anti-Jo-1 Research Articles

Anti-Synthetase Syndrome: An Under-Recognized Entity (P07.220)

Objective: To highlight the in-homogeneity in clinical presentation as well as use of different treatment options in three patients with anti-synthetase syndrome. Background Anti-synthetase syndrome is characterized by a necrotizing autoimmune myopathy (NAM), joint involvement, interstitial lung disease and/or connective tissue disorders (CTD) associated with anti-tRNA- synthetase antibodies as an epiphenomenon. Design/Methods: Case series. Results: 1) A 54 y/o lady presented with three weeks of proximal muscle weakness requiring assistance in getting up from a sitting position. On examination deltoids and hip flexors were weak bilaterally. Laboratory testing revealed elevated creatine kinase (CK = 6090 IU/L), positive ANA 1:40 and Jo-1(>8) antibody. CT chest showed thin-walled cystic emphysematous change in the right lower lobe.2) A 50 y/o man developed difficulty walking and getting up from chair five months prior to his initial visit. Formal muscle strength was normal throughout. He had elevated CK (796 IU/l), aldolase and TSH with positive Anti-PL-12 auto-antibody. CT chest and pulmonary function testing were normal.3) A 62 y/o lady presented with lower extremity weakness, joint swelling, lower extremity rash and shortness of breath for two months. Examination was consistent with proximal muscle weakness. CK (2240 IU/L), ANA (1:640) and Anti Jo-1 (>8) were elevated. CT chest demonstrated fibrotic lung changes with lower lobe predominance.EMG in all patients demonstrated fibrillation potentials and myopathic units. Muscle biopsies were consistent with NAM. Patients 1 and 3 received IVIG and methylprednisone while patient 2 received prednisone and methotrexate. Patients 1 and 2 had complete resolution of symptoms. Conclusions: A high index of suspicion must be maintained for anti-synthetase syndrome in patients with NAM, despite the absence of an identifiable CTD and milder symptoms. NAM may herald the presence of an anti-synthetase antibody the prognostic value of which, is an area of future research. Disclosure: Dr. Mehndiratta has nothing to disclose. Dr. Farheen has nothing to disclose. Dr. Chitravas has nothing to disclose. Dr. Cohen has nothing to disclose. Dr. Katirji has nothing to disclose.

Subacute progressive ophthalmoplegia associated with dermatomyositis

Dermatomyositis is a systemic autoimmune disorder that primarily affects the skin and skeletal muscle in the extremities, and is characterized by weakness of the proximal groups of limb muscles. Extraocular muscle involvement is a very rare manifestation of dermatomyositis [5, 8]. We herein report a patient who manifested dermatomyositis with subacute progressive ophthalmoplegia. The patient was a 53-year-old Japanese male who presented with myalgia and difficulty in climbing stairs. He developed progressive diplopia with eyelid edema and ocular pain 2 weeks after presentation, followed by difficulties in raising his arms. No autoimmune, endocrinopathy, or malignant diseases were observed. The physical examination revealed the presence of Gottron’s papules on the dorsal surface of the hands, and a neurological examination showed symmetrical weakness of the proximal muscles, including the upper limbs muscles, and bilateral ophthalmoplegia with total limitations of eye movements (Fig. 1). There was no weakness of the facial muscles or bulbar palsy. Laboratory tests revealed an increased creatine kinase (CK) level (10,808 U/l; normal range, 25–190). There was no abnormal thyroid function or serum autoantibody, including antinuclear antibody, anti-acetylcholine receptor antibody, and anti-thyroid antibodies. No malignant tumors, including thymoma or thymic hyperplasia, were observed using whole-body CT and PET imaging. Intravenous edrophonium had no effect on the ophthalmoplegia. The repetitive nerve stimulation test was normal. The muscle biopsy at the left vastus medialis muscle revealed inflammatory myopathic changes, which showed the invasion of mononuclear cells into the interfascicular septae and within the fascicles, perifascicular atrophy, and variations in the muscle fiber size. An immunohistochemical analysis showed the mononuclear cells to be CD4and CD8-positive lymphocytes. Ragged red fiber or cytochrome c oxidase-negative fibers were absent. The patient was treated with 60 mg/day oral prednisolone. His ocular impairment, weakness of the proximal muscles, and elevated CK values became markedly improved 1 month after the steroid therapy. Orbital magnetic resonance imaging (MRI) scans revealed an increased thickness of the extraocular muscles on T1-weighted images (Fig. 2a) and high-intensity signals of the extraocular muscles on fat-suppressed T2-weighted images (Fig. 2c), which were both improved after the steroid therapy (Fig. 2b, d). No myositis-associated autoantibodies, including anti Jo-1, PM-Scl-100, PL-7, PL-12, EJ, OJ, KS, M2, Ku (p70/80), SRP, Rib-P antibodies and the antimitochondrial antibody of M2 subtype, were detectable in the serum. Previous reports have suggested that the ophthalmoplegia observed in inflammatory myopathies is caused by the S. Kono (&) T. Bunai T. Konishi K. Shirakawa H. Miyajima First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, Hamamatsu 431-3192, Japan e-mail: satokono@hama-med.ac.jp

