Thrombocytosis in a patient with NUDT15 homozygous variant: clues in clinical pharmacogenetics

A female patient diagnosed with an undifferentiated connective tissue disorder (UCTD) experienced progressive symptoms including hair loss, vomiting, diarrhoea and abdominal pain accompanied by haematological changes of anaemia, absolute neutropenia with thrombocytosis following 7 weeks of azathioprine therapy. Consequently, azathioprine was discontinued, resulted in hematologic recovery and hair regrowth. Genetic analysis revealed the presence of an NUDT15 polymorphism, indicating impaired thiopurine metabolism. Hair loss was the first symptom, above all others, indicating an early onset of anagen effluvium as a warning sign of myelotoxicity. The reactive thrombocytosis was attributed to cytokine-mediated inflammation involving IL-1 and IL-6, suggesting a combined haematological response to azathioprine. It is recommended that Clinicians perform a preliminary genetic testing to prevent the need for frequent blood monitoring and to avoid myelotoxicity