Evaluation of oral tranexamic acid as a novel treatment for melasma with a high benefit-risk ratio.

BACKGROUND: Melasma is an acquired melanogenesis dysfunction resulting in chronic hyperpigmentation commonly affecting the face and other frequently sun-exposed areas of the body. Melasma typically presents in women of reproductive age and can significantly impact self-esteem, negatively affecting one's quality of life. In the United States, melasma is often treated with application of topical agents that interfere with melanin synthesis, lasers, or chemical peels; however, in some East Asian countries, oral tranexamic acid (TXA) is widely administered to alleviate hyperpigmentation during and after childbirth. TXA is currently only FDA-approved to treat hypermenorrhea and reduce blood loss in surgery but may offer women in the United States an additional therapeutic option to treat melasma. AIMS: The aim of this paper is to evaluate the safety and baseline efficacy of oral transmexic acid as a treatment for melasma. METHODS: We retrospectively surveyed 42 patients of Fitzpatrick skin types III-VI that were prescribed 650 mg of TXA ½ tablet to be taken twice daily by mouth. RESULTS: We found majority of patients saw noticeable improvement in their melasma. Of the 42 patients, only seven experienced side effects. The side effects noted were headaches, malaise and nausea, gastrointestinal upset, congestion, numbness in legs, hypomenorrhea, and hypermenorrhea. Patients who experienced unpleasant side effects discontinued taking oral TXA and were relieved of their symptoms. No long-term side effects were discovered, and the side effects experienced may be due to other confounding factors. CONCLUSION: From this data, we concluded oral TXA is a safe and effective treatment option for patients with persistent melasma.

Randomized, observer-blind, split-face study to compare the irritation potential of 2 topical acne formulations over a 14-day treatment period.

This randomized, observer-blind, split-face study assessed the irritation potential and likelihood of continued use of clindamycin phosphate 1.2%--benzoyl peroxide (BPO) 2.5% gel or adapalene 0.1%--BPO 2.5% gel once daily over a 14-day treatment period in 21 participants (11 males; 10 females) with acne who were 18 years or older. Investigator clinical assessment (erythema and dryness) and self-assessment (dryness and burning/stinging) were performed at baseline and each study visit (days 1-14) using a 4-point scale (O = none; 3 = severe). Transepidermal water loss (TEWL) and corneometry measurements were performed at baseline and days 3, 5, 7, 9, 11, and 14. Lesions were counted at baseline and on day 14. Participant satisfaction questionnaires were completed on days 7 and 14. At the end of the study, investigators reported none or only mild erythema in 86% (18/21) of participants treated with clindamycin phosphate 1.2%--BPO 2.5% gel compared with 62% (13/21) of participants treated with adapalene 0.1%--BPO 2.5% gel. No severe erythema was reported with clindamycin phosphate 1.2%--BPO 2.5% gel. Adapalene 0.1%--BPO 2.5% gel was prematurely discontinued due to severe erythema in 1 participant on day 5 and a second participant on day 9. Additionally, 2 more participants reported severe erythema on day 14. Mean erythema scores were 0.9 (mean change from baseline, 0.7) with clindamycin phosphate 1.2%--BPO 2.5% gel and 1.4 (mean change from baseline, 1.3) with adapalene 0. 1%--BPO 2.5% gel on day 14 (P < .05 for days 6-14). Similar results were seen with dryness. Mean scores were 0.5 (mean change from baseline, 0.4) and 1.0 (mean change from baseline, 1.0), respectively (P < .05 for days 6-14). Self-assessment, TEWL, and corneometry results underscored the investigator clinical assessment. Participant preference and likelihood of continued usage was greater with clindamycin phosphate 1.2%--BPO 2.5% gel. Continued use and efficacy results for the treatment of acne were influenced by the potential of the product to cause irritation and the participant preferences. Irritation potential was more pronounced and severe with adapalene 0.1%--BPO 2.5% gel. Undoubtedly, as a result more participants preferred treatment with clindamycin phosphate 1.2%--BPO 2.5% gel and were more likely to continue to use the product.

