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Raynaud's phenomenon update

Natural history [1]
Results
Transition to other diseases [2]
Results
Calcium channel blockers [3]
Results
Comment

Raynaud's phenomenon is an episodic event where the fingers, toes, ears, nose or jaw become pale and/or blue, often with pain, perhaps in response to cold or some other form of stress. About 1% or so of those with the phenomenon develop a connective tissue disease, most often some form of scleroderma. Studies of Raynaud's phenomenon are not common, even though as many as 1 in 30 to 1 in 10 adults may suffer at some time in their lives.

A Bandolier reader asked for an update on the latest data. Three studies caught Bandolier's attention: a new study on natural history in the community, an older meta-analysis about transition to secondary disease, and a new meta-analysis concerning treatment with calcium channel blockers.

Natural history [1]

The population used for this study was 1,525 participants in an ancillary study of children of original Framingham subjects. A standardised instrument for identifying Raynaud's phenomenon was administered in the early 1990s, and again about seven years later. Cases were identified as having Raynaud's phenomenon if in the last 12 months they met three or four of four criteria:

The study looked at prevalent Raynaud's phenomenon, and incident Raynaud's phenomenon defined as onset within the last 12 months. Those with Raynaud's phenomenon at baseline were further examined at seven years for persistence of the condition, or remission, where Raynaud's phenomenon had resolved.

Results

Baseline and follow up data were complete for 89% of the 1,525 participants, and the average follow up was 7.1 years. The average age was 54 years, with a range of 26 to 81 years. Prevalence was 11% for women and 8% for men, with incidence of about 2% a year (Table 1).



Table 1: Prevalence, incidence, and natural history of Raynaud's phenomenon in the community



Women
Men
Number of subjects
717
641
Baseline prevalence (%)
11
7.8
Baseline incidence (%)
2.2
1.5
Number of cases
78
50
Persisting Raynaud's (%)
36
36
Remitted Raynaud's (%)
64
64


There was no relationship between Raynaud's phenomenon and age, BMI, occupational vibratory tool use, season of examination, place of residence, use of antihypertensive agent, or smoking. Two thirds of those with Raynaud's phenomenon at baseline did not fulfil criteria for Raynaud's phenomenon at follow up (Table 1).

Transition to other diseases [2]

This meta-analysis looked for articles that identified patients with Raynaud's phenomenon, excluded secondary causes, and followed up and re-evaluated patients.

Results

Ten studies included 639 patients. In them, the average age of onset of Raynaud's phenomenon was 34 years (range 23 to 46 years), and average age at entry into studies was 42 years, with Raynaud's phenomenon present for an average of 8 (range four to 21) years. Studies followed up patients with Raynaud's phenomenon for an average of 4.0 years, with 2,531 patient years of follow up.

During follow up, 81 of the 639 patients (13%) developed a secondary disease, 80 of which were connective tissue diseases (Table 2). Two thirds of these were systemic sclerosis. The average rate of transition measured from the onset of Raynaud's phenomenon was 1.4 (range 0.4 to 1.9) per 100 patient years, or 1% a year.



Table 2: Progression to other diseases among 639 people with Raynaud's phenomenon



Transitions
Disease
Number
(total=81)
Percent
Systemic sclerosis
53
65
Mixed connective tissue disease
8
10
Sjögren syndrome
6
7
Rheumatoid arthritis
5
6
Systemic lupus erythematosus
4
5
Vasculitis
2
2
Myositis
2
2
Other
1
1


All studies measured one or more clinical or laboratory variables which potentially were predictors of clinical transition. Positive and negative predictive values calculated from studies are shown in Table 3. The best predictor of transition was abnormal capillary nailfold pattern, but the negative predictive value (Proportion of people with a negative test who are free of the target disorder) was high for several features.



Table 3: Predictive value of clinical and laboratory tests



Predictive value (%)
Variable
Number of trials
Positive
Negative
Abnormal nailfold capillaries
6
47
93
Cutaneous lesions
4
36
97
Positive antinuclear antibody test
9
30
93
Abnormal pulmonary function
4
39
88
Oesophageal dysmotility
4
33
88
Digital ulcer or pits
5
26
75


Calcium channel blockers [3]

This review sought randomised trials in which calcium channel blockers were compared with placebo or other treatments, using standard search strategies, but searching only Medline. The main outcome was standardised to the number of attacks over a week.

Results

Eighteen randomised, double blind, trials with placebo control were included, in which the mean frequency of attacks per week with control was 11 (95% CI 8 to 14). Almost all were crossover trials, lasting one to 10 weeks. Nifedipine at various doses and regimens featured in 13 of the studies. Trial size varied between six and 138 patients. Seven trials had treatment group sizes below 10 patients, and 13 group sizes below 25 patients.

Treatment with calcium channel blockers reduced attacks by five per week, but the largest effects were in the smaller trials. Only four trials had more than 25 patients per group; none showed calcium channel blocker to be better than placebo. These four larger trials reduced attacks by about 1 per week or less. While severity of attacks was also reduced overall, the larger trials showed no effect.

Comment

Sufferers from Raynaud's phenomenon can be given the good news that two thirds are likely to have a spontaneous resolution of symptoms in the future. The bad news is that some of them, 10%, will progress to a more serious condition.

Nor is there much good news on treatment. Only a single meta-analysis could be found, which, despite its headline claims, lent no real weight to the efficacy of calcium channel blockers. Nor did a search for randomised trials reveal any good large trials of sensible interventions with large beneficial effects published in recent years.

References:

  1. LG Suter et al. The incidence and natural history of Raynaud's phenomenon in the community. Arthritis & Rheumatism 2005 52: 1259-1263.
  2. G Spencer-Green. Outcomes in primary Raynaud phenomenon. A meta-analysis of the frequency, rates, and predictors of transition to secondary diseases. Archives of Internal Medicine 1998 158: 595-600.
  3. AE Thompson, JE Pope. Calcium channel blockers for primary Raynaud's phenomenon: a meta-analysis. Rheumatology 2005 44: 145-150.

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