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Scleroderma is characterized by major clinical symptoms, but a number of unrelated disease may mimic these features more or less completely. Even scleroderma itself sometimes presents in an unusual manner. This article deals with uncommon presentations of true scleroderma and its variants and pseudo -scleroderma diseases.
Scleroderma renal crisis is a clinical syndrome of systemic sclerosis that is classically characterized by accelerated hypertension, rapidly progressive renal failure, and hyperreninemia. It has been reported that cocaine may initiate scleroderma in an already susceptible individual or unmask it at an earlier age in subclinical disease. We describe a 46-year-old male patient with a history of heavy cocaine abuse that unmasked scleroderma and precipitated scleroderma renal crisis.
We recently reported on the use of an indirect immunofluorescent method designated the rodent lung assay; this test assesses for the presence of circulating antibodies directed at components of the microvasculature. Serum samples from 49 patients with scleroderma were incubated with rodent lung tissue sections and visualized with fluoresceinated human anti-IgG. The assay also was performed on samples from a control group. Western blot analysis was performed with endothelial cell protein extracts using serum samples from patients with scleroderma and from healthy control subjects. The control subjects had a negative indirect immunofluorescent assay result. In the patients with scleroderma, there was a significant positive correlation between intensity of indirect immunofluorescent staining and pulmonary fibrosis (r = 0.316; P = .0347) and hypertension (r = 0.310; P = .0408). Western blot analysis revealed antibody binding to proteins in extracts of human endothelial cells in all patients in whom there was evidence of pulmonary disease. The indirect immunofluorescent rodent lung assay and Western blot data support a potential role of anti-endothelial cell antibodies in the propagation of scleroderma-associated pulmonary disease.
Scleroderma of the colon is commonly associated with constipation, as was the case in a 70-year-old woman with rectal prolapse described by the authors. The chronic constipation in this patient may have been the cause of her rectal prolapse, but the onset of the prolapse and scleroderma at about the same time suggest that the scleroderma may have been a causative factor. A Ripstein repair of the prolapse was carried out. The authors discuss some of the complications of colonic scleroderma, which include megacolon, transverse and sigmoid colonic volvulus, telangiectasia, stenosis and diverticula and stercoral ulceration.
OBJECTIVE: Scoring poorly on the health assessment questionnaire (HAQ) has recently been shown to be a strong predictor of morbidity and mortality in rheumatoid arthritis (RA), while a good HAQ score is predictive of a better outcome. In patients presenting with early diffuse scleroderma prognosis is variable. Our goal was to determine possible baseline predictors of future good outcomes. METHODS: We used the raw data from two randomized controlled trials (RCTs) in early diffuse scleroderma: methotrexate (Pope et al.) and D-penicillamine (Clements et al.). Subjects in the methotrexate trial were divided into the following groups: (1) those with at least 20% improvement in the primary outcome measurements [patient global assessment, physician global assessment, UCLA skin tethering score, modified Rodnan skin score (MRSS), DLCO as % predicted and HAQ disability] at 1 yr vs (2) the others. Baseline factors (including age, gender, skin scores, physician and patient global assessments, HAQ disability and pain scores, DLCO and physical parameters) were analysed to find baseline variables strongly correlated with later improvement. These variables were explored in the D-penicillamine trial to determine if (in a separate trial) they were still predictive of improved outcome at 1 and 2 yr. Adjusted models were used to find baseline predictors of good outcome. The median HAQ-DI was 1.3 (methotrexate) and 1.0 (D-penicillamine). RESULTS: A baseline HAQ disability score of less than the median was predictive of at least a 20% improvement at 1 and 2 yr with odds ratios of 1.77 to 5.05, in four of the five outcome measurements (in both groups); with strongly significant P values for 3 of 5 outcomes (UCLA skin score, MRSS, patient global skin score; P<0.02) from the methotrexate study group. These three outcomes were strongly correlated with improvement (r between 0.25 and 0.35). Although data from the D-penicillamine trial were less convincing, in both trials the less than median HAQ-DI and HAQ pain scores showed a stronger association with improved outcome, more so than age, gender, skin score and baseline global assessment. CONCLUSION: A low baseline HAQ (defined as less than the median HAQ score) is predictive of improved outcome in diffuse scleroderma at 1 and 2 yr.
