Skin Depigmentation Research Articles

Black Pepper: Its Health Benefits

Black pepper has a scientific name of‘piper nigrum’is an unripe fruit of peppercorn which is dried, it is a flavor enhancer in food, besides also has health benefits, it contains bioactive compound piperine which adds a spicy taste to it being an antioxidant it reduces risk of various life-threatening illnesses (atherosclerosis, cardiovascular disease and neurological conditions) and also increases bioavailability of various nutrients, piperine at any given dose weakens memory impairment, in low dose piperine potentially increases neuronal density in hippocampus. Black pepper boosts HCL in stomach and has antispasmodic properties. Active compounds present play a significance in stimulating leucocytes increasing immunity against various pathogens. It is given along with iron supplements to improve its bioavailability without any adverse reaction. Piper Nigrum given in significant amount enhances learning and memory inadequacy related to AlCl, also exhibits anticholinesterase activity preventing nerve degeneration. In the ongoing COVID scenario biologically active compounds in piper nigrum: piperdardiine and piperanine are markedly effective against COVID‐19, hence is preferred as a medication. Black pepper rectifies the lipid profile, along with degree of total cholesterol, LDL and triglyceride in patients with cardiovascular diseases, piper nigrum being prosperous in having constituents of vanadium in it contributes in boosting and recovering fron cardiac function after a myocardial infarction and dealing with pressure overload–induced hypertrophy by inhibiting protein tyrosine phosphatases. Piper nigrum can boost melanocyte proliferation and bring back pigmentation to depigmented skin, therefore this could possibly be the treatment for vitiligo. Alkaloid constituent of black pepper, bring to bear anticancer properties in a wide range of malignancies.

Vitiligo: An Autoimmune Skin Disease and its Immunomodulatory Therapeutic Intervention.

Vitiligo is a chronic autoimmune depigmenting skin disorder characterized by patches of the skin losing functional melanocytes. Multiple combinatorial factors are involved in disease development, among which immune T cells play a prominent role. The immune cells implicated in melanocyte destruction through adaptive immunity include CD8+ cytotoxic T cells and regulatory T cells, and aberrantly activated skin-resident memory T cells also play a role in melanocyte destruction. Over the past several years, major progress in understanding vitiligo pathogenesis has led to the development of targeted therapies. Janus kinase (JAK) inhibitors, which share the similar mechanism that autoactivates CD8+ T cells in chronic inflammatory diseases, have been reported to have therapeutic significance in vitiligo. Recently, immunomodulatory therapeutic interventions in vitiligo have been emerging. Mesenchymal stem cells (MSCs) regulate cytokine secretion and the balance of T-cell subsets, which makes them a promising cell-based treatment option for autoimmune diseases. The induction of MSC-mediated immunomodulation is complicated and occurs by contact-dependent mechanisms and soluble extracellular vesicle (EV) mediators. EVs released from MSCs contain various growth factors and cytokines with anti-inflammatory effects in the skin immune response. Here, we summarize and discuss the progress to date in targeted therapies that immunomodulate the niche environment of vitiligo, from the clinical trial of JAK inhibitors to the potential of MSCs and MSC-EVs. The available information was collected to highlight the need for further research into the treatment of vitiligo.

Effect of cysteamine hydrochloride-loaded liposomes on skin depigmenting and penetration

