Chromametric assessment of drug skin tolerance: A comparative study between Africans and Caucasians skins.

BACKGROUND/AIMS: During dermatological forms development, one of the simplest non-invasive techniques used to evaluate cutaneous tolerance of formulations is to monitor the color changes using a tristimulus chromameter. Most published tolerance studies involving chromametric measurements are performed on Caucasian subjects. However, in the context of drug formulation for African-type populations, it is not always relevant to transpose tolerance results obtained on Caucasians populations to African-type ones due to histological ethnic differences of the skin. The goal of this work was to assess whether tristimulus chromameter can be used to highlight color variations following the application of dermatological topics on black skin in order to validate skin tolerance studies made on African-type subjects. MATERIALS AND METHODS: After application of two commercial creams with opposite side effects (skin irritation and skin blanching) in both Africans and Caucasians populations, color variations were evaluated using a tristimulus chromameter in L* a* b* color system and compared between both populations. L* indicating color brightness, a* represents green and red directions and b* represents blue and yellow directions. RESULTS: While skin irritation resulted in a significant increase of a* parameter in both studied populations, the skin blanching resulted in a decrease of a* associated with an increase of L* . CONCLUSION: We established that tristimulus chromameter can be used to achieve in vivo skin tolerance study of dermatologic formulations in Africans despite their dark skin even though it appeared less sensitive. This study can speed up the development of dermatological forms dedicated to Africans and/or Caucasians subjects.

Onlay Fascial Grafts to Silicone-Polytetrafluorethylene Composite Implants in Augmentation Rhinoplasty: A Retrospective Study of 241 Cases.

BACKGROUND: Silicone-polytetrafluoroethylene composite implants are fast gaining popularity in Asian rhinoplasty. Nonetheless, implant displacement, erythematous reactions, and infections still occur in the authors' patient group during long-term follow-up. OBJECTIVES: The authors reported successful experience of combining the utilization of silicone-polytetrafluoroethylene composite implants with onlay temporal fascial grafts to circumvent these complications. METHODS: Sixty-four patients of Asian ethnicity underwent augmentation rhinoplasty utilizing an I-shaped composite implant with an onlay fascial graft from January 2015 to June 2018, with a mean follow-up period of 13.5 months. This patient group was compared with a control group of 177 Asian patients who underwent augmentation rhinoplasty utilizing the same composite implant but without the addition of a fascial graft; the control group was treated from February 2012 to June 2015, with a mean follow-up of 42.0 months. Complications were compared between these 2 patient groups, specifically focusing on malposition/deviations, erythema, and infections. RESULTS: There was a marked decrease in complication rates with the addition of an onlay temporal fascial graft to cover the composite implant in augmentation rhinoplasty (7.8% vs 14.7%) as well as the rate of erythematous reactions (0% vs 6.2%, P = 0.04), infection (1.6% vs 1.1%), and implant malposition/deviation (0% vs 4.5%). Harvesting the temporal fascia and fashioning the onlay graft added an additional 33 minutes on average per procedure. No donor site morbidity was encountered. CONCLUSIONS: Although the operative time increased, the benefits of adding onlay fascial grafts to silicone-polytetrafluoroethylene implants in alloplastic augmentation rhinoplasty outweigh the drawbacks, as evidenced by the decrease in erythematous reactions.

Diffuse pruritic erythema as a clinical manifestation in anti-SAE antibody-associated dermatomyositis: a case report and literature review.

