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.

Efficacy and safety of fractional 1064-nm picosecond laser for atrophic traumatic and surgical scars: A randomized, single-blinded, split-scar-controlled study.

OBJECTIVE: A fractional 1064-nm picosecond laser is an efficient and safe treatment for atrophic acne scars. However, evidence of using a picosecond laser for atrophic posttraumatic and surgical scar therapy is lacking. This study aimed to evaluate the efficacy and safety of using a 1064-nm picosecond laser with a microlens array (MLA) for the treatment of atrophic posttraumatic and surgical scars. METHODS: This was a prospective, intraindividual, single-blinded, randomized split-lesion-controlled trial. Twenty-five subjects with atrophic traumatic or surgical scars that existed for more than 1 year were enrolled. All atrophic scars were divided at the midline into two halves and randomly assigned to a treatment or control side. The treatment group was treated with a 1064-nm picosecond laser with an MLA handpiece (spot size: 6-8 mm, fluence: 1.0-1.2 J/cm2 , repetition rate: 5 Hz, three passes) for 3 monthly sessions. The scar volumes were objectively measured using a three-dimensional (3D) photograph at baseline, 1 month after the first and second treatments, and 3 and 6 months after the final treatment. Subjective assessments were conducted by a blinded dermatologist and patients' self-assessment to evaluate improvements at 3 months after the final treatment. RESULTS: The treated sides exhibited a significant volume reduction, with statistically significant improvements over the control group at 1 month after the first and second treatments and at 3 months after the final treatment (p = 0.024, 0.005, and 0.019, respectively). At 3 months after the final treatment, a blinded dermatologist correctly identified the treated side in 24 of 25 patients (96%). The patients rated the improvements as excellent (>75%) and marked (50%-75%) in 36% and 48% of patients, respectively. CONCLUSION: At 3 months, the 1064-nm picosecond laser with a fractionated MLA can significantly reduce the posttraumatic and postsurgical atrophic scar volume in patients with Fitzpatrick skin types III-V. Insufficient data preclude inferences regarding efficacy at 6 months.

Efficacy of Botulinum Toxin A for Scar Prevention After Breast Augmentation: A Randomized Double-Blind Intraindividual Controlled Trial.

BACKGROUND: Botulinum toxin A benefits postsurgical scar prevention by reducing wound edge tension and inhibiting in vitro scar tissue fibrosis. OBJECTIVE: To investigate the efficacy of botulinum toxin Type A (BTX) in improving inframammary scar appearance after primary breast augmentation. MATERIALS AND METHODS: A prospective, double-blinded, randomized controlled trial was performed with 27 participants receiving primary augmentation mammoplasty with inframammary incisions. After skin closure, intradermal injections of BTX were administered to 1 (treated) side of the inframammary incision. The contralateral side was the control. Scars were evaluated at 3 months, 6 months, and 9 months using the Patient and Observer Scar Assessment Scale and multispectral imaging analysis. RESULTS: Overall, 22 patients completed the study. There were no significant subjective differences between the treated and control sides except the patient's treated side had significantly higher scores than the control side at 9 months. The treated side showed significantly smaller scar widths at 6 months and 9 months (p < .001) and better scar surface textures at 9 months (p = .003) than the control side. CONCLUSION: Subjectively, intradermal BTX injection immediately after breast augmentation skin closure caused no significant differences. Objectively, scar width and texture significantly improved at 6 months and 9 months.

Comparison between topical recombinant human epidermal growth factor and Aloe vera gel in combination with ablative fractional carbon dioxide laser as treatment for striae alba: A randomized double-blind trial.

