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.

Immunogenicity, Effectiveness, and Safety of COVID-19 Vaccines among Patients with Immune-Mediated Dermatological Diseases: A Systematic Review and Meta-analysis.

Immunocompromised individuals, primarily attributable to using immunosuppressants, face heightened COVID-19 risks. Despite the proven efficacy of COVID-19 vaccines, their impact on patients with immune-mediated dermatological diseases remains unclear. This study aims to thoroughly examine vaccine immunogenicity, effectiveness, and safety in immune-mediated dermatological disease patients. Clinical studies in adults that compared vaccinated immune-mediated dermatological disease patients with vaccinated healthy controls or unvaccinated immune-mediated dermatological disease patients in terms of vaccine immunogenicity, COVID-19 infection, adverse events, or exacerbation of immune-mediated dermatological diseases were searched via electronic databases. Seventeen studies (1,348,690 participants) were included. Seroconversion rates between immune-mediated dermatological disease patients and healthy controls were not different. However, among individuals aged ≤55 years, immune-mediated dermatological disease patients had lower mean anti-SARS-CoV-2 IgG levels. Immunosuppressed immune-mediated dermatological disease patients also had lower titres and were less likely to achieve T-cell response. In terms of safety, the risk of adverse events was higher in atopic dermatitis patients, but those with psoriasis had a reduced risk. Additionally, immunosuppressed patients had fewer adverse events. Vaccinated immune-mediated dermatological disease patients had a lower risk of COVID-19 infection than unvaccinated patients but a higher risk than healthy controls; however, disease exacerbation may be induced. In conclusion, immune-mediated dermatological diseases showed a reduced vaccine response in our meta-analysis, yet vaccination remained effective against COVID-19 infection and well tolerated.

A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases.

BACKGROUND: Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce. OBJECTIVES: To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination. METHODS: This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination. RESULTS: Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD. CONCLUSIONS: Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.

Genotypic and Phenotypic Characteristics of Co-Trimoxazole-Induced Cutaneous Adverse Reactions.

BACKGROUND: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs). METHODS: The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated. RESULTS: Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE. CONCLUSIONS: Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Trichoscopic Signs in Dermatomyositis, Systemic Lupus Erythematosus, and Systemic Sclerosis: A Comparative Study of 150 Patients.

BACKGROUND: Hair and scalp involvement is prevalent in connective tissue diseases (CTDs). Trichoscopic features may provide a diagnostic implementation and enable differentiation among CTDs; however, a direct comparison of these signs among CTD patients is lacking. OBJECTIVES: To compare trichoscopic findings in dermatomyositis (DM), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) as well as determine their distinctive features and associations with disease activity. METHODS: Trichoscopic photographs were taken from DM, SLE, and SSc patients and further evaluated for hair shaft and scalp surface abnormalities. Data regarding patients' clinical manifestations, laboratory results, and disease activity were analyzed. RESULTS: One hundred fifty participants, consisting of 30 DM, 60 SLE, and 60 SSc patients, were included. Perifollicular red-brown pigmentation, brown scattered pigmentation, and white patches were exclusive findings in DM, SLE, and SSc, respectively (p < 0.001). A multinomial logistic regression analysis revealed that DM demonstrated higher odds for having microaneurysmal blood vessels than SLE and SSc (odds ratio [OR] = 22.22, 95% confidence interval [CI] = 1.73-285.13, p = 0.017, and OR = 15.34, 95% CI = 1.36-177.59, p = 0.029, respectively). Polymorphic vessels forming a telangiectatic network suggested SSc over SLE (OR = 12.83, 95% CI = 1.35-121.98, p = 0.026), while avascular areas were more pronounced in SSc than DM and SLE (OR = 43.24, 95% CI = 5.17-361.67, p = 0.001, and OR = 0.03, 95% CI = 0.01-0.24, p = 0.001, respectively). In a quantile regression analysis, perifollicular red-brown pigmentation, reduction in hair diameter, and the absence of thin arborizing vessels were linked to higher disease activity in DM, SLE, and SSc, respectively (all p < 0.05). CONCLUSIONS: Trichoscopy is a valuable tool possessing diagnostic and prognostic values for CTDs. Specific trichoscopic features allow adequate distinction between DM, SLE, and SSc and may help identify active disease.

