Unraveling genetics of disease: a recently identified rare cause of familial recurrent respiratory infections and orogenital ulcers

H.L. Leavis, R. Berbers, A. van Royen-Kerkhof

Woensdag 20 april 2016

15:00 - 15:10u in Zaal 0.5

Categorieën: Parallelsessie

Parallel sessie: Parallelsessie 4: Case reports/research

Preenting symptoms: A woman in her mid-forties presents with severe bilateral pneumonia requiring surgical pus drainage with negative cultures. She has a history of recurrent upper- and lower respiratory tract infections requiring hospitalisation. She also suffers from oral and vaginal ulcers and acneiform skin disease with a negative pathergy test. Abdominal complaints are so far considered as non-inflammatory.

Her daughter, meanwhile, is referred to pediatric immunology for recurrent upper respiratory tract infections, oral and perianal ulcers.

Clinical findings: Immunological work-up reveals an IgG2/4 subclass deficiency, suboptimal polysaccharide vaccination response and lymphopenia. Biopsy from the genital ulcers is mostly compatible with Behçet disease.

The daughter also has an IgG2/4 subclass deficiency, lymphopenia, and suboptimal vaccination responses.

Initial diagnosis:Combined immune deficiency and Behçet disease

Interventions: Intravenous immunoglobulin substitution resolves infections in both patients. In mother, colchicine insufficiently controls ulcers and GI-complaints. Oral prednisone is effective, but discontinued due to occurrence of depressive symptoms. Because of insufficient effect of azathioprine, infliximab 5mg/kg is added with significant improvement of ulcers. In the daughter, the ulcers are unresponsive to colchicine and dapsone. Prednisone is effective but tapering difficult, despite addition of azathioprine. After initiation of infliximab 5 mg/kg control of ulcerative disease improved significantly.

Follow-up: In patient and daughter a mutation in TNFAIP3 was identified, causing a recently identified early-onset autoinflammatory disease through haploinsufficiency of A20, a potent NF?B inhibitor. These cases illustrate how increased insights into disease genetics can aid in finding effective treatment options in rare immunologic diseases.