Quantitative analysis of nailfold capillary abnormalities in patients with connective tissue diseases

BACKGROUND: Nailfold capillary microscopy has been shown to reflect microvascular disturbances mainly in connective tissue diseases including systemic sclerosis (SSc). METHODS: Nailfold capillary abnormalities were analyzed with a light microscope under immersion oil at magnifications of x60 and x400. RESULTS: Abnormal nailfold capillary pattern in SSc was different from that of systemic lupus erythematosus (SLE) and normal controls, but not from dermatomyositis (DM). Seventy-two per cent of patients with Raynaud's phenomenon showed an abnormal nailfold capillary pattern. In primary Raynaud's phenomenon, 12% of subjects developed undifferentiated connective tissue disease. In undifferentiated connective tissue disease, 23% developed SSc. The apical limb width, capillary width and capillary length of subjects who developed SSc were significantly larger than in those who did not. With regard to the clinicolaboratory findings, the occurrence rate of an abnormal apical limb width, abnormal capillary width, abnormal capillary length, and antinuclear antibody in patients who developed SSc was significantly higher than in those who did not. An abnormal capillary pattern correlated with an elevated pulmonary artery resistance. All the patients with pulmonary arterial hypertension showed an abnormal capillary pattern, decreased diffusion capacity for carbon monoxide, and elevated pulmonary vascular resistance. Nailfold capillary abnormalities show a close relation to pulmonary arterial hypertension. CONCLUSIONS: Nailfold capillary abnormalities are useful for detecting vascular abnormality in clinical practice. These facts stress the importance of nailfold capillary abnormalities in SSc.     

The predictive value of quantitative nailfold capillary microscopy in patients with undifferentiated connective tissue disease

The present prospective study was undertaken to follow the natural history of patients with Raynaud's phenomenon and to document in these patients the frequency with which secondary disorders develop. Seventeen patients with primary Raynaud's phenomenon (PRP) and 43 patients with undifferentiated connective tissue disease (UCTD) were examined after 6–8 years to see whether they had developed into UCTD or systemic sclerosis (SSc), respectively. Their nailfold capillary parameters were analysed statistically to ascertain whether they would predict for the development of the diseases into UCTD or SSc. Two patients with PRP(12%) developed into UCTD, and 10 patients with UCTD (23%) into SSc. In PRP, all three parameters of the patients who developed into UCTD showed a tendency to be larger than in those who did not develop UCTD. In UCTD, the apical limb width ( P  < 0.02), capillary width ( P  < 0.01) and capillary length ( P  < 0.01) of the subjects who developed SSc were significantly larger than those who did not. Of the clinicolaboratory findings in patients with UCTD, the occurrence rate of abnormal apical limb width (relative risk 20.7, P  < 0.01), abnormal capillary width (relative risk 10.7, P  < 0.01), abnormal capillary length (relative risk 9.2, P  < 0.02) and antinuclear antibody (relative risk 9.6, P  < 0.05) showed a significant predictive value for the development of UCTD into SSc. These results indicate that quantitative nailfold capillary microscopy, as well as antinuclear antibody, will provide exact predictive information in patients with UCTD in clinical practice.     

Glucocorticoids in autoimmune connective tissue diseases

ABSTRACT: Glucocorticoids (GCs) are occasionally required for the cutaneous manifestations of autoimmune connective tissue diseases. In general, good therapeutic alternatives with fewer side effects than GCs are available, including anti-inflammatory agents such as antimalarials or dapsone, or immunosuppressives such as azathioprine or methotrexate, and these can serve as GC-sparing agents or can substitute for the use of GCs. When GC use cannot be avoided, it is important to implement a number of recommendations and improvements in dosing and prevention of side effects in order to optimize care. These include using appropriate and adequate doses of GCs initially, appropriate tapering regimens, and proper monitoring, prophylaxis, and treatment for infections, osteoporosis, avascular necrosis, hyperglycemia, hypertension, hyperlipidemia, and glaucoma.     

