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Background. Antinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described. Objectives. To compare clinical features of CSU patients who are positive and negative for ANA. Methods. This was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until July 2021. All patients were investigated for ANA. Clinical feature data was compared between CSU patients with positive ANA and negative ANA groups using the 2-sample t -test and the Mann–Whitney U test for quantitative variables. The chi-squared test or Fisher’s exact test was conducted to explore the association of qualitative variables. Disease relapse and remission were analysed via Kaplan-Meier survival analysis. Results. Of 323 CSU patients, 31% had positive ANA. There were no significant differences in disease severity or impairment in quality of life. Patients with a positive ANA test had significantly lower prevalence of allergic rhinitis ( p = .048 ) and significantly higher level of erythrocyte sedimentation rate ( p = 0.007 ). Kaplan-Meier survival analysis showed that 2% of ANA positive CSU patients achieved remission status after one year and 28% did so after five years. There was no statistically significant difference in time to remission and time to relapse between ANA-positive and negative groups. Conclusion. Positive ANA in CSU patients could not indicate the differences in main disease characteristics from the ANA-negative CSU patients. Investigation for ANA may be useful in CSU patients who are suspected of having autoimmune diseases.

Mast cell activation plays a key role in various allergic diseases and anaphylaxis. Several methods/techniques can be used for detection of mast cell activation. However, there was no previous systematic evaluation to compare the efficacy of each method/technique. The present study thus systematically compared various markers for mast cell activation induced by IgE cross-linking. The widely used RBL-2H3 mast cells were sensitized with anti-DNP (dinitrophenyl) IgE overnight and activated with DNP-BSA (bovine serum albumin) for up to 4 h. The untreated cells and those with anti-DNP IgE sensitization but without DNP-BSA activation served as the controls. Intracellular calcium level gradually increased to ~2-fold at 1 h, reached its peak (~5-fold) at 2 h, and returned to the basal level at 3-h post-activation. The increases in cellular tryptase level (by Western blotting) (~0.3- to 0.4-fold) and average cell size (~2.5-fold) and decrease of nucleus/cytoplasm ratio (~0.4- to 0.5-fold) were marginal at all time-points. By contrast, β-hexosaminidase release and CD63 expression (by both flow cytometry and immunofluorescence detection/localization), secreted tryptase level (by Western blotting), and tryptase expression (by immunofluorescence detection/localization) stably and obviously increased (~10-fold as compared with the untreated control and sensitized-only cells or detectable only after activation). Based on these data, the stably obvious increases (by ≥ 10-fold) in β-hexosaminidase release, CD63 expression (by both flow cytometry and immunofluorescence staining), secreted tryptase level (by Western blotting), and tryptase expression (by immunofluorescence staining) are recommended as the markers of choice for the in vitro study of mast cell activation using RBL-2H3 cells.

The Angioedema Control Test (AECT) is a questionnaire that monitors disease control in patients with angioedema, with a recall period of 4 weeks (AECT-4wk) or 3 months (AECT-3mo).This study investigated the psychometric properties of a Thai version of the AECT.Of 54 patients, 46, 5, 2, and 1 had recurrent angioedema with chronic spontaneous urticaria, hereditary angioedema, idiopathic histaminergic angioedema, and acquired angioedema due to C1 esterase inhibitor deficiency, respectively. The AECT, Angioedema Activity Score (AAS), Dermatology Life Quality Index (DLQI), Angioedema Quality of Life Questionnaire (AE-QoL), and anchors for disease control (numeric rating scale [NRS] and patient global assessment-Likert scale [PatGA-LS]) were used. The patients rated the efficacy of their treatment.Fifty-four and 47 patients completed the AECT-4wk and AECT-3mo, respectively. Both AECT versions showed significant correlations with disease activity (AAS, r = 0.6-0.8), disease control (NRS and PatGA-LS, r = 0.7-0.9), and quality of life impairment (DLQI and AE-QoL, r = 0.6-0.8). Higher correlations were found for the AECT-4wk than for the AECT-3mo. Excellent internal consistency (alpha = 0.98 and 0.97, respectively) and intraclass correlation (0.96 and 0.94, respectively) were found. A cutoff ≥ 10 was confirmed to identify patients with well-controlled disease for both AECT versions (AUCs = 0.89 and 0.97).The Thai version of the AECT is a valid and reliable tool for clinical practice. Due to the shorter recall period, the AECT-4wk may be more accurate than, and preferable to, the AECT-3mo. A cutoff ≥ 10 should be used to identify patients with well-controlled disease.