Anti-small ubiquitin-like modifier-1 activating enzyme (anti-SAE) antibodies have been recently discovered especially for myosin and identified as dermatomyositis (DM) marker. The frequency of anti-SAE antibodies in DM patients is extremely low. Diffuse pruritic erythema may be one kind of clinical manifestations of DM with anti-SAE antibodies. In this report, a 48-year-old female patient with amyopathic dermatomyositis (ADM) carrying anti-SAE antibodies presented diffuse pruritic erythema for 5 months. Diffuse pruritic erythema improved after treatment with prednisolone, cyclosporine, and thalidomide. The clinical characteristics of 75 previously reported cases with anti-SAE antibody-positive DM were reviewed, and the manifestations of the Asian and Western cohorts were compared. It was revealed that the Asian patients were more susceptible to diffuse erythema (17/34 vs. 3/41, P = 0.000), dysphagia (16/34 vs. 10/41, P = 0.040), and interstitial lung disease (ILD) (21/34 vs. 5/41, P = 0.000) compared with the Western patients. The frequency of malignancy in the Asian cohort was significantly higher than that in the Western cohort (10/34 vs. 4/41, P = 0.030).

Quantification of skin erythema response to topical alcohol in alcohol-intolerant East Asians.

BACKGROUND/PURPOSE: Severe alcohol intolerance characterized by flushing, headache, nausea, and tachycardia even after very modest oral alcohol consumption, is common among East Asians (Chinese, Japanese, Koreans) and has been associated with the accumulation of acetaldehyde resulting from genetic polymorphism of aldehyde dehydrogenase (ALDH). These individuals also display erythema of the skin in response to exposure to topical alcohol. We have recently observed that dietary phytochemicals such as sulforaphane can accelerate the disposal of acetaldehyde from cells and animals by inducing ALDH. The goal of this study was to quantify the erythema response of skin to topical alcohol exposure. METHODS: The erythema response of the forearm skin of healthy Japanese with unusual alcohol sensitivity evoked by a range of very low doses of alcohol (2, 4, 8, and 16 µmol/cm2 ) was determined by means of a chromometer, which measures a* values (red-green scale). RESULTS: The magnitude of the a* response (∆a*) to alcohol was time- and dose-dependent, but differed considerably among individuals. It was much higher in those individuals who claimed to be alcohol intolerant, and ∆a* was unrelated to the initial a* values of the skin prior to alcohol challenge. CONCLUSION: The ∆a* index is suitable for the quantitative determination of topical alcohol-induced erythema response, and the evaluation of effectiveness of protective strategies against erythema response.

Skin Erythema, Pigmentation and Hydration Kinetics after Ultraviolet Radiation-induced Photodamage in Southern Chinese Women.

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet (SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses (MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese.

What's new in objective assessment and treatment of facial hyperpigmentation?

Facial hyperpigmentation is common and challenging to treat in darker-skinned populations. A Medline literature search of articles published up to October 2013 reporting the objective assessment of and/or treatment for melasma, postinflammatory hyperpigmentation, dermatosis papulosa nigra, lichen planus pigmentosus, and erythema dyschromicum perstans was reviewed. Objective assessment was only reported for melasma and postinflammatory hyperpigmentation. Furthermore, randomized controlled trial evidence was only reported for melasma. Although progress has been made, there is a need to develop more objective outcome measures and effective treatments for hyperpigmentation.

An exploratory split-face study of a dual-wavelength laser system on erythromelanosis follicularis faciei in Chinese population.

BACKGROUND: Erythromelanosis follicularis faciei (EFF) is clinically characterized by well-demarcated erythema, hyperpigmentation and follicular papules. No satisfactory therapy has been widely accepted. OBJECTIVE: This study was aimed to evaluate the efficiency and complications of a dual-wavelength laser system in the treatment of EFF in Chinese population. METHODS: Twelve Chinese patients with EFF were enrolled in this study. One side of the face was randomized to receive five successions of treatments at intervals of 6-8 weeks, with the other side spared as control. The parameters were set as follows: energy densities of 6.5-7.5 J/cm(2) with pulsed dye laser (PDL) and 35-50 J/cm(2) with Nd:YAG; pulse duration of 0.5 ms with PDL and 15 ms with Nd:YAG; a delay time of 100 ms between delivery of the two wavelengths. The efficacy was evaluated using subjective assessment and non-invasive measurement. RESULTS: After five sessions of treatment, over 40% patients achieved more than 50% (moderate or significant) improvement. The efficacy maintained at 3-month follow-up. The values of erythema index and melanin index on treated side were significantly less than those on untreated side after sessions of treatments. Adverse effects of treated side were limited. CONCLUSION: Using this split-face module, dual-wavelength laser system treatment is proved to be suitable for Chinese EFF. Adverse effects were minimal.

