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."     

Evaluation of the functional parameters in scleroderma cases with pulmonary involvement

To evaluate the relationship between functional changes in the scleroderma patients with pulmonary involvement and the diagnostic tests and to identify the tests that may be helpful in early diagnosis. In this prospective study, 33 scleroderma patients with pulmonary involvement were included. Pulmonary function tests, echocardiography, arterial blood gases, six minute walk tests, thorax high resolution computed tomography were performed and all patients were classified according to MRC dyspnea scores and NYHA(WHO) functional classification. Patients were also asked to conclude Saints Georges Respiratory Questionnaire (SGRQ). DLCO% found to be the earliest deteriorated parameter in our patients. Sensitivity of FVC%/DLCO% ratio, for detecting pulmonary arterial hypertension as a noninvasive method, was found low. SGRQ was found to be correlated with all functional parameters used in scleroderma follow up. Patients with scleroderma should be evaluated for pulmonary involvement and must be followed up ever if they were asymptomatic. Pulmonary function tests, echocardiography, thorax high resolution computed tomography, six minute walk tests are valuable tools that should be used in diagnosis and follow up. NYHA (WHO) functional classification, MRC and Borg dyspnea scores are also helpful for early diagnosis. SGRQ can also be helpful to evaluate the patients functional capacity in diagnosis and follow up as a non invasive parameter.     

Brachial plexopathy associated with diffuse edematous scleroderma

Peripheral nervous system (PNS) involvement is rare in systemic sclerosis (SSc), usually restricted to peripheral nerve entrapment. To our knowledge, only one case of scleroderma with brachial plexus involvement has been reported previously. We report here on a 61-year-old woman with past history of limited cutaneous SSc who developed motor deficiency in the left arm concomitant with diffuse edematous scleroderma without evidence for trauma or compression of the brachial plexus. After six months intravenous pulse cyclophosphamide therapy, dramatic improvement of skin and neurological involvement was observed.     

Homocysteine plasma concentration is related to severity of lung impairment in scleroderma

OBJECTIVE: To investigate the correlation between plasma concentration of total homocysteine and pulmonary involvement in patients with limited or diffuse scleroderma (systemic sclerosis, SSc). METHODS: Seventy-one patients with scleroderma were divided into 3 groups based on pulmonary involvement: Group A comprised patients without lung involvement (9 cases); Group B patients with lung involvement of mild and moderate stages (44 cases); and Group C patients with lung involvement of severe stage and endstage (18 cases). At the time of evaluation of lung involvement all patients underwent determination of plasma homocysteine concentration. Homocysteine concentration was also measured in 30 healthy controls homogeneous for sex and age. RESULTS: In patients with scleroderma the homocysteine concentration was significantly higher than in controls (11.1 and 6.9 micromol/l, respectively; p < 0.001). We found a significant association between plasma homocysteine concentration and severity of lung involvement that was not modified by correction for age, time from the diagnosis, type of scleroderma pattern, and serum creatinine and folate levels. Homocysteine concentration progressively increases in scleroderma patients with more severe pulmonary involvement. Subjects with high homocysteine concentration (i.e., > or = 75th percentile of homocysteine concentration in patients with scleroderma without lung involvement) were mostly present in the group with the greatest lung involvement. CONCLUSION: High level of homocysteinemia is associated with an increased risk of pulmonary disease in patients with scleroderma. We hypothesize that hyperhomocysteinemia may worsen injury of the endothelium, a key lesion in scleroderma disease, favoring the development of lung involvement. Our data support the hypothesis that homocysteine could be involved in the pathogenetic process of scleroderma pulmonary involvement.     

