Aim: Kawasaki disease (KD) is a medium vessel vasculitis of childhood. In infancy KD is often characterized by incomplete and atypical forms. There is paucity of literature on KD in children below 6 months and there are no data from any developing country. This study defines the profile of children with KD below 6 months at our centre.Methods: During January 1994 to March 2015, 460 children were diagnosed with KD and 17 (3.6%) were below 6 months. Diagnosis was based on American Heart Association (AHA) criteria. All children were treated with intravenous immunoglobulin and aspirin; three also received infliximab.Results: Mucosal changes were present in 11 patients (64%); extremity changes in 11 (64%); rash in nine (53%); conjunctival injection in eight (47%); and cervical lymphadenopathy in three (17%). Irritability was noted in 15 patients (88%); four (23%) had respiratory symptoms; and two (11%) had bacille Calmette-Guerin scar reactivation. Fifteen (88%) had incomplete KD. Twelve patients were diagnosed beyond day 10 of illness. Thrombocytopenia was seen in four. Coronary artery abnormalities were present in six (35%) patients. Two children died from disease-related complications -one of these had giant coronary artery aneurysms. Conclusion:Our data show that incomplete forms of KD are commonly seen in children below 6 months of age, thereby resulting in delayed diagnoses. Pediatricians need to have a high index of suspicion of KD when dealing with a young infant with unexplained fever beyond 5 days. The AHA criteria appear to be inadequate for diagnosing KD in infants below 6 months.

Objective Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. Methods A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. Results In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one‐half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. Conclusion This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

BackgroundChronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.ObjectiveTo describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.MethodsA detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.ResultsOf the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)—CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.ConclusionsIn India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.

Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in the ITGβ2 gene. LAD type 2 (LAD2) is caused by mutations in the SLC35C1 gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in the FERMT3 gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in the FERMT3 gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in the ITGβ2 gene, and 4 novel mutations were detected in the FERMT3 gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.

Chronic granulomatous disease (CGD) is the most common symptomatic phagocytic defect. It is caused by mutations in genes encoding protein subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD is characterized by a defective intracellular killing of phagocytosed organisms due to a defective oxidative burst in the neutrophils and macrophages. It is inherited in either X-linked recessive or autosomal recessive pattern. Staphylococcus aureus and Aspergillus species are the most common organisms reported. Infections with Burkholderia, Serratia, and Nocardia warrant a screen for CGD. Suppurative lymphadenitis, cutaneous abscesses, pneumonia and diarrhea constitute the most common problems in children with CGD. A small percentage of children develop autoimmune manifestations (e.g., rheumatoid arthritis, systemic lupus erythematosus, colitis, autoimmune hepatitis) and warrant immunosuppression. X-linked carriers of CGD are at an increased risk of developing autoimmune diseases. Nitroblue-tetrazolium dye reduction test and dihydro-rhodamine assay by flow cytometry are the screening tests for this disorder. While most children do well on long term antibiotic and antifungal prophylaxis, those with severe forms warrant hematopoietic stem cell transplant. The role of regular interferon-γ injections is debatable. Evidence for white cell transfusions is sparse, and gene therapy is under trial.This current review highlights various aspects and studies in CGD. X-linked form of CGD has been noted to carry a poorer prognosis compared to autosomal recessive variants. However, recent evidence suggests that outcome in CGD is determined by the amount of residual NADPH oxidase activity irrespective of mode of inheritance.