In a multicentre study performed by the German Working Group for Dermatological Research a total of 286 female and male patients with circumscribed scleroderma (morphoea) were examined with reference to form and extent of their skin manifestations (e.g. progressive idiopathic atrophodermia, Pasini-Pierini Type) and systemic involvement. On the basis of the literature and our observation of circumscribed scleroderma classification into three types appears to be appropriate: a plaque-type (with generalized circumscribed scleroderma as the most severe variant), a linear type (with pansclerotic disabling morphoea as the most severe variant) and a profound type (with eosinophilic fasciitis as the most severe variant).
Scleroderma is a spectrum of disorders of which juvenile scleroderma forms a part. Fortunately, most children develop one of the localised forms and systemic disease is late. The prognosis of any individual type of scleroderma is dependent upon the subset of the disease, its extent, and internal organ involvement. In childhood, the problem is usually not one of survival, but of morbidity due to atrophy of skin, muscle and bone, with the potential for eventual growth defects and deformity. Drug treatment, when required, is usually directed towards suppressing inflammation and collagen deposition; vascular therapy does not play a major role, but physical therapy is crucial in certain forms of the disease.
Nodular scleroderma is a rare variant of the disease, whose pathogenesis is uncertain. Tenascin is a recently cloned extracellular matrix protein which is thought to be a marker for tissue remodelling. To further investigate the pathogenesis of nodular scleroderma, we have followed up a case of this disease and studied tenascin expression in the nodular lesions and surrounding progressive systemic sclerosis skin. Previously, we demonstrated a long-lasting intermediate level of dermal tenascin expression in progressive systemic sclerosis; morphea and hypertrophic scar lesions showed strong but short-lived tenascin expression. In our current patient, high levels of tenascin were found in the nodules, which rapidly resolved. Thus, the time course of the clinical and histopathological findings together with the tenascin expression were more suggestive of hypertrophic scar than progressive systemic sclerosis. These findings imply that nodular scleroderma has a supplementary pathogenesis, such as itching, in addition to the proceeding systemic sclerosis.
A glycosaminoglycan with scleroderma-inducing effect was isolated and partially purified from the urine of patients with systemic scleroderma. The glycosaminoglycan was an N-sulfated glycosaminoglycuronan and its high total sulfate and 2,5-anhydromannose contents suggest that the glycosaminoglycan is a degradation product of heparin or polysulfated heparin sulfate. Furthermore, the composition of the above glycosaminoglycan was similar to that of the N-sulfated glycosaminoglycan which we observed previously in uninvolved skin of scleroderma.
We present four cases of scleromyxedema with scleroderma-like cutaneous changes mimicking systemic sclerosis and stress the importance of their differentiation from true scleroderma. Scleromyxedema should be recognized as an entity since it differs from scleroderma in the pathogenesis, histopathology of cutaneous lesions, type of visceral involvement (if present), frequent association with paraproteinemia, the course and prognosis.
For the stimulation of research on scleroderma and the prophylaxis of occupational scleroderma-like diseases and the prevention of iatrogenic injuries, respect., it is important to know the inducing environmental substances. Plastics (vinyl chloride, epoxy resins), solvents (chlorinated, aromatic and aliphatic hydrocarbons), drugs (bleomycin, pentazocine), cocaine (abuse) and contaminated rapeseed oil are more or less able to induce scleroderma-like diseases. Vinyl chloride disease is the best known among these. The toxic oil syndrome represents the most inglorious example of the recent time. Paraffin and silicon can act as adjuvants and induce a progressive systemic sclerosis. In our studies it could be shown, that silica is able to induce not only a silicosis, but also a true progressive systemic sclerosis after long term exposure. Acknowledgment of such cases as an occupational disease is justified and regulated by law in the German Democratic Republic.
