Risks of Ruxolitinib in STAT1 Gain-of-Function-Associated Severe Fungal Disease
نویسندگان
چکیده
Heterozygous STAT1 gain-of-function (GOF) mutations are associated with chronic mucocutaneous candidiasis and a broad spectrum of infectious, inflammatory, and vascular manifestations. We describe therapeutic failures with the Janus Kinase (JAK) inhibitor ruxolitinib in 2 STAT1 GOF patients with severe invasive or cutaneous fungal infections.
منابع مشابه
Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation.
BACKGROUND Gain-of-function (GOF) mutations in the human signal transducer and activator of transcription 1 (STAT1) manifest in immunodeficiency and autoimmunity with impaired TH17 cell differentiation and exaggerated responsiveness to type I and II interferons. Allogeneic bone marrow transplantation has been attempted in severely affected patients, but outcomes have been poor. OBJECTIVE We s...
متن کاملDisseminated Tuberculosis and Chronic Mucocutaneous Candidiasis in a Patient with a Gain-of-Function Mutation in Signal Transduction and Activator of Transcription 1
In humans, recessive loss-of-function mutations in STAT1 are associated with mycobacterial and viral infections, whereas gain-of-function (GOF) mutations in STAT1 are associated with a type of primary immunodeficiency related mainly, but not exclusively, to chronic mucocutaneous candidiasis (CMC). We studied and established a molecular diagnosis in a pediatric patient with mycobacterial infecti...
متن کاملWarning to pay more attention to fungal allergic asthma in children
Asthma is a global problem that affects over 300 million people in the world. The main reason of asthma is allergy and atopy. Asthmatic patients are sensitized to allergens that can be resulting asthma attacks. Fungi as an allergen can be sensitized atopic people and present a severe asthma. Fungi have been found in water-damaged homes of asthmatic patients. Allergic asthma is associated with e...
متن کاملRuxolitinib for the treatment of myelofibrosis: its clinical potential
Ruxolitinib is an orally bioavailable, selective Janus kinase (JAK) 1 and 2 inhibitor approved for the treatment of myelofibrosis (MF), a bone marrow disease in which the JAK pathway is dysregulated, leading to impaired hematopoiesis and immune function. By inhibiting JAK1 and JAK2, ruxolitinib modulates cytokine-stimulated intracellular signaling. In a phase II clinical trial in patients with ...
متن کاملSerious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis.
Ruxolitinib (INCB018424) is a JAK1 and JAK2 inhibitor recently evaluated for the treatment of myelofibrosis (MF) in early- and advanced-phase clinical trials. In 2 recent communications that focused on short-term and long-term ruxolitinib treatment outcome, respectively, the drug was shown to be effective in controlling constitutional symptoms and splenomegaly but was also associated with impor...
متن کامل