Chronic urticaria may often be associated with interleukin (IL)-1-mediated autoinflammatory disease, which should be suspected if systemic inflammation signs are present. Here, we report a case of Schnitzler's syndrome without monoclonal gammopathy treated successfully with the IL-1 receptor antagonist anakinra. A 69-year-old man suffered from a pruritic urticarial rash for 12 years. It became aggravated episodically and was accompanied by high fever, arthralgia, leukocytosis, and an elevated C-reactive protein and erythrocyte sedimentation rate. The episodes each lasted for over one week. Neutrophilic and eosinophilic inflammation was found on skin biopsy. However, serum and urine electrophoresis showed no evidence of monoclonal gammopathy. The cutaneous lesions were unresponsive to various kinds of anti-histamines, systemic glucocorticoids, colchicine, cyclosporine, dapsone, and methotrexate, which were administered over a span of 3 years immediately preceding successful treatment. A dramatic response, however, was observed after a daily administration of anakinra. This observation suggests that the correct diagnosis of this case is Schnitzler's syndrome without monoclonal gammopathy. For an adult patient with refractory chronic urticaria and systemic inflammation, Schnitzler's syndrome could be considered as a possible differential diagnosis. Although the typical form of Schnitzler's syndrome exhibits the presence of monoclonal gammopathy as a diagnostic criterion, monoclonal gammopathy may be absent in an atypical form. In such a situation, an IL-1 antagonist should be effective for the management of chronic urticaria.
Aged ; Blood Sedimentation ; C-Reactive Protein/metabolism ; Chronic Disease ; Humans ; Interleukin 1 Receptor Antagonist Protein/therapeutic use ; Leukocytes/metabolism ; Male ; Paraproteinemias/complications ; Schnitzler Syndrome/blood ; Schnitzler Syndrome/drug therapy ; Urticaria/complications

BACKGROUND: POEMS syndrome is a rare paraneoplastic syndrome associated with plasma cell dyscrasia. High-dose chemotherapy followed by autologous stem cell transplantation has shown encouraging efficacy in the treatment of patients with POEMS syndrome. However, there are minimal reports on clinical outcomes after autologous stem cell transplantation for patients with advanced disease and very poor performance status. METHODS: We retrospectively evaluated 9 advanced POEMS syndrome patients, who had an Eastern Cooperative Oncology Group performance status score of 3 or 4, and were treated with high-dose melphalan therapy followed by autologous stem cell transplantation from 2004 to 2011. RESULTS: Eight patients achieved initial hematologic response, 4 of whom had complete responses. At a median follow-up of 44 months (range, 8-94 months), 7 patients were alive, with 3-year overall survival rate of 77.8%. There were no hematologic relapses in the survivors. One patient died of disease progression; the other died of pneumonia despite a hematologic response 3 months after autologous stem cell transplantation. All survivors achieved improvement in general performance status and in clinical response. CONCLUSION: High-dose melphalan followed by autologous stem cell transplantation can be considered a valid treatment option even for patients with advanced POEMS syndrome.
Disease Progression ; Drug Therapy ; Follow-Up Studies ; Humans ; Melphalan* ; Paraneoplastic Syndromes ; Paraproteinemias ; Pneumonia ; POEMS Syndrome* ; Recurrence ; Retrospective Studies ; Stem Cell Transplantation* ; Stem Cells* ; Survival Rate ; Survivors

Monoclonal gammopathy occurs in one-third of the patients with mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). However, monoclonal gammopathy has been rarely reported in Korea. Paraprotenemia accompanying MALT lymphoma is strongly correlated with involvement of the bone marrow, and this involvement leads to the progression of the disease. Here, we present a case of a 66-yr-old man diagnosed with IgM monoclonal gammopathy and stage IV extranodal marginal zone lymphoma of the small intestine, with the involvement of the bone marrow.
Aged ; Antineoplastic Agents/therapeutic use ; Bone Marrow/pathology ; Drug Therapy, Combination ; Electrophoresis, Polyacrylamide Gel ; Humans ; Immunoglobulin M/analysis ; Intestinal Neoplasms/complications/drug therapy/*pathology ; Lymphatic Metastasis ; Lymphoma, B-Cell, Marginal Zone/complications/drug therapy/*pathology ; Male ; Neoplasm Staging ; Paraproteinemias/blood/complications/*pathology ; Positron-Emission Tomography ; Tomography, X-Ray Computed