Severe organ involvement in systemic sclerosis with diffuse scleroderma

OBJECTIVE: To determine the natural history and timing of severe involvement of the kidney, heart, lung, gastrointestinal (GI) tract, and skin in patients with systemic sclerosis (SSc) and diffuse cutaneous involvement. METHODS: This study used the Pittsburgh Scleroderma Databank and included patients with diffuse scleroderma who were seen between January 1, 1972 and December 31, 1995. Patients had frequent follow-ups, and a 95% accountability for these patients was maintained. Severe organ involvement was defined as the presence of any of the following: 1) in the kidney, scleroderma "renal crisis"; 2) in the heart, cardiomyopathy, symptomatic pericarditis, or an arrhythmia requiring treatment; 3) in the lung, pulmonary fibrosis on chest radiograph and a forced vital capacity of <55% of predicted; 4) in the GI tract, malabsorption, repeated episodes of pseudoobstruction, or severe problems requiring hyperalimentation; and 5) in the skin, a modified Rodnan skin score >40. The timing from disease onset to survival for each case of severe organ involvement was determined. RESULTS: Of the 953 patients with diffuse scleroderma, kidney involvement developed in 177 (19%), heart involvement in 143 (15%), lung involvement in 151 (16%), GI tract involvement in 74 (8%), and skin involvement in 233 (24%). Severe skin and kidney involvement occurred during the first 3 years in 70% of those who ever developed these problems throughout a mean of 10 years of followup. Severe heart, lung, and GI tract involvement developed during the first 3 years in 45-55% of those who were ever affected. The survival of patients with severe organ involvement was poor. The 9-year cumulative survival rate of all patients with severe organ involvement was 38%, compared with 72% in patients without such involvement (P < 0.0001). CONCLUSION: This study demonstrates that severe organ involvement in SSc patients with diffuse scleroderma most often occurs early in the course of the disease. Survival for patients with severe organ involvement is markedly reduced. Patients should therefore be monitored very closely during the first 3 years of disease for signs and symptoms that may signal the subsequent development of severe organ damage. Potential disease-modifying therapies must be initiated early to modify the natural history of SSc and to improve survival. Patients who survive the first few years without developing severe organ involvement are less likely to develop such life-threatening involvement later in the disease course.     

The palpable tendon friction rub

Objective. To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc). Methods. SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database. Results. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival. Conclusion. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease-modifying therapy.     

Spontaneous perforation of the small intestine due to scleroderma

Summary We have described a 42-year-old black woman with scleroderma who developed spontaneous perforation of the terminal ileum due to complete collagenous involvement of the bowel wall. Spontaneous intestinal perforation represents a rare complication of scleroderma which can be initially mistaken for pseudoobstruction.     

A modified scleroderma skin scoring method

The extent of skin thickness in scleroderma has been reported to correlate with the degree of internal organ involvement. An objective method for the clinical evaluation of skin involvement (skin score) in scleroderma is described. In this preliminary study, the method was tested in twenty scleroderma patients. An acceptable degree of inter-observer reproducibility was noted. This method is proposed as a means of monitoring the degree of skin involvement and the overall disease activity.     

Muscle involvement in the scleroderma syndromes

Muscle involvement was identified in 14 patients with scleroderma or a connective tissue disease overlap syndrome with predominant features of scleroderma. Patients presented with symmetrical proximal weakness indistinguishable from other inflammatory myopathies. Creatine kinase and electromyography were useful to demonstrate muscle involvement. Muscle histopathology demonstrated primarily the vasculopathy of scleroderma or polymyositis in similar numbers of patients. Scleroderma vasculopathy and polymyositis generally occur without specificity to diffuse scleroderma, the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia syndrome, or an overlap syndrome with arthritis. Polymyositis also occurs when the vasculopathy of scleroderma involves other organ systems.     

Echocardiographic identification of cardiac abnormality in scleroderma and related disorders.

