Clinical aspects of systemic and localized scleroderma

After the skin, the gastrointestinal tract is the most frequently affected organ in systemic sclerosis. Gastrointestinal symptoms already may be present early in the course of the disease and do not necessarily correlate with objective findings. Esophageal dysmotility is not specific for systemic sclerosis but occurs in other connective tissue diseases as well. Peripheral macrovascular disease was shown to be increased in patients with limited cutaneous sclerosis; signs of autonomic dysfunction were found in patients with the CREST (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) variant. Pulmonary involvement was shown to be moderately or severely decreased in 40% of a large cohort of scleroderma patients. In one study, no support was found for the association between pulmonary involvement and gastroesophageal reflux. Peripheral nerve involvement is often subclinical and might be associated with anti-U1-RNP and anti-topoisomerase I antibodies. Internal organs are seldomly affected in localized scleroderma. When occurring in childhood and involving an extremity, localized scleroderma can cause growth failure, resulting in long-term functional disability.     

The negative mucosal potential: separating central and peripheral effects of NSAIDs in man

Mixed connective tissue disease (MCTD) was first reported 25 years ago. This report provides an assessment of the course of juvenile (J) MCTD in 224 patients available in the literature until 1996, including our own 33 patients. Most patients improved and remissions were observed in 3-5% (up to 27%). Among the long-term problems, a loss in joint function was seen in up to 29% of the cases, renal involvement in up to 47%, restrictive lung disease in up to 54% and gastrointestinal manifestations consisting of oesophageal dysmotility in up to 29%. Cerebral involvement was rare but severe. Cardiovascular problems observed include cardiomyopathy, myopericarditis and pulmonary hypertension. Among other long-term problems were Raynaud's phenomenon and scleroderma-like skin changes in up to 86% of the patients. Seventeen of the 224 patients had died (7.6%) because of sepsis or infection (7), cerebral complications (3), heart failure (2), pulmonary hypertension (2), renal failure (2) or gastrointestinal bleeding (1). The mortality rate of JMCTD seems to be in the same range as that of juvenile systemic lupus erythematosus, dermatomyositis and scleroderma. When compared with the other connective tissue diseases, however, mainly minor long-term problems are seen in the surviving patients.     

Heart failure as clinical onset of essential mixed cryoglobulinemia

The case of a 58-year old man affected by heart failure on ischemic basis, as clinical onset of essential mixed cryoglobulinemia (EMC) is reported. Laboratory assays, ECG at rest and exercise electrocardiogram, echocardiogram, myocardial scintigraphy, cardiac catheterization with coronarography, hepatic, bone and kidney biopsies confirmed the diagnosis. Cases of primitive heart involvement are rarely reported and are, usually, due to myocardial infarction. Nevertheless in the published series of cases, heart failure is often coupled with EMC and, not seldom, is the cause of death. In the present case heart failure was the dominant element of clinical symptomatology and wasn't consequent to renal involvement or hypertension, but was sustained by a myocardial contractile deficiency, on ischemic basis, with undamaged coronary circle at angiography. Therefore heart failure was ascribed to an involvement of coronary microcirculation in the course of systemic vasculitis.     

Advances in the diagnosis and management of scleroderma-related vascular complications

Vascular disease is observed in virtually all patients with systemic sclerosis and presents several challenges for the clinician. The alterations in vascular tone noted with Raynaud's phenomenon may have corollaries in both the pathogenesis and management of systemic sclerosis-related internal organ complications. Early recognition of isolated pulmonary hypertension, coronary microcirculatory disease, and scleroderma renal involvement may be the keys to successful outcomes. Future trends in the management of systemic sclerosis may be directed at preventing the development of these vascular syndromes. This may occur through combined therapies directed at the abnormal immune response, disregulated fibroblast function, and resultant abnormal vascular response.     

Sinus arrest developed during gastric cancer operation in a progressive systemic sclerosis patient

We report a case of progressive systemic sclerosis (PSS) who suddenly developed sinus arrest during an operation for gastric cancer under general anesthesia. No abnormalities in her cardiac, respiratory or renal functions had been detected before surgery. The cardiac functions evaluated by echocardiogram before and after pacemaking eliminated heart muscular involvement. We speculated that the operation stress induced by general anesthesia altered the asymptomatic fibrotic sinus into apparent sinus dysfunction. Care should be taken in general anesthesia for scleroderma patients who are free from detectable cardiac manifestations.     

Interferon-gamma in the treatment of systemic sclerosis: a randomized controlled multicentre trial

We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.     