Comparative Analyses of Clinical Features, Histopathology, and CD123 Immunohistochemistry of Oral Lupus Erythematosus, Lichen Planus, and Other Lichenoid Lesions.

BACKGROUND: Oral lupus erythematosus (OLE) and oral lichen planus (OLP) are among the common causes of oral lichenoid lesions (OLLs). The differential diagnosis among causes of OLLs, particularly between OLE and OLP, is challenging as they have significant clinical and histopathological overlap. OBJECTIVES: To compare and summarize the clinical, histopathological, and direct immunofluorescence (DIF) findings between OLE, OLP, and other OLLs and to explore the diagnostic value of CD123 immunohistochemistry. METHODS: A retrospective study on patients with OLE, OLP, and other OLLs was performed between January 2014 and December 2019. The baseline characteristics, the clinical, histopathological, and DIF features, as well as CD123 immunohistochemistry for plasmacytoid dendritic cells (PDCs) were statistically analyzed and compared between groups. RESULTS: Of 70 patients, 12 had OLE, 39 had OLP, and 19 had other OLLs. Oral erosions/ulcers were the most common findings in all three groups. Red macules, telangiectases, and discoid plaques were more common in OLE patients, while OLP cases were typified by reticulated patches (p < 0.05). Additionally, white patches were found more often in other OLLs than in both OLE and OLP (p = 0.002). Histologically, mucosal atrophy, basal vacuolization, and perivascular infiltrate were observed in OLE, whereas OLP specimens possessed mucosal hyperplasia, hypergranulosis, and compact orthokeratosis (p < 0.05). Mucosal spongiosis was a histologic feature that favored other OLLs over OLE and OLP (p < 0.001). Data on DIF were nonspecific for all three conditions. For immunohistochemical staining, the median number of total CD123+ PDCs was observed to be higher in OLE than OLP in the mucosal-submucosal junction (MSJ) (p = 0.021), the superficial perivascular area (p = 0.026), and the superficial and deep perivascular areas (p = 0.001). Likewise, PDCs in clusters ≥2+ were seen in significantly higher numbers on OLE than OLP along the MSJ (p = 0.002), the superficial perivascular area (p < 0.001), as well as the superficial and deep perivascular areas (p = 0.011). CD123+ PDCs were found to be significantly more numerous in both OLE and OLP than other OLLs in all of the abovementioned areas (all p < 0.05). CONCLUSION: While there are some differences in the clinicopathological features between OLE, OLP, as well as other OLLs, a significant overlap remains. The quantity and distribution pattern of CD123 immunohistochemical staining has a diagnostic implication in differentiating OLE from OLP and other OLLs.

Cutaneous, systemic features and laboratory characteristics of late- versus adult-onset systemic lupus erythematosus in 1006 Thai patients.

BACKGROUND: Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. OBJECTIVE: To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients. METHODS: Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. RESULTS: Of 1006 SLE patients, 740 and 226 had adult- (15-50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively (p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. CONCLUSIONS: Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.

Anti-BP180 and anti-BP230 enzyme-linked immunosorbent assays for diagnosis and disease activity tracking of bullous pemphigoid: A prospective cohort study.

