Resistant Vitiligo Treated with Tofacitinib and Sustained Repigmentation after Discontinuation.

64-year-old woman with a history of esophageal strictures presented in 2015 for evaluation of progressive depigmented patches that developed over the preceding year. She was prescribed topical steroids with no improvement. Narrow-band ultraviolet B (NB-UVB) and topical tacrolimus were eventually added to the topical steroids accompanying an oral steroid taper. The patient discontinued topical tacrolimus because of irritation. The patient was lost to follow-up for the next 3 years, during which she did not take any treatment and her vitiligo had worsened (Figure 1). At her visit 3 years later, she repeated an oral prednisone taper and restarted mid-potency topical steroid. In January 2020, the patient was approved for and started oral tofacitinib 5 mg twice daily. Consistent improvement was observed on the subsequent visits in March 2020 and November 2020. The only adverse reaction reported by the patient was an increase in furuncles on her pelvis and thighs.

Scalp microbiome: a guide to better understanding scalp diseases and treatments.

The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.

Adapting with the Pandemic: Modified Mohs Micrographic Surgery Using Rim and Deep Margin Technique.

The COVID-19 pandemic has changed many facets of medical care and has resulted in a rise in delayed treatments across all specialties, including cosmetic dermatology. Delayed care for squamous cell carcinomas (SCC) and basal cell carcinoma (BCC) is not only a burden for medical providers, but also confers a risk to patients, as delayed surgeries are associated with increased metastatic risk and tumor size. Mohs micrographic surgery (MMS) delayed by more than one year leads to increased risk of complications, including bleeding and impaired wound healing, especially in the elderly population. To decrease bleeding risks, we have developed a modified MMS technique known as the "rim and deep margin" technique. Here, we present additional cases using this technique to minimize bleeding and operative time for patients with an increased risk of morbidity. This technique has been used successfully in the past for large tumors and can now be used for patients who have faced delay of care, as evidenced by its success during the COVID-19 pandemic.

Extramammary Paget disease. Part I. epidemiology, pathogenesis, clinical features, and diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

Extramammary Paget disease. Part II. Evidence-based approach to management.

Extramammary Paget disease is a rare cutaneous malignancy that most commonly affects the genitals, perianal area, and axilla of elderly patients. Delays in care often lead to high levels of disease burden for patients. Thus, evidence-based recommendations are paramount in mitigating morbidity and mortality for this unique patient population. This 2-part continuing medical education series provides a complete picture of extramammary Paget disease. Part 2 of this continuing medical education series focuses on the complex management of extramammary Paget disease including surgical and noninvasive therapies, as well as novel approaches for advanced disease.

Assessment of the Efficacy of Tranexamic Acid Solution 5% in the Treatment of Melasma in Patients of South Asian Descent.

Melasma is a common dermatologic condition affecting all skin types. Increasing rates of melasma warrant identification of a reliable topical treatment. In recent years, off-label tranexamic acid (TA) has emerged as a potential treatment of melasma. Although the mechanism of action remains unclear, it is thought that TA inhibits melanin synthesis by blocking the interaction between melanocytes and keratinocytes while reversing the abnormal dermal changes associated with melasma. Our study assessed the efficacy of TA solution 5% for the treatment of melasma in patients with darker skin types.

Comparing the Efficacy for Pulse Versus Continuous Dose Terbinafine Therapy in Patients With Onychomycosis.

Recently, treatment outcomes in patients with toenail onychomycosis have improved considerably due to more effective oral antifungal medications such as terbinafine and itraconazole. These medications can either be used continuously for several weeks at a lower dose or intermittently (pulsed) at a higher dose. Previous literature comparing pulse and continuous therapy has generated mixed results.  Our study aims to compare the efficacy, in terms of clinical cure rate, of continuous vs pulse dose terbinafine regimens for toenail onychomycosis. Sixty patients with onychomycosis of Fitzpatrick skin types IV to VI, between 15 and 65 years of age, were divided into a continuous treatment group receiving 250 mg terbinafine once daily for 12 weeks and a pulse treatment group receiving 250 mg twice daily terbinafine for 1 week repeated every 4 weeks for 12 weeks. Each patient was followed up at weeks 4, 8, and 12.  Efficacy of the continuous treatment group was significantly greater at 76.67% compared with 26.67% in the pulse treatment group. Thus, we conclude that the clinical cure rate of a continuous dose regimen of terbinafine is a superior treatment option for toenail onychomycosis. However, we also suggest further studies including combinations of multiple agents and hybrid regimen models for the optimal onychomycosis treatment.   J Drugs Dermatol. 2023;22(10):     doi:10.36849/JDD.7323R1.

Imaging Tools for Noninvasive Hair Assessment.

Trichology tools historically have been limited in their ability to provide noninvasive detailed assessments of the hair and scalp. Recent advances in diagnostic and treatment monitoring technologies have begun to fill this gap. Global photography previously relied on a film camera and stereotactic imaging equipment but has been simplified by the advent of cameras that use software analysis and provide adjustable outlines to match facial features for the capture of standardized views. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) both enable in vivo visualization of subcutaneous structures and provide new insight into the dynamic subclinical changes of alopecia. Recent efforts focus on training convolutional neural networks to quantify various hair parameters on OCT scans. When scalp biopsy is necessary, trichoscopy, RCM, and OCT can guide in selecting biopsy sites. Because of the growing clinical applications of these technologies, clinicians should be aware of the advantages and limitations of noninvasive hair-imaging tools.

Efficacy of Intralesional Vitamin D3 for Treatment of Verruca Vulgaris: A Randomized Control Study.

