Transcript MEDICAL GRANDROUNDS

MEDICAL
GRANDROUNDS
IVY KATHRYN ILAGAN, MD
August 21, 2008
OBJECTIVES

To discuss an unusual presentation of
infectious mononucleosis.
GENERAL DATA




RC
35 year old male
Married
Filipino
CHIEF COMPLAINT

FEVER
HISTORY OF PRESENT
ILLNESS
 Apparently well
 8 days PTA
 intermittent fever (maximum temperature
40.30C)
 chills
 Headache
 Nonproductive cough
 6 days PTA
 Consult done
 CBC  normal
 systemic viral illness  sent home
 5 days PTA
 still has intermittent fever
 epigastric pain
 Vomiting
 Loose watery stool, 4x
 4 days PTA
 Admitted in a private hospital
 Work-ups done:
• CBC  leukocytosis, predominance of
lymphocytes
• CXR  bibasal pneumonia with
minimal pleural effusion, left
• abdominal ultrasound




minimal ascites
normal liver size with diffuse pattern
splenomegaly
cholecystitis
• Malarial smear  negative
• Chlamydia  negative
• Blood and urine CS  no growth
 Treated as pneumonia and acute
gastroenteritis
 Fever, epigastric pain, vomiting, and
diarrhea persisted, hence transferred
in this institution
REVIEW OF SYSTEMS
General
(-) weight loss
Head and neck
(-) blurring
(-) visual changes
(-) sorethroat


Chest and Lungs
(-) dyspnea
Cardiovascular
(-)
(-)
(-)
(-)
chest pain
palpitations
easy fatigability
orthopnea

Gastrointestinal
(-) hematemesis
(-) hematochezia
(-) melena

Genitourinary
(-) dysuria
(-) hematuria

Hematologic
(-) easy bruisability

Neurologic
(-) changes in behavior
PAST MEDICALL HISTORY






Non-hypertensive
Non-diabetic
Non-asthmatic
No history of pulmonary tuberculosis
No known allergies
No history of trauma
FAMILY HISTORY




Hypertension - paternal side
Diabetes mellitus – maternal side
Asthma - maternal side
No history of blood dyscrasia
PERSONAL AND SOCIAL



Unemployed
15-pack year history of smoking
Occasional alcoholic beverage drinker
PHYSICAL EXAMINATION
 GENERAL SURVEY
 Awake, conscious, coherent, not in respiratory
distress.
 VITAL SIGNS
 BP 130/80mmHg
 HR 90bpm
 RR 20cpm
 T 39.2C
 SKIN/HEAD/EYES/EARS/NOSE/NECK/THROAT
 Good skin turgor
 Pink palpebral conjunctiva, icteric sclerae
 no tonsillopharyngeal congestion
 no cervical lymphadenopathy
 CHEST AND LUNGS
 Symmetrical chest expansion, no retractions
 Crepitant rales, bibasal area
 Decreased breath sounds, right lung base
 No wheezes
 CVS
– Normal rate, regular rhythm, S1>S2 apex,
S2>S1 base, no murmurs, no S3, no S4
 ABDOMEN
– Flabby
– Normoactive bowel sounds
– Soft
– direct tenderness, epigastric area
– palpable liver, up to 4 cm from subcostal
line
– dullness on 9th – 11th ICS (obliterated
traube’s space)
 EXTREMITIES
– No gross lesions
– No hematoma, petechiae, purpura
– No cyanosis
– No edema
– Full and equal peripheral pulses
SALIENT FEATURES

35 year old male

Previously treated in another hospital as pneumonia and acute
gastroenteritis

Abdominal ultrasound done revealed ascitis, cholecystitis, and
splenomegaly

On PE,
– Febrile
– Icteric
– crepitant rales, bibasal area; decreased breath sounds, right lung
base
– palpable liver, up to 4 cm from subcostal line, dullness on 9th-11th
ICS
INITIAL IMPRESSION



Community acquired pneumonia
Hepatosplenomegaly, etiology to be
determined
Cholecystitis
COURSE IN THE WARDS

