If you have Waldenstrom macroglobulinemia or are close to someone who does, knowing what to expect can help you cope. Here you can find out all about Waldenstrom macroglobulinemia, including risk factors, symptoms, how it is found, and how it is treated. Get an overview of Waldenstrom macroglobulinemia and the latest key statistics in the US. Learn about the risk factors for Waldenstrom macroglobulinemia and what you might be able to do to help lower your risk. Know the signs and symptoms of Waldenstrom macroglobulinemia.
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Ophthalmology and Visual Sciences. William E. Flanary, MD ; Thomas M. Meirick, BS; H. Culver Boldt, MD. The patient is a year-old male who presents with worsening vision in both eyes. Since that time, he has noticed a gradual decline in vision in both eyes. He has poorly controlled diabetes mellitus type II with a recent hemoglobin A1c of 8. His diabetes is treated with oral medications. He denies any sudden loss of vision, flashing lights, new floaters, or headaches.
The patient was diagnosed with clinically significant macular edema CSME in the setting of severe non-proliferative diabetic retinopathy in both eyes and was treated with focal laser in the left eye followed by the right eye. He did not notice an improvement in vision after the laser treatment and his visual acuity was essentially unchanged at follow-up. As a result of the improvement in the right eye, STK was given in the left eye which yielded a reduction in macular thickness on OCT and improvement in visual acuity.
Given his favorable response to steroid treatment, he received 1 more dose of STK to both eyes before developing elevated intraocular pressure. Unfortunately, the elevated intraocular pressure was not responsive to topical anti-hypertensive medications and further treatment with steroids was abandoned 2 years after initial presentation. Also over this course, he was found to have proliferative diabetic retinopathy OD that was treated with pan-retinal photocoagulation.
After cessation of steroids, he received regular intravitreal injections with Avastin which failed to impact the macular edema. Due to the lack of response to conventional therapy with persistent macular edema and more than usual venous dilation, screening for underlying metabolic disease or condition causing hyperviscosity which could potentially be contributing to his retinal pathology was arranged.
Pertinent results included:. He was referred to an endocrinologist for further investigation of his anemia and hyperproteinemia. Further testing revealed:. The patient's anemia combined with serum protein electrophoresis showing an IgM monoclonal gammopathy and elevated serum viscosity led to the diagnosis of hyperviscosity syndrome due to Waldenstrom Macroglobulinemia. The patient was referred to the hematology service for further treatment recommendations.
He was initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy upon diagnosis which produced little reduction in IgM levels.
Next, he began scheduled plasmapheresis and IVIG therapy every 4 weeks. With this treatment regimen, his IgM level was consistently maintained in the range and the macular edema in both eyes began to resolve Fig 4.
Despite not responding initially to standard chemotherapy treatments, he has been able to maintain a monthly schedule of plasmapheresis and IVIG for over four years. His macular edema also requires intermittent intravitreal injections of triamcinolone to control.
Waldenstrom macroglobulinemia WM is a lymphoplasmacytic lymphoma characterized by malignant B cells and the accumulation of IgM monoclonal protein in the blood. This gene encodes for a protein involved in the toll-like receptor and interleukin 1 signaling pathways. The accumulation of IgM protein leads to both blood hyperviscosity and high intravascular osmotic pressure 3.
The presence of a large volume of positively charged IgM molecules interacts strongly with red blood cells contributing to blood hyperviscosity. Waldenstrom macroglobulinemia is a rare disease with an incidence of 3 cases per million people per year in the US.
This results in roughly 1, to 1, new diagnoses each year. The major risk factors are male gender, Caucasian race, and age over 60 4. Common exam findings include bilateral retinal vein engorgement, lipid exudates, central and branch retinal vein thrombosis, and flame-shaped hemorrhages, which typically manifest once serum viscosity rises to near 4.
A less common ocular finding is the accumulation of subretinal fluid, as seen in this patient. Several studies have documented the presence of immunoglobulins in the subretinal space of patients with WM and multiple myeloma. Although the exact mechanism for this finding is unknown, multiple theories have been proposed. Klaassen et al suggested that venous stasis retinopathy caused by serum hyperviscosity leads to hypoxia of the retinal vascular endothelial cells.
As a result, there is breakdown of the blood-retinal barrier allowing passage of IgM into the subretinal space 5. This mechanism could easily be exacerbated by comorbid conditions which produce an ischemic state in the retina, particularly diabetic retinopathy, which was documented in this patient more than 20 years prior to the diagnosis of WM.
