Does Polymyalgia Rheumatica Run in Families?
Yes, PMR has a demonstrated genetic component with familial aggregation occurring at rates higher than expected by chance, though the absolute risk remains low and environmental factors likely play an important triggering role.
Evidence for Genetic Predisposition
The clearest evidence comes from familial clustering studies showing PMR and giant cell arteritis (GCA) occur together in families at rates exceeding random chance. A comprehensive review identified a prevalence of familial GCA of 1 in 83 cases (compared to 1 in 250-500 expected by chance), with 96% of sibling pairs showing agreement in clinical presentation (PMR, GCA, or PMR/GCA overlap) 1. This strong concordance within families points to shared genetic susceptibility rather than coincidence.
Specific Genetic Associations
Several genetic markers have been linked to PMR susceptibility and disease behavior:
- HLA-DRB1*0401 alleles are associated with increased risk of relapse in PMR patients 2
- IL-6 promoter -174 G/C polymorphism and GG241 ICAM-1 genotype have been implicated in disease course 2
- DR4 antigen was present in 56% of assessed familial cases, suggesting a genetic predisposition 1
These findings indicate that while PMR has genetic underpinnings, it is polygenic rather than following simple Mendelian inheritance patterns.
Age-Related Immune Alterations
The near-exclusive occurrence of PMR in individuals over age 50 suggests that age-related immune system changes in genetically predisposed individuals contribute to disease development 3. This explains why familial risk doesn't manifest until later decades of life, even in carriers of susceptibility genes.
Environmental Triggers
Despite genetic predisposition, environmental factors appear necessary to trigger disease onset. In familial and conjugal pairs, the average lag between disease manifestation was 5.7 years, with synchronous or close disease occurrence in only 26% of pairs 1. This temporal discordance suggests that while genetics load the gun, environmental exposures (possibly infectious agents, though results remain inconclusive) pull the trigger 3.
Clinical Implications for Family Members
For patients asking about family risk, counsel that:
- First-degree relatives have a modestly elevated risk compared to the general population, but the absolute risk remains low
- Most cases occur sporadically without family history
- Age over 50 remains the strongest risk factor regardless of family history 4
- Family members should be aware of classic symptoms (bilateral shoulder/hip pain, morning stiffness, constitutional symptoms) but routine screening is not indicated 5
Overlap with Giant Cell Arteritis
PMR and GCA are closely interrelated conditions that frequently overlap, with partial or full agreement in clinical presentation observed in 96% of sibling pairs 1. This suggests they share common pathogenic mechanisms and genetic susceptibility 5. Patients with family history of either condition should be monitored for features of both diseases.
Common Pitfall
Do not overstate familial risk to patients—while genetic factors exist, PMR is not a strongly hereditary disease like some other rheumatic conditions. The practical implication is awareness rather than intensive surveillance of family members.