FEVER OF UNKNOWN ORIGIN

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FEVER OF UNKNOWN ORIGIN

• Dr. S. Aswini Kumar. MD.
• Professor of Medicine,
• Medical College Hospital,
• Thiruvananthapuram.

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Definition
Fever of unknown origin (FUO) was defined by
Petersdorf and Beeson in 1961 as temperatures
higher than 38.3C (101F) on several occasions,
a duration of fever of more than 3 weeks, and
failure to reach a diagnosis despite 1 week of
in-patient investigation.
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New classification

• Durack and Street have proposed a new system for
  classification of FUO
• classic FUO,
• nosocomial FUO,
• neutropenic FUO, and
• FUO associated with HIV infection

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Classic PUO
This category corresponds closely to the earlier
definition of FUO , but the new definition is
broader, stipulating three outpatient visits or
3 days in the hospital without elucidation of a
cause or 1 week of "intelligent and invasive"
ambulatory investigation.
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1. Diagnosis ?

• A 50 year old man was admitted with fever of
  three weeks duration. On examination there was
  hepatosplenomegaly. Routine urine and blood
  examinations were normal. Widal test and Mantouex
  test were negative. Chest X-Ray and HIV were
  negative. Liver biopsy showed presence of
  granulomas

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Granulomatous hepatitis

• Systemic Sarcoidosis
• Miliary tuberculosis
• Lymphomas
• Wegeners
• Brucellosis
• Histoplasmosis
• Shistosomiasis

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Liver Biopsy

• To be cultured and retained

• Mehngini/Vims/True cut needle

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2. Diagnosis?

• A 45 year old man was admitted to the CCU with
  acute MI, thrombolysed and reperfused, but then
  went into persistent hypotension following a
  cardiac arrest. He developed fever on Day5.
  Routine blood investigation showed a
  polymorpho-nuclear leucocytosis. Blood culture
  was diagnostic

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Nosocomial FUO
In nosocomial FUO, a temperature of ³38.3C
(101F) develops on several occasions in a
hospitalized patient who is receiving acute care
and in whom infection was not manifest or
incubating on admission. Three days of
investigation, including at least 2 days'
incubation of cultures, is the minimum
requirement for this diagnosis
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Nosocomial FUO

• Post Myocardial infarction syndrome
• Pulmonary thromboembolism
• Occult Nosocomial infection
• Transfusion related viral infections
• Infected intra-vascular lines
• Catheter related infections
• Drug related fever

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Blood Culture

• Method

• Rapid identification

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3. Diagnosis?

• A 30 year old farmer working in a diary farm in
  Tamilnadu was admitted to the ward with low grade
  fever and evening rise of temperature. On
  examination there was generalized lymphadenopathy
  and hepato-splenomegaly. Blood routine, Chest
  X-ray PA view Blood Widal test were negative

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Systemic bacterial infections

• Brucellosis
• Typhoid fever
• Leptospirosis
• Campylobacter infection
• Meningococcemia
• Lymes disease
• Legionaires disease

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Serological Tests

• Methadology

• Widal Test

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4. Diagnosis?

• A 49 year old college Professor came with pain in
  the right loin and fever of one month duration.
  Loss of appetite and loss of weight were present.
  He was investigated for UTI. Repeated URE and
  urine cultures were negative. Renal angle was
  dull but non tender. CT scan of abdomen was
  diagnostic

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Malignancies

• Renal cell carcinoma
• Pancreatic cancer
• Cancer colon
• Lymphoma
• Leukemia
• Hepatoma
• Sarcoma

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Ultra-sound scan in FUO

• Look at

• USS Abd in RCC

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5. Diagnosis?