Analysis of factors related to the development of interstitial lung disease in 206 patients with dermatomyositis

Objective To assess the clinical features and associated factors of interstitial lung disease (ILD) in patients with dermatomyositis (DM).Methods Clinical data were retrospectively analyzed on 206 patients with DM collected at the Department of Dermatology,Huashan Hospital,Fudan University in the past 6 years.Chi-square test and t test were performed for statistical analysis.Results The prevalence of ILD was 49.03％ in the 206 patients with DM.Heliotrope rash on the upper eyelids,Gottron's sign (papules),arthralgia,and cough were correlated with the incidence of ILD in DM patients (all P ＜ 0.05),and of these factors,the prevalence of artharalgia and cough were positively correlated with the incidence of ILD,while the presence of Gottron's papules was negatively correlated.The patients with DM and ILD showed a higher prevalence of abnormal serum levels of lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH) and anti-Jo-1 antibodies,as well as with a poorer pulmonary function,compared with those suffering from DM only (all P ＜0.05).Characteristic imaging findings on computed tomography (CT) scan in patients with DM and ILD included linear opacity (57.4％),high-density patchy opacity (31.7％),reticular opacity (16.8％) and even ground glass-like opacity (13.8％),usually at the bottom or apex of the lungs.Conclusions In patients with DM,the prevalence of artharalgia and cough is positively correlated,whereas the presence of Gottron's papules is negatively correlated,with the incidence of ILD.Characteristic imaging findings on CT scan in patients with DM and ILD are linear opacity,high-density patchy opacity,reticular opacity and ground glass-like opacity at the bottom and apex of lungs. Key words: Dermatomyositis; Lung diseases,interstitial; Factor analysis,statistical

Morbidity and Mortality in Adult Polymyositis and Dermatomyositis

Before the use of corticosteroids, the prognosis for polymyositis/dermatomyositis (PM/DM) was extremely poor. To date, although overall prognosis appears to be better, PM and DM are still considered to be associated with increased morbidity, primarily related to severe muscle weakness and visceral involvement. Recent series underline that only 20% to 40% of treated patients will achieve PM/DM remission, whereas 60% to 80% will experience a polycyclic or chronic, continuous course of the disease. PM/DM further continues to have a great impact on life in medium- and long-term follow-up, as up to 80% of treated patients are still disabled (using Health Assessment Questionnaire scores). The overall mortality ratio in PM/DM patients also remains threefold higher compared with the general population, with cancer, lung, and cardiac complications and infections being the most common causes of deaths. Predictive factors for a poor prognosis in PM/DM patients are older age, involvement of lung and cardiac systems, dysphagia, cancer, and serum myositis-specific antibodies (including coexistent presence of anti-Ro52 and anti-Jo1 antibodies, anti-signal recognition particle antibody, anti-155/140, and anti-CADM-140 antibodies).

A Case of Connective Tissue Disease–Associated Interstitial Lung Disease With Nearly 20 Years of Follow-Up

Patients with advanced interstitial lung disease are at an increased risk of developing primary pulmonary malignancies. Although some literature exists concerning the development of malignancy after lung transplantation, less is known regarding the detection, management, and clinical outcome of unexpected pulmonary malignancy discovered by explant examination. We present a case of a 51-year-old man with a prolonged history of diffuse parenchymal lung disease classified as bronchiolitis obliterans organizing pneumonia and chronic interstitial pneumonia. Although the patient never developed myositis, serologic studies at diagnosis revealed the presence of an anti-Jo1 antibody. Nineteen years after diagnosis, the patient underwent bilateral lung transplantation. Pathological evaluation of the explanted lungs revealed unexpected invasive mucinous adenocarcinoma diffusely involving both lungs and all lobes, with metastatic adenocarcinoma involving hilar lymph nodes and soft tissue. Of note, the patient had a history of recurrent thromboembolic phenomenon previously well-managed with warfarin. Six months before transplantation, the patient developed warfarin-resistant thromboembolic disease requiring low–molecular weight heparin therapy. Although cases of unexpected explant pulmonary malignancy are uncommon, they raise challenging questions regarding the management and prognosis of such patients. Because of the alterations in the background lung parenchyma, detection of underlying malignancy in these patients is difficult for both the radiologist and the pathologist. Factors related to pretransplant screening for malignancy are reviewed. The development of heparin-responsive thromboembolic disease in a patient previously well-managed with warfarin is discussed as a clinical clue to underlying malignancy in this patient.

