SYSTEMIC SCLEROSIS RELATED CALCINOSIS: PATIENTS PROVIDE WHAT SPECIALISTS WANT TO LEARN.

BACKGROUND: Calcinosis is a disabling, rarely discussed manifestation of systemic sclerosis (SSc) for which the natural history and management is understood poorly. OBJECTIVES: To develop a calcinosis specific patient reported outcome measure (PROM) that can be used for future clinical research to test the effects of therapy on scleroderma related calcinosis. METHODS: Patients were selected for participation by their scleroderma physicians. Four focus groups and individual interviews were recorded and transcribed verbatim. Patients were asked to frame questions to help a physician learn if calcinosis was better, worse or the same. Patient transcripts underwent an iterative inductive process (no preconceived coding, content drives coding and analysis) by at least five independent analysts including at least one research team member with SSc. Concepts were triangulated to identify a comprehensive set of meaningful concepts with occurrence quantified per participant. RESULTS: Twenty-three patients (22/23 female, 19/23 white, with mean disease duration 14.8 years) consented and were interviewed. Responses included concepts of self-management strategies and recurrent hypotheses relating calcinosis development to trauma, Raynaud's and cold exposure. We identified discrete concepts such as the perceived association between cold exposure, Raynaud's and calcinosis severity. Calcinosis tended to present along with or soon after SSc diagnosis and remained throughout disease duration - though was not yet compared to report of first Raynaud experience. CONCLUSIONS: Patient observations and self-management behavior provide opportunities for experts to learn from and to preemptively educate physicians and patients. Patients are eager for self-management guidance. These concepts are the groundwork for PROM development. However, patients suggested a composite of scales anchored in pain, size, frequency, number and related impairment may reasonably serve as an interim instrument for SSc calcinosis.

Recognition of pulmonary hypertension in the rheumatology community: lessons from a Quality Enhancement Research Initiative.

OBJECTIVES: The aim of this study was to utilise the Quality Enhancement Research Initiative in Systemic Sclerosis (QuERI-SSc) to measure and reduce a perceived gap in the diagnosis of pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc). METHODS: Rheumatologists enrolled patients with SSc (aged ≥ 18 years) and provided data on a panel of diagnostic tests over 3 years. Pulmonary function testing, echocardiography, 6-minute walk distance, N-terminal pro-brain natriuretic peptide assays, high-resolution computed tomography of the lungs, and ventilation/perfusion scan plus right heart catheterisation (RHC; when appropriate) were emphasised. Exclusion criteria included previously documented PAH, interstitial lung disease, and SSc overlapping with other connective tissue disease. RESULTS: Participating rheumatologists enrolled 207 patients with SSc (90% female; 80% white), with a median age of 57 years and median disease duration of 5 years. A total of 82% of patients were classified as New York Heart Association functional class I and II; of these patients, 177 had an echocardiogram at enrolment and 191 at any time during the study. Of those who met study-specified criteria for RHC at enrolment, only 3 of 7 patients underwent RHC. CONCLUSIONS: The screening algorithm was successful in identifying patients with mild impairment. Although specific tools were recommended for screening PAH in patients with SSc, results indicate that significant diagnostic care gaps still exist in the general rheumatology community. Better understanding and adherence to guidelines could improve the care and, ideally, outcomes of these high-risk patients.

Pulmonary hypertension and interstitial lung disease within PHAROS: impact of extent of fibrosis and pulmonary physiology on cardiac haemodynamic parameters.

