Clinical profile of 300 men with facial hypermelanosis.

Background: Disorders of increased facial pigmentation constitute a major group of disorders in all dermatology clinics. Apart from cosmetic disfigurement, these disorders could significantly affect patient psychology. Therefore, it becomes imperative on the part of clinician to arrive at a conclusive diagnosis so that appropriate therapy could be administered. Aim: To correlate the clinical and histology findings in 70 females 30–50 years of age with persistent facial hypermelanosis. Methods: Following a written, informed consent, a 2 mm punch biopsy was performed from the lesional skin, succeeded by microscopic evaluation and clinical correlation. Results: Out of the 70 patients studied, 31 had melasma, 14 with seborrhoeic melanosis (SM) and lichenoid dermatitis each, four with acanthosis nigricans (AN) and ashy dermatoses, and the remaining three with Riehl’s melanosis. Out of these patients studied, all patients with melasma and AN demonstrated 100% clinicopathologic concordance. Koilocytes were identified in two patients with persistent facial hypermelanosis, and in 17 patients, the histology findings were undecided. Conclusion: Melasma appears to be the most common cause of facial hypermelanosis in females and has demonstrated a 100% clinicopathologic correlation. Subclinical infection with human papilloma virus (HPV) could be a cause of increased facial pigmentation which, if not carefully evaluated, could go undetected. SM still remains a disputable entity. Majority of these disorders are chronic and highly recalcitrant to all conventional therapeutic modalities.

Background: Paucity of literature and non consensus on clinicohistopathological features amongst the nonmelasma facial melanosis for example lichen planus pigmentosus (LPP), pigmented contact dermatitis (PCD), macular amyloidosis, acanthosis nigricans, pigmented demarcation line, post inflammatory hyperpigmentation, etc., make them difficult to diagnose and equally challenging to treat. Materials and Methods: It was a prospective, uncontrolled study, conducted at tertiary hospital at eastern India in 100 patients presenting with facial hyperpigmentation who agreed to undergo 3 mm skin biopsy during Jan 2014 to Jun 2015. Cases of melasma were excluded by clinical, Woods lamp examination and if required dermoscopy. Details of history, physical examination, histopathological examination, and Immunohistochemical studies were recorded. Melan A was used as melanocytic differentiation marker while CD4, CD8 were used as inflammatory markers. Mean ± SD, chi-square test or Fisher's exact test, degree of agreement by Cohen's Kappa were calculated. P-value was considered significant if ≤0.05. Results: 44 males and 56 females (56%) (M: F=1:1.24) with mean age of 45.98 years and median duration of illness of 28 months (5 months-13 years) were studied. Out of 43 confirmed cases of PCD, 16 had associated hypothyroidism (chi square 6.11, P-value 0.0134). Maximum patients belonged PCD (n = 47) followed by LPP (n = 27). Maximum concordance of clinical and histopathological diagnosis was present in PCD and LPP (Cohen kappa more than 0.9). Epidermal atrophy and band like inflammatory infiltrate were statistically significant features in LPP (P < 0.001). There was no histopathological and immunohistochemical correlation. Overall, clinical histopathological concordance rate was 77%. Conclusion: Subset of nonmelasma facial melanosis is difficult to diagnose clinically which require further confirmation by histopathological examination. Small number of patients in other groups apart from PCD and LPP and uncontrolled study were major limitations of this study.

Background: Facial melanosis is a group of heterogenous entities, sharing a common clinical feature of altered pigmentation of the face and thus easily visible cosmetic disfigurement and significant psychosocial consequences. The importance of these disorders is growing, as they form the major percentage of dermatology consultations. Aims: To assess the patients of facial pigmentary disorders for demographic, etiological and clinical profile. Methods: This prospective hospital-based clinical study, conducted in a tertiary center over 1-year, involved 208 patients with facial pigmentary disorders, assessed using detailed history taking and clinical examination for demographic, etiological and clinical data. Relevant investigations including the skin biopsy and patch testing were also done wherever required. Results: The maximum number of patients belonged to 21-40 years age group (56.73%). Females predominated the study, with a female to male ratio of 1.92: 1. Among patients of facial hypermelanosis, melasma was the most common comprising of 73 patients, followed by postinflammatory hyperpigmentation (35), periorbital hyperpigmentation (14), ephelides (10) and lichen planus pigmentosus (9). Riehl's melanosis (8), drug-induced hyperpigmentation (6), naevoid hyperpigmentation (1), acanthosis nigricans (1) and Addison's disease (1) were other hypermelanosis conditions. Pityriasis alba (22) was the most common cause of facial hypomelanosis followed by vitiligo (19), postinflammatory hypopigmentation (8) and leprosy (1). Almost all cases of facial hyperpigmentation gave history of exacerbation following sun exposure. Conclusion: A variety of pigmentary disorders, both hyper and hypopigmentation, with variable clinical presentations and etiological factors, and associated with significant distress affect the face.

