Koichiro Shinoda

Respiratory involvement in IgG4-related Mikulicz’s disease

Abstract‘Immunoglobulin G4 (IgG4)-related disease’ is a new clinical concept of multi-organ diseases, with Mikulicz’s disease (MD) being a clinical phenotype of IgG4-related disease. To clarify the clinical characteristics of respiratory involvement associated with IgG4-related MD, we retrospectively assessed 25 patients with MD, 11 (44%) of whom had allergic symptoms, and 7 (28%) of whom complained of respiratory problems. Thirteen patients (52%) presented with pulmonary and/or mediastinal lesions (P-MD) on chest computed tomography (CT), and 11 (44%) had lesions limited to the lacrimal and/or salivary glands (L-MD). Mean serum total protein, IgG, and IgG4 concentrations were significantly higher and CH50 was significantly lower in the P-MD than in the L-MD group. Immune complex was present only in the P-MD group. Chest CT images showed bronchial wall thickening, consolidation, nodule(s), interlobular thickening, ground glass opacity, pleural thickening/effusion, and mediastinal lymphadenopathy. Five of seven patients who underwent histological examination of the lungs had abundant IgG4-positive plasma cell infiltrates (IgG4/IgG-positive plasma cells >40%), but the other two did not. These findings suggest that respiratory lesions are not rare in patients with IgG4-related MD, and that they present with various manifestations. IgG4-related MD should be differentiated from similar diseases, such as sarcoidosis, bronchial asthma, Sjögren’s syndrome, and malignant lymphoma.

Interstitial pneumonitis associated with infliximab therapy without methotrexate treatment

Tumor necrosis factor (TNF)-α inhibitors are increasingly being used to treat rheumatoid arthritis. Infliximab (INF) is a TNF-α inhibitor that is usually used in combination with methotrexate (MTX). Interstitial lung disease (ILD) during combination therapy has been attributed to MTX rather than INF. However, INF-associated ILD without combination with MTX has recently been reported. We describe herein a case of severe ILD secondary to INF without MTX therapy.

Recurrence of IgG4-related disease following treatment with rituximab

A 54-year-old woman with suspected low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type of the eyelids underwent rituximab-containing chemotherapy. She initially responded to the rituximab therapy, but later experienced two recurrences over a 3-year period. Biopsy specimens and a review of her previous histology revealed that she had had immunoglobulin G4-related disease at the initial presentation. Although IgG4-related disease seems to respond well to rituximab therapy, long-term follow up, including disease monitoring, is needed to evaluate disease remission.

Deforming arthropathy in a patient with IgG4-related systemic disease: Comment on the article by Stone et al

We read with great interest the article by Stone et al published recently in Arthritis Care & Research (1). The authors describe that IgG4-related systemic disease accounts for 9% of all cases of noninfectious thoracic aortitis. The disease is clinically characterized by elevated serum IgG4 concentrations and infiltration of abundant IgG4-positive plasma cells in the various tissues (2–6). We would like to report a destructive arthropathy during a course of IgG4-related systemic disease. A 25-year-old man, who had been diagnosed as having Mikulicz’s syndrome by submandibular gland biopsy specimen indicating marked infiltrates of lymphocytes and IgG4-positive plasma cells, was admitted because of a relapse of polyarthralgia. Enlargement of the symmetrical submandibular glands and swelling of the hand joints with deformity were observed. C-reactive protein levels, serum IgG, and IgG4 were elevated to 2.4 mg/dl, 2,180 mg/dl, and 1,150 mg/dl (normal 70 mg/dl), respectively. Rheumatoid factor and anti– cyclic citrullinated peptide antibodies were negative except for antinuclear antibody in homogeneous (1:1280) and peripheral (1:40) pattern. Histologic examination of the synovium showed papillary proliferation with marked infiltrate of IgG4-positive plasma cells (Figure 1). Destructive arthropathy is one of the characteristics of rheumatoid arthritis (RA). However, hyperplasia of the synovial lining cells, the hallmark of RA (7,8), was not observed in this case. Furthermore, high concentration of serum IgG4 and abundant infiltrations of IgG4-positive plasma cells in the synovium were observed. This makes a great contrast with RA, in which high concentration of IgG1 in sera and dominant IgG1-positive plasma cells in the synovium were noted (9,10). It was reported that arthritis occurs in 10% of patients with IgG4-related systemic disease (3). However, histologic examination of the synovium has not been reported. To our knowledge, we indicate for the first time that IgG4positive plasma cells are abundantly infiltrated in the synovium in a patient with IgG4-related systemic disease. Dr. Tobe has received honoraria (less than

Presenting manifestations of hemophagocytic syndrome in a male patient with systemic lupus erythematosus

10,000 each) from Takeda Pharmaceuticals, Eisai Pharmaceuticals, and Mitsubishi Tanabe Pharma.

