Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers

Papa, Riccardo; Penco, Federica; Volpi, Stefano; Sutera, Diana; Caorsi, Roberta; Gattorno, Marco

doi:10.3390/jcm10091963

Cited by 32 publications

(32 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The clinical success of IL-1 blockade (targeting IL-1α or IL-1β, or both) provides the most convincing evidence of a role for IL-1 in autoinflammatory disease pathogenesis 136 . To that end, empiric trials of anti-IL-1 therapies might be useful in treating patients with either genetically undefined autoinflammatory symptoms or with prominent non-infectious neutrophilia and elevated C-reactive protein or SAA 138 . All three approved IL-1-targeting therapies (Supplementary Table 2 ) have similar safety profiles, with the primary adverse effect being increased risk of non-opportunistic infections, which tend to be mild and can often be treated without withdrawing therapy 139 .…”

Section: Treatment Of Autoinflammatory Diseasesmentioning

confidence: 99%

“…However, a growing number of patients have no clear genetic aetiology. Frequently referred to as syndrome of undifferentiated recurrent fever 138 , 162 or undifferentiated systemic autoinflammatory disease 163 , choosing therapy for these patients is challenging. Fortunately, for patients with features of IL-1 presentations, treatment with IL-1 blockade and colchicine are successful in a significant proportion of patients 138 , 163 .…”

Section: Ongoing Challenges and Future Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

Broderick

Hoffman

2022

Nat Rev Rheumatol

View full text Add to dashboard Cite

Over 20 years ago, it was first proposed that autoinflammation underpins a handful of rare monogenic disorders characterized by recurrent fever and systemic inflammation. The subsequent identification of novel, causative genes directly led to a better understanding of how the innate immune system is regulated under normal conditions, as well as its dysregulation associated with pathogenic mutations. Early on, IL-1 emerged as a central mediator for these diseases, based on data derived from patient cells, mutant mouse models and definitive clinical responses to IL-1 targeted therapy. Since that time, our understanding of the mechanisms of autoinflammation has expanded beyond IL-1 to additional innate immune processes. However, the number and complexity of IL-1-mediated autoinflammatory diseases has also multiplied to include additional monogenic syndromes with expanded genotypes and phenotypes, as well as more common polygenic disorders seen frequently by the practising clinician. In order to increase physician awareness and update rheumatologists who are likely to encounter these patients, this review discusses the general pathophysiological concepts of IL-1-mediated autoinflammation, the epidemiological and clinical features of specific diseases, diagnostic challenges and approaches, and current and future perspectives for therapy.

show abstract

Section: Treatment Of Autoinflammatory Diseasesmentioning

confidence: 99%

Section: Ongoing Challenges and Future Perspectivesmentioning

confidence: 99%

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

Broderick

Hoffman

2022

Nat Rev Rheumatol

View full text Add to dashboard Cite

show abstract

“…Diagnosis of monogenic autoinflammatory diseases was confirmed by Sanger sequencing. Diagnosis of the Syndrome of Undifferentiated Recurrent fever (SURF) in both children and adults was based on patient history of recurrent self-limited febrile episodes accompanied by systemic inflammation without proven infectious or genetic etiology, not fulfilling the criteria for periodic fever, aphthous stomatitis, pharyngitis, and adenopathy (PFAPA) syndrome ( 29 ). In summary, 18/47 (38.3%) patients received anakinra off-label.…”

Section: Resultsmentioning

confidence: 99%

Anakinra in Paediatric Rheumatology and Periodic Fever Clinics: Is the Higher Dose Safe?

