Lyme Disease: The Basics of Prevention

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Lyme disease is a tick-borne illness with a peak incidence in the eastern United States during the summer months of June, July and August. The late manifestations, such as arthritis, can appear at any time during the year. It is most common in the northeast and mid-Atlantic states (from Maine to Virginia), the Midwest (Minnesota, Wisconsin and Michigan) and on the west coast in northern California.

The ticks are carried by mice and deer and are more likely to infect when they are quite small (the size of a poppy seed.) When the ticks change and become larger they are less likely to transmit infection. Ticks are most commonly found on the underside of low-lying shrubs or grass, particularly between grass and forest. They are not common on well-cut lawns, such as a golf course. A tick can attach to a pet and then attach to a human, thereby transmitting the disease. If the tick is removed before it becomes large (engorged with blood) it is very unlikely to transmit Lyme disease.

If a tick is on the skin, but does not bite it cannot transmit disease. If a tick is removed within 48 hours the risk of transmission is quite small. The risk of transmission in one study where a tick was removed before it was engorged in an area where 15% of ticks carried Lyme disease was only 1%.

The best way to remove a tick is with tweezers or your fingers covered with some protection, such as a disposable rubber glove. It is important not to crush the tick. After removing the tick wash the area and your hands with soap and water.

Taking the antibiotic doxycycline to prevent Lyme disease makes sense only under certain conditions: that the tick is a deer tick; that the tick has been attached for more than 36 hours; that doxycycline can be started within 72 hours after the tick has been removed; that the tick bite has occurred in areas of the US where Lyme disease is common; and that the person does not have a contraindication to the use of doxycycline (a tetracycline.)

If a person cannot take doxycycline then no antibiotic should be prescribed as prophylaxis against developing Lyme disease after a suspicious tick bite. Doxycycline is usually given as a single 200 mg dose.
The time between a tick bite and the onset of Lyme disease symptoms is 2 to 3 weeks. The first manifestation is usually a rash. Lyme disease also can cause arthritis, neurological problems, heart conduction abnormalities and other problems. Unfortunately, it takes two weeks for antibodies to appear in the blood making a blood test for Lyme at the time of the tick bite useless.

Are Extra Vitamins a Good Idea?

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The standard authorities state that for most healthy adults consuming a well-balanced diet, multivitamins (which usually contain 50%-150% of the recommended adult daily requirement of the standard vitamins) are not needed. However, some evidence suggests that taking a daily multivitamin causes a small decrease in cancer risk.

All authorities agree that there are important areas where extra vitamins are needed:

It is very important for women who might become pregnant to take a supplemental dose of 400 mcg of folic acid daily. The extra folic acid insures against inadequate reserves and prevents neural tube defects in the newborn such as spinal bifida.

A multivitamin is important for individuals with malabsorption (such as celiac disease, gluten-sensitivity), a vegan diet, alcoholism and certain other chronic conditions.

For other adults folic acid supplementation is unnecessary and perhaps unwise. An increased level of folic acid can mask vitamin B12 deficiency, a very serious deficiency problem, and may stimulate the growth of some cancers.

In order to prevent osteoporosis and decrease the risk of falls (a curious, but substantiated association) adults need a minimum of 800 units of vitamin D daily, taken either through dietary sources or as a supplement. Unlike all other vitamins, vitamin D can be produced by humans internally. In this case sunlight is needed, and exposure is often insufficient.

Dietary sources of vitamin D include milk, yogurt and soy milk—all of which are usually fortified with vitamin D. Salmon, sardines, tuna and cheese are other good sources of vitamin D.

Since vitamin D levels are often low in adults and since vitamin D deficiency causes bone problems and has been possibly linked to other diseases, taking 600-800 units daily, particularly in older adults, seems prudent.

Vitamin A levels are usually normal in the industrialized world and supplementation is not needed and, indeed, may be harmful. Excessive doses in pregnant women can cause abnormalities in the newborn. Additionally, in all adults excessive doses can cause osteoporosis as well as possibly increasing the risk of cancer and cardiovascular disease.

