Appearance Of Hyperpigmentation Research Articles

Impact of Neoadjuvant Concurrent Chemoradiation (NACCRT) on Operability and Survival in Locally Advanced Inoperable Breast Cancer

Inoperable locally advanced breast cancers (LABC) are treated with neoadjuvant chemotherapy (NACT). However, many patients remain inoperable after NACT due to an inadequate response. We, therefore, investigated the role of neoadjuvant concurrent chemoradiation (NACCRT) in this setting. Patients with inoperable Stage III LABC were prospectively recruited in the study between May 2017 and December 2021. NACT consisted of 4 cycles of q3weekly Adriamycin (60 mg/m2) and Cyclophosphamide (600mg/m2), and 4 cycles of q3weekly Paclitaxel (175 mg/m2). Concurrent radiotherapy with 6 MV X-rays was given using a 3D conformal technique to a total dose of 46 Gy (2 Gy/fraction, 5 days/week) to the involved breast, axilla, supraclavicular fossa, and internal mammary chain (upper 3 intercostal spaces) along with the first two cycles of paclitaxel. A 0.5 cm bolus was used to boost the skin till the appearance of hyperpigmentation. All patients were assessed for surgery after the completion of the planned neoadjuvant treatment. Adjuvant treatments were given based on the receptor status. The impact of neoadjuvant CTRT on the pathological complete response (pCR), operability, and survival was analyzed. Event-free survival (EFS) and Overall Survival (OS) were analyzed using the Kaplan-Meier method. The study enrolled 202 female patients with a median age of 52 years, with 23.7% having IIIA, 65.3% IIIB, and 10.8% having IIIC disease. Hormone-receptor (HR) positive disease was observed in 90/202 (44.6%) patients, triple-negative (TNBC) in 50/202 (24.8%) and Her2/neu positive in 62/202 (30.7%) patients. Modified radical mastectomy was performed in 88.1% of patients, with 8.5% remaining inoperable and 3.4% declining surgery due to clinical complete response (cCR). Among the patients who underwent MRM, 65/178 (32.2%) patients had a pCR. pCR was observed in 13/81 (16%) with HR-positive disease, 21/46 (45.6%) with TNBC, and 31/51 (60.7%) patients with Her2/neu-positive disease. Grade 3 skin reactions were observed in 39/202 (19.3%). Postoperative wound morbidity requiring hospitalization was observed in 19/178 (10.6%) patients. The median follow-up was 42 months, with 4-year EFS and OS of 63.8% and 71.5%, respectively. Six out of 7 patients who were in cCR and declined surgery are alive and remain in cCR. On subgroup analysis of Her 2 positive patients, pCR was significantly associated with improved EFS and OS (89.8% vs 33.3%, p = 0.001 and 89.1% vs 44.4%, p = 0.001 respectively). Our study demonstrates the feasibility and efficacy of NACCRT in improving operability, pCR rates and survival outcomes in patients with inoperable LABC. The results suggest that NACCRT can be considered for use in clinical practice with careful patient selection. These findings contribute to the ongoing efforts to optimize treatment for this patient population and warrant further investigation in larger, randomized trials.

The development of flagellate hyperpigmentation after use of bleomycin for sclerotherapy slow flow vascular malformations

Introduction. Bleomycin is a cytotoxic antibiotic that is used as a sclerosing agent for sclerotherapy of vascular anomalies. Bleomycin is characterized by complications: nausea, vomiting, fever, the development of allergies/anaphylaxis, skin discoloration (hyperpigmentation), damage to lung tissue.Aim. To study the frequency of hyperpigmentation after administration of bleomycin for sclerotherapy of vascular malformations with slow flow characteristics. To present our own clinical observation of the development of skin hyperpigmentation after sclerotherapy of venous malformation with bleomycin.Materials and methods. A systematic review was conducted in foreign (PubMed, Web Of Science, Google Scholar, Scirus) and domestic databases (eLibrary) for the period from 2012 to 2022. As a result of the selection, 17 full-text articles remained suitable for their inclusion in the analysis.Results. In the first part of the review, 12 articles were analyzed, describing clinical observations of the development of “flaggelate” hyperpigmentation after chemotherapy of various neoplasms. In the second part of the review, an analysis of 4 articles describing clinical observations of the development of hyperpigmentation after intralesional administration of bleomycin into vascular malformation in 19 patients was carried out. Discussion. The occurrence of specific “flaggelate” hyperpigmentation after administration of bleomycin for sclerotherapy of vascular anomalies with slow flow characteristics is a rare complication. In the analysis carried out, there is no clear connection between the occurrence of hyperpigmentation and excess dosage.Conclusion. To prevent the appearance of hyperpigmentation, it is necessary to avoid excessive traumatization on time and immediately after sclerotherapy, including with ECG electrodes; avoid excessive oxygenation during the provision of anesthesia; it is necessary to avoid excessive insolation within 24–48 hours after sclerotherapy.