OBJECTIVES: Striae distensae are linear atrophic dermal scars. Despite several currently available therapeutic modalities, no consistently effective therapies have been established. This study aimed to evaluate and compare the efficacy of topical recombinant human epidermal growth factor (rhEGF) and ablative fractional carbon dioxide (CO2 ) laser (AFXL) versus ablative fractional CO2 laser and topical Aloe vera gel in treating striae alba. METHODS: A total of 24 participants with striae alba were enrolled. Patients' striae were divided into the left and right sides. Participants were treated with fractional CO2 laser on both sides for three sessions at 4-week intervals. Immediately after the laser treatment, each side of the striae was randomly assigned to either rhEGF or Aloe vera gel treatment. Patients were required to apply the medication twice daily up to 1 month after the last laser treatment session. Texture, average melanin, and melanin variation were assessed at pretreatment, 1 month after the first, second, and third treatments, and 6 months after the last treatment. Participants were asked to complete a self-administered questionnaire. Nine participants underwent skin biopsies of the nontreated and treated striae, which were obtained from each treated side. RESULTS: Both sides of the treatment area showed significant improvement in texture starting from 1-month follow-up, which sustained up to 6 months after the final treatment, albeit without statistically significant difference between the rhEGF- and Aloe vera-treated sides (P < 0.001, 0.003, and 0.002 for the AFXL-rhEGF-treated side and P = 0.024, 0.001, and 0.001 for the AFXL-Aloe-treated side at 1 month after the first treatment, 1 month after the last treatment, and 6 months after the last treatment, respectively). Participants expressed satisfaction with the AFXL-rhEGF-treated side, which showed significantly greater marked improvement (at 50%) than the AFXL-Aloe-treated side at 6 months after the final treatment (P = 0.034). Post-inflammatory hyperpigmentation (PIH) occurred in 95.8% of participants, which decreased after 6 months compared with baseline. Both treatments improved melanin variation at 6 months after the final treatment, although without significant difference from pretreatment between both groups. Skin biopsy revealed a statistically significant increase in epidermal thickness and decrease in elastic fragmentation in both groups. CONCLUSION: AFXL-rhEGF and AFXL-Aloe significantly improved the striae surface texture. PIH was the most common side effect, which improved at 6 months. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The effectiveness of a 595 nm pulsed-dye-laser in the treatment of surgical scars following a knee arthroplasty.

Background: A knee arthroplasty results in a long vertical scar on the knee and has a high risk for the development of hypertrophic or keloid scarring. The purpose of this study is to determine the efficacy and safety of the use of a 595 nm pulsed-dye-laser (PDL) for this type of scar. Methods: This randomized, controlled study was conducted in 40 patients (41 scars) with postoperative knee arthroplasties. Each scar was divided at the midline into two sections and randomized into a laser treated half and a controlled half. The treated half has received three treatments with a 595 nm PDL (10 mm spot size, 0.45 ms, 6 J/cm2). The scar appearances had been evaluated at 6 months using the Vancouver scar scale (VSS). Results: At 6 months postoperative, the laser treated sections had demonstrated significantly better scores in the overall parameters of the VSS. Furthermore, as for the individual parameters, there were significant differences between the treatment sections and control sections with the exception of pigmentation. There were no serious complications. Conclusion: The 595 nm PDL is an effective and safe therapeutic option for the treatment of surgical scars following a knee arthroplasty.

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.

Subcutaneous infiltration of carbon dioxide (carboxytherapy) for abdominal fat reduction: A randomized clinical trial.

BACKGROUND: Noninvasive fat removal is preferred because of decreased downtime and lower perceived risk. It is important to seek new noninvasive fat removal treatments that are both safe and efficacious. OBJECTIVE: To assess the extent to which carboxytherapy, which is the insufflation of carbon dioxide gas into subcutaneous fat, results in reduction of fat volume. METHODS: In this randomized, sham-controlled, split-body study, adults (body mass index, 22-29 kg/m2) were randomized to receive 5 weekly infusions of 1000 cm3 of CO2 to 1 side of the abdomen, and 5 sham treatments to the contralateral side. The primary outcome measures were ultrasound measurement of fat layer thickness and total circumference before and after treatment. RESULTS: A total of 16 participants completed the study. Ultrasound measurement indicated less fat volume on the side treated with carboxytherapy 1 week after the last treatment (P = .011), but the lower fat volume was not maintained at 28 weeks. Total circumference decreased nominally but not significantly at week 5 compared with baseline (P = .0697). Participant body weights did not change over the entire course of the study (P = 1.00). LIMITATIONS: Limitations included modest sample size and some sources of error in the measurement of circumference and fat layer. CONCLUSION: Carboxytherapy provides a transient decrease in subcutaneous fat that may not persist. Treatment is well tolerated.

Pain in naïve and non-naïve subjects undergoing nonablative skin tightening dermatologic procedures: a nested randomized control trial.