Cutaneous adverse events after receiving a COVID-19 vaccine were identified. The disease activity of urticaria after a COVID-19 vaccine has never been explored in chronic urticaria patients.To evaluate disease activity of chronic urticaria after receiving a COVID-19 vaccine.A prospective cross-sectional study was conducted in chronic urticaria patients aged 18 or above who visited Siriraj Hospital between July and September 2021, and received the first and second dose of COVID-19 vaccine. The status prior to vaccination, including disease activity, disease control and disease severity was assessed by a urticaria activity score over seven days, urticaria control test, and modified medication score. The disease activity after vaccination was recorded.A total of 130 patients with a mean age of 45.9 ± 14.7 were enrolled in this study. Adenoviral and inactivated vaccines were administered to 85 (65.4%) and 45 patients (34.6%), respectively. Exacerbation was reported in 20 cases (15.4%) after the first dose and 17 cases (13.1%) after the second dose. Nine patients (45%) reported exacerbation after both the first and second dose. The majority of patients only had wheal, while three patients reported wheal with angioedema. No anaphylaxis was reported. Factor predicting exacerbation was concurrent thyroid disease (aRR 2.78, p0.01).Approximately 15% of chronic urticaria patients reported exacerbation after receiving a COVID-19 vaccination. No serious events were observed. Chronic urticaria patients should be vaccinated against COVID-19 after a discussion of the risk of disease flare-up.

PROPOSE The purpose of this study was to investigate panels of enzyme-linked immunospot assays (ELISpot) to detect drug-specific mediator releasing cells for confirming culprit drugs in severe cutaneous adverse reactions (SCARs). METHODS Frequencies of drug-induced interleukin-22 (IL-22)-, interferon-gamma (IFN-γ)-, and granzyme-B (GrB)-releasing cells were measured by incubating peripheral blood mononuclear cells (PBMCs) from SCAR patients with the culprit drugs. Potential immunoadjuvants were supplemented to enhance drug-induced mediator responses. RESULTS Twenty-seven patients, including 9 acute generalized exanthematous pustulosis (AGEP), 10 drug reactions with eosinophilia and systemic symptoms, and 8 Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) were recruited. The average frequencies of drug-induced IL-22-, IFN-γ-, and GrB-releasing cells were 35.5±16.3, 33.0±7.1, and 164.8±43.1 cells/million PBMCs, respectively. The sensitivity of combined IFN-γ/IL-22/GrB ELISpot was higher than that of IFN-γ ELISpot alone for culprit drug detection in all SCAR subjects (77.8% vs 51.9%, P < 0.01). The measurement of drug-induced IL-22- and IFN-γ releasing cells confirmed the culprit drugs in 77.8% of AGEP. The measurement of drug-induced IFN-γ- and GrB-releasing cells confirmed the culprit drugs in 62.5% of SJS/TEN. Alpha-galactosylceramide supplementation significantly increased the frequencies of drug-induced IFN-γ releasing cells. CONCLUSION The measurement of drug-induced IFN-γ-releasing cells is the key for identifying culprit drugs. The additional measurement of drug-induced IL-22-releasing cells enhances ELISpot sensitivity to identify drug-induced AGEP, while the measurement of drug-induced GrB-releasing cells could have a role in SJS/TEN. ELISpot sensitivity might be improved by supplementary alpha-galactosylceramide. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02574988.

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p p HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Moisturizers play an important role in restoring the skin barrier. They should be used to treat and prevent eczema, especially in atopic dermatitis (AD).To evaluate the factors that influence selection of moisturizers in adult patients with AD and without it. Usage behavior between the two groups was also determined.A cross-sectional web-based survey was performed.A total of 1,195 participants with mean age of 46.5 ± 14.5 were enrolled. Fifty participants (4.2%) met the William's criteria for AD diagnosis. Most participants reported using moisturizer every day or two times per day. A non-sticky moisturizer, followed by pleasant odor were considered important properties. For choosing a moisturizer, personal satisfaction was the most common answer given by participants. The most common locations that participants applied moisturizer were the extremities (85.1%) and face (84.9%). Physicians' suggestion was also a significant factor that led to moisturizer use by AD patients but it was not significant in the non-AD group (29.2% vs 14.7%, p = 0.007, OR 2.4). A pH of 5.5 and the anti-inflammatory property were important factors in choosing a moisturizer in the AD group. Both AD and non-AD participants preferred liquid soap over bar soap in daily life.Our results showed that most participants have basic knowledge of how to use a moisturizer. Physicians' suggestion influenced the selection of moisturizer in AD patients. Thus, physicians should continue to educate in order to achieve good clinical outcomes.

