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Monoclonal Gammopathy of Undetermined Significance

Author/s: 
S. Vincent Rajkumar, Shaji Kumar

Monoclonal gammopathy of undetermined significance (MGUS) is a common premalignant plasma-cell proliferative disorder that is present in approximately 5% of the general population over the age of 50 years.1-4 This disorder is important not only because it is the precursor to plasma-cell cancers, including multiple myeloma, solitary plasmacytoma, and Waldenström’s macroglobulinemia, but also because it is causally related to numerous serious nonmalignant disorders, collectively referred to as monoclonal gammopathy of clinical significance (MGCS).5 MGUS is characterized by a limited yet monoclonal proliferation of plasma cells secreting abnormal levels of immunoglobulins (antibodies) that are identical to each other, with the same amino acid sequence, referred to as monoclonal (M) proteins.6 These secreted M proteins are best appreciated as fully functioning human antibodies present in high concentrations that fortunately lack affinity to self-antigens (autoantibody characteristics) in most persons. As a result, MGUS remains asymptomatic in the absence of malignant transformation in most people. However, there is potential for serious harm if the M protein has or develops affinity for one or more organs in the body, resulting in MGCS.

Keywords 
Paraproteinemias multiple myeloma Monoclonal Gammopathy of Undetermined Significance

Diagnosis and Management of Monoclonal Gammopathy of Undetermined Significance: A Review

Author/s: 
Yuxin Liu, Anna L Parks

Importance: Nearly 5% of adults have the precursor malignant condition monoclonal gammopathy of unknown significance (MGUS). Management centers on differentiating MGUS from more serious conditions to determine additional diagnostic testing, monitoring, and potential therapy.

Observations: MGUS is defined by the absence of end-organ damage or symptoms, a small amount of monoclonal immunoglobulin (M protein), and low volume of plasma cells. MGUS must be distinguished from overt malignant diseases like multiple myeloma (MM), immunoglobulin light-chain (AL) amyloidosis, and monoclonal gammopathy of clinical significance (MGCS), all of which cause organ damage or symptoms. Although testing for M proteins is often prompted by clinical findings (eg, osteoporosis or autoimmune disease), recent evidence from screened populations suggests that previous MGUS disease associations were likely overestimated and that testing for M proteins should be reserved for when malignant disease or MGCS is suspected. Risk of progression to malignant disease ranges from 0.5% to 1%, meaning most patients have indolent disease. Guideline-concordant management of MGUS is determined by predicted risk of progression to malignant disease, which depends on subtype of immunoglobulin, M protein concentration, and free light chain ratio. Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring. Intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals. Advanced molecular testing may improve on current risk stratification to target monitoring and treatment to those with highest risk of malignant progression and avoid overtreatment of those with low-risk disease. Management will also be informed by results of several clinical trials to clarify the risks and benefits of screening, optimal monitoring strategy, predictors of progression, and potential preventive or curative therapies.

Conclusions and relevance: Evidence-based management of MGUS currently rests on separating clinically indolent from high-risk precursor disease. Research using novel detection methods, incorporating molecular testing into risk stratification, and evaluating screening, monitoring, and therapeutic or lifestyle interventions has the potential to improve outcomes.

Keywords 
Monoclonal Gammopathy of Undetermined Significance

Snake Envenomation

Author/s: 
Seifert, S. A., Armitage, J. O., Sanchez, E. E.

Snake envenomation represents an important health problem in much of the world. In 2009, it was recognized by the World Health Organization (WHO) as a neglected tropical disease, and in 2017, it was elevated into Category A of the Neglected Tropical Diseases list, further expanding access to funding for research and antivenoms.1 However, snake envenomation occurs in both tropical and temperate climates and on all continents except Antarctica. Worldwide, the estimated number of annual deaths due to snake envenomation (80,000 to 130,000) is similar to the estimate for drug-resistant tuberculosis and for multiple myeloma.2,3 In countries with adequate resources, deaths are infrequent (e.g., <6 deaths per year in the United States, despite the occurrence of 7000 to 8000 bites), but in countries without adequate resources, deaths may number in the tens of thousands. Venomous snakes kept as pets are not rare, and physicians anywhere might be called on to manage envenomation by a nonnative snake. Important advances have occurred in our understanding of the biology of venom and the management of snake envenomation since this topic was last addressed in the Journal two decades ago.4 For the general provider, it is important to understand the spectrum of snake envenomation effects and approaches to management and to obtain specific guidance, when needed.

Keywords 
Animals Humans Snake Bites Elapidae
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