Treatment of Plaque Psoriasis With an Excimer Laser Utilizing an Optimal Therapeutic UVB Dose Protocol.

Background: Traditionally, treatment with the excimer laser requires determining the minimal erythema dose on healthy skin or using plaque-based induration; however, these protocols often lead to underdosing of psoriatic plaques and reduced treatment efficacy. Objective: To prospectively evaluate the effect of the excimer laser on plaque psoriasis using an optimal therapeutic dose (OTD) protocol. Methods: Subjects with stable plaque psoriasis were tested with the Multi-Microdose (MMD) tip on the XTRAC excimer laser to determine a minimum blistering dose (MBD). Treatment was then initiated at 20% less than the MBD. A single psoriatic lesion was treated once weekly for up to 11 sessions. The change from baseline of the target lesion's modified psoriasis area severity index (mPASI), quality of life and safety were evaluated. Results: Thirteen subjects with a mean age of 48.9±14.9 years and Fitzpatrick skin types I-IV participated in the study. Target plaque mPASI significantly decreased at all time points relative to baseline with significant improvement by the second treatment. Patients reached mPASI-75 within 5±2 sessions. By the end of the study 92% of patients achieved mPASI-75. On average, patients maintained an mPASI score ≥50% for 60 days. Treatment was well tolerated with no erosions or hyperpigmentation. Erythema was the most common adverse event. Conclusion: The OTDTM protocol with the MMD® tip allows determining the optimal dose locally on the psoriatic plaque itself. Consequently, ineffectual dosing levels and treatments are minimized. The OTD protocol reduces treatment frequency from 2-3 times per week to once weekly. J Drugs Dermatol. 2020;19(4):349-354. doi:10.36849/JDD.2020.4891.

Association of Postoperative Antibiotics With Surgical Site Infection in Mohs Micrographic Surgery.

BACKGROUND: Surgical site infection (SSI) is the most frequent complication of Mohs micrographic surgery. Previous studies have identified risk factors for SSI, but it is not known whether antibiotic prophylaxis mitigates this risk. OBJECTIVE: To measure the association between antibiotic prophylaxis and SSI in a convenience sample of Mohs cases and to report on the utility of propensity scoring to control for confounding by indication in registry data. METHODS: Data were drawn from a pilot quality improvement registry of 816 Mohs cases. The relationship between antibiotic prophylaxis and SSI was assessed with logistic regression modeling using propensity score methods to adjust for confounding. RESULTS: One hundred fifty-one cases were prescribed antibiotic prophylaxis (18.5%). Of 467 cases with follow-up, 16 (3.4%) developed SSI. Infection rates were higher in subjects prescribed prophylaxis, but propensity adjustment reduced this effect. Adjusted odds of infection were 1.47-fold higher in subjects prescribed antibiotics and not statistically significant (95% confidence interval 0.29-7.39; p = .64). CONCLUSION: Although there was no significant difference in SSI among patients prescribed prophylactic antibiotics, statistical precision was limited by the low incidence of infection. Larger population-based prospective registry studies including propensity adjustment are needed to confirm the benefit of prophylactic antibiotics in high-risk surgical cases.

Case Report of Multiple Keratoacanthomas and Squamous Cell Carcinomas in a Patient Receiving Pembrolizumab.

PD-1 is expressed on antigen-stimulated T cells and induces a downstream signaling pathway that works by negative feedback to inhibit T cell proliferation, cytokine release, and cytotoxicity. PD-1 antibodies increase tumor cell killing peripherally and have a role in advanced melanoma treatment. We describe a case of an 84 year old female with stage 4 metastatic melanoma in a trial of the PD-1 inhibitor pembrolizumab who developed multiple keratoacanthomas after several months of treatment. While keratoacanthomas have been reported in patients taking BRAF inhibitors, no such reports exist for those on pembrolizumab, making this the first case report to point out this association for further investigative studies.

