OUTLINE:

Case Presentation
Perspectives
Primary Attending Physician’s Introduction
Infectious Disease Specialist’s Perspective
Hematologist’s Perspective
Oncologist’s Perspective
Rheumatologist’s Perspective
Cardiologist’s Perspective
Dermatologist’s Perspective
Neurologist’s Perspective
Pulmonologist’s Perspective
Final Diagnosis
Fever of Unknown Origin – Lecture Proper
Summary Table for the Four Classifications of Fever
Appendix

CASE PRESENTATION
Patient Profile
Male
Middle-aged
From Antipolo, Rizal
Married
Anxious and Sad
Clinical History
Feeling achy and tired
Unusual fever pattern
Elevated pinkish colored rash
Disappeared after some time
Cough with mild shortness of breath
Headache
Physical Examination
Painful joints
Red but not swollen
Several swollen tender neck lymph nodes
Stiff and sore, especially when feverish
Labs
Elevated white blood cell count
Mildly abnormal liver enzymes
PERSPECTIVES
Primary Attending Physician’s Introduction
SHAPE \* MERGEFORMAT
Main Causes of FUO
Undiagnosed
Infectious (TB)
Non-infectious inflammatory diseases
Neoplasms
Inflammatory Causes
Miscellaneous
Drug-related, Pulmonary Fever, Factitious Fever, Hereditary Periodic Fever Syndromes, and Fabry
Disease

Fever without a Source

Fever of 1 week or less
Careful History and PE yields no possible source
3 main considerations:
Infectious
Rheumatologic
Malignant

Infectious Disease Specialist’s Perspective

 Salient Features

Salient feature Rationale Other questions to ask

Identifying data
51 y.o previously healthy male, married Predisposition for diseases (infectious
from Antipolo, Rizal and non-infectious)in certain age
groups, sex, country/region
History of present illness
Fever of 1 week duration which is Fever with an unusual pattern such as Were there any medications taken for
more prominent in the afternoon that occurring in the afternoon with the fever?
resolution by morning is usually Others in the household or neighborhood
associated with pulmonary tuberculosis with the same symptoms?
among other diseases.
Body  malaise Usually  associated  with  fever Ac6vi6es  of  daily  living  impaired?
Chills Not  all  fever  present  with  chills;  may  
help  in  the  differen6al  diagnosis.
May  be  present  in  urinary  tract  infec6on  
and  pulmonary  tuberculosis.
Night  sweats There  are  few  diseases  which  presents  
with  night  sweats,  such  as  pulmonary  
tuberculosis.
Night  sweats There  are  few  diseases  which  presents  
with  night  sweats,  such  as  pulmonary  
tuberculosis.
Unresponsive  to  an6bio6cs History  of  previous  an6bio6c  therapy   What  an6bio6cs?  For  what?  Dosing  or  
will  affect  the  management.    Either  the   frequency?  Compliance?  Side  effects?
previously  used  an6bio6c  will  no  longer  
be  used  or  there  is  shiFing  to  an  
an6bio6c  with  wider  microbial  coverage.
Patches  of  rash May  also  be  associated  with  the  fever;   Is  the  resolu6on  of  the  symptom  
reac6on  to  the  increase  in  body  heat together  with  fever  lysis?  Pruri6c?
Cough Cough  would  point  to  a  possible  focus  of   Was  the  cough  produc6ve?  What  color?  
infec6on  or  possible  affected  organ   Dura6on?  Medica6ons  taken?
system
Headache Usually  associated  with  fever
Myalgia May  be  associated  with  the  fever  or   Generalized?  Localized?  Timing?  
may  point  to  a  different  disease  en6ty   Relieved  by?
such  as  influenza
Past  Medical  History
Elevated  blood  pressure  and  cholesterol   May  affect  management  op6ons   What  are  the  medica6ons  being  taken  
with  regular  intake  of  medica6ons especially  if  there  are  possible  drug  drug   for  these  condi6ons?  What  was  the  
interac6ons  between  proposed   highest  and  usual  BP?  Associa6ng  
treatment  and  current  medica6ons symptoms?
Physical  E xamina5on
Tachycardia Usually  associated  with  fever  wherein  
an  increase  in  1  degree  Celsius  will  
increase  the  usual  heart  rate  of  the  
pa6ent  to  10  more  beats  per  minute.

Definition of FUO
Petersdorf and Beeson (1961)
temperatures of 38.3°C (101°F) on several occasions;
a duration of fever of >3 weeks; and
failure to reach a diagnosis despite 1 week of inpatient investigation.

Durack and Street (new system for FUO classification)

classic FUO;
nosocomial FUO;
neutropenic FUO; and
FUO associated with HIV infection

Diagnostic Algorithm
Comprehensive history
confirm a history of fever and document the fever pattern
Thorough physical examination
Appropriate laboratory testing
Rule out drug fever
 Suspected drug is not the cause if fever persists beyond 72 hours after its removal
After ruling out drug fever, do preliminary laboratory evaluation
complete blood count/diff count
electrolytes
liver function test
erythrocyte sedimentation rate
urinalysis
PPD skin test
Chest X-ray
basic cultures: blood, urine