Skin hyperpigmentation is caused by an excessive production of melanin. Cysteamine, an aminothiol compound physiologically synthetized in human body cells, is known as depigmenting agent. The aim of this study was to evaluate the depigmenting activity and skin penetration of liposome formulations encapsulating cysteamine hydrochloride. First, cysteamine hydrochloride-loaded liposomes were prepared and characterized for their size, polydispersity index, zeta potential and the encapsulation efficiency of the active molecule. The stability of cysteamine hydrochloride in the prepared liposome formulations in suspension and freeze-dried forms was then assessed. The in vitro cytotoxicity of cysteamine and cysteamine-loaded liposome suspensions (either original or freeze-dried) was evaluated in B16 murine melanoma cells. The measurement of melanin and tyrosinase activities was assessed after cells treatment with free and encapsulated cysteamine. The antioxidant activity of the free and encapsulated cysteamine was evaluated by the measurement of ROS formation in treated cells. The ex vivo human skin penetration study was also performed using Franz diffusion cell. The stability of cysteamine hydrochloride was improved after encapsulation in liposomal suspension. In addition, for the liposome re-suspended after freeze-drying, a significant increase of vesicle stability was observed. The free and the encapsulated cysteamine in suspension (either original or freeze-dried) did not show any cytotoxic effect, inhibited the melanin synthesis as well as the tyrosinase activity. An antioxidant activity was observed for the free and the encapsulated cysteamine hydrochloride. The encapsulation enhanced the skin penetration of cysteamine hydrochloride. The penetration of this molecule was better for the re-suspended freeze-dried form than the original liposomal suspension where the drug was found retained in the epidermis layer of the skin.

Systemic Sclerosis in Zimbabwe: Autoantibody Biomarkers, Clinical, and Laboratory Correlates.

IntroductionSystemic sclerosis (SScl) is an autoimmune disease whose prevalence is rarely reported in Africa. Autoantibodies are the biomarkers of the condition, precede overt disease and determine disease phenotypes. SSc specific autoantibodies also vary between racial groupings. Objective: To investigate the clinical and laboratory characteristics of Zimbabwean patients who were reactive SSc specific autoantibodies.Materials and Method240 patients, 173 of them female with SSc specific autoantibodies were included. Autoantibodies were detected by indirect immunofluorescence microscopy and immunoblotting using a panel of 13 SScl (Euroimmun Ag., Germany). Demographic, clinical and laboratory parameters relevant to the monitoring of SScl were captured. These included pulmonary function tests, hematology, clinical chemistry, serology and thyroid function tests. Allergy skin prick tests (SPT) to inhalant and food allergen sources were conducted when indicated.ResultsAll the 240 patients (median age was 36 years) expressed SSc specific autoantibodies. 86% were Black, 11% White and 3% Asian and a fifth (20%) were younger than 16 years. Eleven (4.6%) fulfilled the ACR/EULAR classification of SSc. Clinically they had limited cutaneous (n=6), diffuse cutaneous (n=3) and SScl/inflammatory myopathy overlap (n=2). The most frequently detected antibodies anti-RNA polymerase III (RNAP) 55%, anti-Th/To (28%) anti-RNAP 11 (22%), anti-CENPB (18%) and anti-Scl-70/ATA (13%). Racial variations in the expression of these antibodies were apparent between Black, White and Asian patients. The majority (95%), who did not fulfil the ARA/EULAR criteria were symptomatic. Raynaud’s Phenomenon was documented in 24%. Respiratory symptoms included coughing, dyspnea and wheezing. There was a restrictive ventilatory defect with increased FEV1/FVC ratio. Pruritus, urticaria and skin depigmentation were the main cutaneous features while constipation, bloating, Gastroesophageal reflux disease (GERD) and abdominal pain dominated GI symptoms. Mean blood pressure readings while normal varied with biomarkers. Haematology and biochemistry parameters were within normal reference ranges.ConclusionThe expression of SSc specific autoantibodies is common and associated with known SSc symptoms. The types and frequency of autoantibodies varied with racial groupings. A fifth of the patients were children below the age of 16 years.

Liquid-Liquid Chromatography Separation of Guaiane-Type Sesquiterpene Lactones from Ferula penninervis Regel & Schmalh. and Evaluation of Their In Vitro Cytotoxic and Melanin Inhibitory Potential.

