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Sneddon‐Wilkinson (SW) disease is rare condition which typically occurs in the context of a monoclonal immunoglobulin and treatment options have not been well studied. Here we present a case of a 65‐year‐old female with SW with underlying, otherwise indolent, lymphoplasmacytic lymphoma (LPL) with an IgA paraprotein, who achieved a complete skin remission with the administration of the Bruton Tyrosine Kinase inhibitor (BTKi), acalabrutinib. [ABSTRACT FROM AUTHOR]

AbstractIsolated hypogammaglobulinemia (IH) is an electrophoretic pattern that can be encountered on serum protein electrophoresis (SPEP) and is defined as a decreased but morphologically normal γ-globulin fraction with normal α- and β-globulin fractions. SPEP is mainly used to detect monoclonal proteins which are usually observed as additional peaks in the electropherogram. However, they may also be more discretely present in a significant proportion of patients presenting with IH. Therefore, we aimed to evaluate i) via both retrospective and prospective analysis to what extent paraproteins as identified by immunofixation are present in patients demonstrating IH on SPEP and ii) whether other parameters may predict their presence in IH-patients. For this purpose, we first reviewed historic SPEP- and immunofixation results in our tertiary hospital and determined paraprotein prevalence in this retrospective cohort. This analysis showed immunofixation was requested in only 519/3938 (13.2%) historic IH-results with 52/519 (10%) patients demonstrating paraproteins. Next, various laboratory parameters were compared between paraprotein-positive and -negative patients and subjected to logistic regression models but regrettably, no parameter could be retained as promising predictor of paraproteins. Lastly, to confirm paraprotein prevalence seen in the historical query, we conducted a six-month prospective analysis during which immunofixation was requested more frequently in IH-cases during routine diagnostics and which showed paraproteins to be present in 20/83 (24.1%) of IH-patients. Hence, as up to 24% of patients with IH may harbour paraproteins, one should consider performing follow-up analyses (e.g. immunofixation, urine electrophoresis and/or free light chain analysis) for all IH-cases identified via SPEP. [ABSTRACT FROM AUTHOR]

Background/Objectives: Monoclonal gammopathies, such as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM), are conditions marked by the overproduction of specific monoclonal proteins. Patients with these conditions are known to have a higher risk of fractures compared to the general population, yet there are no established guidelines for assessing or managing their skeletal health. The Trabecular Bone Score (TBS), which can be calculated from DXA images of the lumbar spine, provides additional insights into bone microarchitecture. Methods: This study aimed to determine whether TBS can serve as a supplementary tool in assessing bone loss in MGUS and SMM patients. Conducted from 2020 to 2023, the study involved 148 participants—74 diagnosed with a myeloma precursor state and 74 healthy controls—who underwent simultaneous DXA and TBS measurements. Results: The results indicated a weak positive correlation (R = 0.405) between DXA and TBS T-scores, suggesting that other factors may influence the measurements. When analyzed separately, the correlations remained weak for both MGUS (R = 0.250) and SMM (R = 0.485). Interestingly, discrepancies were noted in T-score classifications; for instance, a patient classified as normal via DXA could be deemed osteopenic or osteoporotic with TBS. Conclusions: Overall, the findings suggest that incorporating TBS alongside DXA can enhance the accuracy of bone density assessments, facilitating earlier diagnosis and treatment initiation for osteoporosis in asymptomatic patients with monoclonal gammopathies. [ABSTRACT FROM AUTHOR]

Background: The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified. Methods: For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records. Results: Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA). Conclusions: In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by unregulated monoclonal proliferation in the bone marrow. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant conditions that can progress to MM. Identifying etiological risk factors for MM and its precursor diseases is crucial for prevention. Obesity, diet, vitamin D levels, and gut microbiota alterations have been identified as lifestyle factors affecting MM and MGUS risk. Upon disease onset, treatment strategies aim to reduce disease burden, enhance prognosis, and optimize patients' quality of life. Nutrition and body weight have been shown to affect disease progression and treatment outcomes. MM patients often present with vitamin D, vitamin B12, and folate deficiencies, which worsen disease prognosis. High body mass index is linked to increased death rates among MM patients and an increased risk of MGUS transformation to MM. Gut microbiota has also been associated with disease progression and response to treatment. This literature review aims to summarize the available evidence regarding the impact of nutrition and nutritional status on MM patients beyond prevention, highlighting the significance of gut microbiome and dysbiosis in MM progression. [ABSTRACT FROM AUTHOR]

Abstract Antiphospholipid syndrome (APS), cryoglobulinemia, and monoclonal gammopathies are variably accompanied by thrombotic complications. We describe a patient with recurrent skin microvascular thrombosis, APS, cryoglobulinemia, marginal zone lymphoma, and IgMκ monoclonal gammopathy, responsive to chemoimmunotherapy. The cryoglobulin fraction contained the IgMκ paraprotein, while antiphospholipid antibodies (aPL) were predominantly in the cryosupernatant. A retrospective analysis of aPL‐positive patients in our institution showed that 8.1% co‐expressed monoclonal gammopathy. These overlap patients had thrombotic complications and most had recurrences. Patients with multiple gammopathies of thrombotic significance may have several autoantibodies and constitute a high‐risk group.

Abstract Background Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. Case presentation a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. Conclusions Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Abstract Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free light chain (FLC) analysis. Alerted by two index cases with clinical impact due to failure of the FLC analysis to indicate a disease progression, we aimed to identify any clinical consequences due to known differences between FLC analysis methods. We applied two FLC analysis methods (Freelite Binding Site [FBS] and N‐Latex Siemens [NLS]) on all patients with MM and monoclonal gammopathy of uncertain significance diagnosed/followed up at Södra Älvsborg Hematology Unit, from April to December 2022. From a total of 123 patients with malignant plasma cell disorder, we identified five cases (4.1%) where solely the FBS method, as opposed to NLS, urine and serum electrophoresis, could support diagnosis or detect progression. The consequences of this discrepancy included not only change of diagnosis or delayed therapy but also change of treatment. Our findings indicate that a stronger awareness of the potential weaknesses of different FLC methods is needed, which calls for a closer collaboration between clinical chemists and hematologists.

Abstract Background Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis. Case presentation A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis. Conclusions MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes. [ABSTRACT FROM AUTHOR]

Background Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study. Methods Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed. Results Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%). Conclusion Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (MoAbs) targeting several cellular receptors have significantly improved the prognosis of multiple myeloma (MM). Their high effectiveness and safety raise the question of whether earlier therapeutic intervention in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) influences the natural course of the disease. MM is preceded by clinically recognized conditions such as MGUS and SMM. Numerous studies are investigating the disease biology and immune profile of SMM and MGUS to unravel the intricate relationship between immunosurveillance and disease progression. The standard approach to MGUS and SMM remains close observation. Early studies indicate benefits in terms of progression or even survival for promptly treating high-risk SMM patients. Ongoing debates are focused on which patients with SMM and MGUS to treat, as well as on determining the optimal therapeutic approach. The first approach aims to cure by attempting to eliminate the pathological clone, while the second approach is preventive, aiming to manage disease progression to active MM and restore the immune system. In this review, we focus on the available and emerging data on early treatment, particularly with MoAbs alone or in combination with other therapies, in SMM and MGUS patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin- 18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases. [ABSTRACT FROM AUTHOR]

Background: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. Case presentation: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. Conclusions: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease. [ABSTRACT FROM AUTHOR]

Background: Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis. Case presentation: A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis. Conclusions: MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy‐related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy‐related peripheral nervous system involvement. [ABSTRACT FROM AUTHOR]