Differentials
Differen5al Reasons  for  R uling  in Reasons  for  R uling  out
Tuberculosis Cough Lymphadenopathy:  of  TB  is  usually  
Fever painless
Night  Sweats
Tachycardia
Malaria Flu  like  symptoms  of  fever,  headache,   Some  pa6ents  may  present  with  
malaise,  fa6gue,  muscle  aches.   diarrhea  and  GI  symptoms.
Paroxysmal  cycle:  chills  1-­‐2  hrs  followed   No  history  of  exposure
by  high  fever  3-­‐4  hrs  and  then  2-­‐4  hrs  of  
profuse  diaphoresis
Typhoid  Fever Fever  pa\ern  is  stepwise,  characterized   Most  documented  typhoid  fever  cases  
by  a  rising  temperature  over  the  course   involved  school-­‐aged  children  and  young  
of  each  day  that  drops  by  the   adults
subsequent  morning;  peaks  and  troughs  
rise  progressively  over  6me
Cough,  dull  frontal  headache,  malaise
Influenza Fever  may  vary  widely  among  pa6ents:   No  ocular  symptoms:  photophobia,  
low  (100°F)  to  high  (104°F).  Some   burning  sensa6ons,  and/or  pain  upon  
pa6ents  report  feeling  feverish  and  a   mo6on
feeling  of  chills
Myalgias  are  common  and  range  from  
mild  to  severe
Frontal/retro-­‐orbital  headache  is  
common  and  is  usually  severe
Weakness  and  severe  fa6gue  may  
prevent  pa6ents  from  performing  their  
normal  ac6vi6es  or  work
Cough  and  other  respiratory  symptoms  
may  be  ini6ally  minimal  but  frequently  
progress  as  the  infec6on  evolves;  may  
report  nonproduc6ve  cough,  cough-­‐
related  pleuri6c  chest  pain,  and  dyspnea
Tachycardia  most  likely  results  from  
hypoxia,  fever,  or  both.
Diagnostics
Differen5al Diagnostic Examinations to be Requested
Tuberculosis CXR
miliary reticulonodular pattern, large infiltrates with pleural
effusion, or interstitial infiltrates with pleural effusion
no  radio  abnormality  early  in  the  course  and  among  HIV  
pa6ents
PPD  skin  test  
wheal  and  flare  (will  not  indicate  whether  ac6ve  infec6on,  
inac6ve  infec6on,  or  just  exposure)  
may  be  nega6ve  in  up  to  half  of  cases
CBC/Diff  count  
anemia  (ACD)  with  leukopenia,  neutrophilic  leukocytosis,  
leukemoid  reac6on  and  polycythemia
LFT  
elevated  ALP,  ALT  and  AST  
could  also  be  secondary  to  long-­‐standing  cholesterol  
problem  if  with  hepa6c  involvement
Sputum  AFB/culture  
demonstra6on  of  acid-­‐fast  mycobacterium
Bronchoscopy/alveolar  lavage  
higher  yield  for  culture
CSF  analysis
Cultures:  blood,  urine,  CSF
Malaria Thick  smear
 demonstra6on  of  plasmodia  but  specia6on  is  not  possible  
done  during  or  soon  aFer  fever  spikes
Thin  smear  
less  sensi6ve  than  thick  smear  but  specia6on  can  be  done  
Typhoid  Fever Clinical  diagnosis
Serologic:  Indirect  hemagglu6na6on/indirect  fluorescent  Vi  
an6body/typhidot  (ELISA)
Culture:  (blood/urine/stool)  
isola6on  of  organism;  mul6ple  cultures
Influenza Clinical  diagnosis
CBC  
leukopenia  with/without  lymphocytosis
CXR  
should  be  clear  to  exclude  pneumonia
Culture  is  an  op6on  (nasopharyngeal/throat  swab)

Primary Diagnosis: Disseminated Tuberculosis

The Philippines ranks ninth on the list of 22 high-burden tuberculosis (TB) countries in the world,
according to WHO’s Global TB Report 2009
In 2007, approximately 100 Filipinos died each day from the disease.
In 2004, the country achieved a TB case detection rate of 72 percent, exceeding WHO’s target of 70
percent, and reached 75 percent in 2007. The DOTS (the internationally recommended strategy for TB
control) treatment success rate has remained around 88 percent since 1999
However, while the national performance levels are already high, many provinces are still below target
levels due to various systemic and social factors, including:
Problem in seeking care due to the stigma of TB
The expanding multidrug-resistant (MDR) TB. WHO has reported extensively drugresistant TB in the
Philippines. The availability of over-the-counter TB drugs and selfmedication by patients continue
to contribute to the emergence of TB drug resistance.
Disseminated TB is life-threatening if not treated promptly and especially for the elderly, infants,and
 people with a compromised immune system.

Treatment Options
Hospital admission
close observation
follow-up every potential lead
As a general rule, antibiotics should not be given empirically as a diagnostic measure.
Treatment should be directed against the underlying pathology.
While waiting for the results of laboratory tests, symptoms may be addressed.
Supportive Treatment
Pharmacologic:
Acetaminophen, Aspirin, or NSAIDs
Non-pharmacologic
Ensure adequate hydration
Proper nutrition
Sponge bath
Hydrotherapy
Use of wet socks
Treatment for disseminated TB
Treatment Goal: eradicate the infection with drugs that target TB.
Main Pharmacologic Treatment: (4 drugs)
Isoniazid
Rifampicin,
Pyrazinamide
Ethambutol
Other drugs: Amikacin, Ethionamide, Moxifloxacin, Para-aminosalicylic acid and streptomycin.
Refer to TB-DOTS

Prognosis
Most disseminated forms of TB respond well to treatment.
Complications of disseminated TV can include:
Adult respiratory distress syndrome (ARDS)
Lung failure
Relapse of the disease
Medicines used to treat TB may cause side effects, including liver problems.
Other side effects include:
Changes in vision
Orange- or brown-colored tears and urine
Rash

Public Health and Psychosociocultural Issues

For the patient, tuberculosis and malaria are differentials.
These two disease entities are endemic in the Philippines and may remain undiagnosed for a long
time.
For TB, the DOTS has gained significant improvements in treating TB patients
Research-oriented countries are focusing on chronic diseases and their complications (e.g. CVD, CA,
DM). Furthermore, HIV is now taking the limelight.
This causes diseases like TB and Malaria to be relegated to the background although they are still
taking many lives each year.

Hematologist’s Perspective
Working Diagnosis: Malaria
Pathophysiology (from Best Practice):
During a blood meal, an infected female Anopheles mosquito injects thousands of malarial
sporozoites, which rapidly enter hepatocytes. Reproduction by asexual fission (tissue schizogony)
takes place to form a pre-erythrocytic schizont. This part of the life-cycle produces no symptoms.
After a period of time, thousands of merozoites are released into the blood stream to penetrate
erythrocytes after attaching via receptors. The time period before merozoites enter the blood is
designated the pre-patent period; this is between 7 and 30 days for P falciparum, but may be much
 longer for P vivax or P ovale because of the possible development of an inactive hypnozoite stage in
the liver. HYPERLINK "http://bestpractice.bmj.com/best-practice/monograph/161/resources/
references.html" \l "ref-16" Most merozoites undergo blood schizogony to form trophozoites,
evolving to schizonts, which rupture to release new merozoites. These then invade new erythrocytes
and the 48-hour cycle continues, sometimes resulting in periodicity of fever. The rupture of
erythrocytes releases toxins that induce the release of cytokines from macrophages, resulting in the
symptoms of malaria. HYPERLINK "http://bestpractice.bmj.com/best-practice/monograph/161/
resources/references.html" \l "ref-17" Some merozoites mature into larger forms called gametocytes,
which reproduce sexually if they are ingested by a mosquito.

