There is confusion about FDA approval of Lyme testing. It has been stated (by IDSA experts) that ILADS associated physicians have essentially created their own laboratories which are not FDA approved. And furthermore, these laboratories and physicians use non-peer-reviewed methods to interpret the results.
This is very misleading at the very least.
Laboratories are licensed by state regulatory agencies. Certified laboratories meet strict standards, including proficiency testing.
The FDA is charged with regulating drugs and medical devices. Test kits, commercially prepared for mass distribution are considered medical devices. This is why the FDA licenses these Lyme Western Blot tests. The FDA has licensed more than 70Lyme Western Blot kits made by varying manufactures. There exists no published data validating any one of these kits let alone all 70 or more.
Standard kits report the 13 Western Blot bands specified by the 1994 Dearborn criteria. This standard was created so that various doctors and scientists could communicate with one another reading from the same sheet of music. This surveillance test, never approved for diagnosis, has no peer-reviewed literature supporting its use - especially in light of FDA approval of so many test kits. In fact, a review of the literature shows investigators have used various Band criteria.
Laboratories producing their own testing kits (not for mass distribution) like Stony Brook and IgeneX do not require FDA approval. In fact, these tests cannot be regulated by the FDA. These laboratories must comply with the same regulations and proficiency tests required by all state licensed facilities.
Specialty laboratories likely do a better Lyme Western blot. For example, Stony Brook Lyme lab only does Lyme Western Blots. IgenX has decades of experience. Clongen and MDL are meticulous.
While mass produced Lyme Western Blot kits report 13 bands. Other maligned specialty labs report 28 or even 52 bands.
As stated in the 1994 report the diagnosis of Lyme is(was) largely clinical.
The question then is: How can more be less?
Thursday, December 29, 2011
Friday, December 23, 2011
Heart Block
I first saw this patient 10 months ago. She had been ill with a disabling multi-system illness for 12 years.
She suffered with many symptoms, including but not limited to: profound fatigue global cognitive dysfunction, joint pains, swelling with effusions, weakness and numerous neurological manifestations. Lyme was suggested. She had a positive Western Blot (10 years ago) an IDSA doctor prescribed two weeks of doxycyline.
An LLMD subsequently prescribed over a year of antibiotics including mincycline and Ceftin. Many symptoms improved, except the over-powering fatigue.
She stumbled along for years off antibiotics, symptoms waxing an waning. Still, she managed to functioned as a high level executive.
As of late she was not doing well at all. When I met her she had been sidelined with disability for more than two years. She had no energy or stamina. She was unable to grocery shop or attend to the most basic activities of daily living. She had perpetual flu-like symptoms - a loss of sensation in her fingers and toes. She was stumbling and falling. Joint pain with swelling had returned. She had global cognitive dysfunction with episodes of syncope, confusion and disorientation. She could not speak well, think clearly or read and write. She was a shell of her former self.
Two months before an IDSA doctor refused to treat her because she had a negative Lyme test.
Despite the fact that she nearly died of complete heart block now treated with a permanent pacemaker. And - despite the fact the attending cardiologist suspected Lyme as the culprit.
I became her doctor.
After months of fits and starts with oral therapy she has no been on IV Rocephin for 3 months and tells me she is getting her life back. She is contemplating starting a new business after two years of complete disability.
Now she gets out of the house and can read. Now she can do many things unthinkable a few months before. She is still very sick with many persisting constitutional and neurological symptoms. Her stamina is poor. After brief activites she requires extensive rest for recuperation. But she tells me she getting better almost on a daily basis. Most of the improvement seen after 2 and 1/2 months of therapy.
Lets look at some labs. These are IgM Western Blot results from three different labs. Labcorp found a 23 band. Clongen reported a 41 band and a weak, 23% of control 23 band reaction. Stony Brook found: Bands, 18,37,58,66,72,93.
The 37 and 93 bands either one alone might be enough to make the diagnosis according to some sources. I do not know why there was no 41 or 23 band found. Different strains of Lyme may be used in different kits lending bias to which bands react.
