Tick Talk: It’s Not All Lyme Disease

Last updated on January 25th, 2023 at 01:11 am

A 32 year old man presents to the ED with fevers and malaise after hiking and camping in Connecticut… do I even need to go into the rest of the history before your mind immediately jumps to “TICK BITE” and then makes the natural leap to looking for a characteristic targetoid erythematous rash?

No one would fault you for making the leap from outdoor recreation in a question stem or patient history to considering Lyme disease, I certainly did it, and the majority of the time, the CDC says you would be right to do so^​1​:

Lyme disease makes up the majority of reported tickborne disease in the US, and although it overshadows the other tickborne diseases by a longshot, it’s important to consider the other causes of tickborne disease – if it’s not on your differential, you won’t diagnose it. So at the end of this article is a quick review on the non-Lyme tickborne diseases (with links below for quick access):

But what do you really need to know when someone comes to the ED with a story concerning for a tick bite and nonspecific symptoms? Let’s break it down:

• The patient may bring you a picture of the tick or the tick itself – I am going to guess you are not a tick expert, but there are some smart people at the University of Rhode Island who are:
  • Send the picture to them – they respond within 24 hours with tick identification
  • Check out their interactive map to see active ticks in your area
• You are not likely to be able to distinguish between the tick borne diseases based just on history and exam alone
  • The exception to this is Lyme/STARI and Rocky Mountain Spotted Fever which show up with a classic rash (erythema migrans and a macular/petichial rash that travels centrally respectively), and Tick Paralysis
• Most tick borne disease is treated with doxycycline, remember the exceptions:
  • Babesiosis – look for hemolysis on the labs, treat with atovaquone and azithromycin
  • Tularemia – presents with local inflammation and regional lymphadenopathy; treat with ciprofloxacin for mild/moderate disease, streptomycin for severe disease
  • Tick paralysis – presents with paralysis/weakness; remove the tick
  • Viral tickborne diseases – this is not an exception, since these present much like Anaplasmosis/Ehrlichiosis, you would treat presumptively with doxycycline

Anaplasmosis

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Anaplasmosis is caused by a bacteria that takes up residence inside our granulocytes (hence the prior name of the disease Human Granulocytic Anaplasmosis (HGA). This disease has been reported to be less severe than its sister Ehrlichiosis (0.3% case fatality vs 1-2.7%), though the presentations are similar, and since case fatality is increasing with more than 50% requiring hospitalization, if your clinical suspicion is high (history of being in an endemic area with flu like symptoms ±tick exposure) or moderate with labs suggestive of Anaplasmosis, treat with doxycycline.^​2,3​

The culprits	Anaplasma phagocytophilum Blacklegged Tick Ixodes scapularisWestern Blacklegged Tick Ixodes pacificus
Geography & season	Upper Midwest and Northeast US; Summer (June, July), second peak in October, November
Early presentation	NON-SPECIFIC: Fevers, chills, headache, myalgias, nausea/vomiting, loss of appetite, cough
Late presentation & severe illness	Respiratory failure, seizures, coma
Risk factors for severe illness	Elderly, immunosuppressed, immunocompromised (HIV)
Diagnosis	Clinical, ↓WBCs (with left shift), ↓Plts, transaminitis, ↑LDH, ↑Alk phos > PCR, serology >> blood smear
Treatment	Adults, children, pregnant patients: doxycycline (will also cover most other tickborne illnesses – not Babesiosis)

Babesiosis

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Babesiosis is one of the tick borne diseases that is NOT treated with doxycycline (!), and will turn up with abnormal labs later in the course. Unfortunately the classic “Maltese Cross” pattern that the parasite makes in erythrocytes is actually pretty rare (I doubt you are looking at your patients’ blood smear anyway). Much like encapsulated bacteria, Babesia can wreak havoc on asplenic patients. Complications arise in over half of patients admitted with severe Babesiosis, with the most common being ARDS; treat with azithromycin and atovaquone in nonpregnant adults with confirmed disease.^​4,5​

The culprits	Babesia microti Blacklegged Tick Ixodes scapularis
Geography & season	Upper Midwest and Northeast US (especially New England); Spring and Summer (May-September, especially June)
Early presentation	Can be ASYMPTOMATIC, NON-SPECIFIC: Fevers, chills, sweats, headache, myalgias, nausea/vomiting, loss of appetite, cough
Late presentation & severe illness	Nausea, vomiting, diarrhea, pulmonary edema, ARDS, splenic rupture/infarct, CHF, renal failure, DIC
Risk factors for severe illness	Elderly, asplenia, immunosuppressed, immunocompromised (HIV)
Diagnosis	Hemolytic anemia (↓H/H, ↓haptoglobin, ↑LDH), transaminitis, thick/thin blood smear (rare to see the classic “Maltese cross”), PCR > serology
Treatment	Adults: azithromycin & atovaquone, Pregnant: clindamycin plus quinine, higher risk of relapse in immunocompromised