OBJECTIVES: We sought to examine the relationship between measures of ILD severity and PH in patients with SSc. METHODS: We identified 55 subjects from 12 PHAROS sites with RHC-proven PH and HRCT evidence of ILD. Subjects with PH due to left heart disease were excluded. Baseline HRCT scans were scored by a standardised system that graded severity of ILD. Summary statistics were generated for baseline characteristics. Spearman correlation and linear regression were used to examine relationships between ILD and PH severity variables. RESULTS: The majority of subjects were white women; nearly half had limited cutaneous SSc. Most subjects were New York Heart Association functional class II or III. Pulmonary function testing revealed moderate restriction (mean FVC 64.3 ± 17.2% predicted) with severe reduction in diffusing capacity (mean DLco 34.2 ± 13.3% predicted). RHC demonstrated mild to moderate PH (mean PAP 35 ± 9 mmHg, mean PVR 5.1 ± 3.7 WU). There was no correlation between severity of ILD (by either HRCT or PFT) and cardiac haemodynamic parameters of PH. CONCLUSIONS: No association between severity of ILD and cardiac haemodynamic profiles were identified in this cohort. We believe this underscores the complex nature of PH and ILD in individuals with SSc. We do suspect that some individuals with SSc-ILD will also have concomitant pulmonary vascular disease but simple assessments to grade severity of ILD - by PFT or HRCT estimates of ILD extent - are likely not enough to reliably distinguish between PAH versus PH-ILD. Further research into how to distinguish and manage these subsets is warranted.

Development of a provisional core set of response measures for clinical trials of systemic sclerosis.

OBJECTIVE: To develop a provisional core set of response measures for clinical trials of systemic sclerosis (SSc). METHODS: The Scleroderma Clinical Trials Consortium (SCTC) conducted a structured, 3-round Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. Round 1 asked the SCTC investigators to list items in 11 pre-defined domains (skin, musculoskeletal, cardiac, pulmonary, cardio-pulmonary, gastrointestinal, renal, Raynaud phenomenon and digital ulcers, health-related quality of life and function, global health, and biomarkers) for SSc clinical trials. Round 2 asked respondents to rate the importance of the chosen items and was followed by a meeting, during which the Steering Committee discussed the feasibility, reliability, redundancy and validity of the items. Round 3 sought to obtain broader consensus on the core set measures. Members also voted on items that had data on feasibility but lacked data on reliability and validity, but may still be useful research outcome measures for future trials. RESULTS: A total of 50 SCTC investigators participated in round 1, providing 212 unique items for the 11 domains. In all, 46 (92%) participants responded in round 2 and rated 177 items. The ratings of 177 items were reviewed by the Steering Committee and 31 items from the 11 domains were judged to be appropriate for inclusion in a 1-year multi-centre clinical trial. In total, 40 SCTC investigators completed round 3 and ranked 30 of 31 items as acceptable for inclusion in the core set. The Steering Committee also proposed 14 items for a research agenda. CONCLUSION: Using a Delphi exercise, we have developed a provisional core set of measures for assessment of disease activity and severity in clinical trials of SSc.

Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases.

This paper reports the experiences of our group with 68 patients with progressive systemic sclerosis (PSS) admitted to hospitals of the University of Pittsburgh Health Center between 1955 and 1981 with scleroderma renal crisis (SRC). The onset of SRC was characterized by four features, namely, onset or aggravation, usually abrupt, of arterial hypertension; appearance of Grade III or IV retinopathy; elevations of peripheral renin activity to at least twice the upper limit of normal; and rapid deterioration of renal function within a period of less than one month. Over 90% of our patients in whom these criteria could be determined had at least three of them present with the onset of SRC. Management of these patients during the first 15 years of this period was uniformly ineffective. Before 1971, no patients lived longer than a year; usual survival ranged from 1 to 3 months. With the advent of renal dialysis and the more effective treatment of severe hypertension, along with the utilization of bilateral nephrectomy in selected anuric patients, some improvement in longevity was achieved. However, only in the past few years have we accumulated a group of 11 patients who have survived for longer than one year. The clinical characteristics of the onset and progression of SRC suggest the sudden imposition of severe stress such as cold or an autoimmune insult affecting vulnerable arteries and arterioles. The renal damage becomes self-perpetuating with extremely high renin activity causing further rise in blood pressure and additional renal and systemic vascular damage. Progress in the last few years seems to have been achieved primarily by the advent of pharmacologic agents that specifically block the effect of angiotensin II by inhibiting the angiotensin I converting enzyme. When diagnosis is prompt and the condition is treated as an emergency with these compounds, we and others have found that normal renal function can be restored in a number of patients. The result is a considerably brighter outlook for patients with this previously rapidly fatal complication of progressive systemic sclerosis.

