Clofazimine-induced cutaneous hyperpigmentation as a source of stigma in the treatment of leprosy: A cross-sectional study.

OBJECTIVES: Cutaneous hyperpigmentation is one of the main adverse effects encountered in patients undergoing leprosy treatment with multidrug therapy (WHO-MDT). This adverse effect has been described as intolerable and capable of contributing to social stigma. The objectives of this study were to quantify the variation in skin colour induced by clofazimine during and after treatment and to assess the related stigma. METHODS: This observational cross-sectional study objectively measured skin colour in 51 patients by reading the individual typology angle (ITA°) with a spectrophotometer, followed by the application of the Stigma Scale of the Explanatory Model Interview Catalogue (EMIC). RESULTS: Skin hyperpigmentation was observed in 100% of the individuals. They showed more negative ITA° values in lesion areas than non-lesion areas, particularly in sun-exposed regions. Clofazimine-induced cutaneous hyperpigmentation was not homogeneous and seemed to follow the lesion locations. The mean EMIC score was 18.8 points. CONCLUSION: All patients presented skin hyperpigmentation caused by clofazimine, detectable through spectrophotometry. Hyperpigmentation strongly impacted the social domain, indicating the intersectionality of disease and skin colour stigma, contributing to the social isolation of these patients. Health authorities should consider the negative impact of clofazimine on treatment adherence.

Optical Coherence Tomography Features of Macular Hyperpigmented Lesions without Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.

PURPOSE: To evaluate the optical coherence tomography (OCT) features of hyperpigmented lesions in the absence of intraretinal hyperreflective foci (IHRF) on OCT in eyes with age-related macular degeneration (AMD). METHODS: We retrospectively analyzed OCT images of eyes with intermediate AMD (iAMD) and macular hyperpigmentation (HP) on color fundus photograph (CFP) but without IHRF on OCT in the corresponding location. The most prominent or definite HP was selected for analysis. The infrared reflectance (IR) image registered with the CFP, and the location corresponding to the HP lesion were defined on the IR image. The location of the HP on the corresponding OCT B-scan was assessed for retinal pigment epithelium (RPE) elevation, acquired vitelliform lesion (AVL), abnormal retinal pigment epithelium + basal lamina (RPE + BL) band reflectivity, RPE + BL band thickening, as well as interdigitation zone (IZ), ellipsoid zone (EZ) and external limiting membrane (ELM) disruption. RESULTS: 49 eyes (39 patients) were included in this study. Forty-six (94%) of the hyperpigmented lesions showed a thickened RPE + BL band. RPE + BL band reflectivity was increased in 37 (76%) of the lesions. RPE + BL band thickening, however, was not correlated with RPE + BL band reflectivity (p-value = 0.31). Either thickening or hyperreflectivity of the RPE + BL band was present in all cases. Twenty (41%) lesions had evidence of ELM disruption, 42 (86%) demonstrated EZ disruption and 48 (98%) had IZ disruption. Five (10%) HPs demonstrated AVL. Among cases with RPE elevation (15 cases, 31%), 10 were classified as drusen, 2 as drusenoid PEDs, and 3 as fibrovascular PEDs. CONCLUSIONS: Thickening and/or hyperreflectivity of the RPE + BL band commonly correspond to regions of macular hyperpigmentation without IHRF in eyes with iAMD.

Novel hyperpigmentation pathophysiology following a prolonged course of imipramine therapy.

Imipramine is a tricyclic antidepressant typically reserved for patients with treatment-resistant mood disorders. A rare side effect of long-term use of imipramine is a slowly progressive melanin-associated, slate gray-blue hyperpigmentation of the skin in a photo-distributed pattern. We report a case of imipramine-induced hyperpigmentation developing 50 years after initiating imipramine therapy, whose lesions were essentially devoid of melanin on histopathological exam. This differs from all other reported cases of imipramine-induced hyperpigmentation in two notable respects. First, the time between initiating imipramine therapy and the onset of pigmentation changes was nearly 30 years longer than prior case reports. Second, the lack of melanin in our samples suggests a divergence from the hypothesized melanin-imipramine complex mechanism of hyperpigmentation. Instead, we propose a novel pathogenesis of imipramine-induced hyperpigmentation that is unrelated to melanin.

[Eritema pigmentado fijo secundario a AINE: Reporte de caso].

