Scleroderma-like Changes Research Articles

Primary Pulmonary Hypertension Is Not Associated With Scleroderma-Like Changes in Nailfold Capillaries

Study objectivesTo determine whether primary pulmonary hypertension (PPH) is associated with scleroderma-like changes in nailfold capillaries. DesignBlinded, prospective, case-control study. SettingUniversity medical centers in Baltimore, MD. PatientsThirty-seven patients with PPH, 15 patients with scleroderma, and 13 healthy control subjects. MeasurementsSubjects underwent nailfold capillary videomicroscopy of the fourth digits of both hands. Capillary images were evaluated by two blinded, trained graders according to standardized criteria for the presence of scleroderma nailfold changes. ResultsThe prevalence of scleroderma-associated nailfold changes in patients with PPH (1 of 37 patients) was dramatically lower than that in patients with scleroderma (9 of 15 patients; p < 0.0001). The distribution of nailfold grades for the PPH patients was indistinguishable from that of the healthy control subjects. ConclusionPPH is not associated with scleroderma-like vasculopathy of nailfold capillaries.

BREAST CANCER AS A COMPLICATION IN WERNER'S SYNDROME

Werner's syndrome is an autosomal recessive disease with premature senility, scleroderma-like changes, characteristic habitus & stature, and often complicated with a malignant tumor. This paper reports on a very rare case of breast cancer as a complication in Werner's syndrome. A 48-year-old female was seen at our department because of 1cm tumor in A region of her left breast. The tumor was diagnosed as left breast cancer (T2a, No, Mo, stage II). Modified radical mastectomy was performed. Pathological diagnosis was solid-tubular carcinoma, f, s, no. DNA ploidy pattern was aneuploidy. Amplification of c-erbB-2 gene was not found. Postoperative course was uneventrul. We should entertain a possible association of breast cancer in the treatment of Werner's syndrome, though it occurs in a low frequency.

Multiple Plaques of Morphea Developing in a Patient With Eosinophilic Fasciitis

<h3>To the Editor.—</h3> Eosinophilic fasciitis (EF) is characterized by sclerodermalike changes associated with peripheral blood eosinophilia, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate.¹Since the first description by Shulman in 1974,²over 200 patients with EF have been described. Whether EF is a variant of scleroderma or a separate disease entity is still unclear. Multiple plaques of morphea developed in our patient 1 year after EF was diagnosed, which suggests a possible relationship between the two disorders. <h3>Report of a Case.—</h3> In January 1989, a 62-year-old white woman with a history of osteoarthritis was referred to the outpatient clinic of our department because of pain and stiffness in the skin of her lower extremities. She had not taken any drugs or L-tryptophan. On examination, the skin of her lower extremities was edematous and indurated. A full-thickness (down to underlying muscle) biopsy specimen from the upper leg revealed a

Cyclosporine: GVHD and beyond

Graft-versus-host disease (GVHD) holds a dual place in contemporary medicine. Clinically, it presents a serious problem in histocompatible bone marrow transplantation, and it is the principal limitation to histoincompatible bone marrow transplantation. Biologically, GVHD is a model for diseases of autoimmunity and immune dysregulation. After bone marrow transplantation, GVHD can present as either of two clinical syndromes: the acute disease, which is characterized by the cytolytic destruction of the recipient's skin, gastrointestinal tract, and liver; or chronic GVHD, in which there are scleroderma-like changes in the skin, gastrointestinal tract, and liver and the development of autoantibodies in the presence of . . .

Transfer of cyclosporine-associated syngeneic graft-versus-host disease by thymocytes. Resemblance to chronic graft-versus-host disease.

Syngeneic rat radiation chimeras treated transiently with cyclosporine (CsA) often develop a GVHD-like syndrome after discontinuing the drug. CsA also causes medullary involution and loss of medullary epithelium in the thymus. Chronic graft-versus-host disease (GVHD), a late occurring syndrome following bone marrow transplantation with many features of autoimmune diseases, is thought by many to result from a thymic deficiency leading to a failure to develop specific tolerance for the host. A direct connection between a thymic deficiency and chronic GVHD was tested by transferring thymocytes from CsA-treated syngeneic Lewis chimeras into irradiated Lewis secondary recipients. Nine of 10 of these recipients had evidence of chronic GVHD in skin biopsies taken at 3 weeks posttransplant or in the autopsies at 5 weeks. Changes included characteristic lichen planuslike infiltrates and sclerodermalike changes in the skin, characteristic infiltrates and myositis of the tongue, often chronic hepatitis with bile duct injury, and interstitial and ductal infiltrates in the serous salivary glands. Immunoperoxidase stains of the skin and tongue infiltrates showed a marked predominance of W3/25+:OX8- lymphocytes. The hair follicles had increased expression of Ia antigen. The thymus in the secondary recipient had variable thymocyte reconstitution of the cortex and a mild to marked reduction in the relative size of the medulla. Stains for cytokeratin showed a moderate to marked reduction of cortical epithelium and marked to total loss of the medullary epithelium. These studies demonstrate that the features of post-CsA syngeneic GVHD resembling chronic GVHD result from an abnormal thymic microenvironment. They also provide additional evidence linking a thymus deficiency with chronic GVHD.

