My husband is 38 years old South Asian American and was in perfectly good health even just three or four months ago. But in the middle of April, he was complaining about a tingling sensation in his right big toe. A few days later he told me he felt the tingling in left foot too. He has lost his appetite to a certain degree and also lost some weight .
I suggested him to visit his GP. But he was not giving attention because that time it is coming and going. But after a few weeks the tingling sensation is spread into both feet and became continuous. Severe burning sensation and difficulties in walking finally alarmed him. Now he has lost his balance in walking to a large extent .
A prominent neurologist in New York conducted a nerve conduction test and he has been diagnosed with severe peripheral neuropathy (PN). So his neurologist prescribed many blood tests on 3rd June. We received partial test results after a week and on our 3rd visit to the neurologist, he said my husband has severe vitamin B12 deficiency and also Lyme disease. His high IgA is most likely caused by Lyme disease. He also referred my husband to a internal medicine doctor and he put my husband on doxycycline for treating Lyme disease and gave a Vitamin B12 shot .
Today we received his full blood test report. It is showing no monoclonal protein (M-protein, M-spike) in serum protein electrophoresis (SPEP). It is written in the comment section that "The SPE pattern appears essentially unremarkable. Evidence of monoclonal protein is not apparent".
But the immunofixation is showing IgA monoclonal protein with lambda light chain specificity.
I read (I am an industrial pharmacist in profession) it many times that immunofixation is more reliable than SPEP. Does the positive immunofixation test for monoclonal protein mean my husband has MGUS or smoldering multiple myeloma?
His other blood results like complete blood test , total protein, albumin / globulin ratio, serum calcium level, BUN, creatinine, alpha / beta / gamma globulin, etc., are within normal range. His hemoglobin range is good too (17.00), so no sign of anemia or other "CRAB" symptoms.
Thanks and regards to all.
Forums
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sadiamitil - Name: Sadia R
- Who do you know with myeloma?: Husband, Osteosclerotic myeloma( POEMS)
- When were you/they diagnosed?: Augus, 2016
- Age at diagnosis: 38
Re: SPEP negative for M-protein, immunofixation positive
Hi Sadiamitil,
Welcome to the forum.
A serum immunofixation (IFE) test is indeed more sensitive than an SPEP at detecting the presence of monoclonal protein.
I would suggest also getting a serum free light chain test and a quantified immunonogloublin test (measures total IgG, IgA, IgM) to get a more complete picture given the IFE results.
Also, note that measuring IgA monoclonal protein can be tricky with an SPEP since other proteins can exist in the same area of the SPEP graph that a potential IgA M-spike would appear in. The other tests I mentioned above would help confirm if you have anything to worry about or not. Depending on the test results, I would also keep in mind the possibility of amyloidosis as your doctor eliminates various possible diseases.
Lastly, the IFE reading might also might just be a transient one-time event, so getting re-tested in a number of months would also make sense.
Welcome to the forum.
A serum immunofixation (IFE) test is indeed more sensitive than an SPEP at detecting the presence of monoclonal protein.
I would suggest also getting a serum free light chain test and a quantified immunonogloublin test (measures total IgG, IgA, IgM) to get a more complete picture given the IFE results.
Also, note that measuring IgA monoclonal protein can be tricky with an SPEP since other proteins can exist in the same area of the SPEP graph that a potential IgA M-spike would appear in. The other tests I mentioned above would help confirm if you have anything to worry about or not. Depending on the test results, I would also keep in mind the possibility of amyloidosis as your doctor eliminates various possible diseases.
Lastly, the IFE reading might also might just be a transient one-time event, so getting re-tested in a number of months would also make sense.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: SPEP negative for M-protein, immunofixation positive
Thanks a lot, Multibilly, for your valuable suggestions. 
I will definitely request his internal medicine doctor to perform serum free light chain test.
I think a quantified immunoglobulin test has been done, because I can see the total value of each immunoglobulin mentioned in his blood report.
His IgA is high, 475 mg/dL (normal range 90-386).
His IgG is 973 mg/dL (normal range 700-1600)
And IgM is 109 mg/dL (normal range 20-172 ).
I cannot see IgE and IgD, cannot understand why so.
Should the urine be tested for monoclonal protein too? Should I request the doctor to refer him to an oncologist?
