Objectives To describe clinical and laboratory features and disease outcome in a cohort of patients referred for suspected periodic fever syndromes.
Methods We reviewed our rheumatology patient database covering period of 1/2005-6/2011 in order to identify individuals with periodic fever syndromes. Based on the latest follow-up data patients were divided into following groups: PFAPA syndrome, PFAPA-like disease, monogenic fevers, undefined recurrent fevers. Follow-up data and between-group comparisons including control group of children with acute febrile infections from general paediatric clinic (for PFAPA only) were retrieved from patient notes.
Results Out of 269 patients referred for unexplained fever 176 (65%) were considered as suspected of having periodic fever syndromes. PFAPA syndrome was diagnosed in 125 cases. Episodic prednisone administered to 77 patients reduced symptoms in 94%. Tonsillectomy led to the full symptom resolution in all 18 patients. Forty-six patients (49%) reached disease remission (1 year without typical episode) after the median of 2.1 years. 11 patients had genetically proven monogenic fevers with mutations in following genes: MVK (N=6), TNFRs (N=3), NLRP3 and MEFV (1 each). All MKD (mevalonate-kinase deficiency) patients had increased IgD, IgA and urine mevalonate, 3/6 patients had severe phenotype requiring biologics (etanercept in 1, anakinra in 2) with good response. TRAPS patients had protracted fevers, myalgia/arthralgia and ocular symptoms, 2 responded to episodic prednisone, one had mild phenotype responding to episodic antipyretics only (mutation R92Q). From remaining 40 patients 15 had undefined recurrent fevers and 25 had PFAPA-like disease. Their clinical characteristics resembled those of PFAPA group but displayed other features (IgA deficiency, raised IgA and/or IgD, frequent upper respiratory infections) on top of PFAPA-like episodes. Their mean Gaslini score was -1,965 (low risk). MVK and TNFRs gene analysis was done in 4 (2 with high IgD) and 3 patients respectively and turned negative. Increased ESR and CRP during febrile episode was lower than in febrile controls (N=18) and normalised during afebrile interval. All had negative mevalonate in urine. Episodic prednisone reduced symptoms in 88%. Colchicine improved episode duration and frequency in 2 patients. Disease remission was achieved in 42% after disease duration of 4.8 yrs. Tonsillectomy induced remission in 1/3 patients only.
Conclusions We present an overview of our fever clinic patient population over the 6 year period. Though PFAPA–type disease is the most frequent diagnosis it can only be confirmed by its ultimate resolution. High degree of suspicion is needed in order to capture clinical and laboratory features suggesting hereditary conditions, especially in countries where genetic analysis is not available. Specialised clinic set-up with pre-defined diagnostic and therapeutic algorithms has helped us to improve our knowledge as well as clinical care in this newly developing area.
Disclosure of Interest None Declared
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