Topical immunotherapy treatment of alopecia areata with diphenylcyclopropenone: Regulatory T cells as biomarkers for treatment response.

Treatment of alopecia areata is often challenging, especially for patients with extended disease. Contact immunotherapy with diphenylcyclopropenone (DPCP) has been reported as an effective topical treatment but the exact immunologic mechanism of diverting the immune response is still unknown. We investigated the efficacy of topical immunotherapy with DPCD in acute, intermediate, and chronic lesions of AA and the response rate was associated with perifollicular infiltrate of T regulatory cells. Approximately two-thirds of our patients (67.5%) had a response rate > 50% after 6 months of DPCP therapy. Patients with acute and intermediate onset of the disease were more likely to respond to the therapy. Although responders demonstrated FOXP3+ positive lymphocytes in immunohistochemistry, this association could not be confirmed by statistical significance (p = 0.052). In patients with multiple lesions, that had different chronological onset, the lesions with more recent onset responded faster than lesions of longer duration.

Total IgE, eosinophils, and interleukins 16, 17A, and 23 correlations in severe bullous pemphigoid and treatment implications.

Bullous pemphigoid (BP) patients are predominantly above 70 years of age, with limited tolerance to the side effects of the immunosuppressive drugs. Advancements in our understanding of the pathophysiology of BP have led to the development of molecules which target specific pathways involved in induction and perpetuation of disease. Patients with BP Disease Area Index above 60 and less than 100 were split into two groups-one with high and the other with normal levels of IgE. The tested parameters included eosinophils' count, total IgE serum level, and interleukins (IL) 16, 17A, and 23 counts in the peripheral blood and skin bulla serum, before any therapeutic intervention. Thirty individuals fulfilled the criteria for enrollment. Patients with high IgE blood serum levels had significantly higher levels of IL17A and normal IL23 levels in blood and bulla serum. Patients with normal serum IgE levels had slightly higher IL23 levels in blood and bulla serum. The eosinophil count was positively related to IL17 blood serum level and negatively related to IL23. IL16 did not differ in the two groups. BP patients may represent a group of patients benefiting most substantially from the introduction of nonimmunosuppressive therapeutics into the treatment regimens for their disease. Clinical criteria and immune biomarkers are needed for making the best therapeutic choice.

A randomized, single-blinded, vehicle-controlled study of a topical active blend in the treatment of androgenetic alopecia.

Αndrogenetic alopecia (AGA) is the most common hair disorder, affecting approximately 50% of men and women. A topical lotion that contains two patented formulas (Redensyl and Sepicontrol A5), has been introduced as an alternative approach to standard therapies for AGA. Forty-four patients with AGA were randomized either to apply the active lotion or the vehicle, twice daily for 24 weeks. Subjects were evaluated at 0, 12, and 24 weeks by clinical examination, photographic documentation, quality of life evaluation (DLQI), and trichogram (anagen-to-telogen ratio). Forty-one patients, 18 males and 23 females, completed the study. Among patients receiving active treatment (n = 26), 7.7% had great improvement, 73.1% had moderate improvement, and 19.2% remained stable. The median self-assessment score increased from 4 at baseline to 6 at 24 weeks (P < .001), while the DLQI improved from 4 to 3, respectively (P < .001). The median anagen-to-telogen ratio increased from 2.25 to 4.00 to 6.02 at weeks 0, 12, and 24, respectively. No significant adverse events were reported. This new topical active blend is effective in the treatment of AGA, with high degree of patients' satisfaction, improvement of quality of life, and an excellent safety profile. Thus, it may represent a useful alternative therapeutic approach for AGA.

Congenital nevus of the nail apparatus--diagnostic approach of a case through dermoscopy.

Melanonychia striata in childhood is primarily due to congenital nevi, but melanoma should be excluded. We report a case in which dermoscopy was used in an attempt to avoid incisional biopsy.

Sebaceous Neoplasms.