Ferula penninervis Regel & Schmalh. is a perennial plant used in Kazakh traditional folk medicine to treat epilepsy, neurosis, rheumatism, gastroduodenal ulcers, dyspepsia, wounds, abscesses or tumors. The aim of this work was to isolate series of sesquiterpene lactones from a crude methanolic root extract and investigate their in vitro cytotoxic potential against androgen-dependent prostate cancer LNCaP and epithelial prostate PNT2 cells, as well as to evaluate their melanin production inhibitory effects in murine melanoma B16F10 cells stimulated with α-melanocyte-stimulating hormone (αMSH). Two new (penninervin P and penninervin Q) and five known (olgin, laferin, olgoferin, oferin and daucoguainolactone F) guaiane-type sesquiterpene lactones were isolated with the use of a simple and fast liquid-liquid chromatography method. Olgin and laferin showed the most promising cytotoxic effects in LNCaP cells (IC50 of 31.03 and 23.26 μg/mL, respectively). Additionally, olgin, laferin, olgoferin, and oferin (10 μg/mL) potently impaired melanin release (40.67–65.48% of αMSH + cells) without influencing the viability of B16F10 cells. In summary, our findings might indicate that guaiane-type sesquiterpene lactones from F. penninervis could be regarded as promising candidates for further research in discovering new therapeutic agents with anti-prostate cancer and skin depigmentation properties.

312 Safety and Efficacy of Ruxolitinib Cream for the Treatment of Vitiligo: 104-Week Data From a Phase 2 Study

Vitiligo is a chronic autoimmune disease resulting in skin depigmentation. Ruxolitinib cream, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated significant repigmentation in a phase 2, dose- ranging, randomized study of adult patients with vitiligo (N=157) when applied to ≤20% total body surface area. Of 80 patients who applied 0.5% ruxolitinib cream once daily (QD), 1.5% QD, or 1.5% twice daily (BID) and completed the 52-week randomized period, 77 continued to apply 1.5% ruxolitinib cream BID in the open-label period for another 52 weeks.

Role of Interleukin 33 in Immune Response Process of Vitiligo Disease

Background: When melanocytes cease to operate, vitiligo develops. It is a skin and mucosa depigmentation condition. Any area of the body can develop well-circumscribed white macules or patches in this disease. Approximately 1-2 percent of the population is affected by Vitiligo. Suppression of tumorigenicity 2 (ST2), a newly discovered member of the interleukin-1 (IL-1) family, acts as a receptor for the IL-1 receptor-like 1 protein (also known as IL-1RL1) while also acting as a ligand for the interleukin-1 receptor-like 1 protein (also known as IL-1RL1) and suppressing tumorigenicity 2. Objective: To study Interleukin 33 (IL-33) in generalized and localized vitiligo patients and to assess their relationship with disease activity. Conclusion: Vitiligo could be associated with increased serum levels of IL-33, which could help as predictor marker of disease activity in vitiligo.

Usefulness of Micro-Punch Skin Grafting for Treatment of Resistant Vitiligo

Background: Vitiligo is a depigmented common skin disorder. The disease may lead to social and psychological distress to the patient. Therefore, a good treatment can improve the patient’s life quality. Punch grafting is a simple and commonly used method of treating vitiligo. However, it is time consuming with the risk of post-operative cobble stoning appearance. We used motorized 0.8 - 1.3 mm micro punch grafting procedure to overcome these limitations. Objective: to evaluate the therapeutic effectiveness of using micro punch grafting to treat vitiligo and adverse events associated with this method. Methods: this was a prospective study for 20 patients with stable vitiligo. They underwent motorized 0.8 - 1.3 mm micro punch grafting from June 2019 to June 2020. Vitiligo treatment with micro punch grafting technique had promising results, and careful assessment of factors associated with the outcome was done. Results: Thirty percent of the patients showed excellent re-pigmentation ≥ 75%. Forty percent of the patients showed moderate re-pigmentation. Twenty percent of the cases showed mild re-pigmentation and only 10% showed no improvement. So overall, the therapy was tolerable. Conclusion: micro punch grafting is an effective way to treat vitiligo; it is also considered a suitable option with tolerable adverse events.

