The n e w e ng l a n d j o u r na l of m e dic i n e

case records of the massachusetts general hospital

Founded by Richard C. Cabot

Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate Editor
Jo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor

Case 6-2011: A 77-Year-Old Man

with Dyspnea, Weakness, and Diaphoresis
Athe M.N. Tsibris, M.D., Jo-Anne O. Shepard, M.D., and Lawrence R. Zukerberg, M.D.

Pr e sen tat ion of C a se

Dr. Gyanprakash A. Ketwaroo (Medicine): A 77-year-old man with a history of ischemic From the Infectious Disease Unit
cardiomyopathy was admitted to this hospital in midspring because of increasing (A.M.N.T.) and the Departments of Radi-
ology (J.-A.O.S.) and Pathology (L.R.Z.),
dyspnea, weakness, and diaphoresis. Massachusetts General Hospital; and the
The patient had been in his usual state of health until 3 days before admission, Departments of Medicine (A.M.N.T.), Ra-
when weakness, loss of appetite, fatigue, and diarrhea developed, followed by diology (J.-A.O.S.), and Pathology (L.R.Z.),
Harvard Medical School — both in Boston.
progressive shortness of breath. On the morning of admission, he awoke with dys-
pnea, which was worse when he was lying flat; he was unable to catch his breath N Engl J Med 2011;364:759-67.
or get out of bed. He was diaphoretic and felt nauseated and weak, with no chest Copyright © 2011 Massachusetts Medical Society.

pain, fever, or cough. The temperature was reportedly 37.8°C. His wife administered
acetaminophen and called emergency medical services personnel. On their arrival, the
patient’s skin was cool and pale, he spoke in sentences of three or four words, and
he used accessory respiratory muscles. The blood pressure was 160/90 mm Hg, the
pulse 96 beats per minute, the respiratory rate 40 breaths per minute, and the oxy-
gen saturation 90 to 91% while he was breathing ambient air. Basilar rales ex-
tended a third to half of the way up both lung fields, and the abdomen was dis-
tended. Oxygen (5 liters per minute) was administered by a nonrebreather mask, and
oxygen saturation increased to 99%. He was taken to another hospital.
On examination, the temperature was 37.2°C, the blood pressure 152/79 mm Hg,
the pulse 93 beats per minute (irregularly irregular), the respiratory rate 24 to 30
breaths per minute, and the oxygen saturation 100% while the patient was breath-
ing supplemental oxygen through a nonrebreather mask. There were coarse rales
bilaterally, the skin was cool and diaphoretic, and respiratory support with bilevel
continuous positive airway pressure was added transiently on arrival, with symp-
tomatic improvement. Electrocardiography revealed atrial fibrillation with inter-
mittent pacing and bifascicular block, with ST-segment depression, T-wave inver-
sion, and Q waves in leads V1 and V2, which were reportedly unchanged from
5 months before. A chest radiograph reportedly revealed mild pulmonary edema
and moderate cardiomegaly. The serum levels of total bilirubin, creatine kinase
MB isoenzymes, and troponin I were normal; other laboratory-test results are
shown in Table 1. Nitroglycerin and furosemide were administered intravenously,
and acetaminophen was given, as well as the patient’s usual doses of digoxin,

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 The n e w e ng l a n d j o u r na l of m e dic i n e

ezetimibe, levothyroxine, lisinopril, sotalol, and
acetylsalicylic acid. The systolic blood pressure
decreased to below 100 mm Hg; the intravenous
nitroglycerin was stopped, and sublingual and
cutaneous nitrate preparations were adminis-
tered thereafter. Approximately 6 hours after
arrival, the patient was transferred by ambulance
to this hospital.
The patient had ischemic cardiomyopathy,
which was associated with an anteroseptal myo-
cardial infarction 30 years earlier. Two years
before admission, echocardiography showed a
left ventricular ejection fraction of 23%. He had
arrhythmias, including atrial flutter and ven-
tricular tachycardia, for which an implantable
cardioverter–defibrillator (ICD) had been placed.

