Case report: Scleromyxedema associated with a monoclonal gammapathy: Successful treatment with intravenous immunoglobulins.

Scleromyxedema is a rare idiopathic fibromucinous disorder characterized by a generalized papular and sclerodermoid cutaneous eruption. Patients often have praraproteinemia and extracutaneous, even lethal, manifestations. Yet the prognostic and therapeutic features of scleromyxedema are poorly documented. High-dose intravenous immunoglobulin (IVIG), used either alone or in conjunction with systemic steroids and/or thalidomide, has been suggested as a first-line treatment. We report the case of a 45-year-old woman diagnosed with scleromyxedema with paraproteinemia that initially did not respond to systemic steroids, retinoids, and thalidomide but greatly improvement in terms of systemic and cutaneous symptoms after treatment with IVIG.

Complete Remission of Advanced Hepatocellular Carcinoma Treated with Sorafenib and Concomitant Appearance of IgG4- related Diseases. A Case Report.

Sorafenib is currently the gold standard therapy for palliative treatment of advanced hepatocellular carcinoma (HCC) in patients with compensated liver disease. There are few cases reported in literature describing patients with HCC achieving a complete remission (CR) due to Sorafenib therapy. We report the case of a 62-year old patient who obtained CR despite single, long drug discontinuation and kept it without any maintenance therapy. Furthermore, this is the first case describing the onset of a likely IgG4-related retroperitoneal fibrosis and cholangitis during Sorafenib administration. Further studies are required to define the predictors of a good response to Sorafenib and to codify a therapeutic maintenance regimen for patients who achieve CR.

Acquired Fanconi syndrome secondary to light chain deposition disease associated with monoclonal gammopathy of renal significance: A case report.

RATIONALE: Renal Fanconi syndrome (FS) is a rare complication of monoclonal gammopathy. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis. Renal impairment in monoclonal gammopathy, without fulfilling the criteria of multiple myeloma, is categorized as monoclonal gammopathy of renal significance (MGRS). PATIENT CONCERNS: A 54-year-old male presented with progressively aggravated bone pain and limitation of activity was admitted to our department. A proximal renal tubular damage was suggested by hypophosphatemia, compensated metabolic acidosis, renal glycosuria, aminoaciduria, and hypouricemia. M-protein of IgA kappa was detected by immunofixation electrophoresis. Mildly increased plasma cells were found in bone marrow cytomorphologic examination. Renal biopsy revealed diffuse linear monoclonal IgA-kappa light chain deposits along tubular basement membranes (TBMs), while lambda was negative. Electron microscopy showed granular electron-dense deposits along the outer aspect of TBMs. DIAGNOSES: The patient was diagnosed as FS induced osteomalacia secondary to monoclonal gammopathy of renal significance (MGRS) (IgA-κ type) and LCDD. INTERVENTIONS: He was treated with bortezomib, supplementation by phosphate, alkali agents, and active vitamin D. He responded well to the treatment symptomatically. OUTCOMES: We reported a rare case of adult acquired FS with hypophosphatemic osteomalacia secondary to LCDD associated with MGRS and the patient was successfully treated with bortezomib. LESSONS: Although few cases of LCDD with isolated symptoms of tubulointerstitial nephropathy, rather than glomerular symptoms have been reported. It still needs to be recognized as a differential diagnosis in monoclonal gammopathy.

Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study.

BACKGROUND: Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes of death and survival rates of RRT for ESRD due to MM or LCDD in the ERA-EDTA Registry. METHODS: Thirteen national registries providing data on patients who started RRT from 1986-2005 to the ERA-EDTA Registry participated. Incidence per million population (pmp) of RRT for ESRD due to MM or LCDD and other causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. RESULTS: Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986-1990 to 2.52 pmp in 2001-2005. MM and LCDD patients compared to non-MM patients were older and a higher percentage was on haemodialysis at day 91 after the start of RRT. The most common causes of death in MM and LCDD patients were malignancy (36.1%), cardiovascular causes (17.2%) and infection (14.7%). MM and LCDD patients had a 2.77 (95% CI, 2.65-2.90) higher risk of death compared to non-MM patients. The unadjusted median survival on RRT was 0.91 years in MM and LCDD patients and 4.46 years in non-MM patients. During follow-up, 35 patients were transplanted and their mean survival was 9.6 years. CONCLUSION: The incidence of RRT for ESRD due to MM or LCDD has increased over the past 20 years in Europe. The median patient survival on RRT for MM and LCDD patients was 0.91 years, compared to 4.46 years for non-MM patients. These results suggest that dialysis, and in selected cases even transplantation, should be offered to MM and LCDD patients.

Bortezomib successfully reverses early recurrence of light-chain deposition disease in a renal allograft: a case report.