Likewise, vitamin E levels are usually adequate and high dose vitamin E (more than 400 units daily) supplementation is unwarranted since excessive vitamin E levels are associated with increased all-cause mortality.

Vitamin C supplementation is safe, but has no proven benefit.

Older persons should consider taking a B12 supplement since levels of this very important vitamin can drop with age. Liver, fish, beef, cheese and eggs are dietary sources of vitamin B12. A vegan diet eliminates many dietary sources, making supplementation necessary.

Statins and Grapefruit

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If you’re taking a statin medication for your cholesterol, you have undoubtedly heard the warning against consuming grapefruits or grapefruit juice. This restriction also applies to a number of other medications including certain cardiovascular medications, anti-cancer agents, antibiotics, antidepressants and others. For a more detailed list and approximations about the extent of the interaction with particular medications click on to the following site: http://www.cmaj.ca/content/suppl/2012/11/26/cmaj.120951.DC1/grape-bailey-1-at.pdf.

The discovery of the interaction was serendipitous. Researchers noticed a higher drug concentration in certain test subjects than others when a medication was initially being tested. Those with an elevated drug level were eventually found to have also consumed grapefruit. Pomelo, lime and marmalade can also produce the same effects.

The compounds in grapefruit responsible for the effect are called furanocoumarins and act by blocking the enzymes in the intestines responsible for the degradation of certain medications. It only takes one glass of grapefruit juice to produce the maximum effect, an effect that persists for longer than 24 hours. Therefore, taking grapefruit juice at a time well-separated from the medication dose is ineffective in solving the problem.

How big an issue does this represent? That depends on a number of factors, particularly on how dependent the medication is on the enzyme that is blocked by the juice. Some medications have a wide “therapeutic range.” In other words, increased blood levels don’t represent much of a concern. On the other hand, some medications have a narrow therapeutic range, with increased concentrations causing serious problems.

Although most statins should not be taken in combination with grapefruit products Crestor (rosuvastatin) and Pravachol (pravastatin) are exceptions since they are not significantly metabolized by the enzyme blocked by grapefruit.

Aspirin and Disease Prevention

AspirinRecently the New York Times ran an op-ed entitled “The 2,000-Year-Old Wonder Drug” extolling the benefits of aspirin for a number of illnesses including cardiovascular disease and cancer. Although quite enthused about aspirin as a disease preventive, the author does advise medical consultation about the risks versus the benefits.

Is aspirin usually a good idea for middle-aged American? For those with known cardiovascular disease it usually is. However, one year ago a large study in the Archives of Internal Medicine did not show a reduction in cardiovascular or cancer deaths in patients without prior cardiovascular disease taking low-dose aspirin. A reduction in non-fatal heart attacks was noted. This benefit, however, was associated with a 30% increased risk of significant bleeding. The authors conclude against the routine use of aspirin for patients at low risk for cardiovascular disease.

More concerning, than the well-known risk of bleeding from the stomach or intestines, is the possibility of bleeding in the brain. Although the absolute risk of intracranial vessel bleeding is small (two hemorrhagic strokes per 10,000 patients taking aspirin) the consequences can be devastating.

Also, does aspirin prevent cancer? The evidence suggests that it is effective in preventing colon cancer and might be effective in preventing other cancers, although the evidence for the latter is less clear. The dose necessary to produce a statistically significant reduction in colon cancer is not certain, but some suggest that a full aspirin (325 mg) rather than low-dose aspirin (81 mg) might be needed.

The increased risk of bleeding associated with any dose of aspirin, and the possibility of greater risk with a higher dose, along with the very useful colon cancer prevention strategy of colonoscopy now in place caused the American Cancer Society not to recommend the routine use of daily aspirin to prevent colon cancer.

Patients at low risk for cardiovascular disease should consult their doctor before committing to a lifetime of daily low-dose aspirin. Low risk is defined as a patient whose 10-year absolute risk of a first coronary disease event is less than 10%. The doctor can calculate the risk by using a formula derived from the Framingham study of cardiovascular disease.