Differentials
Disease Characteris5cs Notes
Influenza influenza  virus,  worldwide  distribu6on,   Influenza  can  be  diagnosed  serologically  
fever,  headache,  dry  cough,  runny  nose,   or  by  isola6ng  the  virus
sore  throat,  myalgia,  malaise
Dengue  Fever Fever,  headache,  nausea,  malaise,   Dengue  can  be  diagnosed  serologically
anorexia,  sore  throat,  severe  myalgias.  
Rash  (centrifugal),  petechiae,  
lymphadenopathy,  conjunc6val  
injec6on,  pharyngeal  erythema,  
rela6ve  bradycardia

Typhoid  fever fever  (stepladder  temperature) Per6nent  Nega6ves:

Headache abdominal  tenderness
Chills diarrhea  (possible  bloody)
abdominal  and  chest  rash  (rose  spots) splenomegaly,  hepatomegaly
joint  pains Bradycardia
proteinuria  (rule  out  in  labs)
TB Fever,  headache,  nausea,  malaise,   Incidence  is  high  in  the  country
anorexia,  sore  throat,  severe  myalgias.  

Diagnostics
Diagnos5cs Expected   Results Clinical  D ecisions
Thick  Blood  Smear Should  demonstrate  parasites   Parasitemia  can  be  calculated  based  
(Quan6ta6ve  test) inside  RBC’s on  the  number  of  infected  RBCs
Thin  Blood  Smear Should  demonstrate  parasites   Treatment  greatly  depends  on  the  
(Qualita6ve  test) inside  RBC’s iden6fica6on  of  the  Plasmodium  
species  responsible  for  the  
infec6on.
LDH  Test   Elevated  LDH  levels  (part  of  triad  of   Indica6ve  of  haemoly6c  anemia  due  
malaria:  thrombocytopenia,  elevated   to  RBC  damage  
LDH  and  atypical  lymphocytes)
CBC  and  WBC  Differen6al,   Normochromic,  normocy6c  anemia Indica6ve  of  platelet  dysfunc6on  
Peripheral  blood  smear Thrombocytopenia  and  Atypical  
lymphocytes
slight  monocytosis,  lymphopenia  
and  eosinopenia,  with  reac6ve  
lymphocytosis  and  eosinophilia  in  
the  weeks  aFer  the  acute  infec6on

Additional diagnostic exams to be requested:

Chest X-ray: To see infiltrates
 AFB smear and culture: demonstration of the inciting organism

Treatment
Chloroquine
Mefloquine
Primaquine
Quinine
Pyrimethamine-Sulfadoxine (Fansidar)
Doxycycline
 Oncologist’s Perspective - Differentials
Differential Diagnoses
Cancer of Unknown Primary
Rule In Rule Out
Fever – due to inflammatory cytokines Unusual pattern of fever
Fatigue and arthralgia ◊ hypermetabolic state and Tender lymph nodes
increased cell turnover
Cough with mild shortness of breath ◊ lung
metastasis?
Headache ◊ vomiting? brain metastasis?
Joint pains ◊bone metastasis?
Tender lymph nodes ◊ firm, mobile, size? Metastasis?
Abnormal liver enzymes ◊ hepatotoxic antibiotic?

Liver metastasis?
Probable organ systems involved
Lungs
Head and Neck
Bone
Liver

Hodgkin’s Lymphoma
Rule In Rule Out
Fever Unusual patterned fever
Presence of 2 out of 3 Tender lymph nodes
B symptoms: fever, night sweats (weight loss) (-) weight loss
Rash- histamine release
Cough and shortness of breath ◊ mediastinal mass,
suggestive of lung involvement
lymphadenopathy

SHAPE \* MERGEFORMAT

Diagnostics
Cancer of Unknown Primary
Diagnostic Exam Information Provided
Electrolytes Na  normal
K    slightly  low
Mg  normal
Phosphorus  normal
Calcium    slightly  low
Urinalysis Normal

Chest and Abdominal CT Scan Chest  minimal  para-­‐aor6c  lymph  adenopathy  of  2cm;  
Mostly  concentrated  on  the  parasternal  region
Abdomen    normal
Hemoccult Negative occult blood
Symptom directed endoscopy Did not consent because there were no abdominal symptoms
PET CT Scan Will be done in 3 weeks
Core needle biopsy of the lymph node Evidence of reactive lymphadenitis
Immunohistochemistry studies Tissue was not enough to do immunohistochemistry stains
Pulmonary Function Test Not done
Hepatitis Panel for Hepatocellular CA Positive antibodies for Hep A, B and C
Bone Scan for Bone Metastasis Deferred
MRI of the brain for head and neck CA Not done until seen by a neurologist
Expected  findings
60%  of  CUPs  are  found  to  be  adenocarcinoma  
5%  Squamous  cell  carcinoma
25%  Poorly  differen6ated

Hodgkin’s Lymphoma
Diagnostic Exam Information Provided
Erythrocyte Sedimentation Rate 5  x  elevated
For  Hodgkin’s  Lymphoma,  it  is  expected  to  be  elevated  
which  confers  worse  prognosis
Not  specific
Lactate dehydrogenase 10x  elevated
For  Hodgkin’s  Lymphoma,  it  is  expected  to  be  elevated
CBC Leukocytosis
For  Hodgkin’s  Lymphoma,  cytopenia  is  expected.  
Platelets  can  be  increased  or  decreased.
Alkaline Phosphatase Elevated
Increased  with  liver  or  bone  involvement

Clinical  presenta6on  and  history  and  risk  factors  must  be  assessed  before  asking  for  specific  tests  for  
Cancer
Un6l  the  results  of  the  excisional  biopsy  then  we  can  ask  for  the  tests
Which  cancer  presents  with  dermatologic  manifes6on
Hodgkin’s  Lymphoma  –  hypersensi6vity  of  exaggerated  propor6ons
Therapy
Chemotherapy
Surgery
Radiotherapy
Immunotherapy
Palliative treatment
 Rheumatologist’s Perspective - DIfferentials
Acute Rheumatic Fever
Considered  as  a  clinical  syndrome
Caused  by  a  streptococcal  infec6on
Usually  present  in  pediatric  pa6ents  (5-­‐12)

Rule In Rule Out

Fever Not common for a middle-aged patient in an acute
Arthralgia setting
Rash Rash
Pharyngitis possible / Evidence of Streptoccocal Does not fully satisfy the Jones Criteria for ARF
infection ARF RARELY presents with lymphadenopathy
Pleuritis possible ARF usually occur two to four weeks after group A
beta-hemolytic streptococcal infection of the
pharynx
Does not normally present with elevated white-
blood-cell count and mildly abnormal liver enzymes

