The Yucatan miniature swine as a model for post-inflammatory hyperpigmentation.

Post-inflammatory hyperpigmentation (PIH) is a hypermelanosis that often occurs secondary to skin irritation or injury, especially in darker skin tones, for which there is currently a lack of effective treatment options. Few preclinical models are available to study PIH. Here, we show that the Yucatan miniature pig consistently develops PIH after skin injuries. Skin wounds were produced on Yucatan pigs by needle punches, full-thickness excisions, or burns. Wound sites were monitored and photographed regularly. Tissue samples were collected after 24 weeks and processed for histology/immunohistochemistry. Skin pigmentation and histologic changes were quantified by computer-assisted image analyses. All injury methods resulted in hyperpigmentation. Melanin content at the histologic level was quantified in the larger (burn and excision) wounds, showing a significant increase compared to uninjured skin. Increased melanin was found for both epidermal and dermal regions. Dermal melanin deposits were primarily clustered around the papillary vasculature, and were associated not with melanocytes but with leukocytes. The Yucatan miniature pig model recapitulates key clinical and histologic features of PIH in humans, including skin hyperpigmentation at both gross and histologic levels, and persistence of dermal melanin subsequent to injury. This model could be used to further our understanding of the etiology of PIH, and for new therapy development.

Idiopathic eruptive macular pigmentation in a pediatric patient and a review of the literature.

Idiopathic eruptive macular pigmentation (IEMP) is a rare, benign, self-resolving melanosis consisting of hyperpigmented macules typically on the face, trunk, and extremities that can occur in children and adolescents and often presents a diagnostic conundrum. We report a case involving an 8-year-old female whose previous clinical presentation was concerning for an atypical presentation of cutaneous mastocytosis or neurofibromatosis. The clinical and histopathologic evaluation was consistent with the diagnosis of IEMP, and no active intervention was pursued. Our accompanying literature review serves to better characterize this condition, highlight key diagnostic features, and emphasize the tendency for spontaneous resolution to avoid unnecessary treatments with limited clinical efficacy.

[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.

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.

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).

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.

Systematic Review of Lichen Planus Pigmentosus in Children.

BACKGROUND: Pediatric lichen planus (LP) is a relatively uncommon condition, with increased presentation in children with darkly pigmented skin. OBJECTIVE: To understand the small subset of children with lichen planus (LP) manifesting as lichen planus pigmentosus (LPP), a form with thin plaques and extensive hyperpigmentation, generally in the absence of signs of inflammation Methods: This article is a systematic review of the English language literature for cases of lichen planus pigmentosus (LPP) in children. RESULTS: Twenty-one cases were identified including 2 that were linear, 3 inverse types, 1 palmoplantar. In larger series, 2–2.8% of children with lichen planus are affected by this sub-variant. One patient had reported associated oral lesions. Oral and topical corticosteroids, topical tacrolimus, and ultraviolet light have been described as successful therapies. CONCLUSIONS: LPP is an uncommon but important variant of lichen planus in children. In the presence of dark hyperpigmentation of the skin, a biopsy can help identify LPP. Clinicians should be aware that LPP can follow four patterns: common, inverse, palmoplantar, and linear.J Drugs Dermatol. 2022;21(7):850-853. doi:10.36849/JDD.6760.

Oral mesotherapy technique for the treatment of physiologic gingival melanin hyperpigmentation using locally injectable vitamin C: a clinical and histologic cases series.