Factors predicting development of renal involvement in progressive systemic sclerosis.

Renal involvement or "scleroderma renal crisis" developed in 60 patients with progressive systemic sclerosis evaluated at the University of Pittsburgh during the period from 1972 to 1982. Forty-seven of these patients had progressive systemic sclerosis with diffuse scleroderma, representing 18 percent of persons with progressive systemic sclerosis and diffuse scleroderma evaluated during this time period. Ten additional patients did not have truncal scleroderma but were suspected of having incompletely developed diffuse scleroderma. Only three patients were classified as having progressive systemic sclerosis with the CREST syndrome. Renal crisis was observed early in the course of the illness, a mean of 3.2 years after onset. During May and June, this complication developed in fewer patients than expected. Thirty-six patients who had diffuse scleroderma and renal involvement after their initial Pittsburgh evaluation were compared with 212 who had diffuse scleroderma without renal involvement during follow-up. The patients with renal involvement had a shorter mean disease duration at the time of their first evaluation (2.4 versus 4.2 years, p less than 0.05) and less frequently had digital pitting scars (29 versus 54 percent), but no other significant clinical, laboratory, or serologic differences were noted. Data available for 31 patients with renal involvement during the six months preceding the onset of renal disease were analyzed. Blood pressure, serum creatinine, urine protein and red blood cells, and plasma renin levels were similar in these patients and the 212 patients without renal involvement. More patients with renal involvement had anemia or clinical evidence of cardiac involvement during this period compared with the patients without renal involvement. During the 12-month period prior to renal involvement, seven of 16 (44 percent) patients with such involvement had an impressive increase in skin thickening on physical examination compared with only 23 of 180 (14 percent) patients without renal involvement at any time during their course. Thus, the subset of patients with diffuse scleroderma who show rapid progression of their skin thickening early in the illness with development of anemia, pericardial effusion, or congestive heart failure have a high risk of "scleroderma renal crisis."

Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma.

Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease.

The electrocardiogram in systemic sclerosis (scleroderma). Study of 102 consecutive cases with functional correlations and review of the literature.

The electrocardiographic findings in 102 consecutive patients with scleroderma were reviewed to determine the frequency and nature of the electrocardiographic abnormalities associated with this disease. Septal infarction pattern unassociated with QRS prolongation was present in 10 percent, compared with none of 96 control subjects (p less than 0.001). Ventricular conduction abnormalities were present in 17 percent. A normal electrocardiogram was obtained in 49 percent. A subset of 48 patients underwent detailed cardiopulmonary evaluation including exercise thallium scintigraphy, rest and exercise radionuclide ventriculography, pulmonary function tests, and chest roentgenography. Functional correlations of the electrocardiographic findings were examined in this subset. Septal infarction pattern (five of 48) and ventricular conduction abnormalities (10 of 48) were both associated with septal or anteroseptal thallium perfusion abnormalities (10 of 15 versus six of 33 of the remainder, p less than 0.005), which were present despite normal coronary angiographic results. Thallium defect scores were greater in patients with septal infarction pattern or ventricular conduction abnormalities compared with the remainder (defect scores 3.0 +/- 2.6 versus 1.4 +/- 2.2, respectively, p less than 0.025). In patients with ventricular conduction abnormalities, both left bundle branch block and right bundle branch block with left anterior fascicular block were associated with abnormal left ventricular function, whereas isolated right bundle branch block or left anterior fascicular block was associated with normal left ventricular function. A normal electrocardiographic finding (19 of 48) was associated with normal left ventricular function at rest (19 of 19). However, 11 of 19 (58 percent) had thallium perfusion defects and four of 19 (21 percent) had an abnormal response to exercise, although in none was the peak ejection fraction less than 50 percent. It is concluded that both septal infarction pattern and ventricular conduction abnormalities are electrocardiographic abnormalities associated with scleroderma heart disease; they appear to be a result of myocardial fibrosis. Some degree of myocardial fibrosis may be present with a normal electrocardiographic result, but significant left ventricular dysfunction is unlikely. Septal infarction pattern and ventricular conduction abnormalities, when present, are indicators of more advanced fibrosis.

