Criteria for Hereditary Recurrent Fevers Gets a Second Look

August 7, 2019

In Europe, an expert panel  is recommending new evidence-based classification criteria for the four classic forms of hereditary recurrent fevers and for non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis.

In Europe, an expert panel  is recommending new evidence-based classification criteria for the four classic forms of hereditary recurrent fevers and for non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA).

The recommendations are outlined in a recent issue of the BMJ journal, Annals of Rheumatic Diseases.

The report, which was led by Marco Gattorno, M.D., of the IRCCS Istituto Giannina Gaslini in Italy, describes new criteria that combines genetic and clinical variables to more accurately diagnose disease without confounding it with autoinflammatory conditions. While a number of classification and diagnostic criteria for hereditary recurrent fever currently exist, they are not sufficiently accurate and do not factor in the results of genetic analysis.

This new classification criteria is intended to be used to help identify which patients can participate in clinical, epidemiological and translational studies, but not as diagnostic criteria.  While “classification criteria” assumes various diseases can mimic hereditary recurrent fever, “diagnostic criteria” are intended to positively rule in a specific diagnosis.

The criteria is based on a study included 360 patients from the Eurofever Registry. Sixty patients each had familial mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome, mevalonate kinase deficiency, cryopyrin-associated periodic syndrome, periodic fever, aphthosis, pharyngitis, and adenitis syndrome, and unrefined recurrent fevers.

Using the standard of more than 80 percent consensus on variables, the review panel agreed on classifications for 78 percent of patients:  56, mevalonate kinase deficiency; 39, tumor necrosis factor receptor-associated periodic fever syndrome; 37, periodic fever, aphthosis, pharyngitis, and adenitis syndrome; 36, Familial Mediterranean Fever; 32, cryopryin-associated periodic syndrome; and 81, unrefined recurrent fevers; and, numerous, but specific physical manifestations, such as urticarial rash, red eye and hearing loss.

This classification criteria may be more effective than previous categorization methods, but additional work is needed to further fine-tune how patients with hereditary recurrent fever are identified, the authors wrote.

“The classification criteria we propose are accurate for the discrimination of one form of autoinflammation from another in the context of the six conditions considered herein, but very much have to be applied judiciously, after careful consideration of confounding diseases,” the authors wrote.

Additional studies are needed to validate these findings, they wrote.

REFERENCE:  Gattorno M, Hofer M, Federici S, et al. “Classification criteria for autoinflammatory recurrent fevers.”Annals of Rheumatic Diseases (2019), doi: 10.1136/annrheumdis-2019-215048.