PUO…. A DILEMMA AT TIMES
Dr. Sumera Batool
PGT, MU-II
Holy Family Hospital,
Rawalpindi.
PATIENT’S PROFILE:
 Name:
 Age:
 Gender:
 Address:
 Education:
 Occupation:
 Marital Status:
 Date of admission:
 Mode of admission:
Mrs. XYZ
44 years
Female
Rawalpindi
Educated
Associate Prof.
Married
26/06/2014
OPD
PRESENTING COMPLAINTS:

Fever for 3 weeks
HISTORY OF PRESENTING ILLNESS:
 My patient was alright about 1 ½ years back when she
started having joint pains mainly involving small joints
of hands with asymmetrical involvement.
 Pain was moderate in intensity usually at morning time
along with mild stiffness.
 There was associated swelling of joints but no redness
or overlying skin changes.
 Pain partially responded to painkillers and remained for
almost 3 weeks till a short course of steroids was
started without any extensive workup and pain settled.
 She again developed joint pains in April 2014 involving
knee joints bilaterally, left wrist and small joints of
hands along with swelling and redness in an additive
pattern.
 Given painkillers and calcium supplements with partial
improvement. At that time baselines and workup for RA
was negative.
 In June 2014 she started developing fever which was
gradual in onset, high grade with chills documented up
to 102/103 F.
 Fever usually comes once or twice daily with no specific
evening rise or night sweats
 There was associated history of body aches and pain
SYSTEMIC INQUIRY:
 GENERAL:
No H/o irritability, weight loss, anorexia
No H/o hair loss, photosensitivity, eye redness.
 GIT:
No H/o vomiting, dysphagia, constipation, heartburn,
abdominal pain, oral ulcers, hematemesis or malena,
 RESPIRATION:
No H/O cough and sputum
No H/o chest pain, dyspnea or hemoptysis.
 CVS:
No H/o chest pain, SOB, orthopnea, PND, pedal edema or palpitations.
Cont…
 CNS:
No H/o headache, numbness &, fits, drowsiness, vertigo, blackouts
confusion, irritability, coma, paresthesias
 GENITOURINARY:
No H/o burning micturition, polyuria
No H/o oliguria, anuria, dysuria, nocturia, incontinence, frequency of
micturition or haematuria.
 LOCOMOTOR:
H/O joint pain and generalized body aches
No H/o stiffness of joints
 ENDOCRINE :
No H/o excessive sweating, no h/o heat and cold intolerance, excessive
thirst, weight loss.
 For fever she was started on multiple antibiotics initially
treated for enteric with IV ceftriaxone, later with
Azithromycin
 When fever did not settle then her blood CP was done
which showed very high TLC of 38,000.
 She got admitted with the suspicion of sepsis and
started on broad spectrum antibiotics after sending
blood and urine C/S.
 Even after one week antibiotics fever did not respond
and c/s were all negative.
PAST MEDICAL/SURGICAL
HISTORY :
 No previous hospital admission, or history of any other
prolonged illness or drug intake, or any surgical
procedure.
GYNEACOLOGICAL HISTORY:
 Menstrual cycle of 5/30
 Married for last 15 years with 2 sons and one daughter
 All SVD, alive and healthy
FAMILY HISTORY:
 Father had IHD.
 No history of HTN, DM, malignancy, or asthma
 No history of breast cancers in close relatives.
PERSONAL HISTORY:
 Non addict , non smoker
SOCIOECONOMIC STATUS :
 She belongs to an upper middle class family.
EXAMINATION
 GENERAL PHYSICAL EXAMINATION:
A middle aged toxic looking female with an average
height and built, lying on bed with
VITALS:
Pulse:
110/min
BP:
110/70 mmHg
R/R:
26/mins
Temp: 102°F
GENERAL PHYSICAL EXAMINATION:
Clubbing
Koilonychias
Leuconychia
Osler's nodes
Janeway lesions
Splinter Hemorrhages
Nail bed infarct
Palmer erythema
Joint deformities
Pallor
Negative
GENERAL PHYSICAL EXAMINATION:
Jaundice
Cyanosis
Rash
Thyroid
Lymph nodes
Pedal edema
Negative
Musculoskeletal system
Inspection of spine:
 The spine was straight with no obvious deformity,
 No abnormality of the gluteal, hamstring, popliteal and
calf muscles.
