A Clinical Criterion to Exclude the Hyperimmunoglobulin D Syndrome (Mild Mevalonate Kinase Deficiency) in Patients with Recurrent Fever

Abstract

Objective.The hyperimmunoglobulin D syndrome (HIDS) is an autosomal recessive autoinflammatory disease caused by mutations in the mevalonate kinase gene. Our objective was to define a clinical criterion able to exclude HIDS without the need of genetic testing.Methods.A recursive partitioning algorithm was applied to derive the clinical criterion in 149 patients with genetic testing in a French laboratory, among whom 35 had HIDS. The criterion was validated in 93 patients with genetic testing in a Dutch laboratory, among whom 28 had HIDS.Results.The most discriminatory composite clinical criterion satisfied by all patients with HIDS in the derivation group was [onset age < 5 years old OR (joint pain during attacks AND length of attacks < 14 days)]. It had a sensitivity of 100% (95% confidence interval 88% to 100%) and a specificity of 28% (95% CI 17% to 40%) in the validation group. If genetic testing had been limited to patients fulfilling this criterion, 18 tests (19%) would have been avoided in this highly selected validation sample, without missing a single patient with HIDS.Conclusion.Even among patients already selected by expert physicians, this criterion could help prevent unnecessary genetic testing, which is resource- and time-consuming.