Le sindromi autoinfiammatorie: quando non è solo PFAPA

PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis) is the most common self-inflammatory disorder in children. The diagnosis of PFAPA is easy, based on Thomas criteria, and the prognosis is good. Differential diagnosis with hereditary periodic fever syndromes (Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TRAPS and CAPS) should be considered only in the presence of red flags such as early onset, severe abdominal complaints, arthritis and severe rashes. Some patients may present distinct clinical entities with periodic fevers that neither meet PFAPA criteria nor hereditary periodic fever syndromes genotypes. Subjects with these “Undifferentiated Periodic Fever” may respond to glucocorticoids or colchicines or to anakinra in the most severe cases and still have an undetermined prognosis.

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Hereditary periodic fever syndromes

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0240 ◽

2020 ◽

pp. 2207-2218

Author(s):

Helen J. Lachmann ◽

Stefan Berg ◽

Philip N. Hawkins

Keyword(s):

Clinical Features ◽

Periodic Fever ◽

Mevalonate Kinase ◽

Tnf Receptor ◽

Aa Amyloidosis ◽

Periodic Fever Syndromes ◽

Hereditary Periodic Fever Syndromes ◽

Hereditary Periodic Fever ◽

Fever Syndromes ◽

Wells Syndrome

The hereditary periodic fever syndromes or hereditary autoinflammatory diseases are disorders of innate immunity that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutations in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), due to mutations in a gene for a TNF receptor; (3) mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin-associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous, and articular syndrome. With advances in genetics, further syndromes are continually being recognized. These are all extremely rare and in the majority are only known to affect a handful of kindred or individuals. Diagnosis relies on recognition of suggestive clinical features that are almost always accompanied by a substantial acute phase response, and is supported by genetic testing. With the exception of FMF, which is a common disease in certain geographic areas, hereditary periodic fever syndromes are rare and easily overlooked in the differential diagnosis of recurrent fevers. Clinical features and management—attacks can be mild to debilitating and short to prolonged, while their most feared complication is AA amyloidosis. Effective therapies are available for some syndromes, for example: (1) FMF—daily prophylactic colchicine prevents clinical attacks and susceptibility to AA amyloidosis, (2) CAPS—treatment with anti-IL-1 agents produces rapid and often complete clinical and serological remission, and (3) TRAPS—anti-IL therapies are extremely effective.

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Hereditary periodic fever syndromes

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.121202_update_001 ◽

2010 ◽

pp. 1760-1766

Author(s):

Helen J. Lachmann ◽

Philip N. Hawkins

Keyword(s):

Periodic Fever ◽

Mevalonate Kinase ◽

Tnf Receptor ◽

Gene Encoding ◽

Kinase Gene ◽

Periodic Fever Syndromes ◽

Hereditary Periodic Fever Syndromes ◽

Hereditary Periodic Fever ◽

Fever Syndromes ◽

Wells Syndrome

The hereditary periodic fever syndromes are autoinflammatory diseases that mostly present in childhood and are characterized by recurrent, self-limiting, seemingly unprovoked episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. Disorders include (1) familial Mediterranean fever (FMF), due to mutation in the gene encoding pyrin; (2) tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS), due to mutation in a gene for a TNF receptor; (3) Mevalonate kinase deficiency and period fever (MKD), caused by mutations in the mevalonate kinase gene; and (4) the cryopyrin associated periodic syndromes (CAPS), which include (a) familial cold urticarial syndrome, (b) Muckle–Wells syndrome, and (c) chronic infantile neurological, cutaneous and articular syndrome. Understanding of the molecular pathogenesis of these disorders provides unique insights into the regulation of innate immunity and inflammation....

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Hereditary periodic fever syndromes

Aktuelle Rheumatologie ◽

10.1055/s-2003-45022 ◽

2003 ◽

Vol 28 (05) ◽

Author(s):

J Frenkel

Keyword(s):

Periodic Fever ◽

Periodic Fever Syndromes ◽

Hereditary Periodic Fever Syndromes ◽

Hereditary Periodic Fever ◽

Fever Syndromes

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IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives

Frontiers in Immunology ◽

10.3389/fimmu.2020.619257 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hana Malcova ◽

Zuzana Strizova ◽

Tomas Milota ◽

Ilja Striz ◽

Anna Sediva ◽

...

Keyword(s):

Periodic Fever ◽

Tumor Necrosis Factor Receptor ◽

Systemic Juvenile Idiopathic Arthritis ◽

Clinical Manifestations ◽

Musculoskeletal Symptoms ◽

Mevalonate Kinase Deficiency ◽

Periodic Fever Syndromes ◽

Therapeutic Uses ◽

Fever Syndromes ◽

Mediterranean Fever

Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still’s disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

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