BACKGROUND: Pain is expected during noninvasive skin tightening and can be anxiety provoking, especially for those who have not had prior treatments. OBJECTIVE: To compare pain reported by patients naïve to nonablative skin tightening energy devices with those who were not naive. METHODS AND MATERIALS: The non-naïve group at least three nonablative laser procedures or one nonablative skin tightening procedure, and the naïve group no previous treatments. Four sites at each of two anatomic locations (periorbital and midface or cheek) were treated in each subject with needle prick, pulsed dye laser, radiofrequency, and ultrasound with the order of the interventions randomized. All interventions except ultrasound were also applied to three abdominal sites. The difference in mean pain scores between naïve and nonnaïve subjects were averaged over the anatomic sites. RESULTS: Ten naïve and 10 non-naïve subjects completed study procedures. Mean pain scores ranged from 1.3 to 4.9. The mean for all naïve conditions was 2.3 ± 1.0, vs 2.2 ± 1.4 for non-naïve conditions. There was no overall difference according to group, device, or anatomic area. CONCLUSIONS: There was no significant difference in pain between naïve and non-naïve subjects undergoing cutaneous energy treatments. Individual devices may elicit more pain at specific anatomic locations.

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.

The comparative effectiveness of suction-curettage and onabotulinumtoxin-A injections for the treatment of primary focal axillary hyperhidrosis: a randomized control trial.

BACKGROUND: Botulinum toxin injections and suction-curettage have been separately shown to be effective in treating axillary hyperhidrosis but have not been compared in the same patients. OBJECTIVE: We sought to compare effectiveness of suction-curettage versus neurotoxin for the treatment of axillary hyperhidrosis. METHODS: Each of 20 patients was randomized to receive toxin injections to one axilla and suction-curettage to the contralateral axilla. The primary outcome measure was reduction of sweat rate measured by gravimetry, and the secondary measure was quality of life as measured by a patient-directed questionnaire. RESULTS: At 3 months posttreatment, toxin injections decreased baseline resting sweat production by 72.1% versus 60.4% (P = .29) for suction-curettage, and baseline exercise-induced sweat production by 73.8% versus 58.8% (P = .10). When patients were stratified into the categories of light and heavy sweaters, there was a difference among heavy sweaters, with exercise-induced sweat production lower by 10.48 mg/min or 34.3% (P = .0025) at toxin-treated sites. Compared with suction-curettage, toxin also resulted in greater improvements in quality of life by 0.80 points (P = .0002) and 0.90 points (P = .0017) at 3 and 6 months posttreatment, respectively, as measured by the patient questionnaire. LIMITATIONS: The follow-up period was limited to 6 months. CONCLUSIONS: By objective measures 3 months after treatment, neurotoxin injections are nominally more effective than suction-curettage in all cases, and markedly more effective in heavy sweaters. Patients have a very significant preference for neurotoxin injections at 3 months, and this is maintained at 6 months.

Efficacy of a triamcinolone acetonide-loaded dissolving microneedle patch for the treatment of hypertrophic scars and keloids: a randomized, double-blinded, placebo-controlled split-scar study.

The treatment of hypertrophic scars (HTSs) and keloids remains a challenge. Intralesional triamcinolone acetonide (TAC) is the mainstay treatment for these conditions. Despite its efficacy, TAC has several adverse side effects, including telangiectasias, skin atrophy, pigmentary changes, and skin necrosis. Dissolving microneedles (DMN) use the poke-and-release method to create microchannels that enhance drug delivery to the target tissue in the dermis, without causing pain and with a decreased risk of transmission of blood-borne diseases. To evaluate and compare the efficacy of a TAC-DMN versus a drug-free DMN patch for the treatment of HTSs and keloids, 20 patients (10 with HTSs and 10 with keloids) received a split-scar treatment: one half of the scar length was treated with TAC-DMNs and the other half was treated with drug-free DMN for three sessions at 14-day intervals. Efficacy was assessed by measuring the scar volume through a multispectral imaging system and using the Patient and Observer Scar Assessment Scale (POSAS). The HTSs treated with TAC-DMNs showed a significant reduction in the mean scar volume 2 weeks after the second treatment and 1 month after the third treatment (p = 0.028 and 0.020, respectively), while the HTSs treated with drug-free DMNs showed no significant reduction in the scar volume. Both sides of the keloids showed no significant reduction in mean scar volume. Using the POSAS, significant improvement in the appearance of both halves of the HTSs was observed 1 month after the treatments. A significant improvement (evaluated by POSAS) was also observed in the keloids treated with TAC-DMNs 2 weeks after the second treatment and 1 month after the third treatment. No significant improvement was observed from the patients' perspective as evaluated by POSAS in the keloids treated with drug-free DMNs. However, no significant difference was observed between the treatment and control halves. TAC-DMN is an effective treatment for HTSs. Increasing the dosage and duration of keloid scar treatment is required in future studies to determine whether it would result in a significant therapeutic outcome. This trial is registered in the Thai Clinical Trials Registry (TCTR20220318004; date of registration, March 17, 2022).

