Mullins’ syndrome: a new gammopathy-related autoinflammatory syndrome resistant to anakinra

Abstract

A 59-year-old Caucasian male had a 28-year history of episodes of recurrent urticaria, fever, periorbital angio-oedema and conjunctival injection. The episodes would be preceded by prodromal symptoms of nightmares, general malaise/fatigue and anterior chest/upper abdominal pain similar to indigestion. This would then proceed to urticaria, which had been described as atypical, not always being raised or palpable but being intensely itchy (Figure 1), as well as fever, periorbital angio-oedema and sometimes gum or jaw pain. Four to 6 h after onset, symptoms would typically proceed to hypotension resulting in the loss of consciousness on several occasions. Attacks would last 3–4 days, and were followed by fatigue lasting 1–2 weeks. Figure 1 Photograph of rash during attacks. Investigations showed a monoclonal immunoglobulin G (IgG) kappa paraprotein that has fluctuated between 14 and 20 g/l throughout the course of his illness, although without increasing trend. He was also found to have low levels of kappa free light chains on urine electrophoresis. He had low C4 complement levels and C3 complement levels at the lower end of the normal range during remission, with raised C3d and elevated amounts of the terminal component complex, consistent with ongoing complement activation. Other investigations taken during remission, including C1 inhibitor levels; full blood count; renal and liver function; thyroid function; erythrocyte sedimentation rate (ESR); and C-reactive protein (CRP), did not show any significant abnormality. Anti-nuclear and anti-neutrophil cytoplasmic antibodies were not detected. Subsequently, he was admitted for observation during an attack. Investigations done at that time showed a markedly increased CRP of >250 mg/l, leucopenia and thrombocytopenia (with a nadir white cell count of 0.7 × 109/l, neutrophil count of 0.1 × 109/l and platelet count of 28 × 109/l) and decreased complement C3 and C4 levels. The ESR did not show a …