IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity.

BACKGROUND: Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences. OBJECTIVE: We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning. METHODS: The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model. RESULTS: Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and ß-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/106 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively). CONCLUSIONS: IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.

Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study.

Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13-8.04; p = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49-4.34; p < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21-4.41; p = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82-33.7; p < 0.001). Kaplan-Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.

Unveiling the role of neutrophils in chronic spontaneous urticaria: Beyond mast cells.

Mast cells and eosinophils are considered pivotal contributors to the pathogenesis of chronic spontaneous urticaria (CSU). However, emerging evidence suggests that neutrophils also play a central role. Cutaneous mast cells and macrophages orchestrate the recruitment of neutrophils through the regulation and activation of diverse processes, including heightened local vascular permeability and chemokine release. Studies have demonstrated increased activation and elevated levels of neutrophil-related cytokines in CSU patients. Moreover, neutrophils have been proposed as antigen-presenting cells during the late-phase reaction of immunoglobulin E-mediated allergy and have been associated with the expression of calcitonin gene-related protein and vascular endothelial growth factor in CSU. Histopathological analysis of lesional skin in CSU patients revealed significantly higher eosinophil and neutrophil counts than unaffected skin. However, the extent of neutrophil infiltration in the skin does not appear to correlate with the number of neutrophils in peripheral blood. The utility of the neutrophil-lymphocyte ratio as a marker for disease activity or remission in CSU remains inconclusive. Neutrophil-targeted therapy may confer benefits for CSU patients who exhibit resistance to antihistamines. Omalizumab has demonstrated its ability to reduce neutrophil counts, the neutrophil-lymphocyte ratio, and the neutrophil-monocyte ratio in peripheral blood. While dapsone and colchicine are recommended as alternative treatment options for CSU, their evidential support from published studies remains limited. Inhibitors targeting interleukin-1 and neutrophil-related cytokines have been proposed as potential therapeutic interventions for patients exhibiting neutrophil predominance. Further research is warranted to gain deeper insights into the involvement of neutrophils in CSU and to explore potential therapeutic interventions.

A double-blinded, randomized, split-side, vehicle-controlled study of the efficacy of cleanser containing Acanthus ebracteatus Vahl., Suregada multiflora, and Acacia concinna in patients with atopic dermatitis: A pilot study.

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.

The validity and reliability of a Thai version of the Angioedema Control Test: Which recall period is preferable?

BACKGROUND: 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). OBJECTIVE: This study investigated the psychometric properties of a Thai version of the AECT. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Perioperative immediate hypersensitivity incidence, clinical characteristics, and outcomes after allergological evaluation: A multi-disciplinary protocol from tertiary hospital, Thailand.

BACKGROUND: Perioperative immediate hypersensitivity reaction (POH) is an immediate hypersensitivity reaction during an anesthesiologist monitored procedure. We report data of clinically-suspected POH (csPOH) patients undergoing an allergist-performed unified diagnostic workup algorithm for POH. OBJECTIVE: To describe the characteristics of patients with csPOH, POH events, and the POH outcomes of procedures after the unified diagnostic workup algorithm for POH. METHODS: A prospective cohort was conducted in adult patients with csPOH at Siriraj Hospital, a tertiary hospital, in Thailand from January 2018 to August 2022. Diagnostic workup for POH by the allergist included an initial assessment, followed by comprehensive allergological evaluation. Patients were then follow-up for POH outcomes during subsequent anesthesia procedures. RESULTS: Of 68 patients were csPOH, only 52 patients were diagnosed with POH by allergists. The incidence was 1:4,304 anesthetic procedures for POH, and 1:11,900 anesthetic procedures for at least grade III POH. Most patients had a grade III (51.2%) or II (46.4%) reaction. The leading identified causative agents were antibiotics (36.8%), antiseptics (21%), latex (13.1%), and morphine (13.1%). Cefazolin and chlorhexidine were the most common antibiotic and antiseptic, respectively. During a median follow-up time of 2.1 years, all 14 patients completing comprehensive allergological evaluation underwent subsequent anesthesia without recurrence of POH. CONCLUSIONS: The incidence of POH at our hospital was comparable to the global incidence. Antibiotics were the most common causative agent. Complete records, collaboration among the multidisciplinary team, and comprehensive evaluation of POH allow for safe subsequent procedures.

Systematic comparisons of various markers for mast cell activation in RBL-2H3 cells.

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, ß-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 ß-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.

Differential cytokine profiles produced by anti-epileptic drug re-exposure of peripheral blood mononuclear cells derived from severe anti-epileptic drug patients and non-allergic controls.

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.

A web-based survey on the behavior of moisturizer used in adults with and without atopic dermatitis in Thailand.

BACKGROUND: Moisturizers play an important role in restoring the skin barrier. They should be used to treat and prevent eczema, especially in atopic dermatitis (AD). OBJECTIVE: 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. METHODS: A cross-sectional web-based survey was performed. RESULTS: 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. CONCLUSIONS: 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.

Disease activity of patients with chronic urticaria receiving COVID-19 vaccines.

BACKGROUND: 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. OBJECTIVE: To evaluate disease activity of chronic urticaria after receiving a COVID-19 vaccine. METHODS: 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. RESULTS: 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, p < 0.01). CONCLUSIONS: 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.

The validity and reliability of the Thai-version of 5-D itch scale.

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.

Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis.

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 < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41-3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79-12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50-16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77-9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97-371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50-21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of 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.

Adult female acne: Clinical characteristics and factors significantly associated with polycystic ovary syndrome.

