Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Effects of a moisturizer containing pseudo-ceramide and a eucalyptus extract on sweating function in adult atopic dermatitis: a double-blind, randomized, controlled left-right comparison clinical trial.

BACKGROUND: Many patients with atopic dermatitis (AD) have a decreased ability to sweat. Several factors can cause decreased perspiration, such as weak tight junctions of sweat ducts, reduced acetylcholine receptor function, and inhibition of perspiration by histamines. Parakeratosis of AD skin also decreases sweating by occluding sweat pores. Increased ceramide levels in the stratum corneum reduce parakeratosis by improving stratum corneum functions. Furthermore, ceramides and/or ceramide derivatives may affect claudin-3 and acetylcholine receptors. OBJECTIVE: In this study, we investigated the efficacy of a moisturizer containing pseudo-ceramide and a eucalyptus extract to increase ceramide levels in the epidermis to improve the sweating ability of patients with AD. METHODS: Nineteen patients with AD applied moisturizers with or without pseudo-ceramide and a eucalyptus extract on the cubital fossa of either arm twice a day for 4 weeks. Skin conditions and sweating ability, measured as the response to acetylcholine stimulation, were evaluated prior to the start of the study (Week 0) and at the end of Weeks 2 and 4. RESULTS: Both moisturizers improved the visually evaluated skin symptoms and skin hydration. However, only the moisturizer containing pseudo-ceramide and the eucalyptus extract significantly improved cutaneous barrier function and significantly increased the ceramide level in the stratum corneum. That moisturizer also increased the sweating volume and shortened the latency time for sweating, an indicator of sweating ability, but the other moisturizer did not. CONCLUSION: Based on these results, the moisturizer containing pseudo-ceramide and a eucalyptus extract helps recover the sweat function of AD patients.

Herb Sanqi-Derived Compound K Alleviates Oxidative Stress in Cultured Human Melanocytes and Improves Oxidative-Stress-Related Leukoderma in Guinea Pigs.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

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.

An Extremely Rare Case of Leukoderma Induced by Cosmetics Containing Ascorbic Acid.

We report the case of a 73-year-old woman with leukoderma induced by cosmetics containing ascorbic acid. She had noticed the sudden appearance of a hypopigmented macule on the cheek within 1 month after use of the cosmetics with the brand name Obaji C Serum. No history of use of rhododenol-containing cosmetics was declared. Histopathological analysis revealed that the number of matured melanocytes was apparently decreased, and T lymphocytes abundantly infiltrated mainly the perifollicular region. In addition to the discontinuation of using Obaji C Serum, phototherapy by excimer light was noticeably effective for repigmentation. To our knowledge, there has been no other report so far showing hypopigmented lesions induced by this cosmetic.

Impact of Jumihaidokuto (Shi-Wei-Bai-Du-Tang) on Treatment of Chronic Spontaneous Urticaria: A Randomized Controlled Study.

OBJECTIVE: To study the effect of Jumihaidokuto (Shi-Wei-Bai-Du-Tang, ) in the management of chronic spontaneous urticaria. METHODS: A randomized two-arm, parallel group study was conducted to compare the effect of Jumihaidokuto (6 g daily) with a control for 8 weeks. Concomitant therapy (e.g., antihistamines) was continued. Twenty-one subjects with severe chronic urticaria were enrolled in this study. The primary treatment outcome was the severity score proposed by the Japanese Dermatological Association. Secondary outcomes were quality of life (Skindex-16), itch intensity (Visual Analogue Scale), and patients' subjective disability due to wheal or itch. After the subjects were randomly assigned to groups by block randomization, 10 received Jumihaidokuto, and 11 did not. All subjects had already taken antihistamines. RESULTS: Improvement was significant when comparing the severity score of the Jumihaidokuto group with that of the control group (P<0.01). Skindex-16 values for both groups gradually decreased in the same fashion. CONCLUSION: Concomitant use of Jumihaidokuto with antihistamine was more effective than antihistamine alone in the management of chronic idiopathic urticaria. (Trial Registration No. UMIN000007251).

Efficacy of a moisturizer containing a pseudo-ceramide and a eucalyptus extract for Japanese patients with mild atopic dermatitis in the summer.