I do not understand not treating heart block with a documented history of Lyme disease. The CDC test is a surveillance test. It has never been validated as a diagnostic test. And the notion that IgG bands show up in late Lyme is not substantiated in any literature I can find.
The highly vaunted NIH/IDSA studies of long-term therapy never included Rocephin use for longer than 10 weeks.
Happy Holidays
She suffered with many symptoms, including but not limited to: profound fatigue global cognitive dysfunction, joint pains, swelling with effusions, weakness and numerous neurological manifestations. Lyme was suggested. She had a positive Western Blot (10 years ago) an IDSA doctor prescribed two weeks of doxycyline.
An LLMD subsequently prescribed over a year of antibiotics including mincycline and Ceftin. Many symptoms improved, except the over-powering fatigue.
She stumbled along for years off antibiotics, symptoms waxing an waning. Still, she managed to functioned as a high level executive.
As of late she was not doing well at all. When I met her she had been sidelined with disability for more than two years. She had no energy or stamina. She was unable to grocery shop or attend to the most basic activities of daily living. She had perpetual flu-like symptoms - a loss of sensation in her fingers and toes. She was stumbling and falling. Joint pain with swelling had returned. She had global cognitive dysfunction with episodes of syncope, confusion and disorientation. She could not speak well, think clearly or read and write. She was a shell of her former self.
Two months before an IDSA doctor refused to treat her because she had a negative Lyme test.
Despite the fact that she nearly died of complete heart block now treated with a permanent pacemaker. And - despite the fact the attending cardiologist suspected Lyme as the culprit.
I became her doctor.
After months of fits and starts with oral therapy she has no been on IV Rocephin for 3 months and tells me she is getting her life back. She is contemplating starting a new business after two years of complete disability.
Now she gets out of the house and can read. Now she can do many things unthinkable a few months before. She is still very sick with many persisting constitutional and neurological symptoms. Her stamina is poor. After brief activites she requires extensive rest for recuperation. But she tells me she getting better almost on a daily basis. Most of the improvement seen after 2 and 1/2 months of therapy.
Lets look at some labs. These are IgM Western Blot results from three different labs. Labcorp found a 23 band. Clongen reported a 41 band and a weak, 23% of control 23 band reaction. Stony Brook found: Bands, 18,37,58,66,72,93.
The 37 and 93 bands either one alone might be enough to make the diagnosis according to some sources. I do not know why there was no 41 or 23 band found. Different strains of Lyme may be used in different kits lending bias to which bands react.
I do not understand not treating heart block with a documented history of Lyme disease. The CDC test is a surveillance test. It has never been validated as a diagnostic test. And the notion that IgG bands show up in late Lyme is not substantiated in any literature I can find.
The highly vaunted NIH/IDSA studies of long-term therapy never included Rocephin use for longer than 10 weeks.
Happy Holidays
Thursday, December 22, 2011
Brown powder
There is always the patient you dread seeing. When I see this particular patient in the waiting room an uneasiness wells up from my gut. Don't misunderstand. She is a lovely person. Maybe it would be easier if she wasn't so nice. It is her disease I take issue with. Progress has been excruciatingly slow with regression the rule. After two years treating her I am frustrated. She knows I can help people. Her son and mother responded beautifully.
She was a park ranger. Now she is disabled, unable to work: Fatigue with a capital F, pain and scrambled brain. She experiences confusion and disorientation at times. She suffers with numerous areas of neurocognitive dysfunction. She has been troubled by severe mood swings with sudden uncontrollable tears.
She has been treated aggressively for co-infections and with intravenous antibiotics.
Finally I insisted again that we go down a different path(having suggested this many times in the past). I referred her to a practitioner of traditional Chinese medicine. She was skeptical given a background in science. Spiritual healing, cupping and acupuncture she felt were of little or no help. But herbs. Herbs were a different story. She was provided with strange bottles containing brown powder and hand written labels. The labels made various claims: anti-Lyme, anti-Bartonella, detoxifying, anti-inflammatory, anti-biofilm and others. Neither she nor I have a clue what is in these foul tasting mixtures to be taken several times daily with water. But they Work. The combination of herbs and antibiotics has been particularly effective.