Identification of the Role of Wnt/β-Catenin Pathway Through Integrated Analyses and in vivo Experiments in Vitiligo.

PurposeVitiligo is an acquired depigmentation skin disease, which affects an average of 1% of the world’s population. The purpose of this study is to identify the key genes and pathways responsible for vitiligo and find new therapeutic targets.MethodsThe datasets GSE65127, GSE53146, and GSE75819 were downloaded from the Gene Expression Omnibus (GEO) database. R language was used to identify the differentially expressed genes (DEGs) between lesional skin of vitiligo and non-lesional skin. Next, the key pathways were obtained by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein–protein interaction (PPI) networks were conducted by STRING database and Cytoscape software. Subsequently, module analysis was performed by Cytoscape. Among these results, the Wnt/β-catenin pathway and melanogenesis pathway caught our attention. The expression level of β-catenin, microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) was detected by immunofluorescence in vitiligo lesions and healthy skin. Moreover, zebrafish was treated with XAV-939, an inhibitor of the Wnt/β-catenin pathway. After that, the area of melanin granules as a percentage of the head area was measured. The mRNA expression of β-catenin, lymphoid-enhancing factor 1(lef1), tyr and mitf were detected by q-PCR (quantitative polymerase chain reaction) in zebrafish (Danio rerio).ResultsA total of 2442 DEGs were identified, including 1068 upregulated and 1374 downregulated DEGs. The key pathways were identified by GO and KEGG analyses, such as “NOD-like receptor signaling pathway”, “Wnt signaling pathway”, “Melanogenesis”, “mTOR signaling pathway”, “PI3K-Akt signaling pathway”, “Calcium signaling pathway” and “Rap1 signaling pathway”. The immunofluorescence results showed that the level of β-catenin, MITF and TYR was significantly downregulated in vitiligo lesional skin. In zebrafish, the mean percentage area of melanin granules and the expression of β-catenin, lef1, tyr and mitf were decreased after treated with XAV-939.ConclusionThe present study identified key genes and signaling pathways associated with the pathophysiology of vitiligo. Among them, the Wnt/β-catenin pathway played an essential role in pigmentation and could be a breakthrough point in vitiligo treatment.

27535 Safety and efficacy of ruxolitinib cream for the treatment of vitiligo: 104-week data from a phase 2 study

Vitiligo is a chronic autoimmune disease resulting in skin depigmentation. Ruxolitinib cream, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated significant repigmentation in a phase 2, dose-ranging, randomized study of adult patients with vitiligo (N = 157) when applied to ≤20% total body surface area. Of 80 patients who applied 0.5% ruxolitinib cream once daily (QD), 1.5% QD, or 1.5% twice daily (BID) and completed the 52-week randomized period, 77 continued to apply 1.5% ruxolitinib cream BID monotherapy in the open-label period for another 52 weeks. Twenty-seven patients (35.1%) discontinued open-label treatment, most commonly because of withdrawal by patient (n = 18). No significant safety signals were observed during the 52-week open-label period; 7 patients (9.1%) had a treatment-related adverse event (TRAE; all grade 1/2). Among patients initially randomized to receive 1.5% ruxolitinib cream BID (n = 33), TRAEs were reported in 11 patients (33.3%) over the 104-week study period, all of which were grades 1 (n = 10) or 2 (n = 1). Regardless of dose at initial randomization, no accumulation of AEs or clinically relevant changes in hemoglobin or platelet levels were observed over the 104-week treatment period. Among all evaluable patients with a Week 104 study visit (n = 55), F-VASI50, F-VASI75, and F-VASI90 were achieved by 83.6%, 65.5%, and 52.7% of patients, respectively; T-VASI50 was achieved by 58.2% of patients. In summary, treatment with ruxolitinib cream was well tolerated over a 2-year period and resulted in substantial repigmentation of vitiligo lesions.

