Parathyroid hormone and calcium metabolism in generalized scleroderma

Summary Parathyroid hormone (PTH) in serum and biochemical parameters of calcium metabolism were analysed in 45 patients with systemic sclerosis. Calcification of the skin and subcutaneous tissue was assessed by X-ray examination of the hands.Analyses disclosed secondary hyperparathyroidism (increased PTH in serum, low calcium ion in serum, decreased urinary excretion of calcium and phosphate), in particular in patients with calcinosis (P<0.05) as compared to those with no calcinosis. The duration of systemic sclerosis was longer in patients with calcinosis (P<0.05).The calcinosis type of systemic sclerosis is characterized by secondary hyperparathyroidism developed during the progression of the disease. A hypothesis is made regarding calcium metabolism in the early nocalcinosis (with increased synthesis of Vitamin D) and late calcinosis types. PTH may stimulate aberrant calcification. The hypothesis implicates that prophylactic treatment with Vitamin D in low dose may prevent calcinosis.     

皮肌炎伴发恶性肿瘤的研究进展

皮肌炎伴发恶性肿瘤是皮肌炎的一个亚型,伴发恶性肿瘤为皮肌炎预后不良的主要因素。恶性肿瘤高危发病时间为皮肌炎诊断前后1年内。与经典型皮肌炎相比,皮肌炎伴发恶性肿瘤具有患者年龄>50岁、Heliotrope征、皮肤坏死及肌炎特异性抗体抗转录中介因子1γ抗体、抗核基质蛋白2抗体阳性等典型的临床特点,这些特点提示需进行恶性肿瘤...     

Soluble CD4 and CD8 in serum from patients with localized scleroderma

Localized scleroderma has been shown to be accompanied by various immunologic abnormalities. To obtain functional information on activated CD4+ or CD8+ T cells, we studied the levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) in serum from patients with localized scleroderma. Serum samples were examined by enzyme-linked immunosorbent assay. The samples were obtained from 49 patients in the following three subgroups: 15 patients with generalized morphea, 22 with linear scleroderma, and 12 with morphea. The levels of sCD4 and sCD8 were significantly elevated in patients with generalized morphea. Furthermore, these patients showed significantly higher levels of sCD4 than those with systemic sclerosis (SSc). The frequency of positivity for IgG anti-single-stranded DNA (ssDNA) antibody was significantly higher in localized scleroderma patients with elevated sCD4 levels than in patients with normal sCD4 levels. The frequency of positivity for antinuclear antibodies, IgM antihistone antibodies, IgG anti-ssDNA antibody and rheumatoid factor, and elevated sCD23 levels were significantly higher in localized scleroderma patients with elevated sCD8 levels than in patients with normal sCD8 levels. Our findings suggest that both CD4+ and CD8+ T cells are activated in vivo in generalized morphea and that the immunologic events in generalized morphea are different from those in SSc.     

Taxane-induced scleroderma

We report five women who presented with scleroderma due to taxanes, mimicking systemic sclerosis. All five patients had received taxane chemotherapy for the treatment of metastatic breast cancer. Marked oedema began first, followed by skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months after the administration of taxane in all patients. Skin biopsies showed full-layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic cell infiltration. These cases resemble systemic sclerosis in terms of their clinical course and histological findings. However, clinical findings including Raynaud's phenomenon and pulmonary fibrosis as well as immunological abnormalities associated with systemic sclerosis were not detected in any of the patients. Although the mechanisms have not been clarified, it should be noted that taxane is causally involved in the formation of scleroderma-like skin conditions.     

Journey of a patient with scleroderma from renal failure up to kidney transplantation

The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.     

A case of nodular scleroderma

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.     

Epithelial-mesenchymal transition in the skin

Epithelial-mesenchymal transition (EMT) plays important roles not only in the morphogenesis but also in wound repair, tissue fibrosis and cancer progression. Recently, regulatory mechanism of this process has been elaborately elucidated. EMT can be a new therapeutic target for treating skin ulcer, fibrosing alopecia, and malignant cutaneous cancers, including squamous cell carcinoma and melanoma.     