BACKGROUND: Skin moisturizing is advocated to take care of the skin of patients with atopic dermatitis (AD). However, many patients stop using moisturizers in the summer because of excessive sweating and high humidity. OBJECTIVES: To examine the efficacy of a moisturizing gel containing a pseudo-ceramide and a eucalyptus extract, which enhances epidermal ceramide synthesis of patients with mild AD in the summer. METHODS: We performed a single-blinded 4-week clinical trial of body care on 44 Japanese subjects who had mild AD. They had not applied any moisturizer on their body in the summer. Twenty-seven subjects used the moisturizing gel containing a pseudo-ceramide and a eucalyptus extract twice a day and the 17 other subjects did not use any moisturizer. Prior to and at the end of weeks 2 and 4, the skin conditions of each subject were evaluated. RESULTS: During the test period, the atmospheric temperature increased and skin dryness and scaling significantly improved with or without application of the moisturizing gel. However, the improvement in dryness of the treated group was significantly higher than that of the nontreated group. Erythema and itchiness were significantly improved only in the treated group. The skin hydration on the forearm increased significantly only in the treated group. Accompanying those improvements, the quality of life of the subjects, evaluated by Skindex-16® , was significantly improved. CONCLUSION: The usage of a moisturizer containing a pseudo-ceramide and a eucalyptus extract is effective for care of the skin of AD subjects even in the summer.

Severe dermatitis with loss of epidermal Langerhans cells in human and mouse zinc deficiency.

Zinc deficiency can be an inherited disorder, in which case it is known as acrodermatitis enteropathica (AE), or an acquired disorder caused by low dietary intake of zinc. Even though zinc deficiency diminishes cellular and humoral immunity, patients develop immunostimulating skin inflammation. Here, we have demonstrated that despite diminished allergic contact dermatitis in mice fed a zinc-deficient (ZD) diet, irritant contact dermatitis (ICD) in these mice was more severe and prolonged than that in controls. Further, histological examination of ICD lesions in ZD mice revealed subcorneal vacuolization and epidermal pallor, histological features of AE. Consistent with the fact that ATP release from chemically injured keratinocytes serves as a causative mediator of ICD, we found that the severe ICD response in ZD mice was attenuated by local injection of soluble nucleoside triphosphate diphosphohydrolase. In addition, skin tissue from ZD mice with ICD showed increased levels of ATP, as did cultured wild-type keratinocytes treated with chemical irritants and the zinc-chelating reagent TPEN. Interestingly, numbers of epidermal Langerhans cells (LCs), which play a protective role against ATP-mediated inflammatory signals, were decreased in ZD mice as well as samples from ZD patients. These findings suggest that upon exposure to irritants, aberrant ATP release from keratinocytes and impaired LC-dependent hydrolysis of nucleotides may be important in the pathogenesis of AE.

Cedar pollen aggravates atopic dermatitis in childhood monozygotic twin patients with allergic rhino conjunctivitis.

We report a case of 7-year-old monozygotic twin patients with atopic dermatitis. The HLA haplotypes were HLA A2, A11, B27, B61, DR1, and DR4. Both serum IgE levels and cedar pollen radioallergosorbent test (RAST) scores were high in the twins (elder/younger sister: IgE: 5170/3980 IU/ml and Japansese cedar pollen: >100/64.0) in contrast to low mite and food RAST scores (Dermatophagoides Pterygonium; 0.59/0.4 and egg white 9.24/4.6). The patients showed positive immediate (20 min in both sisters) and delayed (24 hours in elder sister, 24, 48, 72 hours in younger sister) reactions to a scratch test with Japanese cedar pollen. Skin lesions on the face were aggravated and extended to the trunk and extremities during the Japanese cedar pollen season and gradually subsided in summer. Oral provocation with egg white or cow milk showed no exacerbations, and topical corticosteroid did not improve the eczema. In contrast, successful protection from severe scratching behaviors was achieved by use of topical anti-allergic eye drops and wearing nightgowns made by the mother.

Airborne contact dermatitis due to Japanese cedar pollen.

