Challenges in diagnosing Muckle-Wells syndrome: identifying two distinct phenotypes

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Muckle-Wells syndrome (MWS) diagnosis is complex due to varied symptoms and lack of clear criteria.
• Understanding diagnostic challenges is key for improving patient outcomes.

Purpose of the Study:

• To detail the diagnostic evaluation for MWS.
• To compare patient variables based on childhood versus adult diagnosis.
• To identify factors influencing MWS diagnosis timing and clinical presentation.

Main Methods:

• A cohort study involving 34 MWS patients from two autoinflammatory disease centers.
• Collected demographic, clinical, and preclinical data.
• Utilized comparative analysis for childhood vs. adult diagnoses and correspondence analysis for phenotype identification.

Main Results:

• Median age at MWS diagnosis was 31.5 years.
• Childhood diagnoses featured musculoskeletal symptoms, rash, fever, and abdominal pain.
• Adult diagnoses included musculoskeletal symptoms, rash, fatigue, and notably, hearing loss, which correlated with delayed diagnosis.

Conclusions:

• Distinct MWS clinical phenotypes exist, strongly linked to age at diagnosis.
• An 'inflammatory phenotype' (fever, abdominal pain) is common in childhood diagnoses.
• An 'organ-disease' phenotype (fatigue, hearing loss) characterizes adult diagnoses, informing future MWS diagnostic criteria.