Prognostic importance of cardiac arrhythmias in systemic sclerosis.

Ambulatory electrocardiography was performed in 183 patients with systemic sclerosis recruited from five centers who were selected to reflect a balanced population with respect to disease extent and duration. Ventricular ectopy occurred in 67 percent of patients and was strongly correlated by both univariate and multivariate analyses with total mortality and with sudden death. By multivariate analysis, ventricular ectopy was strongly associated with increasing patient age and with other evidence of cardiac and pulmonary involvement but not with clinical and laboratory measures of duration and extent of systemic sclerosis. Evidence of myocardial fibrosis thought to be secondary to microvascular alteration is common in systemic sclerosis, but the clinical implications of myocardial involvement are less well appreciated. The present data suggest the need for ambulatory electrocardiography in the clinical assessment of selected patients with systemic sclerosis, especially those with cardiac or pulmonary involvement, as well as for studies of the effects of antiarrhythmic therapy.

Pulmonary function in progressive systemic sclerosis. Comparison of CREST syndrome variant with diffuse scleroderma.

The pulmonary function and chest roentgenograms were evaluated in 88 patients with the CREST syndrome variant of progressive systemic sclerosis (PSS or scleroderma). Seventy-two percent of the patients had abnormal pulmonary function. An isolated decrease in diffusing capacity was the most common abnormality noted, followed by restrictive abnormalities and airway obstruction. Chest roentgenograms revealed interstitial infiltrates consistent with pulmonary fibrosis in 33 percent. When compared to a contemporaneous group of 77 patients with PSS and diffuse scleroderma, patients with the CREST syndrome had similar abnormalities on pulmonary function testing and chest roentgenogram. However, patients with the CREST syndrome had a lower mean diffusing capacity despite a higher mean vital capacity; this combination of findings suggests primary pulmonary vascular disease. Calcified granulomata were identified significantly more often in PSS-CREST patients, while superior rib notching occurred exclusively in patients with PSS and diffuse scleroderma. The CREST variant of PSS is associated with frequent roentgenographic and pulmonary function abnormalities similar to those seen in PSS with diffuse scleroderma.

Scleroderma renal crisis.

Renal crisis occurs in systemic sclerosis patients with rapidly progressive diffuse cutaneous thickening early in their disease. SRC is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolytic anemia, and renal failure. This complication, which in the past has been almost uniformly fatal, is now successfully treated in most cases with ACE inhibitors. This therapy has improved survival, reduced requirement for dialysis, and in those on dialysis has often allowed discontinuation of this procedure 6 to 18 months later. Prompt diagnosis and early, aggressive initiation of therapy with ACE inhibitors will result in the most optimal outcome. Chronic nonrenal crisis renal insufficiency is unusual and rarely progresses to significant renal dysfunction.

Scleroderma and pregnancy.

Pregnancy in systemic sclerosis may be uneventful, with both good maternal and fetal outcomes. Because scleroderma is a multisystem disease and complications do occur, however, careful antenatal evaluations, discussion of potential problems, and participation in a high-risk obstetric monitoring program is very important to optimize the best outcome. Because women with diffuse scleroderma are at greater risk for developing serious cardiopulmonary and renal problems early in the disease, they should be encouraged to delay pregnancy until the disease stabilizes. All patients who become pregnant during this high-risk time should be monitored extremely carefully. Although there are some suggestions that there are increases in infertility and miscarriages before disease onset, recent studies show that these issues probably do not have major impact for women with established scleroderma who plan to become pregnant. The high risk of premature and small infants may be minimized with specialized obstetric and neonatal care, however. Renal crisis in scleroderma is the only truly unique aspect of these pregnant, which, unlike blood pressure elevation in nonscleroderma pregnancies, must be treated aggressively with ACE inhibitors. Other pregnancy problems may not be unique to scleroderma, but because it is a chronic illness, any complication carries higher risks for both mother and child. Careful planning, close monitoring, and aggressive management should allow women with scleroderma to have a high likelihood of a successful pregnancy.