25486 Correlation of the Vitiligo Area Scoring Index with patient- and physician-reported measures of clinical improvement in a randomized, double-blind phase 2 study

The Vitiligo Area Scoring Index (VASI) is a quantitative clinical tool that estimates the overall area of vitiligo patches (ie, skin depigmentation) and the degree of macular repigmentation within these patches over time. This analysis aimed to evaluate the correlation between facial and total VASI (F-VASI and T-VASI, respectively) with patient- and physician-reported measures of clinical improvement (Patient Global Impression of Change-Vitiligo [PaGIC-V; 7-point scale] and Physician’s Global Vitiligo Assessment [PhGVA]) in a randomized, double-blind phase 2 study of 157 patients with vitiligo. Among stable patients (ie, no change from baseline in PaGIC-V [score of 4]), VASI scores showed excellent test-retest reliability (≥0.95) at Weeks 12 and 24. Significant differences in VASI were detected among PhGVA categories (mild, moderate, severe) at baseline. The VASI detected change in disease status during the treatment period; the changes were significantly different between patients who showed improvement (PaGIC-V, 1-3) or worsening (PaGIC-V, 5-6) and were related to the PaGIC-V (Pearson’s r ∼0.45, P ˂ .0001). To assess interpretability, an anchor-based approach used PaGIC-V (score of 1 or 2) to define clinically meaningful change (CMC) on the VASI at Week 24; mean percentage CMC was 57% for F-VASI and 42% for T-VASI. Results indicated that a higher percentage of patients treated with 1.5% ruxolitinib cream met or exceeded CMC thresholds vs vehicle on F-VASI (39.4% vs 3.1%; P = .0005) and T-VASI (27.3% vs 0%; P = .002). Analyses of efficacy using the F-VASI and T-VASI reflect meaningful and relevant changes in patients with vitiligo.

Neobenedenia melleni from reef ornamental fish species in a retailer of Southeastern Brazil and its possible role as a mechanical vector of bacterial infection.

Annually, more than 2500 ornamental fish species are traded worldwide. Forty percent of these are from marine water. Some 98% of marine species are wild-caught from their natural habitat, and the majority subsequently exported. Wild fish frequently carry pathogens, which could induce diseases after the stress of capture. Neobenedenia melleni is a platyhelminth that mainly attaches to the skin and eyes of the host. It provokes dermal inflammation, epidermal loss, skin depigmentation, reduction in the number of mucous cells, and, consequently, decreased mucus protection, and declining immunological barriers. This makes fish susceptible to secondary infections. A total of 47 wild reef fish from a retailer were examined, suspected to be infected with ectoparasites. The morphological identification revealed N. melleni as a monogenean agent. One monogenean specimen was collected from the eye of each of the 40 fish analyzed to evaluate possible bacterial secondary infections using the matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) technique. The MALDI-TOF MS identified that 59% of monogenean collected from the eyes had bacteria, including some pathogenic to fish. This led us to believe that the ectoparasite can be a possible mechanical vector of pathogenic bacteria for fish culture and maintenance. The use of praziquantel as an antiparasitic agent is also discussed.

Long-term efficacy and safety of imiquimod 5% and fluorouracil 1% creams in medical monotherapy of complex eyelid basal cell carcinomas.

