Future therapies in melasma: What lies ahead?

Melasma is a common, acquired, symmetrical hypermelanosis. It negatively impacts the patient's quality of life and responds poorly to treatment. Although earlier classified as epidermal and dermal, melasma is now thought to be a complex interaction between epidermal melanocytes, keratinocytes, dermal fibroblasts, mast cells, and vascular endothelial cells. Factors influencing melasma may include inflammation, reactive oxygen species, ultraviolet radiation, genetic factors, and hormones. With a better understanding of the pathogenesis of melasma and the realization that targeting melanin synthesis alone is not very effective, treatments focussing on newly implicated factors have been developed. These include agents targeting hyperactive melanocytes, melanosomal transfer to keratinocytes, defective skin barrier, the mast cells, vasculature, and estrogen receptors as well as drugs with anti-inflammatory and antioxidant activity. Many of these newer agents are botanicals with multimodal mechanisms of action that offer a better safety profile when compared with the conventional drugs. There has also been a focus on oral agents such as tranexamic acid, flutamide, and ascorbic acid. It has been suggested that the "triple therapy of the future" may be a combination of hydroquinone, an antiestrogen and a vascular endothelial growth factor inhibitor, as the "ideal" skin-lightening agent.

An array of unusual clinical features in a woman with amlodipine-induced linear immunoglobulin A disease.

Linear immunoglobulin A disease (LAD) is a rare, autoimmune, vesicular-bullous disease that is either idiopathic or drug-induced, most commonly by vancomycin and in rare instances by amlodipine. In drug-induced LAD, certain uncommon and atypical clinical features can occur. In our patient, a 49-year-old woman with amlodipine-induced LAD, atypical features such as koebnerization and palmo-plantar involvement occurred. She presented with tense, clear fluid-filled vesicles, bullae, and erosions all over her body, especially on the palms and soles, with some lesions showing a string-of-pearls appearance. The lesions were preceded by pruritus, and the patient had changed her anti-hypertensive medication from telmisartan to telmisartan-amlodipine for previous 10 days. Skin biopsy and direct immunofluorescence testing confirmed LAD. During the hospital stay, along with new crops of lesions, a few vesicles were present along the lines where she had scratched and the band of tight elastic sleeves of the sterile gown she wore, which is suggestive of koebnerization. Knowing the atypical manifestations of drug-induced LAD may aid clinicians in determining an early diagnosis, and LAD should be an important consideration in the differential diagnosis of vesiculobullous disease with palmar-plantar involvement. Amlodipine is a commonly used anti-hypertensive drug, so knowledge of its potential to cause this disease is important. Furthermore, knowing the potential for koebnerization, avoidance of trauma and the gentle handling of these patients can lead to early recovery from this self-limiting disease.

Melasma in Men: A Review of Clinical, Etiological, and Management Issues.

Melasma is a common skin condition that affects both men and women. However, it is more commonly seen in women and dark-skinned individuals, such as in Hispanics, Asians, and African Americans who live in areas with intense ultraviolet radiation. Melasma is less common in men, but it negatively affects the quality of life in men as much as it does in women. While melasma has been studied in detail in women, however, there is a paucity of studies on the clinico- etiopathology and therapeutics of melasma in men. This article reviews and discusses important clinical, etiological, and treatment aspects of melasma in men. The authors recommend that clinicians educate their patients on the causes, prevention and treatment methods, and recurrence rates of melasma. The authors also recommend that clinicians take into careful consideration each patient's preferences and expectations when creating treatment regimens, as these might differ greatly among men and their female counterparts.

Medical Management of Melasma: A Review with Consensus Recommendations by Indian Pigmentary Expert Group.

Melasma is one of the most common hyperpigmentary disorders found mainly in women and dark-skinned patients. Sunlight, hormones, pregnancy, and genetics remain the most implicated in the causation of melasma. Although rather recalcitrant to treatment, topical agents such as hydroquinone, modified Kligman's Regime, azelaic acid, kojic acid, Vitamin C, and arbutin still remain the mainstay of therapy with sun protection being a cornerstone of therapy. There are several new botanical and non botanical agents and upcoming oral therapies for the future. There is a lack of therapeutic guidelines, more so in the Indian setup. The article discusses available evidence and brings forward a suggested treatment algorithm by experts from Pigmentary Disorders Society (PDS) in a collaborative discussion called South Asian Pigmentary Forum (SPF).

Evidence-based Review, Grade of Recommendation, and Suggested Treatment Recommendations for Melasma.

Treatment of melasma is known to be less satisfactory, often incomplete, and relapse is frequent. Although many treatment options are available, they are either known to be unsafe on long-term use or their long-term safety profile is unknown. Patients often use various drugs, even topical steroid-based preparation without any medical supervision for long period of time, making the skin unsuitable for many of the drugs available. Thus, there has been gross disparity among the treating physician about what drugs and what regimen are best suitable for various categories of melasma patients and in different situations. With this background, numerous newer drugs, mostly combinations of some proprietary molecules or even unknown plant extracts, have flooded the market for the management of melasma. Information on efficacy or safety of these products are almost unknown. Studies on Asian people, especially Indian population, are far less commonly available. Therapeutic guideline for use on Indian patients with melasma is almost missing. Extrapolation of data from Caucasian people for use on Asian people may not be scientifically justifiable because Caucasian and Asian people are known to have inherent difference in their response as well as tolerance to the drugs used for melasma. With this background, we have extensively evaluated, following a strict, scientifically designed protocol, all the available studies on melasma management till May 2016 and prepared this document on level of evidence, grade of recommendation and suggested therapeutic guideline for melasma as per the method proposed by Oxford Centre of Evidence-Based Medicine. Various ethical, social, logical, regional, and economic issues in the context of Indian and similar populations were given due importance while preparing the suggested therapeutic recommendation.

Initiation of antiretroviral therapy.

With the widespread availability of antiretroviral therapy, there is a dramatic decline in HIV related morbidity and mortality in both developed and developing countries. Further, the current antiretroviral drug combinations are safer and the availability of newer monitoring assays and guidelines has vastly improved the patient management. The clinician needs to evaluate several key issues prior to institution of antiretroviral regimen including the correct stage of starting the treatment and the kind of regimen to initiate. In addition to various disease related factors, it is also critical to assess the patient's general condition including nutritional status, presence of co-morbidities and mental preparedness prior to starting the therapy. The patients need to develop an overall understanding of the treatment and its benefits and the importance of lifelong adherence to the drugs. The presence of special situations like pediatric age, older patients, pregnancy, lactation and presence of opportunistic infections also require modification of the therapy. This review briefly summarizes issues relevant to the clinician prior to the initiation of antiretroviral therapy.