Successful treatment with cyclosporine in a case of progressive interstitial pneumonia associated with systemic sclerosis]

A 55-year-old man was admitted to our hospital with dyspnea on effort and sclerodactyly. The chest radiograph showed reticulonodular shadows in both lower lung fields. A diagnosis of systemic sclerosis was made based on the characteristic skin lesions, interstitial pneumonia and the positivity for anti-Scl-70 antibody. Surgical biopsies were performed, which showed various features characteristic of organizing pneumonia and non-specific interstitial pneumonia. Prednisolone and cyclophosphamide were given to the patient, but clinical symptoms and chest radiographic findings worsened. After cyclophosphamide was replaced with cyclosporine, his symptoms, chest radiographic findings and pulmonary function improved and stabilized. It is suggested that cyclosporine is useful for the treatment of progressive interstitial pneumonia associated with systemic sclerosis.     

A case of diffuse alveolar hemorrhage associated with interstitial pneumonia and systemic sclerosis]

A 73-year-old female with interstitial pneumonia and systemic sclerosis was admitted with bloody sputum and fever. A chest radiograph showed bilateral infiltrative shadows superimposed on interstitial pneumonia. A chest computed tomograph also showed bilateral airspace consolidations and honeycomb formation. Mechanical ventilation was required because of respiratory failure. At intubation, fiberoptic bronchoscopy revealed bilateral bronchi to be filled with bloody secretions. Her serum myeloperoxidase-anti-neutrophil cytoplasmic antibody titer was slightly elevated. Steroid pulse therapy (1000 mg/day methylprednisolone for 3 days) and cyclophosphamide pulse therapy (500 mg cyclophosphamide) followed by 60 mg/day prednisolone was introduced on the basis of a diagnosis of diffuse alveolar hemorrhage. Her respiratory condition improved and chest infiltrative shadows disappeared and weaning from mechanical ventilation was successful. However, she died of ventilation insufficiency due to progression of her chronic respiratory failure. A necropsy specimen obtained from the left lung showed fibrosis, predominantly in peripheral areas of lobules, and accumulation of hemosiderin-laden macrophages, which findings were consistent with usual interstitial pneumonia and diffuse alveolar hemorrhage. A review of the world literature revealed 4 case reports of diffuse alveolar hemorrhage associated with interstitial pneumonia and systemic sclerosis. We should be aware of this rare but serious complication in the management of interstitial pneumonia associated with systemic sclerosis.     

A case of pulmonary lymphangiomyomatosis induced by pregnancy

A 35-year-old primigravida was admitted to the Department of obstetrics complaining of dyspnea and left back pain at 21 weeks' gestation. Chest roentgenogram revealed diffuse reticulonodular shadows predominantly in both lower lung fields and arterial hypoxemia was present. Pulmonary function tests showed restrictive impairment and decreased carbon monoxide diffuse capacity. From these results, interstitial pneumonia was suspected and she was first treated with prednisolone. However during her pregnancy, spontaneous pneumothorax occurred. Following spontaneous delivery of healthy infant at 37 weeks, left chylothorax occurred, and pleurodesis was performed with OK432. Thereafter the histological diagnosis of pulmonary lymphangiomyomatosis was made by transbronchial lung biopsy and treatment of prednisolone was stopped. She was treated with tamoxifen. In addition, progesterone-receptor was detected in the pulmonary tissue obtained at open lung biopsy. She was treated with cyclophosphamide in addition to tamoxifen. At present, shortness of breath has decreased slightly in comparison with one year previously, but no improvement has been seen in lung function tests or chest roentgenogram.     

Chronic dyspnea with Raynaud's phenomenon and elevated ANA: A diagnosis of systemic sclerosis sine scleroderma

