1 - Paediatric Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, EPE;
2 – Paediatrics Department, Child and Women Health’s Department, Hospital do Espírito Santo de Évora, EPE;
3 – Paediatric Cardiology Department, Hospital Santa Marta, Centro Hospitalar Universitário Lisboa Central, EPE;
4 – Haematology Department, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, EPE
Background: One of the goals of immunosuppressive therapy is to diminish the immune response at the time of transplantation to prevent organ rejection. The need for polypharmacy increases the potential for serious drug interactions. They can involve changes in drug absorption, distribution, metabolism or excretion (pharmacokinetic interactions), or involve effects on drug concentration (pharmacodynamic interactions).
Case presentation: A 17-year-old teenager with a personal history of GCM for two years, under immunosuppressive therapy (cyclosporine, azathioprine, and prednisolone) since diagnosis and allopurinol which was started three months before admission, presented with dizziness, diffuse headache and asthenia for 10 days. Two days before admission, a right buttock tumefaction and fever were noted. At admission, he was pale and tachycardic and had an infected pilonidal cyst. There was no signs of blood dyscrasia. Complete blood count revealed severe pancytopenia (severe anemia (Hb 4 g/dL); neutropenia 170/uL and thrombocytopenia 16.000/uL), elevated reticulocytes 10,5%, low folic acid level and elevated c-reactive protein. Electrocardiogram and echocardiogram revealed no “de novo” changes. He was admitted to the pediatric intensive care unit, was transfused (red blood cell and platelets) and was started on broad spectrum antibiotics with good outcome. Azathioprine was suspended on day 2 of admission with gradual improvement of pancytopenia. A pilonidal cyst was drained and he completed 14 days of antibiotics. He also started folic acid supplementation.
Learning Points Discussion: Immunosuppressive treatment in GCM includes cyclosporine which has been associated with prolonged transplant-free survival. This case report describes a myelosuppression probably due to drug interaction (azathioprine and allopurinol). The pathway responsible for the metabolism of azathioprine is xanthine oxidase which is inhibited by allopurinol. Allopurinol has been reported to potentially lead to higher levels of cyclosporine, which can lead to life-threatening myelosuppression. Current recommendations stated that doses of azathioprine should be reduced by 50 to 75 percent when administered concomitantly with allopurinol. In our case, after suspending azathioprine, there was a clinical and laboratory gradual improvement and the adolescent was dismissed clinically well. The follow up showed complete regression of pancytopenia after eight weeks and there was no worsening of cardiac status.