Efficacy and safety of 0.15% isobutylamido thiazolyl resorcinol combined with hyaluronic acid vs 0.15% isobutylamido thiazolyl resorcinol or hyaluronic acid alone in melasma treatment: A randomized evaluator-blind trial.

BACKGROUND: Melasma has a complex pathogenesis, and various aggravating factors contribute to its recalcitrance to treatments. A combination of isobutylamido thiazolyl resorcinol (ITR) and hyaluronic acid (HA) could increase melasma treatment efficacy. AIMS: To compare the efficacy and safety of 0.15% ITR plus HA vs 0.15% ITR or HA alone in melasma treatment. METHODS: Ninety-two patients received ITR 0.15% plus HA (n = 30), 0.15% ITR (n = 31), or HA (n = 31) along with broad-spectrum sunscreen application for 12 weeks. Treatment efficacy was determined using modified Melasma Area Severity Index (mMASI), average melanin and melanin variation with Antera3D® , and safety based on transepidermal water loss. RESULTS: Compared with the HA group, the ITR+HA group showed significantly reduced mMASI at weeks 4, 8, and 12 (p = 0.026, 0.015, and 0.001, respectively), whereas the ITR group showed a significant reduction at week 12 (p = 0.027). There was no significant difference in the mMASI or average melanin level between the ITR+HA and ITR groups. Melanin variation was significantly lower in the ITR+HA group than in the ITR group at weeks 4, 8, and 12 (p = 0.027, 0.019, and 0.023, respectively). CONCLUSIONS: The combination of 0.15% ITR and 0.15% ITR+HA effectively reduced melasma severity. HA could synergistically improve melasma homogeneity.

The Role of In Vitro Detection of Drug-Specific Mediator-Releasing Cells to Diagnose Different Phenotypes of Severe Cutaneous Adverse Reactions.

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.

Contact allergy in eczema patients in Thammasat University Hospital.

Many patients with eczematous dermatitis need continued care in case of a recurrent or persistent skin condition and potential adverse effect of medications. Allergic contact dermatitis should be considered in the differential diagnosis of eczematous dermatitis especially in a patient whose dermatitis is persistent despite appropriate therapies. Patch testing is an essential investigation in patients with persistent eczematous eruption when contact allergy cannot be ruled out. The purpose of this study was to determine the frequency of contact allergy in patients with eczematous dermatitis in Thammasat University Hospital, Prathumthani, Thailand from June 1, 2008 to June 30, 2009 and to identify a possible relationship between sex, age, occupational differences and type of eczema that is associated with positive patch test reactions. A total of 157 patients were patch tested with 23 standard allergens. One or more positive responses were noted in 70 patients (44.6%). The most common allergen was nickel sulfate (26.8%), followed by cobalt chloride (7.6%), p-phenylenediamine (7.0%), fragrance mix (7.0%). Patients who were initially diagnosed with allergic contact dermatitis had significant correlation with positive patch test results to nickel sulfate, cobalt chloride and phenylenediamine (p = 0.00, p = 0.03, p = 0.02, respectively). Patients who were initially diagnosed with endogenous eczema had significant correlation with positive patch test results to colophony (p = 0.04). Contact allergy to fragrance mix was significantly more frequent in patients who had personal history of atopy (p = 0.04). There was no significant correlation between the frequency of contact allergy and sex, age, location of lesion and patient's occupation. In conclusion, this study demonstrated the prevalence in contact allergy in eczema patients in Thammasat University Hospital and compared the results with other region from Thailand. Further study involving many hospitals in various areas in Thailand is needed to provide more insight into contact allergy in Thailand.

Breast implant-associated anaplastic large cell lymphoma in an Asian patient: The first case report from Thailand.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has received increasing interest among plastic surgeons as a long-term complication of breast augmentation. Although the prognosis is usually good, mortality is a possible outcome. Most of the cases reported in the past two decades have been from the United States, Europe, and Australia, whereas cases of BIA-ALCL in Asia remain rare. Herein, we describe the first known case of BIA-ALCL in Thailand, in which a 32-year-old woman developed BIA-ALCL 3 years after breast augmentation using textured implants. The patient underwent bilateral removal of the implants and ipsilateral total capsulectomy. This case report-the first of its kind from Thailand-should increase awareness of BIA-ALCL among plastic surgeons in Asia. The true incidence of BIA-ALCL in Asia may be underreported.