Assessment of Circadian-based Antioxidants Plus a Comprehensive Brightener in Skin of Color Patients With Hyperpigmentation.

Hyperpigmentation disorders disproportionately affect individuals with skin of color. There is an unmet need for safe and effective topical treatments for this population. The efficacy and tolerability of LYT2 in combination with LVS were assessed in skin of color patients with moderate to severe facial hyperpigmentation. A single-arm study was performed in Asian, Hispanic, or African American patients (Fitzpatrick phototypes III–VI). Subjects applied LYT2 and LVS daily, in addition to a basic skincare regimen, for 12 weeks. Overall hyperpigmentation, skin-tone evenness, and radiance were evaluated by the investigator, and subjects completed questionnaires regarding self-perceived efficacy. After 12 weeks, the combination of LYT2 and LVS produced a 23% improvement in overall hyperpigmentation, a 33% increase in skin-tone evenness, and a 51% increase in radiance compared to baseline. At the study conclusion, all patients noted at least a slight improvement in skin condition, and 70% reported good or excellent satisfaction. One subject (8%) experienced a treatment-related adverse event. The combination of LYT2 and LVS was well-tolerated and improved the appearance of hyperpigmentation and overall quality in skin of color. J Drugs Dermatol. 2022;21(4):376-380. doi:10.36849/JDD.6687.

Pigmented contact cheilitis: a systematic review.

Our objective was to carry out a systematic review of available data regarding pigmented contact cheilitis (PCC). Electronic searches were performed using PubMed, Scopus, Embase, Web of Science and LILACS electronic databases. The risk of bias was assessed using the Joanna Briggs Institute tool. A total of 2070 articles were retrieved, with 7 of them reporting PCC cases. Female individuals (n=6/85.7%) were more affected, with a mean age of 32±15.4 years (range: 22-47 years). Ricinoleic acid and gum ester were the most frequently observed allergic compounds, each present in two cases. Three patients had lesions in both lips (42.8%), while three other patients (42.8%) had lesions only in the lower lip. All reported cases presented with multiple pigmented lesions (n=7/100.0%). Associated symptoms involved itching, scaling, swelling, erythema, vesicles and papules. The mean evolution time was 13.5±15.6 months (range: 2-36 months), and the average follow-up time was 12±0 months. This is a condition that often scares the patient due to the unexpected appearance of hyperpigmentation. For this reason, the information transmitted in this review is expected to be relevant so that the health professional can include PCC in their list of differential diagnoses.

Photodermatoses: prevention and treatment

Increased exposure of the skin to sunlight has many negative effects: premature skin aging (photoaging), the risk of various skin cancers, the appearance of hyperpigmentation, and exacerbation of certain skin diseases.

Retinyl propionate and climbazole combination demonstrates clinical improvement to the appearance of hyperpigmentation and deep wrinkling with minimal irritation.