Short-Term and Long-Term Outcome of Anti-Jo1-Positive Patients with Anti-Ro52 Antibody

The aims of the present study were to (1) assess clinical features and long-term outcome in anti-Jo1-positive patients with anti-Ro52 antibody; (2) compare characteristics of anti-Jo1-positive patients with and without anti-Ro52 antibody; and (3) compare features of anti-Ro52-positive patients with and without anti-Jo1 antibody. The medical records of 89 consecutive anti-Jo1-positive patients with antisynthetase syndrome (ASS) were reviewed; 36 of these patients had coexistent anti-Ro52 antibody. Furthermore, the medical records of 13 consecutive anti-Ro52-positive patients without anti-Jo1 antibody were also reviewed. Nine anti-Jo1-positive patients (25%) with anti-Ro-52 antibody achieved remission of ASS, whereas 19 other patients (52.8%) improved and 8 patients (22.2%) worsened their clinical status. Anti-Jo1-positive patients with anti-Ro52 antibody experienced ASS-related complications: interstitial lung disease (n = 28), esophageal dysfunction (n = 9), and joint manifestations (n = 25), including periarticular hydroxyapatite calcifications and erosions of metacarpophalangeal and interphalangeal joints and wrists (n = 3); 7 anti-Ro52-positive patients (19.4%) had cancer. Anti-Jo1-positive patients with anti-Ro52 antibody, compared with those without, more commonly experienced deterioration of myositis and joint involvement, symptomatic form of ILD, and cancer; they also had decreased survival rate (P = 0.05). We further found that anti-Ro52-positive patients with anti-Jo1 antibody, compared with those without, were younger and more frequently exhibited ILD with poorer prognosis. Our series underlines that the presence of anti-Ro52 antibody is associated with a particular phenotype of ASS, leading to more severe myositis and joint impairment. Moreover, the coexistence of anti-Ro52 antibody seems to be associated with an increased risk of cancer. We therefore suggest that anti-Jo1-positive patients should routinely undergo the search for anti-Ro52 antibody, as this autoantibody appears to impact patients' prognosis.

A dermatomyositis and scleroderma overlap syndrome with a remarkable high titer of anti-exosome antibodies

An overlap syndrome of dermatomyositis and scleroderma is reported. The case corresponded to a 27-year-old female with a clinical picture of 14 months evolution, characterized by proximal muscles weakness, erythematous rash in wrists, knees, ankles, Gottron sign, heliotrope periorbital rash and dysphagia. A muscle biopsy was compatible with dermatomyositis; meanwhile the skin biopsy was compatible with scleroderma. Muscle enzymes were increased. Interestingly, the antinuclear antibody determination in HEp-2 cells was positive with a remarkable titer of 81,920 exhibiting a nucleolar pattern. Anti-Jo1 antibody was negative, but anti-PM/Scl-100 positive. The patient received methylprednisolone and cyclophosphamide pulses, with gradual improvement. Present report constitutes a case of overlap dermatomyositis-scleroderma syndrome, with anti-PM/Scl autoantibodies (anti-exosome). The remarkable of this case was the exceptional high antinucleolar antibody titer.

Pneumopathie interstitielle aiguë révélatrice d’un syndrome des antisynthétases

The antisynthetase syndrome is characterized by the presence of myositis, interstitial lung disease, arthritis, Raynaud's phenomenon, mechanics hands and anti-Jo1 antibody (histidyl tRNA synthetase). The prognosis of this syndrome is closely related to the severity of lung disease. Myositis can occur several years after lung disease and some patients with interstitial lung disease associated with anti-Jo1 antibodies will not suffer from muscle disease. We report the case of a 69-year-old man admitted to the medical intensive care unit for acute respiratory insufficiency related to rapidly progressive interstitial lung disease. Antisynthetase syndrome was diagnosed the presence of wrists' arthritis, 'mechanic's hands and anti-Jo1 antibodies. Despite the dramatic efficacy of corticosteroid therapy on ventilation parameters, the patient died from a Pseudomonas Aeruginosa nosocomial ventilator-acquired pneumonia. Our case emphasizes the importance to search for anti-Jo1 antibodies in the presence of interstitial lung disease. During the course of antisynthetase syndrome, the occurrence of interstitial lung disease is almost always constant and is correlated with poor prognosis.

