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Chemotactic disorder — Clinical Guidelines

Overview

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoinflammatory disorder characterized by recurrent episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis, typically presenting in early childhood with an unknown etiology 1 3 8.

Diagnosis

Clinical Criteria: Recurrent episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis, typically lasting 3-6 days 1 3.

Blood Parameters: Neutrophil-to-lymphocyte ratio (NLR) may differentiate PFAPA from streptococcal tonsillitis 1.

Biomarkers: Galectin-3 shows potential as a biomarker to differentiate PFAPA from familial Mediterranean fever 2.

Cytokine Profiles: Elevated IL-6 levels during febrile episodes can distinguish PFAPA from recurrent tonsillitis 4.

Histological Features: Unique histological findings in tonsillectomy specimens may aid diagnosis in adults 5.

Family History: PFAPA often lacks a clear familial pattern, though family history studies are emerging 7.

Management

First-Line: No specific curative treatment; symptomatic management includes antipyretics for fever 1 3.

Adjunctive Treatments: Corticosteroids may be used acutely to reduce symptom severity 1 3.

Tonsillectomy: Potentially beneficial in pediatric patients, but efficacy varies in adults 10 5.

Genetic Considerations: Routine genetic testing is not routinely recommended unless specific mutations are suspected 8.

Special Populations

Pediatrics: Tonsillectomy may be considered effective 1 10.

Adults: Tonsillectomy appears less effective compared to pediatric cases 5.

Comorbidities: Limited data; management should focus on symptom control and addressing comorbidities 3.

Key Recommendations

Use clinical criteria including recurrent episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis for diagnosis (Evidence: Moderate 1 3).

Consider NLR and IL-6 levels as adjunctive diagnostic tools to differentiate PFAPA from other conditions (Evidence: Moderate 1 4).

Symptomatic treatment with antipyretics is recommended; corticosteroids may be used acutely for symptom control (Evidence: Expert opinion 1 3).

Evaluate the potential benefit of tonsillectomy in pediatric patients, acknowledging variable efficacy in adults (Evidence: Moderate 10 5).

Genetic testing is not routinely necessary unless specific mutations are suspected based on clinical presentation (Evidence: Expert opinion 8).

References

1 Onur H, Onur AR. Diagnostic performance of routine blood parameters in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Journal of clinical laboratory analysis 2023. link 2 Batu ED, Vezir E, Öğüş E, Özbaş Demirel Ö, Akpınar G, Demir S et al.. Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?. Rheumatology international 2022. link 3 Banday AZ, Joshi V, Arora K, Sadanand R, Basu S, Pilania RK et al.. Challenges in the diagnosis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome in developing countries-A decade of experience from North India. Frontiers in immunology 2022. link 4 Nakano S, Kondo E, Iwasaki H, Akizuki H, Matsuda K, Azuma T et al.. Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis. The journal of medical investigation : JMI 2021. link 5 Yamahara K, Lee K, Egawa Y, Nakashima N, Ikegami S. Surgical outcomes and unique histological features of tonsils after tonsillectomy in adults with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome. Auris, nasus, larynx 2020. link 6 Ozen S, Kuemmerle-Deschner JB, Cimaz R, Livneh A, Quartier P, Kone-Paut I et al.. International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome. Arthritis care & research 2017. link 7 Manthiram K, Nesbitt E, Morgan T, Edwards KM. Family History in Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome. Pediatrics 2016. link 8 Kubota K, Ohnishi H, Teramoto T, Kawamoto N, Kasahara K, Ohara O et al.. Clinical and genetic characterization of Japanese sporadic cases of periodic Fever, aphthous stomatitis, pharyngitis and adenitis syndrome from a single medical center in Japan. Journal of clinical immunology 2014. link 9 Lin CM, Wang CC, Lai CC, Fan HC, Huang WH, Cheng SN. Genital ulcers as an unusual sign of periodic fever, aphthous stomatitis, pharyngotonsillitis, cervical adenopathy syndrome: a novel symptom?. Pediatric dermatology 2011. link 10 Parikh SR, Reiter ER, Kenna MA, Roberson D. Utility of tonsillectomy in 2 patients with the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Archives of otolaryngology--head & neck surgery 2003. link 11 Arav-Boger R, Spirer Z. Periodic syndromes of childhood. Advances in pediatrics 1997. link

Chemotactic disorder