ABG at room air, RR24
pO2
81.1
pH
7.5
pCO2
31.6
HCO3
24.8
O2 sat
97%
BE
+2.6
TCO2
25.8
- respiratory alkalosis

CXR
– pneumonia, both lower lobes
– minimal pleural effusion
– mild left ventricular enlargement
Pneumonia
5-Jun
Alkaline
Phosphatase
543
TB
1.7
DB – IB
1.3 – 0.4
Na
0.8
Lipase
224
Amylase
28

CT scan of the whole abdomen
– Hepatosplenomegaly
– Consider splenic infarctions
– Minimal ascites
– Prominent retroperitoneal lymph nodes,
which may be reactive in nature
– Minimal bilateral pleural effusion with
compressive atelectasis in both lower
lobes

CT scan of the whole
abdomen
– Hepatosplenomegaly
– Consider splenic
infarctions

Lipase
224
Amylase
28
Alpha fetoprotein
negative
Pneumonia
Hepatosplenomegaly
Acute Cholecystitis
Pneumonia
Hepatosplenomegaly
Pneumonia
Hepatosplenomegaly
Splenic Infarct
Pneumonia
Hepatosplenomegaly
Splenic Infarct
Hematologic
Infectious
Autoimmune
Malignancy
Pneumonia
Hepatosplenomegaly
Splenic Infarct
Hematologic
Hepatosplenomegaly
Splenic Infarct
Infectious
Autoimmune
Hematologic
Hepatosplenomegaly
Splenic Infarct
Infectious
Autoimmune
Infective Endocarditis
Atrial Fibrillation
Hematologic
Leukemia
Polycythemia Vera
Hepatosplenomegaly
Protein C&S Deficiency
Infectious
Salmonellosis
Infectious Mononucleosis
Splenic Infarct
Autoimmune
SLE
Infective Endocarditis
Atrial Fibrillation
Hematologic
Leukemia
Polycythemia Vera
Hepatosplenomegaly
Protein C&S Deficiency
Infectious
Salmonellosis
Infectious Mononucleosis
Splenic Infarct
Autoimmune
SLE
Infective Endocarditis
Day 2
6-Jun
Hgb
Hct
WBC
Seg
11.7
36.9
8.96
26
Lympho
56
Mono
Platelet ct
17
173T
MCV
MCH
83.9
26.6
Alkaline
phosphatase
TB
DB – IB
Na
Day 1
Day 2
5-Jun
543
6-Jun
439
1.7
1.3 – 0.4
0.8
1.2
K
BUN
Creatinine
CO2
Lipase
Amylase
141
3.3
6
0.8
29
224
28
Day 1
Day 2
5-Jun
6-Jun
SGOT
115
SGPT
129
Albumin
2.4
Corrected
Ca
9.26
Glucose
89.91
Cholesterol
119.09
Day 1
Day 2
5-Jun
543
6-Jun
439
Alkaline
phosphatase
TB
1.7
DB – IB
1.2
1.3 – 0.4
SGOT
115
SGPT
129
Hepatocellular/ Cholestatic
Viral Hepatitis
Infectious Mononucleosis
Pneumonia
Hepatosplenomegaly
Splenic Infarct
Hepatocellular/ Cholestatic
Viral Hepatitis
Infectious Mononucleosis
Alkaline
phosphatase

Day 1
Day 2
5-Jun
543
6-Jun
439
Heat fractionation of alkaline
phosphatase 45%
Heated alkaline phosphatase at 560C: 216 U/L
<25% osteoblastic
>25% hepatic
Hgb
Hct
Day 2
Day 4
6-Jun
11.7
36.9
8-Jun
11.7
36.3
Hematologic
Leukemia
Polycythemia Vera
Hepatosplenomegaly
Protein C&S Deficiency
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Autoimmune
SLE
Hepatocellular/ Cholestatic
Viral Hepatitis
Infectious Mononucleosis