Unfortunately she regresses if she stops either the herbs or the antibiotics. Herbs, like antibiotics may be required as maintenance therapy.
Take her off the list.
She was a park ranger. Now she is disabled, unable to work: Fatigue with a capital F, pain and scrambled brain. She experiences confusion and disorientation at times. She suffers with numerous areas of neurocognitive dysfunction. She has been troubled by severe mood swings with sudden uncontrollable tears.
She has been treated aggressively for co-infections and with intravenous antibiotics.
Finally I insisted again that we go down a different path(having suggested this many times in the past). I referred her to a practitioner of traditional Chinese medicine. She was skeptical given a background in science. Spiritual healing, cupping and acupuncture she felt were of little or no help. But herbs. Herbs were a different story. She was provided with strange bottles containing brown powder and hand written labels. The labels made various claims: anti-Lyme, anti-Bartonella, detoxifying, anti-inflammatory, anti-biofilm and others. Neither she nor I have a clue what is in these foul tasting mixtures to be taken several times daily with water. But they Work. The combination of herbs and antibiotics has been particularly effective.
Unfortunately she regresses if she stops either the herbs or the antibiotics. Herbs, like antibiotics may be required as maintenance therapy.
Take her off the list.
Thursday, December 15, 2011
Primay care: Lyme endemic
Follow up visit. I have known this 50 year old male for a long time. He is a chronic depressive type. Divorced poorly. Working two jobs. Antidepressants help and he needs a refill. He mentions as a side bar he had red bumps on his leg 8 weeks ago, thought it was bug bites and went to a walk in clinic. Told - nothing to worry about. he suffers with anxiety and is disease phobic too. Just updating my files. Great. Thanks for the info. This was three visits ago.
No symptoms except the usual fatigue and depressed mood.
I order a few tests, perhaps the wrong test, including a tick borne disease panel. I have Lyme on my brain. Gotta stop that. Surprise(or not). Labcorp CDC positive for Lyme, ELISA and IgM WB. Babesia duncani titer 1:512 cinches the deal.
I carefully query: " Change in fatigue, Headaches, neck pain, change in vision, night sweats, any sweats, air hunger, joint pain, muscle pain, muscle pain, twitching muscles, Numbness and tingling, brain fog, cognitive issues, anything?"
He pauses to think: Maybe a few night sweats, over the last 6 months. Perhaps the heat was up too high, wearing heavy night clothes, not sure. Nothing else.
I treat him with antibiotics and Mepron for a month.
Now the current follow up visit.
Feels the same, except anxiety has increased; now he is worried about these new exotic sounding and frightening diseases.
It would be a lot easier if he was sick. Then I would know what to do.
There are the perils of a primary care practice - seeing patients on the front line. I suspect most patients infected with Lyme are asymptomatic. It is impossible to test this theory. I know many patients infected with Babesia are asymptomatic.
In a specialty Lyme referral practice you don't have to wrestle with these problems. I spent more time thinking about his case than I did the sick patients I saw that day.
Now I know a lot of readers are thinking: Treat him, treat him! Here's the problem. With Lyme you treat until symptoms are gone. What end point do you suggest I use?
I am still scratching my chin.
"
No symptoms except the usual fatigue and depressed mood.
I order a few tests, perhaps the wrong test, including a tick borne disease panel. I have Lyme on my brain. Gotta stop that. Surprise(or not). Labcorp CDC positive for Lyme, ELISA and IgM WB. Babesia duncani titer 1:512 cinches the deal.
I carefully query: " Change in fatigue, Headaches, neck pain, change in vision, night sweats, any sweats, air hunger, joint pain, muscle pain, muscle pain, twitching muscles, Numbness and tingling, brain fog, cognitive issues, anything?"
He pauses to think: Maybe a few night sweats, over the last 6 months. Perhaps the heat was up too high, wearing heavy night clothes, not sure. Nothing else.