Patients with WM often have plasma IgM levels upwards of or more normal with significant serum hyperviscosity. Initial treatment of symptomatic patients should be targeted toward decreasing IgM through plasmapheresis.
Rapid reduction of IgM levels will usually lead to relief of hyperviscosity syndrome complications including reversal of retinal vein engorgement 8. The patient in this case responded well to plasmapheresis and IVIG therapy with reduction of subretinal fluid, flame hemorrhages and vessel tortuosity.
Although these patients are often anemic, red blood cell transfusions should not be done as the ensuing interaction of IgM with donor RBCs may increase serum viscosity. Once the serum IgM level is controlled with a documented decrease in viscosity, most patients require maintenance with chemotherapy. For years, CHOP therapy was the preferred treatment regimen.
Although VEGF inhibitors may aid in reducing intraretinal and subretinal fluid accumulation seen in WM retinopathy, this option should only be considered in conjunction with treatments designed to remove the abnormal IgM complexes from serum.
This case represents a significant diagnostic challenge. Patients with severe nonproliferative and proliferative diabetic retinopathy commonly develop clinically significant macular edema. In the vast majority of cases, patients with a history of diabetic retinopathy would lead the examiner to the probable diagnosis of CSME due to uncontrolled diabetes. However, at what point should other, more atypical etiologies of persistent CSME be considered? In this patient, the lack of a normal response to well-established treatments like VEGF inhibitors and steroids and the significant bilateral venous dilation and tortuosity tipped off the examiner that there may be something else at play masquerading as a common complication of diabetic retinopathy.
For this reason, it's important to keep other etiologies in mind, including paraproteinemias like WM and multiple myeloma 3. Waldenstrom Macroglobulinema-Associated Retinopathy.
Severe intraretinal hemorrhages are present along the arcades. OS: There is mild vessel tortuosity. As in the right eye, there is a neurosensory retina detachment with surrounding macular edema and focal laser scars.
There are several macro aneurysms along the arcades in addition to numerous intraretinal hemorrhages. Figure 2. Optical coherence tomography OCT : 1 year after initial presentation OD: There is a large fovea-involving, serous macular detachment with pockets of overlying intraretinal fluid.
OS: There is a moderately sized fovea-involving, serous macular detachment with minimal intraretinal fluid. Figure 3. Fundus fluorescein angiography: 1 year after initial presentation OD: There is early punctate hyperfluorescence distributed throughout the macula. There is early peri-foveal staining with surrounding hypofluorescence which remains stable into the late frames. OS: There is a similar appearance to the right eye with peri-foveal staining and diffuse punctate hyperfluorescence. Prominent blockage of fluorescein staining is seen due to flame hemorrhages in the inner retina.
Pertinent results included: White Blood Cell: 2. Figure 4. Figure 5. Treatment Patients with WM often have plasma IgM levels upwards of or more normal with significant serum hyperviscosity. Differential Diagnosis This case represents a significant diagnostic challenge. Blood ; Yang G. Blood ; — Mansour AM. Paraproteinemic Maculopathy. Ophthalmology ; American Cancer Society. Waldenstrom macroglobulinemia. Blood ; Reinhart WH.
Plasmapheresis for hyperviscosity syndrome in macroglobulinemia Waldenstrom and multiple myeloma: influence on blood rheology and the microcirculation. Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal hemodynamics in patients with Waldenstrom's macroglobulinemia. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial.
Lancet ; — Share this page:. OD: There is moderate vessel tortuosity. OD: There is a large fovea-involving, serous macular detachment with pockets of overlying intraretinal fluid.
OD: There is early punctate hyperfluorescence distributed throughout the macula.
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. The HPO collects information on symptoms that have been described in medical resources.
Waldenstrom Macroglobulinema-Associated Retinopathy
Ophthalmology and Visual Sciences. William E. Flanary, MD ; Thomas M. Meirick, BS; H. Culver Boldt, MD. The patient is a year-old male who presents with worsening vision in both eyes.
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Both cell types are white blood cells. WM is characterized by having high levels of a circulating antibody, immunoglobulin M IgM , which is made and secreted by the cells involved in the disease. WM is an "indolent lymphoma" i. The WM spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms. WM is a rare disease, with only about 1, cases per year in the United States. WM occurs more frequently in older adults.
Therefore the two entities are not synonymous. The incidence is 1, cases per annum in the United States. The median age of onset is years. A minority of cases occur in late adolescence. Most patients are asymptomatic at the time of diagnosis, which is often incidentally made during blood tests for an unrelated condition.