Evaluation of treatment efficacy of Raynaud phenomenon by digital blood pressure response to cooling. Raynaud's Treatment Study Investigators.

Our previous studies have suggested that digital blood pressure response to cooling could provide a measure of the efficacy of treatments that are administered to patients with Raynaud phenomenon (RP). This method was used on 158 primary RP patients participating in a multicenter, randomized clinical trial that compared the efficacy of sustained-release nifedipine with temperature biofeedback in the treatment of RP. A pill placebo and electromyography served as controls. The response to local finger cooling was measured at 30 degrees, 20 degrees, 15 degrees and 10 degrees C in a temperature-controlled room under standardized conditions. The results showed that, at the 15 degrees C and 10 degrees C local cooling temperatures, the patients in the nifedipine group had a higher mean digital systolic blood pressure, a higher relative digital systolic blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a smaller proportion of subjects with a zero reopening pressure than the patients in the three other treatment groups. These results were statistically significant at 10 degrees C, the nifedipine group being significantly different from all others (p < 0.05); no significant difference was found between the three other treatment groups.

A thermal vascular test for distinguishing between patients with Raynaud's phenomenon and healthy controls. Raynaud's Treatment Study Investigators.

This study tested the reliability and validity of a diagnostic thermal vascular test (TVT) for patients with Raynaud's Phenomenon (RP). The TVT examined digital blood pressure responses to combined cooling and occlusion and was developed as part of the Raynaud's Treatment Study, a multicenter clinical trial comparing the efficacy of biofeedback and pharmacological treatment. A computerized system permitted efficient, accurate, and uniform testing at different geographical sites. A comparison of 199 patients with RP and 52 healthy controls is reported. The TVT showed a sensitivity of 79% and a specificity of 88%. Test-retest reliability was acceptable (r = .80). Addition of a psychological challenge failed to improve the discrimination between patients with RP and controls. The TVT separated patients with RP and controls as well as or better than existing tests and did so with enhanced ease of operation.

Association between cigarette and alcohol consumption and Raynaud's phenomenon.

The association between alcohol and cigarette consumption and Raynaud's Phenomenon (RP) was examined by using data from an American-French collaborative, cross-sectional, epidemiological study in five geographically varied regions (Charleston, South Carolina, USA; and Grenoble, Tarentaise, Nyons, and Toulon, France). Using logistic regression models that take into account the sampling weights, the association was examined stratified by gender and adjusted for age, body mass index, self-perceived health, and education. Overall, neither cigarette nor alcohol consumption showed a significant association with RP. In men, however, a V-shaped relationship between drinking and RP was observed, with mild consumption (1 to 7 drinks per week) exhibiting a protective effect over abstinence, whereas occasional (less than 1 drink per week), moderate (8 to 18 drinks per week) and heavy consumption (more than 18 drinks per week) did not. Among the participants with RP, no significant association was observed between RP attack frequencies and the amount of either alcohol or cigarette consumption. These negative findings suggest that having RP is not strongly affected by alcohol or cigarette consumption.

Different factors influencing the expression of Raynaud's phenomenon in men and women.

OBJECTIVE: To determine whether the risk profile for Raynaud's phenomenon (RP) is different between men and women. METHODS: In this cross-sectional study of 800 women and 725 men participating in the Framingham Offspring Study, the association of age, marital status, smoking, alcohol use, diabetes, hypertension, and hypercholesterolemia with prevalent RP was examined in men and women separately, after adjusting for relevant confounders. RESULTS: The prevalence of RP was 9.6% (n = 77) in women and 5.8% (n = 42) in men. In women, marital status and alcohol use were each associated with prevalent RP (for marital status adjusted odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4-3.9; for alcohol use OR 2.2, 95% CI 1.0-5.2), whereas these factors were not associated with RP in men (marital status OR 1.4, 95% CI 0.6-3.5; alcohol use OR 1.0, 95% CI 0.2-4.4). In men, older age (OR 2.3, 95% CI 1.0-5.2) and smoking (OR 2.6, 95% CI 1.1-6.3) were associated with prevalent RP; these factors were not associated with RP in women (older age OR 0.8, 95% CI 0.4-1.6; smoking OR 0.7, 95% CI 0.4-1.1). Diabetes, hypertension, and hypercholesterolemia were not associated with RP in either sex. CONCLUSION: The results indicate that risk factors for RP differ between men and women. Age and smoking were associated with RP in men only, while the associations of marital status and alcohol use with RP were observed in women only. These findings suggest that different mechanisms influence the expression of RP in men and women.