BACKGROUND: Autoantibodies against BP180 and BP230 play major roles in bullous pemphigoid (BP). We are the first to describe the values of serum anti-BP180 IgG and anti-BP230 IgG enzyme-linked immunosorbent assays (ELISA) for diagnosis and disease monitoring of BP among Thai patients. OBJECTIVE: We aimed to determine the diagnostic performance of anti-BP180 IgG and anti-BP230 IgG in BP, to correlate disease activity with autoantibody levels through follow-ups, and to relate BP comorbidities with disease activity and autoantibody levels. METHODS: Consecutive patients suspected of having BP were included. Skin biopsy, direct immunofluorescence, and serum anti-BP180 IgG and anti-BP230 IgG tests were performed. BP disease area index (BPDAI) was evaluated at diagnosis and throughout follow-ups. RESULTS: Of 131 patients, 68 were diagnosed with BP, and 63 were included as controls. Sensitivity and specificity of serum anti-BP180 IgG were 69.1% and 90.5%, respectively, while those of serum anti-BP230 IgG were 55.9% and 85.5%, respectively. Using anti-BP180 and anti-BP230 IgG antibodies resulted in a 7% increase in sensitivity compared with using anti-BP180 IgG antibody alone. Significant correlation with BPDAI was found for both autoantibodies at diagnosis but only for anti-BP180 IgG at follow-ups (p = 0.013). BP patients with positivity to anti-BP180 or anti-BP230 IgG had significantly higher BPDAI than did those without (p = 0.005). BP was associated with neurological diseases (p = 0.025), while patients with diabetes had higher disease activity (p = 0.010). CONCLUSIONS: While both serum autoantibodies are useful for diagnosing BP in patients with suspicious clinical features, only anti-BP180 IgG allowed prediction of disease activity over time.

The behavior, attitude, and knowledge towards photoprotection in patients with cutaneous/systemic lupus erythematosus: a comparative study with 526 patients and healthy controls.

OBJECTIVE: To evaluate the attitude, knowledge, and behavior towards the sun protection in systemic lupus erythematosus (SLE) patients with and without cutaneous involvement (CLE) compared to non-photosensitive controls and to determine influential factors for photoprotective practices in SLE patients. METHODS: A case-control study was performed. Patients and controls completed a self-reported questionnaire. For SLE patients, the presence of organ involvement, disease activity and laboratory data were acquired from their physical examination and medical records. RESULTS: A total of 263 SLE patients and 263 healthy controls were recruited. SLE patients had statistically significant better photoprotective practices than controls, i.e. exposure to sunlight <1 hour per day (76.1% vs. 48.3%, OR, 3.40; 95% CI, 2.34-4.93, p < 0.001), less outdoor activities (9.8% vs. 19.1%, OR, 0.44; 95% CI, 0.26-0.71, p = 0.003), wore long-sleeved shirts (57.0% vs. 32.7%, OR, 2.73; 95% CI, 1.92-3.89, p < 0.001) and hats (43.8% vs. 26.6%, OR 2.14; 95% CI, 1.49-3.09, p < 0.001). SLE with CLE subgroup had the highest percentage for regular practice in almost all sun protective means compared to SLE without CLE and controls. SLE with CLE patients had more diligent sunscreen application with higher percentage of consistent use (93.7% vs. 59.3%, OR, 11.66; 95% CI, 2.57-52.89, p = 0.001) and adequate application (58.1% vs. 24.6%, OR, 4.24; 95% CI, 1.93-9.30, p < 0.001) compared to those without CLE. Previous and current CLE were influential factors for adherence to photoprotective methods, while the extracutaneous involvement was not. The majority of SLE patients were well acquainted with the harm of sunlight to their diseases (91.6%). However, 40.1% of them did not perceive that sunlight could escalate their internal flare, which may have led to inferior photoprotective practices in patients with extracutaneous involvement. CONCLUSION: SLE patients had good awareness and practiced better photoprotection than controls. The cutaneous sign is a predictor for superior photoprotective behavior. Education regarding the harms of sunlight and the importance of appropriate photoprotection should be emphasized, especially in SLE cases without cutaneous involvement.

Successful treatment of normocomplementemic urticarial vasculitis with omalizumab: A report of three cases and literature review.

Urticarial vasculitis (UV) is a rare form of cutaneous leukocytoclastic vasculitis with persistent urticarial lesions. UV may be severe and refractory to standard treatment including antihistamines, anti-inflammatories, antimalarials, corticosteroids and immunosuppressants. Omalizumab, an anti-IgE antibody, is approved for chronic spontaneous urticaria. However, its benefit for UV remains controversial. We report, herein, three patients with normocomplementemic UV and angioedema. All patients were diagnosed with chronic urticaria preceding the presentation of painful urticarial plaques. The diagnosis of UV was confirmed by skin biopsy and/or direct immunofluorescence. All patients had none or minimal response to standard treatments. Initial omalizumab dosing of 150 mg was administered subcutaneously (SC), however, increment to 300 mg monthly was necessary in 2 patients to control the disease. All 3 patients remained in complete remission after minimum follow up period of 9 months. To conclude, omalizumab has shown to be beneficial for severe normocomplementemic UV in our series.

