Thursday, July 17, 2014

The Lone Star Tick

Recently a 65-year-old female was referred to an ED in the state of Missouri complaining of fevers, chills, headache, diarrhea and vomiting occurring over the last week. 3 weeks prior she had received an orthotopic liver transplant. Her post transplant course was unremarkable and she was discharged on prograf 2mf bid, myfortic 360mg bid, prednisone tapering, Bactrim single strength daily and valcyte 450mg od. She also took thyroid replacement, Januvia, warfarin and aspirin. Past medical history included diabetes, heart failure, dysfunctional uterine bleeding, hypothyroid and PUD. She also had CKD with a creatinine about 1.4mg/dl. On examination her Temp was 38.6, HR 110, BP 113/76 and O2sats 99% on RA. She had no nuchal rigidity but reported a sore neck. She had an erythematous area on her lower back. The rest of her exam was normal.

Her initial labs were:
Hb 6.3, WCC 2.7 (94%neuts, 5.8%lymphs), platelets 35
NA 122, K 5.6, Cl 100, CO2 11, BUN36, Creat 2.3, Gluc 173
Arterial pH 7.31, CO2 20, O2 102
AST 52, ALT 41, AP 155, GGT 171, Bili 0.6, Alb 3.3
UA, No blood, 1+protein, 2 rbc, 2 wbc

She had a normal CT brain and was started on multiple antibiotics in the ED.

On further questioning her daughter reported removing a tick from her back after the patient went out looking at deer close to her house.
Lets pretend the daughter brought in a picture of the tick (see above)!

Lab trends; admission to discharge.
Hb 6.3
WCC 2.7                   1.4           0.6           0.5           0.3           1.2           2.4
94%neut                90            91            87            83            60            59
5.8%lym                 6               6.7           9.2           14            16            28
plt 35                       16            18            24            28            26            31
NA 122                    128         132         135
K 5.6                   
Cl 100
Co2 11
Creat 2.3                 2.2           1.8           1.6                                               1.3
Gluc 173
pH 7.31
CO2 20
O2 102
AST 52                                                                                                               31
ALT 41                                                                                                               31
AP 155                                                                                                              249
GGT 171                                                                                                                            
Bili 0.6                                                                                                               0.8
Alb 3.3
No blood
2 rbc
2 wbc
No lumbar puncture was performed.

To summarize, this lady had constitutional symptoms, fever, neurological symptoms, GI symptoms with a rash and a tick bite. She had pancytopenia, transaminitis, hyponatreamia and renal failure.

Her antiproliferative medication and anti-infective medications were held (Myfortic, valcyte and Bactrim).
IV Doxycycline was commenced.
Sodium and creatinine improved and potassium became low, likely due to GI losses.
Interestingly her leucopenia followed the classical pattern of lymphopenia followed by leucopenia and she required G-CSF. Her transaminases were normal at the time of discharge.

Diagnosis = Ehrlichiosis 

The first case of human ehrlichiosis was described in 1986.
The two most important species to infect humans are Ehrlichia chaffeensis which causes human monocytic ehrlichiosis (HME) and Anaplasma phagocytophilum which causes human granulocytic anaplasmosis (HGA). Both of these diseases have the same vector and have very similar clinical and laboratory features. Ehrlichia ewingii is a less common cause of ehrlichiosis than Ehrlichia chaffeensis.
Ehrlichiae are obligate intracellular bacteria found in membrane bound vacuoles in human and animal leukocytes.

The most endemic area is the southeastern USA – ‘the tick belt’. See the CDC map for the endemic regions in the USA. Cases have also been reported in Europe, Africa, South America and Mexico.

The lone star tick (Amblyomma americanum) is recognized by the CDC as the principal vector of Ehrlichia chaffeensis and Ehrlichia ewingii in the U.S.; both disease agents are responsible for causing ehrlichiosis in humans. White-tailed deer are a primary host of the lone star tick and appear to serve as a natural reservoir for E. chaffeensis. The lone star tick is also a vector of Francisella tularensis, causal agent of tularemia. Adult ticks parasistize deer, cattle, horses, feral swine, sheep, dogs, and humans.

Most infections occur in the spring and summer in the USA.

The clinical manifestations in the elderly and immunosuppressed can be very severe but the following are the usual clinical features:

Fever - Some fevers can be protracted over weeks
Malaise, myalgia, headache and chills – 2/3
Nausea, vomiting and arthralgia – ¼ to ½
Rash (Macular, mucopapular, petechial) – 1/3
Meningism – ¼

More rarely – Seizures, coma, renal failure, heart failure and respiratory failure
There has been a single case of myocarditis and multi-organ failure in a healthy adolescent.

Laboratory findings:
Most common triad is leucopenia, thrombocytopenia and elevated transaminases.

Leucopenia. This tends to be caused by lymphopenia initially followed by neutropenia as in this patient.

Elevated transaminases, LDH and Alk phos
Elevated creatinine

CSF, when neurological symptoms
Lymphocytic pleocytosis and elevated CSF protein

Usually by PCR methods. Note this test may not detect the recently reported third species, E. muris, found in Wisconsin and Minnesota.

Differential diagnosis
This can be a difficult diagnosis to make. It is clinically and geographically similar to RMSF. It can also present like mononucleosis, TTP, hematologic malignancy, cholangitis, the early phases of hepatitis A infection. This is especially so in immunocompromised patients whose clinical features may not be as obvious initially. Common transplant drugs such as Bactrim/Septra, valganciclovir, mycophenolate and azathioprine can also cause cytopenias.

Treatment (adults)
Doxycycline 100mg iv or po bid for about 10 days.
Note this will also treat RMSF which is often confused with ehrlichiosis.

Outcomes. Mortality is about 5%. Most commonly due to viral or fungal super-infections (Invasive aspergillosis, candida, HSV).

This interesting case illustrates the difficulty in diagnosing tick borne infections. They can be lethal and severe in our immunosuppressed transplant population and can be a cause of renal failure in any patient. Also of interest in this case is the lymphocytopenic and neutropenic trending that is usually more peculiar to Anaplasma phagocytophilum which causes human granulocytic anaplasmosis (HGA). We did not test for A phagocytophilum as ehrlichae PCR was positive.

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