Immunomodulation by Schwann cells in disease.

Schwann cells are the principal glial cells of the peripheral nervous system which maintain neuronal homeostasis. Schwann cells support peripheral nerve functions and play a critical role in many pathological processes including injury-induced nerve repair, neurodegenerative diseases, infections, neuropathic pain and cancer. Schwann cells are implicated in a wide range of diseases due, in part, to their ability to interact and modulate immune cells. We discuss the accumulating examples of how Schwann cell regulation of the immune system initiates and facilitates the progression of various diseases. Furthermore, we highlight how Schwann cells may orchestrate an immunosuppressive tumor microenvironment by polarizing and modulating the activity of the dendritic cells.

Review of talimogene laherparepvec: A first-in-class oncolytic viral treatment of advanced melanoma.

Talimogene laherparepvec (T-VEC) is an oncolytic virus based on herpes simplex virus type 1 approved for intralesional treatment of advanced melanoma. In this article, we review the clinical literature on T-VEC for advanced melanoma and provide a practical approach to using T-VEC in the dermatologic surgery and oncology clinic. PubMed was used to conduct a systematic literature review of articles describing the structure, basic science, and clinical and therapeutic properties of T-VEC. The national clinical trials database was also searched for T-VEC clinical trials. Phase I to III clinical trials and early real-world experience have shown the efficacy of T-VEC in advanced melanoma as single or combination therapy with tolerable adverse effects. We conclude that with a standardized clinical approach and training, dermatologists can pave the way in using T-VEC and future oncolytic virus therapies in appropriate clinical scenarios.

Comparing acne follow-up: teledermatology versus outpatient dermatology visits.

The application of teledermatology for evaluating acne patients has yielded comparable therapeutic outcomes with traditional face-to-face evaluation, but follow-up compliance between these modalities is not well-studied. Our objective is to compare the rate and duration of follow-up between acne patients initially evaluated by teledermatology versus in-person outpatient consultation. Electronic medical review of acne patients, 18-35 years-old seen via teledermatology and face-to-face evaluation at the University of Pittsburgh Medical Center between 2010-2018 was performed. Teledermatology patients were less likely to follow-up in the first 90 days (13.0% versus 31.0%, P<0.001) compared to patients seen face-to-face with overall follow-up rates of 22% among both modalities. The median time to follow-up was 45.5 days (IQR: 13/57) in the teledermatology group compared to 64 days (IQR: 56/77) in the face-to-face group (P<0.001). Teledermatology patients were more likely to be treated with oral antibiotics (43.0% versus 28.5%) or oral spironolactone (18.5% versus 12.5%) compared to patients seen face-to-face (P<0.001). Teledermatology poses a promising solution to extend dermatologic care with earlier access to follow-up. Our data demonstrates a need to improve teledermatology follow-up education to improve follow-up care.

Sweet syndrome with pulmonary involvement in a patient with myelodysplastic syndrome.

We report a patient with Sweet syndrome involving the pulmonary system in the context of myelodysplastic syndrome. Although Sweet syndrome may involve a variety of organ systems, the pulmonary system is rarely affected and can result in poor clinical outcomes, including acute respiratory distress syndrome. Both cutaneous and pulmonary symptoms respond well to systemic corticosteroid therapy and early diagnosis and treatment can improve the prognosis. Our case highlights the importance of collaboration between hematologists, dermatologists, and pulmonologists to facilitate effective diagnosis, triage, and treatment of these patients.

A challenging diagnosis of penile sarcomatoid squamous cell carcinoma.

We report a patient with penile sarcomatoid squamous cell carcinoma (SCC) initially misdiagnosed as condyloma acuminatum. Sarcomatoid SCC is a rare, aggressive, biphasic cancer that often presents a diagnostic challenge and carries a poor prognosis, especially after a delay in diagnosis. Although sarcomatoid SCC may exhibit a broad range of clinical features, the expression of p63 and keratin 34?E12 is a common finding. Our case highlights the importance of accurate clinicopathologic correlation to facilitate a timely diagnosis and management of this rare and highly aggressive malignancy.

The ALT-70 predictive model outperforms thermal imaging for the diagnosis of lower extremity cellulitis: A prospective evaluation.

BACKGROUND: We previously demonstrated that dermatology consultation substantially reduces the rates of misdiagnosis of cellulitis; however, broad implementation of dermatology consultation is impractical on account of existing practice patterns and reimbursement systems. Meanwhile, efforts to improve diagnostic accuracy have culminated in point-of-care tools, including the ALT-70 predictive model for lower extremity cellulitis and thermal imaging. OBJECTIVE: To prospectively evaluate the performance of the ALT-70 predictive model and thermal imaging in diagnosing lower extremity cellulitis in a head-to-head comparison. METHODS: We collected ALT-70 and thermal imaging data from patients with presumed lower extremity cellulitis and compared classification measures and accuracy for the ALT-70 predictive model, thermal imaging, and combination testing (ALT-70 predictive model plus thermal imaging). RESULTS: We enrolled 67 patients with ALT-70 and thermal imaging data. The ALT-70 predictive model conferred the highest sensitivity (97.8%) and negative predictive value (90.9%), whereas combination testing had the highest specificity (71.4%) and positive predictive value (86.6%). The ALT-70 predictive model had improved classification measures compared with thermal imaging. Combination testing conferred a marginal benefit compared with the ALT-70 predictive model alone. LIMITATIONS: Single-center design may limit generalizability. CONCLUSION: The ALT-70 predictive model outperformed thermal imaging in diagnosing lower extremity cellulitis. The accuracy of the ALT-70 predictive model was high and consistent with its performance in previously published literature. Broad implementation of the ALT-70 predictive model in clinical practice may decrease the rates of misdiagnosis of lower extremity cellulitis.

