- a Neurovascular Medicine Unit, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine at St Mary's Hospital, London W2 1NY
- b Autonomic Unit, University Department of Clinical Neurology, National Hospital for Neurology and Neurosurgery, Queen Square and Institute of Neurology, University College London WC1N 3BG
- Correspondence to: Professor Mathias
- Accepted 17 June 1997
In Raynaud's phenomenon, cold or emotional stimuli cause digital vasospasm in the fingers and toes, leading to the classic colour triad sequence of pallor, cyanosis, and redness. Secondary Raynaud's phenomenon occurs in association with underlying disease, including neurological disorders.1 We describe Raynaud's phenomenon in patients with sympathetic denervation due to primary chronic autonomic failure.
Subjects, methods, and results
Seventy three patients with primary chronic autonomic failure were assessed for Raynaud's phenomenon. They all had orthostatic hypotension due to sympathetic failure, which was confirmed on detailed investigation.2 Thirty two patients had pure autonomic failure and no other neurological features and 41 had multiple system atrophy (the Shy-Drager syndrome) with parkinsonian or cerebellar features, or both. None had clinical features or disease usually associated with Raynaud's phenomenon. All the patients consented to answer a questionnaire, approved by the ethics committee of St Mary's Hospital, London.
Patients were considered to be positive for Raynaud's phenomenon if they had a definite sensitivity to cold. Overall, 51 patients had Raynaud's phenomenon, all showing the classic colour sequence triad in their hands (1); four patients were unsure of the sequence of colour change (one had pure autonomic failure and three multiple system atrophy). Over half of the patients reported a worsening of the condition in their hands and feet during cold weather. Under half of the patients reported that rubbing and warmth provided relief in their hands and feet within 15 minutes. Overall, 34 patients had Raynaud's phenomenon before being treated for orthostatic hypotension—all were prescribed fludrocortisone and the majority were taking the sympathomimetic vasoconstrictors ephedrine or midodrine. In most patients drug treatment did not worsen the condition. Patients reported similar findings in their hands and feet.
This study confirms that Raynaud's phenomenon and cold sensitivity in the hands and feet commonly occur in patients with sympathetic denervation due to primary chronic autonomic failure. We did not assess the effect of emotional stimuli on Raynaud's phenomenon in our patients. Most patients described the classic symptoms of the phenomenon in their hands and feet. Published data indicate that the prevalence of Raynaud's phenomenon varies from 0.5% to 20% according to population, age, and sex.1 The incidence was considerably higher in our patients with autonomic failure. None of them had an underlying disorder known to be associated with Raynaud's phenomenon, and most were followed up for over 1 year. None of our patients presented with Raynaud's phenomenon; we did not inquire at what stage in their illness it occurred. In most of them drug treatment did not seem to induce or worsen it.
Cold sensitivity in Raynaud's phenomenon may be linked to sympathetic activation.3 Surgical sympathectomy usually is not effective in treating Raynaud's phenomenon, probably because adrenoceptors in limb vessels will still interact after such surgery with circulating catecholamines, including those released from the adrenal medulla. In primary chronic autonomic failure the function of the adrenal medulla usually is impaired but there is pressor supersensitivity to noradrenaline4; whether residual sympathetic activity (however minimal) along with supersensitivity contributes to cold sensitivity and Raynaud's phenomenon is unclear. There was no important difference in the frequency of Raynaud's phenomenon in patients with pure autonomic failure, who have peripheral lesions and low plasma noradrenaline concentrations, when compared with patients with multiple system atrophy, who have central autonomic lesions and basal plasma noradrenaline concentrations usually within the normal range. Calcitonin gene related peptide and nitric oxide seem deficient in primary Raynaud's phenomenon5; it is not known whether such abnormalities occur in primary chronic autonomic failure.
We thank Mrs K Bleasdale-Barr for help with patient recruitment and the questionnaire.
Conflict of interest: None.
Contributors: RM completed the questionnaire after discussion with patients, analysed the data, and helped write the paper. CJM made the initial clinical observations and was closely involved in the construction of the questionnaire, in confirmation of the analysis, and in writing the paper; he will act as guarantor of the study.