The prognostic value of nailfold capillary changes for the development of connective tissue disease in children and adolescents with primary raynaud phenomenon: a follow-up study of 250 patients

To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective tissue disease. We concluded that there were no specific capillary changes predictive for future development of systemic lupus erythematosus, juvenile onset rheumatoid arthritis/rheumatoid arthritis, and undifferentiated connective tissue disease in children and adolescents with Raynaud phenomenon. Most of our study subjects with Raynaud phenomenon who developed these diseases had normal capillary findings or nonspecific changes. Children and adolescents who developed scleroderma spectrum disorders showed a sclerodermatous type of capillary changes 6 months before the expression of the disease, indicating that this type of capillary changes in children and adolescents with Raynaud phenomenon highly correlated with further development of scleroderma spectrum disorders.     

Calcinosis cutis in autoimmune connective tissue diseases

Calcinosis cutis is a chronic condition involving insoluble calcified deposits of the skin and subcutaneous tissue. It is commonly associated with autoimmune connective tissue diseases and can be a source of pain and functional disability. The likelihood of developing calcinosis varies among the autoimmune connective tissue diseases, with systemic sclerosis and dermatomyositis being the most commonly associated. Identification of therapy for this challenging disorder has been hampered by a paucity of large controlled trials. Although there is no uniformly effective treatment for calcinosis cutis, several surgical and medical therapies have demonstrated varying degrees of benefit in the treatment of calcinosis, including surgical excision, laser therapy, extracorporeal shock wave lithotripsy, diltiazem, minocycline, colchicine, and topical sodium thiosulfate, along with others. Recommendations for the diagnosis and therapy of calcinosis cutis in patients with autoimmune connective tissue diseases are discussed.     

自噬在结缔组织疾病中的作用研究进展

细胞自噬是一种通过清除体内功能紊乱的蛋白或受损的细胞器,维持内环境稳态的重要降解过程.自噬还调控多种细胞生物学行为,包括细胞凋亡、代谢、炎症反应、抗原提呈、病原体清除等,与众多疾病密切相关.结缔组织病是一种病因不十分清楚,常伴有免疫学功能异常的一组疾病.而细胞自噬又被认为是调节机体免疫功能的重要机制之一,参与了T、B淋巴细胞的激活及增殖,成为连接固有免疫及适应性免疫的桥梁.因此,通过对细胞自噬在结缔组织疾病中作用机制的研究,为临床医生认识和治疗相关皮肤疾病提供理论依据.     

Update on connective tissue diseases in dermatology

Recent advances in understanding the pathogenesis of autoimmune diseases, including lupus erythematosus, dermatomyositis, and scleroderma, have allowed for reorganization of the classification of these disorders. With these novel stratifications, early identification of rheumatic skin diseases with systemic implications and consistency in designing and executing therapeutic trials will be enhanced. This review will provide a compilation of updates on epidemiology, pathology, evaluation, and classification with a predominant focus on therapeutics, reflecting the growth is this area.     

结缔组织病患者念珠菌深部定植的危险因素分析

目的 了解结缔组织病患者念珠菌深部定植的发生率及相关危险因素.方法 对153例结缔组织病患者和63例健康人的咽拭、中段尿、肛拭标本进行真菌培养,采用Logistic相关回归分析模型,对患者念珠菌深部定植的危险因素进行相关性分析.结果 患者组的念珠菌深部定植率35.29%显著高于健康人组7.94%,菌种分析以白念珠菌最常见.患者组血红细胞计数降低,尿蛋白增多,血清补体(CH50、C3、C4)水平降低,糖皮质激素使用每日均量较高以及广谱抗生素使用与结缔组织病患者念珠菌深部定植有显著相关性;而性别、年龄、身高、体质量、病程、有结缔组织病家族史、既往脏器损害、血白细胞及中性粒细胞计数低下、血小板计数低下、尿红细胞与白细胞异常增多、糖皮质激素使用总量与疗程、某些免疫抑制剂(环磷酰胺、硫唑嘌呤等)的使用、雷公藤的使用总量与疗程、窄谱抗生素的使用等与结缔组织病患者念珠菌深部定植无显著相关性.结论 结缔组织病患者念珠菌深部定植率显著高于健康人,控制相关危险因素将减少念珠菌深部定植的发生.     

Diagnostic significance of autoantibodies in connective tissue diseases

Autoantibodies have become an important diagnostic tool for the diagnosis of connective tissue diseases (CTD) and for defining certain subgroups of these diseases. According to the reationship between clinical symptoms and the specificity of autoantibodies they can be classified into two major groups: (1) marker antibodies which are highly specific for a particular disease entity and (2) symptom specific autoantibodies associated with certain clinical expressions or subgroups. Titers of autoantibodies can vary from low to high but do usually not correlate with the status of disease activity. In order to interpret the significance of autoantibodies in CTD and to predict the course of disease it is necessary not only to identify single autoantibody specificities but to consider the combination in which they appear.     