The elusive gene for keratolytic winter erythema.

Keratolytic winter erythema (KWE), also known as Oudtshoorn skin disease, is characterised by a cyclical disruption of normal epidermal keratinisation affecting primarily the palmoplantar skin with peeling of the palms and soles, which is worse in the winter. It is a rare monogenic, autosomal dominant condition of unknown cause. However, due to a founder effect, it occurs at a prevalence of 1/7 200 among South African Afrikaans-speakers. In the mid-1980s, samples were collected from affected families for a linkage study to pinpoint the location of the KWE gene. A genome-wide linkage analysis, using microsatellite markers, identified the KWE critical region on chromosome 8p23.1-p22. Subsequent genetic studies focused on screening candidate genes in this critical region; however, no pathogenic mutations that segregated exclusively with KWE were identified. The cathepsin B (CTSB) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1) genes revealed no potentially pathogenic variants, nor did they show differential gene expression in affected skin. Mutation detection in additional candidate genes also failed to identify the KWE-associated variant, suggesting that the causal variant may be in an uncharacterised functional region. Bioinformatic analysis revealed highly conserved regions within the KWE critical region and a custom tiling array was designed to cover this region and to search for copy number variation. Although the study did not identify a variant that segregates exclusively with KWE, it provided valuable insight into the complex KWE-linked region. Next-generation sequencing approaches are being used to comb the region, but the causal variant for this interesting hyperkeratotic palmoplantar phenotype still remains elusive. 

UV responses in Native Hawaiians and Pacific Islanders, and Asians residing in Hawai'i and in Maryland.

BACKGROUND: UV exposure causes a wide range of skin damage including cutaneous melanoma. The mechanisms of cellular and molecular damage, as well as those of erythemal and pigmentation responses to UV exposure, have largely been studied in the White population. METHODS: This study systematically investigates responses to UV exposure in the Native Hawaiian and Pacific Islander (NHPI) and Asian populations living in Hawai'i (A/HI) as well as in Asians living in Maryland (A/MD). RESULTS: Our analyses indicate that the NHPI population is less sensitive to UV exposure than the A/HI population. Comparisons between the two Asian groups suggest that, despite slightly but not statistically different baseline constitutive pigmentation (pre-UV exposure), the A/HI and A/MD had similar UV sensitivity, measured as minimal erythemal dose (MED). However, the A/MD population had higher levels of oxyhemoglobin at doses of 2.0, 2.8 and 4.0 MED. Unexpectedly, the A/MD subjects retained higher levels of pigmentation 2 weeks post-UV exposure. CONCLUSION: This study provides insight into UV responses of the inhabitants of Hawai'i and shows that such responses are statistically significant for relatively small samples of NHPI and for A/HI and A/MD.

Eritema pigmentar fixo simulando herpes labial relacionado ao uso de fluconazol / Fixed drug eruption simulating herpes labialis related to fluconazole

O eritema pigmentar fixo geralmente representa uma reação cutânea adversa a medicamentos caracterizada pelo surgimento de lesões eritematosas arredondadas ou ovais que recorrem no mesmo sítio em minutos a horas após uma nova exposição ao medicamento previamente utilizado. As lesões podem ser únicas ou múltiplas e esmaecem em poucos dias deixando pigmentação hipercrômica residual, sendo os anti-inflamatórios e antibióticos, frequentes causadores. Já o herpes labial é causado principalmente pelo HSV1 e se manifesta com vesículas agrupadas sobre base eritematosa com posterior evolução para crostas e pode ser desencadeado por estresse, trauma etc. O objetivo do presente trabalho é demonstrar um caso de eritema pigmentar fixo simulando herpes labial, relacionado ao uso de fluconazol, visto que existem relativamente poucos relatos desta associação na literatura médica...

