Multiple Myeloma (Part 1) - Update on Epidemiology, Diagnostic Criteria, Systemic Treatment and Prognosis / Mieloma múltiplo (Parte 1) - Atualização sobre epidemiología, critérios diagnósticos, tratamento sistêmico e prognóstico

Abstract Multiple myeloma (MM) is a hematological malignancy characterized by unregulated and clonal proliferation of plasma cells in the bone marrow; these cells produce and secrete an anomalous monoclonal immunoglobulin, or a fragment of this, called M protein. The clinical manifestations of MM result from the proliferation of these plasmocytes, the excessive production of monoclonal immunoglobulin and the suppression of normal humoral immunity, leading to hypercalcemia, bone destruction, renal failure, suppression of hematopoiesis and humoral immunity, increasing the risk for the development of infections. The increase in life expectancy of the world population led to a concomitant increase in the prevalence of MM, a pathology that usually affects the elderly population. The aim of this review is to update the reader on epidemiology, diagnostic criteria, differential diagnosis with other monoclonal gam-mopathies, systemic treatment and prognosis of MM.

Resumo O mieloma múltiplo (MM) constitui neoplasia maligna de origem hematológica caracterizada pela proliferação desregulada e clonal de plasmócitos na medula óssea; estas células produzem e secretam imunoglobulina monoclonal anômala, ou um fragmento desta, denominado proteína M. As manifestações clínicas do MM decorrem da proliferação destes plasmócitos, da produção excessiva de imunoglobulina monoclonal e da supressão da imunidade humoral normal, levando à hipercalcemia, destruição óssea, insuficiência renal, supressão da hematopoiese e da imunidade humoral,aumentandooriscoparaodesenvolvimento de infecções. O aumento na expectativa de vida da população mundial levou a concomitante incremento na prevalência do MM, patologia que habitualmente acomete a população idosa. O objetivo desta revisão é atualizar o leitor sobre a epidemiologia, critérios diagnósticos, diagnóstico diferencial com outras gamopatias monoclonais, tratamento sistêmico e prognóstico do MM.

Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance / 中华血液学杂志

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.

Desde la pérdida de la fuerza hasta el compromiso sistémico: serie de casos del síndrome POEMS / From limb weakness to a systemic involvement: Poems syndrome case two report and review of the literature

El síndrome POEMS es un trastorno paraneoplásico raro y poco frecuente, que se presenta principalmente en la sexta década de la vida, caracterizado por el compromiso multisistémico con predominio de neuropatía desmielinizante. Abarca diversas y heterogéneas manifestaciones clínicas y su diagnóstico requiere un alto índice de sospecha. Se presentan dos casos de pacientes que consultaron por cuadros poco frecuentes en los que la pérdida de la fuerza orientó al acercamiento de una afectación multisistémica que concluyó con el diagnóstico de esta enfermedad(AU)

POEMS syndrome is a rare and infrequent paraneoplastic syndrome, which occurs mainly in the sixth decade of life, characterized by multisystem involvement with a predominance of demyelinating neuropathy, which encompasses diverse and heterogeneous clinical manifestations and whose diagnosis requires a high index of suspicion. We present two cases of patients who consulted due to unusual symptoms and whose loss of strength led to an approach due to multisystem involvement that concluded with the diagnosis of this disease(AU)

Co-occurrence of myeloid neoplasm and plasma cell neoplasm

ABSTRACT Co-occurrence of myelodysplastic syndrome (MDS) and plasma cell neoplasm in patients with no history of chemo and/or radiotherapy is rarely reported. Herein, we report a case of a female in her seventieth decade of life who was referred to the hospital for pancytopenia. The patient was asymptomatic and was doing well overall. Serum protein electrophoresis was remarkable for a lambda-restricted monoclonal protein (IgG) estimated at 1.8g/dL. Immunoglobulin G serum level was also elevated, and serum Kappa/Lambda free light chain ratio was decreased. At that time, a bone marrow biopsy showed myelodysplastic syndrome with excess blasts-2 (MDS-EB2) and a monoclonal plasma cell proliferation. Some studies have shown that patients with plasma cell neoplasm could be associated with an increased risk of developing MDS compared to the general population. Based on reviewing the literature, to our knowledge, the pathological mechanism of the co-occurrence of both diseases is not yet clear.

