Tomohiro Kameda

Association of Higher Methotrexate Dose With Lymphoproliferative Disease Onset in Rheumatoid Arthritis Patients

Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX‐associated LPD (MTX‐LPD). Although MTX‐LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX‐LPD in Japanese RA patients and attempted to determine the risk factors for MTX‐LPD development.

Clinical value of 18F-fluorodeoxyglucose positron emission tomography in patients with connective tissue disease.

Connective tissue diseases represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs other than the lung. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is widely used in oncology but may also be valuable in patients with infections or inflammatory disease. The purpose of this article was to assess the clinical value of 18F-FDG PET in patients with connective tissue disease. Our experience demonstrates that 18F-FDG PET is a unique imaging technique for assessing the metabolic activity throughout the body in those with a connective tissue disease. The technique appears to be a promising imaging modality for detecting coexistent neoplastic diseases and other autoimmune disorders.

F-18 FDG PET findings of Takayasu arteritis before and after immunosuppressive therapy.

A 73-year-old woman with a 3-month history of fever of unknown origin underwent F-18 FDG positron emission tomography (PET). The serum C-reactive protein was 9.62 mg/dL. Her systolic blood pressure was 120 and 96 mm Hg in the right and left arms, respectively. FDG PET images demonstrated intense FDG uptake in the aorta and bilateral subclavian and brachiocephalic arteries consistent with Takayasu arteritis. After 6 weeks of immunosuppressive therapy, a follow-up PET scan showed disappearance of the large vessel uptake of FDG. She was asymptomatic, with a normal C-reactive protein (0.06 mg/dL).

Two cases of refractory thrombotic thrombocytopenic purpura associated with collagen vascular disease were significantly improved by rituximab treatment

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels. TTP is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, and its inhibitor. Low ADAMTS13 activity is present in most of idiopathic TTP patients. The prognosis of TTP was improved by plasma exchange treatment, which replaces the ADAMTS13 and removes ADAMTS13 inhibitor. However, ADAMTS13 activity is normal in some TTP patients. These are found among the secondary TTP patients associated with collagen disease, hematopoietic stem cell transplantation, malignancy, or drugs. In addition, most of them do not respond to plasma exchange. On the other hand, several reports demonstrated that rituximab, which is an anti-CD20 monoclonal antibody, is effective for refractory TTP cases caused by ADAMTS13 deficiency. It is considered that the effect of rituximab is associated with disappearance of ADAMTS13 inhibitor. However, rituximab therapy was effective for the TTP patients with normal ADAMTS13 activity in our cases. We considered another mechanism of rituximab for TTP cases.

A case of Evans syndrome combined with systemic lupus erythematosus successfully treated with rituximab

Evans syndrome is a rare autoimmune disorder with unknown aetiology. Although corticosteroids and/or intravenous immunoglobulin (IVIG) are commonly used in its treatment, no standard strategy has been established. We report here a 44‐year‐old male with refractory Evans syndrome combined with systemic lupus erythematosus (SLE) who responded well to rituximab. He was admitted to our hospital with severe bleeding caused by worsening of Evans syndrome. Despite treatment with a high‐dose corticosteroid and IVIG, his thrombocytopaenia and haemolytic anaemia did not improve. We started rituximab at a dose of 375 mg/m2 once a week for a total of two doses. There was significant improvement in his thrombocytopaenia and anaemia 1 month after administration of rituximab. Although the total immunoglobulin G (IgG) level did not change, the titres of platelet‐associated IgG (PA‐IgG) and of an indirect antiglobulin test (IAT) decreased under the treatment with rituximab. It is suggested that rituximab would be a powerful candidate in the treatment of refractory Evans syndrome by depleting abnormal clone‐producing autoantibody.

Improvement of irregularity of brain vessel walls in systemic lupus erythematosus by tacrolimus.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs. Neuropsychiatric SLE develops during the course of the disease in 50% to 74% of SLE patients. The pathogenesis of CNS manifestations is multifactorial. The most common neuropathological finding has, in various studies, been multifocal infarcts. The cerebral vascular lesions in SLE that can cause cerebral infarction can be categorized into thromboembolism and vasculitis. On the other hand, tacrolimus is an immunosuppressive drug used for several autoimmune diseases, which inhibits the calcineurin pathway in T cells and reduces accompanying inflammatory cytokine production. We experienced that treatment of a patient with SLE with tacrolimus and steroid pulse therapy yielded improvement of vasculitis of brain vessels on magnetic resonance angiography. We suggest that tacrolimus may play an important role in the treatment of vasculitis of SLE.

