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Thermographic and Symptomatic Effect of a Single Dose of Sildenafil Citrate on Raynaud's Phenomenon in Patients with Systemic Sclerosis: A Potential Treatment
To the Editor: Raynaud's phenomenon (RP) associated with systemic sclerosis (SSc) can be difficult to treat and therefore potential treatments warrant further investigation. We performed a pilot study to see if sildenafil citrate (Viagra TM , Pfizer) could provide any benefit in these patients. We assessed objective skin temperature responses to mild cold challenge post-sildenafil dosing, and subjective symptomatic relief to patients with RP and SSc. RP was defined by characteristic skin color changes, with at least 6 episodes a week 1 . All patients were women, nonsmokers, and postmenopausal or using adequate contraception. Clinical assessment consisted of items in Table 1. Dynamic thermal imaging of the hands was used to quantify skin temperature changes, and digital temperatures were taken simultaneously. Measurements were performed in a temperature-controlled thermal physiology laboratory (24 ± 1ºC). A standardized mild cold challenge test was performed 1 after acclimatizing for 30 minutes. Thermal images of the hands were collected every minute for 15 minutes post-challenge. Individual finger skin temperature responses were processed (FLIR ThermaCAM Researcher) to calculate 2 measures, (1) the area under the curve (AUC) between 1 and 15 minutes post-cold challenge and (2) the percentage recovery to mean baseline temperatures at 15 minutes post-cold challenge. Pre- and post-treatment visual analog scale (VAS) of the hands were also measured. A low VAS indicated a greater feeling of cold discomfort. The patients attended on 2 occasions, being given 50 mg sildenafil on visit 1 and 75 mg sildenafil on visit 2. A baseline cold challenge was performed, the sildenafil was then administered, and after 60 minutes the assessments and cold challenge were repeated. Blood pressure (BP) was measured at 15-minute intervals up to 90 minutes post-dosage.
Five patients fulfilling the American College of Rheumatology criteria 2 for the classification of SSc were recruited. Three patients underwent study at both the 50 mg and 75 mg dosage, 2 declined further participation at the higher dose, one because of a deterioration in SSc, and the other because she had a headache after visit 1. This was the only adverse event reported. The AUC and percentage recovery to baseline temperatures were calculated for each digit. Of the 5 patients, 3 had clear and significant improvements in digital temperature responses to mild cold challenge (Figure 1). The fourth patient took only 50 mg of sildenafil and showed no significant change in digital temperature responses. Comparisons for Patient 1 could not be made as digital temperatures at 60 minutes were too low for cold challenge testing post-drug. However, this patient did show a finger temperature flush at 30 minutes post-dosing with 75 mg of sildenafil.
VAS improved overall, with median increases in VAS of + 10 mm for 50 mg and + 15 mm for 75 mg dosages, using post-dose/pre-dose data. Table 1 shows patient details and VAS scores. There was a small hypotensive effect, following drug administration for both dosages. At 50 mg mean BP dropped from 128/75 mm Hg to 86/67 mm Hg, at 75 mg sildenafil mean BP dropped from 113/73 mm Hg to 100/72 mm Hg. There were no clinical manifestations of hypotension. No patient had digital ischemic lesions at the time of the study. Our study shows that sildenafil citrate produced quick thermographic and symptomatic improvement in patients with SSc and RP, and was well tolerated. The use of a single dose would suggest that patients with RP could use the drug on an "as required" basis prior to when they knew they would be exposed to cold. This could be useful as RP occurs episodically. It may, however, also be useful to take sildenafil regularly, perhaps starting at a dose of 50 mg bd, especially during periods of cold weather. These results warrant a randomized, controlled study on a larger group of patients with SSc. NAMITA KUMAR, MMEd, MRCP, Research Registrar; BRIDGET GRIFFITHS, MD, MRCP, Consultant Rheumatologist, Musculoskeletal Unit; JOHN ALLEN, PhD, Medical Physicist, Regional Medical Physics Department, Freeman Hospital, Newcastle-upon-Tyne, NE7 7DN, UK. ACKNOWLEDGMENTS Thanks to Prof. Alan Murray without whose support this work would not have been completed. The tablets for this study were provided by Pfizer. Pfizer has not been involved with any other aspects of this study.
1. Coleiro B, Marshall SE, Denton CP, et al. Treatment of Raynaud's phenomenon with the selective serotonin reuptake inhibitor fluoxetine. Rheumatology Oxford 2001;40:1038-43. 2. American College of Rheumatology Preliminary criteria for Systemic Sclerosis. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:581-90.
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