Jones Criteria
2 Major + 1 Minor OR
1 Major +2 minor
With evidence of Streptococcal infection
Minor
Prolonged  P-­‐R  Interval
No  prolonga6on
Sinus  tachycardia
Arthralgia  
Fever
Supporting evidence
Laboratory Findings: elevated ESR and CRP
Supporting evidence
Throat culture
(+)  alpha  hemoly6c  strep
ASO titer
200  (twice  elevated)
Treatment
Penicillin
High dose salicylates (4-8 g/ day)
NSAIDS
Steroids
Public Health
Developing countries:
Affect  nearly  20  million  people  
One  of  the  leading  causes  of  cardiovascular  death  during  the  first  5  years  of  life
470,000 new cases of ARF worldwide
Most  in  developing  countries  and  usually  among  indigenous  groups
Mean incidence 19:100,000

Rheumatoid Arthritis
 Rule In Rule Out
Fever Patient may not satisfy the 2010 ACR criteria for RA
Arthralgia

2010 American College of Rheumatology (ACR)

No pathognomonic test is available to help confirm the diagnosis of RA

Diagnosed through:
(1)  Clinical
(2)  Laboratory  findings
Markers  of  inflamma6on
Hematologic  parameters
CBC
Synovial  fluid  analysis
No  consent
Immunologic  parameters
Rheumatoid  Factor    nega6ve
An6nuclear  an6bodies    nega6ve
(3) Imaging
X-­‐ray
MRI
Bone  scan
Ultrasound
Was  not  done
Densitometry
Not  requested
Treatment
Non-­‐pharmacologic
Educa6on
Physiotherapy,  physical  therapy
Orthopedic  measures
Pharmacologic
DMARDS
Glucocor6coids  
NSAIDS
Analgesics
Public Health
Worldwide  prevalence:  1-­‐2%
Increases  with  age
More  common  in  women  over  55  y.o  
Family  history  –  most  important  risk  factor
80-­‐90  DALY  rates  for  100,000  inhabitants  for  the  Philippines
Increased  risk  for  infec6on  ranging  from  5.3  to  14.9%
Persistent  inflamma6on  in  1-­‐2  RA  joints  that  is  out  of  propor6on  with  the  other  joints  should  be  
considered  for  a  superimposed  infec6ous  arthri6s

Juvenile Rheumatoid Arthritis (Still’s disease)

Auto-­‐immune  disease
E6ology  is  not  well  established
Pain  dura6on  must  be  established
Should  be  present  6  weeks  prior  to  onset  of  symptoms

Rule In Rule Out

Spiking quotidian Fevers Hepatic dysfunction seen in chronically ill patients
Overt Arthritis Need to check ESR if highly elevated
Characteristic fleeting rash most apparent with fever Need to check peripheral smear for microcytosis
spikes
Lymphadenopathy
Increased white blood cell count

Clinical Manifestations
Fever
Anemia
High  ESR
Headaches
Age:  over  50  years  old  with  other  manifesta6ons
i.e.  malaise,  fa6gue,  anorexia,  weight  loss,  sweats,  arthralgias,  and  associated  polymyalgia  rheuma6c

Laboratory
Markers  of  inflamma6on  (ESR)
Hematologic  parameters  (CBC)
Liver  func6on  tests
Kidney  func6on  tests  (crea6nine)
Immunologic  parameters  (IgG,  complement  levels)
Biopsy
Neutrophil  count    shiF  to  the  leF
RF  (-­‐)  and  ANA  (-­‐)    rule  in  S6ll’s  disease
Alkaline  phosphatase  is  normal
Immunologic  parameters
IgG  elevated
Complement  level

Treatment
NSAIDs
Steroids  (i.e.  prednisone)
An6-­‐rheuma6c  agents  (i.e.  cyclophosphamide,  methotrexate)
Intravenous  gammaglobulin  (IVIG)
Monoclonal  chimeric  an6-­‐TNFα  (i.e.  infliximab)
IL-­‐1  blockade

Public Health
Very  rare  in  adults
Usually:  20-­‐35  years  of  age
Present  with  high  intermi\ent  fever,  joint  inflamma6on  and  pain,  muscle  pain  with  fevers  and  develops  
persistent  chronic  arthri6s
95%  of  pa6ents  have  faint  salmon  colored  skin  rashes  

Giant Cell Arteritis

Mononuclear  infiltra6on  of  blood  vessels
Inflamma6on    hardening  of  arteri6es
Rule In Rule Out
 Fever Male
Headache Need to demonstrate:
Patient is over 50 yo High ESR
Malaise Normochromic/slightly hypochromic anemia
Fatigue Need to measure:
Sweats Serum creatinine kinase
Polymyalgia Levels of IgG and complement
Hepatic Dysfunction Confirm diagnosis via biopsy of the temporal artery

Treatment
Prednisone  40-­‐60  mg/dL  for  1  month  (with  gradual  tapering)
Aspirin  (low  dose,  100  mg  PO  1x/day)
Public Health
In  the  US
Incidence:0.5-­‐27  cases  per  100,000  people  age  50  and  above
Scandinavian  countries  have  the  highest  incidence
Incidence  rates  are  higher  in  Caucasians  of  European  descent
Less  common  in  Asians
More  common  in  women
Cardiologist’s Perspective
SHAPE \* MERGEFORMAT
Differentials
Infective Endocarditis
An  infec6on  (usually  bacterial)  of  the  endocardial  surface  of  the  heart  which  produces  severe  valvular  
insufficiency  and  may  lead  to  intractable  conges6ve  heart  failure  and  myocardial  abscesses.  
Acute  endocardi6s  is  a  febrile  illness  that  rapidly  damages  structures,  hematogenously  seeds  
extracardiac  sites,  and,  if  leF  untreated,  progresses  to  death  within  weeks.  
Epidemiology
There  is  no  Philippine  data  on  the  prevalence  of  IE.  However,  in  the  US,  there  are  about  10,000  to  15,000  new  
cases  diagnosed.
There  is  a  male  predominance  of  pa6ents  having  IE  with  male-­‐to-­‐female  ra6o  ranging  from  3:2  to  9:1.  
There  is  an  increased  risk  of  having  IE  as  one  ages,  with  25-­‐50%  of  cases  happening  at  the  age  of  60  years  and  
above
Pathogenesis
Bacteremia  (nosocomial  or  spontaneous)  that  delivers  the  organism  to  the  surface  of  the  valve
Adherence  of  the  organism
Eventual  invasion  of  the  valvular  leaflets
Staphylococcus  aureus  and  Enterococcus  faecalis  are  the  predominant  microorganisms.
Clinical  Manifesta6ons
Bacteremia  (nosocomial  or  spontaneous)  that  delivers  the  organism  to  the  surface  of  the  valve
Adherence  of  the  organism
Eventual  invasion  of  the  valvular  leaflets
Staphylococcus  aureus  and  Enterococcus  faecalis  are  the  predominant  microorganisms.  

