Successful treatment with tocilizumab of pericarditis associated with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease often complicated by vasculitis. Pericarditis is a serious complication caused by vasculitis, resulting in retention of pericardial effusion that sometimes induces cardiac tamponade. We report a patient with RA in whom pericarditis improved after tocilizumab administration. A male patient was diagnosed with RA and chronic renal failure in 1980 and was treated with salazosulfapyridine, but disease activity remained high. In January 2012, at the age of 73 years, he developed organizing pneumonia as a complication and was admitted to our hospital. Treatment with prednisolone 30 mg/day was initiated. However, 20 days after initiation of treatment, chest pain and palpitation developed, and chest computed tomography (CT) and echocardiography (ECG) revealed retention of pericardial effusion without cardiac tamponade. Rheumatoid nodules and interstitial pneumonia were also observed, and serum C3 level was decreased. A diagnosis of pericarditis caused by vasculitis was made based on these findings, and tocilizumab 8 mg/kg was administered. His symptoms improved gradually, and chest CT and ECG showed no pericardial effusion after about 3 weeks. No adverse effects of tocilizumab were observed during the clinical course. Although there are only a few reports of the effects of tocilizumab on vasculitis associated with RA, tocilizumab administration appears worthwhile in RA patients with vasculitis who do not respond to conventional treatment.     

Polymyositis-dermatomyositis-associated interstitial lung disease.

We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously. Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia. Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present. Jo-1 antibody was present in 19 (38%) of 50 patients tested. Synchronous associated malignancy was present in 4 of 70 patients (5.7%). Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1. Treatment usually included prednisone in 40-60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression. Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP. There was no difference in survival between Jo-1 positive and Jo-1 negative groups.     

A case of organizing pneumonia which had to be treated with steroids in the early phase of the disease against delayed resolution of severe pneumonia occurring even after antibiotic therapy]

A 58-year-old male was referred to our division because of antibiotic-resistant pneumonia. A chest X-ray film revealed severe pneumonia over the left lung field but laboratory data showed no leukocytosis. Transbronchial lung biopsy findings showed the evidence consistent with organizing pneumonia. One-month prednisolone therapy produced a disappearance of the pneumonia shadow, but a giant bulla was found at the same site. It was considered that it was necessary to treat this case with a combination of effective antibiotics and steroids in the early phase of the disease.     

Pulmonary tuberculosis with atypical radiological findings in a patient with chronic obstructive pulmonary disease

A 77-year-old-man who had been treated for chronic obstructive pulmonary disease (COPD) was referred to our hospital for further examination of a chest X-ray abnormality. The chest X-ray showed consolidation in the right upper and middle lung field. Chest computed tomography showed an airspace consolidation extending subpleurally and nonsegmentally without nodular lesions. The tentative diagnosis was cryptogenic organizing pneumonia. However, bronchoalveolar lavage fluid was positive for acid-fast bacilli on smear and also positive for tuberculosis PCR, leading to a diagnosis of tuberculous pneumonia. Tuberculous pneumonia in COPD patients can be non-segmental and mimic organizing pneumonia.     

Cryptogenic organizing pneumonia (COP), as presentation of rheumatoid arthritis

We report a 65-year-old caucasian male, who presented criptogenic organizing pneumonia (COP) as first manifestation of rheumatoid arthritis. The patient started with fever, myalgias and progressive dyspnea in October 2004. The chest X-ray (CXR) and high resolution computed tomographic scan (HRCT) showed diffuse alveolar exudates with air bronchogram in both the lungs. An open lung biopsy was done and the histological image was compatible with COP. Six months later, a diagnosis of RA was made. Treatment with oral methotrexate and etanercept was prescribed with improvement in symptoms, physical examination, and laboratory tests. Even though COP after the joint involvement is found more frequently in RA, in rare cases it could be the first manifestation of this illness.     

Organizing Pneumonia as the First Presentation in a Patient with Takayasu Arteritis: A Report of Rare Complication

A 48-year-old woman without any medical history visited an outpatient clinic with a chief complaint of cough persisting for more than 1 year and was diagnosed with organizing pneumonia. Computed tomography showed wall thickening with luminal stenosis of the main branch vessels of the aorta, and a detailed examination including fluorodeoxyglucose-positron emission tomography revealed Takayasu arteritis. There have been some reports of combined organizing pneumonia in similar vasculitis cases, but Takayasu arteritis and organizing pneumonia have not been reported to be associated. This case can be referred to when considering the association of lung lesions with Takayasu arteritis.     