Progress of diagnosis and treatment of monoclonal gammopathy of neural significance / 白血病·淋巴瘤

Monoclonal gammopathy of neural significance (MGNS) belongs to the category of monoclonal gammopathy of clinically significance. It is an early-stage disease that mainly occurs in peripheral nerves and is not sufficient for the diagnosis of multiple myeloma or lymphoma. MGNS needs to be differentiated from neuropathies due to POEMS syndrome and light-chain amyloidosis; if necessary, nerve biopsy can be performed to clarify the relationship between peripheral nerve symptoms and lymphoplasmacytic disease. Treatment of MGNS is recommended to give intravenous gammaglobulin, plasma exchange and targeted anti-lymphoplasmacytic tumour therapy such as CD20 monoclonal antibody. Early recognition and intervention of MGNS, with multidisciplinary cooperation, will help to reduce the risk of malignancy and the incidence of disability.

Familial Waldenstrom macroglobulinemia: report of 6 cases and review of literature / 白血病·淋巴瘤

Objective:To investigate the familial inheritances, clinical features, treatments and outcomes of familial Waldenstrom macroglobulinemia (WM) patients.Methods:The clinical manifestations, laboratory examinations, diagnosis and treatments, and follow-up data of 6 familial WM patients who were admitted to Yancheng No.1 People's Hospital from June 2002 to July 2019 were retrospectively analyzed, and the literature was reviewed.Results:Among 6 WM patients, 4 patients had dizziness and fatigue at the onset, 1 patient had recurrent low-grade fever and abnormal sweating as the first manifestations, 1 patient was hospitalized due to pulmonary infection, and WM was found later. Two brothers of the patients were diagnosed with WM, another 2 brothers of the patients had IgM-type monoclonal gammopathy of undetermined significance (MGUS) during the physical examination. All the 6 patients were middle-aged/elderly men, with a median age of 63 years old (51-70 years old). The median follow-up time were 71.5 months (4-217 months), and by the end of the follow-up (June 2020), 2 cases died of pulmonary infection, and 1 of them developed acute myeloid leukemia; the other 4 cases were in regular chemotherapy. Two IgM-MGUS patients were followed up without symptoms.Conclusions:WM patients have familial aggregation, and their clinical manifestations are highly heterogeneous. Patients with family history may have poor prognosis. It is necessary to strengthen the awareness of WM and family history screening.

Tuberculosis presenting as proliferative glomerulonephritis with monoclonal immunoglobulin deposits / Tuberculosis que se presenta como glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal

Abstract Proliferative glomerulonephritis with monoclonal immunoglobulin deposits is defined as membranoproliferative glomerulonephritis like injury with monotypic Ig deposits restricted to a single light chain isotype.Here we present a patient who presented with hypocomplementemia and nephrotic syndrome, who was initially diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin deposits. He developed disseminated tuberculosis after a brief course of immunosuppression. Successful treatment of tuberculosis resulted in the complete remission of glomerular disease and the disappearance of monoclonal protein. Hence, we believe he had Tuberculosis-related proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Treatment strategies have not been structured due to the rarity of the condition and lack of randomized trials. However, expert opinion suggests clone-based therapy. proliferative glomerulonephritis with monoclonal immunoglobulin deposits with a benign course without clone-based therapy has been reported. Patients seldom respond to classic immunosuppressants. Even some cases experience slowly progressive disease under angiotensin converting enzyme inhibition alone. There are also cases secondary to viral infections. Our case and the particular "benign" cases lead us to an intriguing proposition that proliferative glomerulonephritis with monoclonal immunoglobulin deposits might not be a single disease. A subset of patients may be experiencing infection-related or post-infectious glomerulonephritis presenting as proliferative glomerulonephritis with monoclonal immunoglobulin deposits.