Localized scleroderma: clinical spectrum and therapeutic update

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.     

Elevated plasma endothelin levels in systemic sclerosis

Endothelin is a novel potent vasoconstrictor peptide produced mainly by endothelial cells. Thrombomodulin is a high-affinity thrombin receptor on vascular endothelial cells that plays an important role as a natural anticoagulant. In this study, we measured plasma levels of endothelin and thrombomodulin in patients with systemic sclerosis or Raynaud's disease. Plasma levels of endothelin and the ratio of thrombomodulin to creatinine were significantly increased in patients with systemic sclerosis compared with normal controls, and there was a positive correlation between these two indicators (r=0.615, P=0.004). Moreover, plasma levels of endothelin were significantly higher in patients with diffuse systemic sclerosis than in patients with limited systemic sclerosis. In contrast, plasma levels of endothelin in patients with Raynaud's disease were not significantly increased. These results suggest that increased plasma levels of endothelin and thrombomodulin may reflect microvascular damage in systemic sclerosis.     

Cutaneous concerns of scleroderma patients

The clinical features of facial and oral involvement in scleroderma are striking. We conducted a survey of patients with systemic sclerosis (scleroderma). The purpose of our study was to ascertain what was most bothersome aesthetically to scleroderma patients. We also looked at the differences between age groups and genders. The survey was mailed to 1,000 individuals who subscribe to a national lay group organization. We received 303 completed surveys indicating the patient's age, gender, age at onset of disease, and a checklist of 14 physical variables involving the central face and non-face. The respondents were asked to rate their level of concern [on a scale of great (1) -moderate (2) -little (3) -none (4)] in regards to 14 different physical variables. The respondents consisted of 92% females and 8% males. The mean age was 59 years +/- 13 (SD), and the median age was 60. The mean and median age at diagnosis was 45 years +/- 15 (SD). The percentage of respondents expressing concern for specific features was the following: for thin lips (73%), mouth furrows (80%), loss of facial lines (68%), and a smaller, tighter mouth (77%). There was less concern over the non-face features. The percentage of respondents expressing no concern was the following: for absence of sweating (57%), skin darkening (50%), nail dystrophy (57%), and skin atrophy (63%). There was a highly statistically significant difference (p<0.0001) between those respondents concerned with central face features vs. non-face features. With advancing age and longer disease duration, there was increased concern over the aforementioned central face features (p<0.0001). The vast majority of patients with systemic sclerosis have great concerns over changing facial features, and this worsens with age.     

Anticytoskeletal antibodies in systemic autoimmune diseases

Aim To investiate the presence of antinuclear and anticytoskeletal autoantibodies in patients with systemic autoimmune and connective tissue diseases. Setting 646 sera of 322 patients with systemic sclerosis, systemic lupus eryhtematosus, mixed connective tissue disease, rheumatoid arthritis with or without secondary Sjögren's syndrome, and localized scleroderma, and 127 healthy controls were tested. Methods ‘Routine’ indirect immunofluorescence technique on HEp-2 cells. Results Antinuclear antibodies were found in 45–91.1% of the sera. Anti-intermediate filament antibodies were detected in 24 patients. Eight of the 24 cases had another (second) organ-specific autoimmune disease, mainly chronic active hepatitis or autoimmune thyroid disease.     

