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Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome

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Abstract

The purpose of this study was to analyze the levels of white blood cells and profile of proinflammatory Th1, Th2, Th17, and T regulatory tissue cytokines in the tonsils of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients to contribute to the pathophysiological understanding of the PFAPA syndrome. A cohort of PFAPA patients who had tonsillectomy during 2010 and 2011 was included and compared to control patients who had tonsillectomy for tonsillar hypertrophy. White blood cell counts were measured during flares in PFAPA patients and before tonsillectomy in the control group. Cytokine gene expression was analyzed in removed tonsils by real-time PCR. Nine PFAPA patients with a median age of 5.3 years (1.7–8 years) and 17 hypertrophic tonsils of patients with a median age of 4.8 years (2.3–8.4 years) participated in this study. Tonsillectomy was performed during afebrile period between PFAPA flares. Three of the nine patients had recurrent episodes of aphthous stomatitis without fever after tonsillectomy. Leukocyte and neutrophil counts were higher in PFAPA patients compared to controls (p < 0.05). Eosinophil counts were lower in PFAPA patients during flares (p = 0.006). IL-1β, TNF-α, TGF-β, IL-17, and IFN-γ levels were similar in the tonsils of patients and controls. IL-4 gene expression in the tonsils was lower in PFAPA patients compared to those of the controls (p = 0.04). Proinflammatory, effector, and regulatory cytokine gene expression in tonsil tissue of PFAPA children removed in a noninflammatory asymptomatic interval and in control patients were similar. However, IL-4 cytokine gene expression in the tonsils and peripheral blood eosinophils were lower in the PFAPA patients suggesting a potential pathogenesis pathway based on an inhibition of Th2 responses.

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Abbreviations

PFAPA:

Periodic fever aphthous stomatitis, pharyngitis, and adenitis

IL:

Interleukin

TNF-α:

Tumor necrosis factor-alpha

TGF-β:

Transforming growth factor-beta

IFN-γ:

Interferon-gamma

CBC:

Cell blood count

ESR:

Erythrocyte sedimentation rate

CRP:

C-reactive protein

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Acknowledgments

We are indebted to Paula Bedregal, M.D. and Jaime Cerda, M.D. for their help in the statistics assessment and to the members of the Department of Otorhinolaryngology for performing the tonsillectomies.

Source of funding

This work was partially funded by the Division of Pediatrics, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

Disclosures

None.

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Authors and Affiliations

  1. Division of Pediatrics, Facultad de Medicina, Pontificia Universidad Católica de Chile, Lira 85, 5th floor, Santiago, Chile

    Patricia M. Valenzuela, Andrea Araya, Claudio I. Pérez, Carolina Serrano, Paul R. Harris & Eduardo Talesnik

  2. Department of Otorhinolaryngology, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile

    Ximena Maul & Constanza Beltrán

Authors
  1. Patricia M. Valenzuela
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  2. Andrea Araya
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  3. Claudio I. Pérez
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  5. Carolina Serrano
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  6. Constanza Beltrán
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  7. Paul R. Harris
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  8. Eduardo Talesnik
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Correspondence to Patricia M. Valenzuela.

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Valenzuela, P.M., Araya, A., Pérez, C.I. et al. Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Clin Rheumatol 32, 1743–1749 (2013). https://doi.org/10.1007/s10067-013-2334-z

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  • DOI: https://doi.org/10.1007/s10067-013-2334-z

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