Lyme arthritis and reactive T cells

A friend told me that a new mouse study gave us the answer regarding Lyme arthritis. 

Not quite.  The study was done at the University of Utah (U of U) in mice.  Mice with Lyme arthritis had severe inflammation with thickened synovium. Low levels of spirochetes, referred to as residual bacteria were usually found in the joints. The pathology and immunology revealed the basis for the inflammation was abnormal T cells. This has been described in the past. 

The germ response immune system has two primary legs:  Killer T Cells vs antibodies (behaving badly).  Most autoimmune diseases -- based on current knowledge are due to antibody responses. 

The first leg, the T cell leg is referred to as the innate immune system.  The antibody side -- connected with B cells comprises the acquired immune responses.  

This is the simplest and easiest way to understand the dichotomy.

Patients may go to rheumatologists and report they have fully tested, they don’t have any autoimmune diseases. Rheumatologist only test for things like rheumatoid factor, CCP antibodies, ANA antibodies and a host of other antibodies. Antibodies which attack our healthy tissues. Not poorly acting T cells.  Commercially available tests only measure autoimmune antibodies. 

There likely exist numerous autoimmune disorders for which there is no available test. The rheumatologist should say that based on currently available tests there is no evidence of an autoimmune disease. 

Lyme arthritis is autoimmune without antibodies.  We know the immune system frequently struggles to make Lyme antibodies, explaining some negative tests in Lyme infected individuals.  

There is no test, especially one that would be agreed upon.

The autoimmune, inflammatory reactions were associated with a small number of residual Lyme bacteria.   Small numbers of spirochetes, stubborn and hard to eradicate may cause a lot of inflammation as we have long suspected. 

There are two belief systems here.

One can choose to believe that the T cell response is part of a self-perpetuating process irrespective of residual or germ. In this case, powerful immune suppressing drugs and/or surgical removing of the synovium, the joint lining is the way to go. Not my opinion.

I have found that long term antibiotics, including IV antibiotics work for most patients. 

This is the rub:  Lyme bacteria are the oxygen which feed the fire – the inflammatory T cell medicated response.  Take away the oxygen and the fire goes out -- the joints improve. 

Lyme is in Utah.

Of course, people (most people,) are not mice. You cannot necessarily generalize mice data to people.

Of course in the film “A hitchhiker’s guide to the galaxy” (spoiler) we ultimately learn that white mice run the world and we humans are the guinea pig test subjects. 

You never know.

Lyme: my new and improved approach to patient care.

I am excited about my new approach to patient care. 

The EPCDS concept (exhaustion/fatigue, pain and cognitive dysfunction/brain fog has led to a change in philosophy and approach.  

A patient has criteria for CFS, fibromyalgia, POTS, MCAS, Lyme and coinfections. These issues have arisen in the treatment of several patients over the past 2 days. 

First, I address fatigue. (Treating symptoms is not applying a bandaid.  When symptoms improve function improves. When function improves the immune system and other systems work better, facilitating the healing process. These patients are beyond fatigue and exhaustion; getting out of bed is a struggle.  I first look at sleep. I review meds. Many meds contribute to sleep problems and may exacerbate POTS and MCAS.  BP meds can be a problem.  A patient I saw today is taking a BP med Cozaar. Without getting into pharmacology, in some cases Cozaar may contribute to fatigue and exacerbate POTS.  Inderal, a beta blocker taken to prevent migraines may be similarly problematic. Another patient seen today with POTS is taking Abilify for bipolar 2. This med can cause orthostatic hypotension/POTS.  Other options are preferred.  Meds are a problem frequently and must be carefully reviewed. 

Sleep is horrible for these patients. Sleep is fragmented and unrefreshing.  My last patient today falls asleep in front of the TV in the living room at 3 am; wakes up at 6 am to let the dog out; and, it is only then that she goes her bed/bedroom to sleep for another 3 hours. She is nonfunctional without stimulants. Not surprising.  We always have to go back to sleep hygiene and help patients make changes if possible. Changing behavior is not easy. CBT (cognitive behavioral therapy) may help.  Perhaps we fix sleep and the patient will still be exhausted. That’s OK we have still made an important inroad.  There are various medications which may help patient sleep.  I have found that patients with chronic insomnia may only respond to cocktails of meds.  Specific drugs might be considered in each patient.  For example, the sedating muscle relaxer Flexeril has been shown to help patients with tinnitus and may also help fibromyalgia pain. The med may not be tolerated because of a hangover the next day; adjustments can be made.  Patient may only sleep with: Restoril, doxepin, gabapentin and possibly others.  Restoril may help with anxiety. Doxepin may help with mast cell activation. Gabapentin may help with central pain and neuropathic pain.  

