Background/Purpose:

Autoinflammatory diseases (AIDs), aka, periodic fever syndromes include monogenic diseases, such as familial Mediterranean fever (FMF), cryopyrin-associated periodic disease (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and hyper IgD periodic syndrome (HIDS), and polygenic disease like NOD2-associated AID (NAID). A diagnosis of these diseases is clinically challenging in adults, and it often relies on genetic testing. Our aim is to study the disease frequency and report our diagnostic experience.

Methods:

A total of 266 adult patients with clinical phenotypes at presentation were referred due to a concern for AIDs to our Adult AID Clinic at Cleveland Clinic between November 2009 and February 2015. All patients were genotyped for NOD2mutations or periodic fever syndrome panel in commercially available genetic testing centers, depending on a clinical suspicion of an individual disease. The case definition included patients of 17 years of age and older and the definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. The patient electronic medical records were examined for demographic, clinical and genetic data. The frequency of positive genetic testing was calculated to estimate the concordance between the clinical diagnosis and genetic confirmation.

Results:

Of 266 patients, 79 (26.4%) were diagnostic of AIDs, including 54 cases of NAID, 13 FMF, 6 TRAPS, 5 CAPS and 1 HIDS. Of the 143 patients at risk for NAID, 37.8% were confirmed to have NAID, with 85% specificity of the NOD2 genetic testing. Thirteen (44.8%) of 29 patients clinically suspicious for FMF had positive genetic testing. Six (9%) of 66 patients had positive testing for TRAPS. Five (21.7%) of 23 patients had positive testing for CAPS. Only one out of 5 patients was tested positive for HIDS. The demographic and genetic data of these patients with definite AIDs are summarized (Table 1). The frequencies of the genetic tests among these patients were higher (all Ps <0.001) as compared to the literature controls (Table 2). These data demonstrated that the AIDs diagnosed in our Clinic included NAID, FMF, TRAPS, CAPS and HIDS in a descending order. The concordance between the clinical suspicion and positive genetic testing results was higher for FMF and NAID, but it was extremely low for TRAPS. Since these AIDs share overlapping clinical phenotypes and are indistinguishable frequently, the most commonly encountered diseases, NAID and FMF, should be preferably considered. Given the extreme rarity of TRAPS and HIDS in adults and very low genetic detection rate, we suggest caution be exercised to order the genetic testing for these two disorders. 

Conclusion:

Our study demonstrates that NAID and FMF are relatively common in adults. TRAPS and HIDS are extremely rare and the concordance between clinical suspicion and positive genetic testing is very low for both diseases. To be cost-effective, an ordering of genetic testing for AUIDs should highly consider both the disease frequency and stringent phenotypes, and a consultation with experts should be encouraged.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adult-autoinflammatory-disease-frequency-and-our-diagnostic-experience-in-an-adult-autoinflammatory-clinic/