Although pathologic examination may readily disclose cardiac abnormality in patients with scleroderma, clinical identification of primary heart involvement can be difficult. In order to assess left ventricular systolic function, chamber size and wall thickness, and to determine whether pericardial effusion is present, echocardiograms were obtained in 11 patients with progressive systemic sclerosis (PSS) and in 13 patients with forms of scleroderma in which visceral involvement has been considered rare or absent: three with CREST syndrome, three with morphea, three with diffuse fasciitis with eosinophilia, and four with mixed connective tissue disease. Increased left ventricular wall thickness was noted in 13 of 23 (57 per cent) patients who could be evaluated, including six (46 per cent) from subgroups other than PSS. Left atrial dimension was increased in 12 patients (52 per cent) whereas the left ventricular end-diastolic dimension was increased in only three (13 per cent). Mitral valve closure velocity, an index of left ventricular compliance, was diminished in 10 (42 per cent) patients. However, left ventricular systolic contractile performance was normal in all. Pericardial effusion was detected in five patients (21 per cent), including one patient each with morphea, mixed connective tissue disease and diffuse fasciitis. Cardiac abnormalities were evident even in patients with PSS and no renal or severe pulmonary involvement. Thus, primary cardiac involvement, characterized by left ventricular wall thickening, decreased left ventricular compliance, left atrial enlargement and pericardial effusion, may be common in patients with scleroderma. These abnormalities occur in patients with PSS as well as in those with “nonsystemic” forms of scleroderma and are readily detected by echocardiography.     

Localized scleroderma in childhood is not just a skin disease

OBJECTIVE: Juvenile localized scleroderma is usually considered a disease that is confined to the skin and subcutaneous tissue. We studied the prevalence and clinical features of extracutaneous manifestations in a large cohort of children with juvenile localized scleroderma. METHODS: Data from a multinational study on juvenile scleroderma was used for this in-depth study. Clinical features of patients with extracutaneous manifestations were compared with those of patients who had exclusively skin involvement. RESULTS: Seven hundred fifty patients entered the study. One hundred sixty-eight patients (22.4%) presented with a total of 193 extracutaneous manifestations, as follows: articular (47.2%), neurologic (17.1%), vascular (9.3%), ocular (8.3%), gastrointestinal (6.2%), respiratory (2.6%), cardiac (1%), and renal (1%). Other autoimmune conditions were present in 7.3% of patients. Neurologic involvement consisted of epilepsy, central nervous system vasculitis, peripheral neuropathy, vascular malformations, headache, and neuroimaging abnormalities. Ocular manifestations were episcleritis, uveitis, xerophthalmia, glaucoma, and papilledema. In more than one-fourth of these children, articular, neurologic, and ocular involvements were unrelated to the site of skin lesions. Raynaud's phenomenon was reported in 16 patients. Respiratory involvement consisted essentially of restrictive lung disease. Gastrointestinal involvement was reported in 12 patients and consisted exclusively of gastroesophageal reflux. Thirty patients (4%) had multiple extracutaneous features, but systemic sclerosis (SSc) developed in only 1 patient. In patients with extracutaneous involvement, the prevalence of antinuclear antibodies and rheumatoid factor was significantly higher than that among patients with only skin involvement. However, Scl-70 and anticentromere, markers of SSc, were not significantly increased. CONCLUSION: Extracutaneous manifestations of juvenile localized scleroderma developed in almost one-fourth of the children in this study. These extracutaneous manifestations often were unrelated to the site of the skin lesions and sometimes were associated with multiple organ involvement. The risk of developing SSc was very low. This subgroup of patients with juvenile localized scleroderma should be evaluated extensively, treated more aggressively, and monitored carefully.     

Localized scleroderma and systemic sclerosis: Is there a connection?

Excess fibrosis of the skin is a clinical hallmark of both localized scleroderma and systemic sclerosis. Localized scleroderma is generally thought to be a skin-limited disease whereas systemic sclerosis can have a wide range of internal organ involvement. Recent data suggest that a subset of patients with juvenile localized scleroderma can go on to develop systemic involvement of their disease. This raises the question of what the connection is, if any, between localized scleroderma and systemic sclerosis.     

Resolution of renal failure with malignant hypertension in scleroderma. Case report and review of the literature.