Systemic sclerosis (SSc) should be considered in all patients initially diagnosed with idiopathic interstitial lung disease (ILD), even in the absence of classical scleroderma cutaneous features. Systemic sclerosis sine scleroderma (ssSSc) is a rare subtype of SSc, and the diagnosis requires the absence of characteristic skin thickening but the presence of the three following criteria: (A) Raynaud's phenomenon or the equivalent of abnormal nail fold capillaries, (B) positive antinuclear antibody (ANA), typically with nucleolar or speckled immunofluorescence pattern, and (C) at least one internal organ involvement of ILD, renal dysfunction, esophageal/bowel dysmotility or pulmonary arterial hypertension; in the absence of an alternative rheumatological diagnosis. The radiological and histopathological features of systemic sclerosis sine scleroderma-associated interstitial lung disease (ssSSc-ILD) are commonly those of non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) that cannot help distinguish between idiopathic interstitial pneumonia, different types of connective tissue diseases, or even different subsets of SSc. Therefore, other than chest imaging, the use of nail fold capillaroscopy, positive serum ANA antibody, echocardiogram, and esophagram are essential, in conjunction with the clinical presentation for facilitating the diagnosis of ssSSc. We present a case of a 58-year-old woman presenting with chronic dyspnea, a positive review of systems for Raynaud's phenomenon, and found to have elevated nucleolar immunofluorescence pattern of ANA with chest imaging consistent with the diagnosis of ssSSc-ILD. The uniqueness of this case is that despite symptomatic alleviation with oral mycophenolate therapy, our patient's restrictive lung disease on pulmonary function tests continued to decline, requiring initiation of oral nintedanib therapy leading to stability and improvement. However, due to the rarity of ssSSc, the use of oral nintedanib for systemic sclerosis-associated ILD has only been formally assessed on patients with diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis.     

Idiopathic bronchiolitis obliterans organizing pneumonia complicated by transitory cystic lesion in the healing stage]

A 21-year-old man was admitted to our hospital because chest X-ray films disclosed infiltrative shadows indicative of Mycoplasma pneumonia. He experienced fever and dry cough for 2 weeks. Chest X-ray findings showed ground-glass shadows in the lower fields of both lungs. The patient was not responsive to antibiotic therapy (PAPM/BP 1 g/day and CLDM 1,200 mg/day); dyspnea advanced rapidly and spikes of fever persisted. On hospital day 5, chest computed tomographic (CT) films disclosed interstitial shadows in all lower lung fields with dense infiltration. A transbronchial lung biopsy (TBLB) was performed on day 7, and TBLB specimens demonstrated infiltration of mononuclear cells in alveolar septa and organizing exudate in alveolar ducts with polypoid granulation tissue. Bronchoalveolar lavage fluid findings revealed an increase in the total cell count and the percentage of lymphocytes. The CD 4/CD 8 ratio was normal. The findings of other laboratory tests ruled out drug-induced lung disease, infectious disease, and collagen disease. Idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP) was diagnosed. Corticosteroid therapy (methyl prednisolone: 500 mg/day) was started. After 2 weeks of treatment (prednisolone: 30 mg/day), the dyspnea and fever disappeared. Chest CT films showed that the interstitial shadows had largely resolved, but that a large cystic lesion had formed rapidly in the right lower lung field (right S 6). To the best of our knowledge, no cases of BOOP complicated by cystic lesions in the healing stage have been reported to date. We speculated that polypoid granulation in a bronchiole had given rise to a check-valve mechanism. After 2 months of treatment (prednisolone: 15 mg/day), the cystic lesion disappeared. We concluded that the bronchiolar lesion of polypoid granulation had resolved in response to therapy, thus facilitating air-way communication and the release of air from the cyst.     

A case of polycythemia vera associated with idiopathic interstitial pneumonia successfully treated by alkylating agents

A 62-year-old female was referred to our division because of general fatigue, low grade fever and exertional dyspnea for 2 months. Laboratory data and chest roentgenograms on admission revealed polycythemia vera associated with idiopathic interstitial pneumonia. Alkylating therapy with carboquone and cyclophosphamide resulted in the improvement of abnormalities on chest X-ray films which had previously shown decreased lung fields and abnormal interstitial shadows, as well as hematological abnormalities. Six months later, the results of the patient's pulmonary function tests and arterial blood gas analysis became within normal limits. Little information about polycythemia vera associated with idiopathic interstitial pneumonia is available. This case indicated that alkylating therapy with no steroidal combination is effective for idiopathic interstitial pneumonia.     

A case of dermatomyositis which rapidly developed to respiratory failure in the presence of pneumomediastinum

A 49-year-old woman was admitted in February 1987, with a six-month history of joint pain, maculopapular and erythematous rash, proximal muscle weakness and a two-month history of skin ulceration and dyspnea on exertion. Physical examination showed Gottron's papules on her fingers and a faint heliotrope rash. Biopsy of erythematous skin lesions on the shoulder and the back of the hand revealed perivascular inflammatory cell infiltration and tiny ulcerative lesions of the cutaneous tissue. Biopsy of the right quadriceps muscle showed type II fiber atrophy and slight perivascular lymphocytic infiltrate, whereas serum CPK level was within normal range. Chest X-ray film showed granular infiltrates in both lower lung fields. Based on the current findings the case was diagnosed as dermatomyositis associated with interstitial pneumonia. The administration of prednisolone, 30 mg/day resulted in the improvement of the skin lesions and muscle weakness, while the intensity of lung infiltrates was little affected. Three months after steroid therapy, the patient was readmitted because of increasing dyspnea on exertion and multiple skin ulcers. Chest X-ray revealed a small amount of gas in the mediastinum, in addition to slight deterioration of interstitial lung disease. In spite of various treatments for pneumomediastinum, including bed rest, administration of analgesics and oxygen inhalation, it developed rapidly, complicated severe subcutaneous emphysema and right-sided pneumothorax. Although high-dose prednisolone therapy and mediastinal drainage were performed, the pneumomediastinum was not resolved and she died from respiratory failure. At autopsy, predominant histological features of the lungs were acute interstitial pneumonia with hyaline membrane and edematous granulation formation in the alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)     

