Rakesh Kumar, IndiaPostgraduate Institute of Medical Education and Research, Chandigarh Allergy Immunology Unit
Presenter Of 2 Presentations
AN INFANT WITH REFRACTORY AUTOIMMUNE HEMOLYTIC ANEMIA, DISSEMINATED CYTOMEGALOVIRUS INFECTION AND SEVERE MICROCEPHALY: A CLINICAL AND MANAGEMENT CONUNDRUM
Background and Aims
Patients with severe combined immunodeficiency (SCID) usually presents with severe infections. This case is presented to highlight the severe autoimmune manifestation, sever microcephaly and disseminated CMV infection in a child with SCID.
A 2-month-old boy, born to a consanguineous marriage, presented with a generalized erythematous rash and recurrent diarrhoea. At 7 months of age, he developed respiratory distress. At 9 months of age, he started developing recurrent episodes of anaemia requiring packed red cell transfusions. Physical examination revealed failure to thrive and significant microcephaly, bilateral undescended testes, spleno-hepatomegaly and bilateral chest crepitations.
He had anemia and thrombocytopenia. Absolute lymphocyte count was 2.14 x109/L. Peripheral blood smear revealed signs of haemolysis and positive Direct Coombs Test. Blood CMV PCR was positive and viral load was 56722 copies/ml. IgG- 3.33 g/L (3.7-15.80), IgA - <0.17 g/L (0.30-1.30), IgM- 1.19 g/L (0.60-1.20) and IgE <2 IU/ml (up to 32). Lymphocyte subsets showed markedly reduced B cells. Flowcytometry showed CD4/CD8 reversal, decreased naïve T cells, increased HLA DR expression on CD3+ T cells. For autoimmune hemolytic anemia, intravenous immunoglobulin (IVIg) 1 gm/kg was given and also required high dose steroids. He required additional therapy IVIg and oral sirolimus (at 1 mg/m2), following which there was gradual recovery. Possibility of SCID was considered. Whole exome sequencing revealed frameshift mutation in NHEJ1 c.544_545delGA, p.Glu182fs.
Severe microcephaly and growth retardation in context of SCID can be clue toward diagnosis. In patients with refractory severe autoimmune haemolytic anemia, one may consider addition of sirolimus.
LEUKOCYTE ADHESION DEFICIENCY TYPE 1: A DEVELOPING COUNTRY PERSPECTIVE
Background and Aims
Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder caused by defect in expression or function of CD18, a β2 subunit of integrins expressed on surface of neutrophils. This is characterized by early onset recurrent, life- threatening bacterial infections associated with who do not receive hematopoietic stem cell transplant.
Clinical and laboratory features of cases of LAD diagnosed single tertiary centre were retrieved and analysed. Twenty one children amongst these were diagnosed to have LAD type 1. Clinical details and laboratory investigations were analyzed. Diagnosis of LAD 1 was made on basis CD18 expression by flow cytometry.
Mean age of presentation of LAD was 3.3 years (20 days – 15 years), (11 boys, 10 girls). Delayed cord fall (beyond day 15) was noted in 9, while omphalitis was present in 12 patients. Five had history of consanguinity. Two had amyloidosis and Budd-Chiari syndrome respectively. One patient had pyoderma gangrenosum, which was treated immunosuppresents. One patient presented with palatal perforation at the age of 1 month. One patient had umbilical-enteric fistula with non healing ulcers over abdomen. Mean percentage of gated neutrophils showing CD18 was markedly decreased in patients 0.76% (0-0.96%) compared to controls 96.1-100%. Genetic mutation in ITGB2 gene was confirmed in 14 patients. Of these 14 patients, 4 had p.Arg624Ter variant. Fifteen of these children have succumbed to infections, one is doing well on post HSCT.
Children with LAD have a high mortality in resource-limited settings in absence of readily available facilities for HSCT.