Recurrent macrophage activation syndrome due to hyperimmunoglobulin D syndrome: a case-based review

Hyperimmunoglobulin D syndrome (HIDS) is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks with fever, abdominal pain, lymphadenopathy, aphthous stomatitis, and skin lesions. There are few reports on HIDS patients complicated with macrophage activation syndrome (MAS); however, to our knowledge, there is no case of HIDS with recurrent MAS attacks. We report two pediatric patients initially diagnosed as Kawasaki disease and systemic juvenile idiopathic arthritis presented with recurrent MAS episodes with prolonged fever, skin rash, hepatosplenomegaly, cervical lymphadenopathy, aphthous stomatitis, headache, pancytopenia, hyperferritinemia, and hypofibrinogenemia, finally diagnosed as HIDS with a documented homozygous MVK gene mutation. This is the first report on recurrent MAS attacks due to HIDS in pediatric patients who were successful treated with corticosteroids and anti-IL-1 therapies. Thus, clinicians should be vigilantly investigated signs of autoinflammatory diseases in patients with recurrent MAS attacks during their disease course, and HIDS should be considered an underlying disease for triggering recurrent MAS attacks. We have also reviewed the current literature regarding HIDS cases complicated with a MAS attack and summarized their demographic, treatment, and outcome characteristics. Key points • Hyperimmunoglobulin D syndrome should be considered in differential diagnosis in patients who experienced recurrent macrophage activation syndrome attacks.