Resumen La lesión similar a la glomerulonefritis membranoproliferativa con depósitos de Ig monotípicos restringidos a un isotipo de cadena ligera única se conoce actualmente como glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal. A continuación presentamos a un paciente que presentó hipocomplementemia y síndrome nefrótico, al que inicialmente se le diagnosticó glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal. Desarrolló tuberculosis diseminada después de un breve curso de inmunosupresión. El tratamiento exitoso de la tuberculosis dio como resultado la remisión completa de la enfermedad glomerular y la desaparición de la proteína monoclonal. Por lo tanto, creemos que tenía glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal relacionada con tuberculosis diseminada. Las estrategias de tratamiento no se han estructurado debido a la rareza de la afección y la falta de ensayos aleatorios. Sin embargo, la opinión de los expertos sugiere una terapia basada en clones. Se ha informado de glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal con un curso benigno sin terapia basada en clones. Los pacientes rara vez responden a los inmunosupresores clásicos. Incluso algunos casos experimentan una enfermedad de progresión lenta solo con la inhibición de la enzima convertidora de angiotensina. También hay casos secundarios a infecciones virales. Nuestro caso y los casos "benignos" particulares nos llevan a la propuesta intrigante de que la glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal podría no ser una sola enfermedad. Un subgrupo de pacientes puede estar experimentando glomerulonefritis postinfecciosa o relacionada con una infección que se presenta como glomerulonefritis proliferativa con depósitos de inmunoglobulina monoclonal.

Monoclonal gammopathy of undetermined significance clinic during the coronavirus disease-19 pandemic: caring for the vulnerable in an academic medical center

Background: Patients with monoclonal gammopathy of undetermined significance (MGUS) have clinical features including older age, presence of medical comorbidities, susceptibility to infections, and thrombotic tendencies which are relevant when assessing their risk during the coronavirus disease (COVID-19) pandemic. Objective: To study the vulnerability of patients with MGUS during the COVID-19 pandemic, we assessed the local management of MGUS patients and their clinical outcomes. Methods: Retrospective chart reviews were performed for all patients with MGUS seen at a university medical center clinic (2014-2020). Results: A total of 228 MGUS patients were included; 211 patients are alive, 7 patients died before the pandemic, and 10 patients died since the pandemic declaration. The mean age and the overall survival (OS) of the patients who died before versus during the pandemic were 83.0 versus 75.2 years, p = 0.4, and OS 40.6 versus 53.2 months, p = 0.3, respectively. One patient died of COVID-19. Nine patients had venous thromboembolisms (VTE), all of which occurred before the pandemic onset. Conclusions: There were no significant differences found in the mean age or OS of the MGUS patients who died before versus after the pandemic onset. An increase in VTE rates was not seen. Study results are limited by small patient numbers.

Patologías cutáneas asociadas a gammapatías monoclonales: ¿qué sabemos hasta ahora? / Dermatological manifestations of monoclonal gammopathies

Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.

Application of capillary electrophoresis in the diagnosis and differential diagnosis of benign and malignant monoclonal gammopathies / 中华检验医学杂志