Rule In Rule Out

Symptoms of fever, chills and sweats, malaise, There was no heart murmur.
arthralgias Does not explain the rash and the CLAD.
Shortness of breath, cough and tachycardia may be Cannot be ruled out fully without proper diagnostic
symptoms of CHF procedures to fulfill the Duke’s Criteria.
Laboratory manifestations include leukocytosis

Duke’s  Criteria
 Major  C riteria  
1.   Posi6ve  blood  culture  
 Typical  microorganism  for  infec6ve  endocardi6s  from  two  separate  blood  cultures  
Viridans  streptococci,  Streptococcus  bovis,  HACEK  group,  Staphylococcus  aureus,  or  Community-­‐
acquired  enterococci  in  the  absence  of  a  primary  focus,  or  Persistently  posi6ve  blood  culture,  defined  
as  recovery  of  a  microorganism  consistent  with  infec6ve  endocardi6s  from:
Blood  cultures  drawn  >12  h  apart;  or  All  of  three  or  a  majority  of  four  or  more  separate  blood  cultures,  
with  first  and  last  drawn  at  least  1  h  apart.  Single  posi6ve  blood  culture  for  C oxiella  burne5i  or  phase  I  
IgG  an6body  6ter  of  >1:800

2.   Evidence  of  endocardial  involvement  

Posi6ve  echocardiograma
Oscilla6ng  intracardiac  mass  on  valve  or  suppor6ng  structures  or  in  the  path  of  regurgitant  jets  or  in  
implanted  material,  in  the  absence  of  an  alterna6ve  anatomic  explana6on,  or  
Abscess,  or    new  par6al  dehiscence  of  prosthe6c  valve,  or    
New  valvular  regurgita6on  (increase  or  change  in  preexis6ng  murmur  not  sufficient)  

Minor  C riteria  
1.   Predisposi6on:  predisposing  heart  condi6on  or  injec6on  drug  use  
2.   Fever  38.0°C  (100.4°F)  
3.   Vascular  phenomena:  major  arterial  emboli,  sep6c  pulmonary  infarcts,  myco6c  aneurysm,  intracranial  
hemorrhage,  conjunc6val  hemorrhages,  Janeway  lesions  
4.   Immunologic  phenomena:  glomerulonephri6s,  Osler's  nodes,  Roth's  spots,  rheumatoid  factor  
5.   Microbiologic  evidence:  posi6ve  blood  culture  but  not  mee6ng  major  criterion  as  noted  previouslyb  or  
serologic  evidence  of  ac6ve  infec6on  with  organism  consistent  with  infec6ve  endocardi6s

Jones’  Criteria  (refer  to  previous  groups)

Laboratory  Tests
CBC ESR  or  CRP
LFT RF,  ANA
KFT ASO  Titers
Metabolic  profile

Imaging  Modali6es
Chest  X-­‐ray
2D  Echo
Check  for  vegeta6ons
No  doming  of  ventricular  walls,  mild  flu\er  of  aor6c  valve  (sugges6ve  of  sclerosis),  leF  
ventricular  wall  hypertrophy  ◊  hence  not  IE

TB Pericarditis
The  most  common  infec6ous  e6ology  of  constric6ve  pericardi6s  
Constric6ve  pericardi6s  presents  with  a  myriad  of  symptoms  that  may  develop  slowly  over  a  number  of  
years  such  that  pa6ents  may  not  be  aware  of  all  their  symptoms  un6l  ques6oned.  
Due  to:
Direct  progression  of  a  primary  focus  within  the  pericardium,  or
To    reac6va6on  of  a  latent  focus
Rupture  of  an  adjacent  subcarinal  lymph  node
Onset  may  be  subacute  
An  acute  presenta6on  may  be  possible,  with  dyspnea,  fever,  dull  retrosternal  pain,  and  a  pericardial  fric6on  
rub.
An  effusion  develops  in  many  cases
Signs  of  cardiac  tamponade  may  eventually  appear.  
Suspect  if  the  pa6ent  is  in  a  high-­‐risk  popula6on  (HIV-­‐infected,  or  within  high-­‐prevalence  country);  if  
 there  is  evidence  of  previous  TB  in  other  organs
Suspect  if  2D  Echo,  CT  or  MRI  shows  effusion  and  thickness  along  the  pericardial  space.  
Sternal  pain  –  necessary  for  TB  pericardi6s,  but  not  present  to  the  pa6ent

Rule In Rule Out

Acute pericarditis may present with fever, dyspnea, No elevated JVP, ascites, and lower extremity edema.
shortness of breath, fatigue, and CLAD. No pericardial friction rub
Abnormal liver enzymes may indicate liver Does not explain the rash and the painful joints.
congestion

Dermatologist’s Perspective
Additional Questions/Information
Type of Lesion:
Shape & size: Maculopapular, poorly defined
Location: localized to the trunk
Color: light pink
Timing: manifesting at the height of fever & spontaneously disappears
Associated symptoms: (-) pain, pruritus
(-) asthma
(-) pet exposure
(+) allergy to cheese cake

Differentials
Cholinergic urticaria
In cholinergic urticaria, physical stimulus is usually heat or sweat
usually found in men and people aged 10- 30 years
appears rapidly; mean duration of 80 minutes
POSSIBLE STIMULUS: the sponge bath

Drug eruptions
Can be due to a hypersensitivity reaction to the drug, or due to adverse effects of the drugs (such as
release of cell mediators)
Consider medications of the patient:
Hypertensive medications
Antibiotics given
Drugs that can cause urticaria:
Aspirin
Barbiturates
Captopril
Enalapril
Penicillins
Sulfonamides

Inflammatory
Transient rashes occur in inflammatory conditions, such as Still’s Disease

Urticarial Rash secondary to Hep B

Rule In Rule Out
 BASED ON HX patterned fever occurring in the night up History: There is cough with shortness of breath--> may
to dawn indicate a pulmonary focus instead
Antibiotics did not relieve symptoms On PE: stiffness and soreness during fever, not usually seen
Night sweats--feature of Hep B infections in Hepatitis B infections
PE/ Diagnostics--> slightly elevated patched pinkish colored
rash, which disappeared after a while
Tachycardia
Elevated WBC count
Mildly abnormal liver enzymes (indicate hepatic pathology)