Table 1. Laboratory Data.*

Reference Range,
Variable Adults† Other Hospital This Hospital
4 Hr after 14 Hr after 19 Hr after 36 Hr after
Admission Admission Admission Admission
Hematocrit (%) 41.0–53.0 (men) 43.2 43.9 48.8 41.5 36.7
Hemoglobin (g/dl) 13.5–17.5 in men 15.1 15.3 16.5 14.2 12.4
3)
White-cell count(per mm 4500–11,000 5800 7000 8600 8700 4600
Differential count (%)
Neutrophils 40–70 58 62 43
Band forms 0–10 30 27 29
Lymphocytes 22–44 8 4 19
Atypical lymphocytes 0 0 1 0
Monocytes 4–11 4 4 4
Metamyelocytes 0 2 5
Platelet count (per mm3) 150,000–400,000 78,000, enlarged 78,000 52,000 55,000, giant 34,000
forms
Mean corpuscular volume (μm3) 80–100 98.7 98 99 99 98
Activated partial-thromboplastin 21.0–33.0 36.0 (ref 25.3–37.0) 38.4 44.0
time (sec)
Prothrombin time (sec) 10.8–13.4 22.4 27.2 28.7 29.0 22.4
International normalized ratio 2.4 2.6 2.8 2.8 2.1
for prothrombin time
Sodium (mmol/liter) 135–145 136 136 139 142 142
Potassium (mmol/liter) 3.4–4.8 4.1 4.2 4.6 3.7 3.9
Chloride (mmol/liter) 100–108 98 100 97 103 111
Carbon dioxide (mmol/liter) 23.0–31.9 27 15.0 25.0 26.5 19.3
Urea nitrogen (mg/dl) 8–25 32 43 54 59 62
Creatinine (mg/dl) 0.60–1.50 1.71 1.95 2.27 2.71 2.18
Glucose (mg/dl) 70–110 170 127 136 111 113
Phosphorus (mg/dl) 2.6–4.5 3.9 1.3
Magnesium (mg/dl) 1.7–2.4 1.9 2.8 2.9 2.6
Calcium (mg/dl) 8.5–10.5 8.8 8.4 7.4 6.9
Alkaline phosphatase (U/liter) 45–115 28 29 22
Aspartate aminotransferase (U/liter) 10–40 79 243 420
Alanine aminotransferase (U/liter) 10–55 40 75 106
B-type natriuretic peptide (pg/ml) 1452 (ref 0–100)
Creatine kinase (U/liter) 60–400 (men) 106 433 1243 719

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 case records of the massachusetts gener al hospital

Table 1. (Continued.)

Reference Range,
Variable Adults† Other Hospital This Hospital
4 Hr after 14 Hr after 19 Hr after 36 Hr after
Admission Admission Admission Admission
Troponin T (ng/ml) <0.03 0.02 0.01
Lactate (mmol/liter) 0.5–2.2 3.7 2.5
d-Dimer (ng/ml) <500 6225
Lactate dehydrogenase (U/liter) 110–210 938
Iron (μg/dl) 45–160 30
Iron-binding capacity (μg/dl) 228–428 192
Folic acid (ng/ml) 3.1–17.4 >20.0
Arterial blood gas
Fraction of inspired oxygen 0.40 1.00 0.40
pH 7.35–7.45 7.42 7.46 7.41
Partial pressure of carbon dioxide 35–42 48 35 34
(mm Hg)
Partial pressure of oxygen (mm Hg) 80–100 98 397 114
Base excess (mmol/liter) 4.4 1.0 2.9, negative

* Ref denotes reference range at the other hospital. To convert the value for urea nitrogen to millimoles per liter, multiply by 0.357. To convert
the value for creatinine to micromoles per liter, multiply by 88.4. To convert the values for glucose to millimoles per liter, multiply by
0.05551. To convert the value for phosphorus to millimoles per liter, multiply by 0.3229. To convert the value for magnesium to millimoles
per liter, multiply by 0.4114. To convert the values for calcium to millimoles per liter, multiply by 0.250.
† Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at
Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They
may therefore not be appropriate for all patients.