Objective:To evaluate the value of capillary electrophoresis in the diagnosis and differential diagnosis of benign and malignant monoclonal gammopathies (MGs).Methods:A retrospective analysis of the capillary electrophoresis test results of 2 445 newly diagnosed patients at the Affiliated Hospital of Qingdao University from January 2016 to June 2020 was carried out. Capillary zone electrophoresis and immunosubtractive assay were used to detect serum monoclonal protein (MP). The clinical diagnosis and other information of the patients were collected from the clinical database of the Affiliated Hospital of Qingdao University. Kruskal-Wallis rank sum test was used to compare the different amount of monoclonal protein among multiple groups. Receiver operator characteristic curve (ROC) was used to analyze the diagnostic sensitivity and specificity of the monoclonal protein of each type. Youden index was used to calculate the cut-off values.Results:Among the 2 445 patients, 1 183 were positive for monoclonal protein, of which 944 cases were diagnosed as malignant MG, 174 were monoclonal gammopathy of undetermined significance (MGUS), and 65 cases were monoclonal gammopathy of renal significance (MGRS). The percentages of M protein types from high to low is immunoglobulin G(IgG)-κ, IgG-λ, IgA-λ, IgA-κ, free λ light chain, free κ light chain, IgM-κ, double clone, and IgM-λ. The levels of MP of IgG, IgA, IgM and FLC in the malignant MG group were all higher than those in the MGUS group, with statistical significance( P<0.01). The MP levels of IgG and IgA types in malignant MG group were higher than that in MGRS group ( P<0.01). ROC curve analysis showed that the MP of IgG, IgA, IgM and FLC types had good diagnostic efficacy for malignant MG ( P<0.01), and their AUC values were 0.947 (95 %CI 0.926-0.968), 0.930 (95 %CI 0.895-0.966), 0.844 (95 %CI 0.722-0.967) and 0.865 (95 %CI 0.781-0.950), respectively. For IgG, the cut-off value was 14.24 g/L, and the diagnostic sensitivity and specificity were 88.5% and 90.1%, respectively. The cut-off value of IgA was 8.88 g/L, and the sensitivity and specificity of IgA were 87.9% and 81.4%, respectively. For IgM, the cut-off value was 26.93 g/L, and the sensitivity was 64.4% and the specificity was 90.9%. For FLC, the cut-off value, diagnostic sensitivity, and specificity was 7.08 g/L, 85.9%, and 77.8%, respectively. Conclusions:Capillary electrophoresis immunotyping technique can be used to diagnose malignant MG such as multiple myeloma (MM) and non-Hodgkin′s lymphoma (NHL), as well as to screen and track diseases like MGUS and MGRS. Serum MP level can be used to distinguish malignant MG from benign MG effectively.

Monoclonal Gammopathy of Renal Significance (MGRS): Prospects for Treatment in Integrated Chinese and Western Medicine / 中国结合医学杂志

Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.

The 474th case: anemia, ostealgia, proteinuria / 中华内科杂志

A 49-year-old woman was admitted to hospital with intermittent dizziness and fatigue for 7 years. The symptoms were aggravated and accompanied by bone pain for more than 4 months. She was referred to our hospital. Laboratory tests and imaging findings suggested that acquired Fanconi Syndrome (FS) was associated with smoldering multiple myeloma (MM). Renal biopsy and electron microscopy confirmed the diagnosis of proximal light chain tubular disease (LCPT). LCPT causes proximal tubular dysfunction, which is characterized by the cytoplasmic crystal deposition usually kappa monoclonal light chain in the proximal tubule. MM with FS and LCPT is less common in clinical practice because it is difficult to diagnose. This is a typical case focusing on the differential diagnosis of monoclonal gammopathy of renal significance(MGRS) such as LCPT and plasma cells diseases.

Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia

BACKGROUND: Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.METHODS: We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.RESULTS: Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138⁺/CD38⁺/CD19⁺/CD45⁺/CD56⁻).CONCLUSIONS: Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

Henoch-Schönlein purpura nephritis associated with monoclonal gammopathy of renal significance: a case report

Monoclonal gammopathy of renal significance (MGRS) can present with different morphologic features and lead to kidney failure. The Henoch-Schönlein purpura nephritis (HSPN) that cannot be relieved by treatment with glucocorticoid and immunosuppressive agents suggests the presence of monoclonal gammopathy in adult patients. The present study reports on a single case of HSPN associated with IgA-κMGRS. The patient who suffered from recurrent skin purpura for 6 months and nephrotic syndrome for 2 months was admitted to our hospital. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy indicated a Henoch-Schönlein purpura nephritis (HSPN, ISKDC classified as type III) with positive staining with κ-light chain in the glomeruli and renal tubular epithelial cells. Furthermore, skin biopsy showed leukocytoclastic vasculitis and negative staining for Congo red and light chain. Given both the renal and cutaneous involvement, the patient was considered to have HSPN associated with IgA-κMGRS. The patient experienced an exacerbation in his purpura-like lesions and clinical status after treatment with glucocorticoid and immunosuppressive agents. Consequently, the patient was put on a regimen that included dexamethasone (20 mg on the 1st, 4th, 8th, and 11th days of each month, iv) and bortezomib (2.4 mg on the 1st, 4th, 8th, and 11th days of each month, iv). Eight weeks after treatment, he had complete resolution of his cutaneous purpura and his biochemical parameters improved. The latent presence of MGRS in cases of HSPN should be considered in adult patients. Increased cognizance and correct treatment options could improve patient outcomes.

Dysphagia as a Clinical Manifestation of Monoclonal Gammopathy of Undetermined Significance: A Case Report / 대한연하장애학회지

Swallowing can be affected by a variety of systemic diseases. The etiology of dysphagia in the geriatric population is usually overlooked due mainly to a presumed diagnosis of presbyphagia or difficulty in revealing the direct cause. On the other hand, dysphagia can be a meaningful clinical sign of premalignant systemic disease. A 78-year-old man, without any prior medical or family history, was admitted with the chief complaint of dysphagia with recent aspiration pneumonia. Instrumental swallowing tests revealed a severe degree of dysphagia due to decreased laryngopharyngeal sensation and weakness of the pharyngeal constrictor muscles. Extensive workup, including electromyography and laboratory tests, revealed severe sensorimotor peripheral polyneuropathy related to monoclonal gammopathy. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma, which is characterized by the proliferation of monoclonal proteins. These conditions are often associated with peripheral polyneuropathy, ataxia, and sometimes even muscle weakness. Although dysphagia can occur in other systemic disorders, such as vasculitis or paraneoplastic syndrome-related malignancies, there are few reports of dysphagia related to MGUS. The patient was followed up for three years. The MGUS showed no further progression, but the patient showed no improvement, indicating a protracted clinical course and poor prognosis when dysphagia is related to MGUS.

Anti-myelin-associated glycoprotein antibody positive IgM monoclonal gammopathy related peripheral neuropathy: 11 cases and literature review / 中华血液学杂志

Objective@#To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) .@*Methods@#Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed.@*Results@#Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström’s macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved.@*Conclusions@#Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.

Anti-myelin-associated glycoprotein antibody positive IgM monoclonal gammopathy related peripheral neuropathy: 11 cases and literature review / 中华血液学杂志

Objective: To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) . Methods: Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed. Results: Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström's macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved. Conclusions: Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.

Síndrome de POEMS, el desafío diagnóstico de un caso infrecuente / POEMS syndrome, the diagnostic challenge of an infrequent case / Síndrome de POEMS, o desafio diagnóstico de um caso infrequente

Se reporta el caso de un hombre de 45 años con síntomas y signos consistentes con el Sindrome de POEMS (del inglés: polineuropatía, organomegalia, endocrinopatía, gammapatía monoclonal y cambios dérmicos), un raro desorden paraneoplásico. El mismo contaba con antecedentes de tabaquismo, hipotiroidismo y últimamente había perdido 20 kg de peso. Se destaca que una historia clínica y revisión detallada seguida de estudios de laboratorio, radiología y biopsia de médula ósea, entre otros, son herramientas necesarias para reconocer los componentes de este síndrome y no demorar el diagnóstico. El paciente presentó 2 criterios obligatorios (gammapatía monoclonal y neuropatia periférica sensitivo-motora), un criterio mayor (lesión ósea) y varios criterios menores (desórdenes endocrinos, manifestaciones cutáneas, organomegalia). Actualmente se encuentra bajo supervisión hematológica y continúa su seguimiento neurológico, lo que muestra una buena respuesta a la terapia específica. Las enfermedades raras como este síndrome resultan un desafío diagnóstico para los profesionales de la salud.

