IgM Kappa Monoclonal Gammopathy Research Articles

#2996 Diffuse alveolar haemorrhage in antiphospholipid syndrome—a rare case

Abstract Background and Aims Diffuse alveolar haemorrhage (DAH) is a serious manifestation of diseases such as systemic lupus erythematosus (SLE) and, apparently in a paradoxical manner, antiphospholipid syndrome (APS). Inflammation resulting from the deposition of immune complexes in alveolar capillaries appears to contribute to the pathophysiology of DAH, SLE and APS. Symptoms include cough, dyspnoea, haemoptysis or fever. It is associated with a drop in haemoglobin, respiratory failure and diffuse infiltrates on imaging exams. Bronchoscopy is diagnostic. It is important to exclude infection as treatment includes high-dose corticosteroid therapy and other immunosuppressive drugs. We present a challenging case regarding the diagnostic and therapeutic approach to this pathology. Case report This is the case of a 52-year-old Caucasian female, with a history of SLE, APS, splenectomy due to thrombocytopenia, IgM Kappa monoclonal gammopathy and indolent non-Hodgkin lymphoma. She was medicated with prednisolone 5 mg and warfarin (target INR between 2 and 3). The patient was observed due to a 1-day history of fever, nasal obstruction and odynophagia, associated with progressively worsening fatigue. On examination, she was pale, eupnoeic, tachycardic, with bibasal rales and a hyperaemic oropharynx. Lab workup results were the following: haemoglobin 7 g/dL (11.7 g/dL 3 months before), VGM 71 fL, presence of schistocytes, leukocytes 13.7 G/L, neutrophils 11.1 G/L, PCR 4.6 mg/dL, platelets 170 G/L, INR 3.6, aPTT 45 sec, negative D-Dimers, urea 54 mg/dL, creatinine 1.4 mg/dL, LDH 431 IU/L, normal haptoglobin, negative Coombs test. In arterial blood gas analysis, pO2 was 61 mmHg and lactate was 5 mmol/L. Chest X-ray showed bilateral basal cotton-wool infiltrates and chest CT showed bilateral ground-glass pattern. The rest of the investigation included no complement consumption, negative anti-ds-DNA antibody, positive lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein antibodies, negative cryoglobulins and no evidence of progression of the lymphoproliferative disease. She was admitted to the intensive care unit due to suspicion of atypical/viral pneumonia vs. DAH. Oxygen therapy, empirical antibiotic therapy with ceftriaxone and clarithromycin and oral methylprednisolone 1 mg/Kg/day were started. She needed blood transfusion, although without visible blood loss. Bronchofibroscopy was performed, with bronchoalveolar lavage suggestive of DAH, so it was decided to start intravenous pulses of methylprednisolone, plasmapheresis, and intravenous immunoglobulin (IVIG). Warfarin was changed to unfractionated heparin. The patient had clinical, analytical and radiological improvement. Due to the lack of evidence of infection, antibiotics were stopped after 7 days. The patient was discharged under weaning corticosteroid therapy and monthly IVIG (during 5 months), without recurrence in the following year. Conclusion This is a rare case of oligosymptomatic DAH in a patient with SLE and APS. The literature currently available on DAH in the context of SLE or APS is scarce and its treatment is mainly dependent on the experience of each medical centre. Corticosteroid therapy is consensual, with greater variability in other corticosteroid-sparing therapies. In the case of patients with APS, anticoagulation is a challenge, and it is important to resume it as soon as the bleeding is controlled due to the risk of thrombotic events.

Waldenstrom's macroglobulinemia with peripheral neuropathy and favorable long-term treatment responses

Abstract Rationale: Waldenstrom's Macroglobulinemia (WM), is a rare hematological disorder with an indolent course that affects about 1 in 1,000,000 people over the age of 50. The two cases presented here highlight the favorable responses to targeted therapies and that such responses may show a longer progression-free survival than the standard regimens for WM (Dexamethasone + Rituximab + Cyclophosphamide and Bendamustine + Rituximab). Patient concerns: We report 2 Filipino patients with WM presenting with symptoms of peripheral nerve involvement characterized by numbness, dysesthesia and weakness. Diagnosis: Serum immunoelectrophoresis showed distinct bands in IgM and Kappa light chain channels, indicative of IgM kappa monoclonal gammopathy. Bone marrow aspirate flow cytometry showed a B-lymphoid population, bright expression of Kappa light chain surface immunoglobulin, all consistent with a B-cell neoplasm. Interventions: The first case received Dexamethasone + Rituximab + Cyclophosphamide. The second case was successfully treated with Rituximab + Bendamustine. Outcomes: The first case achieved complete remission for 9 years. However, in the 10th year of follow-up, there was recurrence of peripheral nerve symptomatology, which prompted a repeat course Rituximab monotherapy, with favorable response. The second case was successfully treated with Rituximab + Bendamustine over a 3-year course. Lessons: To the best of our knowledge, WM presenting with peripheral neuropathy with a long progression-free survival as described in these patients have not been reported before. The two cases highlight the potentially favorable responses to targeted therapies. Though the possibility of developing recurrence cannot be discounted, favorable outcomes with the use of the standard chemotherapies could still be expected.