Tretinoin for the treatment of photodamaged skin.

Interest in and interventions for photodamaged skin have dramatically increased over the last few years. Although a number of topical therapies have been used for the treatment of photodamaged skin, many therapies remain unproven in efficacy, unapproved, or only supported with limited clinical evidence. Topical retinoids, particularly tretinoin, are the most extensively studied. They have been shown to attenuate and reverse the signs of photodamage, such as coarse wrinkling. In addition, the clinical changes achieved with tretinoin are accompanied by histologic evidence of benefit. The main drawbacks to retinoid use are local irritation and erythema that can limit utility in some patients. New retinoids and formulations specifically optimized to improve cutaneous tolerability have been introduced. Two case reports of patients using low-concentration tretinoin gel 0.05% for the treatment of photodamaged skin are discussed. Over a relatively short treatment period of 4 weeks, tretinoin gel 0.05% was shown to provide both chemoprevention and reversal of photodamage.

Differences in perceived importance and personal use of sun protection among primary care physicians are reflected in their clinical practice.

BACKGROUND: There is inadequate data regarding sun protection awareness, personal practice, and patterns of patient education among primary care clinicians. METHODS: Anonymous surveys were mailed to physicians in the Departments of Medicine, Family Practice, and Pediatrics at our institution. RESULTS: Of the 578 surveys distributed to primary care physicians, 170 (29%) responded. Of the responding physicians, 116 (68%) reported wearing sunscreen whenever outside, 14 (8%) did so daily, and 12 (7%) never wore sunscreen. Additionally, 54 (32%) reported wearing protective clothing consistently and 100 (59%) did so occasionally. Given a list of preventive medicine issues, sun protection was ranked lowest on a 10-point scale (6.7), behind smoking cessation (9.0), active lifestyle (8.2), and cholesterol control (7.4). Pediatricians placed the highest relative ranking (7.7) for sun protection and were most consistent in providing sun protection education, with 60% reporting this practice in over half of visits, compared to 32% of family physicians and 17% of internists. Among attending physicians, 70% reported wearing sunscreen whenever they are outside, compared to 58% of house-staff physicians. Attending physicians reported providing sun protection counseling more frequently than house-staff physicians (33% vs. 8%). The greatest impediments in providing sun protection counseling were inadequate time during office visits, not thinking about sun protection during office visits, and lack of proper training. Limitations The response rate to our survey was relatively low. The perceived importance and personal practice of sun protection at our Midwestern academic institution may not reflect those of physicians practicing in other regions or settings. CONCLUSIONS: Differences in the perceptive importance and personal practice of sun protection are reflected in the self-reported clinical practice of these primary care physicians. This reinforces the opportunity to educate primary care clinicians to join the public health effort to increase sun protection awareness.

Tanning bed exposure increases the risk of malignant melanoma.

BACKGROUND: Epidemiologic studies have associated tanning bed exposure and cutaneous melanoma. The relationship between the extent of tanning bed exposure and the risk of melanoma has not been elucidated in detail. METHODS: Surveys assessing the extent of tanning bed exposure and the history of skin cancer, including malignant melanoma, were collected from academic dermatology clinic patients (n = 1518). Of these, 551 (36.3%) completed all components of the survey. The available medical records, including pathology reports (n = 501; 33%), were reviewed to confirm cases of skin cancer. Data on potential confounding factors, including indoor vs. outdoor occupation and leisure activities, Fitzpatrick skin type, history of blistering sunburn, use of sunscreen and sun protective clothing, history of phototherapy, and level of education, were assessed and compared. RESULTS: Of the patients surveyed, 487 (32.1%) reported tanning bed exposure. Women aged 45 years or younger accounted for about 60% of all tanning bed users. Seventy-nine cases of malignant melanoma were reported, 22 in women aged 45 years or younger. In the entire cohort, the "ever-use" of tanning beds was found to be a significant risk factor for the development of melanoma [P < 0.05; odds ratio (OR), 1.64; 95% confidence interval (95% CI), 1.01-2.67]. The risk was greater in women aged 45 years or younger (P < 0.05; OR, 3.22; 95% CI, 1.01-11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (P < 0.01; OR, 3.18; 95% CI, 1.48-6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI, 1.41-12.02). LIMITATIONS: The study was subject to recall bias, included only patients at a midwestern academic practice, and had a relatively low response rate. CONCLUSION: Exposure to tanning beds increases the risk of malignant melanoma, especially in women aged 45 years or younger. These findings reinforce the hazards of tanning bed exposure.