The case of a 45 - year- old- man whose symptoms and signs were consistent with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes), a rare paraneoplastic disorder, has been reported. He had a previous history of smoking, hypothyroidism and a 20 kg weight loss. It was emphasized that a detailed clinical history and examination followed by laboratory and radiological studies and bone marrow biopsy, among others tests, were necessary in order to recognise the components of this syndrome and not to delay the time of diagnosis. This patient had two mandatory criteria (monoclonal gammopathy and sensorimotor polyneuropathy), one major criterion (bone lesion) and several minor criteria (endocrine disorders, cutaneous manifestations, organomegaly). He is currently under the supervision of the doctors of the hematology department and continues neurological follow-up, having a good response to the specific therapy. Rare diseases like this syndrome are a diagnostic challenge for health professionals.

Informa-se o caso de um homem de 45 anos com sintomas e sinais compatíveis com a Síndrome de POEMS (do inglês: polineuropatia, organomegalia, endocrinopatia, gamopatia monoclonal e alterações cutâneas), um distúrbio paraneoplásico raro. O homem tinha antecedentes de tabagismo, hipotiroidismo e ultimamente tinha perdido 20 kg de peso. Enfatizamos que um prontuario médico e exame detalhado, seguido de estudos de laboratório e radiológicos, e uma biópsia de medula óssea, dentre outros, são ferramentas necessárias para reconhecer os componentes desta síndrome e não demorar o tempo de diagnóstico. Nosso paciente apresentou dois critérios obrigatórios (gamopatia monoclonal e neuropatia periférica sensório-motora), um critério maior (lesão óssea) e vários critérios menores (anormalidades endócrinas, alterações cutâneas, organomegalia). Encontra-se atualmente sob supervisão hematológica e continua seu seguimento neurológico, mostrando uma resposta boa à tera,pia concreta. Doenças raras como essa síndrome são um desafio diagnóstico para os profissionais da saúde.

Clinical features, treatment and follow-ups of Sj(o)gren's syndrome-associated monoclonal gammopathy / 中华风湿病学杂志

Objective To investigate the clinical characteristics,immunological features,treatment and follow-ups of Sj(o)gren's syndrome-associated monoclonal gammopathy (SS-MG).Methods A retro-spective,case-control study was conducted for 18 cases diagnosed with SS-MG and 36 age-and sex-matched non-MG-SS patients from Janurary 2010 to Janurary 2017 in Peking University People's Hospital.The clinical and laboratory features,treatment and follow-ups were recorded and compared.Comparisons between groups were made using t test for normally distributed numerical data,Mann-Whitney U test for non-normally distributed numerical data,and Pearson Chi-square,continuity correction or Fisher's exact tests for categorical data.Results SS patients,when complicated with MG,had significantly increased level of TP [(78± 11) g/L,(71±10) g/L,t=-2.382,P=0.021] and erythrocyte sedimentation rate (ESR) [52.5(45.3) mm/1 h,33.0(42.5) mm/1 h,Z=-2.179,P=0.029],higher prevalence of urine NAG positivity [75％(9/12),28％(7/25),x2=7.298,P=0.007],hypoglobulinemia [33％(6/18),3(1/36),x2=7.407,P=0.006] and thrombotic events [17％(3/18),0％(0/36),P=0.033],and less previous exposure to glucocorticoid [22％(4/18),64％(23/36),x2=8.333,P=0.004],compared to the control group.Primary SS patients complicated with MG had significantly higher ESSDAI [26.0(25.0),12.0 (9.0),Z=-2.724,P=0.006] and Clin EULAR Sj(o)gren's syndrome disease activity index (ESSDAI) [24.0(25.0),10.5 (10.0),Z=-2.523,P=0.011].Among the 18 patients,2 were diagnosed with multiple myeloma,1 was diagnosed with non-Hodgkin lymphoma,and the left were diagnosed as MG of undetermined significance (MGUS).Ten patients were followed up,among whom 2 patients with MGUS experienced increased levels of M protein,newly developed genetic abnormalities,and renal involvement.Conclusion SS patients may be complicated with MG.MGUS is the most common form.However,malignant hematologic disorders are revealed as well.In SS patients with high serum TP and ESR,hypoglobulinemia,tubulointerstitial kidney involvement and unexplained thrombotic events,especially in those with high disease activity,so MG should be an alert for further work-ups,monitoring and treatment.