Receptors for B cell activating factor of the TNF Family (BAFF) are expressed in muscle tissue of myositis patients with anti–Jo-1 or anti–Ro 52/anti–Ro 60 autoantibodies and correlate with plasmacytoid dendritic cell markers

BackgroundA role for B cells in the pathogenesis of myositis is supported by occurrence of autoantibodies. B cell activating factor (BAFF) plays a role in autoantibody production and is inducible...

Painful myositis in the anti-synthetase syndrome with anti-PL12 antibodies

The idiopathic inflammatory myopathies (IIMs) are characterized by muscle weakness, electromyography (EMG), histological and biochemical features of muscle inflammation. Their classification is evolving due to the myositis-associated autoantibody panel. Anti-aminoacyl-tRNA synthetase (ARS) antibodies are detected in 25-30% patients and define the anti-synthetase syndrome (ASS), a spectrum of interstitial lung disease (ILD), arthritis, fever, Raynaud’s phenomenon and mechanic’s hands. Anti-Jo1 antibodies are most common (20%), whereas anti-PL12 antibodies (alanyl-tRNA synthetase) occur in <3% cases. We report a 58-year-old male with IIM associated with anti-PL12 antibodies, who presented with a three-week history of severe widespread muscle pain, without overt muscle weakness. He also reported polyarthralgia, exertional dyspnoea, dry cough and weight loss. Examination revealed low-grade pyrexia, bi-basal crepitations and exquisitely tender muscles. Notably, there was no proximal muscle weakness or neurological deficit. Investigations revealed marked acute phase response (CRP 121 mg/l, ESR 79 mm/hr), polyclonal hypergammaglobulinaemia and raised ALT 276 U/l (0-40). Serology demonstrated high-titre anti-nuclear antibodies (1:1280, speckled). Serum Western blotting revealed anti-PL12 antibodies. No other autoantibodies were detected. Creatinine kinase was elevated 936 U/l (0-200), EMG was consistent with myositis. MRI thighs demonstrated high signal within the semitendinosis muscle. Muscle histology confirmed a florid inflammatory myopathy with disruption, oedema and considerable macrophage and lymphocytic infiltrate of perimysial connective tissue – typical features of ASS. Spirometry was restrictive with reduced corrected gas transfer. CT chest showed non-specific interstitial pneumonia. Prednisolone 60mg daily, resulted in improvement of dyspnoea and normalisation of CRP and CK. Significant muscle pain (requiring morphine) was steroid-responsive, but only to high doses, with recurrence on dose reduction. Pulsed cyclophosphamide was commenced, with improvement in muscle pain after the first dose. Severe muscular pain and tenderness in the absence of weakness, is atypical of ASS and has not been previously reported. Anti-PL12 antibodies are rare, therefore their associated clinical features are not well-described, unlike the Jo-1 syndrome. ILD is common, usually precedes muscle involvement and may occur in isolation. Previous reports suggest that muscle involvement is uncommon and mild (often subclinical). Further reports and prospective studies will help refine the clinical phenotype of anti-PL12 antibody-positive ASS subtype.

Clinical and Serological Features of Patients with anti-Jo-1

Objective: To elucidate the clinical and serological features of patients with anti-Jo-1 antibodies. Methods: Between 2007 and 2010, patients with positive anti-Jo-1 antibodies were enrolled in a study conducted at National Taiwan University Hospital. Their clinical and serological features were obtained by reviewing medical records, laboratory databases, and image studies. Results: On the basis of the information review, 45 patients with positive anti-Jo-1 antibodies were identified. Seven patients had polymyositis, 2 patients had dermatomyositis, and 2 patients had interstitial lung disease (ILD) without evidence of myositis. The most frequent symptoms were joint manifestation and sicca syndrome: 90.9% patients in the myositis/ILD group and 32.3% patients in the non-myositis/ILD group showed joint manifestation, and 45.5% patients in the myositis/ILD group and 44.1% patients in the non-myositis/ILD group had sicca syndrome. Raynaud's phenomenon, fever, and skin rash occurred in 27.2%, 45.5%, and 36.4% of the patients in the myositis/ILD group, and in 20.5%, 17.6%, and 17.6% of the patients in the non-myositis/ILD group. Serological profiles of the patients showed positive antinuclear antibody in 22 patients and positive rheumatoid factor in 10 patients. The initial presentations of 34 patients without myositis or ILD were recorded; the presentations were very heterogeneous. Conclusion: Anti-Jo-1 antibody is one of the most important autoantibodies in idiopathic inflammatory myopathies. In our study, patients with anti-Jo-1 antibodies had highly variable clinical presentations. Our findings also revealed that negative or low titers in antinuclear antibody testing could not exclude the presence of anti-Jo-1 antibody.

