While I was digging around for information about Lyme disease for the Doc Gumshoe epistle a few weeks ago, I kept coming across stuff about other tick-borne diseases, some of which was concerning, to say the least. I knew something about some of them, but one tick-borne illness was totally new to me, and, I suspect, will be totally new to most readers. I’ll start with that one, which is known as Alpha-gal syndrome, and then go discuss some of the other better-known diseases such as babesiosis, Rocky Mountain spotted fever, erlichiosis, and anaplasmosis.

Alpha-gal syndrome

It’s something of a stretch to classify alpha-gal syndrome as a tick-borne disease. Alpha-gal (short for alpha-galactose) is a carbohydrate found in the flesh of most mammals, but not in humans. It becomes a syndrome (a group of related symptoms that can be traced to a common cause) when small amounts of this compound are introduced into the bodies of humans by means of a tick bite. In the case of alpha-gal syndrome, it results in an allergy to alpha-gal itself, and because alpha-gal is found in many of the meat products that are part of the human diet, individuals who develop this allergy cannot eat most meats, such as beef, pork, lamb, rabbit, venison, or indeed meat from any other mammals. This allergy can affect humans and other members of the Catarrhine family, which are mostly old-world monkeys.

When a tick-bite injects a tiny amount of alpha-gal into the body, the person’s immune system recognizes the alpha-gal as a foreign substance and may (or may not) respond by mounting an allergic response. The tick that most often causes the alpha-gal syndrome (AGS) is the lone star tick, which is the most common human-biting tick in the southeastern US states. The lone star tick is also found in some eastern states and parts of the Midwest. That tick is by no means the only tick that transmits the alpha-gal syndrome. Other tick species that may also transmit alpha-gal and cause AGS are, in the US, the black-legged tick; in Central America the Cayenne tick; and in Asia the Asia longhorned tick.

Alpha-gal syndrome is usually the result of repeated tick bites. A person who has experienced a single tick bite can probably avoid the syndrome by taking care not to be bitten by ticks again.

Unlike most allergic reactions which emerge quickly after exposure to the allergen, AGS normally appears about six hours after eating red meat or exposure to other substances containing alpha-gal. These can include gelatin, cow’s milk or milk products, and some pharmaceuticals such as the cancer drug cetuximab (Erbitux).

The symptoms of AGS are many and varied. Among these are hives, itchy rash, nausea, vomiting, heartburn, indigestion, diarrhea, cough, shortness of breath, difficulty breathing, drop in blood pressure, swelling of the lips, throat, tongue, or eye lids, dizziness or faintness, and severe stomach pain. These symptoms can vary considerably. In some cases they are quite mild, but they can range in severity all the way up to an anaphylactic reaction – an extreme allergic reaction which can affect multiple organ systems and requires immediate medical attention.

Reactions to alpha-gal can become more frequent or more severe after repeated tick bites. In some cases, alcohol use, activity and exercise can also affect how the body responds to alpha-gal.

Alpha-gal syndrome was first described in 2009. Since then, according to the CDC, more than 110,000 suspected cases of AGS have been identified. However, cases of alpha-gal are not required to be reported to the CDC, so it is not known how many cases have occurred in the United States.

AGS is very difficult to diagnose. There is no pathogen in AGS. What the tick injects into the person is a miniscule amount of alpha-gal, which is a small simple carbohydrate molecule. Since humans do not normally have alpha-gal in their bodies, it is labeled as an invader by the immune system, and any future exposure to alpha-gal – which, as we have said is abundantly present in most of the meat we eat – provokes an allergic reaction.

Because tick bites are painless, most people who have been bitten by ticks have no idea that they have been bitten. And, because the allergic reactions associated with AGS are slow to emerge, a person experiencing the alpha-gal allergic reaction may not identify it as an allergic reaction. Also, not every exposure to alpha-gal triggers a reaction or follows the same pattern.

These factors make it very difficult for physicians to make the connection between the highly varied symptoms that AGS can present with and alpha-gal allergic reaction itself. In order to make a definitive diagnosis of AGS, the healthcare provider will need to do specific allergy testing, which can include a blood test that looks for immunoglobulin-E antibodies to alpha-gal, and also skin prick tests to confirm the allergic reaction to alpha-gal. Skin prick tests are routinely used to test for allergies. The healthcare provider lightly pierces the patient’s skin with as many as 20 miniscule samples of substances to which the patient might be allergic. An allergic reaction is indicated if the prick mark is red. The reliability of skin prick tests is dubious, since the skin can turn red as a reaction to the prick itself.