An objective method to estimate the severity of Raynaud phenomenon: digital blood pressure response to cooling.

The treatment efficacy of patients with Raynaud phenomenon (RP) is determined from the decrease in severity of this condition, usually based on a decrease in frequency of RP attacks as reported by patients in a diary. Although subjective, this method is still the main endpoint measure in clinical trials. The results of patients' digital blood pressure responses to cooling were compared with the reported RP attack frequency to determine whether the former could be used to estimate the severity of RP. The effect of local finger cooling on the digital systolic blood pressure was tested at 30 degrees C, 20 degrees C, 15 degrees C and 10 degrees C on 136 subjects with RP. The RP attack frequency was dichotomized into daily versus less than daily attacks. The frequency of attacks and the digital systolic pressure (DSP) showed a significant association at all cooling temperatures (those with daily attacks showed lower DSP than those with less frequent attacks). In addition, patients experiencing daily attacks of RP showed a zero reopening pressure at higher local temperatures than those with less frequent RP attacks. These results demonstrate that the response of the digital systolic blood pressure to cooling is closely associated with the RP attack frequency and therefore can be considered as an objective estimate of RP severity. This physiological measurement should be most useful in evaluating the clinical course of RP and the effect of its treatment, provided it is measured under standardized conditions.

Prevalence of Raynaud's phenomenon in 2 ethnic groups in the general population of Estonia.

OBJECTIVE: To compare the prevalence of Raynaud's phenomenon (RP) in 2 genetically different ethnic groups in Estonia: Estonians, who are Finno-Ugric people, and Slavs, who are Indo-European people, and to investigate the risk factors of RP. METHODS: A random sample of 5248 Estonians and 4341 Slavs were surveyed by mail questionnaire (Phase I) for suspected RP. A subsample of 1739 subjects was interviewed and examined (Phase II) to make a formal diagnosis of RP, using the color charts, and to collect additional pertinent information. RESULTS: Of these 1739 subjects examined in Phase II, 226 women and 162 men were diagnosed to have RP. The age adjusted prevalence of RP was significantly higher among Slavs (women 11.4 +/- 1.3%, men 13.0 +/- 1.6%) compared to Estonians (women 7.8 +/- 1.0%, p = 0.023; men 8.2 +/- 1.5%, p = 0.031). Based on logistic regression analysis, the diagnosis of RP among women was associated with a Slavic ethnic origin, the presence of connective tissue disorders or cardiovascular diseases, a family history of RP, a history of dysphagia and frostbite, smoking, and a lower body mass index (BMI). Among men RP was associated with manual work, vibrating tool use, a history of frostbite and injuries to the fingers. older age, and a lower BMI. CONCLUSION: Our results revealed a significant difference in the prevalence of RP between 2 ethnic groups living in the same geographic region. The risk factors associated with RP show considerable sex differences, RP being mostly constitutional in women and occupational in men.

Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison.

