Atrio-ventricular conduction disturbance due to Lyme Carditis
May 2 2019
An active professional sportsman was admitted to our hospital with atrio-ventricular conduction disturbances. Purpose of admission was to insert a definitive pacemaker.
During recording of the symptoms and patient history, the patient mentioned a tick-bite on the neck, followed by the only symptom of atrio-ventricular conduction disturbances, four months later.
Serological tests came back negative for Lyme borreliosis, however, the clinical diagnosis of carditis borreliosa lymei monosymptomatica was made.
The diagnosis was supported only by detecting Borrelia spirochetes under a dark-field microscope. Samples were stored in a serum bank.
Treatment for Lyme borreliosis was started based on the clinical diagnosis, and the status of the patient was regularly monitored by laboratory tests. Symptoms improved, and result of serology came back positive on one occasion during treatment, confirming the clinical diagnosis. (N.B.: the serological finding may be attributed to the immune reaction to the disintegrating spirochetes)
A combined, high-dose, 8-week antibiotic therapy resulted in complete healing, no pacemaker had to be inserted.
At 18-month follow-up the patient was allowed to continue professional sports, he is in the first league. His follow-up for Lyme borreliosis is continued.
Dr Stef, Györgyi *, Dr Bózsik, Béla Pál **, Dr Forster, Tamás, Dr Jebelovszki, Éva, Dr Thury, Attila, Prof. Dr. Csanády, Miklós * Heart Clinic Balatonfüred ** Lyme Borreliosis Foundation Budapest Szent-Györgyi Albert Medical University Szeged, Department of Cardiology, 2nd Clinic for Internal Medicine, Budapest
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**Comment**
A number of important findings:
the only symptom was a heart conduction issue
standard testing was negative
this case would have been missed if it weren’t for a clinical diagnosis
dark field microscopy is much better at revealing Lyme disease
after treatment was started (which served as a provoking agent) serology became positive
a combined, high-dose, antibiotic therapy bypassed the need for a pacemaker
they are smart enough to have lengthy followup as they understand the persistent nature of the organism.
we know of this case thanks to the doctors who wrote about it. How many more cases exist that aren’t on record?
LYME PODCAST: 74-YEAR-OLD WOMAN WITH A TRIPLE TICK ATTACK
Welcome to an Inside Lyme case study. I find that the best way to get to know Lyme disease is through reviewing actual cases. In this case study, I will be discussing a 74-year-old woman with a triple tick attack. This case series will be discussed on my Facebook and made available on podcast and YouTube.
In this episode, I will be discussing a 74-year-old woman with a triple tick attack.
This case was described in the journal Cureus, written by Kumar and colleagues in 2019.
A 74-year-old woman had underlying medical problems. She was a smoker with chronic obstructive pulmonary disease (COPD). She also had hypertension. She was initially treated for pneumonia with ceftriaxone and azithromycin. She was also treated for Babesia.
Her red blood test contained parasites typical of Babesia. That is, they were able to see a parasite typical of Babesia under the microscope. Babesia is a disease from a parasite found in a deer tick. This is the same deer tick that carries the spirochete that causes Lyme disease. Over 9% of her red cells contained parasites typical of Babesia.
The doctors added atovaquone for Babesia. Atovaquone is marked under the name Mepron in the US. The doctors also added doxycycline over concerns that the woman might also be infected with Lyme disease. She was quite ill. She was also placed on a respirator. She required medications to raise her blood pressure.
The doctors prescribed erythrocytapheresis due to the severity of her illness and the high number of parasites in her red cells. During erythrocytapheresis, some of the red blood cells are removed and replaced with blood from a donor. The number of parasites dropped from 9 to 5.54 percent, but the woman remained in shock. Her kidneys function worsened, which was believed due to hemolysis.
The woman’s blood test was positive for Lyme disease and Anaplasmosis.
The doctor made one last antibiotic change. The doctors changed the treatment for Babesia from atovaquone and azithromycin to clindamycin and quinine. Clindamycin and quinine are still used for difficult to treat cases of Babesia. She improved enough to take her off the respirator. Her blood counts and kidney function returned to normal after 14 days of treatment.
There have been a number of studies showing three or more pathogenic infections in the same tick. “The incidence of a three pathogen infection is rare” writes Kumar. In actual practice, I have seen individuals with three pathogens who have not been published.
I support the Kumar’s call for a low level of suspicion; “A low threshold for suspicion should be held for a co-infection when patients exhibit a presentation that would be atypical for single pathogen exposure. A delay in diagnosis can lead to prolonged disease duration and increases the comorbidities associated with the infectious state.”