Severe autoimmune hemolytic anemia associated with IgM warm auto-antibodies in primary Sjögren’s syndrome

Hemophagocytic syndrome (HPS) is an unusual but sometimes fatal disorder. We reported a case of 21-year-old man who developed HPS and SLE simultaneously. Febrile pancytopenia, hyperferritinemia, and abnormal liver function tests were observed. Hemophagocytic cells were observed by means of bone marrow biopsy and diagnosed as HPS. The patient was treated with high-dose prednisolone, resulting in an excellent outcome. Early diagnosis of HPS by bone marrow biopsy is important for the successful treatment.

Primary pulmonary lymphoma presenting with multiple lung nodules.

Primary Sjögren’s syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren’s syndrome developing severe autoimmune hemolytic anemia. The patient’s red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren’s syndrome.

Reversible posterior leukoencephalopathy syndrome in a patient with systemic sclerosis.

A 71-year-old man taking methotrexate for rheumatoid arthritis presented with a dry cough. A chest X-ray and subsequent computed tomography (CT) of the chest revealed bilateral multiple lung nodules with mediastinal lymphadenopathy (Figure 1A). [F]Fluorodeoxyglucose–positron emission tomography with CT (F-FDG PET/CT) revealed uptake by the lesions (Figure 2). Transbronchial lung biopsy revealed diffuse large B-cell lymphoma (Figures 3A and B) positive for Epstein-Barr virus (Figure 3C). We diagnosed this case as “other iatrogenic immunodeficiency-associated lymphoproliferative disorders with histological features of diffuse large B-cell lymphoma (DLBCL),” which is most common in patients treated with methotrexate. In this case, methotrexate cessation resulted in regression of the nodules 3 months later (Figure 1B). Primary pulmonary lymphoma represents 3–4%of extranodal non-Hodgkin’s lymphoma, less than 1% of non-Hodgkin’s lymphoma, and only 0.5–1% of primary pulmonary malignancies (1). Lung involvement of primary pulmonary lymphoma is frequently bilateral, manifested as nodules or masses that may undergo cavitation (2–4). Air bronchograms, pleural effusions,

Simultaneously developed polymyositis and autoimmune hepatitis.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical entity first described by Hinchey et al. in 1996. It is characterized by reversible white matter edema predominantly involving the parietal and occipital lobes of the brain. Clinical findings include headache, altered mental status, seizures, and vision deficits. Reversible posterior leukoencephalopathy syndrome has been reported in various settings such as hypertensive encephalopathy, eclampsia, neurotoxicity of immunosuppressive drugs, uremic encephalopathy, and collagen vascular diseases. We describe a patient with systemic sclerosis (SSc) presenting sudden seizures and visual disturbance, whose neuroimaging studies were consistent with RPLS. A 30-year-old woman with SSc was admitted to the hospital because of a seizure. Several hours before admission, she had complained of worsening bioccipital headaches, nausea, vomiting, and binocular blurriness of vision and she had jerking movements of her arms and legs. Emergency services personnel were called, and en route to our hospital, her blood pressure was 140/102 mm Hg. She had a generalized tonic-clonic seizure, which was controlled by anticonvulsant. Laboratory examination revealed the following: serum creatinine, 0.5 mg/dL; white blood cell count, 12,100/KL; hemoglobin, 13.5 g/dL; platelet count, 344,000/KL; and lactate dehydrogenase, 280 IU/L. AntiYnuclear antibody 1:320 (nucleolar pattern) and antiYScl-70 antibody were positive. Lupus anticoagulant and anticardiolipin antibodies were negative. Plasma aldosterone concentration and plasma renin activity (PRA) were 278 ng/dL (reference range, 3Y12 ng/dL) and 18.2 ng/mL per hour (reference range, 0.2Y2.7 ng/mL per hour), respectively. A computed tomographic (CT) scan showed bilateral occipital low-attenuation areas involving the white matter, with some involvement of the overlying gray matter (Fig. 1A). Cranial magnetic resonance (MR) images also showed T2-weighted (Fig. 1B) and fluid-attenuated inversion recovery (FLAIR; Fig. 1C) signal hyperintensity in the identical regions of CT findings. Antihypertensive therapy by means of captopril and candesartan

Pseudo-Behçet’s disease associated with tuberculosis: a case report and review of the literature

The inflammatory myopaties such as polymyositis (PM) and dermatomyositis (DM) are autoimmune inflammatory muscle disorders characterised by the development of proximal and often symmetrical muscle weakness. Levels of serum muscle enzymes such as creatine kinase (CK), lactate dehydrogenase (LDH), asparate aminotransferase (AST) and alanine aminotransferase (ALT) are usually elevated. However, high levels of AST, ALT and LDH, without a determination of CK, are often misdiagnosed with hepatic diseases. Conversely, concomitant elevations of AST, ALT and LDH along with CK in patients with PM and DM may be considered to be due to myopathy itself even in a case of coexistence of liver injury. Oral administration of prednisolone was begun at a dose of 60 mg/day, resulting in a good outcome.