Contact dermatitis caused by airborne antigen is a well-recognized problem. Previously, airborne contact dermatitis after contact with Japanese cedar pollen [Japanese cedar pollen dermatitis (JCPD)] has been reported in Japan. However, there is still no diagnostic test to evaluate contact dermatitis due to Japanese cedar pollen. Skin tests with Japanese cedar pollen have been used to investigate these patients. A histological analysis was also conducted to clarify the mechanism of JCPD. We performed a scratch-patch test, scratch test and assays for total immunoglobulin E (IgE) and specific IgE in 13 patients suspected to have skin symptoms from Japanese cedar pollen, 5 patients with Japanese cedar pollinosis and 15 control normal subjects. All subjects were tested with Japanese cedar pollen allergen extract. A skin biopsy was performed from a Japanese cedar pollen-scratch-patch-test positive in patients with JCPD. The result after 48 hr of scratch-patch test was compared with the patient's history and the findings of corresponding scratch test and specific IgE. 100% of the 13 patients with JCPD showed a positive scratch-patch-test reaction to Japanese cedar pollen extract. However, 20% of the patients with the Japanese cedar pollinosis without any eruptions showed a positive scratch-patch-test reaction. The percentage of positive results for specific IgE and the scratch test did not differ substantially between Japanese cedar pollionosis patients with a history of chronic erythema after contact with Japanese cedar pollen and those without such a history. No side-effects were observed regarding the scratch-patch test. Control subjects showed 7% positive reaction. Histological examination showed that eczematous change (spongiosis, intracellular oedema and acanthosis), and infiltration of lymphocytes and eosinophils were all observed at the scratch-patch-test-positive sites. We therefore concluded that the use of the scratch-patch test with Japanese cedar pollen extract was useful for accurately diagnosing JCPD.

Japanese cedar pollen as an exacerbation factor in atopic dermatitis: results of atopy patch testing and histological examination.

Atopy patch testing with Japanese cedar pollen extract has been used to investigate patients with atopic dermatitis whose condition is exacerbated by contact with Japanese cedar pollen. Comparative atopy patch testing, scratch tests, and assays for total IgE and specific IgE were performed in 74 patients with atopic dermatitis, 5 patients with Japanese cedar pollinosis and 15 control subjects. A skin biopsy was performed on any sites that were positive to Japanese cedar pollen patch test. The results after 48 h of atopy patch testing were compared with the patient's history, skin scratch test and specific IgE. Twenty-two of the 74 patients (30%) had a history of exacerbation every spring after contact with Japanese cedar. Of these patients 68% showed a positive reaction to Japanese cedar pollen extract, as did 21% of patients with atopic dermatitis without a history of exacerbation by Japanese cedar pollen, 20% of patients with Japanese cedar pollinosis without eruption and 7% of control subjects. A histological examination revealed eczematous changes and infiltration of lymphocytes and eosinophils in atopy patch testing positive sites. In conclusion, atopy patch testing with Japanese cedar pollen extract is a useful method for investigating trigger factors for eczematous skin lesions in a subgroup of patients with atopic dermatitis.

Allergic contact dermatitis induced by rosemary leaf extract in a cleansing gel.

We report a rare case of allergic contact dermatitis due to an extract of rosemary (Rosmarinus officinalis). A 23-year-old woman had begun to notice itchy erythema on her face around one month before presentation. She used various cosmetics and a cleansing gel containing rosemary leaf extract. From the patch test results, she reacted positively to the cleansing gel (1% in distilled water) and the rosemary leaf extract (0.1% in distilled water), one of its ingredients.

[Examination of "areas cutanea" in Yusho patients].

In the field of Dermatology, one of the representatives of oxidative stresses is ultraviolet irradiation. Repetitive ultraviolet exposure results in cutaneous photoaging. Otherwise, polychlorinated biphenyls (PCB) give rise to superoxide, which means Yusho patients have been affected by oxidative stress for more than thirty years. In order to examine the influence of oxidative stress by PCB to the skin, we measured the "areas cutanea" in the inner aspect of upper arm in Yusho patients and in age-matched controls. "Areas cutanea" were significantly smaller in Yusho patients than in controls. Although PCB can give an oxidative stress, the influence seemed to be little to the skin. There might be another mechanisms involved in this result except the oxidative stress by PCB. Further examination should be conducted in the future.

Localized argyria 20-years after embedding of acupuncture needles.

We report a 66-year-old woman with localized argyria caused by embedding of acupuncture needles. Ten years after she had received acupuncture, she noticed two asymptomatic bluish macules on her right arm. A biopsied specimen from the macule revealed many brownish-black granules mainly located around the sweat glands and the blood vessels in the dermis. The X-ray examination of the extremities revealed numerous needle-like fragments around her extremities. "Embedding of needles" induces some serious adverse events. We should know the adverse events for the safety and health of patients.