Background Symptomatic dermographism (SD), the most common form of chronic inducible urticaria, presents with transient wheals accompanied by itching in response to scratching. Little is known about available treatment options and their efficacy in SD. Objective To systematically review the efficacy of treatment options for patients with SD. Methods Using predefined search terms, we searched for relevant literature published until September 2019. The systematic review process was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. Results The 23 studies identified included 15 randomized controlled trials; 22 and 17 assessed treatment responses in patients with SD by provocation/threshold testing and patient/physician clinical assessment, respectively. Thirteen different treatments were investigated in a total of 430 adult patients. The most frequently studied therapy, first-generation H1-antihistamines, showed variable efficacy and significant side effects. In contrast, second-generation H1-antihistamines (2ndAH1), in all studies, were effective and well tolerated. Monotherapy with an H2-antihistamine (AH2) was not effective, whereas adding an AH2 increased the efficacy of treatment with an H1-antihistamine (AH1). SD improved with omalizumab. All other treatments were only investigated in small, unrepeated, and/or uncontrolled studies. There are no studies on updosing of 2ndAH1. Conclusions The available SD studies are heterogeneous, mostly monocentric, old, small, and unrepeated, pointing to a high need for more and better studies. We suggest that 2ndAH1 should be the first-line treatment. In uncontrolled cases, the combination of AH1 and AH2 may be tried. Even though there is no evidence of its efficacy over standard dosage, updosing of 2ndAH1 may be considered based on the extrapolation of evidence from chronic spontaneous urticaria; omalizumab should be added in recalcitrant patients.

BACKGROUND Pruritus is commonly associated with skin disorders. The 5-D itch scale was developed as a specific questionnaire for pruritus. OBJECTIVE This study aimed to evaluate the validity, reliability, and sensitivity to change of the Thai 5-D itch scale in Thai patients. METHODS The Thai Dermatology Life Quality Index (DLQI), patient's global assessment of disease severity (PatGA-VAS), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and seven-day urticaria activity score (UAS7) were evaluated as correlation with Thai 5-D itch scale. Seventy-five stable patients (42 chronic urticaria patients and 33 eczema patients), who had no change in disease severity after 4-weeks were assessed for test-retest reliability. RESULTS Of 130 pruritus patients who were treated at Department of Dermatology, Siriraj Hospital, 65 patients were diagnosed with chronic urticaria. The others were diagnosed with eczema. The validity of Thai 5-D itch scale correlated strongly with Thai DLQI total score (r = 0.76, p < 0.0001) and PatGA-VAS (r = 0.79, p < 0.0001). The strong reliability of Thai 5-D itch scale was demonstrated as intraclass correlation coefficient of 0.90. The changes in Thai 5-D itch scale was correlated with the changes in PatGA-VAS and UAS7 which indicated that the Thai 5-D itch scale had good sensitivity to change (r = 0.66) and (r = 0.67), respectively. CONCLUSIONS The Thai 5-D itch scale is a questionnaire with good validity, reliability and sensitivity to change to evaluate pruritus in Thai patients. This will support the use of 5-D itch scale in practice, in other languages.

Background and Objective: Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states. Methods: CURE data were collected at baseline and 6-monthly follow-ups (FU). Assessments included CSU states using the Urticaria Control Test (UCT), weekly Urticaria Activity Score (UAS7), and Physician Global Assessment (PhyGA) of treatment response. Complete response to treatment (CR, UAS7 = 0), complete control of disease (CC, UCT = 16), and PhyGA = CR were assessed, plus the Dermatology Life Quality Index and the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) sleep domain. Results: Overall, 2078 patients were included. At baseline, 9.8%, 17.9%, and 42.3% of patients had UCT = 16, UAS7 = 0, or PhyGA = CR, respectively, which increased at FU1 and FU2. Patients with higher UCT scores had better sleep and HRQoL. The presence of angioedema without wheals, episodic disease, omalizumab treatment, and male sex were associated with CC (P

Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria where wheals occur after skin contact with water. Information on clinical manifestations and treatment outcomes is limited, which makes the management of AquaU challenging.To systematically review disease features and relevant triggers of AquaU and patients' response to treatment.Related articles were searched by use of the terms "aquagenic urticaria" and "aquagenic angioedema" until June 2021 and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.A total of 77 patients with AquaU were investigated in 59 studies including 47 case reports and 12 case series. AquaU predominantly presented in women (47 patients, 61%), and the mean age of onset of the disease was 19.6 ± 10.8 years (range: 0-54 years). Wheals commonly occurred in localized areas and regardless of the water temperature. Based on the reviewed evidence, AquaU can be classified as familial AquaU (FAquaU, 18.2%) and acquired AquaU (AAquaU, 81.8%). Although many treatments were used in both subtypes of AquaU, the use of second-generation HAquaU is proposed to be classified into 2 subtypes, FAquaU and the more common AAquaU. Treatment with a 2