J Drugs Dermatol. 2017;16(5):513-515.

Proliferative activity in melanocytic nevi from patients grouped by age with clinical follow-up.

Any mitotic activity in a melanocytic nevus is a source of concern about the biologic potential of that lesion, especially in an adult. Previously diagnosed benign melanocytic nevi in individuals from six different age groups were re-examined; mitotic figures were counted in routine hematoxylin and eosin-stained sections; Ki-67 nuclear positivity was assessed by immunohistochemistry. Mitoses were seen in 0-14.3% of nevi in all groups of patients >1 year of age; 55.6% (5/9 cases) of nevi in patients <1-year old had mitoses identified histologically. Ki-67-positive melanocytes were seen in all cases of those lesions in infants (less than 1-year old) and only in a minority of lesions from the other age groups. The maximum and mean numbers of Ki-67-positive melanocytes per square millimeter were highest in patients <1-year old (16.7 and 5.6, respectively), and decreased in all other groups. Follow-up data were available in the majority of the patients. There were no examples of malignant melanoma in the various age groups. We conclude that proliferative activity in benign melanocytic nevi decreases with age, however, proliferative activity can be seen at any age and its significance must be judged in the context of other histopathologic features.

Emerging Oral Immunomodulators for the Treatment of Psoriasis: A Review of Phase III Clinical Trials for Apremilast and Tofacitinib.

BACKGROUND: Increased knowledge of the molecular regulatory mechanisms that contribute to the pathogenesis of psoriasis and other inflammatory diseases has created new opportunities for the development of targeted drug therapy for inflammatory conditions. Two new oral medications, apremilast and tofacitinib, have been developed for their immunomodulatory properties, and their potential efficacy in treating psoriasis is being evaluated. METHODS: We reviewed phase III randomized, placebo-controlled clinical trial results for apremilast and tofacitinib for efficacy and safety in psoriasis. RESULTS: Psoriasis Area and Severity Index (PASI) 75 after 16 weeks for apremilast was between 28.8% and 33.1%. PASI 75 was 39.5% after 12 weeks on tofacitinib 5 mg, and 63.6% after 12 weeks on tofacitinib 10 mg. Common side effects for both drugs included nasopharyngitis and upper respiratory tract infections. Gastrointestinal disturbance was common for apremilast. Dyslipidemia and infections were more common with tofacitinib than placebo. CONCLUSION: Both new oral medications, apremilast and tofacitinib, appear to be effective in treating psoriasis

Anti-IL-23 Phase II Data for Psoriasis: A Review.

BACKGROUND: Monoclonal antibodies that target both Interleukin (IL)-12 and IL-23 have shown great efficacy in the treatment of psoriasis. Recent evidence suggests that IL-23 serves a more critical role than IL-12 in the pathogenesis of psoriasis, leading to the development of monoclonal antibodies that specifically target IL-23. METHODS: We reviewed the results of the phase II clinical trials for the anti-IL-23 agents tildrakizumab and guselkumab, in order to assess the efficacy and safety profile of each agent. RESULTS: By week 16, the proportion of patients achieving Physician Global Assessment (PGA) score of clear (0) or minimal (1) and Psoriasis Area and Severity Index (PASI 75) was above 70% among the most efficacious dosage of each agent (P < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar, with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections, cough, and headache. CONCLUSION: The anti-IL-23 agents demonstrated a rapid clinical improvement and favorable short-term safety profile. The results of the phase II trials support IL-23 as an essential target in psoriasis treatment.

Apremilast and adalimumab: a novel combination therapy for recalcitrant psoriasis.

