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?:abstract
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Signal Transducer and Activator of Transcription 1 Gain of Function (STAT1-GOF) is a primary immunodeysregulatory disease in which a subset of patients have features of autoimmunity and autoinflammation Enteropathy with growth failure and nutrient wasting is a more common feature of immunodysregulation Ruxolitinib is a Janus kinase-STAT inhibitor that has been shown effective for the treatment of immunodysregulatory features in STAT1-GOF Our patient is a 13 year old male with STAT1-GOF (c 983AG p H328R) with severe total parenteral dependent enteropathy that led to growth failure (weight 28 5kg) Treatment with ruxolitinib led to resolution of diarrhea, return of normal diet, and catch up growth A dose of 12 5mg twice daily was initially started but was decreased to 12 5mg every morning and 10 mg every evening due to elevated transaminases and thrombocytopenia Over the following year the patient thrived gaining 7 5kg with normal every other day stools Despite weight gain, he remained stable on the same dose of ruxolitinib As he outgrew his dose, he developed an increased frequency of upper respiratory infections (Parainfluenza, Coronavirus, Rhinovirus) One year after initiation of ruxolitinib, he again developed profuse watery diarrhea that was Norovirus positive (weight 36kg, BSA 0 9) He was placed on bowel rest and ruxolitinib was dose escalated with a goal of 15mg/m2/day When he reached 15mg twice daily, enteropathy completely resolved but liver function tests began to rise He gained weight and began thriving after 2 weeks of therapy Six months later, enteropathy is controlled, and transaminases have remained elevated (ALT 88 IU/L, AST 73 IU/ml) but stable The appropriate dose and pharmacokinetics for ruxolitinib for the treatment of immunodysregulatory symptoms in pediatric patients has not been thoroughly studied The dose used was extrapolated from data on the use of ruxolitinib in pediatric myelofibrosis A dose of 15mg/m2/day appears to provide the most benefit with tolerable adverse effects This dose should be maintained in order to prevent recurrence of disease related manifestations
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