Dermographism is the most common form of chronic inducible urticaria. However, the natural history and clinical course of patients with dermographism in tropical countries has not fully been described.To examine clinical features, natural history and clinical course of dermographism in Thai patients according to their experiences.A cross-sectional, internet-based survey was conducted in 2021. All study respondents completed a 45-item questionnaire that was circulated on social media regarding dermographism.Among the 2,456 respondents who reported dermographism, 1,900 had symptomatic dermographism (SD), while 556 had simple dermographism (SimD). Of the respondents who reported SD and SimD, the female to male ratio was 2.2:1 and 2.4:1, respectively. The median age of the first episode of SD and SimD was 16 and 15 years, respectively. Older age, greater body weight, cardiovascular diseases, allergic conjunctivitis, atopic dermatitis, changes in temperature, and family history of dermographism were all factors linked to an increased probability of SD. Half of the respondents with SD reported moderate itch severity. Moreover, about half of SD and almost all of SimD respondents let the wheal resolve on its own. Second generation HThis survey highlights several aspects of dermographism in Thai patients which can be useful for healthcare providers. SD is troublesome and affects the quality of life of many patients, leading some to seek medication themselves.

BACKGROUND Adult female acne (AFA) may be different from adolescent acne, and may be a sign of polycystic ovary syndrome (PCOS). The objective of the study was to investigate the clinical characteristics of AFA, and the factors significantly associated with PCOS in AFA. METHODS AFA patients aged 25 years or older were enrolled. History taking and dermatologic examinations were performed by dermatologists. PCOS was diagnosed by gynaecologists. Perimenopausal acne (aged 45 years or older) and the Dermatology Life Quality Index (DLQI) were also evaluated. RESULTS Among 208 patients, mean age was 31.8 ± 7.1 years and 47.1%, 26.9%, and 26% had persistent, late-onset, and recurrent acne, respectively. The common aggravating factors included pre-menstruation (72.6%) and stress (53.8%). Recurrent acne was significantly aggravated by cosmetic products. Higher body mass index (BMI) was positively correlated with acne severity. Acne lesions were predominately located on both cheeks (87.0%) and at the perioral area (81.7%). PCOS was identified in 48.1%. Younger age (≥25 to

Background Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited. Objectives We sought to meta-analyze and review the efficacy and safety of ColdU treatments. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Suitable reports were identified by searching PubMed, Scopus, and Web of Science. Our systematic review included 16 studies, 9 of which met the eligibility criteria for the meta-analysis. We analyzed the effects of treatments on critical temperature thresholds (CTTs) and critical stimulation time thresholds (CSTTs), as well as on rates of complete response and adverse events. Results Our pooled meta-analyses showed that nonsedating second-generation H1-antihistamines (nsAHs) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own standard doses and placebos. In 4 studies involving CSTTs, updosing of nsAHs also resulted in significantly better CSTTs than their own standard doses or placebos. Omalizumab resulted in a marked reduction of CTTs in H1-antihistamine–resistant patients. Of 118 adverse events in 8 studies, standard-dose nsAHs, updosed nsAHs, and omalizumab produced lower numbers of adverse events than first-generation antihistamines. Conclusions Our study showed that greater dosages of nsAHs were more effective than standard dosages in controlling ColdU symptoms. Increasing the dosages was not significantly associated with higher adverse event rates. Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are the most common severe cutaneous adverse drug reactions (SCARs). Anti-epileptic drugs are one of the most common drugs causing SCARs. Cytokine profiles of SCARs during culprit drug exposure have never been characterized. This study aimed to identify cytokine patterns between SCARs and non-SCARs in epilepsy patients and the patterns of DRESS and SJS/TEN. Epilepsy patients that showed allergic responses to anti-epileptic drugs that manifested as SJS/TEN or DRESS were recruited. Epilepsy patients with no drug allergy symptoms and healthy people were also recruited as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with assigned anti-epileptic drugs according to the lymphocyte transformation test (LTT). LTT and measurement of cytokine levels in supernatants were performed on day six of cell cultivation. This study identified different cytokine expression patterns between SCAR and non-SCAR in epilepsy patients. Significant levels of IL-10, IL-12, IL-17, and GM-CSF were detected in non-SCAR epilepsy. However, the levels of IL-2, IL-5, IL-13, and IFN-gamma were significantly higher in supernatants of PBMCs of DRESS cultivated with AEDs relative to those of SJS/TEN. These cytokine levels were positively correlated with the cell proliferation index. Production of IL-5 and IL-13 was a unique characteristic of DRESS PBMCs. This study was the first to demonstrate distinct differences in cytokine levels between SCAR and non-SCAR PBMCs in epilepsy, which could help explain the immune-pathomechanism of drug hypersensitivity in SCARs. Different patterns of cytokine production and cell proliferation between DRESS and SJS/TEN in AED hypersensitivity were also demonstrated. Production of IL-5 and IL-13 might be a promising marker to define drug hypersensitivity in DRESS.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