Background: Fixed erythema pigmento (FPE) is an allergic drug reaction, the pathophysiology of which is not exactly known. It is more common in women with location on the face. Clinical presentation: round or oval red-purple macule, well defined, with swelling, pain, itching, and burning. Diagnosis is clinical, oral chal- lenge is contraindicated due to possible severe reaction. On withdrawal of the drug, residual violaceous hyperpigmentation remains. Case report: 34-year-old female diagnosed with allergic rhinitis and asthma. She received treatment with ibuprofen and cephalexin 1 month ago due to dental infection. For the past 2 weeks, she has presented dermatological lesions characterized by hyperpigmentation under the lower eyelids, accompanied by pain, burning, and itching. On physical examination, well-defined red-purple pigmentation was observed in both periocular regions. The challenge test is not justified, the clinical history is the diagnostic pillar. The indication is to stop the medication immediately and continue monitoring. Conclusions: EPF is a drug reaction related to drug use. It creates a challenge for diagnosis due to poor knowledge of the characteristics of the dermatosis and poor clinical and pharmacological questioning. The EPF approach requires knowing the clinical characteristics of this dermatosis, making a differential diagnosis with other lesions and indicating the suspension of the responsible medication.

Antecedentes: El eritema pigmentado fijo (EPF) es una reacción alérgica medicamentosa, de la cual no se conoce con exactitud la fisiopatología. Es más frecuente en la mujer con localización en la cara. Presentación clínica: mácula redonda u oval de color rojo-violáceo, bien delimitada, con edema con dolor, prurito y ardor. El diagnóstico es clínico, contraindicado el reto oral por posible reacción grave. Al retirar el fármaco, queda una hiperpigmentación residual violácea. Reporte de caso: Femenina de 34 años con diagnóstico de rinitis alérgica y asma, Recibió tratamiento con Ibuprofeno y cefalexina hace 1 mes debido a proceso infeccioso dental. Desde hace 2 semanas presenta lesiones dermatológicas caracterizadas por hiperpigmentación debajo de párpados inferiores, acompañado de dolor, ardor y prurito. A la exploración física en ambas regiones perioculares se observa pigmentación bien delimitada rojo-violáceo. La prueba de reto no se justifica, la historia clínica es el pilar diagnóstico. La indicación es suspender el medicamento de inmediato y vigilancia continua. Conclusiones: El EPF es una reacción a medicamentos relacionada con el consumo de fármacos. Genera un desafío para el diagnóstico debido al pobre conocimien- to de las características de la dermatosis y un deficiente interrogatorio clínico y farmacológico. El abordaje del EPF requiere conocer las características clínicas de esta dermatosis, realizar el diagnostico diferencial con otras lesiones e indicar la suspensión del medicamento responsable.

[A man with brown discolorations]. / Een man met bruine vlekjes.

A 58-year-old man presents with spontaneous brown discolorations of his mouth and hands. Our differential diagnosis included Peutz-Jeghers syndrome, Laugier-Hunziker syndrome or Addison's disease. There were no polyps in a previously performed colonoscopy and no other systemic symptoms. We made the diagnosis Laugier-Hunziker syndrome, a benign skin disorder that doesn't require treatment, confirmed by skin biopsy.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

BACKGROUND: Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. CASE PRESENTATION: We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. ASSESSMENT: Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. DIAGNOSIS: A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. CONCLUSION: This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Inherited Reticulate Pigmentary Disorders.

Reticulate pigmentary disorders (RPDs) are a group of inherited and acquired skin conditions characterized by hyperpigmented and/or hypopigmented macules. Inherited RPDs include dyschromatosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria (DUH), reticulate acropigmentation of Kitamura (RAK), Dowling-Degos disease (DDD), dyskeratosis congenita (DKC), Naegeli-Franceschetti-Jadassohn syndrome (NFJS), dermatopathia pigmentosa reticularis (DPR), and X-linked reticulate pigmentary disorder. Although reticulate pattern of pigmentation is a common characteristic of this spectrum of disorders, the distribution of pigmentation varies among these disorders, and there may be clinical manifestations beyond pigmentation. DSH, DUH, and RAK are mostly reported in East Asian ethnicities. DDD is more common in Caucasians, although it is also reported in Asian countries. Other RPDs show no racial predilection. This article reviews the clinical, histological, and genetic variations of inherited RPDs.