Aspirin is the wonder drug touted in the New York Times but, as usual in medical matters, every situation is different.

Chronic Lyme Disease

Lyme disease is usually divided into three stages: early localized disease, early disseminated disease and late Lyme disease. The first stage is characterized by the characteristic rash with or without systemic symptoms such as fever, body aches and joint pains. Early disseminated disease is characterized by rashes and/or neurologic symptoms and/or heart problems. Late Lyme disease is associated with arthritis, usually involving one or a few large joints, particularly the knee, and/or neurological problems. The neurological problems can involve the brain, the covering of the brain or a specific nerve possibly creating headaches, paralysis, or nerve pain. Arthritis symptoms, particularly if only the knee is involved, can appear to be a solitary problem, with no clue that the problem is caused by Lyme disease.

Early disseminated disease occurs weeks to several months after the initial infection from the tick bite. These symptoms can be the first manifestation of Lyme disease since 20% of people with the disease do not recall any rash and approximately 25% of people with the disease do not recall a tick bite.

Late Lyme disease occurs months to years after the tick bite and, as in the case with early disseminated Lyme disease, the history of a rash or tick bite might not be present or a history of having had the earlier stages of Lyme disease. The symptoms include arthritis, predominantly of the large joints, especially the knees. Neurological symptoms can also occur.

Symptoms usually resolve gradually, as they do in most infectious diseases, after a full course of antibiotics. Post-Lyme disease syndrome refers to symptoms such as headache, muscle pain, joint pain and fatigue that persist, but generally resolve after six months to one year.

A confusing issue develops when a person who has, by all accounts, been successfully treated for Lyme disease suffers continuing health problems that do not resolve with time. This situation has been termed chronic Lyme disease by some and is the subject of much dispute.

Briefly, certain doctors and advocacy groups maintain that, in these situations, the symptoms are caused by Lyme disease that failed to be eradicated by the standard treatments. Medical authorities counter that the persisting symptoms are due to another illness that, perhaps, was triggered by Lyme disease.

The “other illness” suggested is often either fibromyalgia or chronic fatigue syndrome. Both usually respond poorly to any one of a number of medications or treatments traditionally employed. Many, if not most, physicians suspect that fibromyalgia and chronic fatigue syndrome are, at the root, psychological problems.

You can imagine how frustrated a person feels who had been totally healthy, was bitten by a tick, became ill with Lyme disease, failed to improve after treatment, and is now told he has a psychological illness! Personally, I think that the development of symptoms compatible with fibromyalgia or chronic fatigue syndrome after Lyme disease is further proof that these illnesses are not psychological.

I suspect that chronic Lyme disease is not due to the persistence of the Lyme organism, but that the Lyme organism has triggered some other illness. Therefore, additional antibiotics directed at Lyme would be pointless, and possibly harmful.

What to do? It is necessary to search for other illness triggered by Lyme. I have seen cases where Lyme triggers an arthritic illness. What initially was arthritis caused by the Lyme organism is now arthritis caused by another arthritic disease, itself triggered by Lyme. Look closely at the blood for autoimmune markers. If the symptoms suggest arthritis get treatment for arthritis even in the absence of confirmatory blood tests.

Persisting fatigue with or without bodily pain is usually the most troubling symptom for patients with “chronic Lyme disease.” Long courses of antibiotics are ,almost always, fruitless. A more productive approach is to start fresh, evaluating each symptom as a new issue using standard, individualized treatments as needed. For instance, despite the patient’s firm belief that persisting Lyme infection is causing severe fatigue treating fatigue with medications known to improve it can be very worthwhile. A creative and unprejudiced approach, as usual in medicine, offers the best chance for success.

Is my tiredness normal or do I have a problem?

Most fatigue is normal, reflecting inadequate sleep, overwork or stress. Normal fatigue is usually relieved by a good night’s rest or, at most, a relaxing weekend. When this is not the case, conditions and illnesses that cause fatigue should be considered.

As common in medicine, history is most important. How long has the fatigue been going on? When the onset can be traced to a lifestyle change – different work schedule, new marriage, etc. – the answer usually relates to the change with causes such as inadequate relaxation or new stresses.