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Antigens, CD5/*metabolism ; Antineoplastic Agents/therapeutic use ; B-Lymphocytes/immunology/metabolism ; Bone Marrow/pathology ; Cryoglobulinemia/diagnosis ; Cyclophosphamide/therapeutic use ; Diagnosis, Differential ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Glomerulonephritis/*diagnosis/pathology ; Humans ; Kidney/pathology ; Middle Aged ; Paraproteinemias/diagnosis ; Prednisolone/therapeutic use ; Vincristine/therapeutic use ; Waldenstrom Macroglobulinemia/*diagnosis/drug therapy/pathology

An 8-year-old male Austrian Pinscher and a 14-year-old male Golden Retriever were presented for evaluation due to unexplainable high fructosamine values despite euglycemia and epistaxis in combination with polydipsia/polyuria, respectively. Blood analysis revealed severe hyperglobulinemia, hypoalbuminemia and markedly elevated fructosamine concentrations in both dogs. Multiple myeloma with IgA-monoclonal gammopathy was diagnosed by serum and urine electrophoresis including immunodetection with an anti-dog IgA antibody and bone marrow aspirations. Diabetes mellitus was excluded by repeated plasma and urine glucose measurements. Fructosamine values were positively correlated with globulin, but negatively correlated with albumin concentrations. These cases suggest that, as in human patients, monoclonal IgA gammopathy should be considered as a possible differential diagnosis for dogs with high fructosamine concentrations.
Animals ; Blood Proteins/analysis ; Dog Diseases/*blood/drug therapy ; Dogs ; Fructosamine/*blood ; Immunoglobulin A/*metabolism ; Male ; Melphalan/therapeutic use ; Multiple Myeloma/complications/drug therapy/*veterinary ; Myeloablative Agonists/therapeutic use ; Paraproteinemias/blood/complications/drug therapy/*veterinary

We report a case of multiple myeloma showing marked differences in serum Immunoglobulin G (IgG) levels between serum protein electrophoresis and turbidimetry. A 47-yr old man was admitted to our hospital due to severe back pain and diagnosed as having IgG-kappa type multiple myeloma. Serum protein level was 14.4 g/dL at the time of diagnosis. Serum IgG level was 8.5 g/dL by serum protein electrophoresis, but 11.6 g/dL by turbidimetry. The patient's clinical conditions had improved after receiving VAD (vincristine, adriamycin, dexamethasone) and VTD (vincristine, thalidomide, dexamethasone) chemotherapy and there were no differences in IgG levels between electrophoresis and turbidimetry when serum IgG levels were less than 3.0 g/dL. According to this, we considered that both protein electrophoresis and turbidimetry should be needed to quantify serum immunoglobulins for diagnosis and follow-up of the patients with monoclonal gammopathy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Electrophoresis, Agar Gel ; Humans ; Immunoglobulin G/*blood ; Immunoglobulin kappa-Chains/blood ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis ; Nephelometry and Turbidimetry ; Paraproteinemias/drug therapy ; Time Factors

Primary systemic amyloidosis is associated with plasma cell dyscrasia, such as multiple myeloma. The amyloid fibrils in the disease are composed of amyloid light (AL) protein that is derived from immunoglobulin L chain. Cutaneous manifestations are presented in about 20~40% of patients with mainly petechia, purpura on flexural area of the body and waxy, translucent papulonodules. We report a case of primary systemic amyloidosis associated with multiple myeloma occurring in a 76-year old woman who had suffered from ecchymotic purpura on periorbital and flexural area with hemorrhagic bulla for one year. She also had macroglossia with grouped papulonodules on her tongue, and peripheral neuropathy. The final diagnosis was confirmed by positive PAS, Congo-red stain and specific serum/urine electrophoresis. She had been treated with several cycles of chemotherapy; however, she expired from various complications of the disease, such as congestive heart failure, renal failure, and secondary bacterial infection.
Aged ; Amyloid ; Amyloidosis* ; Bacterial Infections ; Diagnosis ; Drug Therapy ; Electrophoresis ; Female ; Heart Failure ; Humans ; Immunoglobulins ; Macroglossia ; Multiple Myeloma* ; Paraproteinemias ; Peripheral Nervous System Diseases ; Purpura ; Renal Insufficiency ; Tongue

Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are both lymphoproliferative disease occurring in different stages of B cell oncogeny. An increased incidence of secondary malignancies in patients with CLL is well recognized, however, the coexistence of both disorders in the same patient was very rare. Furthermore, clonal relationship between these diseases has not been clearly established. We report the occurrence of MM during the course of CLL. A 68-year-old patient was presented with general weakness and bone marrow aspiration showed a hypercellular marrow with 80% mature lymphocytes. At 5 months after diagnosis of CLL, bone marrow of the patient showed increased immature plasma cells. Serum protein electrophoresis showed monoclonal gammopathy and serum immunoelectrophoresis IgG kappa type monoclonality. The patient received six cycles of VAD (vincristine, adriamycin, dexamethasone) chemotherapy, but died of pneumonia and sepsis.
Aged ; Bone Marrow ; Diagnosis ; Doxorubicin ; Drug Therapy ; Electrophoresis ; Humans ; Immunoelectrophoresis ; Immunoglobulin G ; Incidence ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Lymphocytes ; Multiple Myeloma* ; Paraproteinemias ; Plasma Cells ; Pneumonia ; Sepsis

BACKGROUND: M protein, as a marker for monoclonal gammopathy, has been evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). Recently a highly sensitive, automated immunonephelometric assay for measurement of free light chains (FLCs) in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. METHODS: We measured the concentration of kappa and lambda FLCs in 120 healthy individuals aged 20 to 80 years to establish the reference range of kappa and lambda FLCs and kappa/lambda FLC ratio and in 61 serum and 14 urine samples from patients with multiple myeloma (MM) to examine the correlation between the amount of M protein indirectly calculated on PEP and the direct measurement of FLCs. RESULTS: The concentrations of kappa and lambda FLCs and the kappa/lambda FLC ratio in healthy individuals were not significantly related to age or sex. The 95 percentile reference ranges for kappa FLC, lambda FLC, and kappa/lambda FLC ratio were 8.5-23.7 mg/L, 9.5-23.5 mg/L, and 0.67-1.38, respectively. On the PEP performed with MM specimens, 18 cases did not show the evidence of M protein. But, they revealed abnormal FLC concentrations on FLC assay and a significant correlation was found between the amount of M protein and the concentration of kappa and lambda FLC. However, inconsistent results such as the concentra-tion of kappa+lambda FLCs being more than the total protein in urine or M protein in serum were found in 5 of the 14 urine and 1 of the 61 serum samples of MM patients. CONCLUSIONS: FLC assay showed a good correlation with PEP and was more sensitive and accurate than PEP. Therefore, FLC assay is useful for diagnosing and monitoring monoclonal gammopathy at an early stage of the disease and during a remission state after chemotherapy or peripheral blood stem cell transplantation.
Drug Therapy ; Electrophoresis ; Humans ; Multiple Myeloma* ; Paraproteinemias ; Peripheral Blood Stem Cell Transplantation ; Reference Values*

The coexistence of non-Hodgkin's lymphoma and multiple myeloma is very rare and the coexistence of nasal NK/T-cell lymphoma and multiple myeloma has never been reported in the literature. Recently, a 63-year-old woman was presented with small amount of hematemesis. Bone marrow showed increased immature plasma cell (72.5%). Serum protein electrophoresis showed monoclonal gammopathy (6.5g/dL). Serum immunoelectrophoresis showed IgG and kappa type monoclonality. Microscopic examination of left nasopharynx and inferior turbinate revealed nasal NK/T-cell lymphoma. Six cycles of CHOP (cyclophosphamide, daunomycin, vincristine, prednisone) chemotherapy induced the complete remission of both tumors, but died of cerebral involvement of NK/T-cell lymphoma in 12 months after the diagnosis.
Bone Marrow ; Daunorubicin ; Diagnosis ; Drug Therapy ; Electrophoresis ; Female ; Hematemesis ; Humans ; Immunoelectrophoresis ; Immunoglobulin G ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Middle Aged ; Multiple Myeloma* ; Nasopharynx ; Paraproteinemias ; Plasma Cells ; Turbinates ; Vincristine