Nine months before admission, atrial fibrilla-
tion had developed and an ablation procedure
was performed; sinus rhythm had predominated
since then. The patient also had hypothyroidism,
hyperlipidemia, hypercholesterolemia, and hyper-
tension, and he had had a transient ischemic
attack, a stroke (suggestive of emboli) while he
was receiving therapeutic anticoagulation, a di-
verticular bleed 2 months before admission, and
an appendectomy 3 months before admission.
Other medications included fenofibrate and war-
farin. He had no known allergies. He was retired,
had returned from a prolonged wintertime trip to
Florida 3 weeks before admission, and lived with
his wife in a wooded suburban community in
the Northeast, with no pets. The patient and his
wife had traveled extensively through the United
States but not internationally. He had stopped
smoking 35 years earlier and did not drink al-
cohol or use illicit drugs. His children were
healthy, and he had no contact with sick persons.
On examination, the patient was diaphoretic.
The weight was 79.6 kg, the temperature 36.6°C,
the blood pressure 90/54 mm Hg, the pulse 85
beats per minute (atrial fibrillation with paced
beats), the respiratory rate 22 breaths per minute,
and the oxygen saturation 95% while the patient
was breathing 40% oxygen by face mask. The
jugular veins were distended to the angle of the
jaw, the lung sounds were diminished and in-
cluded faint bibasilar rales, and the remainder of
the examination was normal. The level of digoxin
was therapeutic, and the level of thyrotropin was
normal; other test results are shown in Table 1.
Oxygen supplementation and additional furose-
mide were administered. The urine output totaled
1975 ml that day, resulting in some improve-
ment in the patient’s symptoms; he remained
fatigued and dyspneic after minimal activity.
During the night, tachypnea and diaphoresis
recurred and were followed by short runs of ven-
tricular tachycardia; magnesium sulfate was ad-
ministered. Fourteen hours after admission, the
patient was diaphoretic, with cool and clammy