Background Barrier repair therapy is the key management approach for both eczematous and non-lesional skin of atopic dermatitis. The use of appropriate cleansers to enhance skin hydration is an adjunctive treatment that increases topical drug penetration. Anti-inflammatory properties of various medicinal plants in tropical Asia have been reported. Objective Investigate the efficacy of herbal cleanser containing a combination of herbal extracts from Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna on seemingly intact skin in patients with atopic dermatitis by measuring improvements in the skin barrier function. Methods This 2-week pilot study was a split-side, randomized, double-blinded, vehicle-controlled trial. All patients (n = 30) were asked to use both a cleanser with an active formulation containing the herbal extracts and a vehicle- controlled cleanser on each side of mid-volar forearm. Biophysical assessments including transepidermal water loss (TEWL), skin hydration, skin pH, and skin roughness were performed at baseline and upon study completion. Results Compared to baseline, the median percentage change in TEWL at the end of the study was significantly greater for the active side 10.4 (-19, 20.7) g/m2h than the control side -13.2 (-28.7, 9.1) g/m2h; p = 0.01. The median percentage change of skin hydration, skin pH, and skin roughness of the active side compared to the control side had no a statistical significance. Conclusions This cleanser is beneficial when used as adjunctive therapy. Further studies should evaluate its anti- sinflammatory properties in the remedy or active phase of atopic dermatitis or other inflammatory skin diseases.

Many topical agents are available for treating the acute phase of acne; however, few agents have been proven beneficial during the maintenance phase. Objective. To evaluate the efficacy and safety of moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid during the maintenance phase of mild to moderate acne in Thai patients. Methods. One hundred and ten patients with mild to moderate acne vulgaris were initially treated with a fixed combination of adapalene 0.1%/benzoyl peroxide 2.5% gel once daily for 8 weeks. Fifty patients who achieved at least 50% reduction in lesion counts or at least a 2-grade improvement in the Investigator’s Global Assessment (IGA) grade from baseline were enrolled in the maintenance phase, which was an investigator-masked, left-right comparison, randomized, controlled, intraindividual study. Moisturizers with and without the active study ingredients were applied twice a day to each side of the face, respectively, for 12 weeks. Assessments included acne lesion counts, acne severity by IGA scoring, skin bioengineering measurements, and skin tolerability as assessed by both patient and physician. Results. The treatment group had a significant reduction in the mean counts of noninflammatory, inflammatory, and total lesions compared to the vehicle group at week 12 and also between baseline and week 12. There was no significant difference in the mean scores for skin dryness, stinging/burning, or pruritus at any time point between groups. Conclusions. Moisturizer containing licochalcone A, 1,2-decanediol, L-carnitine, and salicylic acid reduced acne lesions and prevented the development of new lesions during the maintenance phase. This trial is registered with ClinicalTrials.gov registration no. NCT04002024.

Chronic spontaneous urticaria (CSU) is characterized by the presence of wheals and/or angioedema that occurs daily or almost daily at least two times per week for more than 6 weeks. More than 30% of patients with moderate to severe CSU are affected for longer than 5 years. Here, we report a patient with recalcitrant CSU whose symptoms were completely controlled with omalizumab and added-on ciclosporin. A 56-year-old Thai female presented at the Siriraj Urticaria Clinic with recurrent wheals and sporadic angioedema for 20 years. Her previous medication included desloratadine 20 mg/day, fexofenadine 720 mg/day, ranitidine 300 mg/day, and intermittent systemic corticosteroids, all of which failed to control her symptoms. We added ciclosporin 100 mg twice per day (3 mg/kg/day). One week later, our patient decided to discontinue ciclosporin by herself due to a worsening of her wheals, pruritus, and dyspnea. We then added omalizumab subcutaneous injection (150 mg at the beginning, 300 mg at 2 weeks, and 300 mg at 4 weeks) with no significant improvement. We decided to re-prescribe add-on ciclosporin 100 mg twice per day (3 mg/kg/day) together with subcutaneously injected omalizumab 300 mg every 2 weeks. After two months, this combination treatment led to complete symptom control, and prednisolone could be discontinued. Omalizumab in combination with ciclosporin for treatment of refractory CSU resulted in a markedly positive clinical response.

