Peritoneal melanosis associated with metastatic melanoma previously treated with targeted and immune checkpoint inhibitor therapy.

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.

Post-Inflammatory Hyperpigmentation: A Review of Treatment Strategies.

Post-inflammatory hyperpigmentation (PIH) is a reactive process resulting from increased melanin or abnormal distribution of melanin secondary to inflammatory skin conditions, dermatologic therapies, and external stimuli. Because PIH is a common condition that has a substantial effect on the quality of life, an understanding of its treatment modalities is essential. Though there are many therapeutic strategies for hyperpigmentary conditions such as melasma that are described in the literature, fewer studies focus on PIH. This article aims to provide a comprehensive literature review of therapies specifically used to treat PIH, such as topical combinations, chemical peels, and lasers. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4887.

The Therapeutic Use of Antioxidants for Melasma.

Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.

Melasma and thyroid disorders: a systematic review and meta-analysis.

BACKGROUND: Thyroid hormones may play a key role in melasma; however, melasma link with thyroid disorders remains controversial. OBJECTIVES: To compare the serum levels of thyroid-stimulating hormone (TSH), T4, T3, anti-thyroid peroxidase (anti-TPO), and antithyroglobulin between patients with melasma and control group using meta-analysis. METHODS: We screened 10 databanks and search engines, searched mesh and nonmesh terms. The identified evidences were reviewed and quality assessed using the Newcastle-Ottawa Scale (NOS). The heterogeneity between the primary results was investigated using Cochrane and I-square indices. Random effect model was applied to combine the standardized mean differences of thyroid function indicators between patients with and without melasma. P values meta-analysis was used to investigate the association between anti-TPO and melasma. RESULTS: We included seven studies, 473 cases, and 379 controls that had been investigated. The total standardized mean differences (95% confidence intervals) of TSH, T3, T4, and antithyroglobulin antibody between cases and controls were estimated to be 0.33 (0.18, 0.47), -0.01 (-0.20, 0.19), -1.50 (-2.96, -0.04), and 0.62 (0.14, 1.11), respectively. The corresponding figures among women were 0.35 (0.17, 0.52), 0.10 (-0.17, 0.38), -2.75 (-6.30, 0.81), and 0.99 (0.14, 1.83), respectively. P value of meta-analysis showed a significant relationship between anti-TPO serum level and melasma (Fisher = 26.80, P = 0.020). CONCLUSION: Serum levels of TSH, anti-TPO, and antithyroglobulin antibody were significantly higher in patients with melasma than those without melasma. Moreover, these differences were more severe among women with melasma.

CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma.

The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1ß, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.

Association between oral candidiasis and low CD4+ count among HIV positive patients in Hoima Regional Referral Hospital.

BACKGROUND: The aim of this study was to determine the prevalence of Human Immune Virus (HIV) related oral lesions and their association with Cluster of Differentiation 4 (CD4+) count among treatment naïve HIV positive patients. METHODS: This was a descriptive and analytical cross sectional study. Participants were 346 treatment naïve HIV positive adult patients. These were consecutively recruited from Hoima Regional Referral hospital between March and April 2012. Data collection involved interviews, oral examinations and laboratory analysis. RESULTS: A total of 168(48.6%) participants had oral lesions. The four commonest lesions were oral candidiasis (24.9%, CI = 20.6-29.7%), melanotic hyperpigmentation (17.3%, CI = 13.7-21.7%), kaposi sarcoma (9.3%, CI = 6.6-12.8%) and Oral Hairy Leukoplakia (OHL) (5.5%, CI = 3.5-8.4%). There was significant association between oral candidiasis and immunosuppression measured as CD4+ less than 350 cells/mm3 (OR = 2.69, CI = 1.608-4.502, p < 0.001). Oral candidiasis was the only oral lesion significantly predictive of immunosuppression (OR = 2.56, CI = 1.52-4.30, p < 0.001) with a Positive Predictive Value (PPV) of 48.2%, Negative Predictive Value (NPV) of 74.3%, 38.1% sensitivity and specificity of 81.4%. CONCLUSION: Oral candidiasis can be considered as a marker for immunesuppression, making routine oral examinations essential in the management of HIV positive patients.

Inflammatory features of melasma lesions in Asian skin.

Melasma is triggered by various factors including ultraviolet radiation and estrogen; however, its pathogenesis is unclear. To investigate the inflammatory features of melasma lesions as triggers for this disorder, 197 women with melasma who attended Asan Medical Center and Kangskin Clinic, Seoul, from June 2011 to October 2011 completed a questionnaire concerning triggering or aggravating factors. These cases were divided into "non-inflammatory" and "inflammatory" groups. Skin biopsies and immunostaining for CD68, CD117, and leukocyte common antigen (LCA) were performed in the lesional and peri-lesional skin of ten cases in the non-inflammatory group and nine cases in the inflammatory group. Among the 197 subjects (mean age, 41.5 years; mean age of melasma onset, 33.8 years), 50 patients (25.4%) were categorized into the inflammatory group. This group comprised cases that had inflammatory symptoms and events that triggered the melasma lesions. The lesional dermis contained more CD68(+) melanophages, CD117(+) mast cells, and LCA(+) leukocytes in the inflammatory group than in the non-inflammatory group. Inflammatory clinical features and an increased number of inflammatory cells in the lesion may be involved in the development of melasma in Asian skin.

Genetic and phenotypic relationships between immune defense, melanism and life-history traits at different temperatures and sexes in Tenebrio molitor.