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 The n e w e ng l a n d j o u r na l
skin and increasing somnolence. The axillary
temperature was 37.2°C, the blood pressure
133/77 mm Hg, the pulse 80 to 90 beats per
minute, the respiratory rate 36 breaths per min-
ute, and the oxygen saturation 97% while he was
breathing 40% oxygen by face mask. Breath
sounds were coarse, with no rales or wheezing.
Serum levels of total and direct bilirubin, total
protein, albumin, cholesterol, low-density lipo-
protein, amylase, and lipase were normal; other
test results are shown in Table 1. Urinalysis
showed clear yellow urine, a pH of 5.5, a specific
gravity of 1.015, 1+ ketones, 3+ blood, 2+ pro-
tein, and 5 to 10 red cells and 0 to 2 white cells
per high-power field. A chest radiograph showed
mild pulmonary venous hypertension, atelectasis
in the base of the left lung, a small pleural effu-
sion on the left side, and mild cardiomegaly.
Two hours later, 16 hours after admission, a
prolonged episode of ventricular tachycardia (190
beats per minute) was recorded on a monitor and
converted to sinus rhythm by means of overdrive
pacing. The patient was unresponsive; the blood
pressure was 69/41 mm Hg and the oxygen satu-
ration 87% while he was breathing 40% oxygen
through a nonrebreather mask. The trachea was
intubated, and intravenous fluids and vasopres-
sors were administered. The patient was trans-
ferred to the coronary care unit. Transthoracic
echocardiography revealed a left ventricular ejec-
tion fraction of 15%, with a diffusely hypoki-
netic right ventricle and a right ventricular sys-
tolic pressure of 36 mm Hg, and no vegetations.
Vancomycin, cefepime, and metronidazole
were administered. An abdominal radiograph
showed no evidence of bowel obstruction or
perforation. Specimens of blood and sputum
were cultured. That night, the temperature rose
to 39.4°C. The next day, the results of a diagnos-
tic test were received.
Differ en t i a l Di agnosis
Dr. Athe M.N. Tsibris: This 77-year-old man with
known cardiovascular disease presented with an
acute illness and the systemic inflammatory re-
sponse syndrome, which rapidly progressed to
shock. Although acute exacerbations and compli-
cations of his chronic medical conditions (e.g.,
congestive heart failure and known arrhythmias)
no doubt contributed to this presentation, I be-
lieve an overwhelming systemic infection most
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of m e dic i n e
likely precipitated his hospitalization and subse-
quent hemodynamic collapse. May we review the
imaging studies?
Dr. Jo-Anne O. Shepard: A chest radiograph showed
pulmonary venous hypertension, moderate car-
diomegaly that had increased since a study that
was performed 7 months earlier, atelectasis in
the base of the left lung, and a small pleural ef-
fusion on the left side (Fig. 1).
Dr. Tsibris: This patient’s initial presentation,
with weakness and worsening dyspnea, is consis-
tent with exacerbation of congestive heart fail-
ure. Diaphoresis and the development of fever and
hypotension raise the likelihood that infection is
the cause of his cardiac decompensation. Notable
laboratory findings include immature neutrophil
forms that are circulating in the peripheral blood
(“left shift”), absolute lymphopenia, azotemia, in-
creased aminotransferase levels without elevations
in the levels of alkaline phosphatase and biliru-
bin, and elevations in lactate dehydrogenase levels.
There are many causes of septic shock that are
consistent with this presentation, so we need a
way to limit and focus our differential diagnosis.
The immune status of the patient is an important
consideration; no overt immunosuppression is
evident, but his advanced age confers a relatively
immunosuppressed state. Immunosenescence, a
decline in immune-system function with age, is
increasingly well characterized and affects both
innate and adaptive immunity.1,2 Immunosenes-
cence may predispose the elderly to more frequent
and more severe infections than the nonelderly,
and when we cross a list of infections in the elder­
ly with a list of causes of septic shock — keeping
in mind this patient’s presentation — I believe
we can limit our discussion to five infectious
processes: pneumonia, infective endocarditis,
infectious diarrhea, bacteremia, and tickborne
illnesses.
Pneumonia
Bacterial pneumonia is significantly more likely
in patients more than 65 years of age than in
those less than 45 years of age and warrants con-
sideration in an elderly patient presenting with
fever and dyspnea.3 Concomitant diarrhea and
mild hyponatremia raise concern for Legionella
pneumophila; cough and pleuritic chest pain, how-
ever, were not reported, and the absence of an
infiltrate on the chest radiograph makes pneu-
monia of any kind an unlikely diagnosis. Dehy-
 case records of the massachusetts gener al hospital

dration may obscure the visualization of pulmo-

nary infiltrates, but it would be difficult for us to
make a case for volume depletion in this fluid-
overloaded patient. The patient’s advanced age
should not preclude consideration of human im-
munodeficiency virus (HIV) infection4; Pneumo-
cystis jiroveci pneumonia is known to present
without infiltrates. Patients over the age of 65,
however, accounted for 0.3 to 0.4% of total diag-
noses of acquired immunodeficiency syndrome
in the United States from 2002 to 2006.5 In the
absence of any known risk factors, HIV infection
and P. jiroveci pneumonia are not likely, but test-
ing for HIV may nonetheless be warranted.

