Case Presentation: A 48 year old woman with a history of stroke, idiopathic intracranial HTN, type 2 DM, HTN, and obesity, presented a few hours after developing increasing confusion and lethargy. For 2 weeks, she also reports headache, neck pain, poor appetite, nausea, rare vomiting, and occasional diarrhea. Exposure history notable for owning a dog, and residence in the Midwestern USA.At the local hospital, she was febrile, hypotensive and somewhat confused. There was concern for sepsis, so she was started on IV fluids, vancomycin and ceftriaxone. She did not require vasopressors. CT Head was negative. She was then transferred to our tertiary medical center. On arrival, she was febrile to 103.2F. Labs revealed Na 131, Cr 2.79. WBC 4.88 K/uL, Hgb 13.0 g/dL, Plt 45 K/uL. ALT 149 U/L, AST 289 U/L. INR 1.2. CK 1508 U/L. Procal 6.3 ng/mL. Hospital Day 1 passed uneventfully. However, that first evening she became increasingly somnolent with fever up to 103F. On Hospital Day 2, she remained febrile, and now unable to follow commands, and only oriented to self. Additional labs revealed ferritin 10749 ng/mL, fibrinogen 402 mg/dL, TG 312 mg/dL, CRP 142 mg/L, IL2-R 5529 pg/mL. CTAP revealed hepatosplenomegaly. LP revealed glucose 116, protein 155, WBC 15 with 30% neutrophils, RBC 391. Infectious disease was consulted. With her fever without a clear source, risk factors, and clinical picture, we started doxycycline 100mg IV q12h. Hematology was consulted with concern for hemophagocytic lymphohistiocytosis (HLH). H-Score was 224. However as the infectious workup was pending, steroid treatment was deferred. On Day 3, she remained altered and febrile (peak 104.7F). Bone marrow biopsy was completed. After an interdisciplinary risk-benefit discussion, we started Dexamethasone 25 mg IV daily. By Day 4, she was much more alert with decreased fever. Then by Day 5, her fevers had completely resolved. Anaplasma PCR resulted positive. Unfortunately, bone marrow biopsy pathology was nonspecific. In the following days, she continued to improve. We continued Dexamethasone 25 mg for a total 7 day course, with plans for a 4 week taper. On Day 10, we discharged her home with complete resolution of her fever and confusion. Final diagnosis was severe anaplasmosis complicated by HLH.
Discussion: Although rare, with less than 8,000 cases of anaplasma and ehrlichiosis annually in the USA, if there is suspicion for tick borne illness, empiric doxycycline should be started. Risk factors include geographic travel/residence, animal exposure, and immunosuppression, while clinical clues include characteristic rash, thrombocytopenia, and transaminitis. HLH is an excessive inflammatory response triggered by infection, malignancy or rheumatologic conditions. To date, there have only been a handful of case reports documenting severe anaplasmosis or ehrlichiosis complicated by HLH. The HScore can be used to estimate likelihood, and is based mainly on the presence of fever, hepatosplenomegaly, cytopenia, high ferritin, high triglyceride, and low fibrinogen. Bone marrow biopsy may not always be sensitive. Workup for an inciting cause and then treatment of the cause is crucial, especially in infectious cases. Anti-inflammatory medication can be considered for severe/refractory cases.
Conclusions: Fever without a source in the setting of possibly tick-borne illness should lead to consideration of starting doxycycline. Severe cases of anaplasmosis and ehrlichiosis should also prompt evaluation for HLH, which responds well to treatment of the inciting cause.