Light-Chain Deposition Disease (LCDD) frequently recurs after renal transplantation, displaying a pernicious course. Herein we have described a 39-year-old Caucasian man with a history of immunoglobulin G-kappa multiple myeloma who failed two chemotherapy regimens, but ultimately responded to the combination of thalidomide, bortezomib, and dexamethasone followed by high-dose melphalan and autologous stem cell transplantation 3 years prior to transplantation, during which time he showed no evidence of persistent or recurrent disease. At 3 days following spousal living related renal transplantation, he displayed a rapid deterioration of renal function requiring dialysis therapy. This episode failed to respond to empiric antirejection therapy including anti-thymocyte globulin, plasmapheresis, and anti-CD20 monoclonal antibody. Increasing evidence suggested recurrence of LCDD, including positive immunofluorescence staining of basement membranes and vessels for kappa light chains as well as free kappa light chains in his urine and serum. Following suspension of sirolimus, he was initiated on and responded to bortezomib (1.3 mg/m(2)) with discontinuation of dialysis within 3 weeks and progressively improving renal function. His maintenance therapy, in addition to six 2-week-long cycles of bortezomib separated by 1-week rest periods, includes cyclosporine (50 mg twice daily), prednisone (10 mg daily), and curcumin (9 g daily). In sum, bortezomib rescue therapy salvaged a spousal renal transplant afflicted with recurrent LCDD.

Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance.

A 60-year-old woman was admitted because of multiple bone pain. Examination revealed hypophosphatemic osteomalacia and acquired Fanconi syndrome. Further exploration revealed monoclonal gammopathy of undetermined significance (MGUS) excreting urinary Bence Jones protein (kappa light chain). Renal biopsy showed non-specific tubulointerstitial nephritis, yet neither crystalline inclusions in the cytoplasm of the tubular epithelium nor myeloma casts nor amyloid deposits were found. She was treated with supplementation by phosphate, alkali agents, and vitamin D, and responded well to the treatment symptomatically and biochemically. MGUS was observed without chemotherapy. Myeloma had not developed after 10 months follow-up.

Hypophosphatemia associated with paraproteinemia: a case report and review of the literature.

The differential diagnosis for hypophosphatemia is long, and involves complex, overlapping physiological systems. Practitioners are often guilty, however, of simply supplementing phosphate without fully investigating the etiology of the problem. The purpose of this case presentation is to illustrate a case of spurious hypophosphatemia that initially led to unnecessary phosphate replacement in a woman with undiagnosed multiple myeloma. An 85-year-old African American woman was admitted to the hospital for congestive heart failure exacerbation. The patient was incidentally found to be profoundly hypophosphatemic and was also diagnosed with multiple myeloma at this hospitalization. Normal phosphorus levels were difficult to maintain despite aggressive replacement. A serum sample initially reported to have an abnormally low phosphorus concentration on the Beckman CX7 analyzer was reanalyzed with the Kodak Ektachem 700 system, revealing the phosphorus concentration to be towards the higher limit of the normal range on the same sample. We conclude that clinicians should proceed with caution before aggressively treating abnormal phosphorus levels in patients with known paraproteinemia. Conversely, unexplained phosphorus abnormalities should bring disorders associated with paraproteinemia, such as multiple myeloma, into the differential diagnosis. Knowledge of how various phosphorus assays are affected by paraproteins is essential to guiding diagnosis and treatment. We also review mechanisms of reported interference with common assays.

VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy.

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72-year-old man suffering from neuropathy associated with monoclonal gammopathy.

Microvasculitic paraproteinaemic polyneuropathy and B-cell lymphoma.

Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic neuropathies than is generally recognised, producing tissue destruction by convergent immune and physical mechanisms. We present a patient with a clinical syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma. Microvasculitic changes were present in the first nerve biopsy, and the second showed extensive destruction of neural architecture and deposition of IgM-related material. A 2-stage pathogenic cascade is postulated and explored with a review of the relevant literature.

Acquired Fanconi's syndrome associated with monoclonal gammopathies.

Franconi's syndrome is a rare complication of the monoclonal gammopathies characterized by diffuse failure in reabsorption at the level of the proximal renal tubule resulting in glycosuria, generalized aminoaciduria, and hypophosphatemia. Current evidence suggests monoclonal light chains that are incompletely digested in renal tubule lysosomes cause renal injury. The light-chain fragments serve as a nidus for crystal formation, and the crystals interfere with a broad range of apical membrane transporters. Franconi's syndrome is predominantly associated with monoclonal kappa in the urine, but rare instances of FS caused by lambda light chains have been described. Overt hematologic malignancies such as multiple myeloma, Waldenström's macroglobulinemia, or other lymphoproliferative disorders occur in one third of patients. Clinical manifestations include slowly progressive renal failure and bone pain caused by osteomalacia. The osteomalacia is caused by chronic hypophosphatemia and may be exacerbated by secondary hyperparathyroidism and renal tubular acidosis. Treatment consists of supplementation with phosphorus, calcium, and vitamin D. The osteomalacia is often completely reversible with mineral supplementation. Patients with an associated symptomatic malignancy or rapidly progressive renal failure may also benefit from chemotherapy. The prognosis is good in the absence of overt malignant disease.

[The risk of a multiple myeloma in patients with paraproteinemia: a myeloma risk score developed in the region of the Comprehensive Cancer Center West]. / De kans op de ziekte van Kahler (multipel myeloom) bij patiënten met een paraproteïnemie: myeloomrisicoscore, ontwikkeld in de regio van het Integraal Kankercentrum West.