Cutaneous warts are benign epithelial lesions caused by human papillomavirus and are common entities, affecting nearly 10 percent of the United States population. While most warts spontaneously resolve, the immunocompromised are susceptible to recalcitrant warts which often require medical treatment. Most current therapies use either physical or chemical destruction for wart removal, but these treatments are associated with adverse effects. Intralesional vitamin D3 has the potential to demonstrate a stronger treatment response due to its ability to stimulate the immune system at the injection site via cell-mediated immunity. We sought to test the efficacy of intralesional vitamin D3 for wart treatment in a sample size of 70 patients over a three-month period. Efficacy was determined as "excellent" if there was greater than a 90-percent reduction in both size and number of lesions, "good" if there was a 60 to 89-percent reduction, and "fair" if there was less than a 60-percent reduction. Treatment efficacy was excellent in 20 (28.6%) patients, good in 29 (41.4%) patients, fair in 18 (25.7%) patients, and poor in three (4.3%) patients. Patients in the younger age group had a higher treatment efficacy compared to other treatment groups. Thus, intralesional vitamin D3 has promising qualities as a treatment for cutaneous warts and should be considered at the clinician's disposal. Vitamin D is an innovative approach for treating warts without the various side effects posed by other commonly used agents. The unique features of this treatment modality including its simplicity, safety, and efficiency make it a promising option for a very common cutaneous condition.

Muir-Torre Syndrome: A Cutaneous Finding Amidst Broader Malignancies.

Muir-Torre syndrome (MTS) is a rare autosomal dominant genetic condition resulting from microsatellite instability which is caused by mutations in DNA mismatch repair genes. This disorder predisposes individuals to skin tumors and visceral malignancies and may be precipitated in immunocompromised or transplant patients. MTS requires close cancer surveillance for the patient and family because of the tendency to develop aggressive internal malignancies and sebaceous carcinoma. Immunohistochemistry and or genetic testing can confirm the diagnosis of MTS. This review offers an update to the guidelines, diagnosis, and management of MTS while offering a unique perspective on an important but lesser-known syndrome.

Occult squamous cell carcinoma within lichenoid dermatitis: three examples of cryptic cancer detection.

Lichenoid dermatitis can be a perplexing entity encompassing an array of cutaneous disorders. Two hundred forty-three (243) cases of otherwise unclassifiable lichenoid dermatitis were examined histologically employing a special cytokeratin stain. Occult squamous cell carcinoma was detected in three of the 243 cases, uncovered by special immunohistochemistry staining within histologic specimens of lichenoid dermatitis. We recommend staining for cutaneous cancer becoming a routine practice in evaluating cutaneous lichenoid dermatitis.

Birt-Hogg-Dubé syndrome: Another mTOR phenomenon.

Birt-Hogg-Dubé syndrome is an uncommon autosomal dominant systemic disorder with cutaneous findings notable for fibrofolliculomas or trichodiscomas on the scalp, face, neck, and trunk. These cutaneous signs are associated with bilateral renal cell carcinoma, benign renal cysts, pulmonary cysts, and spontaneous pneumothorax. Given its autosomal dominant inheritance pattern, the successful diagnosis of Birt-Hogg-Dubé syndrome (BHDS) may elucidate a diagnosis in family members. BHDS results from a mutation in the FLCN gene encoding the folliculin protein, a transcriptional regulator of the mammalian target of rapamycin signaling pathway. Like tuberous sclerosis, BHDS's clinical features may subside with the use of oral rapamycin for mammalian target of rapamycin inhibition, a theoretical concept meriting exploration. Although its prevalence in the general population has been estimated at 2 cases per million, BHDS has been detected in a few patients from the nearby Portuguese-lineage quarter of the city of Newark, a disproportionate prevalence possibly explained by the founder effect.

Lichen planus pemphigoides: A unique form of bullous and lichenoid eruptions secondary to nivolumab.

The widespread use of PD-1 inhibitors to treat various solid tumors has brought certain challenges for the clinician, including immune-related adverse events (irAEs). Cutaneous toxicities are among the most observed irAEs. Bullous and lichenoid dermatoses following PD-1 inhibitor therapy have been described. Here we report a novel case of lichen planus pemphigoides, featuring characteristics of both bullous pemphigoid and lichen planus, in a patient treated with nivolumab for renal cell carcinoma. We subsequently review all three cutaneous conditions which may arise in the context of PD-1 inhibitor therapy.

Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease.

Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson's correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. Heart disease is the major clinical manifestation of BTHS with a high incidence in early life. Although the genetic basis of BTHS and tetralinoleoyl cardiolipin deficiency in BTHS-affected individuals are well-established, downstream metabolic changes in cardiac metabolism are still uncovered. Our study aimed to characterize TAZ-induced metabolic perturbations in the heart. Control (PGP1-TAZWT) and TAZ mutant (PGP1-TAZ517delG) iPS-CM were incubated with 13C6-glucose and 13C5-glutamine and incorporation of 13C into downstream Krebs cycle intermediates was traced. Our data reveal that TAZ517delG induces accumulation of cellular long chain acylcarnitines and overexpression of fatty acid binding protein (FABP4). We also demonstrate that TAZ517delG induces metabolic alterations in pathways related to energy production as reflected by high glucose uptake, an increase in glycolytic lactate production and a decrease in palmitate uptake. Moreover, despite mitochondrial dysfunction, in the absence of glucose and fatty acids, TAZ517delG-iPS-CM can use glutamine as a carbon source to replenish the Krebs cycle.