Background: Protein‐losing enteropathy is a rarely reported feature of CD46‐associated disease and may resemble CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein‐losing enteropathy (CHAPLE) syndrome. Associated hypogammaglobulinemia may be mistaken for primary antibody deficiency. Methods: We describe a 23‐year‐old woman with childhood‐onset enteropathy and hypogammaglobulinemia who had received immunoglobulin replacement for presumed common variable immunodeficiency since age 5. Multidisciplinary reassessment incorporated intestinal and renal histopathology, whole‐exome sequencing, family segregation, and longitudinal evaluation of the response to eculizumab. Results: Duodenal biopsy demonstrated intestinal lymphangiectasia, whereas kidney biopsy revealed chronic thrombotic microangiopathy with concurrent PLA2R‐negative membranous nephropathy. Serum C3 and C4 were within reference ranges. Sequencing identified homozygous CD46 c.565T>G (p.Tyr189Asp), with no pathogenic CD55 variant. The diagnostic laboratory reported the CD46 finding as a variant of uncertain significance. Family segregation and published functional evidence supported its clinical relevance, although patient‐specific functional confirmation was unavailable. Eculizumab promptly improved abdominal pain, vomiting, and oral intake. By April 2026, following dose escalation, serum albumin reached 4.3 g/dL and IgG 554 mg/dL, whereas proteinuria decreased from 5.95 to 2.4 g/day. Conclusion: This case supports considering CD46‐associated disease in adults with a CHAPLE‐like phenotype, particularly when enteric protein loss and hypogammaglobulinemia coexist with renal microangiopathy despite normal C3 and C4. The response to complement blockade supports a complement‐mediated disease process. Documented protein loss should prompt reassessment of a presumptive diagnosis of primary antibody deficiency.

Background/Aim: Data on the course of nonsteroidal anti‐inflammatory drug (NSAID) hypersensitivity in NSAID‐exacerbated cutaneous disease (NECD) are limited. We aimed to evaluate NSAID tolerance in NECD patients with well‐controlled urticaria. Methods: 142 patients with well‐controlled urticaria [Urticaria Control Test (UCT) ≥ 12; Urticaria Activity Score over 7 days (UAS7) ≤ 6] underwent a single blind, placebo‐controlled acetylsalicylic acid (ASA) provocation test. Patients were categorized into three groups based on their treatment; omalizumab, antihistamine, or no treatment. Results: The median age of the patients was 40 years (IQR 31.5–52), and 79.6% were female. The median disease duration of chronic spontaneous urticaria (CSU) was 4 years (IQR 2–8). The ASA provocation test was positive in 29 patients (20.4%). Positive patients had lower UCT and higher UAS7 scores (both p < 0.001). ASA provocation test positivity was more common in the antihistamine group compared to both the omalizumab ( p = 0.001) and untreated groups ( p < 0.001). ROC analysis showed that UCT ≤ 15 predicted ASA provocation test positivity with 72.4% sensitivity and 83.2% specificity, while UAS7 ≥ 4 predicted positivity with 72.4% sensitivity and 86.7% specificity. The negative predictive values (NPV) were 92.2% and 92.5%, respectively. Conclusion: To our knowledge, this is the first study to demonstrate, in a large NECD cohort, that NSAID tolerance can be achieved in patients with well‐controlled urticaria under different treatment modalities, regardless of complete remission status. UCT ≤ 15 and UAS7 ≥ 4 are useful clinical predictors of provocation test positivity and, given their high NPVs, are particularly valuable for excluding positivity.

Background/Objective: The psychological impact of in vivo diagnostic procedures remains poorly understood. We assessed changes in psychological distress and drug hypersensitivity-related quality of life (QoL) throughout a diagnostic evaluation for suspected immediate drug hypersensitivity reactions (IDHRs) and aimed to identify predictors of persistent psychological burden. Methods: This single-center prospective observational longitudinal study included 100 consecutive adults undergoing evaluation for suspected IDHRs. Psychological distress and QoL were assessed using the Depression Anxiety Stress Scale-21 (DASS-21) and the Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q). Assessments were performed before and after each diagnostic phase, including skin tests (STs), placebo, and drug provocation tests (DPTs). Results: The mean age was 44.2 ± 12.5 years, and women comprised 72% of the cohort. Depression, anxiety, stress, and DrHy-Q scores significantly decreased after ST, placebo, and DPT compared with baseline measurements. Across diagnostic stages, depression, anxiety, stress, and DrHy-Q scores were significantly lower during the DPT phase than during the ST and placebo phase in both pre-test and post-test measurements (p < 0.01 for pairwise comparisons). The number of prior HSRs showed a weak but significant positive correlation with DrHy-Q scores. In multivariable linear regression analysis, the number of prior HSRs was the only independent predictor of post-DPT DrHy-Q scores (β = 3.43, 95% CI 1.36–5.50, p = 0.001). Patients who avoided the provoked drug despite a negative DPT had higher DPT-post depression, anxiety, stress, and DrHy-Q scores. Conclusions: Psychological burden progressively decreased over the course of the stepwise diagnostic evaluation for suspected IDHRs, although patients with repeated reactions may benefit from additional support.