Thanks again for your kind help. I wish a long and healthy life to each and every member of this wonderful forum.
Regards
I will definitely request his internal medicine doctor to perform serum free light chain test. I think a quantified immunoglobulin test has been done, because I can see the total value of each immunoglobulin mentioned in his blood report.
His IgA is high, 475 mg/dL (normal range 90-386).
His IgG is 973 mg/dL (normal range 700-1600)
And IgM is 109 mg/dL (normal range 20-172 ).
I cannot see IgE and IgD, cannot understand why so.
Should the urine be tested for monoclonal protein too? Should I request the doctor to refer him to an oncologist?
Thanks again for your kind help. I wish a long and healthy life to each and every member of this wonderful forum.
Regards
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sadiamitil - Name: Sadia R
- Who do you know with myeloma?: Husband, Osteosclerotic myeloma( POEMS)
- When were you/they diagnosed?: Augus, 2016
- Age at diagnosis: 38
Re: SPEP negative for M-protein, immunofixation positive
Hi sadiamitil,
I hope your husband is feeling better after the B12 shot, which I assume is the first of many (true B12 deficiency will usually require weekly injections for a few shots, then twice monthly, then monthly). I'm sorry much still is up in the air after testing and that uncertainty and diagnostic challenges remain.
Patients rarely present with 3 causes (B12 deficiency / Lyme / something else) of one problem (peripheral neuropathy), particularly if that problem is acute. While it is possible, I think you are unfortunately going to have some ongoing uncertainty while your husband has more testing. Medical problems in the young and healthy tend to follow either a single unifying diagnosis / cause (the Oslerian ideal) or true / true-but-unrelated.
For the B12, you'll likely get an anti-intrinsic factor antibody test, and testing for celiac disease and other gastrointestinal causes, and given the weight loss your husband may get an EGD. Are you vegetarians? Is he on meds like metformin or a proton pump inhibitor (PPI), which can affect B12?
Lyme can be a tricky diagnosis and will likely need PCR testing to validate.
As for the immunofixation result, it may be real or it may be a false positive in the setting of inflammation and other immune and inflammatory conditions. Pernicious anemia (one of the causes of B12 deficiency) is due to an antibody-mediated autoimmune condition and travels with other autoimmune illnesses which can affect antibody testing. I imagine Lyme, an infectious illness, can do the same. Conversely, B12 deficiency is sometimes seen in plasma cell disorders. Other cancers can also cause paraproteins (paraneoplastic syndromes).
Common things being common, let's hope for B12 deficiency and a false positive immunofixation result while you are doing all the work needed to be sure it's nothing else. The internist appointment should help sort this all out.
Wishing you both the best.
I hope your husband is feeling better after the B12 shot, which I assume is the first of many (true B12 deficiency will usually require weekly injections for a few shots, then twice monthly, then monthly). I'm sorry much still is up in the air after testing and that uncertainty and diagnostic challenges remain.
Patients rarely present with 3 causes (B12 deficiency / Lyme / something else) of one problem (peripheral neuropathy), particularly if that problem is acute. While it is possible, I think you are unfortunately going to have some ongoing uncertainty while your husband has more testing. Medical problems in the young and healthy tend to follow either a single unifying diagnosis / cause (the Oslerian ideal) or true / true-but-unrelated.
For the B12, you'll likely get an anti-intrinsic factor antibody test, and testing for celiac disease and other gastrointestinal causes, and given the weight loss your husband may get an EGD. Are you vegetarians? Is he on meds like metformin or a proton pump inhibitor (PPI), which can affect B12?
Lyme can be a tricky diagnosis and will likely need PCR testing to validate.
As for the immunofixation result, it may be real or it may be a false positive in the setting of inflammation and other immune and inflammatory conditions. Pernicious anemia (one of the causes of B12 deficiency) is due to an antibody-mediated autoimmune condition and travels with other autoimmune illnesses which can affect antibody testing. I imagine Lyme, an infectious illness, can do the same. Conversely, B12 deficiency is sometimes seen in plasma cell disorders. Other cancers can also cause paraproteins (paraneoplastic syndromes).
Common things being common, let's hope for B12 deficiency and a false positive immunofixation result while you are doing all the work needed to be sure it's nothing else. The internist appointment should help sort this all out.
Wishing you both the best.