皮肌炎多发性肌炎患者间质性肺病病理资料推断性分析

目的 分析皮肌炎(DM)、多发件肌炎(PM)合并间质性肺病(ILD)患者的胸部X线、胸部高分辨CT(HRCT)及肺功能等肺部表现临床特点及其预后.方法 回顾性分析上海长海医院风湿免疫科1999年1月至2007年1月期间收住院的33例DM/PM合并ILD除外感染患者的临床资料.结果 33例ILD患者经胸部X线及HRCT证实.根据临床-影像学特点并结合血气分析、肺功能测定,参照美国胸科学会和欧洲呼吸协会问质性肺炎的分类诊断标准,推断分析病理类型主要为非特异性间质性肺炎(NSIP)(57%)和寻常性间质性肺炎(UIP)(25%). UIP类型预后差、病死率高(70%).结论 结合患者的影像学资料、肺功能、血气分析推断病理类型主要为NSIP和UIP,其中UIP病死率高、预后差.     

A case of chronic interstitial pneumonia with transient acute excerbation induced by dust exposure and spontaneous remission by the admission to hospital]

A 54-year-old man was admitted to our hospital with a chief complaint of dyspnea. He has been a plasterer with exposure to dust for 35 years since the age of 19 years. Initially, nonspecific interstitial pneumonia was diagnosed because of findings of ground-glass opacity without honeycombing on chest radiography and CT scanning. Restrictive and diffusional dysfunction of the lung was observed through pulmonary function testing. Videoscope-assisted thoracic surgery revealed pleural plaques and a lung histology showing usual interstitial pneumonia (UIP). Asbestos bodies and peri-bronchial and vascular dust deposition were detected by microscope. This patient recovered without any medication, with verification from the pulmonary function test results, chest radiographs and CT scanning results. The diagnosis was chronic interstitial pneumonia with transient excerbation. The cause of these pulmonary changes was thought to be dust exposure. Therefore, since dust exposure was avoided after the patient's admission to hospital, dust (including asbestos) exposure may be an important factor in the acute excerbation.     

Two cases of everolimus-associated interstitial pneumonia in patients with renal cell carcinoma

We herein report two cases of everolimus-associated interstitial pneumonia in patients with renal cell carcinoma. A 68-year-old Japanese man (case 1) was admitted to our hospital because of progressive dyspnea, left infiltration and consolidation on chest radiographs. He had started receiving everolimus (10 mg daily) three months before the admission for the treatment of recurrent renal cell carcinoma. Bronchoalveolar lavage fluid taken from his left B(4) showed a marked increase of lymphocytes (42.9%). An organizing pneumonia pattern of everolimus-associated interstitial pneumonia was strongly suspected radiologically, and treatment with high-dose corticosteroids, discontinuation of everolimus and oxygen support was started. The treatment was successful, and the patient recovered with only minor pulmonary fibrotic changes in the left lower lobe. A 57-year-old Japanese man (case 2) was referred to our department for the evaluation of interstitial pneumonia. He had started to receive everolimus (10 mg daily) four months previously. Chest CT demonstrated interstitial pneumonia predominantly in bilateral lower lobes, with small pulmonary metastatic nodules. His pulmonary complications were spontaneously resolved eight days after the discontinuation of everolimus. To the best of our knowledge, Case 1 is the first reported case of successfully treated organizing pneumonia pattern of interstitial pneumonia with acute respiratory failure induced by everolimus in Japan.     

