Nifedipine in the treatment of Raynaud's syndrome

Thirteen patients with Raynaud's syndrome (10 idiopathic and three with scleroderma) were treated with nifedipine or placebo in a double blind crossover study. The immediate response to 20 mg nifedipine or placebo and the response to a three week course of treatment (10 mg nifedipine eight hourly) were assessed by Doppler mapping of digital arteries, finger pulse volume recordings, skin temperature measurements, and arterial Doppler waveform analysis. In addition, the number, duration, and severity of vasospastic attacks were noted, together with patient and observer opinion of each treatment, an overall pain score, and patient preference. There was a significant reduction in the number of attacks and in linear analogue score for pain after three weeks of nifedipine. Patient and observer opinion showed a significant preference for nifedipine. The objective tests, however, failed to detect any significant change in either the short or long term. This study supports the use of nifedipine for the relief of symptoms in selected patients with Raynaud's syndrome and implies that it may have a unique mode of action.     

Significance of anticentromere antibody in idiopathic Raynaud's syndrome

Fifty-eight patients with Raynaud's syndrome who had no evidence of definite underlying connective tissue disease had serum analyzed for the presence of anticentromere antibody using indirect immunofluorescence techniques on HEp-2 cell lines. Eighteen patients (31 percent) were anticentromere antibody-positive. The anticentromere antibody-positive group demonstrated significantly more frequent digital telangiectases, digital edema, elevated levels of immunoglobulins, and low C4 values. Photoplethysmography revealed significantly diminished blood flow in the anticentromere antibody-positive group. Capillary microscopy revealed significantly increased avascularity and number of dilated loops in the anticentromere antibody-positive group. Giant loops were seen exclusively in the anticentromere antibody-positive group. The clinical findings in the anticentromere antibody-positive group are suggestive of a transition to a connective tissue disease with features of the CREST syndrome.     

Medical treatment of Raynaud's syndrome

The authors review the drug treatment of Raynaud's disease. Many substances have been used including nitrate derivatives, calcium antagonists, alpha blockers, angiotensin converting enzyme inhibitors, prostaglandin E1, E2 and I2, and ketanserin. The efficacy of these drugs is often partial and variable. The indications are discussed with respect to the clinical course and etiology of the Raynaud's phenomenon.     

Nifedipine in the treatment of Raynaud's phenomenon. Evidence for inhibition of platelet activation

Platelet activation has been reported to occur in patients with Raynaud's phenomenon; however, the effect of calcium channel blockers and thromboxane synthetase inhibitors has not been previously studied. The effect of two drugs that potentially inhibit platelet activation were studied: nifedipine, a calcium channel blocker, and dazoxiben, a specific thromboxane synthetase inhibitor. Two platelet-specific proteins released during platelet activation, beta-thromboglobulin and platelet factor 4, were measured during a double-blind clinical trial of these two drugs in patients with Raynaud's phenomenon. The plasma beta-thromboglobulin level was significantly elevated in the patient population (53.8 +/- 7.6 ng/ml) during the placebo period compared with that in a normal control population (27.0 +/- 3.1 ng/ml) (p less than 0.01). The plasma platelet factor 4 level was 8.7 +/- 2.2 ng/ml in the patients compared with 6.5 +/- 1.0 ng/ml in the normal subjects (p = NS). These findings indicate the presence of in vivo platelet activation in patients with Raynaud's phenomenon. Nifedipine lowered the levels of beta-thromboglobulin to near the normal range (33.4 +/- 4.6 ng/ml). The inhibition of platelet activation by nifedipine was associated with clinical improvement in Raynaud's phenomenon with fewer and less intense episodes. Beta-thromboglobulin was not lowered by dazoxiben (58.1 +/- 9.0 ng/ml) compared with the placebo. The reduction of beta-thromboglobulin levels by nifedipine indicates that in vivo platelet activation was inhibited by this agent. Since this was associated with a reduced frequency of attacks, it is not clear whether this was a direct effect of the drug on platelet activation, leading to decreased frequency of vasospasm, or an effect on vascular smooth muscle leading to decreased vasospasm and a secondary decrease in platelet activation.     