Protein C normal 4.15
Protein S normal 17
Hematologic
Leukemia
Hepatosplenomegaly
Protein C&S Deficiency
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Autoimmune
SLE
Hepatocellular/ Cholestatic
Viral Hepatitis
Infectious Mononucleosis


p-ANCA negative
Cryoglobulin negative
Hematologic
Leukemia
Hepatosplenomegaly
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Autoimmune
SLE
Hepatocellular/ Cholestatic
Viral Hepatitis
Infectious Mononucleosis


HbsAg negatve
Anti HCV non reactive
Hematologic
Leukemia
Hepatosplenomegaly
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Hepatocellular/ Cholestatic
Infectious Mononucleosis

Peripheral blood smear
– WBCs with atypical forms, platelets appear
increased and in clumps with some giant
platelets noted.


Bone marrrow culture – no growth
Bone marrow biopsy - normal
Hematologic
Pneumonia
Leukemia
Hepatosplenomegaly
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Hepatocellular/ Cholestatic
Infectious Mononucleosis
Hepatosplenomegaly
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Hepatocellular/ Cholestatic
Infectious Mononucleosis
Hepatosplenomegaly
Hematologic
Infectious
Autoimmune
Splenic Infarct
Infective Endocarditis


Blood culture
- Streptococcus viridans
C reactive protein - positive up to 1:8
serum dilutions
2D Echocardiography with color flow
and Doppler study
- Normal, EF 70%. Mitral and tricuspid
regurgitation are trivial.


Transesophageal echocardiography
– No echocardiographic evidence of
endocardial vegetations on the aortic,
pulmonic, mitral and tricuspid valves.
– Intact interatrial septum.
– No intracardiac thrombus formation.

The diagnosis of infective endocarditis
is established with certainty only when
vegetations obtained at cardiac
surgery, at autopsy, or from an artery
(an embolus) are examined
histologically and microbiologically.


The Duke criteria—has been
developed on the basis of clinical,
laboratory, and echocardiographic
findings.
Documentation of two major criteria,
of one major and three minor criteria,
or of five minor criteria allows a clinical
diagnosis of definite endocarditis.
The Duke criteria

Major Criteria
1. Positive blood culture
Viridans streptococci Streptococcus
,
bovis, HACEK group, Staphylococcus aureus,
community-acquired enterococci in the absence of a
primary focus
2. Evidence of endocardial involvement
- Positive echocardiogram
- New valvular regurgitation

Minor Criteria
1. Predisposition: predisposing heart
condition or injection drug use
2. Fever 38.0°C
3. Vascular phenomena: major arterial
emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage,
conjunctival hemorrhages, Janeway lesions


4. Immunologic phenomena:
glomerulonephritis, Osler's nodes, Roth's
spots, rheumatoid factor
5. Microbiologic evidence: positive blood
culture but not meeting major criterion as
noted previously or serologic evidence of
active infection with organism consistent
with infective endocarditis.
Hepatosplenomegaly
Infectious
Splenic Infarct
Salmonellosis
Infectious Mononucleosis
Hepatocellular/ Cholestatic
Infectious Mononucleosis
Hepatosplenomegaly
Infectious
Splenic Infarct
Infectious Mononucleosis
Hepatocellular/ Cholestatic
Infectious Mononucleosis
Hepatosplenomegaly
Splenic Infarct
Hepatocellular/ Cholestatic
Infectious
Infectious Mononucleosis

Monospot test - positive

Started on
– piperacillin-tazobactam 4.5g IV q8
– metronidazole 500 mg IV q8
– vancomycin 1g IV q12
5th HOSPITAL DAY


Blood CS
- Streptococcus viridans
Sensitive to penicillin and ampicillin
Resistant vancomycin
Vancomycin and metronidazole was
then discontinued.
Temperature (Celcius)
39.5
39
38.5
38
37.5
piperacillin-tazobactam 4.5g IV q8
37
Day 1
Day 2
Day 3
Hospital Day
Day 4
Day 5

