Cysteamine Isobionic-Amide Complex Versus Kligman's Formula for the Treatment of Melasma: Equal Efficacy and Rapid Onset of Action.

BACKGROUND: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobionic-amide -- a complex with enhanced depigmenting efficacy -- and compared it to mKF for the treatment of melasma. METHODS: This study involved a total of 80 patients divided into 3 groups: cysteamine-isobionic amide, placebo, or mKF. The modified Melasma Area Severity Index (mMASI) score and spectrophotometric evaluation were conducted at baseline, week 4, week 8, and week 16. Dermatological assessment, patients’ feedback, and satisfaction including quality-of-life scores were also collected. RESULTS: At week 4, cysteamine isobionic-amide and mKF groups showed an equivalent onset of action in terms of mMASI and skin pigmentation contrast reduction. The 2 groups significantly reduced melasma severity and improved the overall skin condition with a comparable efficacy at week 16. Quality of life of melasma patients was significantly improved in the cysteamine isobionic-amide group at week 8 and further at week 16 (P<0.001) compared to the mKF group. Patients’ feedback and satisfaction were higher with the cysteamine isobionic-amide product compared to mKF. CONCLUSION: Cysteamine isobionic-amide provided a rapid onset of action and was as effective as the mKF for the treatment of melasma. The data suggest that cysteamine isobionic-amide could potentially be an acceptable alternative to mKF for the long-term treatment of melasma. J Drugs Dermatol. 2024;23(2):9-16.  doi:10.36849/JDD.7428.

Extension Phase of a Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be associated with increased production and/or reduced clearance of pigmentation in the skin. Multiple pathways are involved in causality. A novel topical product was recently developed, which contains actives that have been validated through in-vitro and clinical studies to counteract pigmentation related to photodamage, PIH, and melasma. This study further evaluates the safety and efficacy of this product for facial dyschromia during an additional 3-month extension period following the completion of the previous 12-week multi-center trial.  Study Design: Subjects from the previous multi-center trial with mild to severe facial dyschromia at baseline were eligible to participate in this 3-month extension study upon completion of that trial. This extension study evaluated the continued use of the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) over a 3-month period. Subjects who were previously randomized to the novel topical product continued using it and for those previously randomized to hydroquinone 4% discontinued its use. Both cohorts continued daily sunscreen use. Blinded investigators assessed subjects at follow-up visits at 16, 20, and 24 weeks. RESULTS: Twenty-six (26) subjects completed the extension phase of the pivotal trial, with 13 subjects in each of the AL and HQ-BREAK cohorts. Significant improvements were seen within the AL cohort from weeks 12 to 24 for facial dyschromia (P=0.0158) and skin tone/clarity/evenness (P=0.0067), while there were no significant improvements seen in the HQ-BREAK cohort. The HQ-BREAK cohort had more subjects who worsened with facial dyschromia and skin tone/clarity/evenness. For the mMASI, the HQ-BREAK cohort demonstrated regression at week 24 compared to week 12, while the AL cohort instead experienced continued improvement. This difference was found to be significant (P=0.02). No study-related adverse events were reported for either cohort.  Conclusion: A novel topical product designed to counteract various steps in pigmentation pathways using PATH-3 Technology has been demonstrated to be safe and effective in treating facial dyschromia on a long-term basis. In contrast to the significant rebound experienced by subjects with HQ, the AL cohort continued to demonstrate ongoing improvement. J Drugs Dermatol. 2024;23(1):1266-1270.     doi:10.36849/JDD.7622.

Comparing the Efficacy and Tolerability of Moderate to Severe Hyperpigmentation and Skin Unevenness.