I agree with the doctor’s concerns with the reliability of testing for Babesia. Kumar writes, “A blood smear is the gold standard for the diagnosis of Babesiosis, however, if a patient has a low level of parasitic load, PCR is more sensitive.”
Kumar also raised concerns about the reliability of testing for Anaplasmosis. Anaplasmosis has been seen in red cells in some patients. “PCR and serological testing are also available, which are more sensitive than a thin smear.”
Finally, Dr. Kumar advised a longer course of treatment for Babesia. “In case of immunocompromised individuals who are at risk of relapsing Babesia, treatment for a total of six weeks is preferred, including a period of two weeks after parasites are no longer visible on a thin smear” writes Kumar.
What can we learn from this case?
It is important to look for a tick-borne infection even in patients with an underlying illness.
Patients can suffer from more than one tick-borne infection at the same time.
Their illness can be severe.
What questions does this case raise?
Would Babesia have been discovered without seeing the parasite under the microscope?
What is the best combination of treatment and length of treatment to prevent long-term complications?
TREATING TICK-BORNE DISEASE IN MY PRACTICE
In my practice, each individual requires a careful assessment. That is why I order tests a broad range of tests, including blood counts, liver and kidney function, thyroid disease, lupus, and rheumatoid arthritis in addition to tests for tick-borne infections. I also arrange consultations such as neurologists, rheumatologists, and ophthalmologists.
Many patients are complex, as highlighted in this Inside Lyme Podcast series.
We need more doctors with skills diagnosing and treating individuals with more than one tick-borne infection. We could use a reliable test to determine who has a tick-borne infection and when tick-borne infections have resolved. We need to determine the best course of treatment to prevent chronic illness. We hope a professional can use this case to remind them to look for more than one tick-borne infection and treat them accordingly.
We also need to give doctors the freedom to treat these difficult cases without undue interference by colleagues, insurance companies, medical societies, and medical boards.
Inside Lyme Podcast Series
This Inside Lyme case series will be discussed on my Facebook and made available on podcast and YouTube. As always, it is your likes, comments, and shares that help spread the word about this series and our work. If you can, please leave a review on iTunes or wherever else you get your podcasts.
Sign up for our newsletter to keep up with our cases.
References:
Kumar M, Sharma A, Grover P. Triple Tick Attack. Cureus. 2019;11(2):e4064.
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**Comment**
A few details:
She was an avid gardner
It doesn’t specify if she saw a tick or not. The title is misleading because it infers she was bitten 3 separate times when in fact 1 tick bite could transmit all 3 pathogens simultaneously.
The study states that it is COMMON to be infected with 2 pathogens but that being infected with 3 is rare, but that risk increases in endemic areas (like Wisconsin).It is my experience that infection with 3 pathogens or more in WI is fairly common.
They don’t state it but ALL Lyme/MSIDS patients are immunocompromised, which means we typically need longer treatment. Mainstream medicine completely ignores this issue.
The study states: A treatment duration of a total of 10 days has been shown to be highly effective in treating both Lyme disease and human granulocytic anaplasmosis [12-13]. I couldn’t disagree more. The study in reference #12 studied 10 days of treatment to eradicate the EM rash. It’s common knowledge that the disappearance of EM rash does not mean a systemic infection is eradicated. In fact, the EM rash has been known to disappear without any treatment what so ever! The study in reference #13 is really about the increased disease severity in those with Anaplasmosis who had a delay in treatment. The study also admitted that their study may have excluded those with PCR-negative cases as well as the fact they are assuming disease course and severity doesn’t differ with different species.
Lyme disease can cause many disparate symptoms over the course of its progression. It’s often called ‘The Great Imitator’ because many of its generalised symptoms resemble the symptoms of other, more prominent chronic conditions. This makes it very difficult to diagnose, and misdiagnosis rates are suspected to be extremely high. Compounding this is the fact that chronic Lyme is not widely recognised as a legitimate disorder. Despite many thousands of people suffering from long-term Lyme symptoms, hugely different from the accepted acute symptoms, the condition remains an outlier. Therefore, patient and doctor education on Lyme disease in all its forms is not as good as it should be. Many symptoms fall by the wayside because of this, and either go uninvestigated or misdiagnosed. Bladder issues might not be the first thing you associate with Lyme disease; but can Lyme disease cause bladder problems?
What is Lyme disease?