Ehrlichiosis

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Ehrlichiosis leads to more serious complications compared with its relative Anaplasmosis. Case fatality is increasing, 1-2.7% at the time of writing, with more than 50% requiring hospitalization, if your clinical suspicion is high (history of being in an endemic area with flu like symptoms ±tick exposure), or moderate with labs suggestive of Ehrlichiosis, treat with doxycycline.^​3,6​

The culprits	Ehrlichia chaffeensis, E. ewingii, or E. muris Blacklegged Tick Ixodes scapularisLone Star Tick Amblyomma americanum
Geography & season	Southeastern and South central US (NY, NC, AR, MO); Summer (June, July)
Early presentation	NON-SPECIFIC: Fevers, chills, headache, myalgias, nausea/vomiting, loss of appetite, cough
Late presentation & severe illness	Meningoencephalitis/AMS, respiratory failure, seizures, coma
Risk factors for severe illness	Elderly, immunosuppressed, immunocompromised (HIV)
Diagnosis	Clinical, ↓WBCs (with left shift), ↓Plts, transaminitis, ↑LDH, ↑Alk phos, CSF lymphocytic pleocytosis and elevated CSF protein levels > PCR, serology >> blood smear
Treatment	Adults, children, pregnant patients: doxycycline (will also cover most other tickborne illnesses – not Babesiosis)

Rocky Mountain Spotted Fever

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Though initially presenting with nonspecific symptoms Rocky Mountain Spotted Fever (RMSF) gives itself up with its characteristic rash which starts on the extremities and makes its way towards the trunk/head. The primary cause of severe disease is delay in treatment, which is likely secondary to to delay in diagnosis; don’t wait for the rash to develop – if you have strong clinical suspicion, treat with doxycycline.^​7,8​

The culprits	Rickettsia rickettsii American Dog Tick Dermacentor variabilis, D. similisBrown Dog Tick Rhipicephalus sanguineusRocky Mountain Wood Tick Dermacentor andersoni
Geography & season	Mid/South Atlantic & South central US (AR, MO, NC, TN, VA); Summer (June/July) – communities with free-roaming dogs; NOT in the Rocky Mountains region
Early presentation	NONSPECIFIC: Fever, headache, malaise, myalgias, arthralgias, abdominal pain, pedal edema, confusion, conjunctival erythema RASH on day 2-5 (macular blanching erythematous & peripheral → petechial & central)*
Late presentation & severe illness	Meningoencephalitis, respiratory distress/ARDS, cardiac arrhythmias, coagulopathy, GI bleed, skin necrosis
Risk factors for severe illness	Delayed diagnosis/treatment, <4 years old, elderly, immunocompromise, male, chronic alcohol abuse, G6PD deficiency
Diagnosis	Clinical > ↓Plts, serology/PCR >> skin biopsy
Treatment	Adults, children, pregnant patients: Doxycycline (will also cover most other tickborne illnesses – not Babesiosis)

Tick Paralysis

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Tick paralysis is terrifying because it is rarely on our differential when we are seeing patients with weakness or abnormal neurological exam findings in the ED. Our go to are central causes of the presentation, and as you can see below, not considering this diagnosis can be fatal due to eventual respiratory paralysis. The cherry on top of this disease is its frustratingly simple treatment: remove the tick.^​9​

Tularemia

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Yes tularemia, although it is rare, can be transmitted from animals to humans via tick bite. This is a difficult diagnosis to make, not only are the initial symptoms nonspecific, making putting this disease on your differential difficult, but Francisella tularensis is difficult to grow in cultures. Mortality rates have trended down, now <5%. Unless your index of suspicion is high (tick bite and weeks-months of symptoms), treatment is likely going to be started by the inpatient team or primary care doctor.^​10,11​