Dyschromia is the result of irregular facial pigmentation. These cutaneous manifestations can have a significant impact on the quality of life of those affected, especially among females and skin of color. In this randomized, double-blinded, two-cell, single-center, 16-week clinical study, all subjects had moderate to severe (scores 4-9 on the modified Griffiths Scale) hyperpigmentation and skin unevenness of the face such that approximately 20% of subjects had post-inflammatory hyperpigmentation (PIH), 40% had overall mottled hyperpigmentation, and 40% had superficial melasma (Superficial Melasma was determined by Wood's Lamp Assessment). Study participants received either Product A (proprietary new formulation - Cysteamine HSA) or Product B (current marketed product - Cyspera®) and used the test product either in the morning or at night, beginning with every other day application, and then advanced to every day, or as tolerated. The results revealed that both Product A (Cysteamine HSA) and Product B (Cyspera®) had statistically significant improvement in facial hyperpigmentation and skin unevenness, however, Product A (Cysteamine HSA) had better tolerability results for scaling, peeling, burning, stinging, erythema, and dryness, indicating that Product A (Cysteamine HSA) outperformed Product B (Cyspera®). J Drugs Dermatol. 2024;23(1):1260-1265.     doi:10.36849/JDD.7584.

Urinary Bladder "Melanosis": A Case Report and Review of the Literature.

Melanosis of the urinary bladder, so-called melanosis vesicae, is a rare condition characterized by dark, velvety bladder mucosa observed by cystoscopy examination. Up to 20 examples have been reported in the English literature, and the etiology of this disease still needs to be discovered. We present an 82-year-old woman with a history of pelvic organ prolapse-associated urinary symptoms. The patient was found to have pigmented urinary bladder mucosa on cystoscopy and underwent a total hysterectomy and bladder mucosal biopsy. Histologically, pigmented granules were evident in the bladder stroma and epithelium, highlighted by Periodic Acid-Schiff (PAS) stain, suggestive of lipofuscin in nature. We outline the diagnostic features of bladder melanosis, discuss the diagnostic mimickers, and thoroughly review the literature on the subject.

Topical Treatments for Melasma and Post-inflammatory Hyperpigmentation.

BACKGROUND: Dyschromia is one of the most common reasons for patients to seek dermatological care, especially among individuals with skin of color. Most cases present as melasma or post-inflammatory hyperpigmentation (PIH); both are chronic issues requiring long-term treatment. While many pharmaceutical (topical or systemic) or procedural (lasers/chemical peels) options are available, some treatments are not safe/tolerable for long-term use or can induce/exacerbate PIH.  Methods: This qualitative review provides an overview of topical treatments for melasma and PIH, including recent data from an investigator-initiated trial of the retinoid tazarotene.  Results: Topical hydroquinone (HQ) in the form of triple combination HQ 4%/tretinoin 0.05%/fluocinolone acetonide 0.01% cream is the gold-standard treatment for melasma and PIH but should not be used long-term due to safety concerns. Efficacy data for OTC/cosmeceutical products are limited or lacking. Topical retinoids are efficacious and safe, though dose and formulation differences may affect tolerability. Tazarotene 0.045% polymeric emulsion lotion demonstrated good efficacy, safety, and tolerability over 24 weeks in adult female patients with moderate-to-severe melasma and/or PIH. CONCLUSIONS: There are multiple topical treatments available for dyspigmentation. However, many are lacking efficacy data and others are limited by tolerability or safety concerns. Retinoids, such as tazarotene, may be an efficacious and safe treatment for melasma or PIH. J Drugs Dermatol. 2023;22(11):1118-1123     doi:10.36849/JDD.7754.

Prescribing practices of tranexamic acid for melasma: Delphi consensus from the Pigmentary Disorders Society.