Managing AGS is far from simple and straightforward. There is no magic pill that reverses the allergic reactions that persons with AGS will have if exposed to those red meats and other alpha-gal containing substances. Their allergic reactions are apt to manifest whenever they are challenged. Therefore, the only certain way to avoid the AGS allergic reactions is to avoid eating beef, pork, lamb, bison, and all those other red-meat mammals, and also to make note that milk, milk products (including ice cream) as well as some gelatins are possible offenders.

When a person actually develops an allergic reaction, it may be possible to alleviate the reaction with antihistamines. A severe allergic reaction, for example a reaction that severely affects breathing, may require an epinephrine injector. Persons with established AGS would do well to keep an epinephrine injector on hand.

Obviously, the most effective way to fend off AGS is not to get bitten by ticks in the first place. Ticks usually live in the woods or in high grass. In the woods, they would tend to keep off the beaten paths, so to speak, but we can’t be sure. When in tick territory, it’s advisable to wear long sleeves and long pants and to wear a hat and gloves. Insect repellents are a good idea, applied not only to exposed skin, but to clothing itself.

The difficulties of identifying and diagnosing AGS were illustrated in the story of Tom Terner, which was written up in the NY Times. Terner is 64 and has worked in the forest industry for more than 40 years, during which in his estimate he has been bitten by ticks “plus or minus a thousand times.” For several years, from time to time, mostly in the evenings, he would break out in hives. He had no idea of what the cause might be, except that he figured it might have something to do with stress.

According to the Times story, that changed about a year ago, when he was attending an annual meeting of the Florida Forestry Association and went out for a steak dinner. In the middle of the night he woke up and found that his whole body was covered with hives.

In the morning, he had breakfast with another member of the group. It was she who told him about her extreme allergy to red meat, and that the cause was a condition called alpha-gal syndrome. At that moment, Terner realized that AGS was what he had. “I’m like, oh my gosh! She’s telling me what I have!”

A blood test later confirmed that he produced antibodies to alpha-gal. He had no choice but to stop eating red meat. “It’s only fins and feathers now,” he said.

However, he will not stop spending a great deal of time outside. “I’m an avid outdoorsman, and I’m not going to stop that.” But he’ll try to avoid more tick bites, since he has become aware that ticks can cause a range of diseases.
Alpha-gal syndrome has only recently come to the attention of the health-care world, and much of it is relatively obscure. For example, it’s hard to say how long the red-meat allergy persists. Often, allergies diminish over time. My grandfather, for example, was violently allergic to peaches. If he even handled a peach and touched his face with fingers that had touched the peach, he would break out in a rash. But in the last years of his life, in a senior citizens domicile, he could eat peaches with no difficulty, and with great pleasure.

Rocky Mountain spotted fever

Lyme disease can make people feel truly lousy, but it won’t kill them, or as a lot of doctors say about diseases that are classified as non-fatal, “you can die with it, but not of it.” Alpha-gal syndrome can lead to extreme allergic reactions, up to anaphylactic reactions that can be fatal if not countered quickly, but fatalities linked to AGL are very rare. Rocky Mountain spotted fever, in contrast, is the deadliest tick-borne disease. If it is not treated promptly, about a fifth to a third of persons that are infected with the disease will die. Even when treatment with doxycycline is employed (the most effective antibiotic against the disease), the fatality rate is still about 5%.

The pathogen causing Rocky Mountain spotted fever is Rickettsia rickettsii, which is the deadliest member of the spotted group rickettsiae. It is most commonly spread by the three related tick species – the American dog tick, the brown dog tick, and the Rocky Mountain wood tick. (By the way, that pathogen has no connection at all with rickets (one t only) which is a childhood bone disease mostly due to Vitamin D deficiencies.)

Rocky Mountain spotted fever attacks the circulatory system, muscle cells and other body tissues. An immediate effect is leaky blood vessels, leading to excess fluid in body tissues and damage to muscles, nerves, and organs. Symptoms emerge as soon as a couple of days after a bite from an infected tick. The earliest symptoms are fever, headache, nausea and vomiting, and muscle pains. About half of individuals bitten by an infected tick develop a rash within three days. Other symptoms include lack of appetite and sensitivity to light, known as photophobia.

If treatment is not initiated, more severe symptoms are likely to emerge, including confusion, shortness of breath, anxiety, numbness or weakness, and seizures.