Cost-effectiveness of tocilizumab,a humanized anti-interleukin-6 receptor monoclonal antibody,versus methotrexate in patients with rheumatoid arthritis using real-world data from the IORRA observational cohort study

Abstract

Objectives. To evaluate the cost-effectiveness of tocilizumab in patients with rheumatoid arthritis (RA) in a real-world setting in Japan.

Methods. The cost-effectiveness was determined using a Markov model-based probabilistic simulation. Data from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study between April 2007 and April 2011 were extracted using a pair-matching method: tocilizumab group (n = 104), patients who used at least 1 disease-modifying anti- rheumatic drug and in whom tocilizumab treatment was initiated; methotrexate group (n = 104), patients in whom methotrexate treatment was initiated for the first time or after an interruption of 6 or more months. Assuming a 6-month cycle length, health benefits and costs were measured over a lifetime and discounted at an annual rate of 3%.

Results. Compared with methotrexate treatment, lifetime costs and quality-adjusted life years (QALYs) for tocilizumab treatment were approximately 1.5- and 1.3-times higher, respectively. Incremental cost per QALY gained with tocilizumab was $49,359, which was below the assumed cost-effectiveness threshold of $50,000 per QALY. The probability of tocilizumab being cost- effective was 62.2%.

Conclusion. The simulation model using real-world data from Japan showed that tocilizumab (at a certain price) may improve treatment cost-effectiveness in patients with moderate-to-severe RA by enhancing quality-adjusted life expectancy.     

Inflammatory pseudotumor of the lung]

The patient was a 76-year-old man whose chief complaint was a dry cough. His chest X-ray film revealed a large hazy shadow with unclear margin in the left upper lobe. Bronchiolitis obliterans organizing pneumonia was initially diagnosed because transbronchial lung biopsy (TBLB) specimens showed organizing pneumonia with no evidence of malignancy. However, because the hazy shadow increased gradually in size despite steroid therapy. TBLBs were performed several more times to confirm the diagnosis. The last TBLB specimen showed proliferation of fibroblasts and mononuclear cells, with marked infiltration mainly of plasma cells 12 months after the initiation of steroid therapy. Because we were unable to obtain a histological diagnosis by bronchofiberscopy, a left upper lobectomy was preformed and the lesion resected. Histology disclosed inflammatory pseudotumor of a lymphoplasmacytic type with organizing pneumonia. The results of an immuno-histochemical examination confirmed that the proliferating plasma cells were polyclonal. These findings suggest that inflammatory pseudotumors should be taken into account by differential diagnoses of cases of organizing pneumonia that are resistant to steroid therapy.     

A case of migratory air space infiltration after radiation therapy for breast cancer]

A 54-year-old woman underwent conserving surgery for right breast cancer, and received a cumulative dose of 50 Gy of radiation therapy to the remaining part of the right breast. About five months after the termination of irradiation, cough and low-grade fever developed. The chest radiograph showed an infiltrative shadow in the right lung field. Organizing pneumonia was identified in the transbronchial lung biopsy specimen. After prednisolone was given to the patient the clinical symptoms and infiltrates seen in the radiograph disappeared. In the course of tapering the prednisolone dose, new infiltrative shadows developed in the upper right lung and the left lung. The histologic changes were shown by transbronchial lung biopsy to be organizing pneumonia. The increased dose of prednisolone resulted in the rapid improvement of the clinical symptoms and chest radiograph abnormalities. This case suggests that breast radiation after conserving surgery for breast cancer may cause a pathologic process similar to that of bronchiolitis obliterans organizing pneumonia.     

A case of polymyositis complicated with organizing pneumonia: case report and literature review

A 54-year-old man was admitted to hospital with fever, dyspnea, and polyarthralgia. A chest radiograph showed consolidations in the bilateral lungs, and histological examination of transbronchial lung biopsy samples revealed organizing pneumonia. He was also diagnosed with polymyositis because of muscle weakness, elevated muscle enzymes, myogenic findings on the electromyogram, and a positive test for the anti-Jo-1 antibody. Herein, we review 25 cases of organizing pneumonia with polymyositis/dermatomyositis with respect to their clinical features and treatment.     

