Severe dapsone hypersensitivity syndrome in a child
An 11-year-old Korean boy presented with three days of pruritic erythematous rashes on both cheeks in a butterfly distribution, and circumoral pallor. The following day, he developed high fever with rice-grain-sized rashes that spread to the trunk. The patient's medical history revealed that he had been referred to a dermatological clinic at our hospital 2 months prior to presentation due to papular skin lesions on both forearms, elbows, and ankles that had appeared 4 months ago, and were refractory to conventional therapies. A diagnosis of linear IgA bullous dermatosis was made after biopsy, and he was started on dapsone at a dose of 50 mg per day for 4 days, then increased to 100 mg a day, methylprednisolone 8 mg once a day, and ranitidine 75 mg twice a day. A marked improvement of the skin lesions was noted after 6 weeks of treatment, which completed before he came to pediatric clinic with this new facial rash, and fever. Physical examination revealed a lethargic appearance with a temperature of 39.0℃, heart rate of 82 beats/min, respiratory rate of 20 breaths/min, blood pressure of 120/80 mmHg, injected tonsils, hepatosplenomegaly, and bilateral enlargement of lymph nodes in the axillary and inguinal regions up to 3 cm in diameter. Given these findings, the patient was admitted to the pediatric ward with a working differential diagnosis of drug hypersensitivity versus autoimmune disease versus viral infection.\nInitial blood count revealed a total leukocyte count of 600/mm3 (neutrophil 6%, lymphocyte 91%, eosinophil 0%), a hemoglobin of 11.8 g/dL, reticulocyte count of 3.4%, and platelet count of 180.000/mm3. The white blood cell count, checked 5 weeks prior to admission, was 4,000/mm3 with 46% neutrophils. Atypical lymphocytes were observed, and the differential count fluctuated between 4% and 29% during the first 2 weeks of hospitalization (). No eosinophilia was noted. A blood chemistry panel showed an aspartate aminotransferase of 107 IU/L, alanine aminotransferase of 101 IU/L, total bilirubin of 1.1 mg/dL, and a methemoglobin of 1.1%. Serologic tests for Epstein-Barr virus, cytomegalovirus, parvovirus, measles, antinuclear antibody, anti-ds DNA antibody, and lupus anticoagulant antibody were all negative. A polymerase chain reaction assay for 7 species of common respiratory viruses with nasal aspirates was positive for parainfluenza virus. Blood culture results on 1st HD were negative.\nDapsone was stopped immediately after the onset of fever. After admission, antihistamines, ibuprofen, prednisolone, ampicillin-sulbactam and intermittent dexamethasone injection were given. Prednisolone was administered at a dose of 1 mg/kg/day for 8 weeks. A subsequent study with ultrasound and computerized tomography (CT) of the abdomen revealed thickening of the gall bladder wall with some sludge, localized edema around the gall bladder, and moderate hepatosplenomegaly. Persistent fever, vomiting, dyspnea, and hypotension led to sequential blood cultures and ampicillin-sulbactam was replaced by meropenem from 8th HD. Culture results were positive for Klebsiella pneumoniae on the 8th HD, but negative on the 9th HD after introduction of meropenem for 1 day. Analysis of cerebrospinal fluid (CSF) on the 10th HD day showed a leukocyte count of 675 cells/mm3 (lymphocytes 100%), protein level of 136 mg/dL, and glucose level of 46 mg/dL. The CSF cultures for bacteria and fungi were negative. The patient's dyspnea and hypotension improved 2 days later and follow-up CSF study 5 days later showed a leukocyte count of 9 cells/mm3 (lymphocytes 62%, monocytes 38%), protein level of 33 mg/dL, and glucose level of 74 mg/dL. Sepsis, which appeared to be associated with Klebsiella pneumoniae, was followed by colitis, disseminated intravascular coagulation, syndrome of inappropriate antidiuretic hormone secretion, aseptic meningitis, pneumonia, pleural effusions, and peritonitis. Starting on 35th HD, he had renal failure for 10 days with fluctuating serum creatinine levels from 1.8 to 3.5 mg/dL. Chest CT, taken on 38th HD because of recurrent severe productive cough and rales, despite normal chest X-ray finding, showed tubular and cystic bronchiectatic changes (). Out of 19 blood cultures during the hospital stay, there was only one positive result for Klebsiella pneumoniae on 8th HD. The culture results were negative the following day with only three doses of meropenem. At that point, it is uncertain whether it is a rapid response to new antibiotics or contamination.\nThe maculopapular rashes initially developed on the face and trunk of the patient became confluent, spread to involve the entire body, and lately developed secondary desquamative changes in the 7th week of illness. With 2 months of supportive care, most of the patient's systemic symptoms resolved, with the exception of the skin scaling and generalized red tone or 'erythroderma' (), both of which slowly faded over the following 4 months. A severe neutropenia with absolute neutrophil counts ranged from 0 to 36/mm3 that lasted the first 2 weeks of hospitalization. It was slowly replaced by moderate neutrophilic leukocytosis after administration of prednisolone. All of the clinical events that occurred to the patient during the admission period are shown in the diagram ()