OBJECTIVE: To determine the population based prevalence of Raynaud's phenomenon (RP) in 5 geographic regions: one in South Carolina, USA, and 4 in France; to explore the relationship of RP to the climate; to investigate possible risk factors; and to describe the characteristics of RP+ subjects in the general population. METHODS: The study consisted of 2 phases: a telephone survey of a randomly drawn sample of households, with 10,149 completed interviews; these were followed by a face to face interview and clinical evaluation (n = 1,534), including diagnosis of RP. The same methodology was used in all 5 regions: for recruitment of subjects, criteria for RP, method of RP diagnosis, and for gathering additional information. RESULTS: The prevalence of RP was found to be related to the climate. The relationship between RP and climate was complicated, however, by the fact that many subjects had moved between climate zones. The relationship of RP to a cold climate became more evident after taking the migration patterns into account: the majority of RP+ subjects in the 2 coldest regions had lived all their lives in the same or a similar climate zone; the majority of RP+ subjects in the 2 warmest regions had previously lived in a colder climate. Other factors associated with RP were family history of RP, cardiovascular diseases, older age, a low body mass index, use of vibrating tools, and outings of a day or more. The classical triphasic RP was rarely encountered in the general population and the most frequently observed signs and symptoms during an RP attack were blanching accompanied by numbness. CONCLUSION: In addition to being a triggering factor for RP attacks, cold also appears to be an etiologic factor in the pathogenesis of RP. A subclinical cold injury, more likely to occur in colder climates, may be responsible for the "local fault" that has been implicated in the pathogenesis of RP and, in association with other risk factors, may predispose subjects to develop clinical RP.

Prevalence of Raynaud phenomenon in Tartu and Tartumaa, southern Estonia.

The aim of the present study was to estimate the prevalence of Raynaud phenomenon (RP) among Estonians in the general population of Southern Estonia. A random sample of 2626 Estonian subjects from the general population was asked about their fingers' sensitivity to cold and color changes by a mail survey. A subsample of 457 subjects was examined to confirm the diagnosis of RP, using a standard interview assisted by color charts (a color scale and hand photographs). In addition to a short clinical examination, the nailfold capillaries were examined by in vivo microscopy and a blood sample was drawn for ANA testing. The prevalence of RP, based on the presence of blanching, alone or with cyanosis, was 8.3% +/- 0.91% (SE) for women and 7.9% +/- 1.62% for men. The prevalence increased with age and, in men, was related to occupation. Smoking was also associated with RP among men but the effect was difficult to separate from that of the occupational influences because of the high proportion (84.2%) of current and past smokers among male manual workers. RP among the Estonians in Southern Estonia has a lower prevalence than in other countries with comparable climate, its female to male ratio is low, and it is related to occupation and smoking in men.

Prevalence of scleroderma spectrum disorders in the general population of Estonia.

The purpose of this study was to estimate the prevalence of scleroderma spectrum disorders (SDS) in the general population of Estonia while taking into account environmental and ethnic factors. A random sample of 14,467 subjects from the general population were surveyed by mail questionnaire to detect those with suspected Raynaud phenomenon (RP) and SDS. A subsample of 2,154 participants was then seen during the field study to confirm the RP diagnosis and to perform a short clinical examination. Of 581 subjects with RP, 13 cases (all women) were diagnosed as having SDS; based on these findings, the estimated prevalence of SDS in the adult population is 228 per 100,000 (95% CL 121; 391), while in women alone it is 354 per 100,000 (95% CL 188; 605). The best estimate of SD (systemic scleroderma), based on ACR criteria, is 35 per 100,000 (95% CL 4; 127). No significant difference in SDS prevalence was found between the two environmentally different regions we studied. Although statistically not significant, the prevalence of SDS, especially of SD and CREST syndrome, among Russians was higher than among Estonians, as we had hypothesized. The distribution of SDS subtypes also suggests an ethnic difference. The overall prevalence of SD/CREST that we found is higher than that reported in studies not based on a random sample of the general population.

Digital vascular responses to cooling in subjects with cold sensitivity, primary Raynaud's phenomenon, or scleroderma spectrum disorders.

