Mio Nakamura

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.

Depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression.

Psoriasis can be a socially isolating disease due to debilitating physical symptoms and the stigma patients feel because of the appearance of their skin. Mental health comorbidities such as anxiety, depression and suicidal ideation and behaviour (SIB) are prevalent in patients with psoriasis. Patients with mild psoriasis can experience psychiatric comorbidities; however, disorders such as depression and SIB are more common in patients with severe psoriasis or psoriatic arthritis. Psychiatric disorders can both result from and contribute to progression of psoriasis, suggesting that psoriasis and psychiatric conditions, such as depression, may have overlapping biological mechanisms. Proinflammatory cytokines such as interleukin (IL)‐1 and IL‐6 are elevated in both psoriasis and depression, indicating that the inflammatory process may be involved in the progression of both diseases. Elevated cytokine levels in the central nervous system cause physiologic and biochemical changes that may contribute to the development of depression. In this review of the literature, we discuss the evidence that supports the association of psoriasis with mental health disorders and the tools used to detect the presence of these comorbidities. Additionally, we review the most prominent hypotheses on the mechanisms by which the inflammatory response and elevated cytokines can cause depression. These results highlight the role that systemic inflammation plays in the various mental health comorbidities associated with psoriasis, including depression and SIB.

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.

Outcomes of Melanoma In Situ Treated With Mohs Micrographic Surgery Compared With Wide Local Excision

Importance Melanoma in situ (MIS) is increasing in incidence, and expert consensus opinion recommends surgical excision for therapeutic management. Currently, wide local excision (WLE) is the standard of care. However, Mohs micrographic surgery (MMS) is now used to treat a growing subset of individuals with MIS. During MMS, unlike WLE, the entire cutaneous surgical margin is evaluated intraoperatively for tumor cells. Objective To assess the outcomes of patients with MIS treated with MMS compared with those treated with WLE. Design, Setting, and Participants Retrospective review of a prospective database. The study cohort consisted of 662 patients with MIS treated with MMS or WLE per standard of care in dermatology and surgery (general surgery, otolaryngology, plastics, oculoplastics, surgical oncology) at an academic tertiary care referral center from January 1, 1978, to December 31, 2013, with follow-up through 2015. Exposure Mohs micrographic surgery or WLE. Main Outcomes and Measures Recurrence, overall survival, and melanoma-specific survival. Results There were 277 patients treated with MMS (mean [SD] age, 64.0 [13.1] years; 62.1% male) and 385 treated with WLE (mean [SD] age, 58.5 [15.6] years; P < .001 for age; 54.8% male). Median follow-up was 8.6 (range, 0.2-37) years. Compared with WLE, MMS was used more frequently on the face (222 [80.2%] vs 141 [36.7%]) and scalp and neck (23 [8.3%] vs 26 [6.8%]; P < .001). The median (range) year of diagnosis was 2008 (1986-2013) for the MMS group vs 2003 (1978-2013) for the WLE group (P < .001). Overall recurrence rates were 5 (1.8%) in the MMS group and 22 (5.7%) in the WLE group (P = .07). Mean (SD) time to recurrence after MMS was 3.91 (4.4) years, and after WLE, 4.45 (2.7) years (P = .73). The 5-year recurrence rate was 1.1% in the MMS group and 4.1% in the WLE group (P = .07). For WLE-treated tumors, the surgical margin taken was greater for tumors that recurred compared with tumors that did not recur (P = .003). Five-year overall survival for MMS was 92% and for WLE was 94% (P = .28). Melanoma-specific mortality for the MMS group was 2 vs 13 patients for the WLE group, with mean (SD) survival of 6.5 (4.8) and 6.1 (0.8) years, respectively (P = .77). Conclusions and Relevance No significant differences were found in the recurrence rate, overall survival, or melanoma-specific survival of patients with MIS treated with MMS compared with WLE.

Monoclonal antibodies inhibiting IL-12, -23, and -17 for the treatment of psoriasis

ABSTRACT Psoriasis is a chronic, inflammatory, immune-mediated skin condition that affects 3 to 4% of the adult US population, characterized by well-demarcated, erythematous plaques with silver scale. Psoriasis is associated with many comorbidities including cardiometabolic disease and can have a negative impact on quality of life. The current armamentarium of psoriasis treatment includes topical therapies, phototherapy, oral immunosuppressive therapies, and biologic agents. Over the past 2 decades, there has been rapid development of novel biologic therapies for the treatment of moderate-to-severe plaque psoriasis. This article will review the role of IL-12, IL-23, and IL-17 in the pathogenesis of psoriasis and the monoclonal antibodies (ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab) that target these cytokines in the treatment of this disease.

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.

Cutaneous Carcinogenic Risk of Phototherapy: An Updated Comprehensive Review:

Phototherapy is among the oldest and most highly effective treatment modalities available for moderate-to-severe psoriasis. However, concern regarding the potential carcinogenic risk associated with ultraviolet B (UVB) phototherapy and/or psoralen with ultraviolet A (PUVA) has been expressed by both providers and patients. The purpose of this review is to assess the cutaneous malignancy risks of UVB phototherapy and/or PUVA in all skin types, including Caucasian and non-Caucasian patients. We searched the MEDLINE database for original research articles regarding the skin cancer risk of phototherapy. A total of 61 articles were included. In Caucasians, an increased risk of squamous cell carcinoma with PUVA therapy was reported after >250 sessions, whereas studies among non-Caucasians did not show any increased risk. There was no convincing evidence of increased skin cancer risk associated with UVB phototherapy among all skin types. In view of the continued validation of its safety, phototherapy remains a valuable treatment option for patients with moderate-to-severe psoriasis.