Mari Yamasue

Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine

A 58-year-old male was admitted to our hospital because of periungual nailfold an erythema and erythematous rash on the dorsal joints of his hands and feet, but no muscle weakness. He was thus diagnosed to have amyopathic dermatomyositis. He had moderate hypoxemia and his chest computed tomography scans demonstrated bilateral ground-glass opacities, implicating complication with interstitial pneumonia. Therapy was initiated with pulsed methylprednisolone followed by high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine. The skin manifestations improved; however, the pulmonary infiltrates and hypoxemia deteriorated during the 2-month period of the treatment. The treatment was switched from cyclosporine to tacrolimus because of an inadequate clinical response to the therapy, and this resulted in the resolution of interstitial pneumonia. This case indicates that tacrolimus administration should be considered for patients with this life-threatening disorder when it is judged to be refractory to cyclosporine.

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis.

BACKGROUND Pulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated. METHODS We enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined. RESULTS Of 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF. CONCLUSIONS The findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion.

Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic interstitial pneumonias

BACKGROUND AND OBJECTIVE We hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of an acute exacerbation of the idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. The purpose of this study was to examine whether Ang-2 expression was associated with the pathogenesis of AE-IIPs. METHODS Twenty-three patients with AE-IIP patients, 18 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37 idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs) were enrolled. The serum level of Ang-2 was measured by an enzyme-linked immunosorbent assay. RESULTS The serum levels of Ang-2 were higher in AE-IIPs and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were also higher than in IPF patients. There was a positive correlation between the serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a significant positive correlation was found between the serum Ang-2 level and the CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level was not related to survival, the Ang-2 levels significantly declined in survivors during treatment, while they did not change in non-survivors. CONCLUSIONS Increased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIPs.

Pulmonary-Limited Granulomatosis with Polyangiitis Coexisting with Mixed Connective Tissue Disease

Granulomatosis with polyangiitis (GPA) is a systemic disease characterized by necrotizing, granulomatous vasculitis of the upper and lower respiratory tracts and glomerulonephritis, and is classified as a classical or limited form. The classical form of GPA demonstrates the involvement of the upper respiratory tract, sinuses, lungs and kidneys, whereas the limited form is characterized by the lack of the renal involvement with female predominance. On the other hand, mixed connective tissue disease (MCTD) shows the clinical and laboratorial features of systemic lupus erythematosus, systemic sclerosis and polymyositis, along with high titers of anti-ribonucleoprotein antibodies and is characterized by good response to corticosteroid therapy and favorable prognosis. We herein report a patient with a history of MCTD that developed into a limited form of GPA (pulmonary-limited GPA). A 39-year-old woman suffered from persistent cough, left back pain and appetite loss. At 21 years of age she was diagnosed with MCTD, but the persistent administration of prednisolone or immunosuppressants was not needed. On admission, high-resolution chest computed tomography showed bilateral, multiple, poorly circumscribed nodules and masses, some of which showed cavitation. A surgical lung biopsy demonstrated granulomas with vasculitis surrounding the necrotic lesions. She was diagnosed with pulmonary-limited GPA. In conclusion, we should recognize that GPA may develop during the disease course of MCTD even after prolonged disease remission. To prevent progression to an irreversible state, physicians should consider a surgical lung biopsy for the diagnosis in patients suspected of having pulmonary-limited GPA.

Corticosteroid Therapy for a Patient with Relapsing Polychondritis Complicated by IgG4-Related Disease