Toxic oil syndrome: A syndrome with features overlapping those of various forms of scleroderma

Thirty-two toxic oil syndrome (TOS) patients were selected because they presented with sclerodermalike changes and were observed during the first 36 months of evolution of the disease. Initially, these patients presented with a noncardiogenic pulmonary edema, eosinophilia, arthralgia/arthritis, peripheral edema, and myositis. Histologic investigations showed a widespread chronic interstitial infiltrate with lymphocytic vasculitis. They subsequently developed peripheral neuropathy, joint contractures, scleroderma-like changes, Raynaud phenomenon, pulmonary hypertension, sicca syndrome, and liver disease. Biopsy studies during this stage showed fibrosis and obliterating arteriopathy. Late features of TOS are musculoskeletal pain, cramps, livedo reticularis. carpal tunnel syndrome, and digital tuft changes. TOS is a new chemically induced scleroderma-like syndrome with features overlapping those of eosinophilic fasciitis, systemic sclerosis, and forms of localized scleroderma.

Clinico-pathological changes induced in rats treated with amine-curing agent for epoxy resin, bis(4-amino-3-methylcyclohexyl)methane.

Amine-curing agent for epoxy resin, bis(4-amino-3-methyl-cyclohexyl)methane (commercial name; Laromin C) has been suspected to have induced in the workers some toxic signs such as collagen disease like scleroderma or polymyositis. Subacute toxicity of this agent was studied in rats following repeated oral administration. The agent was given orally at 5 dose levels (25 mg/kg to 100 mg/kg per one dose) for periods ranging from 10 days to 4 weeks. After the completion of administration, clinico-biochemical tests and histopathological examinations were carried out. In a few cases, skeletal muscles and choroid plexus of the brain were examined by electronmicroscopy. Clinico-biochemical tests revealed some elevation of muscle-derived components such as GOT and CPK as seen in the myopathic diseases. Histologically, various degrees of atrophy, degeneration and regeneration of muscle fibers and a numerical increase of interstitial cells were observed in the skeletal muscles. Electronmicroscopical examination of the gastrocnemius muscle revealed intrasarcoplasmic osmiophilic round-shaped inclusion bodies, sometimes with lamellar structure, which were suggestive of some lipidosis. The epithelial cells of choroid plexus in the brain ventricles represented various degrees of vacuolar changes lightmicroscopically, which were suggested to be dilated smooth endoplasmic reticulum electronmicroscopically. Although scleroderma-like changes were not observed in our experiments, the results suggest that this amine-curing agent for epoxy resin could be one of the causative agents which induced toxic lesions like some collagen diseases including muscle lesions in the workers. In addition, it is considered that the agent may have systemic toxic effects.

Bullous Sclerodermalike Changes in Chronic Graft-vs-Host Disease

Cutaneous sclerodermalike changes are a well-documented manifestation of chronic cutaneous graft-vs-host reaction. We describe a patient with chronic cutaneous graft-vs-host reaction who developed vesicles and bullae on sclerodermoid skin 18 months after bone marrow transplantation. The vesicles and bullae were subepidermal in location by light microscopy and were associated with dilated lymphatics and a sparse perivascular mononuclear cell infiltrate. No deposition of immunoreactants was seen by immunofluorescent microscopy. Electron microscopy confirmed the presence of a subepidermal blister beneath an intact basement membrane zone and surrounded by marked dermal edema. We postulate that localized lymphedema may play a role in the development of these vesicles and bullae.

Bullous sclerodermalike changes in chronic graft-vs-host disease

Bullous sclerodermalike changes in chronic graft-vs-host disease

Proteoglycans in the Werner syndrome and aging: a review and perspective.