Persons who have experienced a tick bite and begin to feel symptoms of any kind are urged to seek treatment as soon as possible, and not wait until rashes and more severe symptoms emerge. As with many infectious diseases, the earlier treatment starts, the better chance of a good outcome.

Accurate diagnosis of Rocky Mountain spotted fever relies on blood tests and also on skin tests; however, results from these tests usually take more than a week to be available, so it’s a bad idea to wait for results before beginning treatment. The skin test is based on a device like a punch that takes a tiny bit of skin from an area with the rash to examine the skin sample for the pathogen.

The only treatment recommended for Rocky Mountain spotted fever is doxycycline, which is also the recommended treatment for Lyme disease. Some persons are allergic to doxycyline, in which case an alternative is chloramphenicol, which may be somewhat less effective. Generally, treatment with doxycycline leads to considerable symptom relief in about 48 hours, but the drug needs to be continued for the full period prescribed. It’s worth keeping in mind that the medication has more than a single purpose. Yes, it’s meant to relieve the symptoms, but a more fundamental purpose is to eliminate the pathogen.

Persons who recover from Rocky Mountain spotted fever may still have any of a number of long-term consequences, including acute kidney injury, pulmonary edema, anemia, heart disease, internal bleeding, sepsis, partial paralysis, loss of bowel or bladder control, gangrene requiring amputation, encephalitis, or failure of other organs.

Fortunately, Rocky Mountain spotted fever is not very common. There are about 6,000 cases per year in the US. It’s most common in North Carolina, Tennessee, Missouri, Arkansas and Oklahoma, and not so common in the Rocky Mountains, in spite of its name.

This may seem obvious, but sometimes the obvious is worth repeating: the best protection against Rocky Mountain spotted fever – as with Alpha Gal syndrome, Lyme disease, and a couple of others we’ll get to in this piece – is to take whatever precautions are available to prevent getting bitten by ticks.

Babesiosis

A few years ago, a good local friend of ours developed a number of troubling symptoms – fever, debilitating fatigue, headaches, sweating, back pains – and went to the family physician, who quickly diagnosed her as having Lyme disease. This was entirely reasonable. We live in a part of the world where Lyme disease is prevalent, and our friend’s house is on a big partially wooded piece of land with open fields and tall grass.

Of course, her physician treated her with doxycycline. The expectation was that her symptoms would subside fairly quickly, within a couple of weeks. In her case, the symptoms did not subside – they got worse. This should have been a warning to her doctor. Lyme disease symptoms, even untreated, usually moderate somewhat after the initial onset. But when Lyme disease goes untreated for longer periods, the symptoms change and get worse, in many cases.

It was several weeks before she was diagnosed with babesiosis. The same species of deer ticks, Ixodes scapulari, which carry the Lyme pathogen, may also carry at the same time other pathogens. The pathogen that transmits babesiosis is Babesia, a parasite or piroplasm that infects erythrocytes (red blood cells). The initial symptoms are fairly similar to those of Lyme disease. The bulls-eye rashes don’t appear, but then, in many Lyme patients these don’t show up until well after the other symptoms appear, if at all.

Accurate diagnosis of babesiosis depends on identification of the pathogen by means of blood tests. But physicians encountering the symptoms of babesiosis, which are easily confused with those of Lyme disease, are likely to defer a blood test unless the patient’s symptoms persist.

Severe babesiosis brings a number of different symptoms, including jaundice, pallor, dark urine, shortness of breath, and sudden mood changes or extreme emotional reactions.

In the US, the most common cause of babesiosis is a subspecies called Babesia microti. Other Babesia species that sometimes make you sick include B. duncani, B. divergens, B. venatorum and B. crassa.

A potentially useful difference between babesiosis and Lyme is that, whereas in Lyme disease, patients tend to get over the first wave of symptoms as the little spirochetes migrate to other parts of the body, in babesiosis, patients tend to feel worse as the infection progresses. That’s because the parasite is actually destroying their erythrocytes. Erythrocytes are the red blood cells that latch on to oxygen in the lungs and convey it to all the cells in the body, so as the babesia parasite destroys blood cells, the body is deprived of oxygen even though the lungs themselves are working just fine. The condition is called hemolytic anemia, and in some people it can be life-threatening.

