Oropharyngeal dysphagia as a first manifestation of dermatomyositis associated with colon cancer

Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with characteristic skin manifestations. In 15-20% of patients present with dysphagia, it is associated with nutritional deficiency, predisposition to aspiration pneumonia, decreased quality of life and a poor prognosis. There is a well-recognized association between DM and malignancies, including ovarian, breast, lung, and colon cancer. We report a case of a male patient aged 85 with DM associated with colon adenocarcinoma; progressive dysphagia was the first manifestation, and subsequently proximal muscle weakness and typical skin lesions were present. Given the clinical suspicion of DM as a paraneoplastic syndrome, tumor markers were order and a high carcinoembryonic antigen was found. A colonoscopy study and histopathologic examination revealed the presence of adenocarcinoma of the colon.     

Cavitating pulmonary infarcts revealing thromboembolic pulmonary hypertension

Several etiologies are involved in the pathogenesis of cavitating pulmonary disease including neoplastic, infectious or inflammatory processes. Another is pulmonary infarction associated with venous thromboembolism. The lung cavities tend to be located peripherally and are the result of pulmonary embolism. We report the case of a woman with chronic thromboembolic pulmonary hypertension (CTEPH), associated with familial thrombophilia, revealed by cavitating pulmonary infarcts. CTEPH is sometimes diagnosed during an episode of recurrent pulmonary embolism following previously unnoticed lesions. Thrombophilias such as isolated elevated factor VIII are risk factors for CTEPH.     

The role of MRI in the assessment of polymyositis and dermatomyositis

OBJECTIVES: Acute inflammation in idiopathic inflammatory myopathies (IIM) causes oedema that can be visualized by magnetic resonance imaging (MRI). The inflammatory infiltrate in IIM is thought to be frequently in a focal distribution. The aim of this study is to better evaluate the relationship of MR image of thigh muscles to clinical and histological parameters in patients with IIM. METHODS: MRI-short tau inversion recovery (STIR) technique was used to distinguish between affected and non-affected muscles. Computer tomography (CT)-controlled targeted needle biopsy was used for sampling. The intensity of muscle oedema, its extent and total assessment on MRI were evaluated with 10 cm visual analogue scale. The intensity of inflammatory infiltrate was assessed using 5-point grading system. The second MRI and muscle biopsy were performed after the time interval of treatment. RESULTS: MR scans, muscle biopsy and clinical examination were performed in 29 patients with polymyositis (PM) and dermatomyositis (DM). Paired MRI-affected and MRI-non-affected biopsy samples were obtained from 17 cases. In six cases, the biopsy was available for comparison before and after period of treatment. At the initial examination, it was the intensity of oedema on MRI that was associated with clinical status. Mean intensity of MRI findings significantly decreased in 10 patients where the MRI was available also after treatment. The mean intensity of inflammatory infiltrate in PM/DM patients was 2.5 +/- 0.7 for MRI-affected and 1.7 +/- 0.6 for MRI-non-affected muscles (P < 0.001). Mean intensity of inflammatory infiltrate in the MRI-affected muscles in the first examination (n = 6) was 2.2 +/- 0.8 and did not significantly decrease in the second examination in samples taken after the treatment (2.0 +/- 0.9). CONCLUSION: It is mainly the signal intensity in MR scan, which is associated with disease activity in the acute presentation of PM/DM. Muscle biopsy guided by positive MRI finding contains significantly more inflammatory cells than the biopsy taken from MRI non-affected sites. However, even in parts of muscles, which look unaffected on MR scan, the inflammatory cells can be found. The intensity on MR scans decreases significantly after the treatment, but the histologically detected inflammation does not change substantially.     

MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with interstitial lung disease

Idiopathic inflammatory myopathies, such as polymyositis (PM), may present with general symptoms such as fever and fatigue and only minimal muscle weakness, making it difficult to make a definite diagnosis and provide adequate treatment. Here a case is described in which interstitial lung disease was the first and most prominent manifestation of PM. Later, when muscle weakness became apparent and inflammatory muscle disease was suspected the first muscle biopsy was non-diagnostic. However, magnetic resonance imaging (MRI) scans of the clinically weak thigh muscles showed high signal on T(2) weighted images, suggesting muscle inflammation more proximal to the first biopsy site. A second biopsy at this site disclosed typical histopathological findings for myositis. After treatment with prednisolone in combination with cyclophosphamide both pulmonary and muscle function improved. CONCLUSION: MRI scans of muscles may be helpful in selection of a site for muscle biopsy in patients with suspected inflammatory myopathy when a first muscle biopsy turns out to be negative. Additionally, patients with interstitial lung disease of unknown cause should be tested for muscular function to exclude an associated inflammatory muscle disorder.     

Anti‐MDA5‐associated dermatomyositis

Anti‐MDA5‐associated dermatomyositis (MDA5‐associated DM) is an uncommon presentation of idiopathic inflammatory myositis, typically amyopathic, associated with rapidly progressive, treatment refractory interstitial lung disease and poor prognosis, particularly in patients with concomitant rapidly progressive interstitial lung disease (RP‐ILD). We report two cases of MDA5‐associated DM with fatal outcome in one of the patients, despite ‘aggressive triple therapy’ for RP‐ILD.     

Primary lung cancer associated with polymyositis/dermatomyositis, with a review of the literature

It has been suggested that lung cancer is frequently associated with polymyositis/dermatomyositis (PM/DM). The purpose of this study was to describe the clinical features of primary lung cancer associated with PM/DM. We first describe the clinical features of two cases treated in our hospital, and then provide a review of the literature. Finally, 24 patients (five females and 19 males) with primary lung cancer associated with PM/DM are retrospectively evaluated. Histological types of lung cancer were as follows: small cell lung cancer (n=7), squamous cell carcinoma (n=5), adenocarcinoma (n=2), others (n=5), and unknown (4). The onset of PM/DM is frequently observed before the detection of lung cancer. This is the first report to describe the clinical features of lung cancer associated with PM/DM. Received: 10 March 2000 / Accepted: 20 June 2000     

Muscle biopsy findings in inflammatory myopathies

The inflammatory myopathies encompass a heterogeneous group of acquired muscle diseases characterized clinically, by muscle weakness, and histologically, by inflammatory infiltrates within the skeletal muscles. The group of these myopathies comprise three major and discrete subsets: polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM). Each subset retains its characteristic clinical, immunopathologic, and morphologic features regardless of whether it occurs separately or in connection with other systemic diseases. Although the diagnosis of these disorders is based on the combination of clinical examination, electromyographic data, serum muscle enzyme levels, various autoantibodies, and the muscle biopsy findings, the muscle biopsy offers the most definitive diagnostic information in the majority of the cases. This article summarizes the main histologic features that characterize PM, DM, or IBM and emphasizes the main pitfalls associated with interpretation of the biopsies.     

Dermatomyositis

Dermatomyositis (DM) is a systemic inflammatory disease involving skin, muscles and other organs. Immunologically mediated inflammation of small vessels leads to vascular damage, especially of the muscular tissue. Typically DM presents clinically with DM-type local or generalized rash and proximal muscular weakness. Laboratory signs of muscular damage (elevated serum CK, myoglobinuria) may be initially absent. Magnetic resonance tomography frequently shows edema of the involved muscles, while electromyography shows a myopathic pattern with spontaneous activity. Muscle biopsy from involved muscle with histological, immunohistological, histochemical and possibly electron-microscopic examination confirms the diagnosis of inflammatory muscle disease and furthermore of DM-specific muscular findings. Typical findings include the deposition of 5b-9 complement components (membrane attack complex) at the capillaries, perifascicular inflammatory infiltrates composed predominantly of CD4+ T-lymphocytes, B-lymphocytes and plasmacytoid dendritic cells, endothelial swelling and damage, loss of capillaries with perifascicular atrophy and tubuloreticular endothelial inclusions on electron-microscopic examination. Detection of myositis-specific autoantibodies is especially helpful in the diagnosis of early and atypical cases with features of overlapping disease.     