Diagnoses in patients with paraproteinaemia are diverse; few (mostly single centre based) studies are known that describe incidence, diagnoses and follow-up in patients with paraproteinaemia. In the region of the Comprehensive Cancer Centre West in the Netherlands (population 1.6 million, 1992) a population-based registry was set up in the period 1991-1993. Patients (n = 1464; median age: 72 years; range: 16-102) were entered by clinical chemists, internists, haematologists, and pathologists. Multiple myeloma and plasmacytoma were diagnosed in 261 patients (18%), paraprotein-related haematological diseases in 159 patients (11%) and paraprotein-related internal diseases in 210 patients (14%). After bone marrow examination monoclonal gammopathy of unknown significance (MGUS) was diagnosed in 207 (14%) patients. No further diagnosis could be made in 627 (43%) patients mostly for lack of supplementary bone marrow and (or) X-ray examinations. Consequently, more than two-thirds of all patients with a newly found paraprotein did not show any sign of a haematological malignancy. Using these data a 'myeloma risk score' was developed to predict the presence of a multiple myeloma based on paraprotein type and concentration, aiding the physician in determining which patients should undergo further bone marrow and skeletal examinations.

A population-based registry on paraproteinaemia in The Netherlands. Comprehensive Cancer Centre West, Leiden, The Netherlands.

Patients with monoclonal gammopathies comprise a heterogenous group. The few studies on incidence and follow-up are single-centre-based and may reflect referral bias. To avoid this, all patients (n=1275) in midwestern Netherlands with a newly discovered paraproteinaemia in 1991, 1992 and 1993 were included in a population-based registry and divided into four major diagnostic groups: multiple myeloma and plasmacytoma (n=230, 18%), other haematological diseases (n=141, 11%), paraprotein-related internal diseases (n=191, 15%) and monoclonal gammopathy of undetermined significance (MGUS, n=713, 56%). To avoid a possibly erroneous diagnosis, patients who were classified as having MGUS but who did not undergo confirmatory bone marrow examination were included in a separate group 'provisional MGUS' (n=524, 41%), whereas patients who did were classified as having 'definite MGUS' (n=189, 15%). The 'provisional MGUS' patients were relatively older and had more often a poor performance status, but differences between this and the 'definite MGUS' group were otherwise small. Patients complaining of general malaise more often had a full work-up of their paraproteinaemia. Bone pain, hypercalcaemia, high total protein, and high ESR occurred predominantly in the myeloma group, whereas fever or infection was less often seen in these patients. This registry of patients with paraproteinaemias provided valuable data related to all different diseases associated with paraproteinaemia.

High-dose therapy and autologous transplantation in amyloidosis-AL.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.

[Systemic urticaria, sclerosing osteopathy, monoclonal gammopathy (Schnitzler syndrome). Apropos of a case]. / Urticaire systémique, ostéopathie condensante, gammapathie monoclonale (syndrome de Schnitzler). A propos d'un cas.

A 65 years old man has been suffering from the upper limbs and legs for 2 years. Bone pain was associated with a non pruritic chronic urticaria and fever. Bone scintigraphy showed lesions of the lower limbs. X rays showed only one sclerotic bone lesion. Immunoelectrophoretic analysis showed an IgM kappa monoclonal gammapathy. Bone marrow aspirate and bone marrow biopsy were normal. The association of chronic urticaria, bone pain and macroglobulinemia has been first reported by L. Schnitzler. Seventeen other cases have been reported in the literature. The pathogenesis of the syndrome is unknown although anti-interleukin 1 alpha autoantibodies were found in several cases (8 out of 13).

Erosive arthritis in monoclonal gammopathy of uncertain significance: report of four cases.

We report 4 case histories in which an erosive arthritis was associated with the presence of a monoclonal gammopathy of uncertain significance. In all 4 cases, the appearance of paraprotein was noted either before or during the development of the arthritis. Two patients had a rather atypical oligoarthritis, while the others had a rheumatoid-like, symmetric polyarthritis. A synovial amyloid deposit was present in 2 patients, while mild mixed mononuclear infiltrates were the main pathologic finding in the others. In 2 patients, immunohistochemical investigation demonstrated deposits of immunoglobulin-derived material of the same isotype as the monoclonal component in the synovial tissue.

Thrombotic microangiopathy isolated to the central nervous system.

A man with plasma cell dyscrasia and bone marrow infiltration presented with rapidly progressive encephalopathy. Magnetic resonance imaging revealed multiple small areas of abnormal signal that correlated with the autopsy findings of thrombotic microangiopathy isolated to the central nervous system.

Subcorneal pustular dermatosis and IgA paraproteinaemia: response to both etretinate and PUVA.

A non-insulin dependent male diabetic is reported with subcorneal pustular dermatosis associated with intraepidermal IgA deposits and a benign IgA paraproteinaemia. Treatment with dapsone and etretinate was reasonably effective, but etretinate had to be discontinued due to the development of diffuse idiopathic skeletal hyperostosis. His subcorneal pustular dermatosis subsequently flared and was troublesome for 2 years until he was commenced on PUVA, with excellent response.