Relapsing polychondritis (RP) is a rare systemic disorder characterized by recurrent, widespread chondritis of the auricular, nasal, and tracheal cartilages. IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease characterized by the infiltration of IgG4-bearing plasma cells into systemic organs. Although 25% to 35% of patients with RP have a concurrent autoimmune disease, coexistence of RP and IgG4-RD is rare. We herein report a case of RP complicated by IgG4-RD. A 63-year-old man developed recurrent bilateral ear pain and swelling, recurrent blurred and decreased vision, and migratory multiple joint pain, sequentially within one year. Fourteen months after the first symptom, he experienced dry cough and dyspnea with exertion. A computed tomography (CT) scan detected interstitial pneumonia, swelling of bilateral submandibular glands, bilateral hilar and mediastinal lymphadenopathy, and several nodules in bilateral kidneys. His serum levels of IgG and IgG4 were elevated. The biopsy specimen of auricular cartilage showed infiltrations of inflammatory cells and fibrosis consistent with RP. The IgG4-positive cells were not observed in auricular cartilage. The patient met the diagnostic criteria of RP, including bilateral auricular chondritis, conjunctivitis, iritis and polyarthritis. The biopsy specimens of lung and kidney revealed the significant infiltrations of IgG4-positive plasma cells and fibrosis. We also diagnosed him as having IgG4-RD, affecting bilateral submandibular glands, hilar and mediastinal lymph nodes, lungs, and kidneys. Thus, RP preceded the onset of IgG4-RD. Corticosteroid therapy improved the symptoms and CT scan findings. In conclusion, RP and IgG4-RD do coexist; however, the pathogenesis of their coexistence is unknown.

Sarcoidosis Presenting as Bilateral Vocal Cord Paralysis due to Bilateral Vagal Nerve Involvement.

We herein report a rare case of sarcoidosis presenting as bilateral vocal cord paralysis due to bilateral vagal nerve involvement. A 72-year-old woman with uveitis of the left eye complained of hoarseness and aspiration due to bilateral vocal cord paralysis. An endobronchial needle aspiration biopsy specimen of the mediastinal lymph nodes showed non-caseating epithelioid cell granuloma. Total protein and cell concentrations in the cerebrospinal fluid were increased. We diagnosed her to have sarcoidosis with bilateral vagal nerve involvement. Corticosteroid therapy improved her symptoms of hoarseness and aspiration. Sarcoidosis should therefore be taken into consideration as a potential cause of bilateral vocal cord paralysis.

A case of maoto-induced interstitial pneumonia

A 64-year-old man was prescribed maoto, a prevailing Chinese herbal, for a cold with upper respiratory inflammation. Two days later, he developed a high fever, progressive dyspnea and pulmonary infiltration on chest high-resolution computed tomography (HRCT) including diffuse ground-glass opacity mainly around bronchovascular bundles and partial distribution of subpleural cysts resembling honeycombing. Despite the administration of azithromycin and pazufloxacin, the pulmonary infiltration and hypoxemia has rapidly progressed, so he was referred to our hospital. Although fulminant pneumonia or the acute exacerbation of idiopathic pulmonary fibrosis (IPF) was considered, his respiratory symptoms and pulmonary infiltration immediately improved and oxygen therapy was not needed on the fifth hospital day. Based on the clinical course, laboratory findings and the chest imaging findings, drug induced interstitial lung disease was suspected. The drug-induced lymphocyte test (DLST) as well as a scratch test against maoto demonstrated positive results. This is the first case report of maoto-induced interstitial pneumonia that was diagnosed based on the patients clinical course, chest imaging findings and laboratory findings.

Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stain-positive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynauds phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.

Comet Tail Sign in IgG4-related Disease

A 65-year-old man was admitted due to an abnormal chest shadow. Computed tomography revealed enlargement of the submandibular glands and the tail of the pancreas, with mediastinal lymphadenopathy, a small amount of pleural effusion with pleural thickening and a mass-like lesion exhibiting the comet tail sign in the right lower lung (Picture A, B). The serum immunoglobulin-G (IgG) and IgG4 levels were elevated, and an immunohistochemical analysis of the biopsy specimens obtained from the submandibular gland and pleura (Picture C) showed IgG4-positive plasma cell infiltration (C; inset). The administration of corticosteroids resolved the comet tail sign (Picture D), suggesting round atelectasis (1). Round atelectasis is an oval shape tumor-like lesion that shows contact with the pleura and involves convergence of the pulmonary vessels and bronchi. We herein reported a case of IgG4-related disease presenting with the comet tail sign. Regarding the pleurisy noted in this disease, sclerosing inflammation of the visceral pleura may