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rick - Name: rick
- Who do you know with myeloma?: husband
- When were you/they diagnosed?: nov 2015
- Age at diagnosis: 50
Re: SPEP negative for M-protein, immunofixation positive
Hi Sadiamitil,
I would indeed suggest getting an appointment with a hematologist / oncologist that specializes in multiple myeloma. I simply say this since he had a positive immunofixation test for IgA kappa, his IgA is elevated, and he is experiencing peripheral neuropathy. If you let us know what city you are in, folks on this forum can make some recommendations as to where to find some multiple myeloma specialists nearby.
Doing a 24 hour UPEP is not a bad idea (some specialists use them, some don't). However, a serum free light chain assay will be invaluable in helping with a diagnosis given the above test results. A myeloma specialist may also be familiar with and suggest the new HevyLite test, which is especially good at helping sort out and track monoclonal IgA disorders.
I wouldn't worry about measuring quantitative IgD and IgE. Monoclonal disorders associated with IgD and IgE are extremely rare.
I would indeed suggest getting an appointment with a hematologist / oncologist that specializes in multiple myeloma. I simply say this since he had a positive immunofixation test for IgA kappa, his IgA is elevated, and he is experiencing peripheral neuropathy. If you let us know what city you are in, folks on this forum can make some recommendations as to where to find some multiple myeloma specialists nearby.
Doing a 24 hour UPEP is not a bad idea (some specialists use them, some don't). However, a serum free light chain assay will be invaluable in helping with a diagnosis given the above test results. A myeloma specialist may also be familiar with and suggest the new HevyLite test, which is especially good at helping sort out and track monoclonal IgA disorders.
I wouldn't worry about measuring quantitative IgD and IgE. Monoclonal disorders associated with IgD and IgE are extremely rare.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: SPEP negative for M-protein, immunofixation positive
Hello Rick!
Many many thanks for your response. No we are not vegetarian, we eat poultry and red meat except pork and some fishes, eggs (mostly egg white, but sometimes yolk too). But for the last one year, my husband was on an oatmeal diet to lose extra weight and to reduce his slightly elevated cholesterol level. I was always skeptical about any extreme diet .
Yes, I also read that sometimes multiple myeloma or some other forms of malignancies may show false decrease in vitamin B12. But cannot understand why the underlying cause cannot be explained! By the way, his methylmalonic acid level was tested and it is abnormally high, 808 nmol/L (normal range 0-308). I am really confused if this can be falsely increased by multiple myeloma too. His kidney function is good, his Internist told us that on 21st June.
He is always very very tired. This is also worrying me .
The next appointment with his internist is on 7th July. Should we try to get an early appointment? He is saying he cannot understand if his neuropathy is any better after the vitamin B12 shot. He is also on doxycycline for the treatment of Lyme. He was tested twice for it and both times it came positive.
Thanks and regards. Wish you and your family all the best.
Many many thanks for your response.
No we are not vegetarian, we eat poultry and red meat except pork and some fishes, eggs (mostly egg white, but sometimes yolk too). But for the last one year, my husband was on an oatmeal diet to lose extra weight and to reduce his slightly elevated cholesterol level. I was always skeptical about any extreme diet . Yes, I also read that sometimes multiple myeloma or some other forms of malignancies may show false decrease in vitamin B12. But cannot understand why the underlying cause cannot be explained! By the way, his methylmalonic acid level was tested and it is abnormally high, 808 nmol/L (normal range 0-308). I am really confused if this can be falsely increased by multiple myeloma too. His kidney function is good, his Internist told us that on 21st June.
He is always very very tired. This is also worrying me .
The next appointment with his internist is on 7th July. Should we try to get an early appointment? He is saying he cannot understand if his neuropathy is any better after the vitamin B12 shot. He is also on doxycycline for the treatment of Lyme. He was tested twice for it and both times it came positive.
Thanks and regards. Wish you and your family all the best.
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sadiamitil - Name: Sadia R
- Who do you know with myeloma?: Husband, Osteosclerotic myeloma( POEMS)
- When were you/they diagnosed?: Augus, 2016
- Age at diagnosis: 38
Re: SPEP negative for M-protein, immunofixation positive
Hi Multibilly,
Thanks a lot. Hope you are doing fine
We live in Suffolk County, Long Island, Bay Shore, New York. It will be very helpful if I can get any suggestion about the selection of oncologists near me.