Penile terra firma-forme dermatosis in children.

Terra firma-forme dermatosis (TFFD) is a rare, acquired keratinization disorder that predominantly affects children and young adults. Herein, we report three unusual cases of penile TFFD in children and the histopathologic and ultrastructural observations.

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria.

Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. Although Sterile Alpha motif- and SH3 domain-containing protein 1 (SASH1) and ATP-binding cassette subfamily B, member 6 (ABCB6) have been identified as causative genes for this disorder, some cases involve unknown pathogenic genes. In this study, whole-exome sequencing, data analysis, and Sanger sequencing were utilized for a four-generation extended Chinese family with DUH. A single-nucleotide polymorphism (SNP) (c. 517C > T (p.P173S), rs772027021) variant in exon 5 of Period Circadian Regulator 3 (PER3) (NM_001289861) was detected in each affected individual of the DUH family; the c. 517C > T SNP of PER3 (PER3rs772027021 SNP) and a novel mutation in exon 14 of SASH1 (c. 1574C > G (p.T525R)) were both found in the proband. The affected individuals carrying PER3rs772027021 SNP in this family demonstrated mild-pigmented phenotypes compared to those of the proband carrying PER3rs772027021 SNP and SASH1 T525R mutation. Increased melanin synthesis was induced by PER3rs772027021 SNP in the melanocytes of affected epithelial tissues. Mutated SASH1 or PER3rs772027021 SNP alone or cooperation of mutation of SASH1 and PER3rs772027021 SNP synergistically led to increased melanin synthesis and enhanced proliferation of melanoma cells in vitro. We also phenotypically characterized a commercially available zebrafish mutant line harboring the PER3rs772027021 SNP to induce melanocyte proliferation in vivo. Our results are the first to reveal that this PER3 SNP may be pathogenic for a novel DUH subtype with mild hyperpigmented and/or hypopigmented phenotypes and that mutation of SASH1 and PER3 cooperatively promotes hyperpigmentation phenotypes. KEY MESSAGES: PER3 rs772027021 SNP is identified to be associated with hyperpigmentation and/or hypopigmentation phenotype and the novel pathogenic variant of PER3 rs772027021 SNP probably contributed the pathogenesis of DUH. SASH1T525R mutation is confirmed to associate with DUH. A novel autosomal dominant inheritance DUH subtype with mild pigmentated phenotypes is caused by the PER3rs772027021 SNP.

Scleral Discoloration Because of Minocycline Use: A Case Report and Review of the Literature.

In this case report, we highlight minocycline-induced scleral hyperpigmentation, combined with ear and fingernail discoloration that developed after over 15 years of use for rosacea in a 78-year-old male with multiple medical comorbidities. Minocycline, a tetracycline antibiotic, is used to treat rosacea and acne as well as some orthopedic infections. It is typically used for extended periods of time; long-term use of minocycline is associated with hyperpigmentation of the sclera, conjunctiva, retina, teeth, skin, subcutaneous fat, oral mucosa, tympanic membrane, and gingiva. This case highlights that hyperpigmentation is more likely to occur in older patients than in younger patients. Scleral hyperpigmentation is not associated with vision loss; however, cosmetic concerns can prompt discontinuation of minocycline. Nonetheless, after cessation, the lesions persist in some patients. Monitoring for hyperpigmentation in patients using minocycline is important, as the hyperpigmentation is more likely to be permanent with long-term use.

Angiotropic melanocytes: Possibly a distinctive finding in extra-facial acquired dermal melanocytosis.