Infective Endocarditis
The diagnostic Oslerian criteria of bacteremia,
acute valvulitis, peripheral emboli, and immuno-
logic vascular phenomenon have been incorpo-
rated into the modified Duke criteria that em- Figure 1. Chest Radiograph.
phasize echocardiographic and culture evidence A chest radiograph obtained on admission shows pul-
to substantiate a diagnosis of infective endocar- monary venous hypertension, atelectasis in the base
ditis.6 This patient’s echocardiogram did not of the left lung, a small pleural effusion on the left side,
and slight cardiomegaly. An intracardiac defibrillator is
show valvular vegetations, and there are no ma- in place.
jor criteria and only one minor criterion (fever) to
support this diagnosis. In this case, the low clin-
ical suspicion should be sufficient to rule out en- positive organisms are the most common infec-
docarditis. tious agents; however, the incidence of fungemia is
increasing, and gram-negative bacteria can still
Infectious Diarrhea predominate in patients who are older than 65
Elderly patients account for the majority of diar- years of age.9 Sources of community-acquired
rheal deaths in some series, especially if Clostrid- gram-negative bacteremia in the elderly (age, >70
ium difficile is the pathogen.7,8 I would consider years) include the urinary tract (the most likely
the classic pathogenic Enterobacteriaceae (Esche- source), as well as the gastrointestinal tract, re-
richia coli, campylobacter, shigella, salmonella, spiratory tract, and skin and soft tissues. In this
yersinia), Listeria monocytogenes, and less likely, patient, I would be most concerned about diver-
C. difficile in the differential diagnosis. The absence ticulitis and known diverticulosis complicated by
of an antecedent history of questionable food ex- gram-negative bacteremia. The atrial fibrillation
posure or any friends or family members who are predisposes the patient to an atrial thrombus that
similarly ill, however, dampens the enthusiasm could be secondarily infected during a period of
for an Enterobacteriaceae infection. The elderly bacteremia. Gram-positive bacteremia can origi-
are at increased risk for invasive listeria infec- nate from the skin, and in this patient we should
tions, although the classic presentation includes consider an infection of the ICD pocket or a deep-
vomiting, which this patient does not have; men- er infection as a possible source. No major risk fac-
ingitis and cerebritis are also absent in this pa- tors are present for candidemia or fungemia. In-
tient. There is also no evidence of abdominal fluenza, West Nile virus, and enteroviral infections
pain or the marked leukocytosis that is classi- may result in myocarditis, but there is little labo-
cally seen in patients with severe C. difficile colitis. ratory, electrocardiographic, or echocardiographic
evidence to support the diagnosis of myocarditis.
Bacteremia and Viral Infections At this point, a provisional diagnosis of septic
Bacteremia could explain much of this patient’s shock secondary to bacteremia would be reason-
presentation and laboratory abnormalities. Gram- able. Although a wide range of laboratory abnor-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