Nonscarring alopecia in systemic lupus erythematosus: A cross-sectional study with trichoscopic, histopathologic, and immunopathologic analyses.

BACKGROUND: Nonscarring alopecia in systemic lupus erythematosus (SLE) is widely recognized, but reports on its clinical, trichoscopic, histopathologic, and direct immunofluorescence (DIF) features are still limited. OBJECTIVE: To summarize the different clinical patterns, trichoscopic, histopathologic, and DIF features of nonscarring alopecia in SLE and to prove its association with disease activity. METHODS: Patients with SLE with and without nonscarring alopecia had full physical/trichoscopic examination and scalp biopsy. Their disease activity scores and laboratory data were evaluated and statistically analyzed. RESULTS: Thirty-two patients with SLE had different patterns of nonscarring alopecia, including mild diffuse alopecia (43.8% [n = 14]), severe diffuse alopecia (15.6% [n = 5]), patchy alopecia (28.1% [n = 9]), and lupus hair (12.5% [n = 4]). The most common trichoscopic findings were arborizing/interconnecting vessels (83% [n = 26]). Histopathologic examination showed interface changes along the dermoepidermal junction (87.5% [n = 28]) and follicular epithelium (40.6% [n = 13]). On DIF, homogeneous granular deposition was detected along the dermoepidermal junction (78.1% [n = 25]) and follicular epithelium (78.1% [n = 25]). When compared with 10 patients with SLE without alopecia, there was a significantly higher SLE Disease Activity Index 2000 score and prevalence of proteinuria (>1 g/d). LIMITATIONS: This was a small, cross-sectional, single-center study. CONCLUSIONS: Nonscarring alopecia in SLE shows lupus erythematosus-specific changes on histology and DIF. Hair loss in SLE can be considered as an indicator of active disease.

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.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis-Like Lupus Erythematosus.

BACKGROUND/OBJECTIVE: Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like lupus erythematosus is a hyperacute and life-threatening form of cutaneous lupus erythematosus. Because of its rarity, little is known about this entity. We aimed to evaluate the clinical characteristics, laboratory findings, systemic manifestations, treatments, and outcome of SJS/ TEN-like lupus erythematosus. METHODS: We conducted a chart review study from July 2002 to September 2016 of all patients diagnosed with SJS/TEN-like lupus erythematosus who presented with gradual epidermal necrolysis without clear drug or infectious culprit. We evaluate for clinical features, extracutaneous involvement, Systemic Lupus Erythematosus Disease Activity Index, histologic findings, immunofluorescence pattern, serologic abnormalities, treatment, outcome, and recurrence of SJS/TEN-like lupus erythematosus. RESULTS: Of 9074 patients diagnosed with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 6 patients justified the diagnosis of SJS/TEN-like lupus erythematosus (5 SJS/TEN-like acute cutaneous lupus erythematosus, 1 TEN-like subacute cutaneous lupus erythematosus), accounting for 0.07%. Fifty percent had epidermal necrolysis as the initial presentation of lupus with a median time from onset of 1.5 months (0-48 months). The median duration between initial rash and epidermal detachment was 4.5 days (3-14 days). All had internal organ involvement (hematologic and renal) and high Systemic Lupus Erythematosus Disease Activity Index score (median, 19.5 [16-24]). Most recovered with systemic corticosteroids, antimalarial drugs, and/or immunosuppressants. None had disease recurrence. CONCLUSIONS: This is the largest single series of patients with SJS/TEN-like lupus erythematosus. Skin damage is an indicator of disease activity, and careful search for extracutaneous involvement to prevent further complications is mandatory.

Comparison of Q-switched Nd: YAG laser and fractional carbon dioxide laser for the treatment of solar lentigines in Asians.