Besides hemolytic anemia, babesiosis can lead to a number of non-trivial complications, including enlarged spleen or liver, liver or kidney failure, fluid buildup in the lungs (called pulmonary edema), which can lead to heart or respiratory failure, and problems with how the blood forms clots which can lead to bleeding disorders.

Treatment of babesiosis frequently relies on a combination of medications, including drugs that target protozoa (a kind of microbe), antibiotics, and antimalarials, frequently in combination. Some of the agents used are atovaquone, azithromycin, clindamycin, and quinine.

Fortunately, for a disease that is difficult to diagnose, babesiosis is rare. In the US, only about 3,000 cases of babesiosis per year occur. However, the fatality rate is non-trivial – one in ten patients hospitalized with babesiosis do not survive.

As with the other tick-borne disease we have been discussing, preventing babesiosis means avoiding ticks to the greatest extent possible.

Erlichiosis/anaplasmosis

These are similar tick-borne illnesses caused by different, but related, bacterial pathogens. Both attack types of white blood cells – monocytes or granulocytes – and the result can be severe damage to several organ systems. These illnesses are uncommon, so far – the emphasis is on so far! Erlichiosis is somewhat more common in the middle-Atlantic states and the south, whereas anaplasmosis is more common in the northeast. The number of reported cases of these two illnesses is relatively small – in the neighborhood of three cases per million population, perhaps totaling a thousand cases nationwide – but there is evidence that many more persons have been infected without developing symptoms. The fatality rate is somewhere between zero and exceedingly low. Treatment usually consists of relatively short courses of doxycycline.

The small risk from these diseases is somewhat aggravated by their relative rarity. A health-care worker who has not had experience with them might tend to stop the diagnostic process once the more usual suspects had been eliminated. Difficult diagnoses can lead to delays in treatment, or to misdirected treatment. If the patient should happen to be infected with the babesia parasite, but the physician is convinced that Lyme is the default option, the initial treatment is apt to fail, and the patient may be put at considerable risk. The situation calls for patience, persistence and vigilance on the part of physicians and patients alike.

* * * * * * * *

Tick-borne diseases deserve more attention than the health-care community is currently devoting to those frequently elusive illnesses. With the exception of Lyme disease, tick-borne diseases are very difficult to diagnose, and, although – again, with the exception of Lyme – relatively uncommon in most parts of the US. Physicians who live in areas where a particular tick-borne disease is not prevalent are not likely to identify and diagnose that disease. In the previous Doc Gumshoe installment, I described how Ross Douthat’s Lyme disease was, for a long time, undiagnosed because physicians in Washington DC, where he lived, were not familiar with Lyme disease. There’s a significant risk that many persons with active tick-borne diseases go undiagnosed for long periods.

I had an episode of Lyme disease about twenty years ago. I was doing a bit of last-minute garden work just before we were leaving on vacation to Maine. A few days later I began to feel extremely fatigued and developed a fever. I also had what looked like a bite on my leg. We went to a doctor in northern Maine who thought it was likely a spider bite. My symptoms improved somewhat, but when we returned from our vacation I popped in to see my regular MD who instantly recognized the tell-tale bulls-eye rashes as a sign of Lyme and put me on doxycycline for a month. I have had no recurrence of Lyme symptoms, so I’m assuming he was right.

My wife and I don’t live where those tick-borne diseases (other than Lyme) are problems; however, Lyme disease is prevalent around here and we’re extra careful to avoid tick bites, especially after my Lyme episode. When we’re out in our garden or our patch of woods, we use insect repellent. We have showers when we come back indoors, and we do a tick inspection routine afterwards. If we were to find a tick, we have little tweezers to grab the tick. Also, we have our whole property treated a couple of times a year by an outfit that sprays a tick-killing substance all over the place.
Braving the risk of being tedious, I’ll repeat that the best strategy regarding these tick-borne illnesses is to avoid ticks in the first place. It’s no fun, but the alternative is to stay indoors.

While on vacation in Maine these past weeks, I read a highly interesting and somewhat challenging book, Being Mortal, by Atul Gawande. He points out, in riveting detail, that medical science and the health-care system does not always perform to the benefit of the patient. I acknowledge that this is not a cheerful subject, but Gawande’s objective is strongly positive – to determine what the best options are for the individuals who are faced with difficult decisions about their health and their lives. I’ll try to report on Gawande’s perspective in my next bulletin.

Good health and good cheer to all! Best, Michael Jorrin (aka Doc Gumshoe)

[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions.  Past Doc Gumshoe columns are available here.]