To study the long-term efficacy and safety of local application of imiquimod 5% and fluorouracil 1% creams in complex eyelid basal cell carcinomas (BCCs). A retrospective, non-comparative study in biopsy-proven, complex (involving canthi or >50% of eyelid length) eyelid BCC patients who were medically unfit for surgical procedures. All patients were medically treated with either of the creams using fixed-dose regimens for a minimum of 3 months. All received oral vitamin C 500 mg QID for 3 months as an adjunct for collagen healing. A minimum of "post-treatment" follow-up of 12 months was observed. Of total 30 patients, imiquimod 5% and fluorouracil 1% were used in 16 and 14 patients, respectively. The mean age of our patients was 70.5 years. The co-morbidities included - severe coronary artery disease using blood-thinners (n = 19), poorly controlled diabetes (n = 12), poorly controlled hypertension (n = 6), on nebulization (n = 3), and tuberculosis with pulmonary fibrosis (n = 2). Complete clinical tumor resolution was noted in 10 and 8 patients over 12 and 16.5 weeks, respectively, in imiquimod and fluorouracil groups. Periocular skin erythema, chemical conjunctivitis, and skin depigmentation were seen in all the patients of imiquimod group. On the other hand, the local side-effect profile in fluorouracil patients was limited. The medical treatment of complex eyelid BCC is a useful alternative to surgery in the elderly with significant co-morbidities. It provides a promising long-term relief with a tolerable side-effect profile. A prospective, randomized, double-blinded trial would provide stronger evidence for the efficacy of these drugs.

Arbutin as a Skin Depigmenting Agent with Antimelanogenic and Antioxidant Properties.

Arbutin is a compound of hydroquinone and D-glucose, and it has been over 30 years since there have been serious studies on the skin lightening action of this substance. In the meantime, there have been debates and validation studies about the mechanism of action of this substance as well as its skin lightening efficacy and safety. Several analogs or derivatives of arbutin have been developed and studied for their melanin synthesis inhibitory action. Formulations have been developed to improve the stability, transdermal delivery, and release of arbutin, and device usage to promote skin absorption has been developed. Substances that inhibit melanin synthesis synergistically with arbutin have been explored. The skin lightening efficacy of arbutin alone or in combination with other active ingredients has been clinically evaluated. Combined therapy with arbutin and laser could give enhanced depigmenting efficacy. The use of arbutin causes dermatitis rarely, and caution is recommended for the use of arbutin-containing products, especially from the viewpoint that hydroquinone may be generated during product use. Studies on the antioxidant properties of arbutin are emerging, and these antioxidant properties are proposed to contribute to the skin depigmenting action of arbutin. It is hoped that this review will help to understand the pros and cons of arbutin as a cosmetic ingredient, and will lead to future research directions for developing advanced skin lightening and protecting cosmetic products.

Vitiligo – Study In view of familial occurence

Vitiligo – Study In view of familial occurence

Cutaneous melanocytoma associated with vitiligo and leukotrichia in a mixed‐breed pig

AbstractA 7‐month‐old, male castrated mixed‐breed pig presented for evaluation of a 3‐month history of cutaneous pigmented nodular lesions, multifocal leukoderma and leukotrichia. Skin biopsies were performed from pigmented nodules and depigmented skin for histopathology. Additional skin biopsies were collected aseptically for bacterial and fungal tissue cultures. Histopathologic diagnosis was a benign melanocytic neoplasm (melanocytoma) and marked vitiligo. Spontaneous regression of melanocytomas did not occur after 1 year of age as previously reported to occur in several swine breeds. Topical imidazoquinoline amine cream was applied to one melanocytoma three times a week for a month. No clinical improvement in either the melanocytoma or vitiligo occurred. In humans, vitiligo is associated with both neoplastic and benign melanocytic neoplasms; this case illustrates the presence of melanoma‐associated leukoderma in a domestic mixed‐breed pig and emphasises the importance of meticulous skin examination in swine patients with the development of vitiligo.

Granzyme B gene polymorphism in vitiligo: does it have an association?

