Influence of pharmacogenomic polymorphisms on allopurinol-induced cutaneous adverse drug reactions in Thai patients.

BACKGROUND: Allopurinol has been causing substantial morbidity and mortality particularly in Asian population by producing cutaneous adverse drug reactions (cADRs). Nonetheless, there are no data describing whether other genetics are a valid marker for prediction of allopurinol-induced cADRs patients in addition to HLA-B*58:01 allele. The goal of this study was to identify suitable single nucleotide polymorphisms (SNPs) for allopurinol induced cADRs among Thai patients. METHODS: We conducted a case-control association study after enrolling 57 Thai patients with allopurinol induced cADRs and 101 allopurinol-tolerant controls. The genetic biomarkers and associated SNPs located on chromosome 6p21 were examined by TaqMan® SNP genotyping assays in both the cases and the controls. RESULTS: Out of fifteen SNPs in nine genes, we found four combined SNPs (rs3099844 of HCP5, rs9263726 of PSORS1C1, rs9263733 of POLR2LP, and rs9263745 of CCHCR1) were significantly associated with allopurinol-induced cADRs compared to the tolerant controls (OR 73.2; 95% CI 24.2-266.8; P = 1.9 × 10- 24). The overall sensitivity, specificity, positive predictive value and negative predictive value of these combinations were 84%, 94%, 9%, and 100%, respectively. However, the variant alleles of these SNP combinations were detected in 89.5% (51/57) of the cases. Moreover, the HLA-B*58:01 allele was observed in 86.0% of patients with allopurinol-induced cADRs, but only in 4.0% of tolerant controls (OR: 137.2; 95% CI: 38.3-670.5 and p-value = 1.7 × 10- 27). CONCLUSIONS: Thus, this research confirms the association between the specific HLA-B*58:01 allele and all phenotypes of allopurinol-induced cADRs in Thais. Furthermore, there was found the combined four SNPs (rs3099844, rs9263726, rs9263733, and rs9263745) could be used as alternative novel biomarkers for predicting cADRs in patients taking allopurinol.

Efficacy of ceramides and niacinamide-containing moisturizer versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris: A split face, double-blinded, randomized controlled trial.

INTRODUCTION: Topical therapy is the mainstay treatment of acne, and topical retinoids such as tretinoin, tazarotene, and adapalene are recommended as the first-line therapy for mild to moderate acne. However, the cutaneous irritations may occur, and the dermocosmetics are recommended to prevent side effects of anti-acne drugs and adhere to treatment. Thus, this study aims to compare the efficacy and tolerability of ceramides and niacinamide-containing moisturizer (CCM) versus hydrophilic cream in combination with topical anti-acne treatment in mild to moderate acne vulgaris. METHODS: This was an 8-week, randomized, double-blinded, split face study in 40 patients assigned for topical anti-acne medications (5% benzoyl peroxide and 0.1% adapalene gel), then randomly applied CCM or hydrophilic cream. All patients were followed at week 0, 2, 4, and 8 for acne improvement, adverse reactions, biometric, and biophysical evaluation. RESULTS: CCM could significantly improve the non-inflammatory, inflammatory, and total acne lesions compared with hydrophilic cream after week 8 of treatment. Interestingly, there was an improvement of global worst score, hemoglobin index, melanin index, TEWL, skin hydration, sebum production, and skin surface pH, with no statistically significant differences between the two treatments. No serious side effects from clinical application of CCM and hydrophilic cream in mild to moderate acne vulgaris patients. CONCLUSION: Ceramide and niacinamide-containing moisturizer in combination with anti-acne medication can significantly improve acne lesions and decrease cutaneous irritations toward a satisfactory treatment outcome of mild to moderate acne vulgaris.

Novel Application of 1064-nm Picosecond Nd:YAG Laser for Male Androgenetic Alopecia Treatment.