Nifedipine and alpha1-adrenergic blockade in Raynaud's phenomenon

The efficacy of nifedipine and prazosin in the treatment ofRaynaud's phenomenon was assessed in a prospective double-blindrandomized cross-over trial in 15 patients. Each patient receivedone week of nifedipine 20 mg TID, one week of prazosin 1 mgTID, and 2 weeks of placebo. Nifedipine was shown to be effectivein reducing both the frequency and the severity of Raynaud'sphenomenon, whereas prazosin was ineffective. Before initiationof therapy in the 15 patients, pressor responses to the intravenousalpha₁-agonist phenylephrine were assessed in the basal state,30 min after 20 mg oral nifedipine, and 30 min after 1 mg oralprazosin; the shift to the right of the log dose-vasopressorresponse curves to phenylephrine was similar with nifedipineand prazosin.     

Nifedipine in pulmonary arterial hypertension. Importance of Raynaud's phenomenon

We studied (via acute vasodilator testing with nifedipine) 27 patients with pulmonary arterial hypertension (PAH) (11 primary, 16 secondary PAH, [including six patients with Raynaud's phenomenon]) in order to identify predictors of hemodynamic response and specifically to assess whether patients with Raynaud's phenomenon and pulmonary hypertension were more likely to respond to nifedipine. Nifedipine decreased resting mean pulmonary artery (PA) pressure and pulmonary vascular resistance (PVR) in patients with Raynaud's phenomenon (delta PA - 6.8 +/- 10.5 mm Hg; delta PAD - PCW gradient - 9.3 +/- 4.7 mm Hg; delta PVR - 255 +/- 201 dynes.s.cm-5, all p less than .05) versus (delta PA 0.3 +/- 4.0 mm Hg; delta PAD - PCW gradient 0.4 +/- 5.0 mm Hg; delta PVR - 58 +/- 132 dynes.sec.cm-5, all NS), in the patients without Raynaud syndrome. These data suggest that patients with both primary and secondary PAH may benefit from nifedipine therapy, but that patients with Raynaud's phenomenon may respond particularly well, perhaps because of vasodilator-reversible pulmonary vasoconstriction. An alternative hypothesis is that prior chronic vasodilator therapy in the majority of our patients with Raynaud's phenomenon preserved pulmonary vasoreactivity.     

Digital capillaroscopy in idiopathic Raynaud's disease

Nail-fold capillaroscopy is performed on 135 patients with primary Raynaud's disease. There is no significant difference between patients with long clinical story and new ones. The capillaroscopy is highly correlated with severity of vasomotor troubles. Parameters of bad prognosis are a high frequency of morphological abnormalities, venodilation, sludge phenomenon and hemorrhagies.     

Nifedipine and Raynaud's phenomenon associated with connective tissue diseases

We have evaluated the therapeutic effect of the calcium-channel blocking agent nifedipine in Raynaud's phenomenon associated with connective tissue diseases and in idiopathic digital vasospasm. Thirty patients were included in this study: Raynaud's phenomenon was associated with progressive systemic sclerosis (PSS) in ten patients, systemic lupus erythematosus (SLE) in five and rheumatoid arthritis (RA) in three; it was idiopathic (I) in twelve patients. Each patient received, in a double-blind manner and random order, on two consecutive weeks, nifedipine (20 mg three times daily) and placebo. Nifedipine proved to be effective: the mean number of digital vasospastic attacks per week decreased from 20.30 to 5.83 (p less than 0.01). The results in the SLE and RA groups were similar and were pooled. The improvement (in percent decrease) was better in the idiopathic group (90.95) than in the SLE and RA group (78.63, p less than 0.02) and the PSS group (64.02, p less than 0.01).     

Increased alpha-adrenergic responsiveness in idiopathic Raynaud's disease

In our study of 28 patients with idiopathic Raynaud's disease, the patients had significantly greater digital blood flow responses to intraarterial phenylephrine and clonidine than did normal control subjects. There were no group differences in finger blood flow responses to body heating, reflex cooling, digital ischemia, or to intraarterial tyramine or isoproterenol. There were also no group differences in blood pressure or heart rate during any procedure. These results suggest that patients with idiopathic Raynaud's disease have increased peripheral vascular alpha-adrenergic receptor sensitivity and/or density compared with normal persons.     