Repeat CXR
– partial resolution of the bibasal pleural
effusion
– subsegemntal atelectasis are now seen at
right paracardiac and left basal regions
6th HOSPITAL DAY



Tazocin was discontinued
Penicillin G 3M units IV every 4 hours
Gentamicin 70 mg IV every 8 hours.
39.5
Temperature (Celcius)
39
38.5
38
37.5
37
piperacillin-tazobactam 4.5g IV q8
Day 1
Day 2
Day 3
Day 4
Hospital Day
Day 5
Day 6
39.5
Temperature (Celcius)
39
38.5
38
Pen G 3M U IV q4
Gentamycin 70mg
IV q8
37.5
37
Day 1
Day 2
Day 3
Day 4
Hospital Day
Day 5
Day 6
8th HOSPITAL DAY


Day-1 afebrile
No note of recurrence of fever on the
subsequent days.
39.5
39
38.5
38
37.5
37
36.5
36
D2- Pen G
35.5
D2- Genta
35
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Hospital Day
Day 9
Day 10
Day 11
Day 12
Day 13
Day 2
Day 4
Day 6
Day 7
Day 8
6-Jun
8-Jun
10-Jun
11-Jun
12-Jun
Hgb
11.7
11.7
12.2
12.7
12.5
Hct
36.9
36.3
38
40.2
39.5
WBC
8.96
7.05
8.07
9.01
8.79
Seg
26
40
38
41
49
Lympho
56
46
50
49
44
Mono
17
13
11
8
7
Platelet ct 173T
270T
257T
532T
500T
MCV
83.9
82.9
83.2
84.1
84.9
MCH
26.6
26.7
26.7
26.6
26.9
Day 1
Day 2
Day 4
Day 8
5-Jun
6-Jun
8-Jun
12-Jun
Alkaline
543
phosphatase
439
480
TB
1.7
1.2
1
DB – IB
1.3 – 0.4
Na
0.8
0.5 – 0.5
141
138
135
K
3.3
3.9
3.5
BUN
6
13.01
Creatinine
0.8
1.5
Day 1
Day 2
Day 4
Day 8
Day 12
5-Jun
6-Jun
8-Jun
12-Jun
16-Jun
Alkaline
543
phosphatase
439
480
251
TB
1.7
1.2
1
0.7
DB – IB
1.3 – 0.4
0.5 – 0.5
0.2 – 0.5
Na
0.8
141
138
135
136
K
3.3
3.9
3.5
4.1
BUN
6
13.01
16.99
Creatinine
0.8
1.5
1.5
CO2
29
Lipase
224
Amylase
28
SGOT
115
38
SGPT
129
71
FINAL DIAGNOSIS
Infectious mononucloesis
Streptococcus viridans bacteremia
INFECTIOUS
MONONUCLEOSIS



Pfeiffer's disease
Mono – Kissing disease
Glandular fever

Epstein-Barr virus
– The cause of heterophile-positive
infectious mononucleosis (IM)
– Also associated with several human
tumors, including nasopharyngeal
carcinoma, Burkitt's lymphoma, Hodgkin's
disease, and (in patients with
immunodeficiencies) B cell lymphoma.
- Family Herpesviridae
- Consists of a linear DNA core
- Two types of EBV that are widely
prevalent in nature are not
distinguishable by conventional serologic
tests.
Epidemiology





Occurs worldwide.
Most common in early childhood, with a
second peak during late adolescence.
By adulthood, more than 90% of individuals
have been infected and have antibodies to
the virus.
Spread by contact with oral secretions
More than 90% of asymptomatic
seropositive individuals shed the virus in
oropharyngeal secretions.
Manifestations
Symptoms
 Sore throat
 Malaise
 Headache
 Abdominal pain, nausea, or