Background Vitamin D has been reported to be associated with many allergic diseases. There are a limited number of the studies of vitamin D supplementation in patients with chronic spontaneous urticaria (CSU). This study aims to study the relationship between vitamin D and CSU in terms of serum vitamin D levels, and the outcomes of vitamin D supplementation. Methods A literature search of electronic databases for all relevant articles published between 1966 and 2018 was performed. The systematic literature review was done following Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations. Results Seventeen eligible studies were included. Fourteen (1321 CSU cases and 6100 controls) were concerned with serum vitamin D levels in CSU patients. Twelve studies showed statistically significant lower serum vitamin D levels in CSU patients than the controls. Vitamin D deficiency was reported more commonly for CSU patients (34.3–89.7%) than controls (0.0–68.9%) in 6 studies. Seven studies concerned with vitamin D supplementation in CSU patients showed disease improvement after high-dosages of vitamin D supplementation. Conclusion CSU patients had significantly lower serum vitamin D levels than the controls in most studies. However, the results did not prove causation, and the mechanisms were not clearly explained. Despite the scarcity of available studies, this systematic review showed that a high dosage of vitamin D supplementation for 4–12 weeks might help to decrease the disease activity in some CSU patients. Well-designed randomized placebo-controlled studies are needed to determine the cut-off levels of vitamin D for supplementation and treatment outcomes.

Objective To adapted the Drug Hypersensitivity Quality of Life (DrHy-Q) Questionnaire from Italian into Thai and assessed its validity and reliability. Design Prospectively recruited during January 2012–May 2017. Setting Multicenter; six Thai tertiary university hospitals. Study Participants Total of 306 patients with physician-diagnosed drug hypersensitivity. Interventions Internal consistency and test–retest reliability were evaluated among 68 participants using Cronbach’s ɑ and intra-class correlation coefficient (ICC). The validity of Thai DrHy-Q was assessed among 306 participants who completed World Health Organization Quality of Life-BREF (WHOQOL-BREF-THAI). Construct and divergent validities were assessed for Thai DrHy-Q. Known-groups validity assessing discriminating ability was conducted in Thai DrHy-Q and WHOQOL-BREF-THAI. Main outcome measures Validity; reliability; single vs. multiple drug allergy; non-severe cutaneous adverse reactions (SCAR) vs. SCAR. Results Thai DrHy-Q showed good reliability (Cronbach’s ɑ = 0.94 and ICC = 0.8). Unidimensional factor structure was established by confirmatory factor analysis (CFI&TLI = 0.999, RMSEA = 0.02). Divergent validity was confirmed by weak correlation between Thai DrHy-Q and WHOQOL-BREF-THAI domains (Pearson’s r = −0.41 to −0.19). Known-groups validity of Thai DrHy-Q was confirmed with significant difference between patients with and without life-threatening SCAR (P = 0.02) and patients with multiple implicated drug classes vs. those with one class (P < 0.01); while WHOQOL-BREF-THAI could differentiate presence of life-threatening SCAR (P < 0.01) but not multiple-drug allergy. Conclusions Thai DrHy-Q was reliable and valid in evaluating quality of life among patients with drug hypersensitivity. Thai DrHy-Q was able to discriminate serious drug allergy phenotypes from non-serious manifestations in clinical practice and capture more specific drug-hypersensitivity aspects than WHOQOL-BREF-THAI.

Despite widely recommended usage of cyclosporine A (CsA) in chronic spontaneous urticaria (CSU), there is no meta-analysis concerning its efficacy and safety.To meta-analyze and review the efficacy and safety of CsA in CSU.Efficacy was assessed by the relative change in urticaria activity score at 4 weeks and response rates at 4, 8, and 12 weeks. Safety was assessed by analyzing the number of patients with 1 or more adverse event.Eighteen studies (909 participants) including 2 randomized controlled trials were included, with 125, 363, and 266 patients with CSU receiving very low (2 mg/kg/d), low (from 2 to4 mg/kg/d), and moderate (4-5 mg/kg/d) doses of CsA, respectively. After 4 weeks, the mean relative change in urticaria activity score of CsA-treated patients was -17.89, whereas that of controls was -2.3. The overall response rate to CsA treatment with low to moderate doses at 4, 8, and 12 weeks was 54%, 66%, and 73%, respectively. No studies of very low-dose CsA evaluated response rates at 4, 8, and 12 weeks. Among patients treated with very low, low, and moderate doses of CsA, 6%, 23%, and 57% experienced 1 or more adverse event, respectively.Given the limited number and quality of studies, our results should be interpreted with caution. CsA is effective at low to moderate doses. Adverse events appear to be dose dependent and occur in more than half the patients treated with moderate doses of CsA. We suggest that the appropriate dosage of CsA for CSU may range from 1 to 5 mg/kg/d, and 3 mg/kg/d is a reasonable starting dose for most patients.