Timing and velocity randomization similarly affect anticipatory pursuit.

Smooth pursuit eye movements are guided largely by retinal-image motion. To compensate for neural conduction delays, the brain employs a predictive mechanism to generate anticipatory pursuit that precedes target motion (E. Kowler, 1990). A critical question for interpreting neural signals recorded during pursuit concerns how this mechanism is interfaced with sensorimotor processing. It has been shown that the predictor is not simply turned-off during randomization because anticipatory eye velocity remains when target velocity is randomized (E. Kowler & S. McKee, 1987; G. W. Kao & M. J. Morrow, 1994). This study was completed to compare pursuit behavior during randomized motion-onset timing with that occurring during direction or speed randomization. We found that anticipatory eye velocity persisted despite motion-onset randomization, and that anticipation onset time was between that observed in the different constant-timing conditions. This centering strategy was similar to the bias of eye velocity magnitude away from extremes observed when direction or speed was randomized. Such a strategy is comparable to least-squares error minimization, and could be used to facilitate acquisition of a target when it begins to move. Centering was in some observers accounted for by a shift of eye velocity toward that generated in the preceding trial. The results make unlikely a model in which the predictor is disengaged by randomizing stimulus timing, and suggest that predictive signals always interact with those used in sensorimotor processing during smooth pursuit.

Nephrogenic fibrosing dermopathy with systemic involvement.

BACKGROUND: There is a growing literature regarding sclerotic and panniculitic cutaneous conditions seen in patients with end-stage renal disease (eg, calciphylaxis and soft tissue calcification). Nephrogenic fibrosing dermopathy (NFD) is a recent designation to describe cutaneous findings in patients with end-stage renal disease who developed sclerotic plaques with scleromyxedema-like histologic features. Soft tissue calcification is rare in patients with NFD and systemic involvement has not been reported. OBSERVATIONS: We describe a patient with end-stage renal disease who developed diffuse indurated woody plaques consistent with NFD in association with soft tissue calcification with catastrophic sequelae. A deep excisional biopsy specimen from the patient revealed thickened collagen bundles in the reticular dermis, plump bipolar spindle cells, and increased mucin. Focally, there were zones of calcium deposition in dermal collagen without vessel calcification. Autopsy of the patient revealed extensive fibrosis and calcification of the diaphragm, psoas muscle, renal tubules, and rete testes. The patient died 11 months after developing NFD. CONCLUSION: A subset of patients with NFD may have significant systemic involvement.

Practical and experimental consideration of sun protection in dermatology.

Much is known regarding the deleterious effects of ultraviolet radiation (UV) on the skin. As more epidemiologic and basic research continues to characterize the impact of sun exposure and other sources of UV radiation upon the development of cutaneous neoplasm and a variety of photosensitive dermatoses, it is crucial for the dermatologist to promote sun protection among his/her patients as well as the primary care physician who has a greater reach of the community than the skin specialist. Practical steps to achieve optimal sun protection include avoidance of UV radiation, avoidance of photosensitizing drugs, use of photo-protective clothing, and diligent application of broad-spectrum sunscreens. In recent years, novel agents and experimental modalities with the potential to offer enhanced protective effects against deleterious sequelae of sun exposure have been elucidated, e.g. antioxidants, alpha-MSH, polyphenol in green teas, genistein, NF-kB decoy oligodeoxynucleotides, pTpT vaccination, and IL-12. As these new photo-protective tools are being developed by scientists around the world, greater concerted effort is needed to engage public health officials and the media to promote sun protection awareness throughout the general public.