Palpation:
 The spinous processes and paraspinal tissues were
normal and aligned. No focal tenderness elicited on
palpation and percussion.
Movements of Spine:
 Flexion and extension were normal
 Deep bone tenderness was elicited over femur bilaterally
Joint
Inspection
Passive
movement
Active
Movement
Right
Normal(no
tenderness)
Normal
Normal
Left
Normal
Normal
Normal
Right
Normal
Normal
Normal
Left
Normal
Normal
Normal
Right
Normal
Normal
Normal
Left
Normal
Normal
Normal
Normal
Normal
HIP joints
Knee joint
Ankle joint
Small joints of foot
Right
Normal
Normal
Normal
Left
Normal
Normal
Normal
GIT EXAMINATION
ORAL CAVITY:
Unremarkable
ABDOMEN:
INSPECTION:
Flat abdomen, symmetrical, umbilicus central and inverted,
moves with respiration, no superficial veins, striae, pulsations,
visible peristalsis, scar marks.
PALPATION:
Soft, non tender, no visceromegaly
PERCUSSION:
Percussion note normal.
Shifting dullness and fluid thrill -ve.
AUSCULTATION:
Bowel sounds audible, no hepatic or renal bruit.
CNS
EXAMINATION:

Mini Mental State Examination:
Orientation
10/10
Registration
3/3
Attention and
calculation
5/5
Recall
5/5
Language
8/9
CNS
 Higher Mental Functions:
Intact
Mini mental score 28/30
 Cranial Nerve Examination:
 Olfactory nerve :
 Optic nerve:
Pupils:
Light reflex:
Visual field:
Color vision:
Intact
Normal size, symmetrical
Equally reactive to light
Intact
Intact
CNS
 Third, fourth & sixth nerves:

•
•
no nystagmus, no diplopia
no ophthalmoplegia
accommodation and convergence
intact
 Fifth nerve:

•
motor:
sensory:
 Facial nerve:
• close eyes against resistance, Blow air,
show teeth: intact
intact
intact
 Vestibulocochlear nerve :
intact
 9, 10, 11,12th cranial nerve :
intact
CNS
 Motor system:
Right
upper
limb
Left upper
limb
Right lower
limb
Left lower
limb
Fasciculation
Absent
Absent
Absent
Absent
Bulk:
Normal
Normal
Normal
Normal
Tone:
Normal
Normal
Normal
Normal
Power:
5/5
5/5
5/5
5/5
Reflexes
+
+
+
+
Flexor
response
Flexor
response
Planters
CNS
 SENSORY SYSTEM:
Sense of touch, pain, temperature, vibration,
proprioception
Intact.
Cortical sensations
Intact.
No saddle anesthesia.
 CEREBELLUM:
Intact
 SOMI:
Absent
 Fundoscopy exam
Normal
 Pulse :
CVS
82bpm,regular, normal volume,
all peripheral pulses palpable and of normal volume and character
bilaterally
 INSPECTION:
Shape of chest is normal, no obvious deformities, scar marks, prominent
veins, visible pulsations or pigmentation.
 PALPATION:
No tenderness, crepitus, palpable heart sound or thrill.
Apex beat was palpable in the left 5th intercostal space at
midclavicular line.
No left parasternal heave.
 AUSCULATION:
S1 and S2 are of normal intensity.
No other audible heart sounds or murmurs.
No pericardial rub present.
RESPIRATORY SYSTEM
INSPECTION:
R/R : 16 / min, B/L symmetrical shape, chest moving with
respiration B/L equally. No deformity, scar mark, pulsations or
suprasternal or intercostal recession.
