1/51. Paraneoplastic pemphigus with fatal pulmonary involvement in a woman with a mesenteric Castleman tumour.A 42-year-old woman presented with oral and labial erosions, conjunctivitis, facial rash and lichenoid erythematous papules on the trunk. Paraneoplastic pemphigus (PNP) was suspected, and a search for a neoplasm revealed an intra-abdominal Castleman tumour sized 7 x 5 x 6 cm. After removal of the Castleman tumour, the skin and mucosal inflammation gradually subsided over the next 12 months. However, due to irreversible pulmonary involvement the patient died of intractable respiratory distress 2 years after the onset of the disease. Systemic corticosteroids, azathioprine, cyclophosphamide, high-dose intravenous immunoglobulins and thalidomide were ineffective. The diagnosis of PNP was confirmed by keratinocyte antigen immunoprecipitation with the patient's serum.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
2/51. Immunoablative high-dose cyclophosphamide without stem cell rescue in paraneoplastic pemphigus: report of a case and review of this new therapy for severe autoimmune disease.Paraneoplastic pemphigus (PNP) is a refractory and life-threatening autoimmune mucocutaneous disease. We have recently reported the effectiveness and safety of ablative intravenous cyclophosphamide (200 mg/kg daily over 4 days) without stem cell rescue in patients with refractory autoimmune diseases including systemic lupus erythematosus, autoimmune cytopenias, chronic inflammatory demyelinating polyneuropathy, and aplastic anemia. We report chronic lymphocytic leukemia-associated PNP in a patient who presented with extensive and debilitating painful oral ulcerations and received ablative therapy. The patient tolerated the regimen well and showed a slow but sustained improvement despite persistence of the underlying neoplasm. Eighteen months after therapy, the oral ulcerations were almost completely healed and the circulating autoantibodies became negative. Currently, the patient remains on cyclosporine and a low dose of prednisone. This provides further evidence for the efficacy and safety of this regimen in the management of severe autoimmune diseases including PNP.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
3/51. Constrictive bronchiolitis obliterans and paraneoplastic pemphigus.Constrictive bronchiolitis obliterans is rare, and the pathogenesis of the disease often remains unknown. This study reports on the case of a 38 yr-old female with constrictive bronchiolitis obliterans and paraneoplastic pemphigus associated with malignant lymphoma. The patient developed progressive obstructive lung disease. The chest radiograph showed almost normal lungs. Paraneoplastic pemphigus is a newly described syndrome in which patients have autoantibodies binding to some epithelia, including in the respiratory tract. The disease develops in association with non-Hodgkin's lymphomas or other malignant neoplasms. The case presented here suggests that constrictive bronchiolitis obliterans associated with paraneoplastic pemphigus may be one of the facets of autoimmune responses in this context.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
4/51. Paraneoplastic pemphigus: a case of long-term survival associated with systemic lupus erythematosus and polymyositis.A 35-year-old man presented with a generalized bullous eruption and oral ulceration. He had been diagnosed as having systemic lupus erythematosus and pelvic Castleman disease (hyaline-vascular type) in the past. Histologic, direct and indirect immunofluorescence and immunoprecipitation studies confirmed a diagnosis of paraneoplastic pemphigus (PNP). Initially several medical treatments were tried unsuccessfully. The pelvic tumor was surgically removed and the mucocutaneous lesions slowly regressed. Four years after presentation, he developed polymyositis which was completely controlled with short courses of corticosteroids. There was no evidence of relapse of PNP or lupus erythematosus at that time. At the 6-year follow-up he showed no clinical evidence of PNP, lupus erythematosus or polymyositis without requiring immunosuppressive therapy. This case emphasizes the fact that patients with benign-neoplasm-associated PNP may undergo complete remission of the autoimmune disease upon complete excision of the tumor. This case also stresses the possible association of PNP with other autoimmune diseases such as lupus erythematosus and polymyositis.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
5/51. Paraneoplastic pemphigus associated with bronchiolitis obliterans.Paraneoplastic pemphigus (PNP) is an autoantibody-mediated mucocutaneous blistering disease associated with underlying neoplasms. autoantibodies of PNP bind to the plakin family of cytoplasmic proteins and desmogleins of cell-surface target antigens. We describe a 36-year-old female patient with PNP who had non-Hodgkin's lymphoma, and who developed bronchiolitis obliterans and died of respiratory failure. autopsy findings confirmed luminal narrowing of bronchioles by scarring, which is a histopathologic features of bronchiolitis obliterans. After the onset of respiratory failure, the reaction of autoantibodies against the plakins detected by immunoprecipitation at the onset of PNP disappeared with negative immunofluorescence within the bronchial epithelium. It is thought that autoantibodies against some of these antigens play a role in causing acute inflammation of the respiratory epithelium. In treating PNP, the possibility of the patient developing the lethal complication bronchiolitis obliterans should be kept in mind. Furthermore, prevention of the initial autoantibody-mediated injury to the respiratory epithelium should be an important treatment goal.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