Systemic sclerosis.

Systemic sclerosis is a disease characterized by several distinctive features. This disease spares children, and its incidence increases steadily with age. Women are affected more than men, especially during childbearing years. Although there is no overall racial predilection, SSc occurs most frequently and severely in young black women. Family and genetic studies suggest only a weak genetic predisposition, but there are many occupational agents that may be implicated in the pathogenesis. The disease with its involvement in many organ systems results in a significant reduction in lifespan. Improvement in survival of renal crisis has been dramatic with the use of ACE inhibitors. Further epidemiologic studies using subsets of patients with more homogeneous clinical and laboratory features will lead to a better understanding of this complex disease.

Epidemiology and natural history of systemic sclerosis.

Systemic sclerosis is an acquired generalized disorder of connective tissue characterized epidemiologically by several distinctive features. From a demographic viewpoint, the disease spares children and its incidence increases steadily with age among adults; is much more frequent in women, especially during the childbearing years; occurs most frequently and severely in young black women, but overall has no prominent racial predilection. If any conclusions can be drawn here, the strongest influences may be age-related hormonal factor and degenerative vascular processes. Family and genetic studies suggest a weak genetic predisposition. There are many environmental agents which may be implicated in pathogenesis. The result of host factors and environmental "triggers" is a multi-system disease which has as prominent features microvascular injury, immunologic dysregulation, and fibroblast activation. The resulting widespread pathologic process leads to vascular insufficiency and fibrosis, which diminishes the reserve function of many organ systems. The result, a significant reduction in lifespan, with a 10-year survival from diagnosis of under 50 per cent. Further epidemiologic studies should take full advantage of established and newly proposed subsets of patients with homogeneous clinical, laboratory, serologic, and natural history features. The environment-host interactions noted above must be fully explored, especially in early untreated disease, where primary rather than secondary mechanisms are most likely to be operative.

Pregnancy in women with systemic sclerosis.

OBJECTIVE: To determine pregnancy outcomes in women with systemic sclerosis. METHODS: Women of childbearing age with systemic sclerosis seen at the University of Pittsburgh between 1987 and 1996 were observed prospectively. Pregnancy outcomes included abortion, miscarriage, preterm and term birth, and perinatal death. Complications of pregnancy and scleroderma were determined during and after pregnancy. RESULTS: Fifty-nine women with systemic sclerosis had 91 pregnancies during the 10-year period. No increase in the frequency of miscarriage was found, except in those with long-standing diffuse scleroderma. Preterm births occurred in 29% of pregnancies, and all but one of the infants survived. Symptoms related to scleroderma, particularly Raynaud phenomenon, improved during pregnancy, but esophageal reflux became worse. After pregnancy, some women with diffuse scleroderma had increased skin thickening. There were three cases of renal crisis during pregnancy, all in women with early diffuse scleroderma. Four women had five healthy infants while taking angiotensin-converting-enzyme inhibitors. CONCLUSION: Women with systemic sclerosis can safely have healthy pregnancies. Those with early diffuse scleroderma should wait until their disease stabilizes before becoming pregnant to decrease the risk of renal crisis. High-risk pregnancy management should be standard for all scleroderma pregnancies because of the high frequency of premature births.

The use of the Health Assessment Questionnaire (HAQ) to determine physical disability in systemic sclerosis.

The health assessment questionnaire (HAQ), a self-administered instrument to determine physical disability, was completed by 211 patients with systemic sclerosis who subsequently received scleroderma examinations. The mean HAQ disability index for the entire group was 0.92. Patients with high skin scores had significantly higher disability indices as compared to patients with low skin scores (p < 0.001). Higher disability indices were found for patients with joint pain, tendon rubs, and contractures. However, the presence of ulcers on the digital tip did not interfere with patients' abilities to function as measured by this scale. Intensive hand evaluations were performed on a subset of these 211 patients with systemic sclerosis (n = 80). Grip strength, thumb abduction, wrist extension, and motion of the index and middle fingers significantly correlated with the HAQ scores (p < 0.01). The findings from this study suggest that patients with systemic sclerosis have significant physical disability. Furthermore, the HAQ appears to be useful in assisting health professionals in quantitating this disability.