Psoriasis is a chronic immune-mediated inflammatory condition that affects 2-3% of the population. Apremilast was FDA-approved in March 2014 for the treatment of psoriatic arthritis and in September 2014 for the treatment of moderate to severe plaque psoriasis. Apremilast appears to have lower efficacy than some biologic agents such as adalimumab and ustekinumab, which achieve a PASI-75 in approximately 70% of patients after 12-16 weeks of therapy. However, its ease of administration as an oral agent coupled with a mild side effect profile make it an attractive option for psoriasis treatment. Herein, we present a patient with a 17-year history of plaque type psoriasis recalcitrant to topical, oral, and biologic mediations who attained near-complete remission after therapy with a combination of adalimumab and apremilast.

Biologic therapy in erythrodermic and pustular psoriasis.

BACKGROUND: The efficacy of biologic therapy in treating plaque-type psoriasis is well documented. However, there is less data for use in other psoriasis subtypes, such as erythrodermic and generalized pustular psoriasis. OBJECTIVE: We sought to review the safety and efficacy of biologic medications in the treatment of these severe subtypes of psoriasis and to identify strategies to help clinicians optimally manage these patients. METHODS: We searched Pubmed for English language literature that assessed the use of biologic medication to treat erythrodermic or generalized pustular psoriasis. RESULTS: The primary literature included cases reports, cases series, and open-label, uncontrolled trials. There were no head-to-head studies or other controlled trials. In both erythrodermic and generalized pustular psoriasis, infliximab was used to treat over half of the reported cases. Other biologic medications that were successfully used included etanercept, ustekinumab, adalimumab, and anakinra. Most cases reported improvement with biologic therapy. Serious adverse events were reported in 10-12% of the patients. CONCLUSION: Although the evidence is limited, biologic therapy appears to be effective in treating erythrodermic and generalized pustular psoriasis. In order to assess the comparative efficacy and safety of the biologic medications, larger controlled studies are needed.

Successful use of the excimer laser for generalized psoriasis in an ustekinumab non-responder.

Effective treatments for moderate to severe psoriasis are phototherapy and biologics. These treatments are similar in that they both decrease cutaneous immune system hyperactivity yet do so via different mechanisms. Our patient, a 63 year old Asian male had a rapid response to treatment with the high dose excimer laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A pre-treatment biopsy of a psoriatic plaque was found to contain relatively low levels of IFN-γ (Th1) and IL-17 (Th17) secreting T cells. Following treatment with the excimer laser, the patient had a quick improvement in PASI that was reflected by a 3-fold reduction in the number of live T cells found in the post-treatment biopsy. Although ustekinumab and the excimer laser both result in decreased levels of these cytokines, the excimer laser directly causes apoptosis of T cells and induces DNA damage in antigen presenting cells. Thus, the broader effects of phototherapy on immune cells compared to the targeted inhibition of IL-12 and IL-23 by ustekinumab likely account for the superior response observed.

Delusions of parasitosis.

The most common monosymptomatic hypochondriacal psychosis encountered by a dermatologist is delusions of parasitosis. In this condition, patients have an "encapsulated" fixed, false belief that they are infested with parasites or have foreign objects extruding from their skin. The patient will often experience feelings of biting, crawling and stinging related to the delusion. Most patients do not have other major psychiatric problems outside of their encapsulated delusion. The patient usually presents with a long history of symptoms and multiple visits to physicians in more than one specialty. Without an informed approach to these patients that focuses on the development of therapeutic alliance, clinical interactions can become very unpleasant. However, when treated with pimozide, risperidone, or other antipsychotic medications, patients have a very high response rate. Therefore, it is important for dermatologists to be able to handle these cases and know that the development of the therapeutic alliance is the key step to successful management.

Psychodermatology: an overview.

Psychodermatology is an interface between dermatology and psychiatry. The different disorders within psychodermatology can be categorized in 2 ways: by the type of psychodermatologic disorder or by the underlying psychiatric disorder. The types of psychodermatologic disorders include psychophysiological, primary psychiatric, secondary psychiatric, and cutaneous sensory disorder. The psychiatric disorders include anxiety, depression, obsessive-compulsive disorder, and psychosis. This manuscript gives an overview of the different psychodermatologic disorders, underlying psychiatric disorders, and how to manage psychodermatology cases.

