[ ISSN : 2573-3680 ]
Articular Involvement; Systemic Sclerosis; Treatment
Systemic Sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities. The rheumatic involvement of SSc is polymorphic and can reveal the disease or may appear during the course of its progression. Musculoskeletal involvement is dominated by non specific arthralgia, polyarthritis, and bony resorption especially acro-osteolysis. The diagnosis of these rheumatic manifestations is generally based on x rays examination. Musculoskeletal involvement in SSc is generally relieved with Non Steroidal Anti-Inflammatory Drugs (NSAID) or low dose of corticotherapy. The immunosuppressive therapy is used in corticoid-resistant or corticoid-dependent forms such us méthotrexate. The aim of our review is to presents an overview of the different osteoarticular and muscular involvement in SSc, their diagnosis and management.
Systemic Sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and internal organs, pronounced alterations in the microvasculature and frequent cellular and humoral immunity abnormalities [1,2].
Rheumatic manifestations are rare. They may include varying degrees of rheumatic complaints ranging from arthralgias to frank arthritis or bony lesions.
Many patients may develop musculoskeletal symptoms as an early sign of the disease or during the course of their illness. Articular and bone involvement contribute to disability and impaired quality of life and reducing the performance of everyday occupation in SSc.
Treatment of rheumatologic disorders often involves with NSAID, corticosteroids and methotrexate.
Joint involvement in SSc affects 46-97% of patients with SSc [3]. Generalized inflammatory arthralgias with pain and stiffness are the usual presentation of articular involvement. All joints may be affected, mainly the fingers (in particular the Metacarpophalangeal (MCP) and Proximal Interphalangeal (PIP) joints), wrists and ankles. Franck arthritis is less common. The onset of this latter may be acute or insidious, and oligoarticular or polyarticular in pattern [4].
In EUSTAR (EULAR Scleroderma Trials and Research) cohort, frequencies of synovitis and joint contractures were 16%, and 31%, respectively [5]. Synovitis was more frequently detected with ultrasonography (46%) than with clinical examination (15% P < 0.01) [6].
Rheumatoid factor positivity occurs in up to 30% of SSc patients [7]. This is considered as a non specific reactivity. The search for anti-CCP antibodies might be useful in the identification of the infrequent cases of true SSc-rheumatoid arthritis overlap. The synovial fluid is inflammatory. Its analysis reveals increased leukocyte concentrations of more than 2000 cells/mm3 and a predominantly mononuclear infiltrate.
Articular involvement was associated with a more severe disease. Inflammatory joint involvement is considered us bad prognosis and at risk of severe organ damage, especially severe vascular (pulmonary hypertension) and muscular (muscle weakness) involvement [6].
The radiologic findings in the joints are non specific. They include diffuse or periarticular osteopenia, soft tissue swelling, joint space narrowing, subluxations and rarely frank erosions. These articular features may be associated with non-articular abnormalities, in particular skin atrophy, subcutaneous calcinosis and digital tuft resorption, which are among the most distinctive radiographic findings in SSc [8]. The power Doppler ultrasonography was found to be significantly higher than the clinical examination to detect effusion and synovial proliferation. MRI is also a very promising tool to detect synovitis [9].
In the EUSTAR database, the prevalence of tendon friction rubs, defined as a leathery, rubbing sensation detected as the tendon was moved actively or passively, was 11% [5]. These abnormalities are frequent in the tendons of knees, wrists, fingers and ankles, related to fibrinous deposits on the surface of tendon sheaths. In the leg, the tendons of the tibialis anterior and the Achilles tendon are frequently affected than the peroneus muscles [10]. When it occurs in wrist it can be associated with a carpal tunnel syndrome. The data from the EUSTAR database highlighted the independent association in multivariate analysis between tendon friction rubs and digital ulcerations, muscle weakness, pulmonary fibrosis on plain chest X-ray and proteinuria detected with a urinalysis dipstick. Tendon involvement can be considered as a sign highly predictive of bad outcome [11].
Subcutaneous calcifications may be seen as a hallmark of SSc. It can occur in feet, knees and legs. Calcinosis has been strengthened by recent cross-sectional series showing a link between calcinosis, acro-osteolysis and digital ulcerations [12]. Calcinosis and digital ulcers were recently identified as independent predictors of the radiographic progression of acro-osteolysis. These data suggest that patients with severe digital vasculopathy are more at risk to experience radiographic progression of bone resorption and further support the role of vascular injury playing a critical role in such lesions, possibly due to repeated vasospasm.
Bone involvement is dominated by acro-osteolysis, defined as bony resorption of the terminal digital tufts, occurs in about 20% of the patients [13]. Other locations may be concerned such as carpal bones, radius, ulna, ribs, mandible, clavicle, humerus or cervical spine. It is supposed that acro-osteolysis results from impairment of blood supply, although pressure from skin tightening may also play a role [14].
Myopathy involvement is frequent in SSc. It is seen in 80% of SSc patients. This myopathy is often mild, with minor proximal weakness, and normal or slight elevation of Creatine Kinase (CK).