malities may accompany shock, the laboratory Ehrlichiosis

findings in this case point us toward a more Infection with Ehrlichia chaffeensis, a gram-nega-
specific diagnosis. tive coccobacillus, has been described as Rocky
Mountain spotted fever without the rash,11 and
Tickborne illnesses no clinical criteria absolutely differentiate the
This patient lived in a wooded area of the North- two infections. Patients with human monocytic
east and presented in midspring, so we should ehrlichiosis, a zoonosis, commonly present in
pay particular attention to human infections that May through July with fever, malaise, and head-
result from tick exposure. This patient could be ache; dyspnea and diarrhea can occur, and renal
at risk for Lyme disease; however, there is no his- dysfunction is possible. In most cases, leukopenia,
tory of the early localized skin manifestations of thrombocytopenia, and elevated aminotransfer-
Lyme disease, and a disseminated infection lead- ase levels are noted. The illness can range in se-
ing to myocarditis without concomitant neuro- riousness from mild to fatal, with more severe
logic findings would be rare. Diarrhea raises the disease reported in the elderly. Morulae of bac-
possibility of typhoidal tularemia, but this pa- teria are seen in less than 10% of cases on a
tient does not have the cholestasis, jaundice, or Wright–Giemsa stain of a buffy-coat smear.
pulmonary involvement that can be seen in se- Since ehrlichia is most commonly found in the
vere cases. Rocky Mountain spotted fever can south central states of Missouri, Oklahoma, Ten-
present with elevated aminotransferase levels, nessee, and Arkansas, it is not likely to be the
thrombocytopenia, and infrequently azotemia, but cause of this patient’s illness.
in more than 90% of cases it presents with a rash.
When the rash is not present, this diagnosis is Anaplasmosis
made mainly on clinical and epidemiologic Anaplasma phagocytophilum, a gram-negative coc-
grounds. The incidence of Rocky Mountain spot- cobacillus, is the cause of human granulocyto-
ted fever in either Massachusetts or Florida, tropic anaplasmosis, formerly known as human
where this patient has spent most of his life, is granulocytic ehrlichiosis. Human infection with
less than 1 per 1 million persons per year. Fur- anaplasma was first described in the 1990s.12
thermore, the elderly do not have higher infec- It is transmitted most commonly in May and
tion rates of Rocky Mountain spotted fever than June by the deer tick and other ixodes species
the nonelderly; this diagnosis is thus unlikely.10 and has an incubation period of 1 week or less;
The vector epidemiology and clinical presenta- this patient’s illness occurred in midspring.13
tion in this case are most supportive of a diagno- Older people, such as our patient, have higher
sis of babesiosis, ehrlichiosis, or anaplasmosis. infection rates than younger people and are at
risk for more serious illness. The overall mortal-
Babesiosis ity rate is 10%.
Babesia microti is endemic in the Northeast and Anaplasmosis typically presents acutely with
can be acquired through tick bites and blood fever and malaise, similar to this patient’s pre-
transfusions. Patients with babesiosis commonly sentation. Headache is also common, although
present with fever and weakness and without it was not mentioned in this case. Diarrhea can
lymphadenopathy; thrombocytopenia is com- occur, as it did in this patient, and azotemia is
mon, and azotemia occurs in approximately 20% present in 70% of cases. This patient had several
of patients. Elevated aminotransferase levels laboratory-test abnormalities that were consis-
have been reported, usually in the context of el- tent with anaplasmosis, including thrombocyto-
evated alkaline phosphatase and bilirubin levels. penia and elevated aminotransferase and lactate
The most important hallmark of infection with dehydrogenase levels. Interestingly, one of the
this intraerythrocytic parasite is hemolysis. How- most common abnormalities, leukopenia (either
ever, this patient shows no convincing evidence neutropenia or lymphopenia), was absent in this
of hemolysis, such as jaundice, anemia, an elevat- case. These laboratory abnormalities are not re-
ed bilirubin level or reticulocyte count, or a de- lated to pathogen burden and are thought to
creased haptoglobin level. The absence of hemo- occur as a result of the immune responses of the
lysis effectively rules out babesiosis. host.13 Overlap among the clinical syndromes

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 case records of the massachusetts gener al hospital

caused by human monocytic ehrlichiosis, human

granulocytotropic anaplasmosis, and Rocky Moun- A
tain spotted fever is due to their close genetic
relatedness in the family Anaplasmataceae.14
As with ehrlichiosis, the diagnosis of ana-
plasmosis can be made by the identification of
morulae in leukocytes on a peripheral-blood
smear; however, epidemiologic data and nucleic
acid testing are often needed to confirm the di-
agnosis, since it is often difficult to find moru-
lae on a smear. Although ehrlichia infection can
occur in the Northeast, anaplasma is the more
common pathogen in Massachusetts.15-17
B
Summary
In summary, I believe this patient’s clinical pre-
sentation, laboratory abnormalities, and acute
decompensation in the context of known cardiac
disease and limited cardiac reserve are all consis-
tent with a severe infection with anaplasmosis.
The diagnostic test was most likely a peripheral-
blood smear, with morulae seen in neutrophils.

Cl inic a l Di agnosis

Sepsis, possibly due to intraabdominal infection. Figure 2. Peripheral-Blood Smear.

Dr . Athe M.N. Tsibr is’s Di agnosis
Human granulocytotropic anaplasmosis.
Pathol o gic a l Discussion
The blood smear shows a decreased number of platelets
and two neutrophil band forms, one of which contains
a round bluish-purple inclusion adjacent to the nucleus
(Panel A, arrow). Two other neutrophil band forms
contain intracytoplasmic bluish-purple inclusions that
resemble microcolonies of bacteria within endosomes
(Panel B, arrows).