Lyme disease was christened in the town of Old Lyme, Connecticut, in 1975. This is relatively recent for a major disease, which speaks of its insidious nature. Lyme is caused by the bacteria Borrelia burgdorferi, which is spread to humans via the deer (or black-legged) tick in America, and the castor bean tick in Europe. Ticks are conduits of disease-causing bacteria, and often carry many different strains simultaneously. However, not every tick carries Borrelia burgdorferi and not every tick bite from those that do will result in Lyme.
Although the disease is often associated with America, particularly the north-eastern states, it is a global issue. Lyme rates remain alarmingly high in Europe as well as the U.S., with global warming compounding the issue. As the global temperature increases, ticks are able to live longer and migrate further, thereby increasing the instances of Lyme all over the world.
Image by Meli1670 on Pixabay: Despite many thousands of people suffering from long-term Lyme symptoms, the condition remains an outlier.
Acute vs. Chronic Lyme
The initial symptoms of Lyme present much like the flu. They manifest a day or two after the tick bite, and often involve a headache, fatigue, aches and fever – standard flu symptoms. The calling card of Lyme is a distinctive bullseye-shaped rash, which is present at the site of the bite in the majority of cases. If this is present, Lyme can be conclusively diagnosed. However, it is often overlooked, as many times people don’t realise they’ve been bitten. If treated with antibiotics, acute Lyme can be resolved rapidly and successfully for many patients. However, if that window is missed, Lyme will progress to its chronic long-term form, bringing with it a whole host of new, problematic symptoms.
Chronic Lyme represents an interplay between infection symptoms and inflammation symptoms. The former is caused by the underlying Borrelia infection, while the latter is caused by the body’s exaggerated response to the persistent bacteria. Because of this, a wide spectrum of symptoms is possible, varying in severity depending on the patient. The highly resistant Borrelia bacteria can travel and infect various parts of the body, including the neurological system and the pulmonary system.
Can Lyme disease lead to bladder problems?
Can Lyme disease affect your bladder? Some experts say it might. Bladder conditions might seem inferior to more severe issues relating to the brain and heart. But anyone who’s suffered from bladder pain can testify that it’s not a symptom to be taken lightly. The uniform name for frequent urination, bladder pain and inflammation is interstitial cystitis (IC), although a diagnosis of this disorder often means that the root cause is unknown. So does Lyme disease cause interstitial cystitis?
Lyme specialists are claiming there is a frequent crossover between Lyme symptoms and bladder issues, although not many studies have been conducted on this apparent link. There is seemingly also a connection between stomach issues, a common complaint of Lyme patients, and bladder problems. An animal study, conducted in 2006, found that in rodents, Borrelia burgdorferi is most often found in the bladder. While this and the anecdotal evidence are intriguing, it remains an unexplored area in the field of Lyme disease.
Image by Qaudronet_Webdesign on Pixabay: Can Lyme disease cause frequent urination? Some experts are suggesting it might.
Another, more recent study has provided a more concrete link in humans. This one found that voiding dysfunction (a catchall term used to describe poor coordination between the bladder muscle and the urethra) can appear as an early or late stage symptom of Lyme. Micturition (urination) disorders can subsequently occur via two paths. The first involves the Borrelia bacteria directly invading the bladder. The second occurs as a by-product of neuroborreliosis, a symptom of Lyme caused by the Borrelia bacteria breaching the blood-brain barrier and inflaming the brain. This is a serious manifestation of chronic Lyme disease, which has repercussions for many different areas of the body.
Seven out of seven patients who suffered from Lyme encephalomyelitis (inflammation of the brain) reported reflex response problems with their bladders.
While it seems conclusive to say that there is some link between chronic Lyme disease and bladder problems, most doctors won’t have the necessary Lyme education to correctly diagnose it as such. Lyme specialists (like BCA-clinic in Germany) are few and far between; and until more medical professionals are aware of the insidious dangers of chronic Lyme in all its potential forms, patients will continue to suffer sustained misdiagnoses.
People with interstitial cystitis feel like they have a bladder infection that never goes away. It doesn’t respond to antibiotics, and urine cultures are typically negative. Because these patients are often treated repeatedly with antibiotics, however, they frequently end up having chronic urinary tract infections with antibiotic-resistant bacteria induced by taking antibiotics. The condition occurs more often in women than men at a 5:1 ratio.
I’m starting to hear from chronic Lyme patients who suffer from bladder pain and symptoms consistent with IC. I’m also hearing from men with chronic Lyme who have bladder symptoms and chronic prostatitis (chronic infection of the prostate gland).