We are feeling overwhelmed by everything. It is a lot to process all of a sudden. We feel our life is just turning upside down just in a few weeks. Our 3rd marriage anniversary (16th June) was spent by my trying to hide tears and his forced laugh in our favorite restaurant.
Thank you again!
With best regards.
Thanks a lot. Hope you are doing fine
We live in Suffolk County, Long Island, Bay Shore, New York. It will be very helpful if I can get any suggestion about the selection of oncologists near me.
We are feeling overwhelmed by everything. It is a lot to process all of a sudden. We feel our life is just turning upside down just in a few weeks. Our 3rd marriage anniversary (16th June) was spent by my trying to hide tears and his forced laugh in our favorite restaurant.
Thank you again!
With best regards.
-
sadiamitil - Name: Sadia R
- Who do you know with myeloma?: Husband, Osteosclerotic myeloma( POEMS)
- When were you/they diagnosed?: Augus, 2016
- Age at diagnosis: 38
Re: SPEP negative for M-protein, immunofixation positive
Hi Sadiamitil,
Welcome to the forum. I'm sorry you and your husband are going through all of this. It is very stressful.
Now that you've had the immunofixation result showing the IgA monoclonal protein, you need to get to the bottom of it. The other names for this is "monoclonal gammopathy". Combined with the fact that he has symptoms (rather than simply incidentally finding the monoclonal protein), I wouldn't settle for "let's just watch and test again in a few months." The list of things that can cause monoclonal protein is huge, but one of the most significant is plasma cell disease. Plasma cell disease includes MGUS, smoldering myeloma, multiple myeloma, and plasma cell leukemia. Importantly, it also includes AL amyloidosis. When you said his "presenting symptom" was peripheral neuropathy, a little bell rung in my head, because AL amyloidosis is notorious for causing peripheral neuropathy.
As I said before, there are a lot of other causes of monoclonal protein, many of which are benign, but you need to get to the bottom of it. This is not an easy task. It is going to involve a lot of appointments, tests and biopsies. And time, unfortunately. This will feel more like a marathon than a sprint, so pace yourselves.
The best way to sort this out is to go straight to a heme/ onc doctor that specializes in plasma cell disease and multiple myeloma.
Your location is good for this - there are a lot of myeloma specialists around the NYC area, though I don't know any of them personally. It seems a lot of myeloma patients go to Sloan Kettering.
Maybe others who are actually treated in NY can give you some names?
Tracy
Welcome to the forum. I'm sorry you and your husband are going through all of this. It is very stressful.
Now that you've had the immunofixation result showing the IgA monoclonal protein, you need to get to the bottom of it. The other names for this is "monoclonal gammopathy". Combined with the fact that he has symptoms (rather than simply incidentally finding the monoclonal protein), I wouldn't settle for "let's just watch and test again in a few months." The list of things that can cause monoclonal protein is huge, but one of the most significant is plasma cell disease. Plasma cell disease includes MGUS, smoldering myeloma, multiple myeloma, and plasma cell leukemia. Importantly, it also includes AL amyloidosis. When you said his "presenting symptom" was peripheral neuropathy, a little bell rung in my head, because AL amyloidosis is notorious for causing peripheral neuropathy.
As I said before, there are a lot of other causes of monoclonal protein, many of which are benign, but you need to get to the bottom of it. This is not an easy task. It is going to involve a lot of appointments, tests and biopsies. And time, unfortunately. This will feel more like a marathon than a sprint, so pace yourselves.
The best way to sort this out is to go straight to a heme/ onc doctor that specializes in plasma cell disease and multiple myeloma.
Your location is good for this - there are a lot of myeloma specialists around the NYC area, though I don't know any of them personally. It seems a lot of myeloma patients go to Sloan Kettering.
Maybe others who are actually treated in NY can give you some names?
Tracy
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Tracy J - Name: Tracy Jalbuena
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: 2014
- Age at diagnosis: 42
Re: SPEP negative for M-protein, immunofixation positive
Tracy,
I'm curious. Why are you so convinced that the immunofixation test has to be correct – that this definitely is a case of monoclonal gammopathy? It's a single test, the SPEP isn't showing an M-spike, and there seem to be other factors that could cause the immunofixation to register a false positive (which would not be unheard of).
