Discussion
There are mutations of the STAT1 gene with function gain and loss of function. Autoimmunity findings predominate in mutations with function acquisition, and immune deficiency findings predominate in those with loss of function. The N397D mutation detected in the NGS panel in our patient is the second case in the literature, and similar skin infections with the first detected case were observed with plaque in the mouth and recurrent pneumonia. Bone marrow transplantation was planned as a treatment for our patient. Current therapy for patients with gain of function STAT1 mutations is based on the use of long-term antifungal and antibacterial drugs (3). Candida albicans is a fungus that causes invasive or chronic mucocutaneous disease in immunocompromised patients (1). CMC typically begins in early childhood, although it may first present up to the third decade of life, and signs and symptoms varied within and between families (4). CMC is common in patients with other clinical signs carrying various inborn errors of immunity, including mutations in STAT3, IL12B, IL12RB1 and AIRE. All these defects are associated with impaired IL-17 immunity. IL-17A, IL-17F and/or IL-22 play an important role in mucocutaneous immunity to C. albicans (1).
Some patients have been treated with ruxolitinib, G-CSF, GM-CSF, and intravenous immunoglobulin (3). Ruxolitinib is JAK1/JAK2 inhibitor. Treatments targeting the JAK-STAT pathway, such as the JAK1/2 inhibitor ruxolitinib, which has been approved for myelofibrosis treatment, have shown significant clinical efficiency and might become the treatment of choice for severe CMC resistant to antifungals (4). Progression of infections during ruxolitinib treatment in patients despite continued aggressive antifungal therapy is of concern. Indeed, infections are possible complications of ruxolitinib therapy, therefore, it should be followed carefully (2). Using a dephosphorylation assay demonstrate the disease control (5).
Hematopoietic Stem Cell Transplantation (HSCT) provides an alternative therapeutic option for STAT1 GOF mutations who have an resistant disease course despite conventional therapy (6). It has been done in many cases and has been successful. Previously a patient with complete functional absence of STAT1 who underwent HSCT from an unrelated donor, successfully cured (7). Aggressive treatment of complications, close monitoring and early HSCT should be provided for before development of end organ damage (6).