BACKGROUND/OBJECTIVE: Solar lentigines are benign pigmented lesions that occur mostly on sun-exposed areas. Q-switched and ablative lasers are effective for removing these lesions but the high incidence of postinflammatory hyperpigmentation raises concern in darker skin types. The objective of this study is to compare the efficacy and degree of postinflammatory hyperpigmentation with the Q-switched Nd:YAG and fractional carbon dioxide (CO2 ) laser for treatment of solar lentigines in Asians. STUDY DESIGN: Twenty-five Thai patients (skin phototype III-IV) with at least two lesions of solar lentigines on upper extremities were enrolled in this study. Two lesions were randomly selected for the treatment with a single session of Q-switched Nd:YAG or fractional CO2 laser. Outcomes were evaluated using physician grading scale, colorimeter, and patient self-assessment at 6 and 12 weeks after treatment. Side effects were recorded. RESULTS: A total of 532 nm Q-switched Nd:YAG laser showed significant improvement of pigmentation over fractional CO2 laser at 6th and 12th week by both colorimeter assessment and physician grading scale (P < 0.05). No significant difference in postinflammatory hyperpigmentation from both lasers was observed. In terms of patient self-assessment, 80% of the patients treated with 532 nm Q-switched Nd:YAG laser had excellent results compared to 8% in fractional CO2 laser group. However, fractional CO2 laser treatment had faster healing time and less pain score compared to Q-switched Nd:YAG laser. CONCLUSIONS: Q-switched Nd:YAG is superior to fractional CO2 laser for treatment of solar lentigines but requires longer healing time and produces more pain. The incidence of postinflammatory hyperpigmentation was not significantly different with both lasers. Further studies are needed to obtain the proper parameter and the treatment frequency of fractional CO2 laser in solar lentigines.

A comparative study of combined treatment with fractional carbon dioxide and targeted ultraviolet B phototherapy for facial vitiligo.

Facial vitiligo is associated with considerable psychological impact. The management is challenging and requires multidisciplinary treatment. Adding fractional carbon dioxide (CO2) to the conventional treatment has been reported as an effective modality. This study aimed to evaluate the efficacy of combined fractional CO2 laser, targeted ultraviolet B (UVB) phototherapy, and topical steroid on facial vitiligo. A prospective, randomized, split face study was conducted on 14 patients with symmetrical non-segmental facial vitiligo. Ten sessions of fractional CO2 laser was performed on the lesions on one side of face with 2-week interval. Immediately after laser, the lesions on both side of face were treated with 10 sessions of 2-week interval targeted UVB phototherapy and twice daily application of topical 0.05 % clobetasol propionate cream. The patients were followed up for 12 weeks after the last treatment. Clinical improvement was graded by blinded dermatologists and patients using a quartile grading scale. Twelve out of 14 patients completed the study. The degree of improvement was not different between both sides in nine patients. One patient showed more improvement on the combined laser side, and two patients showed inferior results on the combined laser side. Two patients with lesser improvement on the laser-treated side had positive Koebner phenomenon on the non-facial area. The combined treatment with laser, targeted UVB, and topical steroids are not superior to targeted UVB and topical steroids in facial vitiligo. Furthermore, laser may retard the response to the standard treatment in patients with Koebner phenomenon on non-treated areas.

Panitumumab-Induced Periorbital Dermatitis: A Case Report.

Panitumumab is a recombinant, fully humanized immunoglobulin G2 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is approved for the first- and second-line treatment of advanced wild-type KRAS colorectal cancer. Although common cutaneous side effects include acneiform dermatitis, folliculitis, and xerosis, ocular toxicities have occasionally been reported. Herein, we report the case of an 81-year-old Thai female with chemorefractory advanced stage sigmoid colon cancer who developed isolated periorbital dermatitis following treatment with panitumumab plus modified FOLFOX6. The cutaneous adverse reaction recurred after subsequent infusions; however, it was alleviated by topical therapy. To our knowledge, panitumumab-induced periorbital dermatitis is exceptionally rare. To raise awareness of potential periocular cutaneous side effects in patients taking EGFR inhibitors, the published literature regarding periorbital dermatitis induced by these agents has also been reviewed in this article. Periorbital dermatitis should be considered as a potential cutaneous reaction following panitumumab administration, and should be promptly treated.

Novel genetic variants of HLA gene associated with Thai Behcet's disease (BD) patients using next generation sequencing technology.