The Werner syndrome (WS), like several other “segmental progeroid syndromes,” provides a valuable system for investigating the genetic control of longevity and age-related pathology (Martin, 1978). In WS, except for short stature, symptoms develop in adult life and include graying and generalized loss of hair, juvenile cataracts, scleroderma-like changes in the skin, and high incidence of neoplasms. Epstein et al. (1966) noted that many of the changes in WS in vivo were suggestive of an impairment in the development and metabolism of connective tissue. Clinically, a prominent feature is atrophy of the skin over areas in which the subcutaneous adipose tissue is depleted, resulting in a shiny smooth skin which cannot be lifted or is actually adherent to the underlying tissue. There is usually atrophy of the underlying connective tissue, musculature and fat, and development of hyperkeratoses over the bony prominences. The hyperkeratoses often become ulcerated. WS patients show an increase in occurrence of mesenchymal type tumors such as fibroliposarcomas, osteogenic sarcomas, hemangiolipomas and menigiomas. Japanese researchers (Tonkunaga, et al., 1975; Goto and Murata, 1978; Zebrower et al., 1984) have identified another connective tissue-related clinical characteristic: excessive excretion of hyaluronic acid in urine. Although these clinical manifestations are reminiscent of the aging process, there is still uncertainty as to whether this syndrome is truly a caricature of aging. Part of this uncertainty arises from the paucity of information concerning the molecular events associated with aging at the tissue and cell level. More specifically, little is known about those changes that take place within specific connective tissues of patients with the Werner syndrome.KeywordsHyaluronic AcidChondroitin SulfateDermatan SulfateKeratan SulfateLate PassageThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Scleroderma-like changes in insulin-dependent diabetes mellitus: clinical and biochemical studies.

Children with insulin-dependent diabetes mellitus (IDDM) were examined for scleroderma-like changes of digital sclerosis and joint contractures. Of the 104 patients, 19 (18%) demonstrated these features; five patients had both multiple joint involvement and skin changes; three were studied in detail. All three had restrictive pulmonary disease. Histopathology of skin in these three patients demonstrated increased accumulation of collagen in the lower dermis. In two of the patients, the extractability of collagen in 0.5 N acetic acid was decreased by about 50% as compared with normal controls, which suggests increased cross-linkage of collagen. In addition, the mean nonenzymatic glycosylation of collagen in these three patients was 13 times that of controls. The results indicate that distinct histopathologic and biochemical changes can be detected in the skin of these patients. The results further support the hypothesis that nonenzymatic glycosylation may alter the turnover of collagen, thus contributing to the development of a scleroderma-like syndrome with skin, joint, and pulmonary findings in patients with IDDM.

Neuromuscular disorders in a new toxic syndrome: electrophysiological study--a preliminary report.

The electrophysiological features in 145 patients with a new toxic syndrome related to ingestion of adulterated oil are described. Myalgia, joint limitation, weight loss, cramps, progressive weakness and wasting, sensory disturbances that can be asymmetrical or patchy, and scleroderma-like changes were the main clinical features. The electrophysiological findings suggest that the neuromuscular impairment in the new toxic syndrome is a slowly progressive mixed axonal neuropathy, which starts asymmetrically in some patients, with involvement of proximal and distal muscles as well as paraspinal and respiratory muscles. Muscle and nerve biopsies confirm the neuropathy, and show severe perineuritis and perineurial and perimysial fibrosis. The single fiber electromyography (SFEMG) study showed increased motor unit fiber density directly related to the time after onset of the illness. Unstable complex potentials were found after 6 months of evolution, which suggests that an effective collateral reinnervation was delayed following a long period of progressive denervation.

Rheumatology: An Annotated Bibliography of Recent Literature

Rheumatology: An Annotated Bibliography of Recent Literature

Scleroderma-like changes in chronic graft vs host disease

Scleroderma-like changes in chronic graft vs host disease

Scleroderma-like Changes in Chronic Graft vs Host Disease

A case of chronic graft vs host disease had scleroderma-like skin changes. Clinical progression was from poikiloderma to scleroderma, and histopathological changes and results of direct immunofluorescence were noted. It is probable that both cell-mediated (T-cell) and humoral (B-cell) mechanisms contribute to the pathogenesis of the graft vs host reaction.

Werner Syndrome Disputed-Reply

<h3>To the Editor.</h3> —A syndrome represents "a set of symptoms that occur... in a morbid state."1 In Werner syndrome, no biochemical defect has yet been demonstrated and no laboratory test or histopathologic feature is pathognomonic, and so the diagnosis must be based on the presence or absence of characteristic signs and symptoms. The characteristic features of Werner syndrome include growth arrest; premature graying, balding, arteriosclerosis, and cataracts; scleroderma-like changes of the extremities; reduction of muscle mass and subcutaneous tissues; chronic ulcers, particularly of the feet; beakshaped nose; impaired carbohydrate tolerance; hypogonadism; osteoporosis; localized soft tissue calcification; thin, high-pitched voice; circumscribed hyperkeratoses; and a history of consanguinity or familial involvement. Our patient had most of these features and, in addition, died suddenly at age 47 after our communication (90:53-56, 1973) was submitted. Premature death is another characteristic of Werner syndrome. A moderate variation occurs in the appearance and severity of separate

