Benjamin Farahnik

The role of IL-17 in vitiligo: A review

IL-17 is involved in the pathogenesis of several autoimmune diseases; however its role in vitiligo has not been well defined. Emerging human and mouse studies have demonstrated that systemic, tissue, and cellular levels of IL-17 are elevated in vitiligo. Many studies have also shown significant positive correlations between these levels and disease activity, extent, and severity. Treatments that improve vitiligo, such as ultraviolet B phototherapy, also modulate IL-17 levels. This review synthesizes our current understanding of how IL-17 may influence the pathogenesis of autoimmune vitiligo at the molecular level. This has implications for defining new vitiligo biomarkers and treatments.

Recent advances in phototherapy for psoriasis.

Phototherapy involves repeated exposure of the skin to ultraviolet light to treat various inflammatory skin conditions such as psoriasis. Recent studies have identified specific immunologic effects of phototherapy that may underlie phototherapy efficacy. Furthermore, recent advancements have been made in developing safe and effective targeted phototherapy modalities for difficult-to-treat areas such as scalp psoriasis. Targeted phototherapy in the form of the excimer laser holds potential for more aggressive, effective treatment and long-lasting remission of psoriasis. Phototherapy is now also used successfully with biologic agents as combination therapy to treat recalcitrant psoriasis. Therefore, though one of the oldest therapeutic modalities for psoriasis, phototherapy remains a mainstay treatment with promise for further advancement.

Demyelinating disorders secondary to TNF-inhibitor therapy for the treatment of psoriasis: A review

Abstract Background: Tumor necrosis factor-α inhibitors (TNFi) are the most widely used systemic treatments for patients with psoriasis and psoriatic arthritis. There currently exists a U.S. Food and Drug Administration issued warning label on all TNFi for “rare cases of new onset or exacerbation of central nervous system demyelinating disorders.” The aim of this review was to update the incidence of TNFi-induced demyelinating diseases. Methods: Pubmed database was searched for safety data regarding demyelinating disease secondary to TNFi therapy prescribed for psoriasis. Results: In clinical trials: 6990 patients had received treatment with etanercept with one reported case of multiple sclerosis; 5204 patients were treated with adalimumab with no cases identified and 2322 patients were treated with infliximab with one case of demyelinating polyneuropathy. Outside of clinical trials: 19 individual cases of demyelinating disorders from TNFi treatment have been reported. Conclusion: Although there is potential for TNF blockade to lead to demyelination of the central and peripheral nervous systems, the results of the present review suggest that demyelinating diseases associated with TNFi are extremely rare. TNFi are not recommended for use in patients with a personal history of demyelinating disease. However, with clinical vigilance and individualized treatment regimen, TNFi may be safe for use in other patients.

The Patient’s Guide to Psoriasis Treatment. Part 1: UVB Phototherapy

BackgroundPsoriasis is a chronic immune-mediated disease that affects 2–3% of the world population. Ultraviolet B (UVB) phototherapy is an effective treatment for psoriasis compared to other systemic treatments. Currently there is a lack of easily accessible online patient educational material regarding this form of treatment.ObjectiveTo present a freely available online guide and video on UVB treatment that is informative to patients and increases the success and compliance of patients starting this therapy.MethodsThe UVB treatment protocol used at the University of California—San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving UVB treatment.ResultsWe created a printable guide and video resource that reviews the fundamentals of UV light, UVB safety considerations, flow of treatment, side effects, and post-phototherapy skin care.ConclusionThis guide serves as a valuable resource for patients preparing for UVB phototherapy, the clinicians who treat them, and trainees wishing to learn more about this form of therapy.

The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury

As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies.

Eczema as an adverse effect of anti-TNFα therapy in psoriasis and other Th1-mediated diseases: a review

Abstract Introduction: There have been rare reports of eczema occurring as an adverse effect of anti-tumor necrosis factor-alpha (TNFα) therapy. Methods: A literature search was conducted on PubMed for articles describing new onset or worsening of preexisting eczema during anti-TNFα therapy for the treatment of various inflammatory diseases. Results: Eczema as an adverse effect of anti-TNFα therapy may occur in approximately 5–20% of patients with various Th1-mediated inflammatory diseases such as psoriasis, inflammatory arthritis and inflammatory bowel disease. Personal history of atopy appears to increase this risk. Out of the anti-TNFα agents indicated for the treatment of moderate-to-severe psoriasis, infliximab may be more strongly associated with development or exacerbation of preexisting eczema. Discussion: Inhibitors of key mediators in the Th1 pathway such as TNFα are successful therapeutic targets for the treatment of various inflammatory conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. Blocking the Th1 pathway may create an imbalance favoring increased activity of the opposing Th2 pathway implicated in inflammatory conditions such as eczema. Further research is needed to better understand the role of the Th1/Th2 balance in various inflammatory diseases and how the immunologic environment is affected by immunotherapies.

