and pertinent safety information will be discussed for each new therapy. As our knowledge of the underlying pathogenesis of psoriasis and PsA deepens, it enables the development of more targeted therapies in the management of these conditions.

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.

Acitretin.

Acitretin, a synthetic retinoid, is the pharmacologically active metabolite of etretinate. It is currently approved by the US Food and Drug Administration for the treatment of severe psoriasis in adults and has been established as a second-line therapy for the treatment of psoriasis resistant to the use of topical therapy. It is also an option for generalized pustular psoriasis, palmoplantar pustulosis, exfoliative erythrodermic psoriasis, and severe psoriasis in the setting of acitretin. It also has been shown to have chemo-preventative characteristics. Acitretin is limited by its teratogenicity and therefore considered inappropriate in most female patients of childbearing age. Common side effects include mucocutaneous dryness and elevated triglycerides.

Therapeutic application of machine learning in psoriasis: A Prisma systematic review.

Dermatology, being a predominantly visual-based diagnostic field, has found itself to be at the epitome of artificial intelligence (AI)-based advances. Machine learning (ML), a subset of AI, goes a step further by recognizing patterns from data and teaches machines to automatically learn tasks. Although artificial intelligence in dermatology is mostly developed in melanoma and skin cancer diagnosis, advances in AI and ML have gone far ahead and found its application in ulcer assessment, psoriasis, atopic dermatitis, onychomycosis, etc. This article is focused on the application of ML in the therapeutic aspect of psoriasis.

Psoriasis: Embarking a dynamic shift in the skin microbiota.

Recent interest has arisen regarding the role of microbiome and its composition in the pathogenesis of psoriasis. Numerous studies have shown that there are alterations in skin flora arrangement between normal individuals and psoriatic patients. Psoriasis exacerbation could be interconnected with epidermal or mucosal colonization with streptococci, Malassezia, Staphylococcus aureus, or Candida albicans. The role of cutaneous and gut microbiome in psoriasis pathogenesis has recently been studied in both human and animal models. In this review, we try to evaluate various pathogenic mechanisms linking the microbiota and psoriasis. The literature research included peer-reviewed articles which included clinical trials, original reports, and scientific reviews. MEDLINE and PubMed databases were searched from January 1990 to March 2021, including the reference lists of articles meeting our criteria.