Ankle Ulcer Sign of Werner's Syndrome

In 1934, Oppenheimer and Kugel1distinguished the 2 conditions originally reported by Werner in 1904 and Rothmund in 1868 and established the criteria for the eponymic Werner's syndrome as we know it today. We are presenting another case of this rare disorder in which chromosomal studies were performed. The brother of the patient in question was briefly seen, but unfortunately could not be studied, although he also exhibited some classical signs of the same condition. The fully developed syndrome creates a remarkably constant picture, although incomplete forms have been reported. Detailed listings of these changes can be found in most of the medical literature on Werner's syndrome.2In brief, the usual changes of this particular form of progeria are (a)premature senility(premature baldness and gray hair; juvenile cataracts, arteriosclerosis); (b)scleroderma-like changes, clinically not histologically (atrophic skin and loss of subcutaneous tissue; circumscribed hyperkeratosis of soles; tightness

Roentgen findings in progeria.

Progeria is a rare disease of unknown etiology characterized by premature senility, retarded development, and death at an early age. Its roentgenographic features have been mentioned briefly in the study of about 30 cases reported since Hutchinson's original publication in 1886 (3, 5, 7, 10). The purpose of the present paper is to describe the typical roentgen manifestations of progeria as observed in 3 patients. Clinical Features The characteristic features of progeria appear at the beginning of the second year in a child who was normal at birth and during the first year of life. Failure to gain weight and to develop normally is first noted, with signs of rapid aging and a typical facial configuration with a beaked nose, receded chin, and baldness. Scleroderma-like changes occur in the skin, together with atrophy of the nails and subcutaneous tissues. Extension of the joints is limited. The veins are unusually prominent, especially on the head, and in some cases there are areas of brown pigmented skin over the body. Severe arteriosclerotic changes occur in this disease and patients may die prior to adolescence with occlusive coronary artery disease and myocardial or cerebral infarction (2, 6). Arthritic changes of the hands and hemiplegia have been reported, appearing as early as five years of age (8). There is no mental retardation. Progeria has been attributed to a dysfunction of the anterior pituitary (9) and to an inborn error of metabolism involving an enzyme of the energy metabolism cycle (1) . In spite of the severe arteriosclerosis found in some of these patients, the values of circulating lipids and lipoproteins have been reported by Keay and co-workers (6) to be normal. Roentgen Findings Skull: The head of the patient with progeria appears large in contrast to the small trunk and extremities, but skull measurements are within normal limits for the age. The cranial vault appears thin, with narrow diploic space; the fontanelles remain open and sutural bone formation may occur. A craniofacial disproportion is noted in the roentgenograms, due to a small and narrow maxilla contrasting with the normal breadth of the skull. The orbits are small and the palate is high and arched. The mastoid areas are poorly developed, and the sella turcica is sometimes enlarged. There is overcrowding of the teeth due to a delay in primary dentition: the mandible appears retrognathic and hypoplastic, with short rami and increase of its obtuse angulation (Fig. 1). Trunk: The chest is narrow, pyriform in shape, with thin, slender, osteoporotic ribs. The heart shadow is enlarged in some cases. The clavicles are short, markedly thin, tapering off at the ends, especially at the medial third. The vertebrae retain their infantile “fish-mouth” appearance (4), with notched, ovoid bodies (Fig. 2). The pelvis develops normally but reveals an extreme degree of bilateral coxa valga (Fig. 3). Extremities: The long bones are very thin and the femurs may be slightly bowed.

Werner's syndrome with a report of two cases

Two cases of Werner's syndrome are presented, with a discussion of the important clinical features of this entity which include short stature, premature senility, juvenile cataracts, scleroderma-like changes, skin ulcers over the feet and ankles, and certain endocrine abnormalities. The diagnosis depends upon the physician's awareness of this entity and can usually be made by general inspection of the patient. The etiology of Werner's syndrome is unknown. Hereditary factors seem to be important. Although endocrine abnormalities are usually present, they are variable in their occurrence and probably are of no etiologic significance. An endocrine evaluation of our patients revealed that both had a decrease in glucose tolerance. One patient had clinical hypogonadism and both had osteoporosis. There was no evidence of primary thyroid, parathyroid or pituitary abnormality. In both cases there was evidence of arteriosclerosis. The S f 12–20 and S f 20–100 values of the sera were normal in one patient and elevated in another. Treatment is not specific and is directed toward manifestations such as cataracts, diabetes mellitus, skin ulcers and hypogonadism.