Clinical and immunological profile of SLE: some unusual features

OBJECTIVE: To study the clinical and immunological profile of children with systemic lupus erythematosus (SLE). DESIGN: Retrospective hospital based study. SETTING: Tertiary level center of North India. SUBJECTS: Sixteen children in the age group 4-12 years. METHODS: Medical records of children with SLE were analyzed. Clinico pathological features were compared with 2 other series from India. RESULTS: Mean age of children at the time of diagnosis was 10 yr and 8 (50%) children were less than 10 yr of age. The female to male ratio was 7:1. Fever (56.2%), rash (87%) and arthritis (87%) were the common clinical manifestations, Renal involvement was noted in 56.2% of cases. Other clinical features included hemolytic anemia (31.2%), thrombocytopenia (18.6%) and Raynaud's phenomenon (12.5%). Cardiac involvement in the form of severe myocarditis and endocarditis occurred in one patient each. Pulmonary hypertension was the presenting feature in one child with right heart failure. One child had multiple sclerosis along with SLE--a rare combination. ANA positivity was seen in all children. Five children died; two had severe cardiac involvement. Three children had renal involvement and one died of pulmonary hypertension. Two-thirds of subjects with renal involvement improved after therapy according to NIH, Bethesda protocol. CONCLUSIONS: SLE must be considered in any child with multisystem disease, as the disease may have certain unusual presentations.     

Nephrosclerosis: current status

Nephrosclerosis is the most typical and widespread renal manifestation of hypertension and can be judged as the pathological hallmark of essential hypertension. Nephrosclerosis is an important and frequent cause of progressive renal disease, however, information in the literature on the risk of developing renal failure in the course of essential hypertension is sparse. Traditionally, nephrosclerosis was thought to result from glomerular ischemia. Alternatively, glomerular sclerosis in hypertension may result from glomerular hyperperfusion or hypertension. Studies in experimental models of renal disease have identified a promising intervention with either Ca antagonists or angiotensin-converting enzyme inhibitors. Application of these therapies to patients with nephrosclerosis should await the results of careful clinical trials.     

Systemic sclerosis with pulmonary involvement and right ventricular failure in a child

We report a very rare case of systemic sclerosis in a 6-year-old girl. She presented with diffuse scleroderma, Raynaud's phenomenon, pulmonary interstitial fibrosis, pulmonary hypertension, and right ventricular failure. The diagnosis was confirmed by skin manifestations, high resolution computed tomography, cardiac catheterization, and anti-nuclear antibodies. Nifedipine, prednisolone, digoxin, and furosemide were given. There was remission of the right ventricular failure and dyspnea, and the skin showed partial improvement. The patient remained asymptomatic for a year. The symptoms of respiratory and right heart failure developed again after an episode of lower respiratory tract infection and she eventually died. We discuss the clinical manifestations, treatment, and outcome.     

Progressive systemic sclerosis: rare localization of the maxillofacial district

The authors focus on a case of scleroderma, or progressive systemic sclerosis. Scleroderma is a disease of unknown cause, characterized by an abnormal synthesis of connective tissues that causes a sclerosis of the skin involving organs and systems at various levels. It may appear in different forms and may involve, although not frequently, the maxillofacial district. The authors examined a 21-year-old woman who had been diagnosed with systemic progressive sclerosis in 1994. The patient showed a strong limitation of oral aperture, evidenced by an electrognathographic test, and osseous changes. Panoramic and full-mouth intraoral radiographs showed a complete agenesis of coronoid processes on both sides, whereas the angles and the rising branches of the mandibular and periodontal ligaments appeared normal. The patient was diagnosed as having maxillofacial localization of scleroderma with involvement of coronoid processes bilaterally.     

Scleroderma renal crisis. 7 cases and review of the literature

We report a series of seven patients who had scleroderma renal crisis. Their primary clinical and laboratory features along with the details of their management were compared with those of similar cases from the literature. The seven patients died within one to four months of the diagnosis with a pattern of acute renal failure, left ventricular failure and malignant hypertension. Histopathologic examination was performed in four of the patients, in two of whom it revealed thickening of the wall of the interlobular arteries related to the scleroderma, and in the other two patients nonspecific lesions of malignant hypertension. This histopathologic particularity led us to propose, on the basis of multiple renal biopsies performed in patients with scleroderma, a lesion chronology of the kidney in patients with scleroderma. Nevertheless, the triggering factors and pathophysiologic mechanisms of scleroderma renal crisis remain unclear and its prognosis is severe. Early treatment with angiotensin-converting enzyme inhibitors and other vasodilatators administered intravenously can prevent death and dialysis.     

