A large single-center cohort of bare lymphocyte syndrome: Immunological and genetic features in Turkey.

Major histocompatibility complex class II (MHC-II) deficiency or bare lymphocyte syndrome (BLS) is a rare, early-onset, autosomal recessive, and life-threatening inborn error of immunity. We aimed to assess the demographic, clinical, laboratory, follow-up, and treatment characteristics of patients with MHC-II deficiency, together with their survival. We retrospectively investigated 21 patients with MHC-II deficiency. Female/male ratio was 1.63. The median age at diagnosis was 16.3 months (5 months-9.7 years). Nineteen patients (90.5%) had parental consanguinity. Pulmonary diseases (pneumonia, chronic lung disease) (81%), diarrhoea (47.6%), and candidiasis (28.6%) were common. Four (19%) had autoimmunity, two developed septic arthritis, and three (14%) developed bronchiectasis in the follow-up. Three patients (14%) had CMV viraemia, one with bilateral CMV retinitis. Eight (38.1%) had lymphocytopenia, and four (19%) had neutropenia. Serum IgM, IgA, and IgG levels were low in 18 (85.7%), 15 (71.4%), and 11 (52.4%) patients, respectively. CD4+ lymphocytopenia, a reversed CD4+/CD8+ ratio, and absent/low HLA-DR expressions were detected in 93.3%, 86.7%, and 100% of the patients, respectively. Haematopoietic stem cell transplantation (HSCT) was performed on nine patients, and four died of septicaemia and ARDS after HSCT. The present median age of patients survived is 14 years (1-31 years). Genetic analysis was performed in 10 patients. RFX5 homozygous gene defect was found in three patients (P1, P4 and P8), and RFXANK (P2 and P14) and RFXAP (P18 and P19) heterozygous gene defects were found in each two patients, respectively. This large cohort showed that BLS patients have severe combined immunodeficiency (SCID)-like clinical findings. Flow cytometric MHC-II expression study is crucial for the diagnosis, differential diagnosis with SCID, early haematopoietic stem cell transplantation (HSCT), and post-HSCT follow-up. Genetic studies are required first for matched family donor evaluation before HSCT and then for genetic counselling.

Cupressus arizonica: an emerging aeroallergen for East Mediterranean children.

Background/aim: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia. Materials and methods: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy. Results: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC- subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC- subgroup during the relevant pollen season. Conclusion: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean.

The treatment journey of children with moderate to severe atopic dermatitis in Türkiye: unmet needs.

BACKGROUND: Atopic dermatitis (AD) substantially burdens individuals, families, and healthcare systems. We aimed to document the treatment journey of pediatric patients with moderate-to-severe AD in a referral center based in our country. METHODS: This retrospective study reviewed patients aged 1-18 years diagnosed with AD, seeking systemic treatment recommendations from the "pediatric allergy and dermatology multidisciplinary team meeting". RESULTS: Over the 14-month study period, 30 (12.5%) of 240 AD patients were evaluated in the pediatric dermato-allergy team meetings. The median age of the patients was 13.66 years (Q1-Q3: 7.94-17.27), of whom 60% were male. The median annual healthcare visits for AD were 4 (Q1-Q3: 1.00-8.75). Among the study group, 70% were sensitized to aeroallergens, and admission markers included total IgE (median: 1980 IU/mL, Q1-Q3: 794.50-5446), and eosinophil counts (median: 650, Q1-Q3: 275-1275). All patients utilized intermittent and/or continuous topical corticosteroids (CS), with 56.6% employing short-term/long-term topical tacrolimus. Over the past two years, systemic CSs were utilized in 93.3% of the patients, whereas 57.1% received more than one course. Approximately 43.3% of the patients agreed to receive systemic cyclosporine treatment, with only 30.8% benefiting and 3.3% reporting adverse effects (hypertrichosis and cellulitis). Three patients self-funded dupilumab, all benefiting without adverse effects. Omalizumab, mycophenolate mofetil and narrow-band  ultraviolet (UV) treatments were used in one patient each, with limited benefit observed. Health insurance did not grant approval for a Janus kinase inhibitor for one patient. CONCLUSIONS: Managing moderate to severe AD is complex and costly, considering disease heterogeneity, comorbidities, care pathways, and health system challenges. Addressing the unmet needs should be a priority in Türkiye's healthcare systems.