Periodic Fevers and Autoinflammatory Syndromes
Children with these rare inflammatory syndromes typically present with recurrent or persistent fever together with systemic features.
Common clinical clues include:
- rash
- joint pain or arthritis
- abdominal pain
- mouth ulcers
- red eyes
- neurological symptoms
If left untreated, some of these conditions can lead to amyloidosis, which may be life-threatening.
Spectrum of syndromes
These conditions form a spectrum of autoinflammatory disease. Advances in genetics and understanding of inflammatory pathways continue to improve diagnosis and treatment.
Monogenic syndromes include familial Mediterranean fever (FMF), mevalonate kinase deficiency (Hyper-IgD syndrome), TRAPS, and cryopyrin-associated periodic syndromes (CAPS) such as FCAS, Muckle–Wells syndrome and CINCA/NOMID. These conditions often have a strong family history, and genetic testing is available.
Non-monogenic and related conditions include PFAPA, cyclic neutropenia and CRMO. These are often diagnoses of exclusion, and their features may overlap with infection or malignancy.
Diagnostic challenges
These conditions often have overlapping clinical features, making diagnosis challenging. It is essential to exclude infection and malignancy first. Genetic testing is available for some conditions and is likely to expand further in future.
Further information: Recognising recurrent fever syndromes
Management
Management requires specialist multidisciplinary care. Treatment increasingly involves precision immunotherapies targeting inflammatory pathways, including IL-1 inhibitors, TNF inhibitors and JAK inhibitors. These therapies can lead to significant improvements in symptoms and quality of life, but long-term specialist follow-up is required.
Further information and support: http://autoinflammatory.org
Spotlight: CRMO (Chronic Recurrent Multifocal Osteomyelitis)
CRMO is an autoinflammatory bone disorder that can mimic infection.
Typical features include:
- sterile bone inflammation (negative cultures)
- multiple bone sites involved (commonly tibia, ribs, clavicle, vertebrae and pelvis)
- recurrent bone pain, with or without swelling
Any new bony swelling (with or without pain) must be investigated to exclude malignancy and infection, often requiring biopsy.
Management may include NSAIDs, bisphosphonates (e.g. pamidronate), and immunosuppressive therapy.
Key points for healthcare professionals
- Persistent or recurrent fever with systemic features should prompt consideration of autoinflammatory syndromes
- Always exclude infection and malignancy before confirming diagnosis
- In suspected CRMO, biopsy is often required to exclude cancer
- Early recognition and targeted therapy can significantly improve outcomes