Split-face comparative study of 1550 nm fractional photothermolysis and trichloroacetic acid 15% chemical peeling for facial melasma in Asian skin.

Fractional photothermolysis (FP) therapy and chemical peels have been reported to be effective in patients with recalcitrant melasma. However, there is little information to compare the efficacy of single treatment session in Asian women. The aim of this study was to examine the efficacy, long-lasting outcomes and safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were randomly treated with a single session of 1550-nm FP on one cheek, and with a 15% TCA peel on the other cheek. Outcome measures included an objective melasma area severity index and subjective patient-rated overall improvement at 4 and 12 weeks after treatment. Melasma lesions were significantly improved 4 weeks after either treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation developed in 28% of patients at 4 weeks but resolved in all but one patient by 12 weeks. There was no difference between FP treatment and TCA peeling with respect to any outcome measure. FP laser and TCA peel treatments were equally effective and safe when used to treat moderate-to-severe melasma, but neither treatment was long-lasting. We suggest that multiple or periodic maintenance treatments and/or supplemental procedures may be required for the successful treatment of melasma in Asian women.

Bilateral milia en plaque in a 6-year-old Chinese boy.

Milia en plaque is a rare variant of miliathat occurs spontaneously on an erythematous base without identifiable causative factors. Approximately 40 cases have been recorded in the literature. Most occurred in the periauricular area, affected middle-aged patients, and showed a predilection for women. Here, we report a case of milia en plaque on the bilateral posterior helices in a 6-year-old Chinese boy.

Annular erythema associated with Sjögren's syndrome: review of the literature on the management and clinical analysis of skin lesions.

Annular erythema has been recognized to be a specific, cutaneous manifestation associated with Sjögren's syndrome. Based on a search of the literature up to 2007, annular erythema with Sjögren's syndrome (AESS) preferentially occurs in Asian but not in Western populations. However, the precise clinical course and standard regimen for the management of AESS have remained obscure, primarily because of its rare occurrence in Western populations and the fact that most Asian cases are isolated reports. In this study, 28 cases of AESS from our department and 92 cases distilled from the literature were enrolled in a retrospective study to evaluate the clinical characteristics and most desirable management of this skin manifestation in Sjögren's syndrome. We found that 75% of all cases with AESS were positive for both anti-SSA and anti-SSB antibodies. Multiple therapeutic options are available to treat AESS, including oral steroids. Several anti-malaria drugs or tacrolimus ointment have also been reported to be effective against AESS. AESS is a distinct clinical entity, and a small dose of prednisolone (approx. 10 mg) is sufficient to control diseases activity, except in some cases with systemic manifestations, and this treatment has a more rapid clinical effect than topical steroids.

CHILD syndrome: the NSDHL gene and its role in CHILD syndrome, a rare hereditary disorder.

BACKGROUND: CHILD syndrome, a rare hereditary disorder of keratinization (MIM 308050, 300275), is the acronym proposed by Happle to name a rare entity, characterized by congenital hemidysplasia, icthyosiform nevus and limb defects, ranging from digital hypoplasia to icthyosiform nevus and ipsilateral limb defects, ranging from digital hypoplasia to complete amelia. PATIENTS AND METHODS: A 9-month-old female infant presented with skin and limb defects involving the right side of her body. Clinical and laboratory evaluation was performed, including DNA sequence analysis of the NSDHL gene. RESULTS: Our patient presented with some of the typical clinical characteristics of CHILD syndrome, i.e. two large erythematous plaques with sharp borders, covered with yellow, wax-like scaling, on the right axilla and on the right groin, dysplastic right hand and alopecia of the right occipital area. The diagnosis was confirmed by DNA screening analysis, that detected a missense mutation c.314C-->T;p-A105V, in the coding region of the NSDHL gene (exon4) of our patient. CONCLUSIONS: This is the first report of CHILD syndrome ever reported in Greece. We suggest that the diagnosis of the syndrome is important for patient information and genetic counselling.