OBJECTIVES: Vitamin C (ascorbic acid) is widely used in dermatology for skin depigmentation. However, there are very few clinical studies on the efficacy of vitamin C in gingival depigmentation. This preliminary case series aims to present the clinical effectiveness, histologic changes, and patient-reported outcomes of intra-epidermal vitamin C injections (oral mesotherapy) for managing patients with gingival melanin hyperpigmentation. METHOD AND MATERIALS: Five patients were administered locally injectable vitamin C (once per week for 4 to 5 visits) in maxillary or mandibular anterior pigmented gingiva. The depigmentation effect was evaluated using the Dummett Oral Pigmentation Index (DOPI) and Gingival Pigmentation Index (GPI). Digital photographs were used to assess gingival luminescence (L*) and pigmented surface area (PSA). Parameters were recorded at baseline and at 1 and 3 months. Melanocyte histopathologic count was determined at baseline and at 3 months. Pain, gingival color change, and patient satisfaction scores were also assessed. RESULTS: Median GPI, DOPI, and PSA were significantly reduced (P ≤ .05) from baseline to 1 month. There was no statistically significant change from 1 month to 3 months. L* value significantly increased from baseline to 3 months. A median pain score of 3 (scale of 0 to 10) was observed on the day of the procedure. A score of 3 (scale of 0 to 4) was reported for the gingival color and scores 3 and 4 (scale of 0 to 4) for the overall patient satisfaction. CONCLUSION: Oral mesotherapy using locally injectable vitamin C is a nonsurgical, minimally invasive, and efficient technique for gingival depigmentation. Indian patients were satisfied with the gingival color obtained and the overall treatment experience. CLINICAL IMPORTANCE: As all the branches of medicine, specifically dentistry, direct to minimally invasive approaches, mesotherapy shows great importance to reduce the surgical interventions, especially when esthetic outcomes are needed. Oral mesotherapy using locally injectable vitamin C can be a useful nonsurgical technique for achieving gingival depigmentation in the esthetic zone.

Primary Localized Cutaneous Amyloidosis Secondary to Sand Rubbing in a Wrestler.

A 40-year-old male, wrestler since 15 years of age presented with asymptomatic hyperpigmentation over both his both upper extremities for 10 years. There was no history of preceding itching or redness; of using a nylon brush, scrubbers, or sponges during bathing; or of excessive towel rubbing after bathing and applying cosmetics; however, he had been rubbing sand over both arms for 15 years. He had no personal or family history of atopy, diabetes, or thyroid disease. Cutaneous examination revealed the presence of symmetrical sharply defined reticulate brownish hyperpigmentation over both arms and favoring the left (Figure 1). Dermatoscopy revealed multiple uniform small brown fine streaks radiating from the center becoming reticulated (Figure 2). Hematologic and biochemical studies, in particular thyroid studies, were normal. Histopathologic examination revealed an amorphous eosinophilic deposit in the papillary dermis suggestive of macular amyloidosis (MA) (Figure 3). Methyl violet stain revealed amyloid positive areas (Figure 4), and a diagnosis of MA was made. With the cessation of the sand rubbing and the application of tacrolimus ointment (0.1%), the lesions slowly diminished. (SKINmed. 2022;20:141-143).

An unusual case of comedones.

We present the case of a 71-year-old woman with widespread comedones since adolescence. Histological examination revealed branching hyperpigmented rete ridges and cystically dilated follicular infundibulum containing laminated keratinous debris. We explore the differential diagnosis in the context of other reticulate hyperpigmentation disorders.

Imipramine-Induced Cutaneous and Iris Hyperpigmentation: A Case Report and Literature Review.

Objective: To describe a novel case of imipramine-induced hyperpigmentation and characterize the literature pertaining to imipramine-induced hyperpigmentation to this point.Data Sources: PubMed and Google Scholar were searched through July 2021 utilizing various combinations of imipramine, discoloration, and hyperpigmentation. The references of initial articles were searched for more case reports and imipramine-related literature. Also, articles that cited the references identified in the literature search were reviewed using Google Scholar. Only articles published in English were included.Study Selection: A total of 19 cases of imipramine-induced hyperpigmentation were found in 15 publications to date. All cases were included to determine the variation in clinical presentations of this rare condition.Data Extraction: The case reports were reviewed in their entirety for information concerning patient demographic, clinical presentation, histologic findings on biopsy, and treatment options for imipramine-induced hyperpigmentation.Results: This presentation, to our knowledge, represents the third case of imipramine-induced iris hyperpigmentation, the first case of iris hyperpigmentation occurring in a blue-eyed individual, and the first report to include pictures of the hyperpigmented irides. A novel proposed pathophysiologic mechanism is also provided.Conclusions: Imipramine is a tricyclic antidepressant with a rare side effect of cutaneous and iris hyperpigmentation. Granular dermal deposits in microscopy appear to be the cause of this discoloration. Treatment primarily focuses on discontinuing imipramine or laser therapy.

Radiofrequency Irradiation Mitigated UV-B-Induced Skin Pigmentation by Increasing Lymphangiogenesis.