Cytomegalovirus Retininis in a Patient with Waldenstrom Macroglobulinemia

A 62-years-old woman presented with microcytic hypochromic anemia, diffuse adenopathy, , and hepatosplenomegaly, was diagnosed as having Waldenst?m Macroglobulinemia by blood serum electrophoresis which detected a IgM-KAPPA monoclonal gammopathy, besides the results of immuno-phenotypic characteristics of neoplastic B-lymphocytes present in bone marrow positive for CD19, CD20, FMC7, CD79; and not reactive for CD23, CD5 and CD38. MYD88 mutation was absent. The patient underwent a week intermittent chemotherapy (oral scheme: Predinisone Session [CurrentTestPartID] mg and Chlorambucil 2 mg during 5 months) and then, without adequate therapeutic response, it was reset including intra-venous anti-CD20 monoclonal immunoglobulin (Rituximab, for 4 months). The patient had a good response to the therapy. However, almost a year after Rituximab scheme started, patient complained of sudden decrease of visual acuity (20/200) according to the Snellen chart with floaters, only in the left eye. CD4 T cell count was 205 cells/mm3, relatively reduced when compared to a health person because of the chronic use of immunosuppressant drugs and the down modulation due to the inflammatory stress state seen at a hematological lymphoproliferative disease. Fundoscopy findings were compatible with CMV retinitis , confirmed by CMV-DNA PCR in plasma samples with a high viremia (3.102 copies/mL). Plasma cytokines were measured to see the inflammatory response Intravenous Ganciclovir 500mg every 12 hours for 2 weeks was administered. Granulocyte colony-stimulating factor was used to manage neutropenia. Visual acuity improvement was observed (20/40).

Coexistence of Charcot‐Marie‐Tooth disease type 1A and anti‐MAG neuropathy

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate.

Leukocytoclastic Vasculitis in a Patient with Type 1 Cryoglobulinemia

Cutaneous manifestations of type 1 cryoglobulinemia are usually related to vascular occlusion by noninflammatory thrombosis; rarely is leukocytoclastic vasculitis seen in type 1 cryoglobulinemia. We report the case of a 64-year-old male who presented with isolated cutaneous leukocytoclastic vasculitis that was initially attributed to essential mixed cryoglobulinemia after thorough diagnostic evaluation. A lack of adequate clinical response to therapy prompted further investigation, including cryoprecipitate electrophoresis and immunofixation, which revealed an IgM kappa monoclonal gammopathy consistent with type 1 cryoglobulinemia. A renewed search for an underlying malignancy led to the discovery of early Waldenstrom's macroglobulinemia. Although leukocytoclastic vasculitis is more characteristic of mixed cryoglobulinemia, it can be a presenting manifestation of type 1 cryoglobulinemia.

Immunotactoid glomerulopathy with massive bone marrow deposits in a patient with IgM kappa monoclonal gammopathy and hypocomplementemia

A case of immunotactoid glomerulopathy with an amyloid-like material in the glomeruli and bone marrow is described. Clinically the patient was diagnosed as having severe nephrotic syndrome, hypocomplementemia, and IgM kappa monoclonal gammopathy. Immunotactoid glomerulopathy is an unusual cause of glomerulonephritis, characterized by Congo red[ndash ]negative, amyloid-like deposits in the glomeruli. This unusual case presentation shows that immunotactoid glomerulopathy may be a manifestation of systemic disease. This patient also presented with hypocomplementemia, an extremely rare associated finding that has been reported previously in only four cases of immunotactoid glomerulopathy. [copy ] 2001 by the National Kidney Foundation, Inc.

Xanthogranulomatose ⊙ nécrobiotique: manifestation cutanée d'une IgM monoclonale

Necrobiotic xanthogranulomatosis is a rare cutaneous disorder usually associated with monoclonal gammopathy. Most frequently, cutaneous lesions involve the face (periorbital region) and the trunk, and are characterized by indurated xanthomatous plaques and nodules. We describe a patient presenting with necrobiotic xanthogranulomatosis that was unusual, as it was associated with IgM kappa monoclonal gammopathy of undetermined clinical significance and because no periorbital involvement was observed. Necrobiotic xanthogranulomatosis should be distinguished from other cutaneous manifestations associated with plasma cell dyscrasias, such as normolipemic plane xanthoma. It can be associated with IgM gammopathy.

A cryoglobulin with cold agglutinin and erythroid stem cell suppressant properties

A 93-year-old woman presented with profound anemia (hematocrit 23% [0.23]); there was clumping of her red cells in test tubes and on peripheral blood smears. There was also a marked decrease in erythroid precursors in the bone marrow and reticulocytopenia in the peripheral blood. An IgM kappa monoclonal gammopathy was found in low concentration (approximately 1%) in her serum, and the cold agglutinins had a titer of 2560. However, the cold agglutinin titer of the supernatant after cryoglobulin precipitation was 40. Redissolving the cryoglobulin in the supernatant resulted in a cold agglutinin titer of 1280. Moreover, the addition of the patient's whole serum inhibited erythroid colony formation in culture. The inhibition was removed by cryoprecipitation of the cryoglobulin. The patient was given steroid therapy, to which she responded with reticulocytosis and an elevation of hematocrit. By 3 months, the cold agglutinin titer had fallen to 10. She remained well 4 years later. Whereas reports of cryoprecipitable cold agglutinins are rare, this case is unique because there have been no previous reports that these cold active proteins also have erythroid stem cell-suppressant properties.