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).