Our Three Musketeers: A Case Series of NLRP-3 Associated Cryopyrinopathies
Sumanth Madan1, Spoorthy Raj1, Sudeep Rath1
1Department of Clinical Immunology and Rheumatology, Amrita Institute of Medical Sciences, Kochi, India.
Abstract:
Autoinflammatory diseases affecting the NLRP3 gene are rare autosomal dominant disorders presenting with episodic organ limited and systemic inflammation. We report three patients with cryopyrinopathies. Our first case is a 4-year-old boy with a history of periodic fever, failure to thrive, and raised intracranial pressure. The second case is a 6-year-old boy with similar complaints, also with bilateral uveitis. The third is a 24-year-old gentleman with periodic fever and early hearing loss, also with a novel presentation of sacroiliitis. Our case series demonstrates that there should be a low clinical threshold indicating genetic testing in any child who displays features of autoinflammation in combination with an urticarial rash, musculoskeletal manifestations, hearing loss, and chronic aseptic meningitis with macrocephaly. Furthermore, despite anakinra being a cornerstone in treating NLRP-3 AID, there is an unmet clinical need to provide access to alternatives such as colchicine and thalidomide in resource-limited settings.
Insights
Autoinflammatory diseases linked to the NLRP3 gene cause episodic inflammation. Early genetic testing is crucial for children with autoinflammation symptoms, and alternative treatments are needed in resource-limited settings.
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- Autoinflammatory diseases (AIDs) affecting the NLRP3 gene are rare, autosomal dominant disorders.
- These conditions present with episodic, organ-limited, and systemic inflammation.
- Cryopyrinopathies are a subset of NLRP3-associated AIDs.
Purpose of the Study:
- To report three distinct cases of cryopyrinopathies.
- To highlight key clinical features and diagnostic considerations.
- To discuss treatment challenges and unmet needs in resource-limited settings.
Main Methods:
- Case series reporting on three patients with cryopyrinopathies.
- Clinical data collection including symptoms, medical history, and diagnostic findings.
- Review of current treatment strategies and access to alternative therapies.
Main Results:
- Case 1: 4-year-old boy with periodic fever, failure to thrive, and raised intracranial pressure.
- Case 2: 6-year-old boy with similar symptoms and bilateral uveitis.
- Case 3: 24-year-old gentleman with periodic fever, hearing loss, and sacroiliitis.
Conclusions:
- A low threshold for genetic testing is recommended for children with autoinflammation, urticarial rash, musculoskeletal issues, hearing loss, and chronic aseptic meningitis with macrocephaly.
- Anakinra is a primary treatment, but access to alternatives like colchicine and thalidomide is critical in resource-limited environments.
- This case series underscores the importance of timely diagnosis and accessible treatment options for NLRP3-associated autoinflammatory diseases.
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