Critical tissue ischaemia in scleroderma: a note of caution.

Critical tissue ischaemia in scleroderma: a note of caution Vascular features dominate the clinical presentations of systemic sclerosis. Raynaud's phenomenon is the most typical presenting symptom. Renal involvement in early diffuse scleroderma and isolated pulmonary hypertension in late limited scleroderma are major causes of morbidity and mortality due exclusively to vascular change. A Raynaud-like transient vasoconstrictive response to cold has been suggested from clinical studies of the cardiac, pulmonary and renal circulations.'3 The clinical phenomenology is traditionally attributed to the ubiquitous presence of a fibrotic arteriosclerotic lesion of varying severity.4 Physiological vasoconstriction superimposed on the fixed occlusive luminal hyperplasia is seen as an adequate explanation for transient ischaemia, that is, Raynaud's phenomenon, and should be viewed as amenable to therapy. Of more dire clinical consequence is irreversible occlusion with attendant critical tissue ischaemia and subsequent tissue injury. There are few reliable data on factors involved in the initial pathogenesis and continuing evolution of the intimal hyperplasia and endothelial dysfunction which is typical of systemic sclerosis. There are virtually no data that explain the remarkable differences in clinical severity, pace of development, and patterns of visceral distribution of vascular injury between patients and classes of patients. This lack of basic understanding should not encourage nihilism by the bedside clinician. While fibrotic vascular occlusion is currently an untreatable lesion, a variety of potentially controllable factors should be considered in either or both intermittent vasoconstriction and irreversible vascular occlusion. For example, in vivo platelet activation is well documented in systemic sclerosis. Local adherence to damaged endothelium and circulating platelet aggregates as microemboli are two mechanisms for occlusion. Local release by activated platelets of thromboxane A2 and serotonin is a mechanism for vasoconstriction.5 Critical tissue ischaemia is a complex and multifactorial biological process. Many of the accepted participatory factors are well-documented in scleroderma including impaired vasomotion of afferent arterial circulation, enhanced neutrophil and platelet adherence to damaged endothelium, altered microcirculatory hydrostatics, and impaired venous outflow. Endothelial expression of ELAM-1 (endothelial leucocyte adherence molecule) is present in the microvasculature at very early stages of scleroderma6 as are peri-intimal foci of adherent neutrophils. Irrespective of the mechanism of initial injury, the endothelial response includes a number of pro-constrictive and/or prothrombotic elements including increased endothelin-1 release,7 diminished reserve of plasminogen activator8 and decreased production of endo-thelium dependent relaxing factor (nitric oxide). The complexity of the process suggests that no single therapy is adequate. Iloprost, a carbaprostacyclin, is …