B cell cytopenia in two brothers with hyper-IgD and periodic fever syndrome.

Unlabelled: We report on two brothers with hyperimmunoglobulinemia D (patient 1: serum immunoglobulin D [IgD] concentration initially 61 IU/ml, later on 340 IU/ml; patient 2: serum IgD concentration 144 IU/ml; normal <100 IU/ml, 97th centile) and periodic fever syndrome (HIDS). Both are compound heterozygous for the mevalonate kinase (MVK) mutations V377I and I268T. They developed significant B cell cytopenia (7%, 129/microl and 11%, 132/microl, respectively; normal ranges 12-22%, 300-500/microl) with hypogammaglobulinemia (IgG 5.48 g/l and IgG 5.22 g/l, respectively; normal range IgG 6-13 g/l). Furthermore, the clinical spectrum shows an interesting atypical autoinflammatory symptomatology. The therapy consisted of prednisone, azathioprine, and intravenous immunoglobulins (IVIG), which results in reduced incidence and severity of febrile attacks.

Conclusion: The pathogenesis and clinical presentation of HIDS is still not fully understood and show a great variability. To our knowledge, severe B cell cytopenia in children with HIDS has not been reported before. Furthermore, the therapy of febrile episodes is still performed on an individual basis in affected patients.