Treatment of Inverse/Intertriginous Psoriasis: Updated Guidelines from the Medical Board of the National Psoriasis Foundation.

Inverse or intertriginous psoriasis commonly involves skin fold areas including the axillae, perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and retroauricular folds. After reviewing the literature for new treatments, a task force was convened to update a consensus on inverse psoriasis therapy. Short-term treatment continues to be low-potency topical steroids. In order to avoid steroid-induced adverse effects, long-term therapy includes topical immunomodulators, calcitriol, and calcipotriene. Second and third-line therapies include antimicrobials, emollients, and tar-based products. Inverse psoriasis resistant to topical therapy has been shown to respond to botulinum toxin injections, excimer laser therapy, and certain systemic agents (such as anti-TNF and anti-IL12/IL23 therapy). Based on promising results from case reports and prior clinical experience, these systemic agents should be strongly considered in inverse psoriasis resistant to topical therapy. However, they need further evidence-based evaluation. The use of randomized trials and objective severity indices may allow for more robust therapeutic data.

J Drugs Dermatol. 2017;16(8):760-766.

Characteristics and outcomes of nonmelanoma skin cancer (NMSC) in children and young adults.

BACKGROUND: Pediatric and young adult nonmelanoma skin cancer (NMSC) is rare and traditionally associated with predisposing heritable or congenital conditions. Clinical characteristics, outcomes, and iatrogenic risk factors have not been well described. OBJECTIVES: We sought to characterize clinical features, potential risk factors, and gaps in care associated with NMSC in children and young adults. METHODS: This was a retrospective chart review of children and young adults with squamous and basal cell carcinoma. RESULTS: We identified 28 patients with a total of 182 NMSC tumors. Of patients, 50% had predisposing conditions, and 46% had exposure to iatrogenic risk factors of prolonged immunosuppression, radiation therapy, chemotherapy, voriconazole use, or a combination of these. Of patients with iatrogenic risk factors, 62% developed subsequent cancerous or precancerous skin lesions. No patient was found to have chemotherapy or voriconazole exposure as a sole risk factor. Mean time to diagnosis of NMSC was 948 days with initial misdiagnosis in 36% of patients. The majority of patients underwent surgical excision. LIMITATIONS: This was a retrospective single institution study with a small number of cases. CONCLUSIONS: Physicians should be aware of risk factors associated with NMSC in children and young adults to provide appropriate counseling and early diagnosis and treatment.

Ion-specific effects on prion nucleation and strain formation.

Ordered, fibrous, self-seeding aggregates of misfolded proteins known as amyloids are associated with important diseases in mammals and control phenotypic traits in fungi. A given protein may adopt multiple amyloid conformations, known as variants or strains, each of which leads to a distinct disease pattern or phenotype. Here, we study the effect of Hofmeister ions on amyloid nucleation and strain generation by the prion domain-containing fragment (Sup35NM) of a yeast protein Sup35p. Strongly hydrated anions (kosmotropes) initiate nucleation quickly and cause rapid fiber elongation, whereas poorly hydrated anions (chaotropes) delay nucleation and mildly affect the elongation rate. For the first time, we demonstrate that kosmotropes favor formation of amyloid strains that are characterized by lower thermostability and higher frangibility in vitro and stronger phenotypic and proliferation patterns effectively in vivo as compared with amyloids formed in chaotropes. These phenomena point to inherent differences in the biochemistry of Hofmeister ions. Our work shows that the ionic composition of a solution not only influences the kinetics of amyloid nucleation but also determines the amyloid strain that is preferentially formed.

Assessing quality of life in patients with autoimmune bullous diseases using the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life questionnaire finds similar effects in women as men.

In autoimmune bullous diseases (AIBDs), autoantibodies loosen molecular adhesions in the skin and/or mucosa and lead to blisters and erosions. Immunosuppressive drugs reduce mortality of the AIBD; therefore, patients will have to live longer with comorbidities. Objective: This study aims to determine the quality of life of AIBD patients undergoing systemic treatment while investigating the survey's relationship with various factors. Methods: In this 2-step cross-sectional study, we initially included 53 consecutive pemphigus patients to investigate reliability and validity of the Persian version of Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaire. Then, we conducted the study on 119 AIBD patients, currently under treatment at an AIBD clinic in Iran. Results: The mean TABQOL score for our patients was 13.87 ± 7.51. The highest TABQOL was for epidermolysis bullosa acquisita (24 ± 8.485) followed by pemphigus foliaceus (20.5 ± 14.181) and the lowest for pemphigus vulgaris (13.24 ± 6.54). There was no significant difference between patients' TABQOL scores and their gender, history of rituximab injection, and disease severity scores. We only found a positive correlation between TABQOL and prednisolone dose. Conclusion: Treatments of AIBD considerably impact the quality of life of patients and an impairment in quality of life is correlated to higher doses of prednisolone.