BACKGROUND: Acquired dermal melanocytosis is a heterogenous group of hyperpigmented lesioins which predominantly involve the face. AIM: The aim of this study was to study the clinical presentation and histopathology of cases with extra-facial acquired dermal melanocytosis. METHODS: Retrospective record analysis was performed between May 2016 to August 2019 to retrieve cases of extra-facial acquired dermal melanocytosis seen at the out-patient department of dermatology at the All India Institute of Medical Sciences, Jodhpur. Consecutive cases with histopathologically proven diagnosis of acquired dermal melanocytosis were included. Documentation of variation in clinical presentation and histopathologic findings was done in light of the existing literature. RESULTS: Overall, four cases of extra-facial acquired dermal melanocyosis (female:male = 1:3) were seen during the study period. The lone case on head and neck involved the ear lobule and peri-auricular area. The other three cases had involvement of the hand. The histopathology confirmed the diagnosis of dermal melanocytosis but revealed peculiar findings of angiotropic melanocytes and dilated capillaries. LIMITATIONS: Small sample size and lack of comparison with perilesional normal skin were the limitations of this study. CONCLUSION: The findings of angiotropic melanocytes may be unique to extra-facial acquired dermal melanocytosis. This might indicate interaction between dermal melanocytes and capillary endothelial cells. This finding along with dermal capillary ectasia may indicate a possible role for vascular lasers in the management of these disorders.

Disseminated papular variant of Dowling-Degos disease: Histopathological features in POGLUT1 mutation.

Dowling-Degos disease is a rare benign genodermatosis. It is characterized by lentiginous hyperpigmentation and reddish-brown papules and plaques. The flexor sides and intertrigines are often affected, but the clinical appearance may vary. Mutations in different genes are responsible for the clinical manifestation. While mutations in the keratin 5 (KRT5) gene favor a reticular distribution pattern, mutations in the POGLUT1 gene lead to a disseminated, papular clinical picture. Acantholytic variants of Dowling-Degos disease have historically been referred to as Galli-Galli disease, but our case study shows that the histopathological changes can vary even within a single patient. To date, no standardized therapy concept exists. The main focus is on keratolytic measures, with varying response. New therapeutic approaches using laser technology appear to be a promising treatment option.

Pigmentary anomaly caused by mosaic 3q22.2q29 duplication.

A 39-year-old woman sought advice regarding potential risks to her offspring due to previous possible diagnosis of incontinentia pigmenti. She had linear hyperpigmentation along the lines of Blaschko affecting the upper and lower limbs, and skin-coloured papules on the left palm. Ophthalmoscopy revealed hypopigmented spots in the macular region of the retina in each eye due to focal areas of depigmentation of the retinal pigment epithelium. An array comparative genomic hybridization on DNA extracted from a skin biopsy revealed a 63.63-Mb duplication, arr[GRCh37] 3q22.2q29(134212001_197837069)x3, on the long arm of chromosome 3. This case is an example of genetic mosaicism resulting from a de novo genetic defect arising at some point in embryonic development. Click here for the corresponding questions to this CME article.

S2k guideline: Laser therapy of the skin.

This guideline aims to improve the efficiency and safety of lasers and optical radiation sources with similar effects (especially IPL). Laser therapy of skin lesions with an increased amount of melanocytes should be performed with caution. Laser treatment of pigmented melanocytic nevi is not recommended. The guideline contains recommendations regarding the treatment of lentigines and café-au-lait spots, non-pigmented dermal nevi, Becker nevus, nevus of Ota/Hori/Ito and melasma. Further recommendations focus on the treatment of skin lesions without an increased amount of melanocytes (ephelides, postinflammatory hyperpigmentation including berloque dermatitis, seborrheic keratoses, traumatic/decorative tattoos and metallic deposits), hypopigmentation (vitiligo), benign non-pigmented neoplasms (fibrous papule of the nose, nevus sebaceus, epidermal nevus, neurofibroma, sebaceous gland hyperplasia, syringoma, xanthelasma palpebrarum), inflammatory dermatoses (acne papulopustulosa/conglobata, acne inversa, granuloma faciale, lichen sclerosus, lupus erythematosus, psoriasis vulgaris, rosacea, rhinophyma), wrinkles/dermatochalasis/striae, hypertrichosis, scars (atrophic, hypertrophic; keloids, burn/scald scars), laser-assisted skin healing, onychomycosis, precancerous lesions and malignant tumors (actinic keratoses/field cancerization, cheilitis actinica, basal cell carcinoma), vascular skin lesions (angiokeratoma, angioma, hemangioma, malformation, spider veins, granuloma telangiectaticum (pyogenic granuloma), rubeosis (erythrosis interfollicularis colli, ulerythema ophryogenes), nevus flammeus, telangiectasias and Osler's disease (hereditary hemorrhagic telangiectasia) and viral skin lesions (condylomata acuminata, mollusca contagiosa, verrucae planae juveniles/vulgares/ verrucae palmares et plantares).