Prognostic Factors of Survival in Patients with Dermatomyositis and Polymyositis

Background: To determine the incidence, characteristics, and prognostic factors of mortality in patients with polymyositis (PM) and dermatomyositis (DM). Materials and Methods: Medical records of 151 PM/DM patients treated at Chang Gung Memorial Hospital between 2000 and 2007 were retrospectively reviewed. Results: Twenty-five (16.6%) of the 151 PM/DM patients had associated cancer. Thirty-two (21.2%) of the 151 PM/DM patients had interstitial lung disease (ILD). During follow-up, 30 (19.9%) patients died. Overall patient cumulative survival rates were 81.0, 77.6, and 74.6% at 1, 2, and 5 years, respectively. In univariate analysis, old age at PM/DM onset, cancer, ILD, DM, diabetes mellitus, low creatine phosphokinase (CPK) level, and use of intravenous immunoglobulin were associated with increased mortality (p=0.018, 0.011, ＜0.001, 0.002, 0.001, 0.009, and 0.007, respectively). Multivariate analysis excluding anti-Jo-1 antibody was performed after adjusting for CPK level. Only ILD (OR=12.93, 95% CI=3.97-42.13, p＜0.001) and cancer (OR=4.10, 95% CI=1.21-13.91, p=0.023) were associated with mortality. If the anti-Jo-1 antibody was included in multivariate analysis (n=80), then ILD (OR=15.40, 95% CI=2.68-88.02, p=0.002) and DM (OR=12.56, 95% CI=1.21-130.62, p=0.034) were associated with increased mortality. Conclusion: This study underlines the high mortality rate that associated with PM/DM. Survival time was significantly shorter for patients with ILD, cancer or DM than those without.

Benign Pneumatosis Intestinalis in a Patient with Juvenile Dermatomyositis

To the Editor: Juvenile dermatomyositis (JDM) is an autoimmune vasculopathy involving primarily the proximal muscles and skin but can involve other organ systems, particularly the gastrointestinal (GI) tract1. In the presence of cutaneous vasculitic ulcerations, one needs to monitor for signs and symptoms suggestive of GI vasculopathy2, which can lead to bowel ischemia, necrosis, ulceration, and perforation1,2,3,4,5. The presence of gas in the bowel wall, also referred to as pneumatosis intestinalis (PI), is an ominous finding when it is due to a GI vasculopathy3. PI is a radiographic finding that is associated with both benign and life-threatening causes. The benign variant of PI has been described in relation to immunosuppressive therapy6 and to JDM itself7. We describe a child with JDM complicated by cutaneous ulcerations and benign PI. An 8-year-old girl, following a 1-month history of rash and fatigue, was diagnosed with JDM based on the presence of Gottron sign, heliotrope rash, symmetric proximal muscle weakness, elevated serum muscle enzymes [creatine kinase (CK) 533 U/l (normal 44–189); lactate dehydrogenase 442 U/l (normal 142–261); aldolase 9.3 U/l (normal 0–7.6)] and findings consistent with myositis on magnetic resonance imaging of the proximal hip and shoulder girdle muscles. Antinuclear and anti-Jo1 antibodies were … Address correspondence to Dr. Scuccimarri; E-mail: rosie.scuccimarri{at}muhc.mcgill.ca

