The genetics of alopecia areata: What's new and how will it help our patients?

In the United States, alopecia areata (AA) is the most prevalent autoimmune disease, affecting approximately 5.3 million people, including males and females of all ages and across all ethnic groups. AA affects more individuals than most other autoimmune diseases combined, and yet despite its prevalence, there is little information on the underlying pathogenesis and there are currently no evidence-based treatments available to treat or cure this disease. Genetics has provided a valuable tool for gaining insight into disease pathology. We recently completed the first genome-wide association study (GWAS) in AA and successfully identified at least eight regions in the genome with evidence for association to AA. Importantly, this work identifies a discrete set of genes, some of which have been well studied within the context of other autoimmune diseases and already have targeted therapies available or in development. The insight that we have gained through our GWAS sets the stage for the rational development of novel effective therapeutic approaches and heralds in an exciting new era with the commencement of translational research in AA based on genetic findings.     

Onycholysis associated with paclitaxel

Chemotherapeutic agents are known to cause a myriad of cutaneous side effects that the dermatologist is often called upon to identify and treat. The taxoid drug paclitaxel is commonly used in oncology. To date, there have been few adverse dermatologic effects reported secondary to paclitaxel use. This is in contrast to the related drug docetaxel. We report a case in which paclitaxel caused onycholysis and nail loss in a patient being treated for lung cancer. To our knowledge, this finding has not previously been reported in the American dermatologic literature, though it has been reported in association with docetaxel use. It is important for clinicians to recognize that onycholysis can be associated with paclitaxel. Prompt recognition may prevent the unnecessary use of antibiotics or antifungal medications. Discontinuation of paclitaxel chemotherapy generally is not required, and regrowth of nails can be expected following completion of therapy.     

Basal Cell Carcinoma: An Evidence-Based Treatment Update

Background

Basal cell carcinoma (BCC) is the most common skin cancer. Surgical excision remains the standard of treatment, but several alternative treatment modalities exist.

Objectives

This review aims to provide a current analysis of evidence for the treatment of BCC; specifically, which treatments have the lowest recurrence rates and the best cosmetic outcomes.

Methods

We searched PubMed (January 1946 to August 2013), Ovid MEDLINE (2003–August 2013), the Cochrane Central Register of Controlled Trials (January 1993 to August 2013), and the Cochrane Database of Systematic Reviews (The Cochrane Library Issue 9, 2013) databases for randomized controlled trials, systematic reviews, or comparative studies for the treatment of BCC.

Results

We found 615 potential articles. Two independent reviewers selected 40 studies: 29 randomized controlled trials (RCTs), seven systematic reviews, and four nonrandomized prospective trials. Treatment modalities reviewed include surgical therapy, radiotherapy and cryotherapy, photodynamic therapy (PDT), topical imiquimod, topical 5-fluorouracil (5-FU), topical solasodine glycoalkaloids, topical ingenol mebutate, intralesional 5-FU, intralesional interferon (IFN), and oral hedgehog pathway inhibitors.

Conclusions

The available data suggest that surgical methods remain the gold standard in BCC treatment, with Mohs micrographic surgery typically utilized for high-risk lesions. Suitable alternate treatment options for appropriately selected primary low-risk lesions may include PDT, cryotherapy, topical imiquimod, and 5-FU. Radiotherapy is a suitable alternate for surgical methods for treatment in older patient populations. Electrodesiccation and curettage (ED&C) is a commonly used primary treatment option for low-risk lesions; however, there were no RCTs examining ED&C that met our inclusion criteria. New hedgehog pathway inhibitors are promising for the management of advanced BCC; however, side effects are a concern for some patients, and much remains to be learned regarding optimal treatment length, risk of recurrence, and potential development of resistance. There is insufficient evidence at present to make recommendations on topical solasodine glycoalkaloids, topical ingenol mebutate, and intralesional 5-FU and IFN-α. Overall continued research on the efficacy of treatment modalities is needed. In particular, studies should include histologic ascertainment of clearance, long-term follow-up, stratification based on tumor subtype, and comparison with surgical outcomes.     

Efficacy and safety study of tazarotene cream 0.1% for the treatment of brittle nail syndrome

Brittle nail syndrome refers to nails that exhibit surface roughness, raggedness, and peeling. It is a common problem, with a higher prevalence among elderly patients. The goal of this study was to determine if tazarotene cream 0.1% ameliorates the signs and symptoms of brittle nails. In this open-label, single-center trial, participants applied tazarotene cream to the nails twice daily for 24 weeks. Signs and symptoms were rated by the investigators and by the participants during treatment and 12 weeks after discontinuation. Twenty participants were enrolled in the study; 1 participant withdrew prior to the 4-week followup visit. Of the 18 participants available for analysis (1 participant was excluded because baseline photographs were not available) for the primary end point of improvement in the physician global improvement assessment (PGIA), all 18 participants achieved improvement of the target nails at week 12 as well as 16 participants (88.9%) at week 24. All 18 participants had improvement in the PGIA score 12 weeks posttreatment at week 36. The physician global assessment (PGA) improved for 14 of 19 participants (73.7%) at both weeks 12 and 24; at week 24, 4 of 19 participants had achieved a PGA score of none. At week 36, 17 of 19 participants (89.5%) agreed that their nails had improved overall. Only 1 participant (5.3%) reported mild local irritation. This study demonstrated that tazarotene improves some of the changes noted in conjunction with brittle nail syndrome with minimal to no irritation.     

Nephrogenic fibrosing dermopathy (scleromyxedema-like illness of renal disease)

Nephrogenic fibrosing dermopathy or scleromyxedema-like illness of renal disease is a recently reported disorder. It manifests as scleromyxedema-like skin lesions without associated paraproteinemia, occurring in the setting of renal disease. In the majority of cases skin lesions of nephrogenic fibrosing dermopathy develop after hemodialysis or renal transplantation; however, the origin is still unknown. We report 4 new cases of nephrogenic fibrosing dermopathy and review the literature. The clinical and histopathologic features, differential diagnosis, possible etiology, and treatment options are reviewed.     

The diagnosis and treatment of nail disorders: systemic antifungal therapy

Systemic antifungals have been used in the treatment of fungal infections since the introduction of griseofulvin in 1958. Since then, new antifungal medications have been introduced, broadening the spectrum of therapies available. Onychomycosis is one of the most common complaints presented to the dermatologist. Fungal infection of the nails, though usually not an urgent medical condition, can be extremely distressing to the patient. Since current topical antifungal medications have little or no efficacy in the treatment of fungal infections of the nail, it is incumbent upon the dermatologist to be familiar with the use of systemic antifungals in the treatment of onychomycosis. In this article, the treatment of fungal infections of the nail with systemic antifungals is discussed. A brief review of the most common types of nail fungal infection is presented and the use of systemic antifungals relevant to dermatology is addressed.