The culprits	Francisella tularensis Lone Star Tick Amblyomma americanum American Dog Tick Dermacentor variabilis, D. similis Rocky Mountain Wood Tick Dermacentor andersoni
Geography & season	South central United States, the Pacific Northwest, and parts of Massachusetts; Summer/warmer months (May-August)
Early presentation	NONSPECIFIC: fever, malaise, anorexia, headache Dependent on inoculation site but usually accompanied by regional lymphadenopathy – skin ulcers, eye irritation/inflammation, sore throat, cough, chest pain, dyspnea
Late presentation & severe illness	Prolonged fever, weight loss, adenopathy, weakness/fatigue lasting weeks-months, can progress to sepsis, renal failure, rhabdomyolysis, and hepatitis
Diagnosis	Clinical, Serology, PCR, culture
Treatment	Severe illness: streptomycin or gentamicin (aminoglycosides) Mild or moderate: Adults: Ciprofloxacin (fluoroquinolones); Children: Gentamicin

Other Tickborne Diseases

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Borrelia miyamotoi

Detected in blacklegged ticks and Western blacklegged ticks, this disease presents similarly to Anaplasmosis/Ehrlichiosis with nonspecific symptoms. PCR and serology is available, and the CDC in partnership with state health departments helps monitor B. miyamotoi infections. Treated with 2-4 weeks of doxycycline.^​12​

Bourbon virus

This is another tickborne disease with nonspecific symptoms, although it presents with leukopenia and thrombocytopenia similar to Anaplasmosis/Ehrlichiosis. Bourbon virus is relatively new, so time will tell on what diagnostics will be available. Unlike those Anaplasmosis and Ehrlichiosis, Bourbon virus is not treated with doxycycline (supportive care is the official answer), though given the similarity in presentation, these are patients who will likely be treated with the antibiotic.^​13​

Colorado tick fever

This is a viral tickborne disease with nonspecific symptoms (half of patients had a biphasic fever) though some patients had a rash. Most patients had self limited mild disease and recovered, with some experiencing weakness/fatigue for several weeks; in rare cases there was stiff neck and confusion. Similar to Bourbon virus, given the similarity of presentation to Anaplasmosis/Ehrlichiosis, these patients will likely be treated with doxycycline, though the official answer is supportive care only.^​14​

Heartland virus

This is another viral tickborne disease with nonspecific symptoms though the CDC specifically states that it may be accompanied by some mild leukopenia, thrombocytopenia, and transaminitis. It even goes as far to state that it presents similarly to Anaplasmosis/Ehrlichiosis. Once again, supportive care is the official answer for treatment, but given the similarity to the presentation to the aforementioned diseases these patients will likely receive doxycycline.^​15​

Powassan disease

Another viral tickborne illness that seems to be increasing in cases reported in the northeast and Great Lakes regions of the US. Initial presentation is nonspecific, though this virus can cause more severe illness including meningitis/encephalitis, with as many as 1 out of 10 people with severe illness dying, and half of people who survive having long-term issues with headaches, loss of muscle mass and strength, and memory. Diagnose with serology or PCR and the treatment is supportive. ^​16​

Other Spotted Fever Group Rickettsioses

There actually more Rickettsia species that cause different spotted fevers, though they present similarly with a dark eschar at the site of the bite, nonspecific symptoms, and then a rash. R. parkeri rickettsiosis, Pacific Coast tick fever (Rickettsia species 364D), and rickettsialpox (R. akari) are all less severe than Rocky Mountain spotted fever, but difficult to distinguish early on in the disease course – which is perfectly fine since they are all treated with doxycycline.^​17​

STARI (Southern tick-associated rash illness)

The aptly named “STARI” is caused by a bite from the Lone Star tick which causes a rash that appears strikingly similar to the erythema migrans from Lyme fame. The cause of STARI isn’t known, nor is whether antibiotics are beneficial or necessary; but it looks like Lyme – treat with doxycycline.^​18​

Tickborne relapsing fever (TBRF)

Defined by recurrent bouts of nonspecific symptoms (fever, headache, myalgias/arthralgias, nausea), TBRF is linked to the Western US and usually sleeping in “rustic, rodent-infested cabins in the mountains”, unless you’re in Texas, in which case it’s linked to cave exposures. These bouts of symptoms tend to last about 3 days and resolve for about one week before recurring in a similar cycle. It’s caused by a Borellia species and the spirochete can be seen in the blood smear, and you can also get serology or culture to confirm. Treat with doxycycline, though if your patient has CNS involvement or is pregnant, ceftriaxone can be used. Watch for Jarisch-Herxheimer reaction in the first 4 hours after initiating antibiotics (worsening of symptoms secondary to release of toxins/cytokines from dying bacteria).^​19​

Cite this post: Arman Hussain, MD. “Tick Talk: It’s Not All Lyme Disease”. GW EM Blog. January 14, 2023. Available at: https://gwemblog.com/non-lyme-tick-diseases/.

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