Unilaterally dominant chronic idiopathic interstitial pneumonia complicated by pulmonary thromboembolism

A 51-year-old Japanese man was admitted to our hospital with the complaint of exertional dyspnea. A diagnosis of chronic idiopathic interstitial pneumonia (C-IIP) was made on the basis of findings of hypoxemia, restrictive ventilatory impairment, and interstitial shadows disclosed by chest roentgenograms. Chest computed tomographic (CT) scans clearly demonstrated left-side dominance of fibrotic changes. Dynamic CT and magnetic resonance angiography revealed the presence of thrombi in the left pulmonary artery. Lung scintigrams showed mismatching between ventilation and perfusion in the left lung. Pulmonary arteriography confirmed the diagnosis of left pulmonary thromboembolism (PTE). This was a rare case of PTE and C-IIP in which fibrotic changes occurred predominantly in the left lung field.     

A case of dermatomyositis complicated with pneumomediastinum that was successfully treated with cyclosporin A]

We reported the case of a 39-year-old man with dermatomyositis (DM) complicated with subcutaneous emphysema and pneumomediastinum during steroid therapy. The patient had complained of muscle weakness, dyspnea and skin eruption on his anterior chest wall 6 months prior to admission. He was diagnosed as having DM on the basis of an elevation in myogenic enzymes, myogenic changes in electromyography, a skin biopsy and a muscle biopsy. Chest roentgenogram revealed interstitial pneumonia (IP) in the lower lobes of the lungs. The administration of prednisolone (60 mg/day) was initiated, which resulted in improvement of DM. Fifteen days after the initiation of the steroid therapy, the patient developed subcutaneous emphysema and pneumomediastinum. Additional administration of cyclosporin A (CsA) enabled us to rapidly taper the dose of prednisolone without aggravating the diseases. Several reports have shown that vasculitis might be involved in the pathogenesis of pneumomediastinum in DM patients. Infection and tissue fragility due to steroid therapy worsen the outcome of those patients. CsA therapy may improve the outcome through the anti-vasculitic- and steroid sparing-effects.     

甲磺酸伊马替尼致间质性肺炎1例并文献复习

目的 提高对甲磺酸伊马替尼所致间质性肺炎的认识,做到早期诊断和治疗,改善患者预后.方法 对北京大学首钢医院呼吸内科诊治的1例甲磺酸伊马替尼致间质性肺炎患者的临床资料进行回顾性分析,并进行相关文献复习.结果 患者女性,小肠间质瘤术后服用甲磺酸伊马替尼3个半月后出现水肿、呼吸困难,入院后胸部CT提示双肺弥漫分布的斑片影,BALF显示细胞总数升高(0.54×109/L),其中淋巴细胞56％.除外感染、自身免疫性疾病和其他药物因素,诊断甲磺酸伊马替尼导致的间质性肺炎,停止服用伊马替尼3周后患者呼吸困难无改善,后加用糖皮质激素治疗,激素治疗约2周后患者呼吸困难明显减轻,胸部CT双肺斑片影较前部分吸收,激素治疗4个月后复查胸部CT病变较前明显吸收,但遗留肺间质纤维化改变,停用激素治疗.随访患者未再服用甲磺酸伊马替尼,2年及5年后胸部CT较前无明显变化,3年后患者因小肠间质瘤复发再次手术切除.结论 服用甲磺酸伊马替尼后出现呼吸困难症状应考虑间质性肺炎可能,早期诊断、停药和应用糖皮质激素治疗可获得显著效果,停药后应长期随访患者基础疾病及肺部情况.通过这此例报道并进行文献复习有助于提高对甲磺酸伊马替尼所致间质性肺炎的认识.     

A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine]

A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.     

A case of idiopathic nonspecific interstitial pneumonia and autoimmune hemolytic anemia after complete cure of polymyalgia rheumatica]

In 1997, at the age of 68, a man was admitted with polymyalgia rheumatica, which was successfully treated with oral prednisolone. In 1999, a chest X-ray revealed that he had interstitial changes in both lung fields. Because there were no symptoms, he was observed without treatment. However, from around 2003, he began to experience gradual progression of severe dyspnea on exertion. He was admitted to our hospital in 2004, at the age of 75, and we found interstitial lung deterioration. Nonspecific interstitial pneumonia (NSIP) was diagnosed because of the increase in the number of lymphocytes in bronchoalveolar lavage fluid and CT findings. He was also found to have autoimmune hemolytic anemia (AIHA). Treatment of AIHA with 1mg kg prednisolone led to improvement of not only the anemia but also the interstitial pneumonia. The coexistence of both idiopathic interstitial pneumonia and autoimmune hemolytic anemia is very rare. Moreover, this is the first report of polymyalgia rheumatica occurring prior to these two diseases.     

