Monogenic interferon-mediated diseases: novel phenotype and genotype characteristics from a Saudi population.

OBJECTIVES: IFN-mediated diseases are mendelian innate immunodysregulatory disorders that present early in life with fevers, sterile organ inflammation, and a high type-I IFN-response gene signature in peripheral blood cells. To date, monumental discoveries of novel genetic variants with various phenotypic features have been recognised. We aimed to describe the genotype and phenotype findings in Saudi children diagnosed with autoinflammatory interferonopathy and to report novel findings. METHODS: This is a descriptive retrospective cohort study of children with genetically confirmed type I interferonopathies. Medical records were reviewed for demographic, family history, clinical and laboratory data. All patients underwent genetic testing. RESULTS: A total of 20 patients (11 females) were included in the study. Sixteen patients (80%) presented within the first 2 years. The median age of disease onset was 0.87 years (IQR: 0.5-2) and the median age of diagnosis was 4.5 years (IQR: 2-7.5). The rates of consanguinity and family history of affected members were high (88% and 47%, respectively). Among the cohort of patients, whole exome sequencing was conducted for 15 patients. Three patients underwent targeted gene tests, and 2 patients had a leukoencephalopathy genetic panel. Eight patients were diagnosed with Aicardi-Goutières syndrome, attributed to variants in the RNASEH2A, RNASEH2C, and IFIH1 genes. Additionally, 2 patients were identified with STING-associated vasculopathy with onset in infancy linked to the TMEM173 variant. One patient exhibited chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature due to PSMB8, and another patient had DNase II. Moreover, 8 patients presented with rare interferonopathy conditions, including three with ISG15, 3 with ZNFX1, 1 with the SOCS1 variant, and 1 the STAT1 variant. Of 12 variants, six (50%) found to have novel genetic variants. The most frequent features were fever (75%), neurology (70%), mucocutaneous (60%), gastrointestinal (50%), and pulmonary (50%). Hypogammaglobinaemia and recurrent infections were seen in (45%) and (20%), respectively. Fifteen patients (75%) had elevated inflammatory markers. The majority of patients received intensive treatment, including corticosteroids, JAK inhibitors, IVIG, and various immunosuppressive agents. Despite these interventions, a partial response to treatment was observed, and cumulative disease damage primarily manifested as growth failure and developmental delay. CONCLUSIONS: Our findings support the previous reports; early-onset fever, neurology, and respiratory features should raise the suspicion of interferonopathies. However, there is eminent evidence of phenotypic variability. Our data also expanded the spectrum of clinical findings in relation to novel genetic variants.

Graft Versus Host Disease Following HLA-Matched Sibling Donor Compared with Matched Related Donor for Hematopoietic Stem Cell Transplantation for the Treatment of Severe Combined Immunodeficiency Disease.

BACKGROUND: One of the limiting factors for successful hematopoietic stem cell transplantation (HSCT) is graft versus host disease (GVHD). The EBMT/ESID guidelines for HSCT in severe combined immunodeficiency (SCID) recommend no GVHD prophylaxis for a matched sibling donor (MSD). OBJECTIVE: To determine the risk of GVHD in MSD HSCT for SCID patients compared to matched related donor (MRD). METHODS: This retrospective cohort study compares MSD with MRD and the outcome of GVHD in all SCID patients who underwent HSCT between 1993 and 2013. All statistical analyses were done using IBM SPSS statistics software. RESULTS: One hundred forty-five SCID patients underwent 152 HSCTs while 82 (54%) received GVHD prophylaxis. GVHD occurred in 48 patients (31.5%); 20/48 (42%) had GVHD prophylaxis compared to 28/48 (58%) that did not, P = 0.022. Acute GVHD occurred at a higher trend in MSD, 37/120 (30.8%), compared to MRD, 6/32 (18.8%), P = 0.17. We also analyzed the outcome according to the period of HSCT. The first period was 1993 to 2003, 48 HSCTs, 43 MSD, 5 MRD; all patients had GVHD prophylaxis, and there was no difference in GVHD. The second period was 2004 to 2013: of 104 HSCTs, 77 had MSD and 27 had MRD; GVHD prophylaxis was used in 22.1% of MSD and 63% of MRD, P = 0.000. GVHD was significantly higher in the MSD (40.2%) compared to MRD (18.5%) patients, P = 0.041. CONCLUSION: GVHD prophylaxis in MSD transplant should be considered in SCID patients.

Esophageal foreign bodies in children: Emphasis on complicated cases.

BACKGROUND: Esophageal foreign bodies (EFBs) are a relatively common clinical problem in pediatric patients. The majority of EFBs pass harmlessly through the gastrointestinal tract; however, some EFBs can cause significant morbidities. This study was conducted to review our experience in managing esophageal foreign bodies in pediatric patients, with an emphasis on the management and outcomes of complicated cases. METHODS: Between March 1995 and March 2013, the records of all children up to the age of 12 years who were admitted to King Khalid University Hospital, Riyadh, Saudi Arabia, with a final diagnosis of EFBs were reviewed. The medical records were analyzed with respect to demographic data, presenting symptoms, workup investigation, management, complications, and outcomes. RESULTS: Seventy patients were identified (38 boys and 32 girls). The ages ranged from 5 days to 12 years (mean: 4.4 years). Fifty-three (75.7%) patients presented within 24 hours. Thirteen (18.6%) patients had underlying predisposing factors. The most common EFB, found in 30 (42.8%) patients, was a coin. Witnessed ingestion of a FB was documented in 52 (74.2%) patients. The most common symptoms were drooling of saliva in 42 (60%) patients, followed by vomiting in 36 (51.4%) patients. Four (5.7%) patients presented with complications secondary to FB impaction, including hypopharyngeal wall perforation, acquired esophageobronchial fistula, localized esophageal perforation with inflammation, and perforation with stricture formation. The follow-up period ranged from 2 to 12 months, and all patients had complete recovery without any sequelae. CONCLUSION: EFBs are a relatively common problem in pediatric patients, and underlying predisposing factors to EFB impaction are not uncommon. Long-retained EFBs are associated with a higher incidence of complications. Rigid esophagoscopy was successful in extracting most of the EFBs and was shown to be a safe and effective procedure.