Localizations and consequences

The symptoms of amyloidosis depend on the type of precursor, the amount of deposits and their location. In systemic amyloidosis almost every organ may be involved. Cardiac involvement is severe, especially in AL amyloidosis, responsible for restrictive cardiomyopathy with right ventricular failure, leading rapidly to death. Renal amyloid deposition causes nephrotic syndrome with hypertension and renal failure. Neurological complications include peripheral neuropathy with dysautonomia cerebral involvement (dementia, cerebral haemorrhages). Arterial deposits are common in systemic senile amyloidosis, and may cause ischaemia. Osteo-articular damage is mainly seen in patients on long-term haemodialysis. Liver enlargement is often the only manifestation of hepatic amyloidosis. Digestive tract involvement includes macroglossia deposits in salivary glands and disturbances in gastrointestinal motility. Pulmonary amyloidosis causes nodular or interstitial infiltrates. Cutaneous lesions are various. Localized amyloidoses include goiter, breast and vesical involvement which can be difficult to differentiate from neoplasm, as well as ocular amyloidosis mimicking posterior uveitis.     

Exercise capacity and mid-term survival in patients with tricuspid atresia and complex congenital cardiac malformations after modified Fontan-operation

A 68-year-old man experienced systemic pruritus since he was 63 years old, and systemic sclerosis and skin pigmentation were observed when he was 64. When he developed dyspnea the same year, he was admitted and SSc was diagnosed on the basis of the clinical and skin biopsy findings, lung fibrosis on X-P and TBLB findings. At 65, his dyspnea reappeared along with elevated blood pressure, acute renal failure and lung congestion, and he was diagnosed as having a scleroderma renal crisis (SRC) from the clinical and renal biopsy findings. Hemodialysis was started because he showed mental disturbance, and this and other acute symptoms were subsequently reduced. As he showed no recovery from his renal failure, the patient has been maintained on hemodialysis for over four years now. In the meantime, his sclerosis has improved and antinuclear antibody almost disappeared. Hemodialysis appears to be the most likely reason for his improvement, although spontaneous remission, D-penicillamine and angiotensin converting enzyme (ACE) inhibitor therapy may also have contributed, considering the short period and the small amount of drugs given until improvement.     

Exogenously acquired Clostridium septicum gas gangrene--a case report

Hepatic involvement is frequently in systemic amyloidosis but major clinical symptoms due to portal hypertension or liver failure are rare. To date all treatment modalities proven in these patients have failed. Thus, prognosis is dismal with progressive deterioration in liver function. We describe a patient with massive liver involvement by primary amyloidosis, manifested by severe intrahepatic cholestasis. Up to now 25 similar case have been reported in the English literature. In this subset of patients the most frequently recorded cause of death was renal failure accelerated by hyperbilirrubunemia. In our patient a downhill course was characterized by fatal renal hepatic failure after an hemoperitoneum, probably as a delayed complication of liver biopsy. Although not all authors agree, an added risk of bleeding after liver biopsy have been pointed out in hepatic amyloidosis. This kind of problem recommends the use of tissue other than liver, or a transjugular hepatic biopsy for diagnostic purposes. Also, of interest in the present cause is the autopsy findings of pancreatitis associated to pancreatic amyloidosis, a complication which have been described in previous reports.     

Recurrent acute scleroderma renal crisis complicated by thrombotic thrombocytopenic purpura

Acute renal crisis as an early manifestation of scleroderma is underemphasized, and its recurrence after initial successful therapy is rare. We describe a 32-year-old woman who presented with scleroderma renal crisis. A second episode of apparent renal crisis, however, was complicated by thrombotic thrombocytopenic purpura, which led to pancreatitis, a large cerebral infarction, and fatal outcome despite intensive therapy. This case illustrates the complexity and severity of diffuse systemic sclerosis presenting with multiple, major organ complications.     

Current therapy of chronic renal failure

The course of chronic renal failure is generally progressive and mediated by several factors that operate in combination. Several extrarenal events which may cause transient or permanent deterioration of renal function, are important, because their correction may slow the progression of renal disease e.g. volume disorders, infection, nephrotoxic agents. In progression of chronic renal disease leading factors are hypertension, proteinuria and high protein/phosphorus intake. Number of evidence suggests that ameliorating hypertension, reducing proteinuria slow the progression of chronic renal failure. Clinical studies in diabetic nephropathy demonstrated that the renoprotective effect of ACE inhibitors was independent of their effect of systemic blood pressure. In ESRD patients access for renal replacement therapy should be obtained as early as possible. An A-V fistula may take several weeks to mature especially in diabetic or elderly patients. Early dialysis has been advocated in diabetic patients. In general, patients can start ESRD therapy when residual kidney function drops to 5-10% of normal value. High quality of dialysis should be provided to the uremic patient with respect of successful renal transplantation.     