To evaluate a combination of retinyl propionate and climbazole (RPC) compared to 0.1% retinol for its efficacy, tolerance and ageing appearance. Forty-five healthy Caucasian females, ages 40-70, with moderately photodamaged facial skin, were recruited for a 16-week randomized, double-blind, IRB-approved facial study. The efficacy of RPC treatment was compared to 0.1% retinol, in the same product base formulation, with twice daily, split-face product application. Changes in overall photodamage, fine lines and wrinkles, pigmentation and irritation were visually evaluated and measured by instrumentation. Subjective appraisal of efficacy was self-assessed from images where subjects were blinded to treatment and time point. Irritancy potential was also evaluated in a 5-day randomized, double-blind, IRB-approved patch study. Treatment with RPC resulted in significant (P < 0.05) improvement in ageing attributes compared to 0.1% retinol treatment, with minimal irritation. More than 50% of subjects showed improvement to deep wrinkles in the crow's feet area after 5 weeks of product application, and continued improvement to deep wrinkles was observed throughout the course of the study. Similarly, improvement was observed for the appearance of lines and wrinkles in the nasolabial fold (NLF) and for mottled hyperpigmentation. The results from subjective self-assessment confirmed in vivo clinical assessments. In a separate patch study, significantly less irritation was observed with the RPC product as compared to the 0.1% retinol control product. RPC delivered significant skin anti-ageing benefits comparable or greater than 0.1% retinol, with minimal irritation.

HYPERPIGMENTATION OF THE SKIN: MODERN VIEWS ON ETIOLOGY AND PATHOGENESIS (PART 1)

Brief literature review of the etiology and pathogenesis of hyperpigmentation on the basis of modern scientific publications is presented. The review focuses on actively studied mechanisms of melanin synthesis in norm and pathology, the physiology of pigment cells (melanocytes), their interaction with other structures of the epidermis and dermis and on the mechanisms of regulation of melanogenesis. The main factors influencing the appearance of hyperpigmentation are described.

Facial primer provides immediate and long-term improvements in mild-to-moderate facial hyperpigmentation and fine lines associated with photoaging.

BackgroundPhotoaged skin results from various environmental factors, most importantly chronic sun exposure. Dyschromia and fine lines/wrinkles are common clinical manifestations of photodamaged skin.PurposeThis single-center clinical trial was conducted to assess the efficacy and tolerability of a new multifunctional facial primer (camouflage, broad-spectrum SPF 50, and a treatment for hyperpigmentation) when used by females with mild-to-moderate facial hyperpigmentation and fine lines due to photoaging over a course of 12 weeks.Patients and methodsSubjects were provided test material (Even Up-Clinical Pigment Perfector) and supporting products to use on their face and neck. Products were used according to specific application instructions. Clinical grading for efficacy and tolerability assessments were performed by an expert grader at baseline, baseline (post-application primer), week 4, week 8, week 12, and week 12 (post-application primer). Standardized digital photographs were taken, and self-assessment questionnaires were conducted.ResultsTwenty-eight female subjects completed the 12-week trial. The facial primer improved scores for the appearance of hyperpigmentation and other photoaging parameters immediately after the first application. The treatment also showed a progressive improvement in the clinical assessment of hyperpigmentation and other photoaging parameters over the 12-week trial. These long-term benefits can be attributed to an improvement in the underlying skin condition. The facial primer was well tolerated. Subject questionnaires showed that the product was highly rated at all visits.ConclusionThe facial primer was shown to be effective and well tolerated for immediate and long-term improvement in the appearance of mild-to-moderate hyperpigmentation and fine lines associated with photodamage when used over a 12-week period.

A regulator of ubiquitin-proteasome activity, 2-hexyldecanol, suppresses melanin synthesis and the appearance of facial hyperpigmented spots

2-Hexyldecanol has long been used in skin-care products, but has not previously been reported as an active ingredient for skin benefits. To evaluate 2-hexyldecanol in in vitro and ex vivo systems and, if found to be active, progress it to topical clinical testing to determine effects on pigmentation in skin. 2-Hexyldecanol was tested in melanocyte cell culture systems (B16 mouse melanoma cells and normal human melanocytes) for its effect on proteolytic activity and melanin production, in the absence and presence of the proteasome-specific inhibitor, MG132. It was further tested in a human skin explant model for its effect on melanin production. Lastly, topically applied 2-hexyldecanol was evaluated for its effect on the appearance of facial pigmentation in an 8-week, randomized, double-blind, vehicle-controlled, split-face incomplete block design study in Chinese women. In submerged cell culture, 2-hexyldecanol upregulated proteolytic activity and decreased melanin synthesis. These effects were antagonized by the proteasome-specific inhibitor MG132. MG132, tested in the absence of 2-hexyldecanol, increased melanin production. In a human skin explant model, topical 2-hexyldecanol suppressed the production of melanin vs. a vehicle control. In a human clinical study in Chinese women (n = 110 observations per test material), a 2-hexyldecanol-containing formulation significantly reduced the appearance of facial hyperpigmented spots vs. its control. These data indicate that regulation of proteasome activity is a viable target for control of melanin production, that 2-hexyldecanol upregulates proteasomal activity in melanocytes, and that topical 2-hexyldecanol reduces the appearance of hyperpigmentation.