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 <33 years), premenstrual flare, and irregular menstruation, but not hirsutism or androgenetic alopecia, were associated with PCOS in univariate and multivariate analysis. Perimenopausal acne was identified in 6.7%. The total mean DLQI score was 8.0 ± 5.4 (range from 0 to 23). CONCLUSIONS: Persistent acne with moderate severity was common in AFA patients and higher BMI was associated with acne severity. PCOS should be screened in AFA patients with younger age, premenstrual flare, and irregular menstruation.

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

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.

Treatments of cold urticaria: A systematic review.

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.

Reliability and validity of the Thai Drug Hypersensitivity Quality of Life Questionnaire: a multi-center study.

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.

Cutaneous toxicities of epidermal growth factor receptor inhibitors: A prospective study in 60 Asian patients.

BACKGROUND: Several prospective studies have been conducted in epidermal growth factor receptor (EGFR) inhibitor-related cutaneous reactions in Caucasian patients, but prospective studies in Asian populations are scarce. OBJECTIVE: To investigate the cutaneous side effects of EGFR inhibitors in Asian cancer patients and to assess tumor response to dermatologic manifestations. METHODS: Sixty patients with lung or colorectal cancer who were receiving EGFR inhibitors were prospectively followed for at least one year by oncologists and dermatologists. RESULTS: Of 60 patients (33 males, 27 females), 46 lung cancer patients received erlotinib (n=29) and gefitinib (n=17). Cetuximab was prescribed in 14 colorectal cancer patients. Fifty-eight patients (58/60, 96.7%) developed cutaneous reactions. The most common reactions were xerosis (82.8%), acne (79.3%), and skin desquamation (62.1%). Most reactions were mild and well-tolerated. Of 14 patients who had severe reactions, temporary treatment interruption was necessary in 3 patients and a decreasing dose was required in another 3 patients. There were no statistically significant differences in type, severity, or number of cutaneous reactions between responders (29/58) and non-responders (29/58) to EGFR inhibitors. At median follow-up time of 11.92±1.08 months, no patient died from cutaneous toxicities. Nine patients died from cancer and 11 patients lost to follow-up. CONCLUSION: In this Asian population, almost all patients (96.7%) developed cutaneous toxicities of EGFR inhibitors. Xerosis, acne, and desquamation were common in Asian cancer patients. Most reactions were mild and well tolerated. Due to limited number of patients, this study did not show significant associations between cutaneous toxicities and tumor response.

Immunologic Studies of Progesterone-Induced Neutrophilic Urticaria.

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.

Validity, reliability and interpretability of the Thai version of the urticaria control test (UCT).

BACKGROUND: The Long Form and Short Form of the German (original) version of the Urticaria Control Test (UCT) have shown to be valid and reliable instruments for assessing patients with all types of chronic urticaria (CU). The cutoff scores for identifying patients with well-controlled disease were ≥ 24 and ≥ 12 for Long and Short Forms, respectively. However, the sensitivity to change and minimal clinically important difference (MCID) of the UCT have never been systematically evaluated. This study aimed to investigate the validity, reliability, screening accuracy, sensitivity to change and MCID of the linguistically validated translation of the UCT into the Thai language for assessing CU in the Thai population. METHODS: A structured translation and pre-testing were done to cross-culturally adapt the UCT for the Thai language. All measurement properties of both forms of the Thai UCT were validated in 169 patients with CU. RESULTS: There were strong correlations between the Thai UCT score and disease activity, health-related quality of life impairment, and disease control (all correlations ≥ 0.7). Good internal consistency and excellent intra-rater reliability were demonstrated. The same cutoff scores to define patients with well-controlled disease should be used as those recommended for the original UCT version. MCIDs equated to increase in scores of 6 and 3 for the Long and Short Forms, respectively, of the Thai UCT should be used to identify patients who had minimal responses. Score increments of ≥ 10 and ≥ 6 for Long and Short Forms, respectively, should be used to define patients who had marked responses. CONCLUSIONS: This study confirmed the applicability of the UCT for use in Thailand, a country that has a very different language and cultural setting than that of Germany and the United States. Further studies are required to examine the suitability of the UCT for use in the pediatric population.

Clinical features of chronic urticaria in aging population.

BACKGROUND: Different clinical features of skin diseases have been addressed between aging patients and non-aging patients. However, data focusing on the clinical features of chronic urticaria (CU) in aging patients especially in the Asian population are still limited. OBJECTIVE: This study aimed to investigate the clinical characteristics of CU in aging and non-aging patients in the Asian population. METHODS: Case records of 1622 CU patients attending the Urticaria Clinic, Department of Dermatology, Siriraj Hospital, Mahidol University, Thailand between 2000 and 2013 were retrospectively reviewed. All CU patients older than 60 years were recruited. Twice the number of CU patients who were non-aging were enrolled using a systematic sampling method. RESULTS: Of the 1622 CU patients, 67 (4.1%) were aging patients. From these, 134 non-aging patients with CU were recruited. The majority of patients for both groups were female, with 67.2% and 77.6% of the aging and non-aging groups, respectively. In both groups, the most common cause of CU was chronic spontaneous urticaria. In the aging group, positive autologous serum skin test, anti-thyroid antibodies and antinuclear antibodies were found more commonly than in the non-aging group, without a statistically significant difference. The mean duration of the disease tended to be shorter in the aging group. CONCLUSION: Our study showed that CU in aging patients was uncommon (4.1%). Aging patients with CU seemed to have shorter disease duration and higher percentages of autoantibodies than non-aging patients with CU without a statistically significant difference.