Life-threatening systemic symptoms in a cystic fibrosis patient

Gohy, Sophie [UCL] Froidure, Antoine [UCL] Lebecque, Patrick [UCL]

Case report A 20-year-old male patient with cystic fibrosis (CF) (F508del/F508del, last FEV1: 92% predicted) was admitted for the sudden occurrence of high-grade fever, FEV1 drop (72% predicted) without increased cough, malaise, diffuse pain and generalized lymphadenopathies. Initial check-up revealed the presence of very recent bilateral hilar lymphadenopathies along with a marked inflammatory syndrome (WBC: 35,680/µl, neutrophils: 28,220/µl, CRP: 163mg/L). Within 24 hours, the patient developed a whole body non-pruritic purpuric rash. Despite broad-spectrum IV antibiotherapy (Tobramycin and Ceftazidim), daily fever persisted (up to 40°C). On the 6th day, the clinical picture worsened and became life-threatening with evidence of impaired renal function (glomerulopathy), multiple serositis, need for supplemental oxygen, hepatic cytolysis and coagulation abnormalities. Both C3 and C4 levels were drastically low. At this point, all non-essential drugs were stopped with the exception of Glazidim. Within the following 7 days, clinical, biological and radiological features all improved. The patient was released under the outpatient treatment prescribed before his hospitalization and without a precise diagnosis as all hematologic, autoimmune and viral detection tests were negative. He came back 2 days later due the recurrence of malaise, fever, rash and biological abnormalities. This time, he also had elevated blood eosinophil count. Oral antibiotherapy (Rifampicin and Moxifloxacin) were immediately interrupted and the picture resolved quickly. The patient then disclosed that he kept taking these drugs (that were no more prescribed) till day 6 of the hospitalization. We concluded that our patient suffered from a drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, with Rifampicin being more likely the causal agent than Moxifloxacin. Discussion From 2008, most Belgian CF patients are adults (≥ 18 years). Antibiotics are a major part of the treatment and adverse drug reactions are frequent, especially to IV antibiotherapy. Life-threatening reactions associated with systemic symptoms are very rare however and no case of DRESS syndrome has been published in CF patients. DRESS syndrome is a rare and potentially lethal condition occurring in about 1/10.000 expositions to a putatively causative drug. Symptoms often involve skin, liver, kidneys, lungs and heart. Diagnosis is challenging as patients might have been exposed to the causative agent for weeks or months and as increased prevalence of systemic disorders (sarcoidosis, Crohn’s disease…) has been reported in CF. Both Moxifloxacin and Rifampicin have been described to induce a DRESS syndrome, the latter being more often involved. In CF patients who are receiving long-term multiple treatments, iatrogenic complications are an ever growing concern.