The effects of a daily facial lotion containing vitamins B3 and E and provitamin B5 on the facial skin of Indian women: A randomized, double-blind trial

The B vitamins niacinamide and panthenol have been shown to reduce many signs of skin aging, including hyperpigmentation and redness. To measure the facial skin effects in Indian women of the daily use of a lotion containing niacinamide, panthenol, and tocopherol acetate using quantitative image analysis. Adult women 30-60 years of age with epidermal hyperpigmentation were recruited in Mumbai and randomly assigned to apply a test or control lotion to the face daily for 10 weeks. Effects on skin tone were measured using an image capturing system and associated software. Skin texture was assessed by expert graders. Barrier function was evaluated by transepithelial water loss measurements. Subjects and evaluators were blinded to the product assignment. Of 246 women randomized to treatment, 207 (84%) completed the study. Women who used the test lotion experienced significantly reduced appearance of hyperpigmentation, improved skin tone evenness, appearance of lightening of skin, and positive effects on skin texture. Improvements versus control were seen as early as 6 weeks. The test lotion was well tolerated. The most common adverse event was a transient, mild burning sensation. Daily use of a facial lotion containing niacinamide, panthenol, and tocopheryl acetate improved skin tone and texture and was well tolerated in Indian women with facial signs of aging.

Reduction in the appearance of facial hyperpigmentation by topical N‐undecyl‐10‐enoyl‐l‐phenylalanine and its combination with niacinamide

N-undecyl-10-enoyl-L-phenylalanine (Sepiwhite), N-undecylenoyl phenylalanine), a reported alpha-melanocyte-stimulating hormone (MSH) receptor antagonist, has been observed to reduce melanin production in cultured melanocytes. In other testing, niacinamide has been found to inhibit melanosome transfer in cultured cells and to reduce the appearance of hyperpigmented spots in clinical studies. Since these two agents function by different mechanisms, we conducted two studies to determine if their combination is more effective than niacinamide alone in reducing facial hyperpigmentation. Two double-blind, 10-week (2-week washout + 8-week treatment), left-right randomized, split-face clinical studies were conducted. In one, two groups of Japanese women applied one of two pairs of test emulsion formulations: a vehicle control and a 5% niacinamide formulation (n= 40), or a 5% niacinamide and a 5% niacinamide plus 1%N-undecylenoyl phenylalanine formulation (n = 40). Each formulation was applied to the randomly assigned side of the face. In the second study, Caucasian women applied one of three emulsions: vehicle control, 5% niacinamide formulation, or combination 5% niacinamide plus 1%N-undecylenoyl-phenylalanine formulation to the randomly assigned side of the face (n = approximately 60 treatment sites per formulation). In both studies, hyperpigmented spots were evaluated at weeks 4 and 8 by quantitative image analysis. In both studies, the combination formulation was significantly more effective than the vehicle and the 5% niacinamide formulation in reducing the appearance of hyperpigmentation after 8 weeks. The combination of 5% niacinamide and 1%N-undecylenoyl phenylalanine is an effective anti-aging technology for use on facial skin.

