Overt and occult rheumatic diseases: the child with chronic fever

Abstract

Identification of the genes involved in hereditary periodic fever syndromes has led to the recognition of a new pathophysiological category, the autoinflammatory disorders. The main non-hereditary autoinflammatory disease in childhood is systemic juvenile idiopathic arthritis (sJIA), others being the chronic infantile neurological cutaneous arthropathy (CINCA) syndrome and the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. Familial Mediterranean fever (FMF) has been traced to mutations in the MEFV gene. Mutations in the MVK gene, encoding the enzyme mevalonate kinase, cause the hyper-IgD periodic fever syndrome (HIDS). The tumour necrosis factor(TNF)-receptor-associated periodic syndromes (TRAPS) have been linked to mutations in theTNFRSF1A gene, encoding a TNF-alpha receptor, and the CIAS1 gene is mutated in familial cold autoinflammatory syndrome. We discuss how this knowledge has influenced diagnosis and treatment of these rare genetic disorders and how it might change our approach to the more common rheumatic diseases.

Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants?

“…The clinical picture may be further exacerbated by headache, abdominal pain, nausea, vomiting, chills, malaise, myalgia, and arthralgia. [2][3][4] Symptoms dramatically reduce within 2-4 h following a single dose of prednisolone (1-2 mg/kg/day), which may also be used as a diagnostic criterion. 5 The aims of this study were therefore to clarify the clinical clues that will facilitate the identification of PFAPA, which is a clinical diagnosis, and to investigate the efficacy and safety of colchicine prophylaxis in a large cohort.…”

Autoimmune Hepatitis Type 2 Arising in PFAPA Syndrome: Coincidences or Possible Correlations?

“…All the main causes of recurrent fever, such as cyclic neutropenia, familial Mediterranean fever (MEFV), Hibernian fever, and hyperimmunoglobulin D (IgD) syndrome, were excluded according to specific diagnostic criteria. 12 In particular, MEFV was excluded for lack of serosal involvement, absence of other cases in the family, and negative MEFV gene mutation analysis; hyperIgD syndrome was excluded on the basis of the patient's normal level of serum IgD (measured on 2 occasions at least 1 month apart) and the absence of mevalonate kinase mutations; and cyclic neutropenia was excluded because of persistent normality of the patient's neutrophils during and between attacks.…”

Is there a role for the otolaryngologist in PFAPA syndrome?

“…Since the periodic fever syndromes are often similar, it has been postulated that gene mutation may have some role in the etiology [19]. [6].…”