Painful myositis in the anti-synthetase syndrome with anti-PL12 antibodies

The idiopathic inflammatory myopathies (IIMs) are characterized by muscle weakness, electromyography (EMG), histological and biochemical features of muscle inflammation. Their classification is evolving due to the myositis-associated autoantibody panel. Anti-aminoacyl-tRNA synthetase (ARS) antibodies are detected in 25-30% patients and define the anti-synthetase syndrome (ASS), a spectrum of interstitial lung disease (ILD), arthritis, fever, Raynaud’s phenomenon and mechanic’s hands. Anti-Jo1 antibodies are most common (20%), whereas anti-PL12 antibodies (alanyl-tRNA synthetase) occur in <3% cases. We report a 58-year-old male with IIM associated with anti-PL12 antibodies, who presented with a three-week history of severe widespread muscle pain, without overt muscle weakness. He also reported polyarthralgia, exertional dyspnoea, dry cough and weight loss. Examination revealed low-grade pyrexia, bi-basal crepitations and exquisitely tender muscles. Notably, there was no proximal muscle weakness or neurological deficit. Investigations revealed marked acute phase response (CRP 121 mg/l, ESR 79 mm/hr), polyclonal hypergammaglobulinaemia and raised ALT 276 U/l (0-40). Serology demonstrated high-titre anti-nuclear antibodies (1:1280, speckled). Serum Western blotting revealed anti-PL12 antibodies. No other autoantibodies were detected. Creatinine kinase was elevated 936 U/l (0-200), EMG was consistent with myositis. MRI thighs demonstrated high signal within the semitendinosis muscle. Muscle histology confirmed a florid inflammatory myopathy with disruption, oedema and considerable macrophage and lymphocytic infiltrate of perimysial connective tissue – typical features of ASS. Spirometry was restrictive with reduced corrected gas transfer. CT chest showed non-specific interstitial pneumonia. Prednisolone 60mg daily, resulted in improvement of dyspnoea and normalisation of CRP and CK. Significant muscle pain (requiring morphine) was steroid-responsive, but only to high doses, with recurrence on dose reduction. Pulsed cyclophosphamide was commenced, with improvement in muscle pain after the first dose. Severe muscular pain and tenderness in the absence of weakness, is atypical of ASS and has not been previously reported. Anti-PL12 antibodies are rare, therefore their associated clinical features are not well-described, unlike the Jo-1 syndrome. ILD is common, usually precedes muscle involvement and may occur in isolation. Previous reports suggest that muscle involvement is uncommon and mild (often subclinical). Further reports and prospective studies will help refine the clinical phenotype of anti-PL12 antibody-positive ASS subtype.

An unusual association: anti-Jo1 and anti-SRP antibodies in the serum of a patient with polymyositis

The idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by chronic inflammation, resulting in the progressive weakness of the proximal muscles. Myositis-specific or myositis-associated autoantibodies can often be found in serum of polymyositis and dermatomyositis patients. This autoantibody presence may play a significant role in patient diagnosis and classification. We present a female polymyositis patient characterized with serious muscle weakness and lung involvement. Anti-Jo1 antibodies were detected in the patient's serum at the time of diagnosis. After 5 years of treatment and surveillance, recent laboratory analysis showed the presence anti-SRP antibody in her serum.

Myositis-specific and myositis-associated antibodies in overlap myositis in comparison to primary dermatopolymyositis: Relevance for clinical classification: Retrospective study of 169 patients

Objective The current study was performed in order to determine the prevalence of different myositis-specific and myositis-associated antibodies, as well as their association with clinical characteristics, disease course and response to therapy in 169 Hungarian patients with idiopathic inflammatory myopathy. Methods Sera of 130 primary and 39 overlap myositis including systemic sclerosis (13), rheumatoid arthritis (12), systemic lupus erythematosus (5) and Sjögren's syndrome (9) cases were analyzed. Antinuclear antibody, scleroderma-associated antibodies (anti-centromere, anti-topoisomerase I), anti-Jo-1, anti-PL-7, anti-PL-12, anti-Mi-2, anti-SRP and anti-PM-Scl, anti-Ku, anti-SS-A, anti-SS-B, anti-U1snRNP were tested. Autoantibody results were compared with clinical characteristics, disease course of overlap versus primary myositis patients, as well as with response to therapy. Results Associated connective tissue disease occurred in 23.1% of the patients. Myositis-associated antibodies were found in 8.5% of primary myositis patients, indicating that 11 additional primary myositis patients (23% vs. 29.6%) can be classified as overlap in all cohort according to the newly proposed diagnostic criteria. Polymyositis was found to be the most common myositis form in overlap myositis (87.2%), while scleroderma was the most common disease associated (33.3%). ANA was positive in 25.4% of primary and in 61.5% of overlap myositis cases. Altogether 39.6% of myositis patients ( n = 67) had autoantibodies, most commonly anti Jo-1 (18.3%) correlating with a polycyclic disease course. Conclusion Inclusion of myositis-specific and associated antibodies into the newly proposed diagnostic criteria for inflammatory myopathies is of great importance in order to determine subclasses and to introduce adequate therapy in time.

