Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3. Low levels of interleukin (IL)-6-dependent phosphorylation and nuclear translocation (or accumulation) of STAT3 were observed in Epstein-Barr virus-transformed B lymphocytes (EBV-B cells) from all STAT3-deficient patients tested. The immunologic phenotype was characterized by high serum IgE levels (96% of the patients), memory B-cell lymphopenia (94.5%), and hypereosinophilia (80%). A low proportion of IL-17A-producing circulating T cells was found in 14 of the 15 patients tested. Mucocutaneous infections were the most frequent, typically caused by Staphylococcus aureus (all patients) and Candida albicans (85%). Up to 90% of the patients had pneumonia, mostly caused by Staph. aureus (31%) or Streptococcus pneumoniae (30%). Recurrent pneumonia was associated with secondary bronchiectasis and pneumatocele (67%), as well as secondary aspergillosis (22%). Up to 92% of the patients had dermatitis and connective tissue abnormalities, with facial dysmorphism (95%), retention of decidual teeth (65%), osteopenia (50%), and hyperextensibility (50%). Four patients developed non-Hodgkin lymphoma. The clinical outcome was favorable, with 56 patients, including 43 adults, still alive at the end of study (mean age, 21 yr; range, 1 mo to 46 yr). Only 4 patients died, 3 from severe bacterial infection (aged 1, 15, and 29 yr, respectively). Antibiotic prophylaxis (90% of patients), antifungal prophylaxis (50%), and IgG infusions (53%) improved patient health, as demonstrated by the large decrease in pneumonia recurrence. Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented.

Cataract surgery with primary intraocular lens implantation in children with uveitis: long-term outcomes.

PURPOSE: To report long-term outcomes of cataract surgery with primary posterior chamber intraocular lens (IOL) implantation in children with chronic uveitis. SETTING: Department of Ophthalmology, Pitié-Salpêtrière Hospital, Paris, France. DESIGN: Case series. METHODS: This case series comprised patients younger than 16 years with chronic uveitis who underwent phacoemulsification with primary implantation of a heparin surface-modified poly(methyl methacrylate) posterior chamber IOL in the capsular bag. The intraocular inflammation was fully controlled for at least 3 consecutive months before surgery in all cases. The main outcome measures were final corrected distance visual acuity (CDVA), postoperative inflammation, complications, and level of immunosuppressive treatment. RESULTS: Twenty-two eyes of 16 children (7 girls, 9 boys; median age at surgery 9.5 years old) were included. Underlying uveitic entities were juvenile idiopathic arthritis in 9 patients; idiopathic uveitis in 4; and Behçet disease, sarcoidosis, and varicella zoster-associated uveitis in 1 patient each. The final CDVA was 0.3 logMAR or better in all cases. Postoperative complications included posterior capsule opacification requiring laser capsulotomy in 2 eyes, glaucoma in 4 eyes, and cystoid macular edema/macular dysfunction in 3 eyes. The mean dose of oral prednisone was 29.5 mg/day preoperatively and 8.13 mg/day at the last follow-up. The median follow-up was 6 years (range 5 to 19 years). CONCLUSION: The results indicate that uveitis is not a formal contraindication to primary IOL implantation in the management of pediatric cataract surgery in cases with full control of intraocular inflammation. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.