The relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis: An observational study.

PURPOSE: This study aimed to investigate the relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis among patients from a dental metal allergy clinic over a period of 8 years. METHODS: This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009 and March 31, 2016. Diagnoses of skin diseases, periodontal records, dental metal series patch test results, and electron probe microanalysis (EPMA) data were obtained from medical records. Relative risk (RR) values were estimated from these data. RESULTS: Of the 359 patients who underwent the patch test, 241 showed a positive reaction. Of the 187 patients who underwent EPMA, 113 had allergenic metals in their dental prostheses. These patients were suspected to have a dental metal allergy. Furthermore, 150 of the 436 patients were diagnosed with palmoplantar pustulosis (PPP). The RR of metal allergy between patients with PPP and healthy subjects was 3.88. The RR of periodontal disease between patients with PPP and PPP-negative patients in the national average was 2.54. CONCLUSION: In this study, both dental metal allergy and periodontitis showed a high RR for PPP.

A missense mutation in the death domain of EDAR abolishes the interaction with EDARADD and underlies hypohidrotic ectodermal dysplasia.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal-dominant or autosomal-recessive inheritance trait. X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms are caused by mutations in either EDAR or EDARADD genes. METHODS: We analyzed the DNA from a Japanese patient with HED through direct sequencing, and also performed functional studies for the mutation. RESULTS: We identified a homozygous missense mutation c.1073G>A (p.R358Q) in the EDAR gene of the patient, which was a nonconservative amino acid substitution within the death domain of EDAR protein. We demonstrated that the p.R358Q mutant EDAR protein lost its affinity to EDARADD, leading to reduced activation of the downstream NF-κB. CONCLUSION: Our data further suggest the crucial role of the EDAR signaling in development of hair, teeth, and sweat gland in humans.

Rhododendrol-induced leukoderma update II: Pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments in comparison with vitiligo.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.

Rhododendrol-induced leukoderma update I: Clinical findings and treatment.

Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.

Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma.

Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.

Case of allergic contact dermatitis due to 1,3-butylene glycol.

1,3-Butylene glycol (1,3-BG) is widely used in cosmetics, including low-irritant skin care products and topical medicaments, as an excellent and low-irritation humectant. We report a case of allergic contact dermatitis caused by 1,3-BG. A 28-year-old woman suffered from an itchy erythematous eruption on her face. By 2 days of closed patch testing, her own cosmetics and many of the hypo-irritant skin care products showed positive results. A second patch testing showed positive reaction to 1,3-BG (1% and 5%). 1,3-BG was a common component in most of the products that had elicited a positive reaction in the first patch testing. Although allergic contact dermatitis due to 1,3-BG is not so common, we have to consider 1,3-BG as a possible contact allergen in the patients presenting with allergic contact dermatitis due to various cosmetics.