Pediatric recurrent fever and autoinflammation from the perspective of an allergist/immunologist

Abstract

Autoinflammatory diseases are monogenic and polygenic disorders due to dysregulation of the innate immune system. The inherited conditions have been clustered with primary immunodeficiencies in the latest practice parameters; however, these diseases have unique clinical presentations, genetics, and available therapies. Given the presentation of fevers, rashes, and mucosal symptoms observed in many of these syndromes, patients are likely to present to an allergist/immunologist. Although there has been attention in the literature to diagnosis and treatment of rare, genetically defined autoinflammatory disorders, physicians are challenged by increasing numbers of patients with intermittent or periodic fevers who face unnecessary morbidities due to a lack of a diagnosis. The broad differential of diseases presenting with fever includes autoinflammatory syndromes, infections associated with immunodeficiency and/or allergies complicated by infection, and less commonly, autoimmune disorders or malignancy. To address this challenge, we review the history of the medical approach to fever, current diagnostic paradigms, and controversies in management. We describe the spectrum of disorders referred to a recurrent fever disorders clinic established in an Allergy/Immunology division at a tertiary pediatric care center. Finally, we provide practical recommendations including historical features and initial laboratory investigations that can help clinicians appropriately manage these patients.

Keywords: Pediatrics; autoinflammation; periodic fever; recurrent fever.

Figure 1.. The allergist/immunologist as a jack of all trades.

Clinical assessment by an allergist/immunologist can stratify the recurrent fever patient into one or a combination of disorders of immune dysregulation.

Figure 2.. Proposed algorithm for the evaluation of pediatric recurrent fever.

Initial considerations and diagnostic workup to begin to stratify the patient with recurrent fever. N.B., patients should be evaluated on an individual basis, and may require additional workup from that described here. CBC, complete blood count; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; Hib, Haemophilus influenzae type b; IBD, inflammatory bowel disease; SAA, serum amyloid A; S. pneumo, Streptococcus pneumoniae.