3 Ticks, 3 Misses

My first summer as an attending, I worked in an emergency department (ED) in the middle of a farm field. The building was new, the nursing staff had been there 30 years, and the admitting physicians were the same octogenarian internists who had seen me for strep throat when I was a kid. It was the hospital of my childhood, and on a Saturday night in late July, it sent me a man in his 50s looking sicker than his vitals said he should be. He drove himself in. Four days of fever, a headache he could not shake, and a week spent clearing brush on the back of his property. Platelets in the 60s, white count under 4, AST and ALT roughly tripled, LDH climbing. No rash. The intern and I spent 20 minutes together working out how we were going to make this stick as an admission, because this was not a hospital where soft admits went easy at 3 a.m., and the internist on call was going to want more than a viral syndrome and a bag of fluids before he picked up the phone. We called down to the lab and asked if we could come look at a smear ourselves. The tech was surprised, then delighted. By the time the intern and I walked in, she had already pulled a slide, stained it, and set the scope to the exact field she wanted us to find. Small ring forms inside red cells, and in 1 corner a clean Maltese cross. She confirmed it for us (she'd even pre-positioned the reference book next to the microscope open to the relevant page). We carried the finding back upstairs, and the admitting physician took the patient (with a raised eyebrow or two). Atovaquone and azithromycin went up that night. He moved to the floor in the morning and walked out on day 4. That case was more than a decade ago. It was the textbook answer for a South Jersey summer, and the textbook was right. What I did not understand at the time is how much of the textbook was about to rewrite itself. The tick map of 2010 is not the tick map of 2026. Ixodes scapularis is active more months of the year than it used to be. Amblyomma americanum, the Lone Star tick, has pushed north into New Jersey, New York, and southern New England and is now established where it was a curiosity 15 years ago.1 Deer populations are up, small-mammal reservoirs are stable, and winters no longer knock vector density back the way they once did. Powassan case counts have roughly doubled every 5-year window since 2010. Suspected alpha-gal cases have crossed 110,000. Babesiosis is nationally notifiable and rising in regions that used to call it a coastal New England problem. Three tickborne infections that were fringe on the July differential 15 years ago have moved into the middle of the list. The emergency physician who waits for a bull's-eye rash, or who remembers ticks as a problem “upstate,” is practicing off an old map and is going to miss real disease in his or her own ED. Alpha-gal syndrome is a delayed IgE-mediated reaction to galactose-α-1,3-galactose, a sugar found in the tissue of every nonprimate mammal.2 A bite from an alpha-gal-sensitizing tick, most often the Lone Star, triggers the antibody. Weeks to months later, the patient eats beef, pork, lamb, or venison and develops anaphylaxis 2 to 6 hours after the meal. The 2-to-6-hour delay is the diagnostic trap. The anaphylaxis is not reflexively connected to food, because the food was the night before. Patients present in the middle of the night with urticaria, angioedema, hypotension, or GI symptoms, and the standard triage question of “what did you eat?” is already useless. When anaphylaxis has no clear trigger, ask about red meat eaten the previous evening, and ask about tick exposure in the last several months, not the last several days. Ask about hidden mammalian products. Gelatin capsules are among the long list of things that carry alpha-gal and have been implicated. The patient with recurrent “idiopathic” anaphylaxis who just had a porcine valve replacement or started a new capsule formulation deserves an alpha-gal IgE send-out. ED management is plain anaphylaxis care. The diagnosis is outpatient, but the recognition is ours. Missing it means sending the patient home with “maybe avoid shellfish” when the problem is the cheeseburger. Powassan is worth knowing about mostly because it's a viral encephalitis that will not be HSV and it will not be nothing. It has a transmission window short enough that as little as 15 minutes of attachment can spread the virus. The old reassurance of “it was not on you long enough” died with Powassan's rise. Clinically it looks like viral encephalitis. Fever, headache, altered mental status, seizures, focal deficits. Case fatality runs around 10%, and roughly half of survivors carry long-term neurologic sequelae. It does not change the ED algorithm much. For summer encephalitis with a negative HSV PCR, consider calling the state lab or discussing with ID, and start empiric acyclovir. Powassan can remain on the differential until serology returns. There is no antiviral therapy for it. IVIG has been used anecdotally in severe disease, and early neurocritical care probably matters more than any specific drug. The point is that HSV-or-bust is no longer the whole story for encephalitis in tick-endemic areas, and it sucks when you miss it. A single I. scapularis bite can deliver Lyme, anaplasmosis, babesiosis, and Powassan simultaneously.3 In parts of the Northeast, up to 40% of Ixodes ticks carry more than 1 pathogen. If the patient in front of you fits Lyme but looks sicker than Lyme should look, something else is on board. Anaplasmosis and ehrlichiosis share a laboratory signature that should be burned into EM muscle memory: thrombocytopenia, leukopenia, and transaminitis in a febrile patient from May to October. That triad should always prompt consideration of empiric doxycycline. Peripheral smear can show morulae inside granulocytes for anaplasma and inside monocytes for ehrlichia, but sensitivity is low, 20% to 80% depending on parasite burden, and I am under no misconceptions that most emergency physicians are going to be eager to pull out a microscope. But if you are willing to give it a shot, remember that a negative smear does not exclude the diagnosis, and a positive smear would likely benefit from some reassurance from the lab tech before calling ID. Treatment does not wait for either result. Babesia is the one that does not respond to doxycycline, and the one most findable at the bedside. The organism lives inside red blood cells as small ring forms, and in higher parasitemia produces the classic Maltese cross tetrad. It looks like malaria because it is an intracellular organism, and the same thick and thin smear you would prepare for a malaria slide will show it. In fact, at most hospitals, when I want a smear even for TTP, I have to order it as a “Malaria Smear.” If you can see it, you can make the diagnosis yourself and call medicine with an answer rather than a question. Let them doubt your rickettsial prowess. Treatment is atovaquone plus azithromycin for mild-to-moderate disease, and clindamycin plus quinine, often with exchange transfusion. For severe disease. I would call ID. The asplenic, the elderly, the immunosuppressed, and the HIV-positive do not get mild babesiosis. If any of those factors are in the chart and the patient has summer fever in tick country, the threshold for empiric treatment drops and the threshold for calling ID and heme-onc drops with it. Parasitemia above 10%, hemolysis, renal failure, or ARDS should trigger an exchange transfusion call. Fever, thrombocytopenia, and transaminitis in summer should always prompt consideration of empiric doxycycline. The triad catches anaplasmosis, ehrlichiosis, and Rocky Mountain spotted fever. Missing any of them is worse than treating when you are wrong. Doxycycline in children under 8 is safe for short courses. American Academy of Pediatrics (AAP) and Centers for Disease Control and Prevention (CDC) updated this years ago. Stop letting the old enamel rule delay treatment. Ten to 14 days does not stain teeth, and the alternatives are materially worse. In the rare event you have the time, desire, and friends in the lab, give a shot to pulling the smear yourself. Babesia rings and Maltese cross in red cells are the most bedside-findable of the group. Anaplasma and ehrlichia morulae are harder but occasionally visible. When you find something, ask the tech to overread before you call ID. The smear is not the diagnostic standard, but it can produce a same-hour answer when the PCR is 2 days out. On a personal note, this can be some fulfilling stuff. There is no true rapid bedside test for tickborne disease. The hospital I was working in still had Weil-Felix agglutination on its paper lab menu, a rapid rickettsial test in name that no one in the building had ordered in a decade. It would not have helped. Reference-lab multiplex PCR panels today return in 24 to 72 hours (I can't remember how long it took back then). Empiric doxycycline is functionally the rapid test. Treat, then confirm. Ask about tick bites at 8 weeks, not 8 days. Alpha-gal sensitization is weeks to months out. Late Lyme is months out. The relevant exposure window is longer than the intake form allows. A single Ixodes bite delivers multiple pathogens. If the clinical picture is worse than the Lyme you diagnosed, treat for anaplasma and send a babesia smear and PCR. Doxycycline covers Lyme, anaplasma, ehrlichia, and RMSF. It does not cover babesia. Absence of rash rules out nothing. Thirty percent or more of confirmed Lyme presents without erythema migrans.4 Absence of a remembered tick bite rules out less. For summer encephalitis with a negative HSV PCR, consider calling the state lab or discussing with ID, and start empiric acyclovir. Powassan can remain on the differential until serology returns. Alpha-gal screens are not stat. Recognize, stabilize, refer. Audit the medication list. Capsules, heparin exposures, and recent valve replacements have all precipitated reactions, and all belong on the ED history.5 The man with babesiosis went home on day 4. The internist admitted him without much argument once we handed them a diagnosis. None of that was my finding in any meaningful sense. The tech saw it before I did, and the old docs on the floor had been treating tick-borne illness longer than I had been alive. The vectors are moving, the pathogens are mixing, and the first emergency physicians who see the redrawn map are going to be the ones working in the same kind of farm-field community hospitals I started in. If you think it might be a tick, treat it like a tick. Call the lab before you call ID. And if you have a few minutes and a willing tech, go look at the slide yourself. CME for InFocus Earn CME by completing a quiz about this article. You may read the article here or on our website, and then complete the quiz, answering at least 70% of the questions correctly to earn CME credit. The cost of the CME exam is $10. The payment covers processing and certificate fees. Visit http://CME.LWW.com for more information about this educational offering and to complete the CME activity. This enduring material is available to physicians in all specialties, nurses, and other allied health professionals. 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