Relationship between serum antinuclear antibodies and clinical manifestations in patients with systemic sclerosis.

objective To investigate the clinical relevance of antinuclear antibodies (ANA)in patients with systemic sclerosis(SSc).Methods Clinical data were collected from 283 patients with SSc admitted to Peking Union Medical College Hospital(PUMCH)from 1981 to 2009.A retrospective analysis was carried out.Results In the 283 patients,253(89.4%)were female.The mean age at onset was 35.9±12.6 years and mean disease duration 4.3 ±4.5 years.There were 125(44.2%)patients with diffuse SSc(dcSSc) and 158(55.8%)with limited cutaneous SSc(lcSSc).Of all the patients,96.8%were positive for ANA,54.4% for anti-Scl-70 antibodies,6.4%for anticentromere antibodies(ACA),23.7%for anti-ribonucleoprotein(RNP) antibodies,7.1%for anti-Sm antibodies,25.1%for anti-SSA antibodies,7.1%for anti.SSB antibodies,and 1.1%for anti-Jo-1 antibodies.No patients were positive for anti-rRNP antibodies.Only one patient was positive for both anti-Scl-70 antibodies and ACA.The positivity rate of ACA in patients with leSSe was higher thanthat in those with dcSSc(P<0.05).Conclusion The detection of antinuclear antibodies is helpful for the diagnosis,classification,prognosis evaluation and management of SSc. Key words: Seleroderma,systemic; Antibodies,antinuclear; Retrospective studies

A 36-year-old woman with recurrent high-grade fevers, hypotension, and hypertriglyceridemia

History of the present illness The patient had been admitted 6 months earlier to an outside hospital with a high-grade fever, an erythematous rash on her lower extremities, and pain in her legs. She had a history of bipolar disorder and schizoaffective disorder, and had been treated with the antipsychotic medications ziprasidone and quetiapine fumarate. An initial evaluation for infections was negative, and broadspectrum antibiotics failed to relieve the fever. The patient’s fevers were attributed to the neuroleptic malignant syndrome (Table 1). Her fevers continued unabated to temperatures as high as 103°F, despite discontinuation of her antipsychotic medications and treatment with bromocriptine. She was transferred to another hospital for further evaluation and management. At the transfer hospital, the patient exhibited a transient increase in her creatine kinase level to 1,389 units/liter (normal value 240). Assays for antinuclear antibodies, antibodies to double-stranded DNA, and extractable nuclear antigens (Ro, La, Sm, and RNP) were negative, as were anti–Jo-1 antibodies. A magnetic resonance image of the lower leg showed muscle edema with localized infarction. A muscle biopsy showed perivascular inflammatory infiltrates consistent with an inflammatory myopathy. Prednisone 60 mg/day was started and azathioprine was considered, but the patient’s localized rash and leg pain resolved spontaneously before treatment with azathioprine was started. The patient was prescribed a tapering course of prednisone for presumed dermatomyositis, and did not experience recurrent episodes of fever, rash, or leg pain while receiving glucocorticoids (Table 1). No photographic record of the patient’s original rash exists. Within one week of discharge, the patient developed recurrent fevers and was readmitted to a third hospital. Her dose of prednisone at that time was unknown. She was later found to have a urinary tract infection caused by Escherichia coli and was treated with trimethoprim/sulfamethoxazole. Despite antibiotic treatment, the patient continued to have intermittent high-grade fevers and episodes of hypotension, with blood pressure as low as 70/40 mm Hg (Table 1). She was transferred to a fourth hospital. Upon transfer, the patient had a temperature of 104°F, sinus tachycardia (140–160 beats/minute), hypotension, and a hematocrit of 20%. There was no rash despite the development of intermittent high-grade fever. Multiple cultures were negative for infection. The patient underwent a bone marrow biopsy that showed a hypercellular marrow, and a peripheral smear showed some dysplastic myeloid forms and blasts. These were interpreted as being consistent with reactive changes associated with anemia of chronic disease. A second muscle biopsy finding showed mild perivascular inflammatory infiltrates in the endomysium, consistent with an inflammatory myopathy. However, further analysis by electron microscopy and immunohistochemical staining demonstrated no definitive evidence of such a condition. Antibodies against the membrane attack complex of complement, the major histocompatibility complex, CD20, CD3, laminin , Brown-Brenn stain, and NADH reductase were negative. The final interpretation of the muscle biopsy finding was nonspecific and possibly the result of trauma or ischemia at needle entry sites. The patient continued receiving prednisone without a Richard C. Chou, MD, PhD (current address: DartmouthHitchcock Medical Center, Lebanon, New Hampshire), Judith A. Ferry, MD: Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Charles A. Dinarello, MD: University of Colorado School of Medicine in Denver, Aurora; Paola Dal Cin, PhD: Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Address correspondence to Richard C. Chou, MD, PhD, Section of Rheumatology, Department of Medicine, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756. E-mail: Richard.C.Chou@hitchcock. org. Submitted for publication January 29, 2009; accepted in revised form September 14, 2009. Arthritis Care & Research Vol. 62, No. 1, January 15, 2010, pp 128–136 DOI 10.1002/acr.20024 © 2010, American College of Rheumatology

