Fatigue

Patients with Lyme disease are incredibly poly-symptomatic or pan-symptomatic; in other words, they frequently have every conceivable symptom and some that were not conceivable. Still on average, the three most devastating symptoms in chronic Lyme disease are: fatigue, pain and cognitive dysfunction. Let me attempt to address fatigue. Then the others.

Fatigue is feeling very mysterious thing. Words like fatigue or exhaustion do not begin to describe what many patients experience. Patients frequently report that it is difficult to move their head off the pillow in the morning – the thought of taking a shower (the thought, not the action) is daunting. This experience describe something which is qualitatively different from what most of us think of as fatigue or exhaustion. I don’t have a name for it.

Where does fatigue come from where is it localized? It seems to be a brain issue. A recent study from Stanford University School of medicine has found structural, MRI changes in patients suffering with chronic fatigue syndrome. There is reduction in a white matter content, particularly in the non-dominant hemisphere in an area called the arcuate fasciculus. The level of symptomatology correlated with the extent of anatomical change. Interesting. 

Medical doctors are quick to diagnose Lyme patients with a psychological disorder: just what long-suffering souls, marginalized by mainstream medicine want to hear (for the millionth time) I suspect infectious disease doctors would be displeased if psychiatrist diagnosed Chagas disease or tularemia and  rheumatologist would take offense with psychiatrists diagnosing scleroderma or sarcoidosis. Specialist: stick to your own fields. If you don’t know what’s wrong simply say I don’t know what’s wrong; don’t make up a diagnosis, the wrong diagnosis, one that stigmatizes, ignores, marginalizes and disparages your patient, thank you.

Fatigue is associate with so many different medical disorders. Generally, most doctors quickly rule out obvious disorders such as hypothyroidism. That is about as far as they go. (They frequently get that one wrong too). Most doctors cannot comprehend fatigue that Starbucks can’t fix. 

There are some other common causes of fatigue which need to be examined. It is not unusual for me to see a patient who has suffered with fatigue for years who has never had a sleep study. The polysomnogram, the basic sleep study will frequently find: obstructive sleep apnea, central sleep apnea, abnormal sleep architecture with loss of deep sleep and/or REM sleep, restless leg syndrome and periodic limb movement disorder. When patients say they are able to quickly fall asleep or take a nap on command, a second study called an MSLT, multiple sleep latency tests should be also ordered to rule out narcolepsy.

Of course chronic infections do cause fatigue, especially those involving the central nervous system. I find that my patient who failed previous therapy need more intensive, frequently intravenous antibiotic therapies. Even the NIH sponsored studies show improvement of fatigue with intravenous Rocephin. 

If the patient was well before Lyme disease I assume Lyme and related infection is the primary cause of his/her fatigue. Looking for things such as mycotoxin exposure and heavy metal exposure may be worthwhile in patients with chronic symptoms. In my experience, inadequate treatment of Lyme disease, babesiosis and/ or other co-infections is frequently an issue.

Of course patients suffering with chronic Lyme are depressed. Only rarely does the treatment of depression significantly improve the fatigue. (Many doctors become hung up with this answer). Patients have trouble falling asleep and staying asleep. They have disrupted circadian rhythms, stay up at night and sleep during the day. I believe it is okay to treat  symptoms. A lack of sleep contributes to a cascade of falling dominoes leading to neuro-endocrine and immune dysfunction making everything worse. Medications for sleep may include trazodone, Ambien, Lunesta or Restoril. Klonopin in particular is useful when restless leg syndrome, anxiety or pseudo-seizure like activity is present.

A word about the treatment of depression. Patients with CNS infection have excessive neurotoxins floating around such as quinolinic acid. Patients may have glutamate excitotoxity. This means their brains are very sensitive to the neurotransmitter glutamate or glutamic acid. Lamictal may be the drug of choice; this agent needs to be titrated carefully because of the risk of serious skin disorder. Patient may paradoxically worsen with SSRIs like Prozac and Zoloft; Wellbutrin may be better tolerated. 

Fatigue can be treated with a wide variety of stimulants. Changing brain chemistry can help. Nuvigil has been a particularly helpful drug although insurance companies are loath to pay for it. Alternatively, ADD drugs like Ritalin and Adderall may be used with varying degrees of success. When these medications are effective improvements in function help the overall healing process.

Adrenal fatigue is real. Endocrine dysfunction of various kinds may occur. Chronic illness overwhelms the neuro-endocrine axis. Blood tests, saliva test and urine test may be helpful; adrenal supplements may be very helpful.

Other treatments occasionally help such as low dose naltrexone and now oxytocin therapy.

Lyme patients have an incredibly complex illness: do not overlook a wide array of possible contributing factors.

Sudden tearfulness

Sudden weepiness, tearfulness, crying at commercials – all for no apparent reason is a common complaint amongst those suffering with Lyme disease. Why does this occur?

It is easy to find lengthy symptom lists for: Lyme disease, confections, Babesia, Bartonella, chronic fatigue syndrome, fibromyalgia, gluten sensitivity, adrenal fatigue and other overlapping conditions.

Many symptoms on the various lists are repeated over and over frequently leading to more confusion.

It is not possible to diagnose a coinfection based on a single symptom.

However, some symptoms – particularly when seen in constellations along with other symptoms, may be fairly specific for a particular coinfection syndrome. 

Sudden unexpected tearfulness seems to fall within this category.

Babesia?

Classic symptoms are night sweats, air hunger, recurring flulike symptoms, low grade fevers, chills, dry cough, headaches, muscle pain and depression.

I think weepiness can be added to this basic symptom list. 