When is the fatigue most apparent? Weekday fatigue absent on weekends would certainly suggest factors such as stress and overwork. One caveat: most fatigue, whatever the cause, improves with a good, relaxing weekend but, if the fatigue is due to an illness, the fatigue might improve over the weekend but should not be entirely gone.

Weekday fatigue might be the result of “sick building syndrome,” an often overlooked cause. Most office buildings built since the 1970s are sealed making it impossible to open a window. If the HVAC does not provide enough fresh air the irritation from air contaminated by building chemicals, mold, etc. causes nasal and sinus symptoms with resulting fatigue.

What about fatigue that is more noticeable on the weekend than during the work week? It happens more often than you might think. Assuming that the weekend is not loaded with a stress that is less apparent than that noted during the week, several factors are often responsible.

Obviously too much socializing, partying and drinking could well be the cause, but these are usually obvious to the person. A more subtle reason for fatigue more apparent on the weekend than during the week is, oddly, too much sleep. Many people get an “overslept” sensation when they sleep in on a Saturday or Sunday.

Fatigue due to too much sleep is a curiosity noted more commonly in patients with allergies and sinus problems than it is in the general population. People with this condition need a fixed amount of sleep and should not sleep more than the usual required hours.

Other causes of weekend fatigue would include allergic exposure that does not occur during the week. Outdoor activities with resultant exposure to airborne allergens can cause fatigue as well as typical allergy symptoms.

Of course, too much alcohol on the weekend can cause fatigue. Sometimes the relationship isn’t obvious. Some individuals have an allergic response to alcohol, particularly red wine, producing fatigue the following day after amounts that were quite reasonable.

If I’m not fatigued on a vacation does that mean my fatigue is due to stress? Not necessarily. A change in climate is quite helpful for people with fatigue related to allergies. A person might be tired in a rainy area of the country that is laden with mold but feel quite good in the clean, dry desert. Additionally, there might be some airborne irritant present at home or in the office that’s not present in the vacation home or hotel room.

When trying to find an answer for the symptom of fatigue keeping a fatigue diary can be quite helpful. Noting any activities, sleep patterns or locations that improve fatigue can offer an important clue.

Causes of Fatigue that Slip Through the Cracks

I consider fatigue caused by sinus and nasal issues to be the most common cause of otherwise unexplained chronic fatigue. I’ll describe the evidence for this opinion later but, for now, let’s consider some medical causes that can be missed.

An interesting study examined the amount of iron in the blood of women who were not anemic. Usually an iron deficiency, if severe enough, causes anemia but this study was limited to patients with mild iron deficiency, enough to be noted when examining the blood specifically for iron stores but not enough to cause anemia.

The distinction is an important one. Prior to this study physicians usually thought that iron deficiency would not cause fatigue if the deficiency was not severe enough to cause anemia. The study went on to measure the level of fatigue before and after iron replenishment. The level of fatigue dropped after the iron stores were returned to normal.

Two points are evident from this study: The lack of anemia does not rule out iron deficiency as a cause of fatigue. Additionally, measuring iron stores as simply the level of iron in the blood is inadequate. The iron stores must be measured as “ferritin” a simple and inexpensive blood test but one not always done when evaluating a person for fatigue.

Occasionally low thyroid causes fatigue despite a normal TSH—the usual screening test for low thyroid. TSH comes from the pituitary and increases in the event of a failing thyroid usually providing the earliest clue that the level of thyroid hormone is inadequate.

Occasionally the pituitary is the problem and although the TSH should be climbing as the thyroid fails, it does not. Checking the actual levels of thyroid hormone (T4 and T3) will pick up a thyroid problem even in the event of pituitary insufficiency.

Sometimes an arthritis disease can cause even in the absence of severe arthritis symptoms. Almost always the severity of the arthritic disease seems quite proportionate to the complaint of fatigue. Occasionally this is not so. A person might have rheumatoid arthritis with minor joint problems but have significant fatigue. Treating the rheumatoid arthritis usually causes substantial reduction of fatigue.