Genetic Association of Co-Trimoxazole-Induced Severe Cutaneous Adverse Reactions Is Phenotype-Specific: HLA Class I Genotypes and Haplotypes.

Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTX-induced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.

The Clinical Effect of Oral Vitamin D2 Supplementation on Psoriasis: A Double-Blind, Randomized, Placebo-Controlled Study.

BACKGROUND: There are limited randomized controlled trials of oral vitamin D supplementation in psoriasis, especially in Asia, and the results are inconclusive. OBJECTIVE: To investigate the clinical effect of oral vitamin D supplementation on psoriasis. METHODS: Patients with psoriasis were randomized to receive vitamin D2 60,000 IU or similar-looking placebo pills once every 2 weeks for 6 months. The primary outcome was improvement of the Psoriasis Area and Severity Index (PASI) score at 3 and 6 months after treatment. Serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein and adverse events were monitored. The chi-square test, Fisher's exact test, Student's t-test, and Spearman's correlation analysis were used in statistical analysis. RESULTS: Of 50 subjects screened, 45 were eligible and randomized to the oral vitamin D2 group (n=23) or placebo group (n=22). At enrollment, the mean PASI score was 4.45, and 26.7% of patients had vitamin D deficiency. At 3 months, the oral vitamin D2 group had significantly higher PASI improvement than the placebo group (mean PASI improvement: 1.43 versus [vs.] -0.33, p-value=0.034; mean %PASI improvement: 34.21% vs. -1.85%, p-value=0.039). The mean serum 25(OH)D level was significantly higher in the oral vitamin D group than in the placebo group (27.4 vs. 22.4 ng/mL, p-value=0.029). Serum 25(OH)D concentrations were significantly inversely correlated with PASI scores at the 6-month follow-up. No major adverse event was observed overall. CONCLUSION: Oral vitamin D2 supplementation in patients with psoriasis increased the serum vitamin D level and significantly improved the treatment outcome without increasing adverse events. TRIAL REGISTRATION: This trial is registered with Thai Clinical Trials Registry TCTR20180613001.

Analysis of HLA-B Allelic Variation and IFN-γ ELISpot Responses in Patients with Severe Cutaneous Adverse Reactions Associated with Drugs.

BACKGROUND: The prevention and confirmation of drug-induced severe cutaneous adverse reactions (SCARs) are difficult. OBJECTIVE: To determine the benefit of HLA-B allele prescreening and the measurement of drug-specific IFN-γ-releasing cells in the prevention and identification of the culprit drug in patients with SCARs. METHODS: A total of 160 patients with SCARs were recruited from 6 university hospitals in Thailand over a 3-year period. HLA-B alleles were genotypically analyzed. The frequencies of drug-specific IFN-γ-releasing cells in patients with SCARs were also measured. RESULTS: The drugs commonly responsible for SCARs were anticonvulsants, allopurinol, beta-lactams, antituberculosis agents, and sulfonamides. If culprit drugs had been withheld in patients carrying known HLA-B alleles at risk, it would have prevented 21.2% of SCAR cases, mainly allopurinol- and carbamazepine-related SCARs. Culprit drug-specific IFN-γ-releasing cells could be identified in 45.7% (53 of 116) of patients with SCARs caused by 5 major drug groups, particularly in patients diagnosed with drug reactions with eosinophilia and systemic symptoms (DRESS) (50.0%), followed by Stevens-Johnson syndrome/toxic epidermal necrolysis (46.0%), and acute generalized exanthematous pustulosis (31.3%). According to our study, high frequencies of drug-specific IFN-γ-releasing cells were significantly demonstrated in patients who suffered from DRESS phenotype, having anticonvulsants or the drugs belonging to the "probable" category based on the Naranjo algorithm scale, as the culprit drugs. CONCLUSIONS: HLA-B prescreening would succeed in preventing only a minority of SCAR victims. Drug-specific IFN-γ-releasing cells are detectable in almost half of patients. Better strategies are required for better SCAR prevention and culprit drug confirmation.

Treatment of keratosis pilaris with 810-nm diode laser: a randomized clinical trial.

