First patients with hyperimmunoglobulinemia D syndrome from the United States.

Abstract

In their article Grose et al.1 provide much needed information on two patients with possible hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Thus far HIDS has mainly been diagnosed in European patients and no cases from the United States were known.2 From 1992 onward the International Hyper-IgD study group has maintained a case registry that collects the clinical data on all known HIDS patients to improve awareness of, facilitate diagnosis of and investigate novel therapies for this syndrome.2 Including the cases presented by Grose we now have accurate clinical data on 74 HIDS patients. The clinical features of the described patients are characterized by short bouts of periodic fever accompanied by skin lesions and arthralgias which might very well be compatible with HIDS. The diagnosis of HIDS is made on the basis of the clinical history and elevated serum IgD concentrations (>100 units/ml).2 Although the clinical picture is compatible with HIDS, the reported IgD concentrations of these patients, being 15 mg/dl (106 units/ml) and 9 mg/dl (63 units/ml), are rather low. However, these values may underestimate the true figure because IgD is susceptible to spontaneous fragmentation during storage and shipping which interferes with the single radial immunodiffusion used to measure IgD.3 Of special interest is the occurrence of 2 cases in one family. Indeed HIDS appears to be a familial disorder with an autosomal recessive hereditary trait; thus far 12 families with 2 or more affected family members are known to us. Recently we have initiated efforts to localize the gene encoding for HIDS.4 We were able to exclude the gene causing familial Mediterranean fever (another periodic fever syndrome) as the primary disease locus for HIDS, but more families are needed to identify the HIDS gene. Grose et al. suggest that the patient described in the initial report of IgG4 deficiency could suffer from HIDS because she had concomitant elevated IgD and IgA concentrations. This patient, a 36-year-old Caucasian woman, suffered from recurrent infections of the upper and lower respiratory tract. In our opinion the diagnosis of HIDS in this patient is unlikely because HIDS patients do not present with recurrent infections and reported serum IgG4 concentrations are normal in these patients.2 Furthermore the combination of elevated serum IgD and IgA concentrations is not unique for HIDS but is also seen in other patients without HIDS.5 Joost P. H. Drenth, M.D., Ph.D.; Corry M. R. Weemaes, M.D., Ph.D. Nijmegen, the Netherlands