Anticentromere antibodies in rheumatologic practice are not consistently associated with scleroderma

Anticentromere antibodies identified by indirect immunofluorescence are a valuable aid to the diagnosis and prognosis of patients with systemic sclerosis since they are associated in 50% to 80% of cases with limited cutaneous systemic sclerosis, a pattern usually associated with a good prognosis. We studied clinical presentations in rheumatology patients with anticentromere antibodies by indirect immunofluoresence and by ELISA and/or Western blot, but without scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic patients with centromere antibodies met these criteria, seven women and one man, with a median symptom duration of six years (range 1-20 years). Four had Sj?gren's syndrome, one had isolated xerostomia, one systemic lupus erythematosus, one seronegative symmetric polyarthritis and one primary biliary cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight patients was similar to that in the patients who had at least Raynaud's phenomenon. Given the low incidence of scleroderma, these data illustrate the poor predictive value of anticentromere antibodies for the diagnosis of scleroderma in rheumatology clinic patients.     

Leukotriene receptor blockade in experimental heart failure

The pathophysiological role of endogenous leukotrienes in cardiovascular control and the regulation of renal function in congestive heart failure is not known. Therefore, in six conscious dogs with or without heart failure induced by right ventricular pacing (270/min, 10 days) we studied the effects of the leukotriene receptor antagonist FPL55712 on hemodynamics, plasma hormones and renal function. In healthy dogs, FPL55712 (1 mg kg-1 + 0.01 mg kg-1 min-1 i.v.) had little effect on hemodynamics, only reducing heart rate by 11% and insignificantly increasing systemic vascular resistance. Plasma levels of norepinephrine (-57%), renin (-30%) and aldosterone (-24%) were significantly decreased. Renal function parameters were not changed. In dogs with heart failure, FPL55712 significantly increased systemic vascular resistance (+16%) and decreased cardiac output (-15%). Plasma hormone levels were not changed, but renal plasma flow was decreased (-13%) and glomerular filtration rate (+12%), renal vascular resistance (+13%) and filtration fraction (+23%) were increased. It is concluded that there is no evidence for a contribution of endogenous leukotrienes to the systemic vasoconstriction in experimental heart failure. Whether the increase in systemic and renal vascular resistance induced by the leukotriene antagonist in dogs with heart failure reflects a role for endogenous leukotrienes with vasodilator action is still unclear and deserves further investigation.     

Schistosoma mansoni: the varying occurrence of repetitive elements in different strains shows sex-specific polymorphisms

In this Grand Round, two children are described with atypical generalized scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti-inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was unsuccessful in reversing the sclerodermatous changes and growth arrest. Dietary intake analysis and extensive GI investigation were performed in both. In one case, resting energy expenditure (Ee) was repeatedly measured. His intake did not meet requirements for growth. Supplemental tube feeding (900 kcal in 6 h) was commenced, causing an increase in weight from 11 to 16 kg. The other patient refused supplementary tube feeding and no weight gain has been observed for 5 yr. In conclusion, early-onset generalized scleroderma in the absence of visceral involvement, but with growth failure, may represent an atypical form of systemic sclerosis. The response of the two patients to conventional therapy was disappointing. However, the rapid catch-up growth induced by tube feeding observed in one patient underlines the importance of adequate dietary management.     

Gouty arthritis in nodal osteoarthritis

OBJECTIVE: To analyze the clinical features and identify factors associated with the development of gouty arthritis in nodal osteoarthritis (OA). METHODS: Thirty-two consecutive patients (21 women and 11 men, mean age 75.8 years) with both nodal OA and crystal proven acute gout and/or tophi of distal/proximal interphalangeal (DIP/PIP) joints were studied between 1986 and 1994. RESULTS: Tophi of DIP and/or PIP joints were present in 29 (90%) patients; alone in 9 and together with acute DIP or PIP gouty arthritis in 20. Three patients had acute DIP or PIP gouty episodes but no digital tophi. Mean pretreatment serum urate was 614.9 +/- 163.2 (range 422-1088 mumol/l). Risk factors for gout included diuretic use (81%), renal failure (59%), hypertension (66%), alcoholism (22%), prophylactic low dose ASA (20%), and a positive family history (16%) of patients. CONCLUSION: The coexistence of gouty arthritis in nodal OA is important to recognize and treat, particularly in elderly women with renal failure, hypertension, or cardiac failure who are receiving longterm diuretic therapy.