The value of thoracoscopic sympathectomy in the treatment of Raynaud's syndrome]

On the basis of a follow-up period lasting at least 6 years concerning 23 patients, in whom on account of a Raynaud-syndrome a thoracoscopic sympathicotomy in the region Th 2-5 was carried out in most cases bilaterally in two sessions, in comparison with the sympathicectomy performed in major surgery can be established:no mortality, no serious complications, duration of stay in hospital 5-7 days, no absolute healing. In a follow-up period of the same length in an approach of major surgery absolute healings are possible, but only in 35%. This gain is loaded by a longer stay in hospital of at least 10 days and a mortality of 4.3% as well as by a complication rate of 6-41%, to which in 8-13% of the cases a Horner-syndrome comes. Therefore, before an approach in major surgery a thoracoscopic intervention is to be tried. The thoracoscopic operators should strive for a sympathectomy with destroy of the ganglia Th 2 and 3 instead for a sympathicotomy.     

Controlled double-blind trial of the clinical effect of nifedipine in the treatment of idiopathic Raynaud's phenomenon

Twenty-six patients with idiopathic Raynaud's phenomenon participated in a double-blind, crossover clinical trial comparing the clinical effect of nifedipine with that of placebo. Four patients discontinued the study because of side effects and one patient defaulted at the return visit. Nifedipine significantly reduced frequency and severity of attacks (p less than 0.01). In an overall evaluation of drug effectiveness, 19 of 21 patients preferred nifedipine to placebo (p less than 0.01). Nifedipine proved to be effective in the treatment of idiopathic Raynaud's phenomenon, but side effects should be expected in some 30%.     

Interferon-induced Raynaud's syndrome

OBJECTIVE: To review the clinical features, diagnosis, treatment, and outcome of interferon-induced Raynaud's phenomenon. METHODS: The medical literature was reviewed from 1967 to November 2001 with the assistance of a MEDLINE search using the key words: Raynaud, Interferon, ischemia, thrombosis and necrosis. A qualitative review was performed after the articles were abstracted and the relevant information was summarized. RESULTS: Twenty-four cases of interferon-induced Raynaud's phenomenon (including our patient) are described. Interpheron-alpha was the most common causative agent (14 cases). The symptoms appeared weeks to years after beginning treatment and varied from mild vasospasm to occlusion of digital arteries and tissue necrosis (14 cases), sometimes necessitating finger amputation (6 patients). Digital plethysmography, arteriography and capillaroscopy were valuable diagnostic tools. In 4 cases, cardiac, ophthalmic, or central nervous system drug-induced ischemia accompanied the peripheral Raynaud's phenomenon. Of the 15 cases with a documented outcome, withdrawal of the drug alone resulted in complete (6 patients) or partial (1 patient) recovery. In the others, supportive therapy was needed. The recovery period lasted from 2 weeks to 3 months. In 2 patients, continuation of treatment was possible. CONCLUSIONS: Raynaud's phenomenon and related complications must be recognized as possible side effects of interferon therapy. Early diagnosis and withdrawal of the drug may prevent unnecessary morbidity and disability.     

Esophageal motility in Raynaud's disease, systemic scleroderma and presclerodermal Raynaud's syndrome

Fifty-five consecutive subjects with Raynaud's phenomenon were submitted to esophageal manometry. According to the results of clinical examination and periungual capillaroscopy, they were divided into three groups: sixteen patients presented presclerodermal Raynaud's phenomenon, and nineteen, systemic sclerosis; twenty others had Raynaud's disease. Twenty volunteers formed the control group. Esophageal motor disorders were observed in the group with presclerodermal Raynaud's phenomenon, affecting the esophageal lower sphincter and the peristalsis of the body of the esophagus. In the group with systemic sclerosis, these motor disorders were associated with alterations in the amplitude and the duration of contractions. Esophageal motility was normal in subjects with Raynaud's disease. We can conclude that: 1) esophageal motor disorders can be seen in presclerodermal Raynaud's phenomenon. The kind of abnormalities observed at this stage of the disease are in favor of an early alteration of the neurogenic component of esophageal motility; 2) there is no relationship between esophageal motor disorders and Raynaud's phenomenon in scleroderma.