Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome associated with cefotaxime and clindamycin use in a 6 year-old boy: a case report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening idiosyncratic drug reaction. It presents with extensive rash, fever, lymphadenopathy, hematologic abnormalities (eosinophilia and/or atypical lymphocytosis) and internal organ involvement. It has been described in association with more than 50 drugs. To the best of our knowledge neither cefotaxime nor clindamycin has been previously reported to induce DRESS syndrome in children. Clindamycin was reported only in adults as a cause of DRESS syndrome in the literature. In this report, we aimed to present a child with DRESS syndrome that developed after cefotaxime and clindamycin treatment. A 6-year-old boy was diagnosed with the left lower lobe pneumonia and pleural effusion. Parenteral cefotaxime and clindamycin were then started, after which the patient improved clinically and was discharged 7 days later with oral amoxicillin clavulanate treatment. After four days he was readmitted to the hospital with fever and cough. Chest X-ray revealed left lower lobe pneumonia and pleural effusion. We considered that the pneumonia was unresponsive to oral antibiotic treatment, and therefore parenteral cefotaxime and clindamycin were re-administered. As a result, his clinical and radiological findings were improved within 10 days. On the 12th of day of hospitalization, the body temperature has risen to 39°C, which we considered to be caused by antibiotics and stopped antibiotic treatment. At the same day he developed generalized maculopapular erythematous rash, which was considered an allergic reaction secondary to antibiotics. Despite the antihistaminic drug administration, the clinical status quickly deteriorated with generalized edema, lymphadenopathies and hepatosplenomegaly. Laboratory tests revealed a white blood cell count of 4300/μl, a lymphocyte count of 1300/μl, a hemoglobin level of 11.2 gr/dl, a platelet count of 120.000/μl, an eosinophilia ratio of 10% on peripheral blood smear, a C-reactive protein level of 20 mg/dl, a procalcitonin level of 23.94 ng/ml and an erythrocyte sedimentation rate of 48 mm/h. Anti nuclear antibody, anti-double stranded DNA, the serologic tests for Epstein Bar virus, herpes simplex virus, parvovirus, mycoplasma, toxoplasmosis, rubella, cytomegalovirus were all found negative. Bone marrow aspiration was consistent with an autoimmune reaction. An echocardiographic examination was normal. Thoracic tomography revealed multiple enlarged axillary, supraclavicular and anterior mediastinal lymph nodes. As the patient met 8 out of 9 RegiSCAR criteria for the diagnosis of DRESS, we started pulse methyl prednisolone (30 mg/kg/day) for three days followed by 2 mg/kg/day. On the 2nd day fever resolved and cutaneous rash and edema improved. Ten days after developing eruptions the patient was discharged. To our knowledge, we report the first pediatric case of DRESS syndrome following treatment with cefotaxime and clindamycin. Pediatricians should be aware of this potential complication associated with these commonly prescribed antibiotics.


Introduction
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening idiosyncratic drug reaction. It presents with extensive rash, fever, lymphadenopathy, hematologic abnormalities (eosinophilia and/or atypical lymphocytosis) and internal organ involvement. The incidence of this syndrome ranges from 1/1,000 to 1/10,000 after drug exposure. Adults are more commonly affected than children [1].
Approximately 50 drugs (sulfa derivates, antidepressants, nonsteroidal anti-inflammatory drugs) may induce DRESS syndrome, but it is most commonly induced by anticonvulsants (phenytoin, phenobarbital, carbamazepine) and antibiotics [1,2]. It has been described in association with more than 50 drugs.

Patient and observation
A 6-year-old boy was diagnosed with the left lower lobe pneumonia and pleural effusion and was put on parenteral cefotaxime and clindamycin treatment. He then improved clinically and was discharged 7 days later with oral amoxicillin clavulanate treatment.
After four days, however, he was readmitted to the hospital with fever and cough. A chest X-ray revealed left lower lobe pneumonia and pleural effusion. As a case of complicated pneumonia was considered, we started parenteral cefotaxime and clindamycin treatment, 10 days after which his clinical and radiological findings were improved. At the 12 th of day of hospitalization, however, he developed at 39°C, which we considered as a side effect of antibiotics. Therefore, antibiotic treatment was stopped. At the same day, he also developed a generalized maculopapular erythematous rash, which was considered an allergic reaction secondary to antibiotics ( Figure 1).
The pathogenesis of DRESS syndrome has not been elucidated.
The reported mortality of the syndrome ranges between 10% and threatening internal organ involvement, such as in renal or respiratory failure [10]. Pulse methyl prednisolone treatment was also reportedly administered in a pediatric case of DRESS syndrome secondary to anticonvulsant use [11,12]. Gancyclovir has been suggested in patients with severe signs and the confirmation of a major viral reactivation of HHV-6 [10].

Conclusion
The diagnosis of the DRESS syndrome should be highly suspected in patients with fever, skin rash, liver involvement, hypereosinophilia and lymphadenopathy that develop during the use of a culprit drug.
We report the first case of DRESS syndrome associated with cefotaxime and clindamycin exposure in a 6-year-old boy. Early recognition of the signs of the DRESS syndrome and immediate cessation of the suspected drug are the most important steps for an appropriate management of the syndrome. Pediatricians should be careful about this potential complication associated with these commonly prescribed antibiotics in pediatric practice.