Sebaceous neoplasms describe a group of tumors with sebaceous differentiation commonly seen in lesions located primarily in the face and neck. The majority of these lesions are benign, while malignant neoplasms with sebaceous differentiation are uncommon. Sebaceous tumors present a strong association with the Muir-Torre Syndrome. Patients suspected with this syndrome should undergo neoplasm excision, followed by histopathologic and additional immunohistochemistry and genetics examinations. Clinical and dermoscopic features of the sebaceous neoplasms, as well as management procedures collected from the literature analysis regarding sebaceous carcinoma, sebaceoma/sebaceous adenoma, and sebaceous hyperplasia are described in the current review. A special note is made for describing the Muir-Torre Syndrome in patients presenting multiple sebaceous tumors.

Persistent erythematous lesion of the vulva: a diagnostic and treatment challenge.

The painful, erythematous and eroded vulva often proves to be a diagnostic problem both clinically and histologically. Its differential diagnosis includes both non-neoplastic and neoplastic diseases like Bowen's disease and squamous cell carcinoma (SCC). We report the case of a 62-year-old woman diagnosed, after considerable delay, with Bowen's disease of the vulva that eventually progressed to invasive SCC, despite the treatment with imiquimod 5% cream. Our case indicates, on one hand, that dermoscopy could contribute to the accuracy of the pre-operative clinical diagnosis. On the other hand it confirms the fact that treatment of Bowen's disease of the vulva could be rather intriguing. Although imiquimod 5% cream is an effective, non-invasive treatment option for large lesions or poor healing sites, it should be administered with great consideration in carefully selected cases.

Elderly patients with psoriasis: long-term efficacy and safety of modern treatments.

OBJECTIVE: The increasing number of elderly psoriatic patients presents a challenge for dermatologists. Biologicals and small-molecule inhibitors in the general population have demonstrated a sufficient efficacy and safety profile; yet, studies about their use in the geriatric population are lacking. In this study, we evaluated the efficacy and safety of biological and apremilast among psoriatic patients ≥65 years old. MATERIALS AND METHODS: Clinical records of patients over 65 years old receiving biological drugs or apremilast were retrospectively reviewed. Efficacy was evaluated using Psoriasis Area and Severity Index (PASI) score at treatment onset and weeks 12, 24, 52 and 3 years. Adverse events were also recorded. RESULTS: A total of 154 patients with a mean age of 70.7 ± 6.3 years-old were included in our study. Secukinumab, ustekinumab and brodalumab showed fast-acting results, while the sustained efficacy of secukinumab, ustekinumab, infliximab, adalimumab and brodalumab was also notable. Overall, 30 out of 154 (19.5%) patients reported side effects. Lower respiratory system infections (n = 6; 3.9%) and hepatic enzyme elevation (n = 6; 3.9%) were the most frequently observed events. CONCLUSIONS: Biologicals and apremilast demonstrate adequate efficacy in elderly psoriatic patients. Incidence and severity of reported adverse events were similar to those reported among patients of younger age in relevant clinical studies.

The role of prostaglandins in androgenetic alopecia.

BACKGROUND: Though androgenetic alopecia (AGA) is one of the most common diseases affecting both sexes and all races, its pathogenesis is not completely clarified. The aim of this study was to investigate the role of the four major prostaglandins (PGs) (PGE2 , PGD2 , PGF2α , and PI2 or prostacyclin) in the pathogenesis of AGA in males and females. METHODS: Human scalp biopsies were obtained from 30 adults (17 males and 13 females) suffering from AGA and from 30 healthy adults (18 males and 12 females). In each subject, two skin biopsies were performed, one from the frontal bald area and another one from the occipital area with normal hair growth. In the healthy group, biopsies were taken from both areas too. In each sample, all four PGs were measured. RESULTS: In the patient group, PGD2 and prostacyclin or PGI2 levels were increased in bald compared to haired scalp. On the contrary, measurements of PGE2 and PGF2α showed that they were diminished in bald areas compared to haired areas. PG levels in healthy samples were comparable to the haired areas. CONCLUSION: These results support that there is a fine balance between these four proteins in scalp hair follicles, and its maintenance may be crucial for hair growth. Furthermore, their receptors could be potential targets for treatment of AGA.

Under Development JAK Inhibitors for Dermatologic Diseases.