Objectives To study the role of granzyme B (GZMB) gene polymorphism (rs8192917) in patients with nonsegmental vitiligo and to correlate the results with the available clinical information. Background Vitiligo is considered the most common acquired disease of depigmented skin characterized by depigmented patches of the skin, hair, and mucous membranes owing to destruction of melanocytes. Vitiligo is a multifactorial polygenic condition with a multifaceted pathogenesis, linked to both genetic and nongenetic aspects, such as autoimmune, cytotoxic, oxidant–antioxidant, and neural therories working in performance. Patients and methods GZMB gene polymorphism (rs8192917) was identified using real-time PCR technique in 40 patients having nonsegmental vitiligo and 40 age-matched and sex-matched healthy controls. Assessment of disease severity was done using Vitiligo Area Severity Index score, and disease activity was assessed using Vitiligo Disease Activity score. Results CC and TC genotypes were significantly higher in the patients' group [P = 0.005; odds ratio (OR) = 7.2, 95% confidence interval (CI) = 1.61–32.2 for CC and OR = 1.86, 95% CI = 0.42–8.15 for TC], with significant statistical preponderance of C allele in cases (P = 0.001; OR = 3.05, 95% CI = 1.55–6.01). Conclusion GZMB gene polymorphism (rs8192917) is associated with the susceptibility to nonsegmental vitiligo in a sample of Egyptian population.

Analysis of genotype-phenotype relationships in 90 Chinese probands with Waardenburg syndrome.

Waardenburg syndrome (WS) is a phenotypically and genetically heterogeneous disorder characterised by hearing loss and pigmentary abnormalities. We clarified the clinical and genetic features in 90 Chinese WS probands. Disease-causing variants were detected in 55 probands, for a molecular diagnosis rate of 61%, including cases related to PAX3 (14.4%), MITF (24.4%), and SOX10 (22.2%). Altogether, 48 variants were identified, including 44 single-nucleotide variants and 4 copy number variants. By parental genotyping, de novo variants were observed in 60% of probands and 15.4% of the de novo variation was associated with mosaicism. Statistical analyses revealed that brown freckles on the skin were more frequently seen in probands with MITF variants; patchy depigmented skin, asymmetric hearing loss, and white forelocks occurred more often in cases with PAX3 variants; and congenital inner ear malformations were more common and cochlear hypoplasia III was exclusively observed in those with SOX10 variants. In addition, we found that ranges of W-index values overlapped between WS probands with different genetic variants, and the use of the W-index as a tool for assessing dystopia canthorum may be problematic in Chinese. Herein, we report the spectrum of a cohort of WS probands and elucidate the relationship between genotype and phenotype.

Novel Chemically Modified Curcumin (CMC) Analogs Exhibit Anti-Melanogenic Activity in Primary Human Melanocytes.

Hyperpigmentation is a dermatological condition characterized by the overaccumulation and/or oversecretion of melanin pigment. The efficacy of curcumin as an anti-melanogenic therapeutic has been recognized, but the poor stability and solubility that have limited its use have inspired the synthesis of novel curcumin analogs. We have previously reported on comparisons of the anti-melanogenic activity of four novel chemically modified curcumin (CMC) analogs, CMC2.14, CMC2.5, CMC2.23 and CMC2.24, with that of parent curcumin (PC), using a B16F10 mouse melanoma cell model, and we have investigated mechanisms of inhibition. In the current study, we have extended our findings using normal human melanocytes from a darkly pigmented donor (HEMn-DP) and we have begun to study aspects of melanosome export to human keratinocytes. Our results showed that all the CMCs downregulated the protein levels of melanogenic paracrine mediators, endothelin-1 (ET-1) and adrenomedullin (ADM) in HaCaT cells and suppressed the phagocytosis of FluoSphere beads that are considered to be melanosome mimics. All the three CMCs were similarly potent (except CMC2.14, which was highly cytotoxic) in inhibiting melanin production; furthermore, they suppressed dendricity in HEMn-DP cells. CMC2.24 and CMC2.23 robustly suppressed cellular tyrosinase activity but did not alter tyrosinase protein levels, while CMC2.5 did not suppress tyrosinase activity but significantly downregulated tyrosinase protein levels, indicative of a distinctive mode of action for the two structurally related CMCs. Moreover, HEMn-DP cells treated with CMC2.24 or CMC2.23 partially recovered their suppressed tyrosinase activity after cessation of the treatment. All the three CMCs were nontoxic to human dermal fibroblasts while PC was highly cytotoxic. Our results provide a proof-of-principle for the novel use of the CMCs for skin depigmentation, since at low concentrations, ranging from 5 to 25 µM, the CMCs (CMC2.24, CMC2.23 and CMC2.5) were more potent anti-melanogenic agents than PC and tetrahydrocurcumin (THC), both of which were ineffective at melanogenesis at similar doses, as tested in HEMn-DP cells (with PC being highly toxic in dermal fibroblasts and keratinocytes). Further studies to evaluate the efficacy of CMCs in human skin tissue and in vivo studies are warranted.