Protein-losing gastroenteropathy associated with primary Sjögren's syndrome: a characteristic oriental variant.

Protein-losing gastroenteropathy (PLGE) is a rare manifestation of primary Sjögren's syndrome (SS). We report a case of a 41-year-old Japanese man, who is the first male patient, with PLGE associated with primary SS. Although serum anti-SSA and SSB antibodies were detected, he had no subjective sicca symptoms. He had multiple annular erythema: a characteristic skin manifestation of Asian SS patients. A diagnosis of PLGE was made from results of (99m)Tc-labelled albumin scintigraphy and a faecal alpha-1-antitrypsin clearance test. Intravenous administration of high-dose glucocorticoid was not effective, but pulse methylprednisolone therapy alleviated disease manifestations. As all cases of PLGE associated with primary SS have been reported from East Asia, this complication could be essentially limited to Asian patients.

Serious hand-and-foot syndrome in black patients treated with capecitabine: report of 3 cases and review of the literature.

Hand-and-foot syndrome (HFS) is one of the well-known adverse events associated with capecitabine, a prodrug of 5-fluorouracil (5-FU). HFS, also known as erythrodysesthesia, manifests as acral erythema with swelling and dysesthesia of the palms and plantar aspects of the feet, and, in the absence of dosage reduction or stoppage of the drug, progresses to moist desquamation and ulceration with serious infections and loss of function. In black patients, we observed that capecitabine given in the recommended dosage leads to hyperpigmentation of the palms and soles, followed by a distinct keratodermalike thickening not seen in white patients. Furthermore, in patients with a precarious peripheral vasculature, this condition evolves rapidly into grade 3 HFS, with ulceration and infection. We report our experience with capecitabine in 3 black patients and contrast it to that of 2 white patients. A brief review of the literature on fluoropyrimidines and HFS follows.

Reliance on erythema scores may mask severe atopic dermatitis in black children compared with their white counterparts.

BACKGROUND: The prevalence of atopic dermatitis (AD) has been shown to be higher in London-born black Caribbean children than in their white counterparts, but little is known about the severity of the disease. OBJECTIVES: To carry out a longitudinal survey to investigate potential risk factors for AD severity in children. We report our findings in relation to differences in disease severity between white and black children and the effect of inclusion and exclusion of erythema scores on this comparison. METHODS: The recruited children were identified by their general practitioners (GPs) as having presented with AD, and the U.K. diagnostic criteria for AD were used to verify the diagnosis. Interview and clinical examination of children took place up to four times, 6 months apart. Each time, the same observer assessed AD severity using the SCORAD (SCORe Atopic Dermatitis) index. Potential risk factors and confounders were evaluated with a five-page questionnaire. Non-parametric tests were used for statistical analysis and the study participant remained the unit of the analysis. RESULTS: In total, 137 children (82 urban and 55 rural) were recruited, and each seen up to four times. This gave 380 observations (69% of an expected 548). The urban population contained 42 (51%) white children, 26 (32%) black children and 14 (17%) from other races. The rural population was entirely white. The 14 children from other races were completely excluded from the statistical analysis. The black children were all born in the U.K. On crude analysis, children with black skin showed a non-significantly lower risk of severe disease when compared with white children (odds ratio, OR 0.84; 95% confidence interval, CI 0.4-1.76; P = 0.65), while a highly significantly increased risk was found after adjusting for erythema score (OR 5.93; 95% CI 1.94-18.12; P = 0.002). The difference remained significant even after controlling for other potential confounders. CONCLUSIONS: Black children with AD are about six times more at risk of having severe AD than their white counterparts. GPs and dermatologists should note that erythema can be a misleading indicator of severity in black children. Difficulties of assessment due to skin pigmentation might mean that severe cases are not being detected and appropriately treated.