Molecular targeting therapies represent a new exciting era in dermatology. A promising novel drug class, subject of intense research, is Janus kinase (JAK) inhibitors. Multiple cytokine receptors signal through the Janus kinase and signal transducer and activator of transcription (STAT) pathway. The pathway plays a central role in innate and adaptive immunity, and haematopoiesis. The understanding of the contribution of JAKs to the immunologic processes of inflammatory diseases led to the development of JAK inhibitors, initially for rheumatologic and hematologic diseases. Soon, their efficacy in some dermatologic conditions was also demonstrated, and today their role as therapeutic agents is thoroughly researched, mainly in atopic dermatitis, psoriasis, vitiligo, and alopecia areata. JAK inhibitors can be administered orally or used topically. As they are relatively new treatment modalities in dermatology, many questions concerning their efficacy and safety remain unanswered. Data from ongoing trials are eagerly awaited. Here, we summarize under development JAK inhibitors for dermatologic diseases.

Precision Medicine and the Practice of Trichiatry: Adapting the Concept.

Evidence-based medicine (EBM) aims for the ideal that healthcare professionals make conscientious, explicit, and judicious use of the best available evidence gained from the scientific method to clinical decision-making. It seeks to assess the strength of the evidence for benefits of diagnostic tests and treatments, using techniques from science, engineering, and statistics, such as the systematic review of medical literature, meta-analysis, risk-benefit analysis, and randomized controlled trials. The limited success rate of EBM therapies suggests that the complex nature of hair loss may be inadequately served by the present levels of evidence, and that physicians treating hair loss may have fallen short of adequately researching a robust evidence to underpin their practices. Against this backdrop, the concept of precision medicine (PM) is evolving. PM refers to the customization of medical care to the patient's individual characteristics based on the patient's genetic background and other molecular or cellular analysis, while classifying patients into subpopulations that differ in their susceptibility to a particular medical condition, in the biology or prognosis of those medical conditions, or in their response to a specific treatment. With the advances in hair research, the powerful tools of molecular biology and genetics, and innovative technologies, we have the robust scientific data and tools to adapt the concept of PM to the practice of trichiatry. Finally, databases pertaining to the development and efficacy of PM must be analyzed and be used to form the basis of evidence-based personalized trichiatry.

Targeting IL-23 in psoriasis: current perspectives.

The recent advances in the understanding of psoriasis pathogenesis have clarified the pivotal role of interleukin (IL)-23. It is a heterodimeric cytokine consisting of two subunits, the unique p19 and the p40, which are shared with IL-12. The basic role of IL-23 in psoriasis is the activation and maintenance of the T-helper 17 pathway. New research findings indicate that IL-23 is more important than IL-12 in the pathogenesis of psoriasis. Based on that background, the selective targeting of the IL-23p19 subunit emerged as an attractive therapeutic option and led to the development of a new category of biologic agents. Three monoclonal antibodies that selectively inhibit the IL-23p19 subunit, guselkumab, tildrakizumab, and risankizumab, are in the pipeline for the treatment of moderate-to-severe psoriasis. In this article, we review the most recent efficacy and safety data regarding these IL-23p19 inhibitors.

Clinicopathologically problematic melanocytic tumors: a case-based review.

BACKGROUND: In spite of recent advances in the histopathological and molecular diagnosis of melanocytic neoplasms, a certain proportion of these lesions remain a daunting challenge for both the clinician and the pathologist. OBJECTIVES: To emphasize the importance of close collaboration between clinicians and pathologists in case of problematic melanocytic lesions. PATIENTS: We report and discuss 5 problematic scenarios of melanocytic lesions, including tumoral melanosis, nevoid melanoma, lentiginous melanoma, spitzoid melanoma and BAPoma that may pose diagnostic difficulties in our practice. CONCLUSIONS: Clinico-dermoscopic-pathological correlation, with incorporation of all the available data, in problematic melanocytic skin neoplasms is of paramount importance for accurate diagnosis.

Trichologist, Dermatotrichologist, or Trichiatrist? A Global Perspective on a Strictly Medical Discipline.

