Juvenile-Onset Immunodeficiency Secondary to Anti-Interferon-Gamma Autoantibodies.

Immunodeficiency secondary to anti-interferon-gamma (anti-IFN-γ) autoantibodies was first described in 2004 as an acquired defect in the IFN-γ pathway leading to susceptibility to multiple opportunistic infections, including dimorphic fungi, parasites, and bacteria, especially tuberculosis and non-tuberculous mycobacterium (NTM) species. It has so far only been described in adult patients. We present 2 cases of disseminated NTM infections in otherwise immunocompetent children. A 16-year-old girl with Sweet's syndrome-like neutrophilic dermatosis developed recurrent fever and cervical lymphadenitis secondary to Mycobacterium abscessus. A 10-year-old boy with a history of prolonged fever, aseptic meningitis, aortitis, and arteritis in multiple blood vessels developed thoracic vertebral osteomyelitis secondary to Mycobacterium avium complex. Both patients were found to have positive serum neutralizing anti-IFNγ autoantibodies. Testing for anti-IFNγ autoantibodies should be considered in otherwise healthy immunocompetent hosts with recurrent or disseminated NTM infection. This represents a phenocopy of primary immunodeficiency which has been recently described only in adults. We report the first two cases of this phenomenon to affect children.

Approach to difficult-to-treat asthma in childhood: a narrative review.

ABSTRACT: Asthma is a major chronic disease affecting children, and children with difficult-to-treat asthma account for a disproportionate share of resource utilisation and healthcare costs. This review presents a comprehensive and up-to-date overview of the treatment strategies in difficult-to-treat paediatric asthma. Mimickers of asthma must first be ruled out, and the diagnosis confirmed with objective tests whenever possible. The effect of comorbid conditions such as obesity, smoking, other atopic conditions and psychosocial factors on asthma control and severity should be considered. Treatment can then be optimised by implementing personalised strategies, including the use of appropriate drug delivery devices and adherence monitoring. Biologics can be an alternative treatment option for selected patients but should not be a substitute for addressing poor adherence. Many patients with difficult-to-treat asthma may not have severe asthma, and the physician should work with patients and families to achieve good asthma control via an individualised approach.