The overlap between inflammatory myositis and SSc is less frequent. This manifestation is characterized the presence of AntiPM/Scl antibodies.
The management of articular involvement is essentially symptomatic. The joint symptoms respond to simple NSAID treatment or small doses of corticosteroids (<10 mg/day) and do not require more intensive therapy. The risk of renal crisis with the use of corticotherapy should be carefully considered. Corticosteroid can be injected in the joint or under the retinaculum in the case of tenosynovitis.
Methotrexate may be used for the treatment of inflammatory arthritis and sub-cutaneous route is preferred to improve absorption. Other immunosuppressive drugs may be used, such as azathioprine or cyclophosphamide.
Lam and al [15] reported the efficacy of TNFα inhibitors on inflammatory joint symptoms in a retrospective study performed on 18 patients treated with etanercept during a 2-66 month period. Fifteen of these 18 patients had positive responses with a significant decrease in synovitis and complete resolution of joint symptoms in some patients.
Despite these encouraging results, it seems reasonable to avoid TNFα inhibitors in SSc because of some rare cases of fatal exacerbation of fibrosing alveolitis which have been reported in an SSc patient [16]. Controlled trials regarding the efficacy for joint symptoms and safety of TNFα inhibitors in SSc are needed.
Rituximab (RTX), a chimeric monoclonal antibody against the protein CD20 that demonstrated efficacy in RA, could represent an alternative to TNFα inhibitors in SSc. Recent studies suggest a possible promising therapeutic effect of RTX in SSc patients with clinical symptoms, namely the improvement of articular involvement [17].
There is also no actual robust data in favor of the use of tocilizumab and abatacept for the treatment of inflammatory joint disease related to SSc. SSc related myopathy does not usually require any specific therapy. However, in the case of overlap between SSc and inflammatory myositis, corticosteroids and immunosuppressive may be added to the conventional treatment of SSc. The surgery of the hand for SSc is sometimes needed. It includes pain relief, repositioning of the digits, arthrodesis and arthroplasty [4].
Musculoskeletal involvement is frequent in SSc. Although the understanding of osteoarticular pathogenesis has significantly increased in the last few years, optimal treatments of inflammatory joint disease remain to be determined and appear as a major challenge for improving SSc morbidity and patients’ quality of life. Despite encouraging preliminary data large randomized controlled trials are mandatory before drawing any conclusion.
N, Abourazzak FE and Harzy T. Musculoskeletal Involvement in Systemic Sclerosis. SM J Clin Med. 2015; 1(2): 1009.
The purpose of this statement is none other than to highlight the importance of ethical standards and quality required in basic and applied research currently being done so we can subsequently inform health care professionals of new developments that are taking place in this area.
Ma. Esperanza Rodríguez-van Lier*
Chemotherapy is commonly used in cancer treatment. So far, chemotherapy agents can be categorized into three types: classical chemotherapeutic drugs, molecular target agents and cellular machineries target drugs.
Ziyou Wang1,2 and Zunnan Huang1,2*
Blood transfusion can cause some transfusion adverse reactions. In order to understand the incidence of adverse transfusion reactions, we performed a meta-analysis in Chinese hospitals. Of 809 literatures, seven studies involving a total of 211, 050 patients with blood transfusion treatment were included in this meta-analysis. Meta-analysis showed that the total incidence of adverse reactions was 0.4% [95% CI (0.2, 0.9), P < 0.0001]. Further subgroup analysis showed that the incidence of febrile and allergic reactions was 0.2% [95% CI (0.1, 0.5), P < 0.0001] and 0.2% [95% CI (0.1, 0.3), P < 0.0001], respectively. The common blood components caused adverse reactions were red blood cell, plasama, and platelet in clinical practice.
Yulu Gao1 , Qinyun Li2 , Zongshuai Gao2 , Yunxia Zhu4 , Yanqiu Liao5 , Changtai Zhu2 *# , Yongning Sun3 *#
Background: CT scanning remains one of the most routinely used diagnostic tools in a setting of Interstitial Lung Disease (ILD). New and improved technologies, such as High Resolution Computer Tomography (HRCT) have revolutionized the quality of imaging, leading to a prominent increase in number of incidental findings that may or may not be of any clinical significance. The aim of this study was to evaluate the prevalence of incidental findings on thoracic CT and their clinical significance.
Methods: Retrospective analysis was conducted on a cohort of 84 patients referred to our academic center as cases of ILD. Patients were referred for further evaluation between January 2000 and January 2014 and were followed over the disease course. CT scans were done annually as part of clinical management and patients were screened for any incidental findings. All incidental findings were reviewed, recorded in a clinical database and followed up on subsequent visits.
Results: 25 (30%) patients were found to have incidental findings. Liver abnormalities were found in 12 (14.29 %) patients. 11(13.10 %) patients were reported to have coronary artery calcifications. 5 (5.95 %) and 3 (3.57%) patients had thyroid abnormalities and renal cysts, respectively. A malignant lesion was found in 1 patient each in liver and thyroid abnormality subgroup.