Few dermatologic problems carry as much emotional overtones as the complaint of hair loss. The best way to alleviate the distress related to hair loss is to effectively treat it. In fact, one of the oldest medical professions is the Egyptian physician who specialized on diseases of the head. And yet, from ancient Egypt down to modern times, human hair has been the object of superstition and mystery. Remarkably and despite the genuine advances in effective medical treatments, hair cosmetics, and surgical procedures, phony hair loss solutions continue to be marketed with an amazing success. In 1860, a quasi-scientific interest in hair loss and hair care originated in a London barbershop and became known as trichology, with the Institute of Trichologists being founded. Other corporations successively followed internationally, but it was only in 2010 that the term dermatotrichologist was proposed for board-certified dermatologists dealing with the scientific study of the hair and scalp, in contrast to the trichologist who is rather associated with laity and cosmetics than with medical professionalism, or - worse - offers opportunities to possible imposters with a primary commercial interest. The new term "trichiatrist" is proposed, literally meaning the "medical treatment of the hair," to designate the strictly medical professional dealing with the hair and scalp in health and disease. Trichiatrists differ from trichologists by virtue of being physicians. The quality and stringency of their graduate medical training is identical to that of other physicians.

Basal Cell Carcinoma in a Childhood Cancer Survivor: What Neurosurgeons Should Avoid.

Among childhood cancer survivors (CCSs), non-melanoma skin cancer (NMSC) is the most common type of second malignancy. Morbidity related to the development of NMSC in this group of patients may be sometimes unpredictable and difficult to manage. We present the case of a 49-year-old female who was a CCS and developed giant superficial basal cell carcinomas (sBCCs) over the previously irradiated field of the scalp. BCC involved the atrophic skin overlying the catheter of the peritoneal cerebral shunt that was set there for the management of hydrocephalus. Topical treatment with imiquimod 5% resulted in local skin reaction that was further complicated with catheter exposure. The patient underwent an emergency neurosurgery for reposition of the cerebral shunt. Subsequent treatment with imiquimod resulted in complete resolution of sBCC. Given the increased risk for the development of BCCs in CCSs, awareness of neurosurgeons is crucial. Avoidance of setting the catheter of the cerebral shunt within the radiotherapy field is highly recommended, in order to avoid unnecessary future surgeries and subsequent morbidity, as in our case.

Epidemiological trends in skin cancer.

Skin cancer, including melanoma and non-melanoma skin cancer (NMSC), represents the most common type of malignancy in the white population. The incidence rate of melanoma is increasing worldwide, while the associated mortality remains stable, or is slightly decreasing. On the other hand, the incidence for NMSC varies widely, with the highest rates reported in Australia. In the current review, we highlight recent global trends in epidemiology of skin cancer. We discuss controversial issues raised in current epidemiological data, we analyze the most important risk factors associated with the development of melanoma and NMSC and the impact of skin cancer on health care services. Furthermore, we underline the pressing need for improved registration policies, especially for NMSC, and lastly, we refer to the ongoing primary and secondary prevention strategies and their outcomes so far.

Rosacea and Helicobacter pylori: links and risks.

Rosacea is a chronic skin disease characterized by facial erythema and telangiectasia. Despite the fact that many hypotheses have been proposed, its etiology remains unknown. In the present review, the possible link and clinical significance of Helicobacter pylori in the pathogenesis of rosacea are being sought. A PubMed and Google Scholar search was performed using the terms "rosacea", "H.pylori", "gastrointestinal disorders and H.pylori", "microorganisms and rosacea", "pathogenesis and treatment of rosacea", and "risk factors of rosacea", and selected publications were studied and referenced in text. Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others. We conclude that further studies are needed in order to fully elucidate the pathogenesis of rosacea.

Spotlight on vismodegib in the treatment of basal cell carcinoma: an evidence-based review of its place in therapy.

Vismodegib is approved for the treatment of adult patients with metastatic (mBCC) or locally advanced basal cell carcinoma (laBCC) that have recurred following surgery or for those who are not good candidates for surgery (risk/benefit ratio is against patient's benefit, either because of the general condition or because of the expected morbidity from the surgery) or radiation therapy. This article provides an evidence-based review of its current place in therapy. Analytically, the clinical implications in the management of laBCCs and mBCCs and possible new indications, including the neoadjuvant use before surgical excision, are discussed, while in the end, the challenges regarding class-related adverse events and their optimal management are highlighted.