Fever, Chills, and Altered Mental Status How Broad Should the Differential Diagnosis Be?

Transcription

1 Fever, Chills, and Altered Mental Status How Broad Should the Differential Diagnosis Be? Kelly Letsinger, M.D. Antonio Abbate, M.D. Constantine Michaelides Virginia Commonwealth University Medical Center

2 Introduction Fever, chills, and altered mental status are common presentations of many illnesses. A thorough history, physical exam, laboratory data, and additional studies can help elucidate an etiology. It is essential to truly investigate a patient s presentation as crucial clues may be ignored when another diagnosis seems more obvious.

3 History of Present Illness 59 year old man presents to the emergency room in June for recurrence of fever, chills, and altered mental status. Seen by urology 8 days earlier to prepare for transurethral resection of the prostate. U/A showed urinary tract infection, but results not reviewed. 3 days later, normal cystoscopy and urinary catheter (large postvoid residual). Levofloxacin for previous urinary tract infection (culture growing Enterococcus).

4 History of Present Illness 2 days later, patient went to emergency room for 1 day history of fever, chills, anorexia, and malaise. Levofloxacin changed to amoxicillin based on sensitivity results. Returned to emergency room again 2 days later for continued symptoms with added complaint of headache.

5 Medical History Benign Prostatic Hypertrophy with obstruction Chronic Obstructive Pulmonary Disease Positive cardiac stress test Hypertension Osteoarthritis Gastroesophageal Reflux Disease Hyperlipidemia

6 Social History Quit smoking 25 years ago Rare alcohol Denies drug use Recent travel to Germany returned 2 weeks ago after being there for 4 weeks Works as outdoor safety instructor for Army soldiers

7 Medications Atrovent 2 puffs twice daily Aspirin 325mg daily Finasteride 5mg daily Ibuprofen 300mg three times daily Lovastatin 40mg each night Metoprolol 12.5mg every 12 hours Omeprazole 20mg twice daily Nitroglycerin sublingual prn NKDA

8 Physical Exam BP 135/79 HR 97 RR 18 T Pox 96% on RA General appears ill, moderate distress Chest clear to auscultation Cardiovascular regular rhythm, normal rate, no murmurs Abdomen mild suprapubic tenderness, no rebound or guarding. Normal BS. No hepatomegaly. GU no urethral discharge. Urinary catheter in place. Clear urine. Skin warm. 7mm slightly raised erythematous elongated lesion on right superior medial thigh with small central ulceration, slightly tender. Neuro cranial nerves intact. Alert and oriented X3 with mild confusion. No meningeal signs.

9 Chest X-ray

10 Labs on Day of Presentation Neut-72%, Lymph-22%, Mono-5% Ca-8.4 Mg-1.6 Phos-1.4 Urinalysis neg leuk, neg nit, >80 ketones, mod blood, 6-14 RBC, no WBC

11 Initial Management Based on his recent urinary tract infection and continued fevers and chills with altered mental status, the patient was presumed to have treatment failure. His antibiotics were changed to amoxicillin/clavulanate. The patient showed no improvement overnight. His mental status acutely worsened.

12 Subsequent Laboratory Data Seg-54% Band-12% Lymph-25%, Mono-9% Albumin-3.0 AlkPhos-78 AST-212 ALT-206 Protein-5.5 Bili-1.2 CSF unremarkable no cells

13 Hospital Course After noting the elevated transaminases, leukopenia, and thrombocytopenia, tick-borne illness entered the differential diagnosis. On furthing questioning, the patient revealed multiple tick exposures, most recently one week ago, resulting in the erythematous lesion described on physical exam. He reported removing the ticks as soon as they were seen.

14 Tick Bite Photo courtesy of

15 Case Summary 59 year old man presents in June with fever, chills, headache and altered mental status Elevated transaminases, leukopenia, thrombocytopenia TICK EXPOSURE

16 Hospital Course Doxycycline immediately added to antibiotic regimen. Elevated transaminases, leukopenia, thrombocytopenia, fevers, chills, mental status, and headaches normalizing within 24 hours.

17 Laboratory Data HGE IgM/IgG RMSF IgM/IgG ALL NEGATIVE Lyme IgM/IgG CSF Lyme PCR Q fever Typhus Hepatitis A,B,C HIV

18 Laboratory Data 2 weeks later HGE IgM 1:320 HGE IgG 1:512

19 Discussion Ehrlichiae are intracellular bacteria that grow within membranebound vacuoles (morulae) in human and animal leukocytes. Picture courtesy of

20 Discussion Human Granulocytic Ehrlichiosis - HGE (also called Human Granulocytic Anaplasmosis) - caused by Anaplasma phagocytophilum. Vector = Ixodes scapularis (same as for Lyme disease and Babesiosis). Animal reservoir = white-footed mouse Most cases occur in North Central and Northeastern United States. Pictures courtesy of

21 Discussion Most cases occur in spring and summer. Graph courtesy of

22 Discussion Ehrlichiosis is a relatively rare disease not reportable in all states, so true annual incidence unknown up to 16 cases per 100,000 in endemic areas Graph courtesy of

23 Virginia Data data revealed 0.1 Ehrlichiosis cases per 100,000. All were white. 2 were female, 6 were male Total N umber of Reported Ehrlichiosis Cases Data courtesy of Virginia Department of Health

24 Presentation of Ehrlichiosis Usually present with nonspecific signs and symptoms Most common symptoms - fever, headache, malaise, and muscle aches. May complain of nausea, vomiting, diarrhea, cough, joint pains, confusion, or rash. Leukopenia, thrombocytopenia, and elevated liver enzymes most common lab abnormalities

25 Diagnosis/Prognosis Diagnosis PCR peripheral smear (morulae) antibody titers (usually undetectable until 2-3 weeks after onset of illness need at least a 4-fold rise or fall of titer between the acute and convalescent stage) 2-3% can die if untreated.

26 Conclusions Critical clues leading AWAY from urinary tract source: normal urinalysis after antibiotics elevated liver enzymes, leukopenia, and thrombocytopenia. Fever, chills, and headache during spring or summer should prompt consideration of tick-borne illness. Patients can directly provide helpful information regarding differential diagnosis this patient would have quickly provided tick exposure history if asked!

27 Conclusions It is essential to always perform a thorough history and physical. Zebras can be hiding amongst the horses!

28 References 1. UpToDate.com Human Ehrlichiosis and Biology of Ehrlichiae 2. CDC.gov Human Ehrlichiosis in the United States 3. Vdh.state.va.us 4. Dermatlas.com 5. Fishbein, DB, Kemp, A, Dawson, JE, et al. Human ehrlichiosis: Prospective active surveillance in febrile hospitalized patients. J Infect Dis 1989; 160: Bakken, JS, Dumler, JS. Human granulocytic ehrlichiosis. Clin Infect Dis 2000; 31: Dumler, JS, Bakken, JS. Ehrlichial diseases of humans: Emerging tick-borne infections. Clin Infect Dis 1995; 20: Parola, P, Raoult, D. Ticks and tickborne bacterial diseases in humans: an emerging infectious threat. Clin Infect Dis 2001; 32: Everett, ED, Evans, KA, Henry, RB, McDonald, G. Human ehrlichiosis in adults after tick exposure. Ann Intern Med 1994; 120: Bakken, JS, Krueth, J, Wilson-Noldskog, C, et al. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275:199.