STAT3 gain of function (GOF) mutated patients are characterized by short stature, early-onset multisystem autoimmune disease, lymphoproliferation, susceptibility to bacterial, viral, fungal, and mycobacterial infections. We present the treatment response of a patient with STAT3 GOF mutation and a severe clinical phenotype.
12 year-old boy was admitted for severe eczema that started at age one month. At two years of age he developed recurrent respiratory tract infections. He received high dose steroids for interstitial lung disease which resulted in severe steroid toxicity. On referral to the immunology service, his physical exam revealed very short stature, cushingoid aspect, severe eczema, rhonchi in lower lung fields, clubbing and hepatosplenomegaly. A previously described GOF missense mutation in STAT3 [c.C1938A (p.N646K)] was identified , and its GOF attribute was verified by hyperphosphorylated STAT3 in response to IL-6 signaling. Combined therapy with tociluzumab and ruxolitinib was initiated. After initiating the therapy, his steroids could be tapered off without worsening his lung functions. By the fifth month of the therapy his skin eczema and lung functions were improved, and his oxygen requirement was decreased.
STAT3 GOF disease should be considered in cases of immune dysregulation with features of severe eczema, short stature, lymphoproliferation and interstitial lung disease and concomitant autoimmunity.
Combinatorial inhibition of the JAK-STAT pathway may provide more effective disease control and outcome.