A note of caution: The vast majority of individuals with unexplained fatigue and very minor arthritis symptoms do not have positive blood tests for arthritic diseases. Even when the blood tests turn out positive the blood abnormality is, almost always, at a low level, unrelated to the minor arthritis. In these cases treating the person as if the individual did have a serious arthritis disease does not improve the fatigue. In short, arthritis blood tests in the setting of unexplained fatigue are often a “red herring,” but not always.

Occasionally a person may have unexplained fatigue due to a liver problem in the absence of abnormal screening liver function tests. Usually other screening tests, however, denote inflammation.

As mentioned before, the best screening tests to determine if, what appears to be unexplained fatigue, is actually caused by a medical problem are the erythrocyte sedimentation rate (ESR) and the C-reactive protein. Both of these are elevated by any process that causes inflammation. Usually any medical disease that causes fatigue causes inflammation as well.

The ESR and CRP won’t tell you the cause of the problem but do let you know that there is a problem. The absence of ESR or CRP abnormalities does not mean that the cause of fatigue is not physical. However, when these tests are elevated a physical cause of fatigue becomes much more likely.

Zithromax and Sudden Death

A recent study in the New England Journal of Medicine described an increased risk of death from cardiovascular causes in patients taking azithromycin. Azithromycin (Z-pack, Zithromax) is a very commonly used antibiotic and this warning merits concern.

The increased risk of cardiac death relates to the tendency of azithromycin to increase the risk of an irregular heartbeat. In this study a similar risk of increased cardiac death was noted in patients who took levofloxacin but not in patients who took amoxicillin.

The increased risk was small (47 additional deaths per 1,000,000 courses of treatment) and largely limited to patients with very significant heart problems. This increased risk is probably significantly less than that which had been noted with erythromycin in the past.

Since vulnerability is limited mostly to patients with significant heart problems (the top 10% severity of heart disease in this study) and, presumably, patients taking a number of cardiac medications some caution is needed when prescribing to these patients. Since the blood concentration of azithromycin causes the problem, particular caution is needed in patients with very severe heart disease who are also taking cardiac medications that will raise the blood concentration of azithromycin such as diltiazem and verapamil.

Types of Fatigue

Over 100 years ago William Osler, the father of internal medicine, divided fatigue into three types. The first is the lassitude and malaise associated with systemic illness such as tuberculosis, cancer, rheumatoid arthritis, etc. The second is the weakness associated with muscle and nerve disorders resulting from ordinary exertion. The last is a painful weariness – the cause of which often eludes investigation.

These categories provide a useful framework in attempting to diagnose the cause of an individual’s fatigue. Duration further categorizes the symptom. Most patients with prolonged, unexplained fatigue have the third type of fatigue described by Osler, a painful weariness.

Fatigue that is less than one-month in duration is often due to a passing virus, stress, or other causes that are difficult to define. The relatively brief nature of the problem eliminates the need for an intense medical investigation, and, unless the problem becomes recurrent, it can be dismissed as one of life’s minor problems.

Persistent, significant fatigue, however, is not a minor problem. Even a loss of 10% of a person’s vigor removes enthusiasm and joy from the day’s tasks. Fatigue pulls down the mood and makes everything an effort. Approximately 15% of the general population suffers from chronic fatigue, unrelieved by rest, lacking an adequate medical explanation.

Approximately 25% of patients visiting a medical doctor complain of fatigue. Less than half will be explained by a medical illness.

Fatigue caused by medical conditions has certain characteristics. A serious medical problem will occasionally present itself as unexplained fatigue before other symptoms become apparent but, inevitably, other symptoms will appear. For instance, a person with pancreatic cancer may first notice fatigue before the appearance of abdominal pain and the other symptoms of cancer occur. Therefore, the longer fatigue persists without other symptoms, the less likely a serious medical condition will serve as the eventual explanation.

Fatigue caused by a medical problem has other characteristics as well. Usually patients with typical, diagnosable, medical problems note that their energy is highest in the morning and slowly winds down over the course of the day as if the store of vigor slowly depletes. A nap may recharge the person.