Insect cuticle melanism is linked to a number of life-history traits, and a positive relationship is hypothesized between melanism and the strength of immune defense. In this study, the phenotypic and genetic relationships between cuticular melanization, innate immune defense, individual development time and body size were studied in the mealworm beetle (Tenebrio molitor) using three different temperatures with a half-sib breeding design. Both innate immune defense and cuticle darkness were higher in females than males, and a positive correlation between the traits was found at the lowest temperature. The effect of temperature on all the measured traits was strong, with encapsulation ability and development time decreasing and cuticle darkness increasing with a rise in temperature, and body size showing a curved response. The analysis showed a highly integrated system sensitive to environmental change involving physiological, morphological and life-history traits.

Comparison of oral manifestations with CD4 count in HIV-infected patients.

AIM AND OBJECTIVE: This study was carried out with the primary aim of correlating oral changes and general changes of HIV-infected patients with their CD4 count. MATERIALS AND METHODS: 124 patients were selected, and after taking their informed consent, they were subjected to detailed history taking and thorough clinical examination. Specific oral lesions and general physical changes were recorded. Every patient was subjected to laboratory investigation for CD4 count. All these findings were tabulated. The clinical observation and laboratory findings were subjected to critical analysis and correlated. Statistical test, i.e. Student's " t" test, was applied and objective conclusions were drawn. RESULT: Out of 124 patients, 40 had oral candidiasis, 6 had oral hairy leukoplakia, 12 had periodontal disease, 20 had xerostomia, 30 had melanin pigmentation, while 4 had HSV2, and atypical ulceration. Out of 40 patients with oral candidiasis, 28 patients had CD4 count <200 (group A), 10 patients were in group, B (CD4 count 200-500 cell/mm 3 ) and 2 patients in group C(CD4 >500 cell/mm 3 ). Oral hairy leukoplakia occurred in equal proportions in group A and B. These periodontal diseases were more commonly in group B; xerostomia and melanin pigmentation was equally seen in group A and B. CONCLUSION: Oral candidiasis, oral hairy leukoplakia, linear gingival erythema, necrotizing ulcerative gingivitis, and necrotizing ulcerative periodontitis are specific oral indicators which will definitely suggest to the dental surgeon that the disease is running a rapid downhill course and due to this the oral physician is in a position to raise a suspicion and alert the general physician regarding the declining immune status of patient.

Immunophenotypic markers to differentiate between benign and malignant melanocytic lesions.

BACKGROUND/AIMS: The authors investigated the expression of S100A1, S100A6, S100B, MelanA, and CEA in conjunctival naevi, primary acquired melanosis (PAM), conjunctival melanoma, and uveal melanoma in order to assess their potential usefulness in the pathological differential diagnosis of these entities. METHODS: Paraffin embedded sections of 18 conjunctival naevi, 14 PAM, 16 conjunctival melanomas, and 20 uveal melanomas were immunostained for S100A1, S100A6, S100B, MelanA, and CEA, and expression was scored semiquantitatively. RESULTS: Expression of S100A1 differed significantly between conjunctival naevi and conjunctival melanoma, with percentages of positive cells of 30.6% and 71.4%, respectively. Conjunctival melanomas had high average scores for S100A1 and S100B (71.4%, 62.9%, respectively), while uveal melanomas also had high S100A1 but low S100B scores (88.5%, 18.5%, respectively). MelanA was highly variable; naevi and uveal melanoma had higher average scores than conjunctival melanoma. CEA was hardly detectable in all four groups. CONCLUSION: S100A1 seems to be a possible candidate to differentiate conjunctival naevi from conjunctival melanoma. S100B seems to differentiate between uveal melanoma and conjunctival melanoma. However, the study size was small and therefore the data have to be confirmed by others.

Localized melanosis in an immunocompromised patient with local metastatic melanoma.

BACKGROUND: Melanosis is a rare, but well recognized late complication of some cases of metastatic melanoma. The precise pathogenesis is unclear. Most described cases report diffuse metastases and diffuse melanosis. OBJECTIVE: To present a case of localized melanosis secondary to locally metastatic melanoma without evidence of systemic involvement in a renal transplant patient. METHODS: Case report and literature review. RESULTS: We describe a case of localized melanosis in an immunocompromised patient without evidence of systemic metastases. The patient underwent limb perfusion and her immunosuppressive therapy has been stopped. The melanosis has not regressed; however, there has been no systemic involvement and her transplanted kidney is still functioning well. CONCLUSION: To our knowledge this is the first report of this phenomenon in an immunocompromised host.

Immunohistochemical detection of the c-met proto-oncogene product in the congenital melanocytic nevus of an infant with neurocutaneous melanosis.

Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) demonstrate extensive pigmented nevi in both skin and leptomeninges of the central nervous system resembling human neurocutaneous melanosis. We immunohistochemically detected HGF/SF receptor, Met, in a congenital nevus of an infant with neurocutaneous melanosis, indicating that deregulation of HGF/SF-Met signaling in the critical period of development may lead to this fatal syndrome.

HMB-45 antibody reactivity in pigmented lesions of the conjunctiva.

Conjunctival pigmented lesions, including ten compound nevi, three subepithelial nevi, two acquired melanoses, and six melanomas, were examined histologically and immunohistochemically to determine the specificity of mouse monoclonal HMB-45 antibody for these lesions. Eleven of 13 nevi, two of two acquired melanoses, and six of six melanomas stained with this antibody. Conjunctival melanomas showed intense and diffuse cytoplasmic staining; compound nevi and subepithelial nevi showed less intense but diffuse reaction. There was strong staining in melanocytic cells at the junction of the epithelium and substantia propria in compound nevi and acquired melanoses. Unlike skin nevi, conjunctival nevi show HMB-45 reactivity in their stromal components. Immunoreactivity to HMB-45 does not distinguish benign from atypical or malignant melanocytic lesions of the conjunctiva.