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Patients with systemic sclerosis present a great many challenges to doctors, one of them being to ¢nd a way of accurately determining the extent of a disease which today is reliant on expensive invasive procedures. Another challenge is ¢nding a parameter for disease activity that can be used to monitor e¤cacy of treatment. In this issue, Majewski et al. (pp. 207 ^ 210) compare staging of disease in 13 patients with di¡use systemic scleroderma, 23 patients with limited systemic scleroderma, 7 with Raynaud's phenomenon and 25 healthy controls. The strengths of this work are that the number of patients included in the study is high, staging has been performed carefully, and a broad range of parameters is studied. The results show that soluble TNF-alfa-RI, sIL-2R and PIIINP were signi¢cantly elevated in patients compared with controls. These markers were also signi¢cantly more frequent among patients with di¡use disease compared with those with limiteddisease.TNF-alfa-RIandPIIINPshowed thebest correlation to disease extent.TNF-alfa-RI had the best clinical correlationwithskin,muscleandlunginvolvement,andtheparameter correlatedwith lung disease in systemic sclerosis.There were no correlations with arthralgia, duration of Raynaud's phenomenonordurationofskinsclerosis. Interestingly, therewasnocorrelation between the ``immunemarkers''andANA. The conclusions drawn from this study indicate there may be an advantage in using new in£ammation parameters ^ especially sTNF-alfa-RI ^ to facilitate documentation of disease extent and ^ and perhaps more importantly ^ in monitoring the e¤cacy of the treatment. The well-known serological markers of ANA are less helpful. Further examination of these parameters during treatment is needed. One word of caution though is that 3 out of 13 patients with systemic sclerosis did not have increased levels of TNF-alfa-RI in serum. Thus, biology is never simply ``black-or-white''.

What Biochemical Markers are Best for Measuring the Extent of Disease in Patients with Sclerosis?