Background Delayed pressure urticaria (DPU) is characterized by recurrent erythematous and often painful swelling after the skin is exposed to sustained pressure. Treatment is challenging. Antihistamines, the first-line and only approved treatment, are often not effective. Objective To systematically review the treatment options for DPU. Method A literature search of electronic databases for all relevant articles published till April 29, 2019, was conducted using the search terms "delayed pressure urticaria" and "pressure urticaria." This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Results Twenty-one studies (8 randomized controlled trials [RCTs], 10 retrospective cohort studies, and 3 open-label prospective studies) were included. Second-generation H1 antihistamines (sgAHs) were effective in 3 RCTs. The combination of an sgAH and montelukast (2 RCTs) or an sgAH and theophylline (1 non-RCT) was more effective than the sgAH alone. The disease improved with omalizumab (4 non-RCTs), sulphones (3 non-RCTs), oral prednisolone (1 RCT and 2 non-RCTs), intravenous immunoglobulin (1 non-RCT), and gluten-free diet (1 non-RCT). There are no studies on updosing of antihistamines over standard dosage in DPU. Conclusions Overall, the quality of studies on DPU is low. Because of the lack of other evidence, antihistamines remain the first-line therapy. Updosing of sgAHs could be considered in patients with uncontrolled symptoms on the basis of the extrapolation of evidence from chronic spontaneous urticaria, even though there is no evidence of its efficacy over standard dosage. Addition of montelukast may be considered. Omalizumab or sulphones may be used in treatment-resistant patients. High-quality DPU studies should be conducted.

Purpose To review the clinical features and natural courses of cold urticaria (ColdU) in a tropical country. Methods A retrospective chart review was performed of patients who visited Siriraj Urticaria Clinic, Siriraj Hospital, Bangkok, Thailand, and were diagnosed with ColdU between 2007 and 2018. Data on provocation and threshold tests, clinical courses, and laboratory work-up were analyzed and compared with data reported by studies in temperate countries. Results Of 1,063 chronic urticaria patients, 27 (2.5%) were diagnosed with ColdU, with a mean age of symptom onset of 34.8 years. Half of the patients had a history of atopy, and 1 (3.7%) had a history of anaphylaxis. All patients were positive to 1 of 3 provocation tests: an ice cube test; TempTest 4.0; or a tray filled with ice, salt and water. Thirteen patients underwent the ice cube test, and all had positive results. TempTest was performed on 15 patients, 8 of whom had positive results, with a mean critical temperature threshold (CTT) of 21.0°C. All of the 7 patients who had a negative TempTest result later produced positive results to the immersion of their hand and forearm in a tray filled with ice, salt, and water. All patients were treated with H₁-antihistamines, the vast majority (96.3%) being non-sedating H₁-antihistamines. Some (14.8%) needed to be administered oral corticosteroids, ciclosporin, or omalizumab. Six patients (22.2%) were in remission. A Kaplan-Meier survival curve demonstrated 5-year and 10-year remission rates of 13.8% and 42.6%, respectively. Conclusions The rate of anaphylaxis in patients with ColdU in a tropical country was lower than those reported by other studies conducted intemperate climates. On the other hand, the number of female patients, mean age at symptom onset, atopy rate, rate of concomitant chronic spontaneous urticaria and mean CTT were higher.

In addition to serving as a stress regulatory/response protein, heat shock protein 60 (Hsp60) also plays important roles in disease mechanism and progression. This chapter summarizes all aspects of the current knowledge on Hsp60 related to various skin diseases, including acne, atopic dermatitis (AD), dermatitis herpetiformis (DH), vasculitis, Behcet’s disease (BD), microscopic polyangiitis (MPA), systemic sclerosis (SSc), dermatomyositis, lichen planus (LP), and psoriasis. The data have shown that not only human Hsp60 but also its homologs in bacteria or microbes (e.g., GroEL) are involved in immune response and inflammatory cascade of these skin diseases. Furthermore, Hsp60 expression is also associated with severity of some diseases. Therefore, Hsp60 can be considered as a potential target for future development of a useful biomarker for diagnostics and prognostics in skin diseases. Moreover, it may also serve as a new therapeutic target for better treatment outcome.