Dr. Lawrence R. Zukerberg: Review of the peripheral-
blood smear revealed toxic granulation and vacu-
olization of the neutrophils and occasional Döhle’s
bodies in the neutrophils. Some of the neutro-
phils contained intracytoplasmic bluish-purple
inclusions, and some of these resembled micro-
colonies of bacteria within endosomes (Fig. 2A
and 2B). The inclusions suggested infection with
ehrlichia or anaplasma, and their location in neu-
trophils rather than in monocytes suggests ana-
plasma. A. phagocytophilum resides within granu-
locytic endosomes and grows to form morulae
(microcolonies). Transmission is similar to that
of Lyme disease and babesiosis, which all have
the same tick vector, and coinfection with more
than one organism is documented in 1 to 9% of
ticks or patients.13,18 Although most cases occur
in persons who have been bitten or exposed to
ticks, occasional cases have been documented in
deer-meat cutters and through mother-to-infant
transmission or blood transfusion.19,20
A specimen of blood was sent to a reference
laboratory for nucleic acid testing, which was
positive for A. phagocytophilum DNA and negative
for ehrlichia. This confirmed the diagnosis of
anaplasmosis.
Dr. Eric S. Rosenberg, M.D. (Pathology and Medi-
cine): Dr. Ketwaroo, would you tell us what hap-
pened to this patient?
Dr. Ketwaroo: Once the diagnosis of anaplas-
mosis was made, the administration of doxycy-
cline was begun. Since the patient was critically
ill, empirical antimicrobial therapy with vanco-
mycin and cefepime was continued until he was
clinically stable. He was treated with doxycycline
for approximately 10 days, which we thought

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 The n e w e ng l a n d j o u r na l of m e dic i n e

was an adequate duration of therapy for anaplas-
mosis. He spent several days in the coronary
care unit, and we had a difficult time weaning
him from the ventilator. He eventually required
a tracheostomy, and approximately 1 month af-
ter admission, he was discharged from the hos-
pital with a tracheostomy mask to administer
oxygen through the tracheostomy. He was read-
mitted to the hospital several times for dyspnea
and once for atrial fibrillation with rapid ven-
tricular response. Five months after his initial
presentation, he died at a rehabilitation facility.
No postmortem examination was performed.
Dr. Rosenberg: Is there anaplasma in Florida, and
if so, could he have acquired this infection while
in Florida?
Dr. Tsibris: Ehrlichia and anaplasma are pres-
ent and reported primarily in north and central
Florida and the Florida panhandle. This patient’s
infection was certainly acquired in Massachu-
setts, however. Anaplasma typically is manifest-
ed in the elderly within 7 days after infection,
which is more rapid than for other rickettsia-like
illnesses, which can manifest symptoms any-
where from 1 to 3 weeks after infection.
Dr. Nancy Lee Harris (Pathology): In retrospect,
did the patient remember any tick exposure?
Dr. Ketwaroo: His wife gardens and said that
she had found several ticks on herself, but ap-
parently her husband had not mentioned that he
had found ticks on himself. At the time of ad-
mission, the patient was somewhat confused, and
we were not able to obtain additional history
from him.
A Physician: Do anaplasma organisms have any
resistance to doxycycline? If you had suspected a
tickborne illness, would you have just treated him
with doxycycline?
Dr. Tsibris: Doxycycline resistance has not been
described in anaplasma infections. Empirical
doxycycline therapy will treat tickborne illnesses
such as Lyme disease, ehrlichia, or anaplasma
but would be a poor choice for treatment of ba-
besiosis or tularemia. Therefore, it is important
to make a specific diagnosis.
PATHOL O GIC A L DI AGNOSIS
Anaplasma phagocytophilum infection (human gran-
ulocytotropic anaplasmosis).
This case was presented at the Medicine Case Conference.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Drs. Gail E. Semigran and Bruce D. Walker for
helping with the preparation of the case history.

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