Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India.

Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

'Quality of Life' of Parents of Children Suffering from Pediatric Malignancies in a Low Income Setting.

OBJECTIVES: To evaluate the impact of pediatric malignancies on quality of life (QOL) and psychological status of parents and to correlate it with well-matched controls and socioeconomic status. METHODS: A prospective comparative cross-sectional study was conducted. Seventy parents of children diagnosed with pediatric malignancies within the last three months were enrolled in the study group (SG) and 50 matched parents of healthy children as the control group (CG). Assessment was done by WHOQOL-BREF questionnaire, Depression Anxiety Stress Score (DASS) scale and Kuppuswamy scale. Data analysis was done by using Statistical Package for social sciences (SPSS) version 20.0. p value <0.05 considered as significant. RESULTS: Mean score of QOL for SG in physical health domain (D1), psychological health (D2), social relationships (D3) and environment health (D4) was 48.64, 43.07, 47.36, and 40.58 respectively whereas that of CG was 79.38, 76.32, 80.58 and 72.86 respectively and the difference was statistically significant (p value <0.001). The environmental domain (D4) had the lowest mean score amongst all domains in the SG. QOL was maximally affected by the parameter sleep, depression, personal relationship and lack of information in the respective domains. Mean depression, anxiety and stress score of SG was 23.43, 20.33, 23.56 respectively whereas that of the CG was 7.1, 8.06 and 8.54 respectively and this was statistically significant (p value <0.001). The QOL of SG in D1 for the lower socioeconomic class was 48.86 and for the upper class was 63 and this difference was statistically significant (p value <0.015). Similarly in D2 and D4 the QOL scores went higher with the socioeconomic class and this was statistically significant (p value < 0.007 and p value <0.030 respectively). CONCLUSIONS: SG had poorer QOL and were significantly more depressed, anxious and stressed. It is concluded that effective interventions are needed to aid these families to improve outcomes by delivering the benefit of vastly improved therapeutic strategies in this field.

Human Leukocyte Antigen-B27: The Genetic Predisposition Leading to Reactive Arthritis during Induction Phase Chemotherapy for Acute Myeloid Leukemia.

We report a case of reactive arthritis (ReA) during induction phase chemotherapy of a 15-year-old male patient with acute myeloid leukemia (AML) M4 with inv(16), most probably due to a genetic predisposition of being human leukocyte antigen b27 (HLA-B27) positive. The episode of ReA recurred during consolidation therapy; however, the patient was asymptomatic after the completion of treatment. The link between HLA-B27 and a large family of inflammatory rheumatic diseases is a well-established fact, but interestingly, there is also a molecular link between HLA-B27 and hematological malignancies. This case brings to our notice, the common immunological, molecular, and microbiological link between AML, HLA-B27, and ReA. It also emphasizes the fact that clinicians should have a high index of suspicion of HLA-B27 positivity, if a case of AML develops arthritis during chemotherapy, since early introduction of immunosuppressive medications for arthritis may reduce morbidity and prevent delay in the administration of further chemotherapy cycles.

Juvenile granulosa cell tumor associated with Ollier disease.

Juvenile granulosa cell tumor (JGCT) is a rare neoplasm of childhood. Interestingly, it is known to be associated with Ollier disease, which is a rare bone disease characterized by multiple enchondromatosis. There is paucity of literature about the co-occurence of these two conditions. However, this association is noteworthy because these two conditions share a common pathogenesis. We report a case of JGCT in a 2.5-year-old female child in which multiple enchondromas mimicking bony metastasis were an incidental finding during routine workup for tumor staging, thus leading to a diagnosis of Ollier disease.