Histamine elevation in familial Mediterranean fever: A study from the Juvenile Inflammatory Rheumatism cohort

Abstract

Background: Familial Mediterranean Fever (FMF) is the most frequent monogenic autoinflammatory disease (AID). Some patients have persistent symptoms despite colchicine intake. Mast cells (MC) are innate immune cells involved in inflammatory conditions including AID. Their activation is responsible for various symptoms such as abdominal pain, bloating and pruritus.

Objective: Our objective was to evaluate features of a systemic MC activation in FMF adult patients.

Methods: FMF adult patients prospectively filled a MC activation survey and usual MC mediators (tryptase and histamine in whole blood, plasma and urine) were measured. They were compared with a healthy control group (HC) and a systemic mastocytosis (SM) group. When digestive biopsies were realized during follow-up, MC infiltration in digestive mucosa was analyzed in FMF, in comparison with SM, Crohn disease (CD) and normal biopsies.

Results: Forty-four FMF patients, 44 HC and 44 SM patients were included. Thirty-one (70%) FMF patients had symptoms of mast cell activation, versus 14 (32%) in the HC group (p = 0.0006). Thirty (68%) FMF patients had at least one elevated MC mediator: mainly whole blood histamine, in 19 (43%) and urinary histamine, in 14 (32%), which were significantly higher than in HC subjects. MC infiltration was comparable in FMF digestive biopsies, biopsies of CD and normal biopsies but was lower than in SM biopsies.

Conclusion: FMF patients show frequent symptoms of MC activation and an increase of blood or urinary histamine never described before in this disease. This suggests an implication of MC and possibly basophils in FMF pathophysiology.

Keywords: Basophils; Familial Mediterranean fever; Histamine, Mast cells; Mast cell activation.