Dermal macrophages containing melanin increase skin pigmentation since dermal melanin removal is slower than epidermal melanin removal. Lymphatic vessels are also involved in melanin clearance. We evaluated whether radiofrequency (RF) irradiation induced an increase in HSP90, which promotes lymphangiogenesis by activating the BRAF/MEK/ERK pathway and decreasing tyrosinase activity, in the UV-B exposed animal model. The HSP90/BRAF/MEK/ERK pathway was upregulated by RF. Tyrosinase activity and the VEGF-C/VEGFR 3/PI3K/pAKT1/2/pERK1/2 pathway, which increase lymphangiogenesis, as well as the expression of the lymphatic endothelial marker LYVE-1, were increased by RF. Additionally, the number of melanin-containing dermal macrophages, the melanin content in the lymph nodes, and melanin deposition in the skin were decreased by RF. In conclusion, RF increased HSP90/BRAF/MEK/ERK expression, which decreased tyrosinase activity and increased lymphangiogenesis to eventually promote the clearance of dermal melanin-containing macrophages, thereby decreasing skin pigmentation.

Implications of Oxidative Stress in the Pathogenesis and Treatment of Hyperpigmentation Disorders.

Oxidative stress represents an imbalance between the generation of reactive oxygen and nitrogen species and the ability of antioxidant systems to decompose those products. Oxidative stress is implicated in the pathogenesis of hyperpigmentation, hypopigmentation, melanoma, and other skin diseases. Regulatory networks involving oxidative stress and related pathways are widely represented in hypopigmentation diseases, particularly vitiligo. However, there is no complete review into the role of oxidative stress in the pathogenesis of hyperpigmentation disorders, especially regarding associations involving oxidative stress and cellular signaling pathways. Here, we review oxidative and antioxidant systems, oxidative stress-induced signal transduction mechanisms, and effects of antioxidant drugs used in preclinical and clinical settings in hyperpigmentation disorders.

Topical Cyperus rotundus essential oil for treatment of axillary hyperpigmentation: a randomized, double-blind, active- and placebo-controlled study.

BACKGROUND: The oil of the grass Cyperus rotundus (purple nutsedge) is an effective and safe treatment option for a variety of conditions. It has anti-inflammatory and antipigmenting properties. There have been no clinical trials comparing topical C. rotundus oil with skin-lightening treatments for axillary hyperpigmentation. AIM: To assess the efficacy of C. rotundus essential oil (CREO) in treating axillary hyperpigmentation, and compare with another active treatment hydroquinone (HQ) and a placebo (cold cream) in this study. METHODS: The study included 153 participants, who were assigned to one of three study groups: CREO, HQ group or placebo group. A tri-stimulus colorimeter was used to assess pigmentation and erythema. Two independent experts completed the Physician Global Assessment, and the patients completed a self-assessment questionnaire. RESULTS: CREO had significantly (P < 0.001) better depigmenting effects than HQ. CREO and HQ did not differ significantly in terms of depigmentation effects (P > 0.05); however, there were statistically significant differences in anti-inflammatory effects and decrease in hair growth (P < 0.05) in favour of CREO. CONCLUSIONS: CREO is a cost-effective and safe treatment for axillary hyperpigmentation.

[Laugier-Hunziker syndrome : A rare differential diagnosis of mucocutaneous hyperpigmentation]. / Laugier-Hunziker-Syndrom : Eine seltene Differenzialdiagnose der mukokutanen Hyperpigmentierung.

Laugier-Hunziker syndrome (LHS) is characterized by lentiginous hyperpigmentation of the oral mucosa and lips. In addition, longitudinal melanonychia and palmoplantar hyperpigmented lesions may occur. LHS is a clinical diagnosis of exclusion. Herein, we report the case of a 66-year-old woman with LHS. The clinical and histopathologic features of LHS are presented and important differential diagnoses are discussed.

Dowling-Degos Disease Presenting With Associated Epidermal Inclusion Cysts: A Case Report and Review of the Literature.

ABSTRACT: Dowling-Degos Disease (DDD) is a rare and disfiguring autosomal dominant genodermatosis characterized by reticulate hyperpigmented macules or follicular comedone-like papules in the intertriginous areas that typically presents in the third or fourth decade of life. It is a progressive disease that is often treatment-resistant. Although its association with hidradenitis suppurativa has been well described, DDD has also been less commonly reported in conjunction with other dermatologic diseases with unknown etiologic associations. Herein, we present a case of DDD with associated epidermal inclusion cysts and conduct a literature review of dermatologic conditions reported in association with DDD.