• A 14 year old boy was admitted with high grade
  fever and pallor. On examination no
  hepatosplenomegaly, lymphadenopathy or bone
  tenderness were present. The blood counts were as
  follows Hb 8gm, TC 3800, P8 L86 E4 M2, ESR 20
  mm in 1st hr. Platelet count 2.5 lakhs, BT 130
  CT 330

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Neutropenic FUO
Neutropenic FUO is defined as a temperature of
38.3C (101F) on several occasions in a patient
whose neutrophil count is lt500/L or is expected
to fall to that level in 12 days. The diagnosis
of neutropenic FUO is invoked if a specific cause
is not identified after 3 days of investigation,
including at least 2 days' incubation of cultures
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Neutropenic FUO

• Neutropenic patients are susceptible to focal or
  systemic infections
• bacterial and fungal infections, bacteremic
  infections, infections involving catheters and to
  perianal infections.
• infections due to HSV and CMV
• consequences of untreated infections catastrophic

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Bone Marrow studies

• Yields

• Bone marrow needle

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6. Diagnosis?

• A 55 year old woman presented with high grade
  remittent fever and severe pain in the right
  shoulder. No pallor/lymphadenopathy. Liver was
  palpable 8 cm below the costal margin. Soft and
  non tender. X ray chest and fluoroscopy showed
  elevated right hemi diaphragm with reduced
  movements

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Pus somewhere

• Pancreatic abscess
• Pelvic inflammatory disease
• Prostatic abscess
• Tubo-ovarian abscess
• Sub diaphragmatic abscess
• Dental abscess
• Liver abscess

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CT Scan as a tool in FUO
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7. Diagnosis?

• A 19 year old girl was diagnosed to have
  infective endocarditis, because she had fever,
  pallor and systolic murmur. Repeated blood
  cultures were negative and she did not improve
  with antibiotics given for SBE. After 4 weeks she
  was skin and bones and still febrile. This time
  CXR was diagnostic

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Bacterial Infections

• Miliary tuberculosis
• Pulmonary Tuberculosis
• Tuberculous pleural effusion
• Tuberculous pericarditis
• Lung abscess
• Bronchiectasis
• Empyema

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Chest X-Ray in FUO

• Diagnosis from CXR

• Encysted Empyema in CXR

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8. Diagnosis?

• A 25 year-old woman was admitted with a suspicion
  of rheumatic fever. A mid-diastolic murmur was
  audible to 4 out of 11 post graduate doctors in
  medicine who examined the case. ECG did not show
  RVH nor was there any straightening of the left
  border of heart in the chest X-ray PA view.

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Cardiac Causes of FUO

• Left atrial myxoma
• Sub acute bacterial endocarditis
• Prosthetic valve endocarditis
• Aortic dissection
• Tuberculous pericardial effusion
• Chronic constrictive Pericarditis
• Post myocardial infarction syndrome

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ECHO in FUO

• Diagnosis by ECHO

• Vegetation in ECHO

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9. Diagnosis?

• A 45 year old man , who returned from Mumbai
  where he was working as a taxi driver for the
  past twelve years. He was admitted with low grade
  fever and cervical lymphadenopathy. He was
  undergoing treatment from various hospitals for
  irritable bowel syndrome since last six months

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HIV associated FUO
HIV associated FUO is defined by a temperature
of 38.3C (101F) on several occasions over a
period of 4 weeks for outpatients or 3 days for
hospitalized patients with HIV infection. This
diagnosis is invoked if appropriate investigation
over 3 days, including 2 days incubation of
cultures, reveals no source.
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Human Inmmuno Deficiency

• HIV Infection as such
• Pulmonary Tuberculosis
• Pneumocystis Infection
• Toxoplasmosis
• Cytomegalovirus infection
• M. Avium or M. Intracellulare
• Non-Hodgkins Lymphoma

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HIV testing in FUO

• IV Generation Screening

• CD4 counts and HIV RNA copies

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10. Diagnosis?

• A 15 year old boy was admitted with history of
  fever of seven days duration. Clinical
  examination showed a generalized maculopapular
  rash and generalized lymphadenopathy,
  hepatosplenomegaly. All the routine
  investigations for a underlying bacterial
  infection were found negative

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Viral Infections

• Infectious Mononucleosis
• Hepatitis A B C D and E
• Ebstein Barr virus infection
• Cytomegalovirus infection
• Parvovirus infection
• Dengue hemorrhagic fever
• Lymphocytic chorio-meningitis

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Virology in FUO

• Availability limitation

• H1N1 Serology

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11. Diagnosis?

