The electronic publication OncologyLife has recently posted a very interesting article regarding the importance of defining, understanding, and treating clinically significant associations of having MGUS. If you are an MGUS patient it will be well worth your time for a complete read at this link.

Please allow me to also quote the author of the article, Sandra Mazzoni, DO, in the opening paragraph:

“It is critical to recall that monoclonal proteins can be produced by both plasma cells and B cells and identifying the source will determine the treatment in many cases. A referral to a center with multidisciplinary care is best practice to ensure appropriate workup in a timely manner.” 

MGUS types and variations include: 

Monoclonal Gammopathy of Dermatologic Significance (MGDS)

MGDS includes a variety of skin issues driven by the clonal B cell or plasma cell protein production and associated changes of the immune system.  Seeing a dermatologist for skin biopsies is essential in most cases. 

Cryoglobulin Vasculitis

Cryoglobulins are immunoglobulins in the blood that cool down core body temperature in the arms and legs. Type I (monoclonal) and type II (mixed with a monoclonal component) are associated with monoclonal gammopathy. Skin effects can include small spots with bleeding under the skin, purple colored spots or patches, skin ulcers, color change in fingers, skin tissue death, and skin ulcers. Treatment is either targeted to B cells or plasma cells depending on what is driving the monoclonal protein.

Scleromyxedema 

This is a condition associated most with IgG kappa monoclonal gammopathy. This is not scleroderma. Skin lesions are waxy, firm plaques or small, raised, tender bumps on the skin.  This condition can lead to heart block, difficulty of the heart to pump blood, swallowing difficulties, hoarseness, lung disease, kidney failure, and carpal tunnel. This is treated with  immunomodulatory drugs (IMiDs) like lenalidomide or pomalidomide and steroids. There is a role for proteasome inhibitors like bortezomb and autologous stem cell transplant in IMiD-refractory cases.

Dermato-neuro syndrome can develop which can cause death and is noted by a an ill feeling with a fever that can progress to confusion, memory loss, vertigo, stroke, psychosis, fatigue, convulsions and a coma.  Treatment consists of steroids, intravenous immunoglobulin (IVIG), and plasmapheresis (plasma exchange; PLEX).

TEMPI

TEMPI—or widened blood vessels on the skin, having too many red blood cells, having a monoclonal gammopathy, fluid buildup above the kidney, and the heart not pumping out fully oxygenated blood. —has an unclear mechanism. These patients respond well to plasma cell–directed therapies.

Schnitzler Syndrome

These hives/skin rash are driven by increased IL1. It is typically seen with IgM monoclonal gammopathy with systemic symptoms that include fever, arthritis, joint stiffness, bone pain, abnormal lymph node size, and an enlarged liver. The disease has an indolent course with a low-risk of progression to Waldenström or B-cell lymphoma. The rash is treated with IL1 inhibitors.

Sweet Syndrome

This is a fever and painful skin rash. Treatment of the rash is a combination of steroids and therapy targeted at either the B cell or plasma cell clone producing the monoclonal protein.

Pyoderma Gangrenosum

Most often associated with inflammatory bowel disease and arthritis, this causes large and painful ulcers and sores on the skin and has been reported in up to 20% of cases of IgA monoclonal gammopathy. These cases can progress to multiple myeloma, so patients should receive plasma cell–directed therapy. Unfortunately, these patients often prove to be refractory to treatment.

Editor's Note: Additional information about this condition includes the following, shared by an MGUS patient.

• Pyedorma gangrenosum happens in 5 person in 1 million / per year (chances = 1/200.000)
• We also know that MGUS represents 23% of the pyoderma gangrenosum cases with a prevalence of 60% of IGA, which means 15% of the PG have MGUS IgA. This means that 1 case of IgA MGUS + PG in 1 million/year is found.
• IgA happens in 20% of MGUS.
• MGUS has a prevalence of 3% in the population above 50. We can therefore speculate that around 1/500 person of the global population has IgA MGUS.
• In short, the likelyhood of having PG because you have MGUS IgA is really lower than 20%, even in a lifetime of 40 years, we are probably closer to 1 case / 2000 personns / year, so in your lifetime of 40 years the risk is 1/50

Monoclonal Gammopathy of Neurologic Significance (MGNS)

There exists a wide range of monoclonal protein–driven neurologic conditions. Presenting symptoms may include muscle weakness, neuropathy (sensory and/or motor), muscle atrophy, and poor muscle control that causes clumsiness. These cases should be assessed by both a hematologist and a neurologist where a typical workup will include a neurological assessment, imaging, biopsy, and laboratory tests. A bone marrow biopsy is essential in these cases for both diagnosis and to guide treatment.

Monoclonal Gammopathy of Renal Significance (MGRS)

Monoclonal gammopathy with above-normal protein in the urine and/or worsening kidney function requires a biopsy for diagnosis. The source of the monoclonal protein production with a bone marrow biopsy and advanced imaging (like an MRI, PET-CT scan, etc.) can be helpful.

Treatment is focused on stopping the M-protein while saving kidney function. Additional kidney tests can be helpful to determine the source of the issue. 

Monoclonal Gammopathy of Skeletal Significance

There is more evidence emerging regarding an association between monoclonal gammopathy and skeletal changes. With POEMS it is common to see bone lesions. The International Myeloma Working Group recommends bisphosphonate use in all cases of monoclonal gammopathy with osteopenia or osteoporosis.

Monoclonal Gammopathy of Hematologic Significance

Even small plasma cells or B-cell clones can alter the bone marrow environment and immune response, leading to different acquired blood disorders. These are complex conditions that warrant the help of a blood cancer expert.

Treatment is a combination of plasma cell-directed therapy and immunosuppression. Cyclosporine, with or without steroids, is the most used immunosuppression regimen. 

In short, if you are an MGUS patient, ensure that you are being seen by an expert and alert them to any additional symptoms you may be experiencing. You can connect with other patients with MGUS and caregivers by joining our MGUS/Smoldering Myeloma Chapter at the button below. 

Join MGUS & Smoldering Myeloma Chapter