I treat him with antibiotics and Mepron for a month.
Now the current follow up visit.
Feels the same, except anxiety has increased; now he is worried about these new exotic sounding and frightening diseases.
It would be a lot easier if he was sick. Then I would know what to do.
There are the perils of a primary care practice - seeing patients on the front line. I suspect most patients infected with Lyme are asymptomatic. It is impossible to test this theory. I know many patients infected with Babesia are asymptomatic.
In a specialty Lyme referral practice you don't have to wrestle with these problems. I spent more time thinking about his case than I did the sick patients I saw that day.
Now I know a lot of readers are thinking: Treat him, treat him! Here's the problem. With Lyme you treat until symptoms are gone. What end point do you suggest I use?
I am still scratching my chin.
"
Monday, December 12, 2011
Lyme Western Blots: another look
In October 1994 at a weekend conference, a group of experts developed criteria for the the definition of Lyme surveillance testing. The outcome of this conference led to a maelstrom of controversy which continues.
The test has never been re-evelated even though two key bands: 34 OspB and 31 OspA were ommitted.
It was decided that a two tier protocol should be followed. The criteria for the IgM Western Blot came from the work of Engstrom et al. Three strains of Lyme were found to perform equally well. The 23 band, identified as the OspC band, the 39 band, and the Fla (41) band were chosen for the assay. A positive result was 2/3 of these bands. It was noted that the 37 band could be added and that 2/4 of these bands would increase the accuracy of the test. (not accurate)
Dressler et al proposed a different criteria for IgM scoring. A different strain of Lyme was used which did not express the 39 band well. A positive result was the presence of 2/8 bands: 18,21,28,37,45,58 and 93. This test performed about as well as the above test.
Two radically different test and test criteria were found to produce almost the same results!
Padula et al found the 23 band to be of diagnostic significance, especially in early Lyme - and that "this protein may be poorly expressed in a number of North American strains of Borrelia burgdoreri." Weinstein and Johnsone report: "Despite these limitations, the proposed criteria for a positive immunoblot in late Lyme disease - at least 5 or the 10 specified IgG bands - seemed to stand up reasonably well in other laboratories...The criteria (will) be used..pending further studies."
What studies?
Where did the 37 band go?
Stony Brook reports it.
Ah, the missing band that would have made the CDC test more accurate by its own admission.
Two labs prepare their own Lyme Western Blot kits: IgeneX and Stony Brook. IgeneX has developed criteria for a positive result (IgG and IgM) - sounds like the Dressler criteria. They report a positive result if there is a reaction with two highly specific bands, inclding: 23,31,41,34,39,and 93.
Different assays have produced different bands. Dressler reported a 21 band. Stony Brook only reports a 20 band.
Are you as confused as I am?
In addition, in my experience I have found reported Western Blot results differ amongst commonly used "LLMD" laboratories.
In 1994 Gubler reports the two tier test is not the gold standard. (culture is). He states that "in the not too distant future, the development of new tests that use a cocktail of recombinant antigens or chimeric antigens(will increase)the sensitivity and specificity of serological tests for B. burdorferi."
Its been more that 17 years. We are still waiting.
The test has never been re-evelated even though two key bands: 34 OspB and 31 OspA were ommitted.
It was decided that a two tier protocol should be followed. The criteria for the IgM Western Blot came from the work of Engstrom et al. Three strains of Lyme were found to perform equally well. The 23 band, identified as the OspC band, the 39 band, and the Fla (41) band were chosen for the assay. A positive result was 2/3 of these bands. It was noted that the 37 band could be added and that 2/4 of these bands would increase the accuracy of the test. (not accurate)
Dressler et al proposed a different criteria for IgM scoring. A different strain of Lyme was used which did not express the 39 band well. A positive result was the presence of 2/8 bands: 18,21,28,37,45,58 and 93. This test performed about as well as the above test.
Two radically different test and test criteria were found to produce almost the same results!