Introduction There is ambiguity regarding usage of tranexamic acid for melasma in India, be it in its pre-administration evaluation, administration route, dosing or monitoring. Hence, we conducted this study to understand various tranexamic-acid prescribing patterns and provide practical guidelines. Materials and methods A Google-form-based questionnaire (25-questions) was prepared based on the key areas identified by experts from the Pigmentary Disorders Society, India and circulated to practicing dermatologists across the country. In rounds 2 and 3, the questionnaire was re-presented to the same group of experts and their opinions were sought. The results of the practitioners' survey were denoted graphically alongside, to guide them. Consensus was deemed when at least 80% of respondents chose an option. Results The members agreed that history pertaining to risk factors for thromboembolism, cardiovascular and menstrual disorders should be sought in patients being started on oral tranexamic-acid. Baseline coagulation profile should be ordered in all patients prior to tranexamic-acid and more exhaustive investigations such as complete blood count, liver function test, protein C and S in patients with high risk of thromboembolism. The preferred oral dose was 250 mg orally twice daily, which can be used alone or in combination with topical hydroquinone, kojic acid and sunscreen. Repeated dosing of tranexamic-acid may be required for those relapsing with melasma following initial tranexamic-acid discontinuation. Coagulation profile should ideally be repeated at three monthly intervals during follow-up, especially in patients with clinically higher risk of thromboembolism. Treatment can be stopped abruptly post improvement and no tapering is required. Limitation This study is limited by the fact that open-ended questions were limited to the first general survey round. Conclusion Oral tranexamic-acid provides a valuable treatment option for melasma. Frequent courses of therapy may be required to sustain results and a vigilant watch is recommended for hypercoagulable states during the course of therapy.

Pigmented lesions of the conjunctiva: The sheep and the wolf.

Background: Pigmented lesions in the conjunctiva can be baffling to both the patients and the treating ophthalmologist because of their varied range of presentation and overlapping clinical features. The lesions range from incidental pigment deposition such as mascara and complexion-associated melanosis to malignant melanoma which poses a risk to life. Similarly, the management ranges from observation at regular intervals to aggressive surgery like exenteration. Purpose: We wanted to present a crisp and precise video of the good, bad, and ugly pigmented lesions of the conjunctiva, highlighting their specific clinical features important for the diagnosis and their management. Synopsis: This video describes the myriad of pigmented conjunctival lesions, their diagnostic characteristics, and management based on oncological principles. Link: https://drive.google.com/file/d/1BYJ51rQtqjwM6e73BwrrLqdC1EoXA8Eu/view?usp=sharing. Highlights: : Pigmented lesions can have variable presentation and close mimics, therefore, it is important to differentiate and identify the lesions accurately. This video highlights different pigmented lesions and their individual characteristic features. Video link https://youtu.be/m9tt7dx9SWc.

Unveiling the mystery of Riehl's melanosis: An update from pathogenesis, diagnosis to treatment.

Riehl's melanosis is a hyperpigmentation disorder that has a significant psychological and social impact on individuals. In the past 10 years, new categories have been developed, raising questions about how to classify Riehl's melanosis. The mechanism of this disease remains unclear, although the type IV hypersensitivity response caused by allergic sensitization, as well as genetic, ultraviolet radiation, and autoimmune factors, is to blame. Clinical manifestation, dermoscopy, reflectance confocal microscopy, patch/photopatch testing, histopathology, and a novel multimodality skin imaging system have been used for the diagnosis. A variety of therapies including topical skin-lightening agents, oral tranexamic acid, glycyrrhizin compound, chemical peels, and lasers and light therapies (intense pulsed light, 1064-nm Q-Switched Nd: YAG laser, 755-nm PicoWay laser, nonablative 1927-nm fractional thulium fiber laser, new pulsed-type microneedling radiofrequency), with improved effectiveness. The latest findings on possible biomarkers and their relationship to other autoimmune diseases were also summarized.

[Melanosis of the bladder-a rare diagnosis]. / Melanose der Harnblase ­ eine Rarität.

Melanosis of the urinary bladder is an extremely rare benign condition in which melanin deposits occur in the urothelial and stromal cells. We report such a case in which melanosis of the urinary bladder was detected in a 55-year-old woman with known multiple sclerosis during an extended workup due to urinary urgency complaints. The findings were confirmed by biopsy.

[Analysis of 14 cases of melanosis caused by 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene].

14 workers in the 1, 8-diaminonaphthalene workshop of a chemical company in Nantong City had symptoms or signs of varying degrees of pruritus and pigmentation of the face, neck and waist. Pathological examination of skin biopsies showed hyperkeratosis, the basal cells were liquefied and denatured. Seven workers were eventually diagnosed with occupational melanosis. To explore the causes of occupational melanosis caused by exposure to 1, 8-dinitronaphthalene and 1, 8-diaminonaphthalene, and to provide reference for the prevention and treatment of occupational melanosis in the future, this paper reported 14 cases of melanosis in the skin of workers in chemical industry.