Metastatic vertebral tumor misdiagnosed in magnetic resonance imaging as benign degenerative bone marrow changes: a case report

Many disorders including congenital, degenerative, inflammatory, and neoplastic lesions are associated with low back pain. It is essential to differentiate between malignant disease and the more common causes of back pain. We report a man with low back and right groin pain as a result of metastatic breast carcinoma which was misdiagnosed in magnetic resonance imaging as benign degenerative changes.     

Polymyositis/dermatomyositis-associated lung disease: analysis of a series of 81 patients

The objective of this study was to assess the prevalence, clinical, histological and immunological characteristics, and the long-term outcome of polymyositis- (PM) and dermatomyositis- (DM) associated lung disease, and to define subgroups of lung-associated inflammatory myopathies. This retrospective study included 81 consecutive patients diagnosed with PM/DM. Pulmonary involvement was systematically investigated in relation to clinical symptoms by chest radiography, high resolution computed tomography and pulmonary function testing. Anti-synthetase autoantibodies (ASA) were analysed by ELISA and confirmed by protein and RNA immunoprecipitation methods. Statistical analyses were done with the Student t-test and Fisher exact test. Cumulative survival probabilities were estimated by the Kaplan-Meier method and Cox regression analysis. Fifty patients (61%) presented pulmonary involvement. Thirty-two (39%) had interstitial lung disease and five of them had devastating acute interstitial pneumonia with pneumomediastinum and an unfavorable prognosis. Histology showed diffuse alveolar damage in this subgroup and ASA were negative. Eighteen patients (22%) presented restrictive myopathic lung disease; in three of them respiratory muscles could not maintain ventilation. ASA were positive in 17 of the 50 patients (34%) and were significantly associated with interstitial lung disease (OR: 4.5 [95% CI: 1.3-15.3]), arthritis (OR: 6.0 [95% CI: 1.3-29.2]) and 'mechanic hands' (OR: 8.5 [95% CI: 1.7-41.4]); the presence of these autoantibodies did not imply worse survival prognosis. We concluded that clinical and immunological characteristics allowed the grouping of patients into different types of PM/DM lung-associated disease. Presence of ASA did not affect survival. ASA-negative patients with acute interstitial pneumonitis and pneumomediastinum had an unfavorable prognosis.     

Suspected inflammatory rheumatic diseases in patients presenting with skin rashes

Skin lesions occur, often at very early stages, in many of the most frequent inflammatory rheumatic diseases such as in systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), Sjögren's syndrome, rheumatoid arthritis (RA), and psoriatic arthritis.It is important to recognize the different specific cutaneous lesions in SLE (e.g., “butterfly” rash in acute, annular or psoriasiform photosensitive lesions in the subacute form, and discoid lesions in the chronic form) for an early diagnosis and to estimate the associated risks of internal disease, whereas nonspecific lesions (exanthema, vasculitis, and alopecia) can be part of SLE flares.Cutaneous lesions in DM (Gottron's papules and sign, heliotrope rash, dystrophic cuticles, and nailfold capillary abnormalities) may occur before any clinically evident muscular or systemic organ involvement and are of utmost importance for early diagnosis. The pattern of cutaneous lesions and associated autoantibodies also allow the distinction of different phenotypes, either more prone to life-threatening interstitial lung disease (MDA-5) or with higher risk for neoplasia (TIF1-γ).Many other skin lesions, although not specific, require further investigation to look for a possible underlying inflammatory rheumatic disease: non-pruritic urticarial lesions in anti-C1q-associated urticarial vasculitis, Still's disease or hereditary auto-inflammatory syndromes, transient macular purpura of vasculitis in Sjögren's syndrome, Behçet's disease, or RA, Raynaud's phenomenon in SSc and mixed connective tissue disease, erythema nodosum or other panniculitis in RA, Behçet's disease and SLE, pustular eruptions in Behçet's disease, psoriasis, and hereditary auto-inflammatory syndromes.After reviewing in detail the cutaneous manifestations of the most frequent inflammatory rheumatic diseases, we describe a topographic and morphological approach to skin rashes, calling attention to facial rashes, hand involvement, scalp, nail, or leg lesions or to some morphological aspects of skin lesions (annular, pustular, urticarial, or exanthematous) that may be the initial manifestations of inflammatory rheumatic diseases.The importance of skin lesions is confirmed by their presence as part of the classification criteria of many inflammatory rheumatic diseases. They also contribute to early diagnosis, to characterize disease phenotypes, to aid in effective patient management, and, ultimately, to impact on disease prognosis.     

