Remarkable effectiveness of tocilizumab in familial Mediterranean fever exon 3 variant with severe abdominal pain and PFAPA-like symptoms: a child case report and review of the literature

Abstract

Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. While accompanying severe abdominal pain by serositis is characteristic of typical FMF, periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome (PFAPA)-like symptoms have been observed in atypical FMF harbouring P369S-R408Q mutations in exon 3 of MEFV gene (i.e. exon 3 variants), treatment of which is often difficult. This study describes the clinical findings of a patient with FMF exon 3 variants and the effectiveness of tocilizumab therapy. We also surveyed the literature to identify the characteristics and treatments of MEFV exon 3 variants. An 8-year-old boy with FMF experiencing recurrent fever accompanied by strong abdominal pain and PFAPA-like symptoms was found to possess heterozygous alterations involving E148Q/P369S/R408Q. Corticosteroids produced a partial response, colchicine was largely ineffective, and a persistent cure was not obtained by tonsillectomy. However, further attacks were completely prevented by monthly administration of tocilizumab. We believe this to be a rare case of paediatric FMF exon 3 variants that showed a complete response to tocilizumab. A comprehensive review of 23 reported cases of FMF carrying P369S-R408Q alterations revealed that patients displayed various manifestations, such as abdominal pain, uveitis, osteomyelitis, and renal failure with amyloidosis, in addition to PFAPA-like symptoms. A wide range of responses was seen for colchicine, infliximab, etanercept, adalimumab, anakinra and another adult case of tocilizumab treatment. Tocilizumab therapy for FMF exon 3 variants may prevent the development of amyloidosis, and improve patient quality of life from recurrent fever attacks.

Keywords:

• Familial Mediterranean fever
• severe abdominal pain
• tonsillitis
• tocilizumab
• PFAPA syndrome

Ethical approval

The present report adhered to Declaration of Helsinki. MEFV gene analysis and the treatment were approved by the Ethics Committee of Shinshu University (No. 540 and No. 1691). The consent to use anonymic patient data for the case report was obtained from the parents of the patient.

Patient consent

Written informed consent for publication of their clinical details and clinical images was obtained from the parents of the patient.

Conflict of interest

None.