The Efficacy of Biologic Therapy for the Management of Palmoplantar Psoriasis and Palmoplantar Pustulosis: A Systematic Review.

INTRODUCTION: Palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are diseases affecting the hands and/or feet that can cause marked physical discomfort and functional disability. The tumor necrosis factor-alpha antagonists adalimumab, etanercept, and infliximab, the interleukin (IL)-17A inhibitors ixekizumab and secukinumab, and the IL-23 or IL-12/IL-23 inhibitors guselkumab and ustekinumab have been well studied for the treatment of moderate to severe plaque psoriasis. Less is known about the efficacy and safety of these agents for the treatment of PP (hyperkeratotic and pustular forms) and PPP. The aim of this review was to investigate the efficacy of biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP. METHODS: A systematic search of the medical electronic databases (Medline, Embase, and Cochrane Library) was conducted to identify studies or case reports which both used biologic therapy for the treatment of hyperkeratotic PP, pustular PP, and PPP and reported treatment outcomes. RESULTS: The systematic search identified 579 published articles, of which 44 were included in the analysis. Seven of the articles involved randomized placebo-controlled trials, two were open label trials, and the remaining were cohort studies, case series, or case reports. In the randomized controlled trials on the treatment of hyperkeratotic PP, adalimumab, guselkumab, infliximab, ixekizumab, and secukinumab each demonstrated superiority to placebo at 16, 16, 14, 12, and 12 or 16 weeks, respectively (p < 0.05). For the treatment of pustular PP, ustekinumab 45 mg was not superior to placebo at 12 and 16 weeks, respectively (p > 0.05), although an open label study demonstrated that four of five patients on a therapeutic regimen of ustekinumab 90 mg achieved clinical clearance at 16 weeks. For the treatment of PPP, etanercept and ustekinumab 45 mg were not superior to placebo at 12 and 16 weeks, respectively (p > 0.05). A combined analysis of studies for hyperkeratotic PP demonstrated that 94.7%, 90.0%, 82.5%, 89.1%, and 86.7% of patients experienced an improvement of at least 50% upon treatment with adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab, respectively. In a combined analysis of case reports examining PPP, infliximab showed the greatest efficacy at 100.0% clinical improvement of patients from case reports, followed by ustekinumab at 58.8% clinical improvement. Few serious adverse events were reported, but several were reported in patients treated with infliximab or secukinumab. CONCLUSION: Biologic therapy is effective and well-tolerated for the treatment of hyperkeratotic PP, but less data are available on the treatment of pustular PP or PPP. Adalimumab, guselkumab, ixekizumab, secukinumab, and ustekinumab all showed > 80% efficacy for the treatment of hyperkeratotic PP, while infliximab and ustekinumab showed moderate efficacy for the treatment of pustular PP, and infliximab was the most efficacious treatment for PPP.

Clinical utility of ixekizumab in the treatment of moderate-to-severe plaque psoriasis.

Psoriasis vulgaris is a chronic, immune-mediated systemic disease that affects7.5 million people in the US. It can be treated with many therapies, often in combination, which include topicals, phototherapy, oral systemics, and biologics. Biologic agents target specific components of the immune system involved in the pathogenesis of psoriasis including TNF-alpha, IL-12, IL-17, and IL-23. The biologic ixekizumab, approved for the treatment of moderate-severe plaque psoriasis in the US, targets IL-17. This review describes the role of IL-17 in psoriasis, the mechanism by which ixekizumab targets this cytokine, and the clinical utility of ixekizumab.

The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy.

INTRODUCTION: Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. METHODS: A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. RESULTS: A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA < 3%; p < .001). Patients with genitalia, nails, face, neck and scalp involvement had higher scores compared to patients without involvement (p < .001). CONCLUSIONS: Patients with more extensive disease and specific anatomical involvement experience a greater impact on intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.