Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases

Introduction/objectives The clinicians initially prefer to define patients with the systemic autoinflammatory disease (SAID)'s based on recommended clinical classification criteria; then, they confirm the diagnosis with genetic testing. We aimed to compare the initial phenotypic diagnoses of the patients who were followed up with the preliminary diagnosis of a monogenic SAID, and the genotypic results obtained from the next-generation sequence (NGS) panel. Method Seventy-one patients with the preliminary diagnosis of cryopyrin-associated periodic fever syndrome (CAPS), mevalonate kinase deficiency (MKD), or tumor necrosis factor-alpha receptor-associated periodic fever syndrome (TRAPS) were included in the study. The demographic data, clinical findings, laboratory results, and treatments were recorded. All patients were examined by NGS panel analysis including 16 genes. The genetic results were compared with the initial Federici score to determine whether they were compatible with each other. Results Thirty patients were initially classified as MKD, 22 as CAPS, and 19 as TRAPS. The frequency of clinical manifestations was urticarial rash 57.7%, diarrhea 49.2%, abdominal pain 47.8%, arthralgia 45%, oral aphthae 43.6%, myalgia 32.3%, tonsillitis 28.1%, and conjunctivitis 25.3%, respectively. After NGS gene panel screening, 13 patients were diagnosed with CAPS, 8 with MKD, 7 with familial Mediterranean fever, 5 with TRAPS, and 2 with NLRP12-associated periodic syndrome. The remaining 36 patients were genetically identified as undefined SAID since they were not classified as one of the defined SAIDs after the result of the NGS panel. Conclusions We have demonstrated that clinical diagnostic criteria may not always be sufficient to establish the correct diagnosis. There is still low accordance between clinical diagnoses and molecular analyses. In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should also be kept in mind in the differential diagnosis.

Automated summary

This study found that clinical diagnostic criteria may not always be sufficient to establish the correct diagnosis, with a low accordance between clinical diagnoses and molecular analyses. In cases of patients with preliminary diagnosis of monogenic SAID and negative target gene analysis, other autoinflammatory diseases should also be considered in the differential diagnosis.