Review of autoinflammatory diseases, with a special focus on periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome

Abstract

There have been remarkable developments in the field of autoinflammatory diseases over the last 20 years. Research has led to definitions of new conditions, increased understanding of disease mechanisms and specific treatment. The polygenic autoinflammatory condition of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is the most common autoinflammatory disorder among children in many parts of the world. The clinical features often include clockwork regularity of episodes, prompt responses to corticosteroids and therapeutic effects of tonsillectomy, but the disease mechanisms are largely unknown. Conclusion This review discusses the emerging understanding of autoinflammatory diseases, with special emphasis on PFAPA.

Excessive ENaC-mediated sodium influx drives NLRP3 inflammasome-dependent autoinflammation in cystic fibrosis

“…Autoinflammation is defined as an inappropriate inflammatory response, driven by dysregulated innate immune cells, without any evidence of either antigen-driven T cells, B-cells, or associated autoantibodies (Kastner, Aksentijevich et al, 2010, McDermott & Aksentijevich, 2002, McDermott, Aksentijevich et al, 1999, McGonagle & McDermott, 2006, Pathak, McDermott et al, 2016, Peckham, Scambler et al, 2017, Stoffels & Kastner, 2016. Adaptive immune cells are sometimes recruited in response to the downstream consequences of autoinflammation, with increased susceptibility to infection, and progression autoimmunity and hyperinflammation (Wekell, Karlsson et al, 2016). Based on these data and cited literature presented in this study, CF may be characterised as an autoinflammatory disease, in part driven by aberrant ion flux and recurrent infections.…”

Periodic fever syndromes

“…Characteristically the attacks are so regular as to be predictable 'sometimes to a point that the parents can predict the time' (81). In most children the disease will remit within a few years or by adolescence but attacks have a serious impact on the quality of life of the child and their family (82).…”

Cyclical Fevers in a 4-year-old Boy with IgA Deficiency

“…This is a chronic disease typically occurring in young children under the age of five years old and is characterized by high fevers at four to six-week intervals accompanied by aphthous ulcers, pharyngitis, and cervical adenitis. In between episodes, patients are typically healthy [14].…”

“…While the diagnosis of PFAPA is clinical in nature, laboratory findings may be helpful in narrowing the diagnosis. Leukocytosis, elevated ESR, and elevated C-reactive protein can be seen during episodes but return to baseline between recurrences [14]. Notably, serial CBCs should not reflect cyclic decreases in neutrophil levels, as this would serve to diagnose cyclic neutropenia, a rare immunodeficiency that presents with similar symptoms [19].…”

“…Although the patient did not have any active aphthous ulcers at this most proximal visit, the patient's history of recurrent ulcers suggested several potential autoimmune and autoinflammatory diseases. In the pediatric population, such diseases include inflammatory bowel disease (IBD) [11], Behçet disease [12], recurrent fever syndromes, such as cyclic neutropenia [13] and PFAPA [14], and systemic lupus erythematosus (SLE) [15]. The lack of arthritis or chronic anemia did not support a diagnosis of IBD while the absence of genital ulcers, ophthalmic lesions, and skin lesions opposed a diagnosis of Behçet disease.…”