Gabrielle Brown

Aminolevulinic acid (ALA): photodynamic detection and potential therapeutic applications.

Aminolevulinic acid (ALA) is a heme precursor that may have potential applications for photodynamic detection and photodynamic therapy-based treatment of solid tumors in a variety of malignancies. ALA may have a role in other applications in surgical oncology based on its ability to discriminate neoplastic tissue from adjacent normal tissue. In this review, we provide a comprehensive summary of the published studies of ALA in noncutaneous solid malignancies.

Biologic fatigue in psoriasis

Background: Over the past 15 years, biologic medications have greatly advanced psoriasis therapy. However, these medications may lose their efficacy after long-term use, a concept known as biologic fatigue. We sought to review the available data on biologic fatigue in psoriasis and identify strategies to help clinicians optimally manage patients on biologic medications in order to minimize biologic fatigue. Methods: We reviewed phase III clinical trials for the biologic medications used to treat psoriasis and performed a PubMed search for the literature that assessed the loss of response to biologic therapy. Results: In phase III clinical trials of biologic therapies for the treatment of psoriasis, 20–32% of patients lost their PASI-75 response during 0.8–3.9 years of follow-up. A study using infliximab reported the highest percentage of patients who lost their response (32%) over the shortest time-period (0.8 years). Although not consistently reported across all studies, the presence of antidrug antibodies was associated with the loss of response to treatment with infliximab and adalimumab. Conclusion: Biologic fatigue may be most frequent in those patients using infliximab. Further studies are needed to identify risk factors associated with biologic fatigue and to develop meaningful antidrug antibody assays.

Anti-IL-17 phase II data for psoriasis: A review.

UNLABELLED Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; 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 and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. Methods: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. Results: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; 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 and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. Conclusion: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.

Tumor necrosis factor-α inhibitor-induced psoriasis: Systematic review of clinical features, histopathological findings, and management experience

Background: Tumor necrosis factor‐&agr; (TNF‐&agr;) inhibitors have been reported to induce new‐onset psoriasis. Objective: To better define the demographic, clinical features, and treatment approach of TNF‐&agr; inhibitor‐induced psoriasis. Methods: Systematic review of published cases of TNF‐&agr; inhibitor‐induced psoriasis. Results: We identified 88 articles with 216 cases of new‐onset TNF‐&agr; inhibitor‐induced psoriasis. The mean age at psoriasis onset was 38.5 years. The most common underlying diseases were Crohn disease (40.7%) and rheumatoid arthritis (37.0%). Patients underwent TNF‐&agr; therapy for an average of 14.0 months before psoriasis onset with 69.9% of patients experiencing onset within the first year. The majority of patients received skin‐directed therapy, though patients who discontinued TNF therapy had the greatest resolution of symptoms (47.7%) compared with those who switched to a different TNF agent (36.7%) or continued therapy (32.9%). Limitations: Retrospective review that relies on case reports and series. Conclusion: While TNF‐&agr; inhibitor cessation may result in resolution of induced psoriasis, lesions may persist. Decisions regarding treatment should be weighed against the treatability of TNF‐&agr; inhibitor‐induced psoriasis, the severity of the background rheumatologic or gastrointestinal disease, and possible loss of efficacy with cessation followed by retreatment. Skin‐directed therapy is a reasonable initial strategy except in severe cases.

The role of IL-17 in psoriasis

Abstract Background: Psoriasis is a chronic skin condition traditionally believed to involve the Th1 pathway. Recently, the IL-23/Th17/IL-17 pathway has been highlighted in the pathogenesis of psoriasis and other autoimmune inflammatory conditions. From a clinician’s perspective, we sought to review the basic science data relevant to IL-17’s role in psoriasis pathogenesis. Methods: We performed a Pubmed and Web of Knowledge search for English articles starting from 1990 that discussed the Th17 pathway. Search terms such as “IL-17” and “psoriasis” were utilized. Results: The IL-17 pathway is regulated by IL-23, a cytokine that is vital for the expansion and maintenance of the Th17 cell population. Th17 derived cytokines (IL-17A, IL-17F, IL-17A/F and IL-22) were elevated in both psoriasis-like murine models and human psoriatic lesional biopsies. Ixekizumab (anti-IL-17A) treatment of psoriasis was found to normalize levels of IL-17 downstream gene products. Conclusion: Both preclinical and clinical studies support the central role of IL-17 in the pathogenesis of psoriasis.

Enhancing Patient Satisfaction in Dermatology

Patient satisfaction is an important component of dermatological care that reflects patients’ perspectives on the care they receive. While physicians’ expertise and judgment should always remain the foundation of providing appropriate and effective care, the patient experience can also be influenced by interpersonal relationships, expectations, and a sense of agency in the treatment patients receive. Dermatology providers can use practical techniques such as sitting rather than standing, reframing the concept of cure, and engaging patients in treatment decisions to improve the patient–provider experience and thereby optimize patient satisfaction.

Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

Abstract Background: The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. Methods: In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. Results: To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of “clear” or “almost clear”. Conclusions: Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

The Spectrum of Ideation in Patients with Symptoms of Infestation: From Overvalued Ideas to the Terminal Delusional State

Delusional infestation (DI) is a type of monosymptomatic hypochondriacal psychosis characterized by the steadfast belief that one is infested with living organisms or inanimate material in the absence of objective proof. Although DI is generally regarded as a single psychotic phenotype characterized by either the presence or absence of a delusion, our experience has been that patients with DI present with varying levels of severity represented by various phenotypes along a continuum. Distinguishing where a particular patient presents on this spectrum has allowed us to modify our approach with greater sophistication and thereby optimize management. Our aim is to describe for the first time in dermatology the concept of the DI continuum with support from the psychiatric literature, and to provide practical therapeutic recommendations for each phenotype in the spectrum.

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

Abstract 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.

Clinical Utilization of Repeated Open Application Test Among American Contact Dermatitis Society Members.

BackgroundThe repeated open application test (ROAT) provides useful information regarding allergens in suspected cases of allergic contact dermatitis; however, standardized methodology has not been established. ObjectiveThe aim of this study was to assess how ROAT is used in clinical and research settings. MethodsWe distributed a survey regarding ROAT practice to the American Contact Dermatitis Society and conducted a literature review of ROAT utilization in research. ResultsA total of 67 American Contact Dermatitis Society members participated in the survey. Respondents most frequently recommend application of leave-on products twice daily (46.0%) and rinse-off products once daily (43.5%). The most commonly used anatomical sites include the forearm (38.7%) and antecubital fossa (32.3%). Most respondents continue ROAT for 1 (49.2%) or 2 weeks (31.7%). Literature review of 32 studies (26 leave-on, 6 rinse-off) revealed that application frequency is most common at twice daily for both leave-on (96.2%) and rinse-off (50.0%) products. The most common anatomical site is the forearm (62.5%), with an overall study duration of 3 to 4 weeks (65.6%). ConclusionsWhen comparing ROAT clinical and research practice, the majority trend was consistent for leave-on product application frequency and anatomical site, but not for rinse-off product application frequency, or overall duration. Further research is needed to determine best practice recommendations.