And, interestingly, remembering back to patients from the past, sufferers of IC frequently had chronic pain in other areas of the body. Many of them also had fatigue and symptoms common to fibromyalgia and chronic Lyme disease.
And, according to Dr. Rawls, a former OBGYN,
This makes me believe there has to be a microbial connection. Borrelia, the microbe commonly associated with Lyme disease, could be a culprit. However, I would lay odds on mycoplasma and a closely related bacterium called ureaplasma. About 75% of chronic Lyme disease sufferers have been found to harbor at least one species of mycoplasma.
According to Garth Nicolson, who’s wife survived a lethal form of bioweaponized Mycoplasma,
90% of evaluated ALS patients had Mycoplasma. 100% of ALS patients with Gulf War Syndrome had Mycoplasma and nearly all of those were specifically the weaponized M. fermentans incognitus.
*One of the hallmark symptoms of Mycoplasma is fatigue*
And the bad news for us is that Nicholson’s experience has found Mycoplasma to be the number one Lyme coinfection, and similar to other coinfections can be supposedly cleared for years only to reappear when conditions are right.
Neuroimmunology: What Role for Autoimmunity, Neuroinflammation, and Small Fiber Neuropathy in Fibromyalgia, Chronic Fatigue Syndrome, and Adverse Events after Human Papillomavirus Vaccination?
Fibromyalgia is a disorder characterized by chronic widespread pain and non-pain symptoms, such as fatigue, dysautonomia, and cognitive and sleep disturbances. Its pathogenesis and treatment continue to be the subject of debate. We highlight the role of three mechanisms—autoimmunity, neuroinflammation, and small fiber neuropathy—in the pathogenesis of the disease. These mechanisms are shown to be closely interlinked (also on a molecular level), and the review considers the implementation of this relationship in the search for therapeutic options. We also pay attention to chronic fatigue syndrome, which overlaps with fibromyalgia, and propose a concept of “autoimmune hypothalamopathy” for its pathogenesis. Finally, we analyze the molecular mechanisms underlying the neuroinflammatory background in the development of adverse events following HPV vaccination and suggesting neuroinflammation, which could exacerbate the development of symptoms following HPV vaccination (though this is hotly debated), as a model for fibromyalgia pathogenesis. View Full-Text
FOR MANY LYME DISEASE PATIENTS, THE BACTERIA SEEM TO OUTSMART ANTIBIOTIC TREATMENT. WHY?
It’s a hotly debated topic, and one that is still not completely understood – what causes the persistent symptoms in many Lyme disease patients? Why is it that 10-20% of patients, after early diagnosis and treatment with antibiotics, continue to face long-term, chronic, even debilitating, symptoms including joint or muscular pain, fatigue, and/or neurocognitive problems? And why do patients diagnosed later in their disease often have a more difficult time finding an effective treatment? Key possible culprits, persister bacteria, are under investigation, and researchers are uncovering their fascinating and diverse array of adaptive abilities, with the goal of one day eradicating them and more effectively helping patients.
LYING IN WAIT
Borrelia burgdorferi, the spirochete bacteria that cause Lyme disease, have an elaborate lifecycle, critical for their own day-to-day survival. They have evolved adaptations to multiple, sometimes harsh, environments – moving from bloodmeal-source host animals to ticks, repeating the cycle back into host animals, and sometimes into humans. Persistence is an essential and multi-faceted strategy that B. burgdorferi and other bacteria use to survive and adapt to their highly varied environments.
Unfortunately, these same adaptive abilities may also provide B. burgdorferi the ability to survive an onslaught of antibiotics. In vitro (in culture), treatment with antibiotics kills off most cells, but a small number survive because they adapt to have a new superpower – they are tolerant (although not resistant) to an aggressive antibiotic challenge. Their strategy is to lie dormant during an onslaught of antibiotics, changing their protein composition and shape. When the conditions are just right, and the antibiotics are cleared from the host’s system, they can then transform back into mobile spirochete form (thus giving them the freedom to resurge and multiply). GLA-funded research by Kim Lewis and his team at Northeastern University as well as research by GLA-funded Ying Zhang and his group at Johns Hopkins University revealed this amazing strategy. Their teams independently confirmed the existence in culture of dormant, persister B. burgdorferi, providing evidence that these persisters arise during antibiotic treatment and transform back into mobile spirochetes post-treatment. Whether this phenomenon occurs in patients remains to be shown, but it suggests a way to explain why antibiotic treatment is inadequate in a sizeable proportion of patients.
Interestingly, persistence is not unique to B. burgdorferi. The bacteria that cause other chronic diseases (e.g., tuberculosis, syphilis and leprosy) also form persisters.