A case of Degos disease successfully treated with corticosteroid combined with cyclophosphamide

Degos disease is a rare disorder characterized by systemic vasculitis involving various organs. There is no established, effective treatment for the disorder, and its prognosis is still poor. Combination therapy with corticosteroid and cyclophosphamide is considered effective for vasculitides involving the small arteries such as ANCA-associated vasculitis. We present here a 42-year-old man who developed Degos disease over several months, and was successfully treated using combined treatment with corticosteroid and cyclophosphamide.

Primary central nervous system lymphoma in a rheumatoid arthritis patient treated with methotrexate: a case report

BackgroundRheumatoid arthritis is a systemic inflammatory disease characterized by synovitis and the destruction of articular structures in multiple joints. Methotrexate is recommended as an anchor drug for rheumatoid arthritis treatment to achieve the therapeutic goal of reducing damage to joints and improving clinical score. However, several studies have shown that methotrexate has been associated with the development of lymphoproliferative disorders, namely methotrexate-associated lymphoproliferative disorders. On the other hand, primary central nervous system lymphoma is an aggressive disease with poor prognosis. Both methotrexate-associated lymphoproliferative disorders and primary central nervous system lymphoma are reported to be associated with Epstein-Barr virus.Case presentationA Japanese female patient of between 60 and 70 years of age with rheumatoid arthritis was admitted to our hospital because of sudden convulsion and impaired consciousness. Just before admission, she was treated with adalimumab and methotrexate. Contrast-enhanced computed tomography scan showed a densely stained mass with surrounding edema in both frontal lobes and the left nucleus basalis, and enlarged lymph nodes in the right supraclavicular fossa. We performed a biopsy of the right cervical lymph node, but could not establish a histopathological diagnosis. In situ hybridization showed the presence of Epstein Barr virus, therefore we diagnosed this case as methotrexate-associated lymphoproliferative disorders mediated by Epstein Barr virus after considering the drug history of the patient. After we discontinued methotrexate, patient symptoms gradually improved. The masses at both frontal lobes and the left nucleus basalis were gradually regressed.ConclusionSince the frequency of methotrexate use and the maximum dosage has been increasing, particular attention should be paid to the development of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients who are treated with methotrexate.

A case of catastrophic antiphospholipid syndrome, which presented an acute interstitial pneumonia-like image on chest CT scan

We report the case of catastrophic antiphospholipid syndrome (CAPS) complicated with mixed connective tissue disease (MCTD). A female patient was diagnosed with acute interstitial pneumonia (AIP) with MCTD by chest CT scan. Corticosteroid therapy was refractory for lung involvement, and she died due to acute respiratory failure. The autopsy revealed that AIP was compatible with lung involvement of CAPS. We therefore suggest that chest CT might reveal AIP-like findings in CAPS patients whose condition is complicated with pulmonary manifestations.

Squamous Cell Lung Cancer Associated With Systemic Sclerosis.

We here describe a 50-year-old woman diagnosed with squamous cell lung cancer (SqLC) with underlying interstitial lung disease (ILD) 14 years after a diagnosis of systemic sclerosis (SSc). We reviewed the literature and collected 21 well-documented cases with SqLC associated with SSc including the present case. Several characteristics of SqLC associated with SSc have been found. First, the average age at diagnosis of SqLC is 57 years, which is much younger than that reported for patients without SSc. Second, SqLC could occur even in never or light smokers, although SqLC usually has a strong association with smoking history. Third, two-thirds of the available cases have ILD. In addition, SqLC developed in the area of ILD in most cases with ILD. Fourth, SqLC generally occurs after a long period from the diagnosis of SSc; the average of this interval reaches 12 years. It would be helpful to know these features so that physicians follow up and treat SSc patients adequately.