Padula et al found the 23 band to be of diagnostic significance, especially in early Lyme - and that "this protein may be poorly expressed in a number of North American strains of Borrelia burgdoreri." Weinstein and Johnsone report: "Despite these limitations, the proposed criteria for a positive immunoblot in late Lyme disease - at least 5 or the 10 specified IgG bands - seemed to stand up reasonably well in other laboratories...The criteria (will) be used..pending further studies."
What studies?
Where did the 37 band go?
Stony Brook reports it.
Ah, the missing band that would have made the CDC test more accurate by its own admission.
Two labs prepare their own Lyme Western Blot kits: IgeneX and Stony Brook. IgeneX has developed criteria for a positive result (IgG and IgM) - sounds like the Dressler criteria. They report a positive result if there is a reaction with two highly specific bands, inclding: 23,31,41,34,39,and 93.
Different assays have produced different bands. Dressler reported a 21 band. Stony Brook only reports a 20 band.
Are you as confused as I am?
In addition, in my experience I have found reported Western Blot results differ amongst commonly used "LLMD" laboratories.
In 1994 Gubler reports the two tier test is not the gold standard. (culture is). He states that "in the not too distant future, the development of new tests that use a cocktail of recombinant antigens or chimeric antigens(will increase)the sensitivity and specificity of serological tests for B. burdorferi."
Its been more that 17 years. We are still waiting.
Thursday, December 1, 2011
Chasing the sweats
Let me clarify this confusing post: It is based on a true clinical scenario. I was drawn into a hole chasing Babesia; the symptoms were classic, especially the profound night sweats. The "Babesia" stubbornly wouldn't go away, with everything thrown its way: Mepron, malarone, Artemesia, Coartem and Larium.
I was willing to treat Babesia as a clinical diagnosis with aggressive, long term therapy; positive lab confirmation is rare. I convinced myself that resolution was just around the corner.
I was reluctant to treat Lyme with intravenous therapy(I had been treating Lyme with oral antibiotics) If the clinical picture had been more "Lyme flavored," I may have pulled the trigger for IV therapy more quickly.
The patient had clear symptoms of neuroborreliosis including hallucinations at one point. Still, the clinician could rationalize the marked neuropsychiatric manifestations were the product of cerebral babesiosis.
Over a period of several months the patient requested (stridently) that she needed a PICC and IV therapy.
The diagnosis of tick borne disease is still made clinically. Still, in borderline situations the clinician sometimes turns to laboratory results, as I did here, to help justify the more dangerous step up in therapy.
The patient's mantra for some time was: I need a PICC.
I acquiesced after 9 months of oral therapies.
Incredible improvements with resoltion of both cognitive and physical symptoms were seen within the first month. The so-called classic Babesia symptoms also melted away.
This raises many interesting clinical questions.
I am not offering any clinical advise here. Please do not misinterpret. Every case is different.
In this case, the patient had insights about her care which turned out to be true.
I was willing to treat Babesia as a clinical diagnosis with aggressive, long term therapy; positive lab confirmation is rare. I convinced myself that resolution was just around the corner.
I was reluctant to treat Lyme with intravenous therapy(I had been treating Lyme with oral antibiotics) If the clinical picture had been more "Lyme flavored," I may have pulled the trigger for IV therapy more quickly.
The patient had clear symptoms of neuroborreliosis including hallucinations at one point. Still, the clinician could rationalize the marked neuropsychiatric manifestations were the product of cerebral babesiosis.
Over a period of several months the patient requested (stridently) that she needed a PICC and IV therapy.
The diagnosis of tick borne disease is still made clinically. Still, in borderline situations the clinician sometimes turns to laboratory results, as I did here, to help justify the more dangerous step up in therapy.
The patient's mantra for some time was: I need a PICC.
I acquiesced after 9 months of oral therapies.
Incredible improvements with resoltion of both cognitive and physical symptoms were seen within the first month. The so-called classic Babesia symptoms also melted away.
This raises many interesting clinical questions.
I am not offering any clinical advise here. Please do not misinterpret. Every case is different.
In this case, the patient had insights about her care which turned out to be true.
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