系统性硬化症相关间质性肺疾病的临床特点及危险因素分析

目的探讨系统性硬化症相关间质性肺疾病（SSc-ILD）的临床特点及危险因素。方法收集系统性硬化症（SSc）患者68例,根据有无间质性肺疾病（ILD）分为SSc-ILD组（44例）和单纯SSc组（24例）,分析SSc-ILD患者临床表现、自身抗体、胸部CT、肺功能及超声心动图特点,并与单纯SSc组比较。结果 SSc-ILD组中弥漫性皮肤损害型SSc（dcSSc）21例、局限性皮肤损害型SSc（lcSSc）23例,有呼吸系统表现者34例,其中活动后胸闷/气短30例、干咳18例。抗Scl-70抗体在SSc-ILD和dcSSc中的阳性率分别高于单纯SSc和lcSSc。SSc-ILD最常见的胸部CT表现为磨玻璃影（25例）,其次为网格状影（19例）。28例SSc-ILD行肺功能检测,其中弥散功能减退24例、限制性通气功能障碍13例。8例单纯SSc出现弥散功能减退,其中6例行超声心动图检查,5例有肺动脉高压（PAH）。SSc患者PAH发生率为58.93%（33/56）,ILD同时合并PAH者23例。结论 SSc-ILD以活动后胸闷/气短、磨玻璃影和弥散功能减退常见。单纯SSc若出现弥散功能减退,需警惕PAH可能。dcSSc及抗Scl-70抗体阳性是SSc发生ILD的危险因素。     

Pulmonary changes in progressive systemic sclerosis

The pulmonary changes of progressive systemic sclerosis in 8 cases were reported. The major clinical complaints were unproductive cough and exertional dyspnea. Pulmonary function tests showed restrictive ventilatory defects and impaired diffusing capacity in most of the cases examined. On chest X-rays, diffuse mottling and linear densities were seen in lungs, predominately in the basal regions. On pathological examinations, pulmonary interstitial fibrosis occurred in early stage of the disease. The results showed that pulmonary involvement may be an early event in progressive systemic sclerosis.     

Interstitial lung disease in polymyositis and dermatomyositis: analysis of six cases and review of the literature.

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis, or may occur later in the evolution of the disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. The histopathologic features are those of organizing and interstitial pneumonitis and pleuritis, with variable fibrosis. In the present series, the patients with mixed alveolar and interstitial infiltrates on chest radiograph and organizing pneumonia and bronchiolitis obliterans in addition to interstitial pneumonitis. In one patient evolution from pulmonary inflammation to interstitial fibrosis was demonstrated. The etiology of primary lung disease in PM-DM is not known, but cell-mediated autoimmunity to an unidentified component of lung tissue is suggested. Including the present series, 50 percent of patients have responded favorably to corticosteroids with decreased dyspnea, clearing of the chest radiograph and improved pulmonary function tests.     

A case of nonspecific interstitial pneumonia associated with amyopathic dermatomyositis efficiently treated with a combination of cyclosporin A and prednisolone]

A 36-year-old man was admitted to our hospital complaining of cough, dyspnea on exertion, skin eruptions, and joint pain. Characteristic skin lesions such as erythema around the nails, telangiectasis, and edema of the eyelids were observed in this patient. He had never complained of muscle symptoms, and his laboratory examinations showed no elevation of either CPK or aldolase. From several lines of evidence including the skin biopsy findings, amyopathic dermatomyositis was diagnosed. Chest X-ray films showed subpleural funicular opacities and consolidation in both lower lung fields. Lung biopsy specimens taken under video-assisted thoracoscopic surgery revealed nonspecific interstitial pneumonia, group II. Oral prednisolone treatment was initiated at 60 mg daily together with oral cyclosporin A (100-150 mg daily). The minimum serum concentration of cyclosporin A was maintained between 100 and 200 ng/ml. Respiratory symptoms gradually improved, and the oral prednisolone dose was tapered off. Pulmonary function and chest CT findings showed marked improvement.     

Pneumomediastinum,subcutaneous emphysema,and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis

Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia. The pathophysiological mechanism involved is the emergence of a pressure gradient between the alveoli and surrounding structures, causing alveolar rupture with subsequent dissection of the peribronchovascular sheath and infiltration of the mediastinum and subcutaneous tissue with air. Known triggers include acute exacerbations of asthma and situations that require the Valsalva maneuver. We described and documented with HRCT scans the occurrence of pneumomediastinum after a patient with bleomycin-induced interstitial lung disease underwent pulmonary function testing. Although uncommon, the association between pulmonary function testing and air leak syndromes has been increasingly reported in the literature, and lung diseases, such as interstitial lung diseases, include structural changes that facilitate the occurrence of this complication.