Correlation between screening assay of antinuclear antibody and confirmatory assay of specific antibody

Objective To investigate the correlation between screening assay of antinuclear antibody ( ANA ) and confirmatory assay of specific antibody. Methods Five hundred clinical patients' serum samples were detected by indirect immunofluorescence ( I1F) for screening assay of ANAs and line immunoassay ( LIA) for confirmatory assay of specific ANAs. According to the results of IIF-ANA and LIA-ANAs, 500 samples were divided into 4 groups; IIF-ANA ~+/LIA-ANAs~+ group, IIF-ANA~+/LIA-ANAs~-group, IIF-ANA~-/LIA-ANAs~+ group and IIF-ANA~-LIA-ANAs~- group. The samples in IIF-ANA~-VLIA-ANAs~+ group were collected and rechecked by ELISA and DID for detection of specific ANAs. Results Five hundred clinical samples were identified including 247 cases of IIF-ANA~+/LJA-ANAs~+86 cases of IIF-ANA ~+/LIA-ANAs~- , 152 cases of IIF-ANA~-/LIA-ANAs~- and 15 cases of IIF-ANA~- /LIA-ANAs~+, In IIF-ANA ~+/LIA-ANAs~+ group, 48. 2% ,23. 9% and 27. 9% patients had the titre of IIF-ANA 1:1 280, 1: 80-1:160 and 1:320-1:640. Fifteen cases of LJA-ANAs~+ were identified in 167 cases of HF-ANA(9. 0% ). Among 15 cases of IIF-ANA~-/LIA-ANAs~+ 11 positive cases were identified as anti-SSA and anti-Ro52 positive, which were rechecked by ELISA and DID, and the results were consistent with the prior detection. Other positive cases were identified including 1 case of anti-Histone, 1 case of anti-Scl-70, 1 case of anti-Jo-1 and 1 case of anti-AMA-M2. The positive consistent rates between LJA-ANAs and ELJSA, DID were 100% , 69% respectively. And 8 cases of IIF-ANA~-/LJA-ANAs~+ patients were diagnosed with autoimmune disease after clinical data analysis. Among 86 cases of IIF-ANA ~+ /LJA-ANAs~- , 50.0% and 36.1% patients had the titre of 1: 80-1: 160 and homogeneous fluorescence pattern respectively. There was a significant difference in IIF-ANA~+/LIA-ANAs~- group and IIF-ANA ~+/LIA-ANAs~+ (χ~2 =20.47,12.42, P<0. 05). Conclusions It is recommend that specific antinuclear antibodies can be used once screening assay of ANA is positive. But for clinically suspected AIDS patients, it is necessary to detect for specific antinuclear antibodies regardless of the result of screening assay of ANA. The confirmatory assay of specific antinuclear antibody could not replace the screening assay of antinuclear antibody. Key words: Immunofluorescence antibody technique; indirect; Antibodies; antinuclear; Autoimmune disease

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Among diagnostic progress over the last three years in internal medicine, Antisynthetase Syndrome is now more easily recognised with the diffusion of laboratory tests for research of antibodies against tRNA synthetases (Anti JO1, anti PL7, Anti PL12). In two third of cases, these antibodies are found despite absence of antinuclear antibodies. Hence, we have to search them specifically in patients with polyarthritis associated with myositis, cutaneous manifestations (Raynaud phenomenom and “mechanic’hands”) and interstitial lung disease. Discovery of asymptomatic mutation in the L ferritin coding sequence help us to better understand the “unexplained” hyperferritinemia. Initially described by japonese gastroenterologists, auto immune pancreatitis in fact a part of a systemic sclerosing disease with a biochemical hallmark: in crease of a subclass of immunoglobulins G (IgG4). A new pediatric disease due to a deficiency of the interleukin1 receptor antagonist (multifocal aseptic osteitis, periostitis, stomatitis, disseminated pustulosis) help us to better understand unexplained auto inflammatory diseases. The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia.