Drug Induced Hypersensitivity Syndrome (DIHS) with multi-organ failure with Type I diabetes in infant : A case report

Abstract

Background : Drug induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS) is a well known condition in adults and rare in children. We report an 11 month old boy who presented with multiple seizures associated with febrile respiratory infection for which received ceftriaxone and phenobarbitone prior to referral. Following exposure to these drugs, child developed rash extensive non blanching rash and edema. Child was referred to PICU after 15 days from onset of the rash with multisystem involvement ‘for shock, encephalopathy (GCS 6) & respiratory failure’. Clinical assessment revealed that child had maculopapular rash, extensive erythematous skin lesion, lip erosions with oral mucosal involvement & hepatomegaly. The maculopapular eruption later looked edematous. There was swelling of the face, with marked periorbital involvement without necrosis of the epidermis. Over time the rash faded with exfoliation of skin. Laboratory assessment revealed severe anemia, normal total and differential count without eosinophilia with atypical lymphocytes, thrombocytopenia, raised liver enzymes with normal ammonia and bilirubin, hyponatremia, normal renal functions, CSF normal, Chest X ray normal, brain MRI normal, cardiac echo-coronaries normal. USG abdomen showing hepatomegaly with normal echo texture and normal kidney and other organs without free fluid. Other diagnostic tests revealed that rickettsial antibody, Weil felix, dengue test, leptospira antibody and widal test were negative. Blood culture was sterile. Serum quantitative procalcitonin was within normal limits on admission. With the characteristic rash on exposure to phenobarbitone associated with multiorgan failure, child was treated as Phenobarbitone induced Hypersensitivity Syndrome with methyl prednisolne, IVIG. Child had respiratory failure with renal injury requiring mechanical ventilation and peritoneal dialysis. Child extubated after 5 days, stayed in hospital for 27 days and discharged on oral steroids to be tapered after 6 weeks along with levetiracetam. In subsequent 3-4 months child had fever and tachypnea due to LRTI needing hospitalization in general pediatric ward. Around 6 months following the treatment for DIHS, child had polyphagia, polyuria, and polydipsia associated with weight loss, dehydration and acidotic breathing. On investigation he met the criteria of severe diabetic ketoacidosis (DKA), had low c peptide levels, positive GAD antibodies and high HbA1C with normal thyroid levels. Child was treated as severe DKA and discharged on insulin for long term maintenance of euglycemia. To the best of our knowledge, this is the first case report of association of DIHS with multiorgan failure who subsequently developed Type I diabetes and the youngest infant in the medical literature. This case highlights the importance of identifying DIHS which is a reversible severe drug hypersensitivity reaction and knowledge of number of drugs which can cause this.