Autoantibodies to the heat-shock protein hsp73 in localized scleroderma

We determined the presence of antibodies to the heat-shock protein hsp73 (anti-hsp73) in 57 serum samples from patients with localized scleroderma using an enzyme-linked immunosorbent assay (ELISA). In addition, 30 samples from healthy individuals, 30 from patients systemic lupus erythematosus (SLE) and 32 from patients with systemic sclerosis were assessed. IgG and/or IgM anti-hsp73 antibodies were detected in 33% (19/57) of the patients with localized scleroderma. Among the three subtypes of localized scleroderma, generalized morphoea showed the highest incidence of anti-hsp73 antibodies (40%, 6/15). IgG and/or IgM anti-hsp73 antibodies were also detected in 9/30 samples (30%) from patients with SLE and in 13/32 samples (41%) from patients with systemic sclerosis, while the samples from the healthy controls were all negative for anti-hsp73. By immunoblotting, specific binding of antibodies to hsp73 was confirmed with representative serum samples that were positive for anti-hsp73 in the ELISA. Our findings indicate that the presence of anti-hsp73 is an additional immunological abnormality in localized scleroderma.     

Effect of crosstalk between Th17 and Th9 cells on the activation of dermal vascular smooth muscle cells in systemic scleroderma and regulation of tanshinone IIA

BackgroundTo evaluate the effect of T-helper 17 (Th17) cells and Th9 cells on the activation of dermal vascular smooth muscle cells (DVSMCs) in systemic scleroderma (SSc) and regulation of tanshinone IIA.MethodsThe expression of interleukin 17 receptor (IL-17R) and interleukin 9 receptor (IL-9R) in the skin of SSc patients was assessed by immunofluorescence. The expression of IL-9 and IL-9R mRNA in peripheral blood mononuclear cells (PBMCs) of SSc patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proportion of Th9 cells in PBMCs of SSc patients was sorted by flow cytometry. The effect of IL-9 on the differentiation of Th17 and IL-17 on that of Th9 was detected by flow cytometry. The proportion of Th9 and Th17 cells in SSc patients was detected by flow cytometry. The level of collagen I, III, α-SMA, IL-9R, IL-17R, JNK, P38, and ERK were analyzed using western blot (WB).ResultsTh9 cells were highly expressed in SSc. IL-9 stimulated the differentiation of immature T cells into Th17 cells. IL-17 induced the differentiation of immature T cells into Th9 cells. Tanshinone IIA inhibited the differentiation of immature T lymphocytes into Th17 and Th9. WB showed that the combined action of IL-17 and IL-9 upregulated the inflammation and proliferation of DVSMCs. Anti-IL17, anti-IL9, and tanshinone IIA inhibited the functional activation of DVSMCs.Study limitationsFor Th17, Th9 and vascular smooth muscle cells, the study on the signal pathway of their interaction is not thorough enough. More detailed studies are needed to explore the mechanism of cell-cell interaction.ConclusionsThe current results suggested that Th17 and Th9 cells induced the activation of DVSMCs in SSc through crosstalk in vitro, and tanshinone IIA inhibited the process.     

Epidemiological study of patients with systemic sclerosis in Tokyo

Summary We conducted an epidemiological study of systemic sclerosis in the city of Tokyo using the records of patients who had been registered to receive free medical service for intractable diseases. A total of 636 patients were registered as having systemic sclerosis in 1987, and we sent questionnaires to the doctor of each patient. The contents of the questionnaires included the patient's name, sex, age, occupation, major symptoms, therapy and laboratory findings. We received 357 completed replies, and were able to analyse them. Our study estimated that at 1 January 1988 the prevalence rate in Japan was between 2.1 and 5.3 per 100000. The male/female ratio was 14:1. The ages of the patients when surveyed ranged from 17 to 82 years, with a mean age of 51 years, peaking with the most numerous group being 50–59 years. The characteristic signs of systemic sclerosis were as follows: proximal scleroderma, 75%; sclerodactyly, 91%; pitting scars, 49%; short sublingual frenulum, 49%; pulmonary fibrosis, 45%; diffuse pigmentation, 45%; and phalangeal contracture, 35%. Raynaud's phenomenon was present in 93% of patients, and was the initial symptom in 59% of cases. With respect to specific antinuclear antibodies, anticentromere antibody was present in 19% and antitopoisomerase I antibody was present in 27%.