Infectious Mononucleosis
Rule In
Fatigue/ prolonged malaise on History
Fever and lymphadenopathy are seen in some patients
Maculopapular generalized rash that is usually faint,
evanescent and RAPIDLY DISAPPEARS. Rash is
nonpruritic
Arthralgias and myalgias may occur
Headaches and night sweats on history
Diagnostics--> leukocytosis is seen in infectious
mononucleosis
May also present with elevated liver enzymes
Rule Out
Chills are not common
Although chills can still occur
Following are not seen in the patient:
nausea, anorexia without vomiting (common in IM)
pulmonary involvement is NOT a feature of EBV
mononucleosis
Palatal petechiae of the posterior oropharynx

Primary Impression: Still’s Disease

Rule In Rule Out
BASED ON HISTORY Abdominal pain, swelling
Fever that comes and goes--usually there’s fever in the No hepatosplenomegaly
evening Pain when taking a deep breath
Arthralgia, myalgia More common among women
Skin rashes--usually comes and goes in the fever, not itchy, very rare, 1 in 100,000
transient, salmon pink
Swollen lymph nodes
Weight loss, 30% within 3 weeks
Sore throat
Can present with pulmonary symptoms
LAB: leukocytosis, high ESR and CRP, liver enzymes high,
negative rheumatoid factor

Neurologist’s Perspective
Additional Questions/Information
(+) lethargy, irritability, neck pain, progressive worsening headache
(-) drowziness, seizures, confusion, papilledema, rigidity, CN deficits, apasia, vomiting, motor changes,
psychosis, paralysis, disorientation
Lumbar puncture:
Opening pressure: normal, clear, colorless
CSF analysis: normal sugar, elevated protein, few white cells (0-1)
(-) G/S, antigen detection, CALAS
Culture pending
Brain CT:
(-) vegetations, infarction, abcess, edema

Differentials
TB Meningitis
Rule In Rule Out
 Fatigue/ prolonged malaise on History
Fever and lymphadenopathy are seen in some patients
Maculopapular generalized rash that is usually faint,
evanescent and RAPIDLY DISAPPEARS. Rash is
nonpruritic
Arthralgias and myalgias may occur
Headaches and night sweats on history
Diagnostics--> leukocytosis is seen in infectious
mononucleosis
May also present with elevated liver enzymes
Chills are not common
Following are not seen in the patient:
nausea, anorexia without vomiting (common in IM)
pulmonary involvement is NOT a feature of EBV
mononucleosis
Palatal petechiae of the posterior oropharynx

Viral Encephalitis
Common viral agents: Enteroviruses, HSV, arthropod-borne viruses, HIV
Manifestations:
Headache (Frontal or retroorbital)
Fever
Nuchal Rigidity
Constitutional signs: malaise, myalgia, anorexia, nausea and vomiting, abdominal pain, diarrhea
Mild lethargy and drowsiness
Rule In Rule Out
Philippines classified as an endemic country Focal neurologic disturbances have to be observed
Acute onset of febrile illness w/ the ff. signs & Aphasia
symptoms: Ataxia
Lethargy Upper or lower motor neuron patterns of weakness
Headache Involuntary movements (myoclonic jerks, tremors)
Fever Cranial nerve deficits (ocular palsy, facial weakness)
SSx reflect foci of infection or inflammation in the
brain

Diagnostics
Differen5al Diagnostic Examinations to be Requested
TB  Meningi6s CSF  Analysis:
Elevated  opening  pressure
lymphocy6c  pleocytosis  (10–500  cells/L),
elevated  protein  concentra6on  in  the  range  of  1–5  g/L  
(10–500  mg/dL)
decreased  glucose  concentra6on  in  the  range  of  1.1–
2.2  mmol/L  (20–40  mg/dL).
Viral  encephali6s CSF  Analysis:
Lymphocy6c  pleocytosis  (250-­‐500  cells)
Elevated  protein  (0.2-­‐0.8  g/L)
Normal  glucose
Normal/mildly  elevated  opening  pressure  
(100-­‐350mmHg)
CSF  culture  (poor  sensi6vity)

Primary Impression: Non-neurologic Disease

Pulmonologist’s Perspective
Additional Questions/Information
Normal ABG
Normal BUN, Creatinine
Normal C-ANCA
G/S:
Epithelial Cell < 10
 White Cell > 20
(+) cocci in pairs, cocci in chains, GPB
Sputum Culture showed normal flora
Blood Culture was negative after 48 hrs
Tests requested but not done:
PFT
Bronchoalveolar lavage

Differentials
Tuberculosis
Rule In Rule Out
Cough Acute cough
Intermittent Fever No mention of hemoptysis
Fatigue No mention of weight loss
Night sweats
Shortness of breath
Lymphadenopathy
Abnormal liver enzymes
Endemicity
 Pneumonia (may be bacterial, viral or fungal)
Rule In Rule Out
Cough joint pain
Fever fever pattern
Shortness of breath rash
Lymphadenopathy
Elevated WBC

Pulmonary Symptoms secondary to a primary disease

Rule In Rule Out
Cyclical pattern of fever Travel history not indicated
Feeling of coldness followed by fever and sweating No vomiting
Stiffness No convulsions
Headache
Myalgia
Arthralgia
Elevated liver enzymes

Primary Impression: Pulmonary Tuberculosis t/c Atypical Pneumonia

Final Diagnosis
Considering everything, the primary physician decides to order the following tests:
Blood culture
CBC
Sputum smear and culture
Excisional biopsy of lymph node
Abdominal CT Scan

Patient finally agreed to an excision biopsy of the lymph node.

Histopathology:
Figure 1. Histopathologic picture of the biopsy:
Abundant histiocytes, necrosis without neutrophils.

FINAL DIAGNOSIS: Kikuchi Disease

From Medscape: Kikuchi disease, also called histiocytic necrotizing lymphadenitis or Kikuchi-
Fujimoto disease, is an uncommon, idiopathic, generally self-limited cause of HYPERLINK "http://
emedicine.medscape.com/article/960858-overview" lymphadenitis. Kikuchi first described the
disease in 1972 in Japan. Fujimoto and colleagues independently described Kikuchi disease in the
same year.