We can frequently kill 2 birds with one stone. Sleep, sleep per chance to dream.  When patient report dreams it tells me that REM sleep is present which in some cases is not apparent on sleep studies. Fatigue can certainly be treated with drugs of promote wakefulness like Nuvigil.  Stimulants like Adderall may help.  These drugs are also nootropics and may help improve cognitive dysfunction.  Sleep doctors do not understand the intricacies of such complex patients. 

Pain.  We need to figure out what kind of pain.  The pain may be nociceptive or neuropathic.  The pain may be central.  The pain may be poorly understood as is the case with migraines.  Various pain types are treated differently.  Treating pain and treating sleep may dovetail with each other.  Nociceptive pain, physical pain, is frequently associated with central sensitization – pain amplification.  Patients may have allodynia.  Mild touch causes pain.  These patients do not have a low threshold for pain.  Their pain threshold has been modulated by changes in the central nervous system. An understanding helps the patient and the doctor.   Namenda blocks glutamine and may be effective for fibromyalgia – amplified pain and migraine. Specific drugs target specific types of pain.  Pain drugs can exacerbate or act as a nootropic and relieve brain fog, for example Namenda.  Antidepressant such as amitriptyline and possibly Cymbalta along with anticonvulsants like Neurontin may be helpful.  Other agents such as low-dose naltrexone and medical marijuana are sometimes helpful.  Etc.  Pain is a huge topic and there is much we can do. Unfortunately, many “pain doctors” just hand out prescriptions of Oxys and do their patients a disservice. 

Brain fog I have already touched on.  Treating the underlying illness is important. Still, there are things we can do.  The nootropics, brain drugs mentioned above may be helpful.  Others, for example, magnesium thionate may improve cognition.  Cognitive dysfunction in a young person is something we have to jump on. If neuroborreliosis is the cause intravenous antibiotics may be necessary. In this case, treating the underlying cause takes precedent over managing symptoms. POTS and MCAS can be associated with brain fog and need immediate treatment. We can start MCAS therapy with dietary change and H1, H2 blockers. We may need to prioritize POTS which can be truly disabling. (If MCAS is causing anaphylaxis etc. priorities change). We can juggle many balls if needed. In most cases POTS can be managed well and the treatment is discussed elsewhere.  The treatment of MCAS is discussed elsewhere. Cognitive dysfunction must be carefully evaluated.  If a patient has prominent night sweats, air hunger, bouts of tearfulness and depression babesiosis becomes the first priority. Etc. 

Treatment of chronic infection is addressed from the outset.  However, priorities must be established.  For example, doxycycline alone may be prescribed while sleep and pain and POTS are addressed. Every case is different. 

There is something to be learned from (the best) doctors who treat:  chronic fatigue syndrome, POTS, chronic pain and others. 

What is different in my approach?  I focus on symptoms and function. Patients do much better.  Other specialists may be consulted to cover the bases but sleep specialist, pain specialists and neurologist may not be particularly interested in the care of such patients and label them with: depression – go to the psychiatrist, fibromyalgia – not much can be done or psychosomatic.  The post is intended to give the reader a flavor of the approach and only scratches the surface. These disorders are extremely complex. A lot of thinking and figuring things out is required.

Many disorders may be associated with EPCDS: thyroid disease, adrenal dysfunction, metabolic disorders, genetic disorders, other autoimmune syndromes, cancer, depression, pernicious anemia - B12 deficiency, celiac disease, renal disease, liver disease, heart disease, other chronic infection, sarcoidosis and others. I am sure there are many more. This list is from the top of my head.   The EPCDS syndrome is common. Let's not make assumptions and do our best not to miss anything. 

The information discussed here is evidence based and discussed in peer reviewed journals.

Appointments available. Paradigm Medicine, Rockville MD.

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What is POTS? Corecting the record.

What is really going on with POTS?  Is it a neurological disorder, a cardiac disorder?

Probably neither, the answer may lie within the purview of endocrinology?

There is a genetic component. This is clear. For example, patients with hypermobile joints are more likely to develop POTS.

Nobody knows what causes POTS.  Apparently 10 different theories have been proposed.  It is not due to direct dysfunction of sympathetic and parasympathetic nerves.  It is not due to nerve damage such as what you might find in diabetic autonomic neuropathy. 

Autonomic neuropathy should not be confused with dysautonomia.  The two are quite different. 

The prevailing explanation, according to a recent review, primarily relates POTS to dysfunction of the RAS.  This stands for renin angiotensin system.  Receptors for angiotensin may be off kilter. Angiotensin is messenger molecule or hormone known to be associated with the regulation of blood pressure, constriction of blood vessels and retention of salt and water.  This what I remember from physiology.  It turns out that Angiotensin and its associated receptors have wide reaches effects in a wide array of organs and organ systems– including the cardiovascular and nervous systems. 

So, POTS is an endocrine disorder which may or may not be associated with genetic factors.  It has overlap with other specialties including neurology and cardiology.  

Drugs currently prescribed, including Fludrocortisone, DDAVP and Midodrine directly counter aberrant physiology associated with the disorder as viewed through this lens.