Diabetes is the most common endocrine disorder, affecting 8.3% of the population (1). Skin disorders will be present in 79.2% of people with diabetes (2). A study of 750 patients with diabetes found that the most common skin manifestations were cutaneous infections (47.5%), xerosis (26.4%), and inflammatory skin diseases (20.7%) (2). Individuals with type 2 diabetes are more likely than those with type 1 diabetes to develop cutaneous manifestations. Cutaneous disease can appear as the first sign of diabetes or may develop at any time in the course of the disease. This review provides a brief overview of skin conditions that primary care providers (PCPs) may encounter when treating patients with diabetes. ### Acanthosis Nigricans Acanthosis nigricans (AN) is likely the most readily recognized skin manifestation of diabetes (3). It is present in up to 74% of obese adult patients and can be predictive of the existence of hyperinsulinemia (4). The presence of AN is a prognostic indicator for developing type 2 diabetes. There is also a possible genetic predisposition or increased sensitivity of the skin to hyperinsulinemia in different ethnic groups. At the same obesity rates, prevalence of AN is lowest in whites (0.5%), higher in Hispanics (5%), and even higher in African Americans (13%) (5). AN is a hyperpigmented velvety thickening of skin folds, presenting predominantly in the neck, axilla, and groin areas (Fig. 1). Possible additional presentations could include skin tags and hyperkeratosis. Heredity, obesity, endocrine disorders, certain drugs, and malignancy are associated with AN. Benign AN type 2 is related to type 2 diabetes, and pseudo-AN type 3 is associated with the metabolic syndrome. Type 2 diabetes–related AN has an insidious onset and initially presents as hyperpigmentation. Both underlying conditions present with insulin resistance (3). Children aged 8–14 years who had AN were found to have insulin resistance, …

Background: Facial hypermelanosis is a common pigmentary disorder, which encompasses a wide spectrum of diseases. Hypermelanosis is of great cosmetic concern causing significant distraction leading on to psychological distress. Sun exposure and photosensitizing agents play an important role in pathogenesis of hypermelanosis. Aim: To study clinicoepidemologic patterns of facial hypermelanosis among various age groups. Methodology: Hundred patients with facial hyperpigmented lesions attending dermatology outpatient department in a tertiary care hospital were to be included in this study. Clinical history regarding age, sex, predisposing factors and detailed clinical examination were to be done in all these patients. Result: Among 100 patients of facial hypermelanosis, melasma was the most common pigmentary skin disorder comprising about 32% of patients,second most common entity was post acne hyperpigmentation (14%). Eleven patients with facial melanosis had drug-induced pigmentation, five had periorbitalhypermelanosis, seven of them had friction-induced melanosis, seborrheicmelanosis was observed in six patients, acanthosisnigricans in five patients, lichen planuspigmentosus in five patients, nevus of ota in three patients, fixed drug eruption in two patients and Addison's disease in 1 patient.