6/51. Use of mycophenolate mofetil in the treatment of paraneoplastic pemphigus.Paraneoplastic pemphigus (PNP) is a rare autoimmune blistering disease with circulating antibodies that bind the cell surface of the epidermis and other non-stratifying epithelia, and immunoprecipitate a complex of four or five proteins (250 kDa, 230 kDa, 210 kDa, 190 kDa and occasionally 170 kDa).1,2 Combinations of immunosuppressive agents are usually required to obtain even partial control of the skin lesions.3 mucous membrane lesions are refractory to treatment. We describe a patient with PNP whose skin and oral lesions are quiescent following treatment with oral mycophenolate mofetil.- - - - - - - - - - ranking = 0.053571351807682keywords = complex (Clic here for more details about this article) |
7/51. Paraneoplastic pemphigus caused by an epithelioid leiomyosarcoma and associated with fatal respiratory failure.A patient is described who initially presented with pemphigus vulgaris, limited to the oral cavity, and weight loss. Although the various laboratory studies pointed to the diagnosis of paraneoplastic pemphigus (PNP), the underlying neoplasm was not detected until 6 months later, when the patient developed shortness of breath and routine physical examination on admission revealed an abdominal mass, which eventually was proven to be an epithelioid leiomyosarcoma. In spite of radical excision of the tumour and intensive treatment of the dyspnoea, the patient died of respiratory failure 19 months after the PNP had been diagnosed. early diagnosis of PNP is stressed to possibly prevent fatal pulmonary involvement.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
8/51. classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus.BACKGROUND: Recent studies suggest that paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome involving several internal organs and that the pathophysiological mechanisms mediating cutaneous, mucosal, and internal lesions are not limited to autoantibodies targeting adhesion molecules. OBJECTIVE: To classify the diverse mucocutaneous and respiratory presentations of PNP and characterize the effectors of humoral and cellular autoimmunity mediating epithelial tissue damage. methods: We examined 3 patients manifesting the lichen planus pemphigoideslike subtype of PNP. A combination of standard immunohistochemical techniques, enzyme-linked immunosorbent assay with desmoglein (DSG) baculoproteins, and an immunoprecipitation assay were used to characterize effectors of humoral and cellular autoimmunity in patients with PNP and in neonatal wild-type and DSG3-knockout mice with PNP phenotype induced by passive transfer of patients' IgGs. RESULTS: In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included 240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3. In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle. Autoreactive cellular cytotoxicity was mediated by CD8( ) cytotoxic T lymphocytes, CD56( ) natural killer cells, and CD68( ) monocytes/macrophages. Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets. Keratin 14-positive basal epithelial cells sloughed from the large airways and obstructed small airways. CONCLUSIONS: The paraneoplastic disease of epithelial adhesion known as PNP in fact represents only 1 manifestation of a heterogeneous autoimmune syndrome in which patients, in addition to small airway occlusion and deposition of autoantibodies in different organs, may display a spectrum of at least 5 different clinical and immunopathological mucocutaneous variants (ie, pemphiguslike, pemphigoidlike, erythema multiforme-like, graft-vs-host disease-like, and lichen planus-like). We suggest that the more encompassing term "paraneoplastic autoimmune multiorgan syndrome," or PAMS, be applied. The pathophysiological mechanisms of PAMS involve both humoral and cellular autoimmunity responses. Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity. apoptosis of damaged basal cells mediates epithelial clefting, and respiratory failure results possibly from obstruction of small airways with sloughed epithelial cells.- - - - - - - - - - ranking = 0.053571351807682keywords = complex (Clic here for more details about this article) |
9/51. Paraneoplastic pemphigus without antidesmoglein 3 or antidesmoglein 1 autoantibodies.Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease characterized by IgG autoantibodies that bind to various epithelia and immunoprecipitate a complex of 250, 230, 210, 190 and 170 kDa proteins. A recent study has suggested that PNP patients have antidesmoglein (Dsg) 3 autoantibody and that the antibody plays a pathogenic role in PNP. We report a 72-year-old woman with PNP associated with thymoma and adenocarcinoma of the lung. Diagnosis of PNP was made by the characteristic clinical, histological and immunopathological findings, as well as immunoprecipitation of characteristic 230, 210 and 190 kDa proteins. Using enzyme-linked immunosorbent assay with baculovirus-expressed recombinant proteins, the patient's serum was negative against both Dsg 3 and Dsg 1. This finding is unusual, and it suggests that the target antigen, which is involved in acantholysis, may be other than Dsg 3 in this case.- - - - - - - - - - ranking = 0.053571351807682keywords = complex (Clic here for more details about this article) |
10/51. A novel variant three-way translocation of inversion 16 in a case of AML-M4eo following low dose methotrexate therapy.We report a case of acute myelomonocytic leukemia with eosinophilia (AML-M4eo) in a 65-year-old man following low dose methotrexate treatment for pemphigus vulgaris. Cytogenetic studies at diagnosis revealed a complex karyotype including a reciprocal translocation between 11q14.2 and 16q22, an inversion of chromosome 16(p13.1q22), and an apparently terminal deletion of 7q31. The presence of inv(16) was confirmed by reverse transcription-polymerase chain reaction which demonstrated a Type A fusion transcript derived from the core binding factor (CBF) beta and the smooth muscle myosin heavy chain (MYH11) genes. The patient was in complete hematologic and cytogenetic remission 6 months following intensive chemotherapy. Because AML-M4eo with inv(16) has a favorable prognosis, molecular studies should be performed in case the identification of inv(16) by conventional cytogenetics is difficult due to a complex karyotype.- - - - - - - - - - ranking = 0.10714270361536keywords = complex (Clic here for more details about this article) |
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