Behçet's disease (BD) manifests as an autoimmune disorder featuring recurrent ulcers and multi-organ involvement, influenced by genetic factors associated with both HLA and non-HLA genes, including TNF-α and ERAP1. The study investigated the susceptible alleles of both Class I and II molecules of the HLA gene in 56 Thai BD patients and 192 healthy controls through next-generation sequencing using a PacBio kit. The study assessed 56 BD patients, primarily females (58.9%), revealing diverse manifestations including ocular (41.1%), vascular (35.7%), skin (55.4%), CNS (5.4%), and GI system (10.7%) involvement. This study found associations between BD and HLA-A*26:01:01 (OR 3.285, 95% CI 1.135-9.504, P-value 0.028), HLA-B*39:01:01 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-B*51:01:01 (OR 3.033, 95% CI 1.135-8.103, P-value 0.027), HLA-B*51:01:02 (OR 6.176, 95% CI 1.428-26.712, P-value 0.015), HLA-C*14:02:01 (OR 3.485, 95% CI 1.339-9.065, P-value 0.01), HLA-DRB1*14:54:01 (OR 1.924, 95% CI 1.051-3.522, P-value 0.034), and HLA-DQB1*05:03:01 (OR 3.00, 95% CI 1.323-6.798, P-value 0.008). However, after Bonferroni correction none of these alleles were found to be associated with BD. In haplotype analysis, we found a strong linkage disequilibrium in HLA-B*51:01:01, HLA-C*14:02:01 (P-value 0.0, Pc-value 0.02). Regarding the phenotype, a significant association was found between HLA-DRB1*14:54:01 (OR 11.67, 95% CI 2.86-47.57, P-value 0.001) and BD with ocular involvement, apart from this, no distinct phenotype-HLA association was documented. In summary, our study identifies specific HLA associations in BD. Although limited by a small sample size, we acknowledge the need for further investigation into HLA relationships with CNS, GI, and neurological phenotypes in the Thai population.

Immunogenicity of Intradermal Versus Intramuscular BNT162b2 COVID-19 Booster Vaccine in Patients with Immune-Mediated Dermatologic Diseases: A Non-Inferiority Randomized Controlled Trial.

The intradermal route has emerged as a dose-sparing alternative during the coronavirus disease 2019 (COVID-19) pandemic. Despite its efficacy in healthy populations, its immunogenicity has not been tested in immune-mediated dermatologic disease (IMDD) patients. This assessor-blinded, randomized-controlled, non-inferiority trial recruited patients with two representative IMDDs (i.e., psoriasis and autoimmune bullous diseases) to vaccinate with fractionated-dose intradermal (fID) or standard intramuscular (sIM) BNT162b2 vaccines as a fourth booster dose under block randomization stratified by age, sex, and their skin diseases. Post-vaccination SARS-CoV-2-specific IgG and interferon-γ responses measured 4 and 12 weeks post-intervention were serological surrogates used for demonstrating treatment effects. Mean differences in log-normalized outcome estimates were calculated with multivariable linear regression adjusting for their baseline values, systemic immunosuppressants used, and prior COVID-19 vaccination history. The non-inferiority margin was set for fID to retain >80% immunogenicity of sIM. With 109 participants included, 53 received fID (all entered an intention-to-treat analysis). The fID demonstrated non-inferiority to sIM in humoral (mean outcome estimates of sIM: 3.3, ΔfID-sIM [mean, 95%CI]: -0.1, -0.3 to 0.0) and cellular (mean outcome estimates of sIM: 3.2, ΔfID-sIM [mean, 95%CI]: 0.1, -0.2 to 0.3) immunogenicity outcomes. Two psoriasis patients from the fID arm (3.8%) developed injection-site Koebner's phenomenon. Fewer fID recipients experienced post-vaccination fever (fID vs. sIM: 1.9% vs. 12.5%, p = 0.027). The overall incidence of disease flare-ups was low without a statistically significant difference between groups. The intradermal BNT162b2 vaccine is a viable booster option for IMDD patients troubled by post-vaccination fever; its role in mitigating the risk of flare-ups remains unclear.

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.