There are limited data regarding omalizumab in the treatment of recalcitrant chronic spontaneous urticaria (CSU) in Asian populations. This study evaluated the effectiveness and the proper dosage of omalizumab for Asian CSU patients in a real-life setting.We retrospectively reviewed recalcitrant CSU patients seeking treatment at the Skin Allergy Clinic, Siriraj Hospital during the 3-year period. All patients were treated with omalizumab as an add-on therapy. Standard seven-day urticaria activity score (UAS7) and medication score were used to assess omalizumab response.Of 13 patients, 9 patients (70%) responded well to 150 mg omalizumab injection every month, whereas 4 patients requiring updosing to 300 mg. In the 150 mg group, one patient achieved complete symptom control without antihistamine intake. Most of them required antihistamines without prednisolone and ciclosporin. Onset of omalizumab was fast, usually within the first week. Though only two patients in the 300 mg group achieved complete absence of symptoms, ciclosporin and oral corticosteroids could be discontinued. No patients reported adverse effects.Omalizumab at an initial dosage of 150 mg was effective in the treatment of recalcitrant CSU among Asians. Updosing to 300 mg was required to achieve satisfactory outcomes.

This patient had a two-month history of four clinical manifestations of drug hypersensitivity reactions (DHR): maculo papular eruption, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) and toxic epidermal necrolysis (TEN). The eliciting drugs were rifampicin, possibly gabapentin, levofloxacin, meropenam and/or colistin. Thus, the patient might develop a multiple drug hypersensitivity syndrome. The TEN-like lesion appeared after stopping drugs for two days. A different manifestation of DHR in dependence of drug use suggests that the distinct manifestations of DHRs are due to the stimulation of T cells with distinct functions. The simultaneous appearance of AGEP and DRESS symptoms might be due to the simultaneous stimulation of two (or more) different T cell subsets, which are functionally dominant. Lastly, the appearance and further propagation of symptoms after therapy-stop is a common but somewhat neglected problem in DHR, which raises questions regarding the cause of persisting T cell activation.

Phenytoin (PHE) and carbamazepine (CBZ) are first rank causative drugs that can induce drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Identification of anti-epileptic drugs as a culprit drug has been problematic; hence, in vitro tests could be promising methods to define causative drugs without clinical risk. The aim of this study is to evaluate the efficacy of lymphocyte transformation tests (LTT) and cytokine detection assays in identifying PHE and CBZ as culprit drugs. Peripheral blood mononuclear cells were collected from normal, PHE/CBZ tolerance and PHE/CBZ hypersensitivity cohorts and utilized for cell-culture assays. LTT was performed and culture supernatants were subjected to multiple cytokine detection assays. Our study showed that LTT correlated with outcomes of Naranjo's assessment with statistical significance (r = 0.614). Various sensitivities of LTT and cytokine detection assays were demonstrated. Although both assays provided excellent specificity, LTT yielded higher sensitivity as compared to those of cytokine detection assays in both DRESS and SJS/TEN. Regardless whether specificity is, this is the first report to demonstrate that IL-4 detection assay could enhance sensitivity to identify culprit drug when it was combined with LTT for SJS/TEN patients or it was combined with IL-2/IFN-γ detection assays for DRESS ones.

The HLA-B∗15:02 allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The HLA-B alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of HLA-B alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population. A case-control study was performed by genotyping the HLA-B alleles of Thai carbamazepine-induced hypersensitivity reaction patients (17 MPE, 16 SJS/TEN, and 5 DRESS) and 271 carbamazepine-tolerant controls. We also recruited 470 healthy Thai candidate subjects who had not taken carbamazepine. HLA-B∗15:02 showed a significant association with carbamazepine-induced MPE (P=0.0022, odds ratio (OR) (95% confidence interval [CI]) = 7.27 (2.04–25.97)) and carbamazepine-induced SJS/TEN (P=4.46×10−13; OR (95% CI) = 70.91(19.67–255.65)) when compared with carbamazepine-tolerant controls. Carbamazepine-induced SJS/TEN also showed an association with HLA-B∗15:21 allele (P=0.013; OR (95% CI) = 9.54 (1.61–56.57)) when compared with carbamazepine-tolerant controls. HLA-B∗58:01 allele was significantly related to carbamazepine-induced MPE (P=0.007; OR (95% CI) = 4.73 (1.53–14.66)) and DRESS (P=0.0315; OR (95% CI) = 7.55 (1.20–47.58)) when compared with carbamazepine-tolerant controls. These alleles may serve as markers to predict carbamazepine-induced cADRs in the Thai population.

A 33-year-old woman presented with recurring pruritic, erythematous papules around the mouth and on the hands, of 1.5 years' duration. These flares typically began several days before her menstrual cycle and persisted for approximately 1 week. Physical examination revealed urticarial plaques on the neck. Due to the nature of the eruption, which corresponded with her menstrual cycle, a diagnosis of autoimmune progesterone urticaria was considered and workup pursued.