Pathology of conjunctival melanocytic neoplasms

Abstract Purpose To describe the classification, grading and staging of conjunctival melanocytic proliferation. Methods We have audited our experience with conjunctival melanomas, using a novel mapping system and have found shortcomings in the current Tumour Node Metastasis (TNM) staging system. We have also reviewed our cases of intra‐epithelial melanocytic neoplasia and confirmed other authors’ impressions that conjunctival ‘primary acquired melanosis with atypia’ is histologically similar to cutaneous in situ melanoma. To improve objectivity in the reporting of conjunctival intra‐epithelial melanocytic neoplasia, we propose a scoring system based on pattern of melanocytic infiltration, density of melanocytes &amp; degree of cellular atypia. Results The term ‘conjunctival melanosis’ should be used only to describe the slit‐lamp appearance of hyperpigmentation. Histologically, this abnormality should be categorized as ‘hypermelanosis’ or ‘melanocytosis’. Hypermelanosis can either be primary or secondary to ocular or systemic disease. Benign melanocytosis comprises conjunctival melanocytic hyperplasia and naevi. Malignant melanocytosis is essentially melanoma, which is primary (in situ or invasive) or secondary (i.e., spreading to conjunctiva from adjacent tissues) or rarely metastatic. We suggest that the TNM staging system for conjunctival melanoma should be revised to: (1) include a Tis stage; (2) take account of superficial extent, invasion of adjacent tissues and caruncular involvement, in stages TI to TIII; and (3) to sub‐categorize TIV disease so that there is better correlation with likely mortality. Conclusion We have revised the classification of conjunctival melanocytic proliferations &amp; improved the grading and staging of melanoma. These developments should be useful in treatment &amp; research.

Pigmentation With Doxorubicin Therapy

To the Editor.— Hyperpigmentation of the nails and nail beds attributed to certain antitumor drugs has been described in several reports in the literature. 1-5 The observed pathologic characteristics have usually included the appearance of transverse nail pigmentation after several weeks or several months of drug therapy. We report the appearance of hyperpigmentation over the metacarpophalangeal joints and the interphalangeal joints, as well as homogeneous and transverse pigmentary changes of the nails, following doxorubicin hydrochloride administration. Report of a Case.— A 60-year-old woman showed development of ulcerating, bleeding right chest wall nodules, a nonproductive cough, dyspnea, anorexia, and back pain 15 months after a right radical mastectomy for stage II mammary carcinoma. A biopsy specimen from one of the chest wall nodules demonstrated scirrhous adenocarcinoma. Bilateral pulmonary infiltrates were present in both lungs. A bone scan demonstrated increased tracer activity in multiple osseous sites including two lumbar vertebrae. Therapy with

Hyperpigmentation on Cortisone After Adrenalectomy for Primary Aldosteronism

Hyperpigmentation occurring in, patients with primary adrenal insufficiency, who secrete less than normal amounts of hydrocortisone, has been well recognized1and would be expected to occur in subjects adrenalectomized bilaterally who were not receiving adequate steroid replacement.2The increased pigmentation observed in these patients is related to elevated plasma melanocyte stimulating hormone (MSH) and perhaps also to elevated levels of adrenocorticotropic hormone (ACTH).3Although plasma ACTH and MSH are clearly elevated in states of adrenal insufficiency, the diurnal rhythm for both ACTH and MSH may persist.4,5With physiological doses of cortisone, plasma ACTH5and MSH6values fall to within the normal range. The appearance of hyperpigmentation in a patient already receiving adequate replacement therapy would thus be unexpected and should warrant an evaluation of possible causes. The purpose of this communication is to describe a patient who initially was found to have primary aldosteronism

KERATODERMA AND MELANODERMA ACCOMPANYING THERAPY WITH A GOLD COMPOUND

Cases have been reported in which cutaneous hyperpigmentation appeared on the site of gold dermatitis subsequent to its resolution. There are no reports concerning the development of primary melanoderma, that is, of the spontaneous appearance of hyperpigmentation, without relation to a preexisting eruption. Likewise a search of the literature failed to reveal any reference to a concomitant production of excessive melanotic pigment in the active lesions of gold dermatitis. It is well known that the cutaneous reactions accompanying aurotherapy are multiform. They may appear as exfoliative dermatitis or urticaria or may simulate erythema multiforme, scarlatina, lichen planus, pemphigus or pityriasis rosea. There are few references in the literature to the occurrence of keratoderma following this type of therapy, a condition which is admittedly rare. Pardo-Castello, 1 in discussing a paper by Driver and Weller, briefly reported a case of symmetrical palmar hyperkeratosis which appeared after six injections