Interventional treatments for Hailey-Hailey disease.

Hailey-Hailey disease or familial benign chronic pemphigus is a rare blistering dermatosis that is characterized by recurrent erythematous plaques with a predilection for the skin folds. For extensive Hailey-Hailey disease that is recalcitrant to conventional therapy, laser ablation, photodynamic therapy, electron beam radiotherapy, botulinum toxin type A, dermabrasion, glycopyrrolate, and afamelanotide have been reported as useful treatments, but comparative trials are lacking. This review discusses the various treatment modalities for Hailey-Hailey disease and a summary of the evidence for the most recommended treatments.

Obsessive-compulsive skin disorders: a novel classification based on degree of insight

Abstract Individuals with obsessive-compulsive features frequently visit dermatologists for complaints of the skin, hair or nails, and often progress towards a chronic relapsing course due to the challenge associated with accurate diagnosis and management of their psychiatric symptoms. The current DSM-5 formally recognizes body dysmorphic disorder, trichotillomania, neurotic excoriation and body focused repetitive behavior disorder as psychodermatological disorders belonging to the category of Obsessive-Compulsive and Related Disorders. However there is evidence that other relevant skin diseases such as delusions of parasitosis, dermatitis artefacta, contamination dermatitis, AIDS phobia, trichotemnomania and even lichen simplex chronicus possess prominent obsessive-compulsive characteristics that do not necessarily fit the full diagnostic criteria of the DSM-5. Therefore, to increase dermatologists’ awareness of this unique group of skin disorders with OCD features, we propose a novel classification system called Obsessive-Compulsive Insight Continuum. Under this new classification system, obsessive-compulsive skin manifestations are categorized along a continuum based on degree of insight, from minimal insight with delusional obsessions to good insight with minimal obsessions. Understanding the level of insight is thus an important first step for clinicians who routinely interact with these patients.

Striae gravidarum: Risk factors, prevention, and management

Background Striae gravidarum (SG) are atrophic linear scars that represent one of the most common connective tissue changes during pregnancy. SG can cause emotional and psychological distress for many women. Research on risk factors, prevention, and management of SG has been often inconclusive. Methods We conducted a literature search using textbooks, PubMed, and Medline databases to assess research performed on the risk factors, prevention, and management of SG. The search included the following key words: striae gravidarum, pregnancy stretch marks, and pregnancy stretch. We also reviewed citations within articles to identify relevant sources. Results Younger age, maternal and family history of SG, increased pre-pregnancy and pre-delivery weight, and increased birth weight were the most significant risk factors identified for SG. Although few studies have confirmed effective prevention methods, Centella asiatica extract, hyaluronic acid, and daily massages showed some promise. Treatment for general striae has greatly improved over the last few years. Topical tretinoin ≥ 0.05% has demonstrated up to 47% improvement of SG and non-ablative fractional lasers have consistently demonstrated 50 to 75% improvement in treated lesions of striae distensae. Conclusion Overall, SG has seen a resurgence in research over the last few years with promising data being released. Results of recent studies provide dermatologists with new options for the many women who are affected by these disfiguring marks of pregnancy.

Emerging targeted therapies for plaque psoriasis – impact of ixekizumab

Background Recent studies into the pathogenesis of psoriasis have identified the importance of interleukin 17 (IL-17) in disease activity and have thus provided a new target for biologic therapy. Ixekizumab, the most recent US Food and Drug Administration (FDA)-approved anti-IL-17 biologic agent, appears to be a promising medication for patients suffering from moderate-to-severe plaque psoriasis. Methods We reviewed the results of phase III trials for ixekizumab in order to assess the efficacy, safety, and impact on quality of life of this agent in the treatment of plaque psoriasis. Additionally, we compared these results to phase II and phase III trials for other biologic psoriasis medications including the anti-IL-23 agents tildrakizumab and guselkumab, the combined anti-IL-12 and anti-IL-23 agent ustekinumab, and the anti-IL-17 agents brodalumab and secukinumab. Results Pooled results from individual studies demonstrate that among the most efficacious dosing regimens of these anti-interleukin therapies, ixekizumab achieves higher Psoriasis Area and Severity Index 75 rates and similar or higher static Physician Global Assessment 0-1 rates than the other anti-IL-17 and anti-IL-23 agents. The safety profile of ixekizumab is similar to these agents, with nasopharyngitis, upper respiratory infection, headache, arthralgia, and injection-site erythema as the most commonly reported adverse events. Conclusion Ixekizumab is a highly efficacious, newly FDA-approved treatment for moderate-to-severe plaque psoriasis that demonstrates a robust clinical response, significant improvement in patient quality of life, and a favorable safety profile.