A clinical criterion to exclude the hyperimmunoglobulin D syndrome (mild mevalonate kinase deficiency) in patients with recurrent fever.
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.


CONCLUSIONS
Even among patients already selected by expert physicians, this criterion could help prevent unnecessary genetic testing, which is resource- and time-consuming.
Steichen
Olivier
O
Service de médecine interne, Hôpital Tenon, 4 rue de la Chine, F-75020 Paris, France. olivier.steichen@tnn.aphp.fr
van der Hilst
Jeroen
J
Simon
Anna
A
Cuisset
Laurence
L
Grateau
Gilles
G
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005335:Fever of Unknown Origin / Q000175:diagnosis* / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007589:Job Syndrome / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis* / Q000235:genetics; D010146:Pain / Q000175:diagnosis / Q000235:genetics; D019564:Unnecessary Procedures; D055815:Young Adult