• A sixty year old man was admitted with history of
  fever, headache and vomiting. O/E neck stiffness
  was present. Initial CSF study showed 50cells P60
  L40. Repeat LP showed protein 45mg and sugar
  80mg. Patient did not improve much in spite of
  combined regimen with antibiotics and ATT

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Fungal Infections

• Cryptococcal meningitis
• Aspergillosis
• Blastomycosis
• Candidiasis
• Histoplasmosis
• Mucormycosis
• Sporotrichosis

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CSF Study in FUO

• Highly informative

• Any time investigation

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12. Diagnosis?

• A 20 year-old college student ,while on an All
  India Tour on motor cycle , was involved in a
  road traffic accident and suffered from multiple
  fractures of the femur which necessitated
  multiple blood transfusions. He developed high
  grade fever with chills and rigor after one week

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Parasitic Infections

• Malaria
• Amoebiasis
• Leishmaniasis
• P.carinii
• Toxoplasmosis
• Trichinosis
• Strongiloidiasis

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Peripheral Smear in FUO

• Simple bed side test

• Peripheral smear in Leukemia

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13. Diagnosis?

• A 14 year old girl was suffering from recurrent
  generalized seizures. She was put on
  Phenobarbitone and Dilantin sodium for the same.
  She had persistent low grade fever, but no lymph
  node enlargement or hepatosplenomegaly. Blood
  examination showed evidence of megaloblastic
  anemia

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Drug fever

• Gout
• Hematoma
• Haemolysis
• Cirrhosis of liver
• Pulmonary emboli
• Subacute thyroiditis
• Tissue infarction

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Biochemical Tests in FUO

• Function Tests

• Blood Chemistry

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14. Diagnosis?

• A 30 year old police man came with recurrent
  episodes of abdominal pain and abdominal
  distension, loss of weight and loss of appetite.
  He had fistulectomy on 2 occasions. He was
  weighing only 32kg. Pallor . Abdomen was soft.
  No hepato-splenomegaly.Colonoscopy was diagnostic

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Inflammatory Bowel Diseases

• Crohns disease
• Ulcerative colitis
• Intestinal tuberculosis
• Cholangitis
• Cholecystitis
• Mesenteric adenitis
• Osteomyelitis

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Tissue Biopsy in FUO

• Biopsy specimens

• Advaantages limitations

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15. Diagnosis?

• A 75 year-old man came with fever and headache of
  4 months duration. He had generalized body aches
  and pains.He was admitted to ophthalmic hospital
  one week before for complaints of sudden loss of
  vision in one eye. Routine investigations were
  negative except for a high ESR

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Connective tissue disorders

• Temporal arteritis
• Adult Stills disease
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Poly-arteritis nodosa
• Mixed connective tissue disease
• Relapsing polychondritis

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Collagen Work up in FUO

• ANA Profile

• Direct Immunoflourescence

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16. Diagnosis?

• A 45 year old lady came with generalized
  weakness, loss of weight and frequent loose
  stools. She always felt hot in her body and
  sweated excessively. Fine abnormal movements were
  present in the fingers. She had a fast heart rate
  which was out of proportion to her body
  temperature

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Metabolic disorders

• Hyperthyroidism
• Central causes
• Cerebrovascular accidents
• Encephalitis
• Brain tumor
• Hypothalamic dysfunction
• Pheochromocytoma

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Endocrine Tests in FUO

• Array of tests

• Cover the system

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17. Diagnosis?

• A 19 year-old nursing student attending the OPD
  complained that she had high grade fever on
  several occasions in a a day for past four weeks.
  She was unable to attend the ward examinations
  during this period because of the persistent
  fever. In between the fevers she was apparently
  healthy

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Factitious fever

• Habitual hyperthermia
• Maliganant Hyperthermia
• Neuroleptic Malignant Syndrome
• Afebrile FUO (lt38.3oC)
• Exaggerated circadian rhythm
• Hysterical Fever

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Habitual hyperthermia
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Conclusions
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Thank You for the patient listening