Background: There are limitations and side effects of currently approved treatments for AGA, such as topical minoxidil, oral finasteride, and low-level light therapy. Objective: This study aimed to investigate the potential of fractional picosecond laser (FPL) therapy for promoting hair regrowth. Methods: This was a pilot study in which five male participants were treated with a 1064-nm FPL for mild-to-moderate AGA. The patients underwent three treatments at four-week intervals, followed by a four-week post-procedure assessment. Expert panel assessment score and patient satisfaction was assessed using a seven-point scale. Dermoscopic analysis was conducted to evaluate hair shafts. Adverse effects were also monitored. Results: Clinical improvement was observed at 1 to 4 months after treatment, with a significant increase in expert panel assessment scores (p<0.001). Patient satisfaction with hair density and thickness also improved significantly at 1 and 4 months (p=0.038 and p=0.007, respectively). Adverse effects were minimal and resolved within a week. Dermoscopic analysis showed minimal petechiae with no hair shaft damage. Conclusion: The preliminary study demonstrates the potential of 1064-nm FPL for promoting hair regrowth in male pattern hair loss. Nonetheless, further research is recommended to elucidate and ratify for the optimization of this promising treatment approach.

A 595 nm pulsed dye laser as an adjuvant intervention for post-comedone extraction erythema and comedone reduction: A randomized, split-face controlled trial.

BACKGROUND: Comedone extraction provides greater satisfaction for acne treatment than conventional treatment alone; however, post-comedone extraction erythema (PCEE) remains a concern for patients. OBJECTIVES: To evaluate the efficacy of pulsed-dye laser (PDL) in PCEE and comedone reduction. METHODS: Mild-to-moderate acne patients were randomly allocated in split-face fashion. Three comedones were extracted on each facial side. On the PDL-treated side, 595-nm PDL was delivered to the entire side with an additional shot on three comedone-extracted sites. Erythema index (EI) and total acne lesion counts (TALC) were evaluated at baseline, week 2 and 4. The comprehensive acne severity scale (CASS) was assessed by three blinded independent pediatric dermatologists. Participant satisfaction surveys were completed at the end of the study. RESULTS: Thirty-five participants (age 12.9-24.2 years) showed no differences in the EI and TALC at baseline on both sides. At weeks 2 and 4, the EI on the PDL-treated side was significantly lower (p < 0.001) with a greater EI reduction (p < 0.001) when compared to the control side regardless of gender and menstruation. There was significantly lower TALC on the PDL-treated side at week 2 (p < 0.001) and week 4 (p = 0.02). No complications were noted with high participant satisfaction reported (median 8; IQR 7-9). PDL remained significantly associated with EI improvements after controlling for gender, menstruation cycle, and examination stress. CONCLUSION: PDL can be an adjunctive intervention for the treatment of PCEE and comedone reduction due to its effectiveness and high participant satisfaction.

Unveiling the potential: Enhancing caregiver knowledge through video education to address topical corticosteroid concerns in children with eczematous dermatitis.

BACKGROUND: Concerns about the use of topical corticosteroids (TCS) in pediatric eczematous dermatitis management often hinder effective treatment. Limited data exist regarding the prevalence of these concerns and the effectiveness of interventions. This study aimed to assess the prevalence of TCS concerns among caregivers and determine the effectiveness of video education in mitigating these concerns. METHODS: A single-center prospective study was conducted from 2022 to 2023, involving caregivers of children under 18 years with eczematous dermatitis. Baseline and post-intervention questionnaires were administered after a 4-week period. Caregivers received video education on TCS use, and the TOPICOP score was evaluated before and after viewing the video. RESULTS: The study included 150 caregivers, 85.3% female and 74% had a child with atopic dermatitis. The prevalence of TCS concerns among Thai caregivers was 62%. Following video education, the prevalence of TCS concerns significantly decreased to 10.7%. Mean belief score decreased from 43.81 ± 13.45 to 31.85 ± 16.56, mean worry score decreased from 56.22 ± 18.27 to 40.41 ± 18.55 and mean total TOPICOP score decreased from 50.02 ± 12.65 to 36.13 ± 13.52 (p-value <.001). The intervention also resulted in reduced disease exacerbations, duration of the rash, and duration of TCS use. The optimal TOPICOP cut-off score to predict TCS concerns was identified as 43.06. CONCLUSION: Video education effectively alleviated TCS concerns among caregivers, addressing beliefs, worries, disease exacerbations, and side effects. Integration of this intervention into the management of pediatric eczematous dermatitis can yield optimal outcomes.