The ominous prognosis of rapidly progressive renal failure associated with malignant hypertension in scleroderma has led to aggressive management by dialysis, early bilateral nephrectomy and renal transplantation. We describe a woman with scleroderma who recovered after the development of malignant hypertension and renal failure. Renal biopsy and arteriography demonstrated the classic vascular lesions of scleroderma with secondary cortical ischemia. Of note, plasma renin activity was normal. Review of the literature revealed 40 patients with scleroderma and rapidly progressive renal failure who have been treated by dialysis. Thirteen patients survived, four of whom did not undergo bilateral nephrectomy. In eight patients treated by transplantation, five achieved excellent allograft function although one sustained a late rejection. Analysis of our case and of five recently reported cases of reversible renal failure and malignant hypertension reveals no distinctive features identifying patients with a favorable prognosis, except for the normal plasma renin activity level in our patient. Vigorous control of hypertension and renal failure by drugs and dialysis is recommended. Bilateral nephrectomy should be considered only for patients with refractory hypertension, since recovery of renal function may follow even after months of dialysis. For patients with irreversible renal failure without other major organ system involvement, transplantation is a reasonable alternative to dialysis.     

Noninvasive evaluation of cardiac dysrhythmias, and their relationship with multisystemic symptoms, in progressive systemic sclerosis patients

Fifty-three patients (34 who had diffuse scleroderma, and 19 who had CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias]) were studied by noninvasive procedures, including resting electrocardiogram (ECG), continuous 24-hour Holter ECG monitoring, M-mode echocardiography, and 2-dimensional echocardiography. Only 22 patients (42%) had abnormalities such as conduction defects, supraventricular or ventricular arrhythmias, or ST-T changes detected on resting ECG. In contrast, using Holter monitoring, the number of conduction abnormalities seen increased from 10 to 16 patients and transient ST-T changes increased from 2 to 18 patients. Forty-eight patients had ventricular arrhythmias, with multiform ventricular premature beats in 21 (40%), pairs of runs of ventricular tachycardia in 15 patients (28%), and 1 or more runs of ventricular tachycardia in 7 (13%). Echocardiography detected asymmetric septal hypertrophy in 10 patients, impaired ventricular function in 9 patients, congestive cardiomyopathy in 2, mitral prolapse in 4, and pericardial effusion in 3 patients. Multiform and/or repetitive ventricular premature beats occurred more frequently in patients with echocardiographic abnormalities, but were also present in patients who had normal findings on echocardiographic examination. Cardiac involvement was not correlated with clinical variants of scleroderma (CREST syndrome or diffuse scleroderma), nor with other signs and symptoms of the disease. Thus, cardiac involvement is found much more frequently than would be expected from clinical symptoms or from results of resting ECG alone; therefore, Holter monitoring and echocardiography should be included in the routine workup of patients who have scleroderma.     

Stiff skin syndrome versus scleroderma: a report of two cases

Stiff skin syndrome is a rare cutaneous disease, scleroderma-like disorder that presents in infancy or early childhood with rock-hard skin, limited joint mobility, and mild hypertrichosis. Normally, it occurs in the absence of visceral or muscle involvement. Patients do not present immunologic abnormalities or vascular hyperactivity. We describe two adults who initially were diagnosed suffering from scleroderma but fit criteria for stiff skin syndrome. A review of the clinical range of this disorder and discussion of the differential diagnosis with scleroderma is presented.     

Retrospective studies in scleroderma: skin response to potassium para-aminobenzoate therapy

Analyses were made of University of Michigan Hospital records of 467 patients diagnosed during the period 1948 - July 1980 as having scleroderma (390) or scleroderma associated with manifestations of other collagen disease (77). In all, there were coded 4733 visits or admissions. Demographic characteristics are detailed for the 390 patients with clinical features of scleroderma alone. The principal focus of this report is on degree and extent of skin involvement and response to therapy with potassium para-aminobenzoate (Potaba, KPAB). Ninety percent of 224 patients treated with KPAB experienced mild, moderate, or marked skin softening. Among a parallel group of 96 evaluable patients who did not receive KPAB, less than 20% were noted to have mild or moderate skin improvement at the end of follow-up. The difference in skin softening attained by patients treated with KPAB compared to that of patients who did not receive this medication was significant (p less than 0.0001).     