Disorders of Facial Hyperpigmentation.

Disorders of hyperpigmentation are common and challenging conditions which can arise due to a myriad of etiologic factors. Many of them can present across skin types but are more common in skin of color individuals with Fitzpatrick skin types III-VI. Facial hyperpigmentation, in particular, can have a significant impact on the quality of life of affected individuals due to its increased visibility. This article provides a comprehensive review of disorders of facial hyperpigmentation including epidemiology, pathogenesis, diagnostic considerations, and treatment approaches for these conditions.

A Multi-Center, Randomized, Blinded Clinical Study Evaluating the Efficacy and Safety of a Novel Topical Product for Facial Dyschromia.

BACKGROUND: Dyschromia can be caused by abnormalities in the increased production and/or reduced clearance of pigmentation in the skin. Causes of hyperpigmentation include excessive sun exposure, medications, hormones, post-inflammatory hyperpigmentation (PIH), and medical disorders, such as melasma. A novel topical product was recently developed, which contains actives that have been validated through in vitro studies to counteract various steps in the pigmentation pathways, including photodamage, PIH, and melasma. This study evaluates the safety and efficacy of this product for facial dyschromia. STUDY DESIGN: Subjects with mild to severe facial dyschromia were enrolled to receive either the novel topical product with PATH-3 Technology (Alastin Skincare, Carlsbad, CA) or hydroquinone 4% topical to apply twice daily. Both cohorts received cleanser, sunscreen, and moisturizer. Follow-up occurred at weeks 4, 8, and 12. Blinded investigators used the modified Melasma Area Severity Index (mMASI) and modified Griffiths scales at baseline and final follow-up. Tolerability assessments and subject questionnaires were completed. RESULTS: Forty-three subjects were enrolled and randomized to either the novel topical product (n=22) or hydroquinone 4% (n=21) cohort. At week 12 follow-up, subjects using the novel topical product had significant improvements in mMASI scores for the right cheek (P=0.0097), left cheek (P=0.0123), combined cheeks (P=0.0019), and total facial area (P=0.0046). In contrast, subjects using hydroquinone 4% had no significant improvements in any of these areas. Although both cohorts demonstrated improvements in dyschromia and skin tone, the novel topical product also offered significant improvements in skin radiance (P=0.0015) and skin texture (P=0.0058), which the hydroquinone 4% cohort did not demonstrate. The hydroquinone 4% cohort experienced 5 adverse events, while there were no adverse events associated with the novel topical product. Subjects in the hydroquinone 4% cohort also more frequently experienced burning/stinging, tingling, itching, erythema, and dryness. CONCLUSION: A novel topical product with PATH-3 Technology, designed to counteract various steps in pigmentation pathways, has been demonstrated to be safe and effective in treating facial dyschromia. CITATION: Wang JV, Fabi SG, Mraz Robinson D, et al. A multi-center, randomized, blinded clinical study evaluating the efficacy and safety of a novel topical product for facial dyschromia. J Drugs Dermatol. 2023;22(4):333-338. doi:10.36849/JDD.7340.

Optimizing Melasma Management With Topical Tranexamic Acid: An Expert Consensus.

Because of its complex pathogenesis, chronicity, and high rates of recurrence, melasma is regarded as a challenging skin disorder. Topical treatments are often offered as first-line therapy. However, many patients are unaware that melasma is recurrent and requires long-term management. Hydroquinone is effective for controlling relapses and has become the standard of care for melasma in many countries. Nonetheless, it is limited by its side effect profile. Certain patient profiles who have had prior therapy and/or are refractory to treatment may be offered an alternative, that is topical tranexamic acid (TXA) alone or in combination with other modalities. This review provides a summary of current evidence on topical TXA as a treatment for certain case profiles. This paper aims to fill knowledge gaps in terms of currently available options, highlighting the role of topical TXA alone or in combination with other active ingredients (ie, topical TXA 2% with patented delivery technology). J Drugs Dermatol. 2023;22(4): doi:10.36849/JDD.7104 Citation: Desai SR, Chan LC, Handog E, et al. Optimizing melasma management with topical tranexamic acid: An expert consensus. J Drugs Dermatol. 2023;22(4):386-392. doi:10.36849/JDD.7104.

