There is good evidence that people with primary Raynaud's phenomenon who have normal nail-fold capillary pattern and negative anti-nuclear antibodies (ANAs) are very unlikely to develop an underlying connective tissue disease.

Systematic review

• In a systematic review, meta-analysis was performed of predictors of transition from primary to secondary Raynaud's phenomenon [Spencer-Green, 1998].
• Inclusion criteria were studies of people with a diagnosis at study entry of primary Raynaud's phenomenon (by any published classification criteria), who were evaluated for secondary Raynaud's at entry and on follow up (by laboratory and clinical parameters).
• Medline was searched up to June 1996, and bibliographies were reviewed.
• Eleven studies fulfilled the inclusion criteria, but one was excluded because of insufficient information about the study participants. Meta-analysis was performed on ten studies (n = 631; 2531 patient-years), of which nine measured ANAs and six assessed nail-fold capillary pattern.
• The odds ratio for transition to secondary Raynaud's phenomenon (after adjustment for each other as possible confounders) was 14.6 (95% CI 6.0 to 35.2) for abnormal capillary pattern and 3.0 (95% CI 1.0 to 8.8) for positive ANAs. Together, they have an odds ratio of 22.6 (95% CI 6.9 to 73.9). Whilst both have low positive predictive values (of 47% and 30%, respectively), they have high negative predictive values (each 93%).
• The review has some limitations:
• Although studies were assessed for quality — by a tool developed for the review — there did not appear to be any weighting of the results according to quality.
• A limited sensitivity analysis found no difference in the rates of transition to secondary Raynaud's phenomenon between the highest and lowest quality studies. Further sensitivity analyses were needed to determine the contribution of poor quality studies to the odds ratios.
• It is not clear how other potential confounding factors, such as age and gender, were accounted for.
• These results are not necessarily generalizable to primary care. The study populations were probably people referred to secondary care, and recognizing abnormal nail-fold capillary pattern takes practice [Raynaud's & Scleroderma Association, 2008].

Prognostic studies published subsequent to the systematic review

• One small cohort study included too few people with primary Raynaud's phenomenon (n = 17) for any statistical analysis [Ohtsuka et al, 1998].
• Another longitudinal study followed up 109 people with primary Raynaud's phenomenon and 33 people with possible secondary Raynaud's phenomenon (recruited in secondary care) over a median of 12 years [Ziegler et al, 2003]. Although the authors concluded that initial presence of ANAs, thickening of fingers, higher age at onset, and female sex seemed to be important determinants for possible transition to a connective tissue disease, data were not presented to support these conclusions.
• A cohort study followed up 236 people with primary Raynaud's phenomenon (recruited in an Austrian outpatient clinic) for an average of 11 years [Hirschl et al, 2006].
• Statistically significant increase in hazard for transition to secondary Raynaud's phenomenon was associated with:
• Older age at onset of Raynaud's phenomenon (hazard ratio [HR] per decade 2.59, 95% CI 1.40 to 4.80, p = 0.003).
• Abnormal thoracic outlet test results (HR 2.69, 95% CI 1.12 to 6.48, p = 0.026).
• Abnormal laboratory findings including positive ANAs (HR 24.22, 95% CI 9.30 to 63.09, p < 0.001).
• Abnormal nail-fold capillary microscopy (HR 11.54, 95% CI 4.17 to 31.95, p < 0.001).
• Abnormal chest radiography (HR 44.21, 95% CI 11.29 to 173.16, p < 0.001).
• It is not clear from the paper whether these results include transition from suspected secondary (as well as from primary Raynaud's phenomenon) to confirmed secondary Raynaud's phenomenon. Neither is it clear whether potential confounding variables have been adjusted for.