Factors Associated with Dupilumab Response in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Dupilumab was approved for treating moderate to severe atopic dermatitis (AD). However, a notable subset of patients remains unresponsive and factors associated with dupilumab response remain limited. OBJECTIVE: To review and establish factors related to dupilumab response systematically in AD. METHODS: We searched electronic databases, including PubMed and MEDLINE, Embase, Ovid, and the Cochrane Center of Controlled Trials from inception to March 2023. The primary outcome was factors linked to dupilumab response in AD. The odds ratios and 95% CIs related to a 75% reduction at 12 to 16 weeks in the Eczema Area and Severity Index (EASI) score were synthesized using a random-effects meta-analysis. RESULTS: Of 21 studies involving 5,575 patients with AD, three were post hoc analyses of phase 3 dupilumab studies, 12 were retrospective, and six were prospective studies. Factors associated with favorable responses to dupilumab, defined by the percentage of patients achieving EASI75 at 12 to 16 weeks, included female sex (OR [95% CI] = 2.16 [1.38-3.38]), young age (2.81 [1.64-4.81]), absence of allergic rhinitis (2.64 [1.07-6.50]), low body mass index (1.97 [1.18-3.30]), and low blood eosinophil count (6.47 [3.36-12.48]), with very low certainty of evidence. Age at onset, baseline EASI score, total IgE level, and serum lactate dehydrogenase level were unrelated to dupilumab response. CONCLUSIONS: Female sex, young age, absence of allergic rhinitis, low body mass index, and low blood eosinophil count were associated with a favorable response to dupilumab in patients with AD. These factors should be taken into account when considering dupilumab therapy in clinical practice.

Prevalence and characteristics of adult patients with adult-onset and childhood-onset food allergy.

BACKGROUND: IgE-mediated food allergy (FA) affects health-related quality of life, and may cause life-threatening reactions. Few studies characterizing adult FA patients have been reported, especially first ever reaction (FER) in adult-onset. OBJECTIVE: We describe the characteristics of adult FA patients, especially FER and compare these characteristics between childhood- and adult-onset FA. METHODS: A cross-sectional study of all adult patients visiting the Allergy Clinic, Siriraj Hospital at the outpatient department between January 2009 to December 2019 was conducted. Demographic, clinical data, and first reaction in life data were collected. Adult-onset was defined as ≥ 18 years old. RESULTS: Of 711 patients visiting the clinic, 174 (24.4%) were FA with a median age of 31.0 years (interquartile range 24.0, 44.0 years); 29.3% were male. FA patients had significantly higher prevalence of sensitization to cockroach compared with non-FA patients (67.4% vs. 56.3%); p = 0.016). The three most common food triggers were shellfish (68.0%), wheat (28.7%), and fruit and vegetables (10.0%). Before diagnosis, 56.7% (97/171) experienced at least 1 food-related anaphylaxis. Of the 166 patients compared on age of onset, 127 (76.5%) were adult-onset. In FER, patients with adult-onset had significantly more reactions to fruit and vegetables, more respiratory system involvement, and more other systems involvement [OR 8.95 (1.13, 1157); p = 0.034; OR 3.15 (95%CI 1.30, 8.25), p = 0.011; OR 10.8 (1.35, 1404), p = 0.019, respectively]. In sensitivity analysis, the cardiovascular system involvement was also significantly more common [OR 2.78 (1.05, 9.15); p = 0.038]. CONCLUSIONS: Shellfish was the most common trigger foods in adult FA patients. In FER, anaphylaxis was common for adult-onset. Adult-onset FA patients also had more respiratory, cardiovascular, and other systems involvements than childhood-onset ones. FA awareness, early diagnosis, and proper management are encouraged. Further studies on the adult-onset food allergic patients are required.

Risk Factors, Clinical Characteristics, Management, and Outcomes of Musculoskeletal Fungal Infection at Thailand's Largest National Tertiary Referral Center.

To investigate the risk factors, clinical characteristics, management, and outcomes of musculoskeletal fungal infection in Thai patients, patients aged ≥18 years definitively diagnosed with musculoskeletal fungal infection by culture and/or histopathology at Siriraj Hospital (Bangkok, Thailand) during 2002-2020 were retrospectively enrolled. Twenty-eight patients (median age: 58.5 years [range: 22-81], 57.1% male) with fungal osteomyelitis (n = 22), septic arthritis (n = 1), or fungal osteomyelitis with septic arthritis (n = 5) were included. Immunocompromised status was common (82%). Most patients had de novo infection from hematogenous spreading that usually presented at a single, non-contiguous site. The median symptom duration prior to diagnosis was 2 months. The tibia and knee were the most common site of osteomyelitis (30%) and septic arthritis (72%), respectively. The most common pathogens were Talaromyces marneffei and Cryptococcus neoformans. Organism identification from tissues at the affected sites was required in all cases. Most patients (82%) required combination surgery and systemic antifungal therapy. Among those with complete follow-up (23/28), 61% and 39% had complete and partial responses, respectively. Musculoskeletal fungal infection is an uncommon disease with insidious onset and non-specific manifestations that requires pathogen identification via tissue cultures and histopathologic studies. Combination surgery and systemic antifungal therapy yielded generally favorable outcomes.

Two Novel GATA1 Mutations in Transient Abnormal Myelopoiesis of Thai Neonates with Down Syndrome.

Children with Down syndrome (DS) are 150 times more likely to develop acute myeloid leukemia (ML-DS), compared with those without. One risk factor is transient abnormal myelopoiesis (TAM). Somatic truncating GATA1 mutations are found in most TAM patients and are markers for future ML-DS. We identified two novel frameshift mutations in our seven newborns with DS and TAM: a heterozygous mutation of 17 nucleotide duplication (c.154_170 dup) and a heterozygous 9-nucleotide deletion combined with a 2-nucleotide insertion (c.150_158delins CT). Both mutations introduced a truncated GATA1 protein. Thus, neonates with DS and TAM require frequent ML-DS monitoring.