Topical corticosteroid phobia in adolescents with eczema and caregivers of children and adolescents with eczema: A cross-sectional survey.

Steroid phobia is an increasing phenomenon that affects treatment adherence. The purpose of this study was to assess the prevalence and associated factors of steroid phobia among adolescents with eczema and the caregivers of children and adolescents with eczema by using questionnaires and TOPICOP© scale. The prevalence of steroid phobia is approximately 12% and 37% in the adolescent and caregiver groups, respectively. Caregivers who obtained information about topical corticosteroid (TCS) from dermatologists and whose children had fewer number of flares, demonstrated less concern about using TCS.

The attitudes and expectation of caregivers of febrile child receiving medical services: a multicenter survey in Thailand.

BACKGROUND: Most caregivers may visit pediatric outpatient clinics with high concern of fever and improper antipyretic use. However, studies of concern about fever in Asian countries are still limited. OBJECTIVES: This study aimed to explore caregivers' attitudes, management of their child's fever, factors associated with their high concern, and expectation from medical services. METHODS: A cross-sectional 26-item self-administered questionnaire was used to survey caregivers of 1-month to 15-year-old febrile infants/children/teenagers visiting outpatient clinics in 9 government hospitals from July 2018 to August 2019. RESULTS: One thousand two hundred and six caregivers (67% response rate) completed self-administered questionnaire. The median age of the caregivers and the pediatric patients were 34 years (interquartile range [IQR] 28-40) and 3.3 years (IQR 1.8-6.1), respectively. Approximately 70% of them believed that fever could harm a child, resulting in brain damage or death. Also, 2% managed high doses of acetaminophen and overdosed the child. The high level of concern was significantly associated with acetaminophen overdose (P < 0.001, Kruskal-Wallis test). Caregivers of nonhealth care providers and children's history of febrile seizure were factors related to higher score of concern. Most caregivers expected definite diagnosis (70.7%), antipyretic drugs (67.4%), and blood tests (48.9%). CONCLUSION: Caregivers' high concern of fever existed in Thailand. This may lead to unnecessary high doses of antipyretics. In clinical practice, the high concern of fever is a challenge for caregivers and pediatric health care providers. A better understanding of fever and its consequence should be advocated for proper management of the child's fever.

Toxic epidermal necrolysis after first dose of Pfizer-BioNTech (BNT162b2) vaccination with pharmacogenomic testing.

Toxic epidermal necrolysis (TEN) is a rare and acute life-threatening condition and one of the severe cutaneous adverse drug reactions. There are limited data on TEN from the COVID-19 vaccine regarding its pathogenesis, treatment, and prognosis, particularly in children. We report a case of COVID-19 vaccine-induced TEN and the patient's human leukocyte antigen pharmacogenomic profile.

Recurrent hypoglycemic seizure as a presenting symptom of post-TBI hypopituitarism in children: a case report, review and proposed protocol.

OBJECTIVES: Post-traumatic brain injury hypopituitarism is a common unrecognized condition in children after head injury. Due to its similarity of clinical symptoms with those of head trauma, clinical diagnosis of post-TBI hypopituitarism is challenging. To date, there is no standardized screening protocol for children with history of brain injury. This article demonstrates a case of 14-year-old boy with severe head trauma who developed refractory seizures with episodic hypoglycemia and weight loss. We aimed to focus on the prevalence, clinical courses and clinical implementations of each hormonal axis in children with post-traumatic brain injury hypopituitarism. We also aim to raise awareness of this condition to pediatricians in light of enhancing patient care. METHODS: We have searched for original articles, published in English between year 2000 and 2021. There are 20 related articles, authors reviewed all the articles independently. RESULTS: Prevalence of post-traumatic hypopituitarism ranges from 5-57% in children. Growth hormone is the most commonly affected hormone. The highest prevalence is 42.3% at more than 12 months after the brain injury. The symptoms and severity range from asymptomatic to requiring long-term hormonal therapy. Although normalization of pituitary function is demonstrated at various times after the injury, hormone replacement therapy is still required in some patients. CONCLUSIONS: This is the first report that demonstrates a presenting symptom of hypopituitarism mimic traumatic brain symptoms which result in it being overlooked. This case emphasizes the need to develop pituitary function screening protocols for children with TBI. We have proposed our pituitary screening protocol for children with TBI in this article.

Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and Pharmacogenomics.

SCARs are rare and life-threatening hypersensitivity reactions. In general, the increased duration of hospital stays and the associated cost burden are common issues, and in the worst-case scenario, they can result in mortality. SCARs are delayed T cell-mediated hypersensitivity reactions. Recovery can take from 2 weeks to many months after dechallenging the culprit drugs. Genetic polymorphism of the HLA genes may change the selection and presentation of antigens, allowing toxic drug metabolites to initiate immunological reactions. However, each SCARs has a different onset latency period, clinical features, or morphological pattern. This explains that, other than HLA mutations, other immuno-pathogenesis may be involved in drug-induced severe cutaneous reactions. This review will discuss the clinical morphology of various SCARs, various immune pathogenesis models, diagnostic criteria, treatments, the association of various drug-induced reactions and susceptible alleles in different populations, and the successful implementation of pharmacogenomics in Thailand for the prevention of SCARs.

Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is one of the severe cutaneous adverse drug reactions (SCARs) with high mortality rate and variable long term sequelae, especially in thyroid dysfunction and thyroiditis. In this article, we review clinical course, culprit drugs, onset of diagnosis, and type of thyroid dysfunction in DRESS patients. There were a total of 51 cases including 12 children (aged less than 18 years old) and 39 adults from our review. The most common thyroid dysfunction was Hashimoto's thyroiditis (41/51=80.4%) including anti-thyroid antibody positive (29/51=56.9%), possible/compatible with Hashimoto's thyroiditis (12/51=23.5%) both in the children (n=12) and adult (n=39), Graves' disease/hyperthyroidism (7/51=13.7%) and non-specific hypothyroidism (3/51=5.9%), respectively. The most common culprit drugs and onset of thyroid dysfunction after DRESS diagnosis in children aged less than 18 years include antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) (range 0-8 months, median 2 months) and sulfa groups (sulfasalazine, sulfamethoxazole, sulfonamide) (range 1-4 months, median 2 months). Data of prevalence, type, and clinical course of thyroid dysfunction from DRESS is important for clinicians to recognize for monitoring its sequelae and provide plans for treatment.

Prevalence of skin diseases in school-age children.

BACKGROUND: The prevalence of community-based skin diseases, especially among school-age children, depends on topography, climate, and age of population. OBJECTIVE: We determined the prevalence of skin diseases among community-based primary school-age children and identified demographic characteristics in relation to particular skin conditions. METHODS: This was a cross-sectional descriptive survey study of a subproject school cohort in children aged 5-14 years of 2 community-based primary schools. Demographic data and whole-body skin examination were collected. The association of individual skin conditions was analysed by using bivariate and multivariable binary logistic regression. RESULTS: A total of 556 children were enrolled in this study. Of these, 90.2% had at least 1 skin disease. The most common skin disease was postinflammatory hyperpigmentation (PIH) (58.3%), followed by nevus/mole (40.1%), insect bite reaction (28.0%), acanthosis nigricans (20.0%), acne (13.7%), and pityriasis alba (12.9%). There was an increase of body mass index (BMI) in PIH and acanthosis nigricans with the adjusted odds ratios of 2.01 (95% confidence interval [CI] 1.40-2.87, P < 0.001) and 1.93 (95% CI 1.49-2.49, P < 0.001), respectively. Insect bite reaction was related to PIH with the adjusted odds ratio of 5.66 (95% CI 3.15-10.17, P = 0.001). CONCLUSIONS: The most common skin disease in community-based primary school-age children is PIH which related to acanthosis nigricans and insect bite reaction. A decrease of BMI may lower the risk for PIH and acanthosis nigricans. Education on common skin diseases is recommended for both community-based schools and school-age children.