Enfermedad renal por depósito idiopático de cadenas livianas. Caso clínico / Kidney involvement in idiopathic light chain disease. Report of one case

El Mieloma Múltiple (MM) es la gammapatia monoclonal (GM) que más frecuentemente compromete la función renal, no obstante, un número creciente de enfermedades renales asociadas a GM están siendo reconocidas. Las GM son un conjunto de entidades caracterizadas por la producción anómala y secreción a la sangre de una inmunoglobulina (Ig) monoclonal (de un mismo clon de células plasmáticas) o un fragmento de la misma (cadenas pesadas, ligeras o ambas) que puede depositarse en los órganos de forma organizada como cristales, fibrillas o microtúbulos, o de forma no organizada (granular). Esta Ig llega a depositarse principalmente en el riñón, no sólo porque es un órgano muy vascularizado, sino también porque el túbulo renal tiene un papel predominante en el metabolismo de las Igs. El diagnóstico del compromiso renal ha sufrido cambios en las últimas décadas, siendo cada vez más certero debido al desarrollo e implementación rutinaria de distintas técnicas de laboratorio (tinciones con anticuerpos específicos contra cadenas ligeras kappa y lambda, estudio con microscopia electrónica (ME) y el desarrollo de técnicas cada vez más sensibles para detectar el componente monoclonal en sangre u orina). El compromiso renal en estas patologías frecuentemente se asocia a GM malignas, generalmente asociadas a depósitos de cadenas ligeras. Cada vez son más los casos de disfunción renal asociados a GM, y en muchos de estos es evidente el progreso a enfermedad renal terminal y con altas tasas de recurrencia después del transplante renal.

Multiple myeloma (MM) is the monoclonal gammopathy (MG) that most frequently compromises renal function; however, a growing number of renal diseases associated with monoclonal gammopathies are being recognized. Monoclonal gammopathies (MG) are a set of entities characterized by the abnormal production and secretion into the blood of a monoclonal immunoglobulin (Ig) from a single clone of plasma cells or a fragment thereof (heavy, light chains orboth) which can be deposited in the organs in an organized way such as crystals, fibrils or microtubules, orin an unorganized (granular) form. This Ig is mainly deposited in the kidney, not only because it is a very vascularized organ, but also because the renal tubule plays a predominant role in the metabolism of Igs. The diagnosis of renal involvement has undergone changes in the last decades, being more and more certain due to the development and routine implementation of different laboratory techniques (stains with specific antibodies against kappa and lambda light chains, study with electron microscopy (EM), development of increasingly sensitive techniques for detecting the monoclonal component in blood or urine). Renal involvement in these pathologies is often associated with malignant MG, generally associated with light chain deposits. Increasingly, there are cases of renal dysfunction associated with MG, and progression to terminal renal disease and high rates of recurrence after renal transplantation are evident in many of these.