2022

View full text Add to dashboard Cite

ObjectiveAnakinra has been increasingly used in off-label indications as well as dosing and mode of administration in a variety of inflammatory conditions. We aimed to review our clinical practice and compare treatment outcomes with published data.MethodsClinical data from electronic records were retrospectively reviewed for patients treated with anakinra over the past 6 years for autoinflammatory diseases (AID).ResultsFrom 47 eligible patients (27 female patients), 32 were children. Macrophage activation syndrome (MAS) was the indication for anakinra therapy in 42.6% of patients. Systemic juvenile idiopathic arthritis (SJIA) was the most common underlying diagnosis (19/47) followed by the spectrum of AID. Off-label use was noted in 38.3% patients. Recommended dose was exceeded in 21 children (mean induction dose 5.1, highest dose 29.4 mg/kg/day) and two adults; five patients were treated intravenously. The mean treatment duration for SJIA was 1.4 years, that for AID was 2.2 years, and that for patients with higher anakinra dose was 9.7 (19.3) months. The mean follow-up duration was 2.7 (1.7) years. Treatment was effective in the majority of SJIA and cryopyrinopathy patients as well as those with MAS. Anakinra was well-tolerated without any major adverse effects even in patients with long-term administration of higher than recommended doses including two infants treated with a dose of over 20 mg/kg/day.ConclusionOur results support early use of anakinra in the individually tailored dosing. In patients with hyperinflammation, anakinra may be lifesaving and may even allow for corticosteroid avoidance. Further studies are needed in order to set up generally accepted response parameters and define condition-specific optimal dosing regimen.

show abstract

“… 8 Briefly, the French RMD COVID-19 cohort included paediatric and adult patients with confirmed inflammatory rheumatic and musculoskeletal diseases and highly suspected or a confirmed diagnosis of COVID-19. SAIDs were defined by the international criteria and included the four historical monogenic SAIDs (FMF, TRAPS, CAPS, MKD), undifferentiated SAIDs, 9 adult onset Still diseases (AOSDs) and Behçet’s disease. We assessed and classified the severity of COVID-19 according to the level of care needed for each patient.…”

Section: Methodsmentioning

confidence: 99%

COVID-19 infection among patients with autoinflammatory diseases: a study on 117 French patients compared with 1545 from the French RMD COVID-19 cohort: COVIMAI – the French cohort study of SARS-CoV-2 infection in patient with systemic autoinflammatory diseases

et al. 2022

View full text Add to dashboard Cite

ObjectiveThere is little known about SARS-CoV-2 infection in patients with systemic autoinflammatory disease (SAID). This study aimed to describe epidemiological features associated with severe disease form and death. Mortality between patients with and without SAID hospitalised for SARS-CoV-2 infection was compared.MethodsA national multicentric prospective cohort study was conducted from the French Rheumatic and Musculoskeletal Diseases (RMD) COVID-19 cohort. Patients with SAID were matched with patients with non-SAID on age±7 years, gender and number of comorbidities to consider important confounding factors. Impact of SAID on severity of SARS-CoV-2 infection was analysed using multinomial logistic regression for severity in three classes (mild, moderate and severe with mild status as reference). Fine-Gray regression model for length of hospital stay and binomial logistic regression model for risk of death at 30 days.ResultsWe identified 117 patients with SAID (sex ratio 0.84, 17 children) and compared them with 1545 patients with non-autoinflammatory immune-mediated inflammatory disorders (non-SAID). 67 patients had a monogenic SAID (64 with familial Mediterranean fever). Other SAIDs were Behçet’ disease (n=21), undifferentiated SAID (n=16), adult-onset Still disease (n=9) and systemic-onset juvenile idiopathic arthritis (n=5). Ten adults developed severe form (8.6%). Six patients died. All children had a benign disease. After matching on age±7 years, sex and number of comorbidities, no significant difference between the two groups in length of stay and the severity of infection was noted.ConclusionAs identified in the whole French RMD COVID-19 cohort, patients with SAID on corticosteroids and with multiple comorbidities are prone to develop more severe COVID-19 forms.

show abstract

Syndrome of Undifferentiated Recurrent Fever (SURF): An Emerging Group of Autoinflammatory Recurrent Fevers

Cited by 32 publications

References 29 publications

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

Anakinra in Paediatric Rheumatology and Periodic Fever Clinics: Is the Higher Dose Safe?

COVID-19 infection among patients with autoinflammatory diseases: a study on 117 French patients compared with 1545 from the French RMD COVID-19 cohort: COVIMAI – the French cohort study of SARS-CoV-2 infection in patient with systemic autoinflammatory diseases

Contact Info

Product

Resources

About