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Journal of Clinical Immunology

, Volume 34, Issue 1, pp 104–113 | Cite as

Clinical and Genetic Profile of Children with Periodic Fever Syndromes from a Single Medical Center in South East Michigan

  • Shanmuganathan Chandrakasan
  • Saurabh Chiwane
  • Matthew Adams
  • Basil M. Fathalla
Original Research

Abstract

Objective

To report a cohort of children with periodic fever syndromes (PFS) from Southeast Michigan.

Methods

A retrospective review of medical records for patients referred for periodic fever over 5 years.

Results

Sixty-six patients including 21 FMF, 15 PFAPA, four TRAPS and one patient with combined HIDS and FMF were included. In addition, 25 patients were categorized as clinical PFS (cPFS) based on their clinical features however their genetic workup was either negative or inconclusive. Majority of the patients with FMF were from Middle Eastern background (88 %), but positive family history was noted in only 55 % of cases. Mean age at diagnosis was 40.8 months with a mean delay in diagnosis of 24 months. Most common MEFV mutations were p.M694V and p.M694I. Four patients with TRAPS were from mixed European descent and age at onset of symptoms was 6, 12, 12, and 84 months respectively. TNFRSF1A sequence variants in the TRAPS patients included p.R121Q (R92Q) and p.C99G (C70G); one patient had a rare occurrence of a concurrent p.V726A/-MEFV mutation. One patient with HIDS and FMF presented with atypical overlapping PFS clinical manifestations and genetic evaluation showed a unique combination of p.I268T/p.V377I MVK mutations and p.E230K/-MEFV variant. All patients with PFAPA group were from mixed European descent, symptoms started at a mean age of 34.6 months with a mean delay in diagnosis of 23.3 months. Symptoms started during infancy in six patients. All patients fulfilled the diagnostic criteria for PFAPA. The mean age of onset of symptoms in cPFS group was 17.2 months. Empiric colchicine and glucocorticosteroids controlled flares in majority of patients with cPFS. No evidence of amyloidosis was found in this entire cohort of 66 patients after a mean of 29.2 months of follow-up.

Conclusion

PFS can present with atypical manifestations and should not be excluded based on a negative family history. Concomitant mutations in different autoinflammatory disorders genes can be present and possibly explain atypical manifestations. Various therapies may be considered even if genetic testing is inconclusive or negative.

Keywords

Periodic fever syndromes familial Mediterranean fever HIDS TRAPS PFAPA 

Abbreviations

AID

Autoinflammatory disorders

CAPS

Cryopyrin-associated periodic syndromes

FMF

Familial Mediterranean Fever

HIDS

Hyper Ig-D Syndrome

PAPA

Pyogenic Arthritis, Pustulosis, and Acne syndrome

PFAPA

Periodic fevers with Aphthous Stomatitis, Pharyngitis, and Adenitis syndrome

PFS

Periodic Fever Syndromes

TRAPS

TNF-Receptor Associated Periodic Fever Syndrome

Notes

Disclosures

None

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shanmuganathan Chandrakasan
    • 1
  • Saurabh Chiwane
    • 1
  • Matthew Adams
    • 2
  • Basil M. Fathalla
    • 3
    • 4
    • 5
  1. 1.Department of PediatricsChildren’s Hospital of MichiganDetroitUSA
  2. 2.Division of Pediatric Rheumatology, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA
  3. 3.Division of Pediatric Rheumatology, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA
  4. 4.Weill Cornell Medical CollegeAd DohaQatar
  5. 5.Section of Pediatric Rheumatology, Department of PediatricsHamad General HospitalDohaQatar

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