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Familial scleroderma: nature, nurture or both?
Author(s) -
Englert H.,
RobertsThomson P. J.,
Byth K.,
Manolios N.
Publication year - 2008
Publication title -
internal medicine journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.596
H-Index - 70
eISSN - 1445-5994
pISSN - 1444-0903
DOI - 10.1111/j.1445-5994.2007.01525.x
Subject(s) - medicine , concordance , confidence interval , scleroderma (fungus) , systemic scleroderma , daughter , family history , family member , pediatrics , disease , pathology , family medicine , evolutionary biology , inoculation , biology
Background: The aim of the study was to investigate: (i) familial scleroderma (FS) risk factors, (ii) subtype concordance and (iii) relationship between dates (DSO) and ages (ASO) at scleroderma onset. Methods: Forty‐seven cases (23 families; 25 FS pairs) were identified. Scleroderma disease onset was defined by (i) Raynaud’s onset, (ii) first symptom onset (1SxO), (iii) second symptom onset (2SxO) and (iv) scleroderma diagnosis (SDx). Results: Female : male and limited : diffuse (L : D) ratios were 8.4:1 and 3.3:1. The Raynaud’s onset – SDx interval was longer in limited disease (L : D = 14.6:3.1 years; P = 0.01). Raynaud’s first occurred in 36% women ≥50 years. The median differences in ASO between affected family members were 10–12 years. Disease subtype concordance exceeded discordance (16:9 clusters; ( P = 0.32) 16:7 families; ( P = 0.17)). The observed/expected LL : LD : DD ratios were 14: 8:1/11:7:1 ( P = 0.66). FS affected 34% (95% confidence interval 19–50) sister–sister and 44% (95% confidence interval 27–75) mother–daughter pairs. The second family member’s SDx was made at the same (9%) or a younger age (80%) than the first family member. In 14 LL disease families ASO was closer between sisters than mothers–daughters ( P = 0.07). There was a trend towards closer ages – than dates – at Raynaud’s and 1SxO in scleroderma‐affected family members ( P = 0.054) and closer dates – than ages – at 2SxO ( P = 0.02) and SDx. Conclusion: FS showed female predominance, relatively late onset Raynaud’s, subtype ratios similar to idiopathic scleroderma and earlier SDx in younger family members. Familial L scleroderma has a longer prediagnostic latency than familial D scleroderma. FS is likely under‐ascertained. In LL scleroderma, Raynaud’s/1SxO is possibly more genetically determined and 2SxO/SDx more environmentally determined.