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Major histocompatibility complex class I deficiency results from deleterious biallelic variants in TAP1, TAP2, TAPBP, and B2M genes. Only a few patients with variant-curated TAP1 deficiency (TAP1D) have been reported in the literature and the clinical phenotype has been variable with an emphasis on autoimmune and inflammatory complications. We report TAP1D in a Nepalese girl with a severe clinical phenotype with serious viral infections at a very young age. A novel frameshift termination variant near the protein's amino (N-) terminal was found. Variants in exon 1 of the TAP1 gene (as in our case) have not been reported previously. We also perform a brief review of TAP1D that hints at potential genotype-phenotype correlations. However, these findings need to be interpreted with due prudence given the small number of patients with TAP1D reported thus far. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease is a pediatric, systemic, vasculitic disorder. Its exact etiology is still unknown. Genetic polymorphisms are being investigated as susceptibility factor for this disorder. These are likely to vary among different populations. Aim: To investigate the association of single nucleotide polymorphism (SNP) rs113420705 of CASP3 in Kawasaki disease (KD) from North India. Settings and Design: Observational, case–control study. Methods: Polymerase chain reaction and bidirectional Sanger sequencing was used for determining genotypes of SNP rs113420705 in 45 cases of KD and 50 healthy age- and sex-matched controls. Allele and genotype frequencies were assessed and compared between the groups. Results: Among 45 cases, 32 had TT (71.1%), 13 had CT (28.9%) and none had CC genotype of SNP rs113420705. No significant differences in allele, genotype, or carrier frequencies of rs113420705 were found between the two groups. A comparison was also made between subgroups of KD with coronary abnormality (7 children; 15.5%) and KD with normal coronaries (38 children; 84.4%). The C allele was significantly overexpressed in KD with coronary abnormality group (P = 0.005). However, no difference was noted in the genotype frequencies. Conclusion: CT genotype of rs113420705 of CASP3 showed a trend to significance with the occurrence of KD in children in North India. However, we could not establish any association between minor allele C and susceptibility to KD. C allele appeared to be over expressed in children with KD with coronary abnormalities. Larger studies will help us to reach conclusive evidence applicable to all ethnicities. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after the use of first-line antitubercular drugs (ATDs) is rare and literature regarding DRESS syndrome due to ATDs is scarce in children. We report a young boy with tuberculosis who developed DRESS syndrome after exposure to isoniazid. A 9-year-old boy, diagnosed clinically as pulmonary tuberculosis, presented with fever, fast breathing, maculopapular rash, and one episode of gross hematuria. He had been on 4-drug ATD therapy (isoniazid, rifampicin, ethambutol, and pyrazinamide) for the past 4 weeks. In view of multiorgan involvement and absence of a microbiological diagnosis of tuberculosis, vasculitis was considered and he was treated with steroids. As the child recovered, both corticosteroids and ATD therapy were stopped. At 6 months of follow-up, he was presented with pneumonia. Microbiological diagnosis of tuberculosis was made and 4-drug ATD therapy was reinitiated. After 15 days, he again developed a high-grade fever and rash. On evaluation, isoniazid-induced DRESS syndrome was diagnosed. Subsequently, he received a modified regimen of ethambutol, pyrazinamide, levofloxacin, and linezolid. DRESS syndrome did not recur on these ATDs and the child became asymptomatic. Linezolid was stopped after 3 months of therapy and ethambutol, pyrazinamide, and levofloxacin are being continued. Currently, he has completed 15 months of modified ATD therapy. As a high index of suspicion is required for early diagnosis and management that are crucial to reducing morbidity and mortality, DRESS syndrome should be among the differentials in children with unexplained febrile illnesses. [ABSTRACT FROM AUTHOR]

Evaluation of pediatric hypereosinophilia (HE) is challenging, especially in the tropical developing countries, as appropriate diagnostic facilities may be lacking, parasitic/helminthic infections are common, and existing data on the etiology of severe eosinophilia are sparse. Second, data on long-term follow-up of these children including the temporal course of eosinophilia are also scarce. Besides, questions regarding the coexistence of multiple etiologies and their association with the severity of HE are largely unexplored. These challenges and questions often lead to diagnostic and therapeutic dilemmas. We highlight these difficulties utilizing a real-life clinical description. We emphasize the need for long-term follow-up of such children as HE may be the combinatorial effect of multiple etiologies, rather than a single cause. We also describe an unusual association of severe eosinophilia in a child with toxoplasmosis that was treated successfully with 8-week combination therapy with azithromycin and cotrimoxazole (sulfadiazine and pyrimethamine were not available). [ABSTRACT FROM AUTHOR]