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine.

Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.

Efficacy of 1064-nm Nd:YAG picosecond laser in lichen amyloidosis treatment: clinical and dermoscopic evaluation.

Lichen amyloidosis (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple localized, hyperpigmented, grouped papules, in which the deposition of amyloid materials from altered keratinocytes usually resists to current treatments. We presented two LA patients with non-satisfactory results of topical treatments. After the first treatment using 1064-nm Nd: YAG picosecond (ps-Nd:YAG) laser, there was an improvement with persistence up to 3-month follow up after five sessions of 4-week interval, as well as a decrease in number, thickness, and darkness of lesions from clinical and dermoscopic evaluation. Thus, the ps-Nd:YAG laser could be efficacious for LA treatment.

Genotyping HLA alleles to predict the development of Severe cutaneous adverse drug reactions (SCARs): state-of-the-art.

Introduction: Pharmacogenomics has great potential in reducing drug-induced severe cutaneous adverse drug reactions (SCARs). Pharmacogenomic studies have revealed an association between HLA genes and SCARs including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).Areas covered: Pharmacogenomics-guided therapy could prevent severe drug hypersensitivity reactions. The US Food and Drug Administration (FDA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and Dutch Pharmacogenetics Working Group (DPWG) provided guidelines in the translation of clinically relevant and evidence-based SCARs pharmacogenomics research into clinical practice. In this review, we intended to summarize the significant HLA alleles associated with SCARs induced by different drugs in different populations. We also summarize the SCARs associated with genetic and non-genetic factors and the cost-effectiveness of screening tests.Expert opinion: The effectiveness of HLA screening on a wider scale in clinical practice requires significant resources, including state-of-the-art laboratory; multidisciplinary team approach and health care provider education and engagement; clinical decision support alert system via electronic medical record (EMR); laboratory standards and quality assurance; evidence of cost-effectiveness; and cost of pharmacogenomics tests and reimbursement.

Anthropometric Markers and Iron Status of 6-12-Year-Old Thai Children: Associations and Predictors.

INTRODUCTION: Obesity may be associated with poor iron status. The objective of this study was to investigate the association between different indices of iron status and anthropometric measurements in Thai children. MATERIALS AND METHODS: Anthropometry (weight, height, waist circumference (WC), and body composition assessed by bioelectrical impedance analysis) and iron indices were measured in 336 Thai children aged 6-12 years. Iron deficiency (ID) was defined using two or more of the following: (1) %transferrin saturation (%Tsat) < 16%; (2) serum ferritin (SF) < 15 µg/mL; and (3) soluble transferrin receptor (sTfR) > 5 mg/L. Iron deficiency anaemia (IDA) was defined as haemoglobin < WHO age cutoff combined with ID. Overweight and obesity were defined as body mass index (BMI) standard deviation score (SDS) ≥ +1 SDS or +2 SDS, respectively (WHO growth reference). RESULTS: BMI SDS was significantly positively correlated with sTfR and SF (sTfR, r: 0.209, p < 0.001; SF, r: 0.214, p < 0.001) and negatively correlated with %Tsat (r: -0.132, p = 0.013). Correlations between WC SDS and %fat mass and each iron marker were similar. The percentage with low SF was significantly lower than that using other individual markers. ID prevalence was not significantly different between normal-weight and overweight/obesity groups although a significantly higher proportion of overweight/obese children had sTfR >5 mg/L. Puberty and menarche were significant predictors of ID (puberty adjusted OR: 2.20, 95% CI: 0.43, 11.25; menarche adjusted OR: 6.11, 95% CI: 1.21, 30.94). CONCLUSION: Greater adiposity was associated with poorer iron status. However, SF may not be a good indicator of iron status in Thai children, particularly in those who are overweight/obese, whereas sTfR merits further investigation.