The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is characterized by recurrent febrile attacks with abdominal symptoms, joint involvement, skin lesions, and lymphadenopathy. The syndrome has been diagnosed in 66 patients, most from Europe [1]. The clinical picture and the elevated serum IgD levels (>100 U/mL) complete the diagnosis. Although no treatment is available, a correct diagnosis removes uncertainty and allows the patient to be informed on the benign prognosis of the syndrome.

To our knowledge, HIDS has been diagnosed in only two patients in the United States [2]. Although population variation may explain the lack of cases, we believe that under-reporting of cases plays a substantial role. Possible reasons for such under-reporting include lack of awareness and limited availability of reliable IgD determinations. For example, on the basis of a case history and examination of a serum sample, only 6 of 85 Dutch laboratories could diagnose HIDS correctly. Few specialized laboratories in the United States routinely measure IgD levels. In one study [3], laboratories were asked about measurement of IgD levels. All laboratories used one radial immunodiffusion method to assess IgD and measured only a few (<20) samples weekly [3]. Although this method has a limited sensitivity, the range of serum IgD levels in HIDS is such that the diagnosis should be made. However, most samples in the United States are shipped, and IgD is susceptible to spontaneous fragmentation during storage due to proteolytic enzymes that are present in serum and may influence the results [4]. This problem is avoided in a recently developed enzyme-linked immunosorbent assay (ELISA) used to determine IgD levels in human serum. We use a commercial monoclonal antibody that binds to Fc regions of IgD (Dako, Copenhagen, Denmark) and human serum with known IgD concentration (Behring, Marburg, Germany) as a reference. The lower limit of detection with our ELISA is 3 U/mL.

We found that storing IgD for as long as 5 months or repeated freeze-thawing cycles had no influence on the detection of IgD. This suggests that fragmentation does not influence the results of our assay. The use of an accurate ELISA for measuring IgD levels could enhance recognition of cases of HIDS in the United States.