Scleroderma pericardial disease presented with a large pericardial effusion--a case report

Scleroderma pericardial disease is usually silent and benign. The incidence of pericardial involvement in scleroderma is about 50% according to autopsy results, but symptomatic pericarditis manifests in about 16% of patients with diffuse scleroderma and in about 30% of patients with limited scleroderma. The clinically evident pericardial effusion is rare in scleroderma, although it can be detected in about 41% of patients with echocardiography. In majority of the patients, the pericardial effusion is small and not associated with symptoms. The pericardial effusion manifests usually after the manifestation of the other clinical and serologic features of scleroderma. A case of scleroderma is reported that presented with a large pericardial effusion, which antedated the other clinical and serologic features of scleroderma. The pericardial involvement in scleroderma is reviewed.     

Scleroderma (Progressive Systemic Sclerosis) with Severe Bowel Involvement. Treatment by Extensive Resection of the Small Intestine

Summary: Scleroderma (progressive systemic sclerosis) with severe bowel involvement. Treatment by extensive resection of the small intestine.
A 48-year-old man with previously diagnosed scleroderma with bowel involvement was admitted to hospital with severe malnutrition attributed to malabsorption. Shortly after this, he developed features of intestinal obstruction followed by paralytic ileus.
Due to failure to respond to medical treatment, operation was carried, out. On two occasions adhesions were divided, but the bowel failed to function. At a third operation the proximal half of the small bowel below the duodeno-jejunal flexure was excised. Following this the patient made a good recovery.
Small bowel involvement in scleroderma is discussed. Ma/absorption is probably related to bacterial proliferation in the small bowel secondary to stasis and may be helped by antibiotic drugs. Other disturbances resulting in inability of the bowel to propel its contents may comprise syndromes of obstruction and paralytic ileus. A/though management of scleroderma bowel involvement is usually medical, surgical treatment may be indicated under certain circumstances. It may be life-saving.     

Pulmonary Function in Scleroderma

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.     

Progressive systemic sclerosis sine scleroderma presenting as pulmonary interstitial fibrosis

PURPOSE: The purpose of this work was to report the clinical features of 10 patients with systemic sclerosis presenting with lung disease in the absence of cutaneous involvement (systemic sclerosis sine scleroderma). PATIENTS AND METHODS: The study involved a retrospective review of patients with systemic sclerosis at a tertiary care facility presenting with clinical and/or radiographic evidence of interstitial lung disease in the absence of cutaneous manifestations of scleroderma, and a MEDLINE, computer search for patients who presented with lung disease and later developed taut skin (scleroderma). RESULTS: Ten patients with systemic sclerosis sine scleroderma presenting with pulmonary signs or symptoms were discovered. A positive antinuclear antibody (seven of eight), esophageal dysmotility (eight of nine), restrictive lung disease (six of eight), Raynaud's phenomenon (five of eight), and abnormal nailfold capillaries (six of six) were present in these patients. Six of these 10 patients developed typical scleroderma from four months to seven years after presentation. Lung pathology was examined in six patients and all had changes consistent with interstitial pneumonitis and fibrosis. Four of the 10 patients had occupations that could have exposed them to potential pulmonary toxins. In contrast to patients with typical scleroderma, all 10 patients we discovered were men. conclusions: Systemic sclerosis should be considered in patients with idiopathic interstitial lung disease even in the absence of classic sclerodermatous cutaneous involvement. An esophagram, antinuclear antibody, and widefield nailfold examination may facilitate the diagnosis.