Congenital melanocytic naevus syndrome and Dandy-Walker malformation - a mistaken association: case report and literature review.

Congenital melanocytic naevus (CMN) syndrome, previously termed neurocutaneous melanosis, is a rare disease caused by postzygotic mosaic mutations occurring during embryogenesis in precursors of melanocytes. The severity of neurological manifestations in CMN patients is related to central nervous system abnormalities found at magnetic resonance imaging. The association between CMN and Dandy-Walker malformation (DWM) has been described in the literature, but recent advances in imaging and genetics lead to diagnostic criteria revision. In this paper, we aim to re-evaluate the proposed association by reviewing the available literature and present a patient with CMN and a large posterior fossa cyst.

Melanosis coli: a contrast effect or an oncogenic effect? A large-scale retrospective cohort study.

BACKGROUND: Melanosis coli is characterized by brown mucosa with pigmentation. Studies have showed an increased adenoma detection rate in melanosis patients, whether it is caused by a contrast effect or an oncogenic effect is still controversial. The detection of serrated polys in melanosis patients remains unknown. AIMS: The study aimed to clarify the correlation of adenoma detection rate with melanosis coli and discuss outcomes in less-experienced endoscopists. Serrated polyp detection rate was also been investigated. METHODS: A total of 2150 patients and 39,630 controls were enrolled. A propensity score matching method was used to balance covariates between the two groups. The detection of polyps, adenomas, serrated polyps, and their features was analyzed. RESULTS: The polyp detection rate (44.65% vs 41.01%, P = 0.005) and adenoma detection rate (30.34% vs 23.92%, P < 0.001) were significantly higher, and the serrated polyp detection rate (0.93% vs 1.58%, P = 0.033) was significantly lower in melanosis coli. The percentage of low-risk adenomas (44.60% vs 39.16%, P < 0.001) and polyps with 6 to 10 mm in size (20.16% vs 16.21%, P < 0.001) were higher in melanosis coli. The detection of large serrated polyps was lower (0.11% vs 0.41%, P = 0.026) in melanosis coli. CONCLUSION: Melanosis coli correlates with an increased adenoma detection rate. The detection of large serrated polyps was lower in melanosis patients. Melanosis coli may not be considered a precancerous lesion.

Two different procedures for managing ocular melanosis presenting scleral pigmentation with glaucoma in a Shih-Tzu dog: A case of definitive diagnosis in one eye and a presumed diagnosis in the contralateral eye.

A 12-year-old castrated male Shih-Tzu dog was referred for uncontrolled glaucoma and uveitis with highly pigmented sclera, in both eyes (OU). On ophthalmic examination, the menace response, dazzle reflex and pupillary light reflex were negative OU. The intraocular pressure was 27 mmHg in the right eye (OD) and 70 mmHg in the left eye (OS) despite the administration of antiglaucoma eyedrops. Ultrasound biomicroscopy revealed a closed ciliary cleft OU. Ocular ultrasonography revealed hyperechoic materials in the vitreous OU and retinal detachment OS. When presented for recheck, an extensive malacic corneal ulcer was observed OS. To relieve pain in the blind eyes, enucleation OS and pharmacologic ciliary body ablation (CBA) OD were performed. Histologically, ocular melanosis, which is an inherited disease in the Cairn Terrier breed, was identified in the enucleated eye. The uvea was heavily pigmented. The iris and ciliary body were mildly distorted by a single population of large, round, nonneoplastic cells with pigmented cytoplasm. There was no evidence of an intraocular mass or metastasis before and after intravitreal CBA. This is the first report of bilateral ocular melanosis in a Shih-Tzu dog. Ocular melanosis is a possible differential diagnosis for globe presenting scleral pigmentation with glaucoma in even non-Cairn Terrier breeds and pharmacologic CBA could be considered as a treatment for ocular melanosis with end-stage glaucoma.