A 71 y.o. female sp bilateral lung transplant in 2007 presents with fever, pancytopenia and altered mental status. Her CXR is shown below.

What is the differential?

Our patient had Ehrlichiosis.

Tick-borne rickettsiae in the genera Ehrlichia (lone star tick)and Anaplasma ( Ixodes tick)  are intracellular bacteria that infect animals and man. They present with a febrile illness. The first case of human granulocytic anaplasmosis (HGA) was recognized in Duluth Minnesota in 1990. Ehrlichia chaffensis was first describe in 1987 at Fort Chaffee Arkansas when it was found among military recruits.  Missouri, Arkansas and Oklahoma account for over 1/3 of the cases of Ehrlichia in the US.  The reservoir of the disease is white tailed deer.

Both Ehrlichia(HME) and Anaplasmosis(HGA) have similar presentations including fever, headache, leukopenia, thrombocytopenia and elevated liver enzymes.  Lung infiltrates, noncardiogenic pulmonary edema and ARDS can be seen on CXR.  CSF pleocytosis is identified in 60% of patients who undergo lumbar puncture.  Symptoms begin a median of 9 days after an infected tick bite. Neurologic manifestations are most frequently reported with Ehrlichia.  

Ehrlichia is also an important veterinary pathogen.  It was first described inAfrica in 1935 and is transmitted by the brown dog tick.

The gram negative  bacteria infects granulocytesand replicates in the membrane bound compartments of granulocytes and monocytes.  They form colonies called morulae derived from the Latin word :”morus” for mulberry.  They can be seen in peripheral blood leukocytes. Up to 17% of patients develop life threatening complications although they are much more likely in immunocompromised patients like ours.  

Our patient developed hemophagocytic lymphohistiocytosis (HLH) which is a generalized reaction of the immune system where a  proliferation of morphologically benign lymphocytes and macrophages secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.  Rbcs can be seen in within macrophages in the marrow.  It is characterized by high ferritin, cytopenia, fever and splenomegaly and  is treated with steroids.  Our patient not only received treatment with doxycycline for Ehrlichia but also received steroids for HLH. She was on hemodialysis for renal failure and was eventually transferred to rehab after being in the hospital for two months.

Howard Ricketts, was a pathologist for whom these organisms were named.  Ricketts was devoted to his research and on several occasions injected himself with pathogens to study their effects.  In 1910 he discoveredthe cause of murine typhus and days after isolating the organism, he himself died of the disease.

Ismail N, Bloch K, McBride J.  Human Ehrlichiosis and Anaplasmosis. Clin Lab Med. 2010 30(1); 261-292.

Paddock CD, Sumner JW, Shore GM, et al. Isolation and characterization of Ehrlichia chaffeenisis strains from patients with fatal ehrlichiosis. J Clin Microbiol. 1997;35:2496-2502.

Demma LJ, Holman RC, McQuiston JH.  Human monocytic ehrlichiosis and human granulocytic anaplasmosis in the United States, 2001-2. Ann NY Acad Sci 2006;1078:118-9.