Microcirculatory Effects of Iloprost in Patients with Suspected Secondary Raynaud Phenomenon

Abstract

Background: The clinical efficacy of iloprost, a stable analogue of prostacyclin, in patients with Raynaud's phenomenon (RP) has been widely reported. However, its mechanism of action is still unclear, and also unknown is why the benefit lasts for many weeks after therapy is discontinued.

The aim of the present study was to learn what kind of microcirculatory changes occur in the skin of the affected hand one month after the end of iloprost treatment in patients with RP.

Patients and Methods: Eleven subjects (8 women, 3 men, mean age forty-four years) with RP suspected to be secondary to a collagen disease entered the study and were infused with iloprost up to 2.0 ng/kg/minute for six hours on five consecutive days. At baseline and one month after treatment discontinuation, laser Doppler flowmetry, thermography, and computer-assisted video capillaroscopy of the affected hand were performed.

Results: At the end of follow-up, the mean capillary density as recorded by video capillaroscopy was significantly increased as was the skin temperature in the different areas (fingertip, nailbed, tenar, hypotenar). In contrast, laser Doppler flowmetry revealed no significant changes after therapy.

Comment: The improvement of vascularization of the skin and, therefore, the decrease in avascular areas in patients with RP suspected to be secondary to a connective tissue disease appear to be associated with enhancement of nutritional flow. Rather than rely on an angiogenetic effect of iloprost, these modifications may be related to the drug-induced normalization of the described dysfunctional arteriolar-venular anastomoses in the skin of RP patients through redistribution of flow.

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References

1. Belch, JJF , Drury JK , Capell HA , et al: Intermittent epoprostenol (prostacyclin) infusion in patients with Raynaud's syndrome. Lancet i:313-317, 1983.

2. Dowd PN , Martin MFR , Cooke ED , et al: Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PG12). Br J Dermatol 106:81-89, 1982.

3. Watson HR , Belcher G : Retrospective comparison of Iloprost with other treatments for secondary Raynaud's phenomenon. Ann Rheum Dis 50:359-361, 1991.

4. Cook ED , Kirby JDT , Mant TGK : Double-blind comparison of three days infusion of Iloprost and continuous oral Nifedipine on symptomatology and digital blood flow in patients with Raynaud's phenomenon secondary to systemic sclerosis. In: Angiologie, ed. by Boccalon H. Paris : J. Libbey Eurotext , 1988, pp 555-557.

5. Keller J , Kaltenecker A , Schricher KT , et al: Inhibition of platelet aggregation by a new stable prostacyclin introduced in therapy of patients with progressive scleroderma. Arch Dermatol Res 277:323-325, 1985.

6. Bertele V , Mussoni L , Del Rosso G , et al: Defective fibrinolytic response in atherosclerotic patients. Effect of Iloprost and its possible mechanism of action. Thromb Haemost 60:141-144, 1988.

7. Schulz BG , Muller B : Iloprost antagonizes endothelin-induced vasoconstriction in macro and microcir-culation. Eicosanoid 3:135-138, 1990.

8. Yardumian DA , Isemberg DA , Rustin M , et al: Successful treatment of Raynaud's syndrome with iloprost, a chemically stable prostacyclin analogue. Br J Rheum 27:220-226, 1988.

9. Rademaker M , Thomas RHM , Provost G , et al: Prolonged increase in digital blood flow following Iloprost infusion in patients with systemic sclerosis. Postgrad Med J 63:617-620, 1987.

10.

10. Cimminiello C , Milani M , Pietra A , et al: Deficient fibrinolytic response in patients with Raynaud's phenomenon and its correction with defibrotide. Semin Thromb Hemost 17 (suppl 1):106-111, 1991.

11.

11. Pola P , Tondi P , Serricchio M , et al: New prospects for the treatment of Raynaud's phenomenon using a serotoninergic S2 receptor antagonist (ketanserin) and stable derivates of prostacyclin. Angiology 44:123-128, 1993.

12.

12. Rademaker M , Cooke ED , Almond NE , et al: Comparison of intravenous infusion of Iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: A double blind randomized study. Br Med J 298:561-564, 1989.

13.

13. McHugh NJ , Csuka M , Watson H , et al: Infusion of Iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. Ann Rheum Dis 47:43-47, 1988.

14.

14. Wigley FM , Seibold JR , Wise RA , et al: Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. J Rheumatol 19:1407-1414, 1992.

15.

15. Kyle MV , Belcher G , Hazleman BL : Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon. J Rheumatol 19:1403-1406, 1992.

16.

16. Wollewrsheim H , Thien TH : Transcutaneous po2 measurements in Raynaud's phenomenon. Value and limitations. Int J Microcirc: Clin Exp 7:357-366, 1988.

17.

17. Maricq HR , Spencer-Green G , Carwile Le Roy E : Skin capillary abnormalities as indicators of organ in volvement in scleroderma (systemic sclerosis), Raynaud's syndrome and dermatomyositis. Am J Med 61:862-869, 1976.

18.

18. Maricq HR : Widefield capillary microscopy technique and rating scale for abnormalities seen in scleroderma and related disorders. Arthritis Rheum 24:1159-1165, 1981.

19.

19. Curri SB : Anatomopatologie des relations micro-vas-culo tissulaires dans la Maladie de Raynaud. Symposium European sur le Phenomen de Raynaud, Paris, December 1983.

20.

20. Torley HI , Madhok R , Capell HA , et al: A double blind, randomized, multicentre comparison of two doses of intravenous Iloprost in the treatment of Raynaud's phenomenon secondary to connective tissue diseases. Ann Rheum Dis 50:800-804, 1991.