FEVER OF UNKNOWN ORIGIN – LECTURE PROPER

Definitions
Fever
A state of elevated core temperature which is often but not necessarily part of defensive responses of
multi cellular organism (host) to invasion of live or inanimate matter recognized as pathogenic or
alien by the host.
Pyrogen mediated
Hyperthermia
Unregulated rise in body temperature
Represents failure of homeostasis pyrogens not involved
Petersdorf & Beeson chose 1 week work-up to r/o self-limiting viral illnesses and to allow for sufficient
 time for initial investigations to be completed.
Over the past 40 years, health care has shifted from inpatient to the ambulatory setting. It has now
become widely accepted that the 1-week inpatient investigation be modified to allow for evaluations
to be completed in an outpatient setting.
There are more than 200 causes of FUO reported in the literature

Classification of Fever
Acute Febrile Illness
Prolonged Febrile Illness (see table in the Appendix)
Classic FUO in the immunocompetent
Nosocomial FUO
Neutropenic FUO
HIV associated FUO

Classification of Fever of Unknown Origin

Classical Definition (Durack & Street, 1991; Durack & Street, 1991)
T > 38.3o C on several occasions
> 3 weeks duration
Diagnosis uncertain after 3 days in-house or 3 outpatient visits

Validation of New Definition (Vanderschueren et al. Arch Intern Med 2003; 163:1033-41)
Prolonged febrile illness (PFI) in immunocompetent patients (n = 290)
Illness of at least 3 weeks duration before diagnosis
Temperature > 38.3°C on >3 occasions
No diagnosis at referral
Subgroups of PFI according to the time of diagnosis
Early diagnosis within 3 days
Intermediate diagnosis: between 4 and 7 days
Late diagnosis: after Day 7: 30%
No diagnosis: 33.8%
FUO as defined by Durack & Street includes subgroups B to D. 13.1%
FUO as defined by Petersdorf &Beeson includes subgroups C to D.
Prolonged febrile illness is 23.1%
Case-mix of Vanderschueren study cohort (2003) based on FUO definition used

Nosocomial FUO
Hospitalized
T > 38.3o C
Infection not present on admission
Diagnosis unclear after 3 days with at least 2 days for blood cultures

FUO in the immunocompromised

ANC < 500/mm3
T > 38.3oC
Diagnosis unclear after 3 days with at least 2 days for blood cultures

HIV associated FUO

HIV positive
T > 38.3oC on several occasions
Duration > 4 wks OP or 3 days IP
Diagnosis unclear after 3 days with at least 2 days for blood cultures
FUO: Diagnostic Entities (from 11 case series reporting over 1000 pts.)
SHAPE \* MERGEFORMAT
Best predictor of survival is disease category. Increase in CA; decrease in Infectious Diseases
Overall, 12-35% of pts with FUO will die from FUO-related causes.
52 – 100% of pts. with a dx of malignancy will die within 5 years of dx
8 – 22% mortality among ID causes

Changing Spectrum of FUO

EMBED Excel.Chart.8 \s
Over past 40 yrs, proportion due to ID and CA have decreased. The easy detection of solid tumors and abn.
lymph nodes via UTZ and computed tomography (CT) has resulted in a decline of tumors as a common
cause of FUO.
Pts with undiagnosed FUO used to make up the smallest proportion. At present, the largest proportion who
present with FUO never have a cause identified.
The most common ID causes: TB, intra-abd’l abscesses
Malignancies: Hodgkin’s and non-Hodgkin’s lymphoma
Temporal arteritis: accts for 16-17% of FUO in the elderly

FUO patients at UST Hospital, 1980 – 1991 (n=72)

Dy E, et al. JPSMID, 1992;22:35-40
SHAPE \* MERGEFORMAT

Major Evolutionsin Causes of FUO from Original Article to Present Day

Shift to less infection, less cancer, more inflammatory disease and more ‘unknown’
Much less common for some infections (i.e., abdominal abscess) and tumors (i.e., lymphoma) to go
undetected due to UTZ, TEE, CT, etc.
‘New’ infections: CMV, HIV, Parvo B19, HHV8, PCP, Brucella, Bartonella, Babesia, B. burgdorferi,
Yersinia, SARS
HHV8: human herpesvirus8—the most recently identified human oncogenic herpesvirus. Associated
with Kaposi’s sarcoma, and human lymphoproliferative diseases, such as pleural effusion lymphomas
and multicentric Castleman’s disease.
But first, don’t forget the obvious…
Confirm that a true fever exists.
Daily record of temperatures
Fever pattern: not very helpful
Rule out drug fever.
If possible, D/C all medications early in the evaluation
Suspected drug is not the cause: if fever persists beyond 72 hours after removal of the suspected
drug
Drugs Implicated as a cause of fever

Recommended Diagnostic Tests for which Evidence Exists & are Relatively High Yield
Abdominal CT: 19%
one of the first investigations (after basic work-up)
likely to identify 2 of the most common causes of FUO: intra-abdominal abscess, lymphoproliferative
disorders
Nuclear imaging: as second-step investigation
Positron Emission Tomography: [18 F]fluoro deoxyglucose PET:
total body scintigraphy
high specificity; diagnostically useful in 41 – 69% in 3 FUO case series
very good tracer for inflammatory diseases, esp. temporal arteritis
Technetium-based studies: sensitivity: 40 – 75%; specificity 93 - 94%
 Inferior: Gallium 67, Indium 111 IgG, Indium 111-labeled wbc scans

Ultrasonography
Sensitivity of 80-85% (vs. 90-100% for CT)
UTZ images may be obscured by overlying gas patterns
CT provides better imaging of the retroperitoneum

Duke criteria for IE

IE accounts for ~ 1-5% of all causes of FUO
Duke criteria: specificity in FUO: 99%; sensitivity in non-FUO cases: 82%
TEE (sensitivity: 100%, specificity: 98%) for early detection of valvular vegetations in IE, esp. culture-
negative IE
TTE (sensitivity: 63%, specificity: 98%)

Liver biopsy
Yield of 14 – 17% (in a selected group of FUO patients)
Complications (in pts. w/o FUO): 0.06 – 0.32%
Deaths: 0.009 – 0.12%

Temporal artery biopsy

preferred strategy when likelihood of disease is intermediate
In all patients > 60 with ESR or alkaline phosphatase
Rare complications: damage of the facial nerve, skin necrosis, drooping of the eyebrow

Leg Doppler imaging

when deep vein thrombosis is suspected as cause of fever (2 – 6% of patients
safe procedure; identifies a treatable cause