As a result of intraperitoneal injections in mice of crude glycosaminoglycans obtained from the urine of patients with systemic scleroderma, a fibrotic process similar to the intial changes of human scleroderma was frequently observed, especially in the skin and esophagus when the glycosaminoglycans contained a probable variant of heparan sulfate. Furthermore, the scleroderma-like change was also observed, to some extent, in the ultrastructure of collagen fibers and glycosaminoglycans of the skin.
Renal involvement in systemic sclerosis (SSc) has a negative influence on prognosis. Cases of SSc sine scleroderma have been reported in which organ failure occurred but was not accompanied by cutaneous damage, which in some instances did develop later. We describe a patient who, after 6 months of symmetric polyarthritis, developed rapid progressive renal failure without skin changes. A diagnosis of scleroderma renal crisis, confirmed histologically, was made. Anti-RNAP III antibodies were positive. The patient developed typical scleroderma skin changes after renal failure. Despite treatment, SSc advanced to fatal endstage renal disease.
We report on a 45-year-old painter who developed morphea-like scleroderma. He had been exposed to perchlorethylene for one year while operating a metal degreaser; the perchlorethylene concentration in the workplace ranged between 10 and 25 ppm. Whereas systemic scleroderma has frequently been attributed to solvent exposure in the past, this is only the third description of a morphea-like scleroderma suspected to be related to occupational contact with organic solvents.
Two different forms of scleroderma in one family are described: the mother suffers from systemic sclerosis and her daughter from linear morphoea. The observed HLA antigens indicate that systemic sclerosis and morphoea have various features in common. The immunogenetic data can be used to calculate the aetiological and preventive fractions, which together with environmental hazards and other risk factors describe the HLA-associated potential for provocation of scleroderma.
Circulating endothelial cell growth-inhibitory factor with a molecular weight of 40-60 kDa was described in scleroderma (SSc) sera and shown to have a proteolytic action. In view of the recent demonstration of cellular immune activation in SSc, and because of the description of novel serine proteases in the granules of activated cytolytic T cells (granzymes), we hypothesized that granzymes represent the endothelial inhibitory principal in SSc sera. Granular enzymes were isolated from IL-2-activated nonadherent normal lymphocytes, and a 60-kDa granzyme was isolated using benzamidine-affinity column and molecular sieve column. A polyclonal antiserum was generated by immunizing rabbits with the isolated granzyme. Anti-granzyme antibody abolished SSc serum-mediated EC growth inhibition. Furthermore, a circulating protein similar to isolated granzyme was identified as a 60-kDa band on Western blots of benzamidine column-purified SSc sera. Immunofluorescence studies of SSc skin biopsies using anti-granzyme antibody demonstrated the presence of granzyme reactivity, while healthy control tissues were negative. Moreover, granzyme A gene expression was identified in SSc skin biopsies by a PCR method. The data suggest cytolytic mechanism involvement in the pathogenesis of scleroderma.
A 57-year-old female patient presented with a long history of overlapping autoimmune disease, including limited cutaneous systemic sclerosis, Sjögren's syndrome and primary biliary cirrhosis. Another unusual finding was that the mild skin involvement (limited cutaneous systemic sclerosis, subcutaneous calcinosis) was combined with serious internal organ involvement, including honeycombing and finally scleroderma renal crisis. The most important finding was, that two decades later she developed severe telangiectasia of the gastrointestinal and urinary tract. Furthermore, a specific type of vascular malformation, i.e. gastric watermelon stomach was also found. The chronic gastrointestinal bleeding primarily derived from a watermelon stomach caused protein overload, which provoked the onset of the scleroderma renal crisis that finally led to the patient's death.
Renal crisis is a serious complication of systemic sclerosis. Its occurrence prior to the development of skin sclerosis is exceedingly rare. We report a patient who developed acute renal failure during pregnancy. Renal biopsy showed features compatible with scleroderma renal crisis but typical cutaneous changes were only evident 2 months after the renal episode. The relationship between pregnancy, scleroderma activity and renal crisis is discussed.