Fatigue that remains unexplained usually has different characteristics. Many times, a person has a bimodal curve of energy, worse in the morning, improving with the day, fading in the afternoon, and, finally, getting a second wind at night. A nap can actually worsen things. Additionally, sleeping a long time can produce an overslept sensation.

Patients with less serious medical problems can, in certain circumstances, have fatigue with the absence of other symptoms, as is the case with hypothyroidism. Patients with low thyroid may notice tiredness before the other symptoms appear. These include dry skin, constipation, cold intolerance, etc. Likewise, a patient with anemia can feel tired before noticing other symptoms such as pale skin or obvious blood loss.

Causes of fatigue are often easy to figure out. Usually a visit to the doctor and a standard panel of blood tests provides a definite answer. If, after a thorough exam and appropriate blood tests, no answer is apparent, it is unlikely that a medical explanation will be found.

Sinus Fatigue

A little less than 10 years ago a research project that I had been working on for many years was published in the Archives of Internal Medicine. The observation that propelled me into the relationship described in the article related to my first experiences as a clinician.

I was aware that sinusitis caused fatigue years before I became a doctor because of personal experience and conversations with others who also suffered from sinus problems. I was surprised that my own doctor seemed unaware of the association and I was surprised that fatigue was not listed as a symptom in the general medical texts that I searched in college.

Nothing changed in medical school. Although the lists of illnesses that caused fatigue was quite long, and the lectures on the subject quite thorough, no one that I can recall mentioned sinusitis as a cause of fatigue.

When I first started practice my experience confirmed my own observations that patients with sinusitis were fatigued but, again, a thorough search of the medical literature produced nothing. I then started noticing that patients with a primary complaint of fatigue often, on more detailed questioning, acknowledged sinus symptoms but considered the sinus issue quite minor compared to the more pressing complaint of fatigue.

After trying to redirect the focus towards the sinus issue and initiating treatment, patients would usually notice a great improvement in fatigue. Patients found this puzzling. In fact, often a patient would return months later with the primary complaint of serious fatigue completely having forgotten the link with sinusitis. Once again I would treat the sinusitis and the fatigue would remit.

In the late 1980s I began to see some notice in the medical literature. A consensus conference of ear, nose and throat physicians in 1987 described fatigue as one of the diagnostic criteria for making the diagnosis of chronic sinusitis. I reported several cases of patients diagnosed as having chronic fatigue syndrome who experienced a complete or nearly complete resolution of fatigue following sinus surgery.

Nothing on the subject was mentioned in the internal medicine literature, an unfortunate omission since internists are the doctors who treat fatigue.

I was curious about how common sinus problems are found in patients with a primary complaint of unexplained chronic fatigue. This is how the project unfolded.

I examined 297 consecutive patients who were younger than 41 years, administered a detailed questionnaire and performed a battery of screening laboratory tests. Young patients were chosen in an effort to exclude the illnesses of older age groups that might confound the results.

Of the 297 patients, 65 (22%) noted unexplained fatigue that has persisted for more than one month, fatigue unexplained by the lack of rest, illness, or undo physical or mental exertion. Fifteen (23%) of these patients met the diagnostic criteria for chronic fatigue syndrome, an illness characterized by prolonged and severe fatigue.

When the 65 patients with unexplained chronic fatigue were compared to the remaining group of 232 patients most sinus symptoms were much more common in the group with unexplained chronic fatigue: facial pressure (80% vs 13%), heavy-headedness (80% vs 8%), nasal obstruction (87% vs 42%), frontal headache (53% vs 6%), sore throat (33% vs 8%) and cervical node tenderness (60% vs 6%.)

Of note, symptoms usually associated with unexplained illnesses such as gastrointestinal problems, sleep disturbance, and psychiatric illness were similar in the group with unexplained chronic fatigue when compared to the group with fatigue explained by a physical or mental illness.  However, sinus symptoms were much more common in the former when compared to the latter.

The results confirmed my suspicion that there is a peculiar and predominant relationship between chronic sinusitis and unexplained fatigue.