IMPORTANCE: Keratosis pilaris (KP) is a common skin disorder of follicular prominence and erythema that typically affects the proximal extremities, can be disfiguring, and is often resistant to treatment. Shorter-wavelength vascular lasers have been used to reduce the associated erythema but not the textural irregularity. OBJECTIVE: To determine whether the longer-wavelength 810-nm diode laser may be effective for treatment of KP, particularly the associated skin roughness/bumpiness and textural irregularity. DESIGN, SETTING, AND PARTICIPANTS: We performed a split-body, rater-blinded, parallel-group, balanced (1:1), placebo-controlled randomized clinical trial at a dermatology outpatient practice of an urban academic medical center from March 1 to October 1, 2011. We included all patients diagnosed as having KP on both arms and Fitzpatrick skin types I through III. Of the 26 patients who underwent screening, 23 met our enrollment criteria. Of these, 18 patients completed the study, 3 were lost to or unavailable for follow-up, and 2 withdrew owing to inflammatory hyperpigmentation after the laser treatment. INTERVENTIONS: Patients were randomized to receive laser treatment on the right or left arm. Each patient received treatment with the 810-nm pulsed diode laser to the arm randomized to be the treatment site. Treatments were repeated twice, for a total of 3 treatment visits spaced 4 to 5 weeks apart. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in disease severity score, including redness and roughness/bumpiness, with each graded on a scale of 0 (least severe) to 3 (most severe), between the treated and control sites. Two blinded dermatologists rated the sites at 12 weeks after the initial visit. RESULTS: At follow-up, the median redness score reported by the 2 blinded raters for the treatment and control sides was 2.0 (interquartile range [IQR], 1-2; P = .11). The median roughness/bumpiness score was 1.0 (IQR, 1-2) for the treatment sides and 2.0 (IQR, 1-2) for the control sides, a difference of 1 (P = .004). The median overall score combining erythema and roughness/bumpiness was 3.0 (IQR, 2-4) for the treatment sides and 4.0 (IQR, 3-5) for the control sides, a difference of 1 (P = .005). CONCLUSIONS AND RELEVANCE: Three treatments with the 810-nm diode laser may induce significant improvements in skin texture and roughness/bumpiness in KP patients with Fitzpatrick skin types I through III, but baseline erythema is not improved. Complete treatment of erythema and texture in KP may require diode laser treatment combined with other laser or medical modalities that address redness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01281644.

Multicenter prospective cohort study of the incidence of adverse events associated with cosmetic dermatologic procedures: lasers, energy devices, and injectable neurotoxins and fillers.

IMPORTANCE: Common noninvasive to minimally invasive cosmetic dermatologic procedures are widely believed to be safe given the low incidence of reported adverse events, but reliable incidence data regarding adverse event rates are unavailable to date. OBJECTIVE: To assess the incidence of adverse events associated with noninvasive to minimally invasive cosmetic dermatologic procedures, including those involving laser and energy devices, as well as injectable neurotoxins and fillers. DESIGN, SETTING, AND PARTICIPANTS: A multicenter prospective cohort study (March 28, 2011, to December 30, 2011) of procedures performed using laser and energy devices, as well as injectable neurotoxins and soft-tissue augmentation materials, among 8 geographically dispersed US private and institutional dermatology outpatient clinical practices focused on cosmetic dermatology, with a total of 23 dermatologists. Participants represented a consecutive sample of 20 399 cosmetic procedures. Data acquisition was for 3 months (13 weeks) per center, with staggered start dates to account for seasonal variation. EXPOSURES: Web-based data collection daily at each center to record relevant procedures, by category type and subtype. Adverse events were detected by (1) initial observation by participating physicians or staff; (2) active ascertainment from patients, who were encouraged to self-report after their procedure; and (3) follow-up postprocedural phone calls to patients by staff, if appropriate. When adverse events were not observed by physicians but were suspected, follow-up visits were scheduled within 24 hours to characterize these events. Detailed information regarding each adverse event was entered into an online form. MAIN OUTCOMES AND MEASURES: The main outcome was the total incidence of procedure-related adverse events (total adverse events divided by total procedures performed), as verified by clinical examination. RESULTS: Forty-eight adverse events were reported, for a rate of 0.24% (95% CI, 0.18%-0.31%). Overall, 36 procedures resulted in at least 1 adverse event, for a rate of 0.18% (95% CI, 0.13%-0.25%). No serious adverse events were reported. Adverse events were infrequently associated with known risk factors. CONCLUSIONS AND RELEVANCE: Noninvasive to minimally invasive cosmetic dermatologic procedures, including energy, neurotoxin, and filler procedures, are safe when performed by experienced board-certified dermatologists. Adverse events occur in less than 1% of patients, and most of these are minor and transient.