A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex.

OBJECTIVE: This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)-associated facial angiofibromas. DATA SOURCES: A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis. STUDY SELECTION AND DATA EXTRACTION: Articles written in English and relevant to the topic were included. DATA SYNTHESIS: In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)-approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas. CONCLUSIONS: Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.

How should medical students prepare for a clinical dermatology rotation?

Skin diseases are commonly encountered in medical practice, yet medical students often receive little dermatology training. There is little research on what self-study materials best prepare students. We aim to identify which resources dermatology residents have found to be most useful in preparing for clinical dermatology rotations and dermatology residency. Forty current dermatology residents and fellows responded to our REDCap-generated survey. Data was analyzed using descriptive statistics. Most respondents (N=36, 90%) reported using outside resources to prepare for clinical dermatology rotations and dermatology residency. American Academy of Dermatology (AAD) modules and other online resources were most used (N=31, 77.5%) and most recommended (N=32, 80%). However, 67.5% of all respondents also used printed textbooks in some capacity, but low-to-no cost, usefulness, and easy accessibility of online resources made them more favorable among study participants. Multiple clinical dermatology rotations were recommended for preparing for dermatology residency (N= 34, 85%), as were other rotations, including internal medicine (N=22, 55%) and rheumatology (N=17, 42.5%). Overall, the AAD modules and online resources are most useful when preparing for clinical dermatology rotations because of favorable cost and accessibility. Compared to clinical rotations in other specialties, multiple rotations in dermatology may be most helpful for dermatology residency.

Digital future of dermatology.

Evolution of technology in the past several decades has undeniably transformed the practice of medicine. Dermatology, a field relying on visual cues, has been particularly impacted by advancement in imaging technologies. The purpose of this study was to review the current status as well as digital future of dermatology. The PubMed database was searched for articles pertaining to digital dermatology using search terms digital dermatology, teledermatology, and dermatopathology education. Digital dermatology has found a role in almost every aspect of dermatology: research, dermatology education and training, and clinical practice including disease prevention, diagnosis, treatment, and patient follow-up. Smartphone applications such VisualDx, MyDermPath, YouDermoscopy serve as diagnostic aid tools and can also help increase the user's knowledge of dermatology. Tools such as multispectral digital skin lesion analysis (MSDSLA) improve diagnostic accuracy and lead to fewer unnecessary biopsies. Teledermatology increases patient satisfaction, as they are able to experience shorter waits times and decreased costs. Underserved communities and those in rural settings are more likely to have a dermatologic evaluation by a specialist via teledermatology. Addressing important topics such as legal framework and updating reimbursement policies will allow for a smoother incorporation of digital dermatology into clinical practice and likely benefit patient care.

Morphea With Keloidal Features: A Case Report and Review of the Literature.

Keloidal morphea is a rare variant of scleroderma, which often can be clinically confused with keloid or scar formation. We report a 34-year-old woman with a medical history of asthma and Raynaud's phenomenon, presented for the evaluation and management of multiple erythematous hyperpigmented annular plaques reportedly developed after taking trimethoprim/sulfamethoxazole. An initial skin biopsy showed findings supportive of a drug eruption. She was treated with oral prednisone and achieved some improvement. She presented 1 year later with enlargement of the plaques and emergence of new lesions. Skin biopsies revealed an unremarkable epidermis with marked fibrosis of the mid-to-deep dermis with sparing of the papillary dermis, and superficial and deep perivascular and perieccrine lymphoplasmacytic inflammation. Verhoeff-Van Gieson staining demonstrated the loss of elastin fibers within the fibrotic areas of the biopsy specimens, which supported the diagnosis of keloidal morphea. Her laboratory tests were positive for antinuclear antibody (greater than 1:1280). She continued treatment with oral prednisone and topical steroids, and she showed improvement. This case highlights the importance of differentiating keloidal scleroderma from a hypertrophic scar or keloid to reveal an underlying systemic process. A correlation of clinical and histopathological findings is paramount to reach a correct diagnosis, ensure appropriate treatment, and monitor for comorbid disease.

Hereditary Tumor Syndromes with Skin Involvement.

Cutaneous findings that appear in childhood may be the first sign of a hereditary tumor syndrome. Early detection of genodermatoses allows the patient and at-risk family members to be screened for associated malignancies. This article provides a brief description of the pathogenesis and clinical manifestations of various inherited disorders with skin involvement, along with treatment updates. Advances in molecular-based therapy have spurred development of novel treatment methods for various genodermatoses such as xeroderma pigmentosum (XP) and Gorlin-Goltz syndrome. Further studies are needed to better assess the efficacy of many of these new treatment options.

Pharmacological Inactivation of Src Family Kinases Inhibits LPS-Induced TNF-α Production in PBMC of Patients with Behçet's Disease.

Behçet's disease (BD) is a multisystemic chronic inflammatory disease characterized by relapsing oral and genital ulcers, uveitis, and skin lesions. The pathogenesis of BD is still unknown. Aberrant production of some cytokines/chemokines plays an important role in the pathogenesis of various inflammatory diseases. Revealing a key signaling regulatory mechanism involved in proinflammatory cytokines/chemokines production is critical for understanding of the pathogenesis of BD. The aim of this study was to determine the role of Src family kinases (SFKs) in production of some LPS-induced proinflammatory cytokines/chemokines in peripheral blood mononuclear cells (PBMC) of active BD patients. Chemical inhibition of SFKs activity impaired LPS-induced TNF-α production in PBMC of active BD patients, suggesting that modulating SFKs activity may be a potential target for BD treatment.

Hypereosinophilia in erythrodermic psoriasis: superimposed scabies.

Scabies is a common ectoparasitic disease that can be diagnosed based on the presence of pruritus and typical clinical signs including burrows, vesicles, and erythematous papules. If a desquamative disease such as psoriasis precedes scabies, then the disease course may be altered. Pruritus may be absent and typical scabies lesions may be concealed due to the preexisting disease, resulting in delayed diagnosis. We present 2 cases of scabies in a brother and sister with erythrodermic psoriasis. In both cases peripheral hypereosinophilia suggested scabies. In patients with erythematous scaly inflammatory skin diseases who are treated with immunosuppressive agents, peripheral eosinophilia also could suggest scabies; therefore, a search for sarcoptic mites in skin scrapings should be undertaken.

The effects of oral isotretinoin (13-Cis retinoic acid) on the inner ear: a prospective clinical study.

PURPOSE: The purpose of this study was to investigate the effect of oral isotretinoin, a drug used in the treatment of acne vulgaris, on hearing function determined by serial audiology examinations. METHODS: Forty patients with acne vulgaris were included in this study. Nine patients were excluded from the study because of inconsistent follow-up. The hearing of each participant was tested with pure tone audiometry and transient evoked autoacoustic emissions before and two and four weeks after treatment with isotretinoin (0.3-0.6 mg/kg/day) in the remaining 31 patients (62 ears). RESULTS: The differences between the mean values of the pre-treatment and post-treatment pure tone hearing thresholds at 1000, 2000, 4000 and 6000 Hz frequencies were statistically significant (p < 0.05), but there was no significant difference between the pre-treatment and post-treatment values at 250 and 500 Hz frequencies (p > 0.05). The difference between the pre-treatment and post-treatment signal-noise ratio values of the transient evoked autoacoustic emissions was not significantly different (p > 0.05). CONCLUSION: Our results suggest that the use of isotretinoin may cause bilateral hearing threshold changes. Further animal and human studies are required to investigate and characterize isotretinoin-induced neurophysiological alterations in hearing.