A Case of Autoimmune Polyglandular Syndrome Type 3b Initially Presenting as Generalized Weakness in an Elderly Patient

Introduction: Autoimmune polyglandular syndrome (APS) is a multiorgan genetic autoimmune disease. APS-3B subtype is autoimmune thyroiditis with pernicious anemia. In this case, we will discuss an elderly female patient diagnosed with APS-3B. Case Presentation: A 69-year-old Caucasian female patient with a past medical history of autoimmune thyroiditis presented to the emergency department with a two-month history of generalized weakness and nausea. Associated symptoms included shortness of breath and diarrhea. Review of systems was otherwise unremarkable. Physical exam was positive for depigmented skin macules over the upper extremities. Lab results showed hemoglobin 8.2 [11.7 - 15.5 g/dL], MCV 121[80 - 100 fL], platelets 144,000 [150 - 450 X10E9/L], WBC 1.9 [4.0 - 11.0 X10E9/L], LDH 1153[100 - 235 U/L], TSH 0.28[0.49 - 4.67 uIU/mL], free T4 1.7 [0.61 - 1.60 ng/dL], direct Coombs test negative. Iron saturation 55%, vitamin B12 level <50 [180 - 914 pg/mL], folate >25[>5.8 ng/mL], total bilirubin 2.3 [0.3 - 1.2 mg/dL], haptoglobin <30 [32 - 228 mg/dL], AST 43 [0 - 41 U/L], reticulocyte 1.4%. Blood smear showed absolute neutropenia with flow cytometry unremarkable. Chest x-ray and urinalysis were negative. Immunofixation showed low IgM 44 [45 - 281 mg/dL], low IgG 619 [635 - 1,741 mg/dL]. Intrinsic factor antibodies (IF-Ab) were positive. Hematology reported that hemolytic anemia is less likely given Coombs test was negative. About 1.5% of Vitamin B12 deficiency present with a hemolytic picture due to ineffective erythropoiesis while Coombs test help to differentiate it from autoimmune hemolytic anemia. Diagnosis of pernicious anemia was made and the patient started on vitamin B12 injections. The combination of pernicious anemia, autoimmune thyroiditis, and vitiligo supported the diagnosis of autoimmune APS-3B. There was a normalization of vitamin B12 level and symptomatic improvement on a one-week follow-up. Discussion: The patient was diagnosed with autoimmune thyroiditis in 2014 with positive anti-TPO antibodies and elevated TSH; she required levothyroxine supplementation since diagnosis. Hypothyroidism causes macrocytic anemia, which may delay pernicious anemia diagnosis. APS-3B is associated with HLA-B8 and/or DR3 and DR5. Many studies reported that autoantibodies can be detected before developing symptoms of organ involvement. Thorough family history provides support for autoantibody testing to detect cases of APS-3B earlier. Active surveillance and early diagnosis will help minimize invasive testing such as bone marrow biopsy, so proper history taking is a key factor to early diagnose these conditions. Conclusion: APS-3B is a rare disorder. Diagnosis is difficult hypothyroidism causes macrocytic anemia. Early detection of APS-3B may help to prevent complications that increase the risk of mortality and morbidity, particularly in the elderly population.