Rhinopharyngeal carcinoma and dermatomyositis: description of a clinical case

Nasopharyngeal carcinoma has long been reported as the predominant type of cancer associated with dermatomyositis in many several Asian countries, including Hong Kong, Singapore, and Southern-Cina. Dermatomyositis is one of the idiopathic inflammatory myopathies showing characteristic cutaneous manifestations. Reviews from the western literature have demonstrated that certain cancers, such as ovarian and breast carcinoma in women and lung and prostate carcinoma in men, are highly associated with DM relative to the general population. We report the case of a Caucasian Italian patient with nasopharyngeal carcinoma and dermatomyositis. Considering the rarity of nasopharyngeal carcinoma among whites, both the detection and the report of each new case are noteworthy in defining the geographic and ethnic distribution of this tumor.     

Cavernous pancreatic ductal ectasia with smooth muscle proliferation causing recurrent acute pancreatitis.

BACKGROUND: Pancreatic cystic lesions have various etiologies, including pseudocyst (inflammatory cyst), retention cyst, congenital cyst, and neoplastic cyst. RESULTS: This report describes a previously unreported, unique pancreatic cyst-like lesion causing recurrent acute pancreatitis. A 23-yr-old man had an 8 x 5 x 3-cm pancreatic head mass which contained multiple 3-7-mm cysts communicating with the main pancreatic duct on imaging studies. Pancreatoduodenectomy with mass excision prevented further attacks of acute pancreatitis. Pathological examination showed multiple cystic dilatations of branch pancreatic ducts surrounded by proliferating smooth muscle tissue, probably associated with hamartomatous changes. CONCLUSION: We consider the present lesion to represent cavernous pancreatic ductal ectasia with smooth muscle proliferation because of its striking cholangiopancreatographic similarity to Caroli disease.     

Antisynthetase antibody syndrome: case report and review of the literature

Antisynthetase antibody syndrome is a rare autoimmune disease that may present with variable systemic manifestations, mainly polymyositis, interstitial lung disease, skin lesions, and Raynaud’s phenomenon. This diagnosis should always come to mind in patients that present with signs of myositis, dermatomyositis, or polymyositis associated with interstitial lung disease. On the following paper, we report the case of a 52-year-old man who presented with a 2-month history of asymmetric polyarthralgia, myalgia, weight loss of 8 kg, and progressive muscle weakness associated with dyspnea, orthopnea, and dysphonia. Further tests revealed myositis, interstitial pneumonia, and elevation of anti-Jo-1 antibodies. A diagnosis of antisynthetase antibody syndrome was made and the patient showed good response to treatment with corticoids and methotrexate. Finally, we present a short review of the literature.     