A MASTER OF DISGUISE
How do persisters survive harsh conditions such as antibiotic treatment? For one, they have an altered gene expression profile, producing key proteins which allow them to live in the presence of antibiotics. Throughout its life cycle, B. burgdorferi is a master chameleon, transforming itself from its corkscrew-shaped spirochete form into a variety of shapes, such as round (metacyclic), L-form bacteria, spore-like granules or cysts, and then back again into spirochetes. These different forms can impact diagnosis. For example, there is some limited evidence that B. burgdorferi takes on L-forms in spinal fluid, which could impact methods used for screening when a case of neuroborreliosis (a neurological manifestation of Lyme disease) is suspected, for example.
Yet another strategy used by the wily B. burgdorferi and other bacteria is to invade host cells. For example, the bacterium that causes tuberculosis (TB), Mycobacterium tuberculosis, can exist in a dormant persister state in TB lesions, which necessitates much longer antibiotic treatment in patients than is seen in vitro. Some preliminary findings suggested that in cultured neurons, glial cells, macrophages, and skin keratinocytes, atypical and cystic B. burgdorferi have been found.
PROMISING RESEARCH
Researchers have had very limited success in cultivating replicating B. burgdorferi directly from animals or humans post-antibiotic treatment, which is part of the difficulty in doing experiments on persisters. There is some indirect evidence of persisters from multiple studies in animals (mice, dogs, monkeys) infected with B. burgdorferi and treated with antibiotics. For example, using a mouse model of Lyme disease, after one month of antibiotic treatment, researchers isolated B. burgdorferi DNA and detected non-dividing but infectious spirochetes.
Researchers have also been able to isolate live B. burgdorferi from animals using ‘xenodiagnostic ticks’, in which uninfected ticks feed from an infected animal or human and become infected after feeding. This offers proof that the host was infected with B. burgdorferi. In a study with infected animals who exhibited a clear resurgence of bacteria following antibiotic treatment, B. burgdorferi was then isolated using xenodiagnostic ticks, a strong indication that these are persisters.
When B. burgdorferi-infected nonhuman primates were treated with antibiotics, bacteria were also recovered from multiple tissues, suggesting that bacteria could survive. Signs of inflammation in and around these tissues were also observed.
In an exciting 2019 study, Ying Zhang and team isolated slow-growth forms of B. burgdorferi (including biofilm-like, round body and spirochetes) from culture and compared mice inoculated with these slow-growing forms versus mice inoculated with fast-growing spirochetal B. burgdorferi. The slow-growth persister B. burgdorferi were not only more tolerant to the standard Lyme disease antibiotic treatment with doxycycline or ceftriaxone but they were also associated with more severe arthritis in mice than the fast-growing spirochete form. However, a cocktail of antibiotics – Daptomycin, Doxycycline and Ceftriaxone – did successfully eradicate the infection in the mice infected with slow-growing persisters. Human studies modeled after these would be helpful in understanding the disease course, especially the response to antibiotics.
In other studies, different cocktails of antibiotics, as well as essential oils, have been successful in eradicating B. burgdorferiinvitro. Disulfiram, a drug used for treating alcoholism, has been shown to be extremely effective in eradicating many forms of B. burgdorferi invitro and in mice, and in a small study in humans.
Despite all these promising results in culture and in animals, trials in humans have not advanced well. Based on research done to date, researchers cannot confirm or exclude that live persisters are present in antibiotic-treated patients who have persistent symptoms (i.e., patients with post-treatment Lyme disease symptoms). One large part of the problem is the shortage of confirmed Lyme disease patients for clinical trials, as many patients lack concrete clinical (serological) evidence of having Lyme disease. In three separate clinical trials, only 4% of 5457 patients made it through the screening process to enter a trial.
Altogether, some critical groundwork has been established in the study of persisters. However, studies surrounding persisters are still in early stages, and their connection to ongoing symptoms of post-treatment Lyme and chronic Lyme still warrant more confirmation and extended studies. There is a great need for evidence-based research conducted at all levels of research involving persisters, from in vitro studies through clinical trials. Supporting these efforts calls for improved diagnostics and detection methods for persisters, and an incremental move into larger-scale human studies which confirm the presence of live persisters and explore treatment options. GLA is optimistic that with future studies, there will be new breakthroughs in this very important area.
By Global Lyme Alliance and Dana Barberio, M.S., Scientific/Medical Writer and Principal, Edge Bioscience Communications
Madison Area Lyme Support Group 