Chills
Diarrhea
75 %
47
38
vomiting
17
10
Signs

Lymphadenopathy

Fever

Pharyngitis or tonsillitis

Splenomegaly

Hepatomegaly

Rash

Periorbital edema

Palatal enanthem

Jaundice
95%
93
82
51
11
10
13
7
5
SPLENIC INFARCTION





Splenic infarction during IM is very rare;
To our knowledge, only five cases have previously been reported
The pathogenesis of splenic infarction during IM remains unclear.
In one case report of IM associated with splenic infarction, transient elevation
of antiphospholipid antibodies was found and thought to be responsible for
the splenic infarct.
Acute EBV infection should be considered in the differential diagnosis of
splenic infarction. This diagnosis should also be considered in patients
presenting with unexplained acute abdominal pain.
-Scottish Medical Journal, 2007
Splenic infarction due to infectious mononucleosis
K Ashawesh, R Abdulqawi, BN Chandrappa, K.S. Srinivasan
Department of medicine, Princess Royal Hospital, Telford, UK



Splenic infarction is a rare feature of infectious
mononucleosis
Splenic infarction during acute EBV infection
associated with the transient induction of
antiphospholipid antibodies.
Once other more common causes of splenic
infarction, such as endocarditis and lymphoma,
have been excluded, the possibility of viral-induced
antiphospholipid antibodies should be considered.
-
Journal of clincal virology, 2006
Splenic infarction due to transient antiphospholipid
antibodies induced by acute Epstein-Barr virus infection



18 year old Japanese man, with hereditary spherocytosis (HS)
known to have developed splenic infarction following
infectious mononucleosis (IM).
On day 4 of admission, the patient complained of severe
abdominal pain. Abdominal CT scan revealed findings of
splenic infarction. Two months after the occurrence of splenic
infarction, a splenectomy was performed.
A pathohistologic examination of the resected spleen revealed
no evidence of thrombosis or arterial occlusion. We assume
that the cause of splenic infarction was insufficient blood flow
to oxygenate the entire spleen during the acute enlargement
of the spleen.
- Splenic infarction after Epstein-Barr virus infection in a patient with
hereditary spherocytosis
Suzuki Y, Shichishima T, Mukae M, Ohsaka M, Hayama M, Horie R,
Togano T, Miyazaki K, Ichinoe M, Iwabuchi K, Fujii H, Higashihara
M.
Department of Hematology, Kitasato University School of Medicine,
Sagamihara, Japan
LABORATORY FINDINGS



WBC usually elevated and peaks at
10,000–20,000/L during the second or
third week of illness.
Lymphocytosis with >10% atypical
lymphocytes.
Low-grade neutropenia and
thrombocytopenia are common during
the first month of illness.



Liver function is abnormal in >90% of
cases.
Aminotransferases and alkaline
phosphatase are usually mildly
elevated.
Bilirubin is elevated in ~40% of cases.
Monospot test



Positive for infectious mononucleosis
Specific for heterophile antibodies, not
EBV.
~75% sensitive and ~90% specific
compared with EBV-specific serologies.

Can also be positive in patients with
lumphoma, systemic lupus
erythematosus, viral hepatitis, malaria,
and some GI cancers
SPECIFIC TEST FOR EBV


Epstein-Barr Virus (EBV) viral capsid
antigen IgG and IgM and, EBV nuclear
antigen IgG by immunofluorescence
Epstein-Barr virus antibody titers to
help distinguish acute infection from
past infection with EBV
TREATMENT

Self-limiting

Symptomatic and/or supportive treatments

Rest is recommended during the acute
phase of the infection, but activity should be
resumed once acute symptoms have
resolved.

Nevertheless heavy physical activity and
contact sports should be avoided to
abrogate the risk of splenic rupture, for at
least one month following initial infection
and until splenomegaly has resolved, as
determined by ultrasound.
MORBIDITY AND
MORTALITY


Fatalities from mononucleosis are near
impossible in developed nations.
CNS:
– Meningitis, encephalitis, hemiplegiaand
transverse myelitis.
– Proposed as a risk factor for the
development of multiple sclerosis, but this
has not been affirmed.

Hematologic:
– Autoimmune hemolytic anemia (direct
Coombs test is positive) and various
cytopenias.
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