Background and Aims

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.

Methods

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.

Results

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.

Conclusions

Combinatorial inhibition of the JAK-STAT pathway may provide more effective disease control and outcome.

Background and Aims

Chronic Mucocutaneous Candidiasis (CMC) is chronic, recurrent, noninvasive candida infections of the skin, mucous membranes, and nails. CMC is seen in patients with primary immune defects affecting innate and adaptive immune responses involving Th17 pathway. Here, we described three patients with IL17RA deficiency, ACT1 deficiency and STAT1 gain of function mutation presenting with chronic mucocutaneous candidiasis as different genotypes of CMC.

Methods

We presented here three patients with CMC

Case-1:10 year old girl has been followed for fungal infection in the mouth and folliculitis in the trunk since the age of 1 and diagnosed with ACT 1 deficiency.

Case-2:8 year old male patient was applied for the treatment resistant oral candidiasis since the first year of life and diagnosed with IL17RA deficiency.

Case-3:8 year old male patient was applied due to recurrent oral candidiasis at the age of 2 and candida esophagitis was developed at the age of 7. Previously identified heterozygous STAT1 gain of function mutation was detected in the molecular analysis of the patient.

Results

Mutations affecting the innate and adaptive pathways of fungal immunity have been reported increasing our understanding of fungal immunity. Treatment of CMC patients can be quite complex depending on the symptoms mostly requiring long-term antifungal therapy.

Conclusions

Defining the underlying molecular defect would be essential since STAT1 gain of function mutations may be associated with high mortality and morbidity due to the accompanying findings and JAK inhibitors can be used in the treatment of patients with severe symptoms.