Diagnostic significance of autoantibodies in connective tissue diseases

Autoantibodies have become an important diagnostic tool for the diagnosis of connective tissue diseases (CTD) and for defining certain subgroups of these diseases. According to the reationship between clinical symptoms and the specificity of autoantibodies they can be classified into two major groups: (1) marker antibodies which are highly specific for a particular disease entity and (2) symptom specific autoantibodies associated with certain clinical expressions or subgroups. Titers of autoantibodies can vary from low to high but do usually not correlate with the status of disease activity. In order to interpret the significance of autoantibodies in CTD and to predict the course of disease it is necessary not only to identify single autoantibody specificities but to consider the combination in which they appear.     

肠道菌群失调与皮肤科常见结缔组织病相关性概述

【摘要】 越来越多的研究发现,肠道菌群与结缔组织病具有相关性。本文概述肠道菌群的特点及其在结缔组织病中的作用机制,重点阐述肠道菌群失调在红斑狼疮、系统性硬化病、干燥综合征中的相关性、可能作用机制及相关假说。通过益生菌调节肠道菌群失调可作为这些常见结缔组织病的治疗手段之一。     

Autoimmune connective tissue diseases in the COVID-19 pandemic

Autoimmune connective tissue diseases are a heterogeneous group of clinical entities sharing a common feature-an impairment of structural components like collagen and elastin, arising by autoimmune mechanisms. Because most patients are on a long-term immunosuppressive therapy, which renders them vulnerable to infections, a new challenge appears in front of physicians in the coronavirus disease 2019 (COVID-19) era. Immune mechanisms are substantial for the control and ceasing of viral infections, and their impairment may cause serious complications; however, data from immunosuppressed transplant patients do not reveal a higher frequency or diseases’ severity in those infected by COVID-19. Several immunotherapies used to treat autoimmune connective tissue diseases favorably modulate the immune response of severe acute respiratory syndrome coronavirus (SARS-CoV-2)–infected patients.The present review highlights the problems of susceptibility, severity, and therapeutic options in patients with autoimmune connective tissue diseases during the COVID-19 pandemic. The relationship between autoimmune connective tissue diseases and COVID-19 infection is explained with antiviral protection genes expression, hypercytokinemia, and lymphohistiocytosis/macrophage activation mechanisms. Recommendations concerning therapy for prevention during the pandemic period or in case of concomitant COVID-19 infection are also presented. Clinical trials are ongoing regarding COVID-19 therapy blocking the cytokine response. © 2021 Elsevier Inc. All rights reserved.     

Acid lysosomal hydrolases in systemic sclerosis and other connective tissue diseases

The activities of five lysosomal hydrolases were determined fluorometrically in the serum of patients with systemic sclerosis (PSS), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), or Raynaud's disease (RD). In PSS the β-galactosidase activity was significantly increased compared with controls and the other connective tissue diseases. The β-N-acetyl-glucosaminidase was significantly increased in PSS, SLE and DM. In PSS both enzymes were more active in the early stage of the disease than later. These changes of enzyme pattern seem to be a relatively reliable marker for the differential diagnosis of PSS compared to other connective tissue diseases, especially for RD, in which the β-galactosidase activity was significantly decreased. Further work is required to determine whether these polysaccharide-degrading acid hydrolases play a role in the pathogenesis of PSS.     

Dermoscopy findings of nail fold capillaries in connective tissue diseases

Nail fold (video) capillaroscopy is a well-established technique to assess patients with Raynaud's phenomenon, in whom specific abnormalities of capillaries are predictive of underlying systemic sclerosis and its related diseases (scleroderma spectrum disorder). The typical abnormalities are also found in patients with dermatomyositis and those findings are useful for the assessment of vascular injury and the evaluation of therapeutic effect in patients with scleroderma spectrum disorder and dermatomyositis. Recently, it has been suggested that dermoscopy can replace the capillaroscopy in significant part for detection of nail fold capillary abnormalities. In this review, I summarized the established capillaroscopy findings in connective tissues diseases and tried to apply the findings of dermoscopy to the findings and classification of capillaroscopy.