The expanding spectrum of low-penetrance TNFRSF1A gene variants in adults presenting with recurrent inflammatory attacks: clinical manifestations and long-term follow-up

Donato Rigante, Luca Cantarini, Giampaolo Merlini, Antonio Vitale, Francesco Caso, Orso Maria Lucherini, Paolo Sfriso, Bruno Frediani, Leonardo Punzi, Mauro Galeazzi, Rolando Cimaz, Laura Obici

Risultato della ricerca: Contributo in rivistaArticolo in rivista

53 Citazioni (Scopus)

Abstract

OBJECTIVE: To analyze the clinical manifestations and response to treatment in a cohort of adult patients presenting with recurrent inflammatory attacks and carrying low-penetrance TNFRSF1A variants, as well as to provide data on their long-term follow-up. METHODS: We performed a retrospective chart review of 36 patients carrying low-penetrance TNFRSF1A variants. Moreover, 60 genetically negative patients treated for recurrent inflammatory attacks and 13 patients with structural TNFRSF1A mutations were also analyzed. Detailed demographic and clinical data were collected at the time of molecular screening and at each follow-up visit. Treatments and markers of inflammation were also assessed. RESULTS: Individuals with low-penetrance TNFRSF1A variants have a lower family history for inflammatory attacks and present with a later disease onset compared with patients with structural mutations, but do not differ, in this respect, with genetically negative individuals. Moreover, low-penetrance variants are less frequently associated with a chronic disease course, with clinical manifestations such as abdominal pain and myalgia, and with amyloidosis. A distinctive clinical feature is a higher rate of pericarditis. Interestingly, mutation-negative patients were found to present with a significant history of recurrent pharyngitis during childhood. Patients with low-penetrance variants are mostly managed with short courses of steroids or non-steroidal anti-inflammatory drugs on attacks. Although the need for a biological treatment is significantly lower compared with patients with structural mutations, still approximately 20% of individuals with recurrent inflammatory attacks carrying low-penetrance variants ultimately require these therapies. CONCLUSIONS: Our study confirms that low-penetrance TNFRSF1A variants can be associated with an autoinflammatory phenotype. Although a chronic disease course is rarely observed, some patients ultimately benefit from a biological treatment.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaSeminars in Arthritis & Rheumatism
Volume2013
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • TRAPS

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