OBJECTIVE: To define differences in digital vascular responses to cooling and to determine their usefulness for the differential diagnosis of 4 groups of subjects: patients with primary Raynaud's phenomenon (RP) (n = 96), patients with RP associated with scleroderma (systemic sclerosis, SSc) spectrum disorders (SSc spectrum RP) (n = 108), subjects complaining of cold sensitivity of the fingers (n = 88), and RP negative controls (n = 120). METHODS: Digital systolic blood pressure, digital blood flow, and digital skin temperature were measured in a temperature controlled room at 18 or 23 degrees C; the effect of local finger cooling was tested at 30, 20, 15, and 10 degrees C. RESULTS: Digital blood pressure responses clearly differentiate the 4 diagnostic groups from each other. By contrast, blood flow and skin temperature measurements, although showing different group means, fail to reach statistical significance due to a large variance. Digital pressure responses have high sensitivity and specificity for distinguishing not only between patients with RP and controls, but also between the 2 types of RP. A relative digital systolic pressure (digital systolic pressure over brachial systolic pressure) of less than 70% at low local finger cooling temperatures (15 and 10 degrees C) has a sensitivity of 97.1% in differentiating SSc spectrum RP from primary RP. A zero reopening pressure shows a specificity of 100% at 30 degrees C and 81.7% at 20 degrees C to separate the 2 groups. The zero reopening pressure is seldom associated with clinically visible RP (10.3% among SSc spectrum RP, 4.3% among primary RP). Although the study was not designed to investigate drug effects, our data from patients who failed to abstain from vasodilators, as instructed, show they have a protective effect at 15 and 10 degrees C. CONCLUSION: The digital pressure response to cooling is a useful test for RP and cold sensitive subjects. It has high sensitivity and specificity to differentiate between SSc spectrum RP and primary RP and between primary RP and cold sensitive subjects. Our preliminary data on vasodilator use suggest that the digital pressure response to cooling may also be useful in RP treatment studies.

Office evaluation and treatment of Raynaud's phenomenon.

BACKGROUND: Raynaud's phenomenon, an episodic vascular disorder induced by cold temperatures or stress and characterized by white, blue, and red discoloration of the fingers and toes, may affect up to 20% of the general population. KEY POINTS: Raynaud's phenomenon may exist independently (primary) or in association with an underlying disease (secondary), most commonly systemic sclerosis. The pathophysiologic features include vasospasm, endothelial cell changes, vessel obstructive features, and hemorrheologic factors. Raynaud's phenomenon is the initial manifestation of disease in 70% of patients with systemic sclerosis, in whom it may be present for many years before the development of the connective tissue disease. Patients with primary Raynaud's phenomenon need only conservative management and should be reassured that digital ischemia and loss of tissue occur extremely rarely. Pharmacologic agents that have been studied include vasodilators, platelet inhibitors, serotonin antagonists, and fibrinolytics. CONCLUSIONS: For prognostic and therapeutic reasons, it is important to determine if Raynaud's phenomenon is associated with an underlying condition and if the patient may develop a connective tissue disease.

Digital pressure responses to cooling in patients with suspected early vs definite scleroderma (systemic sclerosis) vs primary Raynaud's phenomenon.

OBJECTIVE: To compare digital vascular responses to local finger cooling in 4 groups of subjects: patients with definite scleroderma (SD, systemic sclerosis) meeting ARA criteria (n = 16), patients with suspected early SD (n = 12), patients with primary Raynaud's phenomenon (RP) (n = 23) and a control group of 29 healthy subjects. METHODS: Their digital systolic pressures were measured at 30, 20, 15 and 10 degrees C finger cuff temperature, in a room kept at 18 degrees C. RESULTS: The results of the digital pressure measurements showed a clearcut difference between the SD, primary RP and control groups, but there was no difference between patients with definite SD and those with suspected early SD. CONCLUSION: Under our experimental conditions, digital pressure response to local cooling separates groups of patients with primary RP and those with secondary RP related to SD from each other and from controls. The similarity between digital pressure responses of patients with suspected early SD and those with definite SD, suggests an early organic involvement of the digital vasculature in SD.

Geographic variation in the prevalence of Raynaud's phenomenon: Charleston, SC, USA, vs Tarentaise, Savoie, France.