I realize that the immunofixation test is more sensitive than the SPEP, the SPEP is particularly inaccurate in cases of IgA monoclonal gammopathies, and Sadiamitil's husband's IgA level is elevated.
But isn't it jumping the gun a bit to assume, unequivocally, that this is a monoclonal gammopathy of some sort?
I'm curious. Why are you so convinced that the immunofixation test has to be correct – that this definitely is a case of monoclonal gammopathy? It's a single test, the SPEP isn't showing an M-spike, and there seem to be other factors that could cause the immunofixation to register a false positive (which would not be unheard of).
I realize that the immunofixation test is more sensitive than the SPEP, the SPEP is particularly inaccurate in cases of IgA monoclonal gammopathies, and Sadiamitil's husband's IgA level is elevated.
But isn't it jumping the gun a bit to assume, unequivocally, that this is a monoclonal gammopathy of some sort?
-
JimNY
Re: SPEP negative for M-protein, immunofixation positive
Hi again sadiamitil,
So the high methylmalonic acid tells you that your husband is in fact B12 deficient and likely has been for some time. (The test is used to confirm B12 deficiency when the B12 itself is borderline on testing and can give some information on the length of the condition; with higher meaning longer.) I hope your husband is getting weekly B12 injections. If not, you can likely call his internist's office and say he needs an appointment for that and additional labs at the least. He will need multiple B12 shots, weekly at first, and then eventually monthly. Test results for the reason for the B12 deficiency might be helpful at the time of the actual internist appointment (pre-visit labs).
Additional tests will sort the underlying cause which is not dietary or other medication. For the B12, he will still need to exclude pernicious anemia (via an intrinsic factor antibody test) and other autoimmune causes (like an ANA), perhaps parasite testing, celiac testing, and may need a gastrointestinal endoscopy. They will ask about alcohol use.
Lyme disease is a two-step testing process, as the initial antibody test has a higher false positive rate. Was his second test a western blot or PCR confirmation? This is to sort a false positive antibody test. If so, he does indeed have both B12 and Lyme.
These conditions alone can make anyone very tired. both cause peripheral neuropathy. Multiple weekly B12 shots may be needed before he feels better, and treating Lyme can be as tricky as diagnosing it.
The immunofixation will also need more attention and testing, but the diagnoses you already have can color the results here. Autoimmune and infectious diseases can effect IgA levels. You might not have what you feel are the right set of answers for much of the summer. I'm still hoping you will have 2, not 3, diagnoses, and clearly sense you will do all you need to sort this all out.
Again, wishing you the best through this trying time.
So the high methylmalonic acid tells you that your husband is in fact B12 deficient and likely has been for some time. (The test is used to confirm B12 deficiency when the B12 itself is borderline on testing and can give some information on the length of the condition; with higher meaning longer.) I hope your husband is getting weekly B12 injections. If not, you can likely call his internist's office and say he needs an appointment for that and additional labs at the least. He will need multiple B12 shots, weekly at first, and then eventually monthly. Test results for the reason for the B12 deficiency might be helpful at the time of the actual internist appointment (pre-visit labs).
Additional tests will sort the underlying cause which is not dietary or other medication. For the B12, he will still need to exclude pernicious anemia (via an intrinsic factor antibody test) and other autoimmune causes (like an ANA), perhaps parasite testing, celiac testing, and may need a gastrointestinal endoscopy. They will ask about alcohol use.
Lyme disease is a two-step testing process, as the initial antibody test has a higher false positive rate. Was his second test a western blot or PCR confirmation? This is to sort a false positive antibody test. If so, he does indeed have both B12 and Lyme.
These conditions alone can make anyone very tired. both cause peripheral neuropathy. Multiple weekly B12 shots may be needed before he feels better, and treating Lyme can be as tricky as diagnosing it.
The immunofixation will also need more attention and testing, but the diagnoses you already have can color the results here. Autoimmune and infectious diseases can effect IgA levels. You might not have what you feel are the right set of answers for much of the summer. I'm still hoping you will have 2, not 3, diagnoses, and clearly sense you will do all you need to sort this all out.
Again, wishing you the best through this trying time.
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rick - Name: rick
- Who do you know with myeloma?: husband
- When were you/they diagnosed?: nov 2015
- Age at diagnosis: 50
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