I have found a striking correlation between this symptom and Babesiosis. 

With treatment, Babesia symptoms can appear and disappear in any order. Usually tearfulness resolves more quickly than other symptoms. Air hunger can remain after the disappearance of night sweats or vice-e-versa. 

Some symptoms are easy to explain. Babesia is a blood parasite, similar to Malaria, it causes periodic rupture of red blood cells leading to a specific inflammatory response hence we see constitutional symptoms like flulike symptoms and night sweats.  Air hunger may be the result of pulmonary inflammation suggested by a mouse model with B. duncani but not B. microti. Usually we makes lists of symptoms without trying to understanding why they occur. I like to try to find explanations. These explanations are speculative.

There is an anatomic center in the brain responsible for rapid changes in emotional responses. How this center is affected is unknown. Interestingly, emotional lability and tearfulness may be seen in patients with a history of traumatic brain injury, pseudobulbar palsy and certain stroke syndromes. Why Babesia causes this reaction is unknown.

Other cerebral parasites may affect the brain in strange, unexpected ways.  Infection with toxoplasmosis is considered benign, without consequences, but patient so infected have a higher incidence of car accidents and suicide per published studies. 

It may be worthwhile to pay attention to this, perhaps, specific symptom: sudden crying for no good reason.

Complex patient with autoimmunity, humoral deficiency treated with combined modalities.

This 42 year old female a had a history of stable Crohn’s disease, otherwise, she was in excellent health until 2009. Previous to the onset of illness she had been an avid athlete who ran 10 miles several times per week. She lives in a neighborhood known to be Lyme endemic. Her dog has recently been treated for Lyme disease. Her husband had a bull’s eye rash 8 years ago and was successfully treated with a short course of doxycycline. She has no recollection of a prior tick bite, flu-like illness or rash of any kind.

Her colitis flared for no apparent reason. She experienced an unusually difficult exacerbation requiring high dose steroids. As the gastrointestinal symptoms cleared she began to experience joint pain which ultimately became wide spread. Inflammatory bowel diseases, Crohn’s and ulcerative colitis can be associated with “extra-colonic” autoimmune manifestation including inflammatory arthritis.  She saw numerous doctors at both the Mayo Clinic and Johns Hopkins who concurred with this diagnosis. Frustratingly, she did not respond as expected. A wide array of immunosuppressive biological agents including Enbrel and Remicade were prescribed over a two year period; during this time her illness became much worse. She became house bound. She suffered with debilitating fatigue, neurological symptoms including tremors, numbness and tingling, weakness, poor balance and progressive cognitive deficits. She saw a homeopath who diagnosed Lyme disease. She was prescribed a wide array of natural therapies which proved to be ineffective. Another LLMD  treated her with IV Rocephin for three months and she continued to steadily feel worse. It was at this point that I first her in my office.

She was disabled by diffuse joint pain, large, medium and small joints, from head to toe. She was in pain management and taking a high dose of  opiod. She was unable to focus or think clearly. Fatigue was beyond description. Lifting her head from the pillow was a task, taking a shower a massive endeavor. She experieneced constant shortness of breath.  She lost considerable weight and muscle mass. She had constant flulike symptoms with low-grade fevers, chills and night sweats. Neurological symptoms included: numbness and tingling, a loss of balance and a loss of coordination, episodes of frank confusion, progressive memory loss, trouble reading and writing, uncontrollable thoughts, irritability, anxiety and depression.

Her examination was remarkable for joint tenderness without swelling or signs of inflammation and and abnormal neurological examination which showed weakness, asymmetric reflexes and a severe loss of sensation of lower extremities. 

Laboratory testing revealed positive revealed a positive IgeneX WB with IgM 39 and 41 bands. Coinfection panel was negative. Blood smear exam showed active parasitemia. 

Intravenous antibiotics in combination and anti-malarial medication were administered for months; the clinical course waxed and waned; a modicum of  durable improvement was seen after 6 months.

She experienced unusually prolonged and recurrent Herxheimer reactions.

 A sleep study showed an absence of both deep sleep and REM.

She was treated aggressively for Lyme and Babesia.

An EMG/NCV showed no significant peripheral neuropathy. A small fiber biopsy was scheduled but not done.

After 7 months of IV antibiotics low pressure hyperbaric oxygen therapy was started and she began to feel better after a few weeks.

She was tested for immune deficiency. Total IgG was borderline low, 400, IgG subclass 2 was 170, below the normal range, the other IgG subclasses and IgM were normal.

Baseline pneumococcal antibody subtypes were obtained: she had no immunity.

A polyvalent pneumococcal vaccine was administered; four weeks following vaccination peumococcal subtype antibodies were drawn and she had virtually no response.

She was diagnosed with a humoral deficiency and was approved for the use IViG. 

She started IVIG.

After 8 months of treatment she has made good progress towards recovery and continues to improve.

Discussion: 

When this patient was evaluated in a major medical center, a wide range of specialists offered opinions through the lens of their areas of expertise. Infectious diseases. Gastroenterology. Rheumatology. Pulmonology. Pain management. Immunology. Neurology. Psychiatry. And perhaps a few more. She has a multi-system illness which does not fit into the established paradigms; these specialist through the myopia of their specialty  have been indoctrinated to believe nothing here resembles Lyme disease, which they have been taught is a straightforward disease, easily treatable. The lead physician who is responsible for tying together all the disparate opinions believes the same. 

The misinformation fed to these specialists comes from a handful of "experts" who refuse to consider they could be wrong. Their views are reinforced because they function within a community of like-minded colleagues.