Acanthosis nigricans (AN) is a pigmentary dermatosis characterized by velvet-like, hyperpigmented, coarse plaques distributed in intertriginous areas. Due to aesthetic concerns, various methods including weight loss and topical agents are used for treatment.1 Trifarotene is a fourth-generation retinoid used for the treatment of acne vulgaris, autosomal recessive congenital ichthyosis, and primary cutaneous T-cell lymphoma.2, 3 Retinoids have been used with success in the treatment of AN; however, no data are available for trifarotene. Here, we report three cases of AN and examine the efficacy and safety of topical trifarotene cream for AN. An 18-year-old male was presented with brownish pigmentation on the neck. A coarse, hyperpigmented skin lesion in the extensor part of the neck was observed (Figure 1A). Dermoscopy demonstrated linear crista cutis and sulcus cutis with dispersed dark brown dots (Figure 1C). We diagnosed the patient as having AN and decided to apply topical 0.005% trifarotene cream 3 times a week. After 5 weeks, marked improvements were observed (Figure 1B,D). In addition, a 14-year-old male and a 16-year-old male had dark patches on the skin with a thick, velvety texture either in the extensor part of the neck or both axillae, and they were both obese (Figure 1E,G). Dermoscopic findings of the patients were similar to that of an 18-year-old patient. There were no symptoms suggesting systemic disease or malignancy. Following a diagnosis of AN, they were both treated with the same regimen as above, and a significant improvement was observed (Figure 1F,H). All patients had no signs of skin irritation during the treatment. All of the patients showed improved skin pigmentation until 3 months after treatment without any other treatment. The prevalence of AN varies depending on comorbidities and other risk factors. Specifically, the incidence of AN increases with age, obesity, and darker skin.4 AN is diagnosed with histological examination characterized by hyperkeratosis, mild acanthosis, and papillomatosis of the epidermis.1 However, AN can be diagnosed by specific clinical findings with dermoscopic features, such as sulci cutis, and hyperpigmented dots.5 The pathophysiology of AN can be described as the proliferation of epidermal keratinocytes and dermal fibroblasts involving various mediators such as insulin, insulin-like growth factor (IGF), fibroblast growth factor receptors, and tyrosine kinase receptors including epidermal growth factor receptor. Insulin resistance might play a central role in AN as insulin at high concentrations could bind to the IGF-1 receptors of keratinocytes and fibroblasts.1, 4 As most cases of AN are related to obesity, weight loss should be considered as the first-line treatment for AN.1 Other conventional treatments for AN include topical and oral retinoids, topical vitamin D analogs, chemical peels, metformin, and rosiglitazone. Topical and oral retinoids reduce the stratum corneum replacement time, resulting in the correction of hyperkeratosis.2 Topical vitamin D analogs suppress keratinocyte proliferation by increasing the intracellular calcium and cGMP levels of keratinocytes. Chemical peels necrotize the epidermis, resulting in re-epithelialization. Metformin and rosiglitazone reduce insulin levels by increasing insulin responsiveness.6 The fourth-generation retinoid trifarotene hydrates the skin by inducing peptidyl arginine deiminase 1 and aquaporin-3 channels. It also loosens the hemidesmosomes connection and intercellular adhesion. Trifarotene can improve skin texture by downregulating matrix metalloproteinases (MMPs).3 Therefore, trifarotene may reduce fine wrinkling, roughness, and mottled hyperpigmentation in AN. In our case series, weight loss was also recommended, but it was unsuccessful. Then trifarotene was applied and improved skin lesions. After treatment, the improvement was maintained, and no side effects were observed. However, histopathological improvement could not be confirmed because skin biopsy was not performed. Further long-term studies, clinical trials with more patients, and comparisons with other treatment regimens are needed. In conclusion, topical trifarotene cream could be a novel, effective, and safe treatment option forAN. WG Lee: writing—original draft preparation; YG Koh: data collection; SH Shin: conceptualization and figure editing; KY Park: supervising, writing—review and editing; HW Lee: conceptualization, writing—review and editing. None. The authors have no conflict of interest to declare. None. The patients in this manuscript provided written informed consent for the publication of their case details and clinical pictures. The data that supports the findings of this study are available in the supplementary material of this article

An otherwise healthy 14-year-old Caucasian girl was referred due to asymptomatic hyperpigmented macules (Figure 1) that had progressively developed over the past year. She did not have pruritus or accompanying systemic symptoms. The skin lesions were disseminated, predominantly involving the anterior neck, abdomen, torso, axillae, and inguinal folds. In the flexural regions, the macules displayed a slightly velvety surface. The face, palms, soles and mucous membranes were unaffected. The remainder of the physical examination, including vital signs, somatometry, physical growth and neurodevelopment, was normal. There was no preceding history of inflammatory or infectious lesions in the affected areas, nor trauma or any recent topical or systemic drug exposure. Laboratory investigations, including metabolic screening, were within normal limits. Skin biopsy revealed acanthosis and basal layer hyperpigmentation with the presence of dermal melanophages. No lichenoid infiltrate, basal layer vacuolar damage or increase in the number of mast cells was identified. Idiopathic eruptive macular pigmentation. Idiopathic eruptive macular pigmentation (IEMP) is a rare, benign and self-limiting pigmentary disorder, with fewer than 40 paediatric cases reported [1]. It occurs from 1 to 31 years of age, predominantly in childhood and adolescence, without sex predilection, mostly in Indian patients [2]. Its pathogenesis remains uncertain; hormonal factors and autoimmunity are thought to trigger melanosis [3, 4]. Clinically, IEMP presents as round or oval, well-defined, non-pruritic, homogenous brown macules and plaques, appearing without preceding lesions, mainly on the trunk, neck and proximal limbs, as in this case. Rare presentations include a Christmas tree pattern, confinement to flexures or a velvet-y surface [5, 6]. Dermoscopy typically reveals linear cristae cutis and sulci cutis [7]. Histopathology is nonspecific but supportive, showing acanthosis, basal layer hyperpigmentation and dermal melanophages [1], and rarely, pigmented papillomatosis [3] (Figures 2 and 3). The main differential diagnoses include friction melanosis, post-inflammatory hyperpigmentation, acanthosis nigricans and fixed drug eruption [2]. The absence of specific triggers, paired with normal somatometry and metabolic screening, ruled these out. Other acquired macular hyperpigmentation disorders of uncertain cause were considered (lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis) however, the absence of erythema, pruritus, basal cell damage or lichenoid infiltrate effectively excluded them [8]. IEMP and related idiopathic hyperpigmentation disorders remain diagnostic challenges due to overlapping clinical and histological profiles. However, awareness is key to avoiding unnecessary therapy. Prognosis is excellent, and spontaneous regression is expected [1], albeit gradual. We would like to thank Dr. Pedro de Vasconcelos for kindly providing the histological photographs included in this paper. The authors have nothing to report. The authors declare that the research presented in this manuscript adheres to the ethical principles outlined by Lisbon Local Health Unit Ethics Committee. All procedures involving human participants were conducted in accordance with the ethical standards of the Lisbon Local Health Unit and the Declaration of Helsinki (1964), as revised in 2013. Written informed consent was obtained from a parent of the patient for publication of this case report and accompanying images prior to the patient's passing. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

The prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans. Nineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans. Anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance. Childhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

Introduction:Lichen planus pigmentosus (LPP) is a distinct clinical entity commonly encountered in the Indian population.Aim:To study the clinicoetiological profile of LPP at a tertiary care hospital.Methods:A total of 100 patients with clinically and histopathologically confirmed diagnosis of LPP were included. Demographic details including the age of onset, duration of disease, symptoms, and family history were obtained. History regarding any precipitating factors, cosmetics, drug intake, and associated cutaneous or systemic diseases was taken. Clinical examination of the skin, oral cavity, hair, and nails was carried out.Results:Of the total 100 patients, 56 (56%) were females and 44 (44%) males with age ranging from 18 to 54 years (mean age - 31.23 years). The duration of disease ranged from 2 to 60 months with a mean of 19.31 months. Cosmetic disfigurement (68%) was the commonest complaint, followed by itching (41%) while, 30% of the patients were asymptomatic. History of topical mustard oil and hair dye application was present in 62% and 48% of the cases each. Other topicals included perfumes (24%), aftershave lotion (36%), and cosmetics (20%). Face (54%) and neck (48%) were the commonest sites affected, followed by upper back (36%), upper limbs, and chest (each 32%). A total of 11 patients showed only flexural involvement. The commonest pattern of pigmentation was diffuse (56%) followed by reticular in 16%. The color of the pigmentation varied from slate grey to brownish-black in varying proportions. A positive association was found between hypothyroidism with diffuse LPP where the P value was <0.001.Conclusion:LPP is a distinct clinical entity caused by diverse etiological factors and shows varied clinical patterns. All the patients should be advised to stop using mustard oil/henna/hair dye/after shave lotions and cosmetics. Hypothyroidism can be considered to be a disease associated with LPP and all the patients should be investigated for the same.

Lichen planus pigmentosus (LPP) is recognized as a rare variant of lichen planus, characterized by dermal hyperpigmentation. Specifically, a particular intertriginous variant of LPP is known as lichen planus pigmentosus inversus (LPPI). In our case, the patient presented with symmetric, hyperpigmented dark brown patches mainly in axillary areas, closely resembling the features of acanthosis nigricans (AN). The differential diagnosis considered included LPPI, AN, post-inflammatory hyperpigmentation related to contact dermatitis, symmetrical drug-related intertriginous and flexural exanthema, fixed drug eruption, and erythema dyschromicum perstans (EDP). Histopathological examination revealed the absence of hyperkeratosis and papillomatosis, typically associated with AN. Dermoscopy revealed diffuse brownish hue along with dots and globules of inconsistent size, which suggests dermal pigmentary incontinence and the likelihood of LPPI. This case illustrates the challenge in differentiating LPPI from similar flexural hyperpigmentation disorders based on the comprehensive approach including thorough history taking, clinical manifestations, histopathological analysis, and dermoscopic examination.

S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part1: Classification, diagnosis, prevention, activity scores.