Skin responses to ultraviolet radiation: effects of constitutive pigmentation, sex, and ancestry.

Constitutive skin pigmentation and skin responses to ultraviolet radiation were measured on a sample of volunteers (n=250) living in State College, PA, USA. The sample was composed of individuals of European American (n=190), Hispanic (n=45), and East Asian ancestry (n=15). Constitutive pigmentation was measured using the Adjusted Melanin Index (AMI), Erythemal Dose Response (EDR) was measured using the slope of a* at 24 h (Deltaa*), and Melanogenic Dose-Response (MDR) was measured using DeltaAM, the slope of AMI at 7 d. The relationships between constitutive skin pigmentation, EDR, MDR, sex, age, and ancestry were investigated. European Americans showed a lower constitutive pigmentation, had a significantly higher burn response (EDR), and had a significantly lower tanning response (MDR) than Hispanics and East Asians. No significant difference is seen between Hispanics and East Asians for either constitutive pigmentation or EDR. Constitutive pigmentation in females was slightly lower than in males in all three samples, but the difference was not significant. While no differences were observed in MDR between sexes, males had a stronger EDR than females regardless of population or constitutive pigmentation level, and this difference was significant in European Americans and Hispanics. We observed no age-related differences in any of the populations or measures investigated. We evaluated the relationship between constitutive pigmentation, EDR and MDR. There was a strong inverse correlation between constitutive pigmentation and EDR in the three samples (European Americans, R2=0.176, P < 0.001; Hispanics, R2=0.204, P=0.009; East Asians, R2=0.223, P=0.098) and a strong direct correlation between constitutive pigmentation and MDR in European Americans and Hispanics (European Americans, R2=0.094, P < 0.001; Hispanics, R2=0.164, P=0.012). In other words, persons with lower constitutive pigmentation both burn more and tan less than persons with higher pigmentation. However, after controlling for constitutive pigmentation, EDR and MDR were significantly correlated in European Americans (R2=0.041 P=0.006). Thus, the general observation that persons who burn more tan less is probable because of the common link that these two phenotypes have with constitutive skin pigmentation and, in fact, once pigmentation has been adjusted for, there is a positive correlation between tanning response and burning response in European Americans.

Phenotype-genotype correlation in 91 patients with familial Mediterranean fever reveals a high frequency of cutaneomucous features.

OBJECTIVES: To describe the clinical manifestations of familial Mediterranean fever (FMF) in 91 patients from 47 families and provide data from the genetic study. P:atients and methods. We conducted a retrospective chart review of 91 patients (including 83 children aged <15 yr) from 47 families through a questionnaire and a specific database. The genetic analysis included complete screening of known mutations of the MEFV gene on chromosome 16p13.3. A positive diagnosis required at least two mutations, one on each chromosome. RESULTS: Our panel included 52 females and 39 males, with a mean age of 7.27 yr. Of the 47 families, 31 were non-Ashkenazi Jews, 10 were Armenians and six were from other ethnic groups. Clinical features included fever (100%), peritonitis (86%), pleuritis (56%), arthritis (34%) and myalgias (27%). We observed a high rate of cutaneous manifestations (47%); erythema, oedema and recurrent oral ulcers were the most frequent. Phenotype-genotype correlations showed a significant association of M694V homozygosity with earlier age of onset (P: = 0.044), fever >39 degrees C (P: = 0. 002), pleural crisis (P: = 0.0044), splenomegaly (P: = 0.0005) and arthritis (P: = 0.001). Associations with mucocutaneous features were as follows: erysipelas-like erythema (P: = 0.012), oedema (P: = 0.61, not significant) and oral ulcers (P: = 0.45, not significant). CONCLUSION: New phenotype-genotype correlations emerged from our study: homozygosity for the M694V mutation was associated with intensity of fever, splenomegaly and with erysipelas-like erythema. Apart from erysipelas-like erythema, no significant association was found between other cutaneous features and the genotype.