A case of myelodysplastic syndrome complicated with organizing pneumonia]

A 74-year-old man had been given a diagnosis of myelodysplastic syndrome (MDS), and had been treated with granulocyte-colony stimulating factor (G-CSF). 1 year later, he suffered from fever and his chest X-ray lung biopsy did not provide a diagnosis, video-assisted thoracoscopic lung biopsy was performed, which yielded a histological diagnosis of organizing pneumonia. His pulmonary disease was diagnosed as secondary organizing pneumonia due to MDS, and was treated successfully with steroids. Vigorous efforts to establish a histological diagnosis is needed for the antibiotics-resistant pneumonia in the case of MDS.     

Organizing pneumonia associated with the use of pegylated interferon alfa

Organizing pneumonia is a well-differentiated clinical and histologic entity whose onset is usually subacute with respiratory symptoms and pulmonary infiltrates. Its origin may be unknown (cryptogenic) or it may be associated with various medical conditions, infectious diseases, or drugs. Diagnosis is confirmed by the presence of foci of organizing pneumonia in lung biopsy specimens. Our patient was a 49-year-old man infected with the hepatitis C virus who was receiving pegylated interferon alfa-2b. He presented with dry cough, fever, dyspnea, and ground glass pulmonary infiltrates. After an open lung biopsy, he was diagnosed with organizing pneumonia. When pegylated interferon was discontinued and corticosteroids started, the symptoms and pulmonary infiltrates disappeared. To our knowledge, this is the second report of organizing pneumonia related to pegylated interferon alfa-2b.     

Bronchiolitis obliterans organizing pneumonia and rheumatoid arthritis

Bronchiolitis obliterans, with or without organizing pneumonia, can be a serious and life-threatening complication of rheumatoid arthritis. We describe a case of bronchiolitis obliterans organizing pneumonia in a patient who recently developed rheumatoid arthritis, presenting as a severe respiratory insufficiency. Diagnosis was made by means of open lung biopsy. Treatment with corticosteroids induced a quick response and substantial improvement of the respiratory symptoms. A simultaneous strong rise in titres of serological tests suggests a relationship between the bronchiolitis obliterans organizing pneumonia and the rheumatoid arthritis.     

A case of cryptogenic organizing pneumonia showing reversed halo sign on computed tomography of the chest]

A 56-year-old female non-smoker complained of general fatigue and pyrexia. Laboratory examination revealed elevation of white blood cells (WBC) 10200/microl and C-reactive protein (CRP) 13.3mg/dl. Chest radiograph showed bilateral patchy and ring-shaped consolidations in both lungs. Chest computed tomography (CT) revealed multiple round ground glass opacities fringed with consolidation, namely the "reversed halo sign". Transbronchial lung biopsy specimens showed polypoid granulation tissue in terminal air spaces, consistent with an organizing pneumonia pattern. Clinical findings suggesting collagen vascular diseases and drug induced lung diseases were not recognized, thus cryptogenic organizing pneumonia (COP) was diagnosed. High dose methylprednisolone therapy improved her condition, and the ring-shaped opacities on chest CT resolved. She relapsed twice during approximately five years after the disease onset. Chest CT at the recurrences revealed subpleural patchy consolidations without formation of the "reversed halo sign". The sign was originally supposed to be specific for cryptogenic organizing pneumonia. However, other diseases like sarcoidosis and paracoccidioidomycosis have been reported to show this sign. The meaning of the "reversed halo sign" should be examined based on the accumulation of more cases.     

A case of polymyositis complicated with organizing pneumonia: case report and literature review

Abstract

A 54-year-old man was admitted to hospital with fever, dyspnea, and polyarthralgia. A chest radiograph showed consolidations in the bilateral lungs, and histological examination of transbronchial lung biopsy samples revealed organizing pneumonia. He was also diagnosed with polymyositis because of muscle weakness, elevated muscle enzymes, myogenic findings on the electromyogram, and a positive test for the anti-Jo-1 antibody. Herein, we review 25 cases of organizing pneumonia with polymyositis/dermatomyositis with respect to their clinical features and treatment.     

Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia

BackgroundPneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients’ mortality.Methods85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care.ResultsPatients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported.ConclusionsTocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.     

Three cases of idiopathic bronchiolitis obliterans with organizing pneumonia

Three patients with bronchiolitis obliterans organizing pneumonia are described. Chest X-ray films showed peripheral densities and pulmonary function tests a restrictive pattern. In all three cases transbronchial biopsy was not useful for diagnosis and we point out the importance of an open lung biopsy in order to make the differential diagnosis with other infiltrative lung disease with a different prognosis and therapy.     

Effectiveness of a two-year tapered course of tocilizumab in patients with giant cell arteritis: A single-centre prospective study

ObjectiveTo evaluate the feasibility of tocilizumab tapering and withdrawal in patients with giant cell arteritis (GCA).MethodsGCA patients eligible for tocilizumab were prospectively enrolled. Tocilizumab was administered weekly for the first 12 months, every-other-week for an additional 12 months, then discontinued. Relapses on tocilizumab were managed with temporary increases in systemic glucocorticoids or addition of methotrexate. Primary outcome was relapse-free survival at month 6 after tocilizumab suspension. Relapse-free survival on tocilizumab, imaging response, and adverse events were evaluated.Results23 GCA patients were enrolled. Reasons for tocilizumab start were relapse (n = 14), persistence of activity (n = 5), or steroid-related adverse events (n = 4). At tocilizumab start, two patients were on methotrexate, which was maintained. Fourteen patients had extracranial vascular involvement on ¹⁸FDG-PET/CT. During the first 12 months, four patients (17%) had clinical relapse. At every-other-week tocilizumab start, all patients were in clinical remission, two patients had active vasculitis on ¹⁸FDG-PET/CT; two patients were on steroid therapy, and four patients were taking methotrexate. Two patients (9%) relapsed while on every-other-week tocilizumab. At tocilizumab suspension, no patient was on steroid therapy and no patient had signs of active vasculitis on ¹⁸FDG-PET/CT. In the 6 months after tocilizumab discontinuation, six patients (26%) relapsed. No new or unexpected safety findings were identified.ConclusionTocilizumab tapered over a two-year period was effective to induce and maintain remission in GCA. Relapses on tocilizumab were minor and responded to incremental changes in therapy. A significant proportion of patients relapsed in the 6 months after therapy suspension.     

Drug-induced lung disease: a pragmatic classification incorporating HRCT appearances

Drug-induced lung disease frequently poses a diagnostic challenge. Knowledge of common radiological patterns of lung involvement and corresponding histopathologic diagnoses can facilitate management of individual patients. We outline a framework for understanding radiological and histologic patterns of drug-induced lung disease. Diffuse forms of drug-induced lung disease include processes that mimic acute respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage. These patterns of drug-induced lung disease are especially common in patients receiving cytotoxic chemotherapeutic agents. Chronic forms of drug-induced lung disease include many of the interstitial pneumonias seen more commonly in patients with idiopathic disease. Bronchiolitis obliterans organizing pneumonia and eosinophilic pneumonia are nonspecific patterns of drug-induced lung disease that are radiologically and histologically indistinguishable from their idiopathic counterparts. In some patients organizing pneumonia and eosinophilic pneumonia mimic the radiological appearance of neoplastic disease.     

急性纤维蛋白性机化性肺炎的临床病理特征

目的介绍一种新近定义的弥漫性急性肺损伤类型-急性纤维蛋白性机化性肺炎,以提高临床医生对其的认识方法分析南京市鼓楼医院确诊的1例患者以及国外有关文献的报道,总结其临床特征。结果急性纤维蛋白性机化性肺炎患者表现为急性或亚急性起病,主要临床表现为呼吸困难、咳嗽、咳痰,肺功能为限制性通气功能障碍和弥散降低,CT可见两肺斑片状实变影,主要病理表现为肺泡腔内可以看到特征性纤维蛋白球以及机化的疏松结缔组织,而没有DAD中的经典透明膜形成。结论急性纤维蛋白性机化性肺炎的病理组织学特点决定了它是一种不同于弥漫性肺泡损伤、机化性肺炎和嗜酸细胞性肺炎的新的肺损伤类型,但其是否为一个独特的疾病综合征有待进一步明确。