We estimated the prevalence of Raynaud's phenomenon (RP) in the general population of 2 geographic areas, Charleston County, South Carolina, USA, and Tarentaise, Savoie, France, using the same methodology in both countries. The first phase of the study, consisting of the telephone survey of a randomly drawn sample of households, yielded 2086 completed interviews in Charleston and 2000 in Tarentaise. Cold sensitivity or unusual digital color changes were reported by 17.9% of the subjects in Charleston and by 31.3% in Tarentaise. In the second phase of the study the diagnosis of RP was made by a medical team. Based on these results, the estimated prevalence of RP is 5.0% (0.8% SE) in Charleston (women 5.7%, men 4.3%) and 16.8% (2.0% SE) in Tarentaise (women 20.1%, men 13.5%).

Capillary abnormalities, Raynaud's phenomenon, and systemic sclerosis in patients with localized scleroderma.

OBJECTIVES AND DESIGN: In vivo capillaroscopic examination was performed on patients with localized scleroderma to determine whether nailfold capillary abnormalities seen in systemic scleroderma (systemic sclerosis) were also present in the localized form. Twenty-seven patients (24 women, three men) were examined by this technique. RESULTS: Only two patients exhibited scleroderma-type nailfold capillary abnormalities similar to those seen in systemic sclerosis. Both patients also suffered from Raynaud's phenomenon and showed evidence of coexisting systemic sclerosis, one on first examination, the other 1.5 years later. Our results are compared with earlier studies reporting such rare coexistence of the two forms of scleroderma. Earlier capillaroscopic work in this disorder is also reviewed. CONCLUSIONS: These results suggest that the presence, in a patient with localized scleroderma, of nailfold capillary abnormalities similar to those seen in systemic sclerosis should alert the physician to a possible association with systemic sclerosis.

Negative symptoms in schizophrenia and nailfold plexus visibility.

Visibility of the nailfold vascular plexus has shown promise as a genetically transmitted marker for liability to schizophrenia. To assess whether this marker is specifically associated with negative or positive symptoms of schizophrenia, we reanalyzed patient data collected 20 years ago, well before interest in the negative/positive symptom distinction. Eighty-four patients, who retrospectively met DSM-III-R criteria for schizophrenia, had been rated for plexus visualization score (PVS) and independently interviewed using the Mental Status Schedule (MSS). Content scales were derived from the MSS to assess negative, positive, and affective symptoms. There was a highly significant correlation between PVS and negative symptoms (including verbal, motor, cognitive and motivational deficits), but not between PVS and positive or affective symptoms. These findings indicate that the negative symptoms of schizophrenia are due to a disease process biologically distinguishable from those causing positive symptoms and that plexus visibility is a risk marker for this pathology.

Demographic, social and clinical correlates of Raynaud phenomenon.

Our study has identified the demographic, social and clinical correlates of primary Raynaud phenomenon (RP) from a case-control study involving 235 subjects who were identified from a population-based prevalence survey of RP. All potential cases and a sampling of probable non-cases, identified by a screening questionnaire, were invited to a medical clinic for diagnostic testing and assignment of case or control status. Odds ratios (OR) for risk indicators for primary RP were estimated using multiple logistic regression to obtain 95% confidence intervals. The regression yielded statistically significant (p less than 0.05) positive associations for sex (OR = 3.0 for females versus males), self-reported alcohol use (OR = 1.1) and diastolic blood pressure (OR = 1.2) in those on antihypertensive medication. A significant (p = less than 0.01, OR = 0.4) negative association was found for Quetelet index (a measure of obesity). Near-significant or suggestive but non-significant negative associations were found between RP and marital status (p = 0.05, OR = 2.5), increased years of education and, for those on antihypertensive medication, higher systolic blood pressure (both p = 0.07).

Major clinical diagnoses found among patients with Raynaud phenomenon from the general population.

This study of 62 individuals with Raynaud phenomenon (RP) drawn from the general population of South Carolina shows a profile of associated diseases that is different from the one reported from hospital based studies. We found that connective tissue diseases affect a much smaller fraction of patients with RP than previously reported. Compared to RP negative controls, our RP positive group was found to suffer more frequently from a variety of diseases, both RP related and not RP related.