NOT RECOMMENDED
Bone marrow cultures
Yield in immunocompetent persons: 0 – 2%
use at your discretion based on circumstances
Uncertain:
Surgical exploration of the abdomen
poor methodological quality of studies
mortality: 4%; post-op complications: 12%
laparoscopy: 44% yield in pre-CT area
role in post-CT era: unclear
Empiric therapy
utility in FUO not studies
may obscure or confuse the diagnosis

Commonly Performed Tests where No Systematic Evidence for FUO Diagnosis Exists to Date
ESR
CRP
PCR
Bone scan
MRI
APPENDIX

SUMMARY TABLE OF THE CLASSIFICATION OF PROLONGED FEBRILE ILLNESS

Summary Classic FUO Nosocomial FUO Immune-deficient FUO HIV-related FUO Definition

>38C > 38C > 38C 38C

> 3 wk 3 days > 3 days > 3 wk for outpatient
> 2 visits or 3d in not present or incubating negative cultures after > 3day inpatient
hospitals on admission 48h HIV infection

Patient Location Community, clinic, Acute care hospital Hospital or clinic Community, clinic
or hospital or hospital

Leading causes Cancer, infections, Nosocomial Majority due to HIV (primary

inflammatory infections, infections, but infection), typical
conditions, postoperative cause documented and atypical
undiagnosed, complications, in only 40-60% mycobacteria,
habitual drug fever CMV, lymphomas,
hyperthermia toxoplasmosis,
cryptococcosis

History emphasis Travel, contacts, Operations and Stage of Drugs, exposures,

animal and insect procedures, chemotherapy, risk factors, travel,
exposure, devices, anatomic drugs contacts, stage of
medications, considerations, administered, HIV infection
immunizations, drug treatment underlying
family history, immunosuppressiv
cardiac valve e disorder
disorder

Examination Fundi, oropharynx, Wounds, drains, Skin folds, IV sites, Mouth, sinuses,
emphasis temporal artery, devices, sinuses, lungs, perianal area skin, lymph nodes,
abdomen, lymph urine eyes, lungs,
nodes, spleen, perianal area
joints, skin, nails,
genitalia, rectum or
prostate, lower
limb deep veins

Investigation Imaging, biopsies, Imaging, bacterial CXR, bact cultures CBC, serologic
emphasis sed rates, skin tests cultures tests, CXR, stool,
biopsies, cultures,
imaging
Management Observation, OP Depends on Antimicrobial Antiviral and
temp chart, situation treatment protocols antimicrobial
avoidance of protocols,
empirical drug vaccines, revision
treatments of treatment
regimens, good
nutrition

Time course Months Weeks Days Weeks to Months

Tempo of Weeks Days Hours Days to weeks

Investigation
 Algorithm for FUO Diagnosis

Categories of FUO
Feature Nosocomial Neutropenic HIV-Associated Classic
Patient’s situation Hospitalized, Neutrophil count Confirmed HIV- All others with
acute care, no either <500/µL or positive fevers for >3 weeks
infection when expected to reach
admitted that level in 1 – 2
days
Duration of illness b b b b
3 days 3 days 3 days (or 4 3 days or three
while under
weeks as outpatient
investigation
outpatient)
visits
Examples of cause Septic Perianal infection, c Infections,
MAI infection,
thrombophlebitis, aspergillosis, malignancy,
TB, non-
sinusitis, candidemia inflammatory
Hodgkin’s
Clostridium diseases,
lymphoma, drug
difficile colitis, drug fever
fever
drug fever
a All require temperatures of >38.3°C (>101°F) on several occasions.
b Includes at least 2 days’ incubation of microbiology cultures.
c M. avium/M. intracellulare.
Source: Modified from DT Durack, AC Street, in JS Remington, MN Swartz (eds): Current
Clinical Topics in Infectious Diseases. Cambridge, MA, Blackwell, 1991.

FEVER OF UNKNOWN ORIGIN (FUO)

Year Level 7 [Module 19: Infectious Module]|January 27, 2011

Team 2|
Page PAGE 15 of NUMPAGES 15

Year Level 7 [Module 19: Infectious Module]

 FEVER OF UNKNOWN ORIGIN (FUO)
Class Presentation and Lecture by Raul Destura, January 27, 2011
M.D.

Team 2|Anna, Gabe, Janka, Stef, Ven, Robert, Claire, Miah, Kim

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Additional Information Provided

Rash  transient, with a questionable history
Cough  intermittently productive, sometimes with scratchy throat
Chest X-Ray on admission
Normal vascular marking & cardiothoracic ratio
No blunting of costophrenic sulci
(+) PPD test at 15mm
CBC  Leucocytosis of 23,000 deviated to the left
Liver function  2x elevated
AFB smear is 3 of 3 negativeC
Culture still pending until 8th week of admission
No consent for bronchoscopy and of CSF analysis
Blood cultures remain negative until 24th hour of admission
Urine is clean, clean catch
TB PCR  no amplifications of microbial DNA
Malarial smear  always a consider because of location
3 collections- normochromic or normocytic
(-) malaria parasite
(+)Typhidot  possible false positive due to cross-linking
(-) Blood, urine, stool exams for enteric pathogens

Addi6onal  Ques6ons  Asked  and  Responses

Family  history  of  Cancer
None
Previous  infec6on
Previous  history  of  influenza  6  months  prior
History  of  smoking
6  pack  years,  stopped  when  35  years
Weight  loss
30%  weight  loss,  in  a  ma\er  of  3  ½  weeks
Occupa6on
Former  CEO  of  SMC

From 1952 to 1994 series:

Infections: 28%
Inflammatory diseases: 21%
Malignancies: 17%
Undetermined: 19%

Infections 61%
Neoplasms 13%
Connective Tissue Diseases 6%
Miscellaneous 4%
Unknown 17%

Additional Information Provided

Dental  procedure  and  dental  caries  present
No  pharyngi6s
No  surgical  implants
No  history  of  IV  drug  use
No  record  of  valvular  heart  defects  or  congenital  defects
27  years  hypertensive
160-­‐170  systolic  and  90-­‐100  diastolic
Hypercholesteremia  being  treated  for  8  mos
Family  history  of  CVD,  ischemic  infarct  and  conges6ve  heart  failure
Sinus  tachycardia
Normal  BMI
Normal  JVP,  ¼  caro6d  bruit  on  the  (R)
Heart  sounds  are  normal
Normal  PMI
No  organomegaly
Onymycosis  on  the  big  toe

Criteria for Fever of Unknown Origin (Durack and Street (1991))

Classical FUO
Fever >= 3.83 degrees celcius on several occasions
Illness >= 3 weeks duration
Diagnosis uncertain after 3 days of in-hospital investigation o 3 out-patient visits