Interferon-γ receptor 1 (INFGR1) deficiency is a severe form of Mendelian susceptibility to mycobacterial disease (MSMD) that characterized by predisposition to infections caused by weakly virulent Mycobacteria and Salmonella. INFGR1deficiency leads to loss of the cellular responsiveness to type II Interferon (INF-γ) which plays a major role in controlling viruses and intracellular bacteria. On the other hand, type I interferons like INF-α and β are critical for defense against viruses. In this report, we examined the response of IFN–β therapy against invasive mycobacterial infection in a patient with INFGR1 deficiency.
A 16-year-old girl presented with disseminated BCGitis early in life that was treated successfully with antimycobacterial medications. Subsequently, she presented with recurrent pneumonia and lymphadenopathy. Her lung biopsy grew multidrug resistant Mycobacterium abscesses. Multiple antimycobacterial medications were tried without improvement. Her genetic testing revealed heterozygous frameshift mutation in INFGR1 (c.819-822delTAAT). By 14 years of age, she started to have persistent headache and brain imaging showed diffuse infiltrative process involving right side of skull base and deep neck spaces with intracranial extension (Fig-1a).Biopsy of extended nasopharyngeal lesion part grew the same Mycobacterium abscesses.
She was started on IFN–β therapy in addition to her previous antimicrobial medications that leads to dramatic response (Fig-1b).
IFN–β might be a useful therapy for invasive CNS mycobacterial infections in INFGR1-deficient patients. While antimicrobial therapies are the definitive curative therapy for mycobacterial infections, the availability of adjunct therapies like IFN- β should enable management of persistent infections especially for those with complete INFGR1 deficiency.