Autoantibodies in Polymyositis and Dermatomyositis

Inflammatory myopathies are a group of acquired diseases, characterized by immunoflogistic processes primarily involving the skeletal muscle. According to recent classification criteria, four major diseases have been identified: polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myositis (NAM). Autoantibodies can be found in the sera of most patients with myositis. Myositis-specific autoantibodies (MSAs) are markers of very specific disease entities within the spectrum of myositis, and target proteins involved in key processes of protein synthesis. Myositis autoantigens comprise the well-defined aminoacyl-tRNA synthetases, the Mi-2 helicase/histone deacetylase protein complex, and the signal recognition particle (SRP) ribonucleoprotein, together with novel targets such as TIF1-γ, MDA5, NXP2, SAE, and HMGCR. Recent studies suggest that autoantigens drive a B cell antigen-specific immune response in muscles. Interestingly, an increased expression of Jo-1 and Mi-2 in regenerating fibers in muscle biopsies from PM and DM patients compared to normal was demonstrated. Myositis autoantigen up-regulation was observed in neoplastic tissues, thus representing a potential link between cancer and autoimmunity in myositis. Non-immunological mechanisms seem to participate to the pathogenesis of inflammatory myopathies; induction of endoplasmic reticulum stress response in response to abnormal muscle regeneration and inflammation has recently been reported in patients with myositis. This review article provides an update of new emerging insights about the clinical and pathophysiologic role of principal autoantibodies in myositis.     

Dermatomyositis and polymyositis: new treatment targets on the horizon

Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies (IIM) with a presumed autoimmune pathogenesis. Typical features are subacute onset, proximal, symmetric muscle weakness, elevated serum creatine kinase, and mononuclear cell infiltrates in the muscle biopsy. Strong support for an autoimmune pathogenesis comes from histopathological findings in biopsies of affected muscles. Furthermore, the association with autoantibodies supports the notion that immune-mediated inflammation is involved. PM and DM may occur in isolation or in connection with a connective tissue disease or cancer. The current treatment for IIM consists of first-line high-dose steroids and various conventional second-line treatments. Improvements in treatment for IIM are hampered by difficulties in the design of trials and the low incidence and prevalence of the disease. Cytokines and chemokines are factors involved in the inflammatory process in IIM, and are candidates for future therapeutic targets. Preliminary data with anti-tumour necrosis factor therapy are not very promising, but results of blockers of the lymphotoxin signalling pathway are to be awaited. Anti-B cell therapy may be a valuable therapeutic option for treatment of refractory IIM. The effects of anti-interferon-alpha in IIM are to be awaited, as are results of other anti-cytokine therapies and anti-chemokine therapy. Outcome measures to be used in clinical trials in II M include at present the core sets of outcome proposed by the International Myositis Assessment Clinical Study Group (IMACS).     

An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer

The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer.     

Clinical significance of magnetic resonance imaging of skeletal muscles in idiopathic inflammatory myopathies of adults]

The purpose of this study was to evaluate the clinical significance of magnetic resonance imaging (MRI) of skeletal muscles in Japanese patients with idiopathic inflammatory myopathies (IIM). MRI was performed in 23 adult patients with IIM, including 10 with polymyositis, 12 with dermatomyositis, and 1 with focal myositis. Seven (73%) of 11 patients with active IIM and 2 (17%) of 12 patients with inactive IIM showed hyperintensity of T 2-weighted images and normal intensity of T 1-weighted images, indicating "edema-like abnormalities" (MRI findings for active myositis). Muscle lipomatosis and fibrosis were demonstrated in four patients and 1 patient, respectively. Considerable selectivity of muscles in developing inflammatory disorders was found. In quadriceps muscles, for example, vastus muscles seemed to be more often affected in DM patients, whereas adductors were more often affected in PM patients. Serial examination of muscle MRIs was carried out in 4 patients and the findings paralleled the disease activities. The muscle MRI findings did not necessarily correlate with other findings, such as the presence of muscle weakness, elevated serum creatine kinase levels, myogenic electromyogram, or muscle biopsy findings. The muscle MRI was considered to be an additional useful tool for the diagnosis, evaluation of disease activity, and planning treatment of IIM.     

Dermatomyositis as an antecedent sign of lung cancer in an eldly patient: a case report

Dermatomyositis (DM) is associated with an increased risk of lung cancer. Misdiagnosed the squamous carcinoma of lung with DM is illustrated by the case who was a 73-year-old male and underwent successful surgical lobectomy presented here. The lack of examination of chest computed tomography (CT) is also emphasized. DM in an adult is a rare clinical entity. To facilitate the preoperative diagnosis and avoid the misdiagnosis of this disease, more etiological factors need to be considered.