Cutaneous hypoxia in patients with systemic sclerosis (scleroderma).

Measurement of transcutaneous oxygen pressure (TCPO2) is an established and noninvasive way of assessing cutaneous hypoxia. Since the degree of oxygenation modulates fibroblast growth and synthesis, we investigated the presence of cutaneous hypoxia in patients with systemic sclerosis (SS). We measured TCPO2 of the involved skin of the dorsal aspect of the forearm in 33 patients with SS and 16 control individuals (normal subjects and patients with Raynaud's disease). The degree of forearm skin thickness was assessed clinically as mild, moderate, or severe. The TCPO2 measurements were obtained at a sensor temperature of 44 degrees C, which causes maximal vasodilation and eliminates the variables associated with vascular tone. Measurements were recorded while patients were breathing room air or 31% oxygen delivered by a Ventimask system (Baxter Healthcare, Ocala, Fla). We also measured the TCPO2 of the medial aspect of the arm when this site was uninvolved. We found that sclerodermatous skin is hypoxic when compared with the uninvolved skin of patients with SS or control individuals. The TCPO2 values were indirectly related to skin thickness; thus, patients whose skin was severely thickened had the lowest TCPO2 values. There was no correlation of TCPO2 values with pulmonary function tests or arterial oxygen pressure. The TCPO2 levels of patients with Raynaud's disease did not differ from other control individuals. The administration of oxygen increased TCPO2 readings in patients with SS to normal values. We conclude that the thickened skin of patients with SS is hypoxic and suggest that TCPO2 measurements may be helpful in objectively assessing the degree of skin thickness. The hypoxia demonstrated in SS skin may play a role in the modulation of dermal fibroblast proliferation and synthetic activity.

Treatment of systemic sclerosis.

Systemic sclerosis is an extremely variable disease in its manifestations and consequently, treatment needs to be individualized depending on the specific problems that each patient has. Limited scleroderma patients have a prolonged duration of Raynaud's phenomenon and puffy fingers before they develop any skin thickening, digital ulcers or gastrointestinal symptoms. They are likely to present with all the classic manifestations of scleroderma. Diffuse scleroderma patients have a much more acute systemic onset with marked whole hand swelling and may initially have only subtle skin thickening. A good understanding of the differences between the natural history of limited and diffuse scleroderma will enable the physician to treat present problems and anticipate future ones more effectively. One should determine which major subset and organ systems are involved before deciding on the appropriate therapy. Advances in organ-specific therapy, particularly calcium channel antagonists in Raynaud's phenomenon, proton pump inhibitors in esophageal reflux, intravenous iloprost and endothelin receptor antagonists in pulmonary hypertension, and ACE inhibitors in renal crisis, have decreased morbidity and mortality in patients with scleroderma. Studies of aggressive therapies to prevent or improve pulmonary fibrosis are in progress. Further clinical experience in wound healing, gastrointestinal malabsorption and physical therapy for loss of motion has helped patients to have a more comfortable life. In recent years, a significant number of controlled clinical trials have been performed and there has been improved understanding of the best way to perform studies and of which patients are most likely to respond to therapy. Penicillamine, methotrexate, photopheresis, relaxin, interferons, and cyclosporine have all been studied in controlled trials with variable outcomes. Although an overall remittive therapy has not yet been determined, new, potentially useful agents are being investigated.

Assessment of kidney involvement.

Scleroderma renal crisis (SRC) represents the classic manifestation of kidney involvement in SSc. It particularly occurs in patients with early, rapidly progressive, diffuse skin involvement. Its detection requires the assessment of a few core set variables: arterial blood pressure, serum creatinine, and urinalysis. In clinical investigations SSc patients developing arterial hypertension after the disease onset (new onset hypertension) without SRC should also be reported.