Correlated improvement of mucosal malignant acanthosis nigricans and metastatic urothelial carcinoma with oncologic therapy

Acanthosis nigricans (AN) has been reported in relation to insulin resistance (IR). We aim to review AN through an endocrine and metabolic perspective focusing on IR in association with metabolic complications such as obesity, diabetes mellitus (DM), and metabolic syndrome (MS) with/without polycystic ovary syndrome (PCOS). We revised English papers on PubMed covering publications from the last 5 years. The current prevalence of AN varies from 4.5 to 74% (or even 100%, depending on the studied population), with equal distribution among females and males. Despite higher incidence with an age-dependent pattern, an alarming escalation of cases has been noted for obesity and MS in younger populations. Most frequent IR-associated sites are the neck, axilla, and knuckles, but unusual locations such as the face have also been reported. Quantitative scales such as Burke have been used to describe the severity of the dermatosis, particularly in correlation with IR elements. Dermoscopic examination are required, for instance, in cases with sulcus cutis, hyperpigmented spots, crista cutis, and papillary projections. A skin biopsy may be necessary, but it is not the rule. Both IR that clinically manifests with or without obesity/MS correlates with AN; most studies are cross-sectional, with only a few longitudinal. The approach varied from screening during school periodic checkups/protocols/programs to subgroups of individuals who were already known to be at high cardio-metabolic risk. AN was associated with type2DM, as well as type 1DM. Females with PCOS may already display metabolic complications in 60–80% of cases, with AN belonging to the associated skin spectrum. AN management depends on underlying conditions, and specific dermatological therapy is not generally required, unless the patient achieves metabolic control, has severe skin lesions, or desires cosmetic improvement. In IR cases, lifestyle interventions can help, including weight control up to bariatric surgery. In addition, metformin is a key player in the field of oral medication against DM type 2, a drug whose indication is extended to PCOS and even to AN itself, outside the specific panel of glucose anomalies. In terms of cosmetic intervention, limited data have been published on melatonin, urea cream, topical retinoids, vitamin D analogs, or alexandrite laser. In conclusion, awareness of IR and its associated clinical features is essential to provide prompt recognition of underlying conditions. AN represents a useful non-invasive surrogate marker of this spectrum in both children and adults. The pivotal role of this dermatosis could massively improve endocrine and metabolic assessments.

Acanthosis nigricans (AN) has been associated with insulin resistance. Individuals with type 2 diabetes are insulin-resistant and, therefore, could be expected to manifest AN. However, the prevalence and predictors of AN are unknown in this population. An outpatient population with Type 2 diabetes (DM) was compared with matched controls (C) for microscopic and clinical AN along with measurement of body habitus, insulin, glucose, and androgen levels. Twenty-four individuals with DM (12M, 12F) from a tertiary care center were compared with 24 C (12M, 12F). Fasting glucose, insulin, sex hormone binding globulin, androstenedione, dihydroepiandrosterone sulfate, and testosterone were measured. Height, weight, waist/hip measures, and a clinical survey for acanthosis were recorded. A 2-mm skin biopsy from midaxilla of the nondominant arm was taken for pathological review. C and DM were matched for age and body mass index (BMI). Prevalence of microscopic AN in C was 12% (3/24) and in DM was 21% (5/24; NS). In C, AN was predicted by waist, waist/hip ratio, and fasting insulin measures, while none of the variables examined was predicative of AN in DM. Microscopic acanthosis nigricans was found in similar numbers of people with DM when compared with C. Fasting insulin levels most strongly predicted the presence of AN in C, while no significant predictors of AN were found in the population with DM.

Background: Acanthosis nigricans (AN) has been associated with insulin resistance. Individuals with type 2 diabetes are insulin-resistant and, therefore, could be expected to manifest AN. However, the prevalence and predictors of AN are unknown in this population. Objective: An outpatient population with Type 2 diabetes (DM) was compared with matched controls (C) for microscopic and clinical AN along with measurement of body habitus, insulin, glucose, and androgen levels. Methods: Twenty-four individuals with DM (12M, 12F) from a tertiary care center were compared with 24 C (12M, 12F). Fasting glucose, insulin, sex hormone binding globulin, androstenedione, dihydroepiandrosterone sulfate, and testosterone were measured. Height, weight, waist/hip measures, and a clinical survey for acanthosis were recorded. A 2-mm skin biopsy from midaxilla of the nondominant arm was taken for pathological review. Results: C and DM were matched for age and body mass index (BMI). Prevalence of microscopic AN in C was 12% (3/24) and in DM was 21% (5/24; NS). In C, AN was predicted by waist, waist/hip ratio, and fasting insulin measures, while none of the variables examined was predicative of AN in DM. Conclusions: Microscopic acanthosis nigricans was found in similar numbers of people with DM when compared with C. Fasting insulin levels most strongly predicted the presence of AN in C, while no significant predictors of AN were found in the population with DM.