Conclusion: Incidental findings are common on thoracic CT scans providing valuable and unexpected findings which warrant investigation by health care providers to exclude malignant processes.
Sonu Sahni1,2*, Sameer Verma1,2, Reeju S Thomas1 , Barbara Capozzi3 and Arunabh Talwar1,2
Hepatitis C Virus infection (HCV) is an increasing public health concern with an estimated 184 million people infected worldwide and approximately 350.000 yearly deaths from HCV-related complications.
Nesrine Gamal and Pietro Andreone*
We report a case of large cell undifferentiated lung carcinoma in a middle aged patient with previously treated tuberculosis and scarring. 20 pack years of smoking history was noted. He presented with metastasis at multiple sites including trochanter, liver and acute bilateral lateral rectus palsy. Chest radiography showed fibrosis of right upper zone with homogenous opacity. Sputum examination for AFB was negative. Computerized tomography of the thorax showed an irregular heterogeneously enhancing mass involving right upper lobe with cavitation, necrosis along with lymph node involvement and the erosion of the 4th rib with liver metastasis. Radiography of hip joint was suggestive of lesser trochanteric metastasis. MRI brain was suggestive of mass at base of brain in parasellar area. Fine needle aspiration cytology and CT guided biopsy confirmed undifferentiated large cell carcinoma of lung. Tuberculosis and smoking may increase the risk of lung scarring and malignancy and pulmonary scarring may be associated with increased lung carcinoma in ipsilateral lung. Clinician needs to be more sensitive to look for malignancy association particularly in patient with or previously treated for tuberculosis and even more emphasis to be laid if scarring of lung is observed.
Sreenivasa Rao Sudulagunta1 *, Shyamala Krishnaswamy Kothandapani2 , Mahesh Babu Sodalagunta3 , Hadi Khorram2 , Mona Sepehrar4 and Zahra Noroozpour1
Sedigheh Mirhashemi1 , Mohammad Hosein Kalantar Motamedi1 *, Amir Hossein Mirhashemi2 and Hamid Reza Rasouli1
We encountered two autopsy cases of huge cardiomegaly with over 1000g in weight. Histochemical characteristics were examined using conventional staining including HE and Azan stains and immunohistochemical staining using antibodies against Complement Component 9 (CC9), RNA Binding Protein Motif 3(RBM3), Endothelial Type NO Synthase (eNOS) and Hypoxic Inducible Factor1α (HIF1). The reactive area with anti CC9 antibody, which presumed to be a marker of hypoxic change of myocardium, overlapped with eosinophilic area by HE and basophilic one by Azan. Although the reactive area with anti CC9 antibody showed relatively weak in the cytoplasm by anti eNOS antibody and no in the nucleus of cardiocytes with anti RBM3 antibody, outside of the reactive area with anti CC9 antibody there were intensive reactivity with anti eNOS antibody in cytoplasm and in a nucleus with anti RBM3 antibody. Anti HIF1 antibody showed weak reactivity with cytoplasm of endocardial cardiocytes and no with cytoplasm of cardiocytes in another area. The results obtained from the present cases revealed that the hypoxic change was equivalent even though the cause of cardiomegaly was deferred between two cases, and conventional staining such as HE and Azan utilized to detect hypoxic change in the heart and immunohistochemical studies seemed to be a useful tool for clarifying the cascade of hypoxic changes in the myocardium.
Satoshi Furukawa1,2*, Mayumi Kataoka1 , Satomu Morita1,2, Akari Uno2 , Masahito Hitosugi2 , Hiroshi Matsumoto1,3 and Katsuji Nishi1,2
A 45-year-old woman with multiple sclerosis was admitted to our hospital after out of hospital cardio-pulmonary resuscitation. The first ECG showed ventricular fibrillation. Following direct current defibrillation and mechanical reanimation, spontaneous circulation was restored and the ECG unremarkable without any signs of ischemia. Coronary angiography showed unobstructed coronary arteries Figure 1, (Panel A). Left ventriculography revealed apical wall obstruction, suggestive of apical aneurysm (Panel B, supplementary videos). Transthoracic echocardiography and Cardiac Magnetic Resonance Imaging (CMR) eventually lead to the diagnosis of a rare case of Apical Hypertrophic Cardiomyopathy (AHC) with ace of spades-form (Panel C,D). The patient underwent Cardioverter-Defibrillator Implantation (ICD) and amiodarone medical therapy for secondary prophylaxis. Patient’s family history and screening for HCM were unsuspicious.
Wiedemann S# *, Heidrich FM# , Speiser U and Strasser RH
We present the case of a 23-year-old female who was 23 weeks pregnant and presented to the emergency room of our Obstetric Department in nausea and vomiting that had been worsening over the course of 2 months with loss of eight kilograms in clinical presentation compatible with hyperemesis.
Elisa Picardo1*, Marco Mitidieri1, Marco Bozzaro2, Roberto Altieri2, Carlo Carmazzi1 and Saverio Danese1