PALPATION:
Trachea is central, no tenderness or crepitus over the chest,
chest movements and expansion (4cm) are B/L equal.
PERCUSSION:
Normal percussion note.
AUSCULTATION :
B/L normal vesicular breathing.
No added sound or pleural rub.
BREAST EXAMINATION:
 Normal nipple position and normal areola.
 Overlying skin normal.
 No palpable lump or tenderness.
FEVER
INFECTIONS
Tuberculosis (esp extra
pulmonary)
Brucellosis
Abdominal/pelvic abscess
Infective endocarditis
Osteomyelitis
HIV
MALIGNANCY
Lymphoma
Leukemia
Neoplasia
ARTHRITIS
AUTOIMMUNE DISORDERS
Systemic lupus
eryhthematosis
Rheumatoid arthritis
Vasculitis
Reactive arthritis
Reiter’s syndrome
Rheumatic fever
Fever and Arthritis
Infections
Tuberculosis
Brucellosis
Infective endocarditis
HIV
Autoimmune disorders
SLE
RA
Vasculitis
Reactive arthritis
RF
Malignancy
Lymphoma
Leukemia
CBC
NEUTR Hb
OS
MCV
HCT
PLT
26/6/1 51.7
4
95%
13.3
80
40.1
233
30/6/1 34.4
4
90%
12.5
81
39
240
1/7/14 33.4
90%
12.6
80
36.8
287
DATE
TLC
Peripheral Film 28/6/14
 Leukocytosis with marked neutrophilia (with left shift)
 Normocytic normochromic anemia
 Adequate platelets seen on smear
DATE
ESR
CRP
28/6/14
81
100
30/6/14
97
>120
 Blood and urine C/S and throat swab showed no growth
RFT/LFT/Sr. Electrolytes
DATE
LFT
RFT
S.Electrolyt-es
7/4/14
N
N
N
26/6/14
N
N
N
30/6/14
N
N
N
Urine R/E
DATE
COLOUR
APPEAR-
PROTEINS
NITRITE
BLOOD
KETONES
WBC
ANCE
20/2/14
Yellow
Clear
Negative
Negative Nil
Nil
0-1
26/6/14
l. Yellow
s.Turbid
Nil
Nil
Nil
2-3
Nil
 CXR-PA :
 USG abd/pelvis :
normal study
hepatosplenomegaly
• Liver is enlarged in size, 16 cm, normal parenchyma, no
focal mass or cyst
• Spleen is enlarged in size, 13 cm, no focal area of
abnormal density
 ECG
Normal
 Typhidot IgM positive
 ASO Titers - Normal
 RA Factor negative done twice
 Anti CCP antibodies negative
 ANA - negative
 Brucella serology done on 30/6/2014
Negative
Test
Date
RESULT
BSF
19/3/14
90 mg/dl
HbA1c
19/3/14
6%
Uric acid
14/3/14
4.4mg/dl
Lipid profile
14/3/14
Normal
TSH
17/6/14
Normal
fT4
17/6/14
Normal
LDH
17/6/14
250 (normal )
Serum Ferritin :
DATE
28/6/14
VALUE
146 ng/ml
Normal range (130 ng/ml)
Autoimmune profile 28/6/14
 ANA negative
 Anti ds DNA antibodies negative
 Anti cardiolipin antibody negative
 ANCA negative
 RA Factor repeat negative
 C3 and C4 levels normal
Autoimmune Profile
 ENA negative
anti sm antibodies
anti RNP antibodies
anti Ro antibodies
anti La antibodies
anti Jo 1 antibodies
anti Scl antibodies
NEGATIVE
X rays Of hands and wrist
 Normal
2 D ECHO & TOE
 LV EF 60%
 Normal sized cardiac chambers
 Good LV systolic function
 No gross regional wall motion abnormalities
 Valves appear normal
 No clot and no pericardial effusion
CT Scan chest, abdomen and
pelvis
Conclusion:
 Hepatosplenomegaly and bulky uterus with anterior
wall fibroid
 Liver is enlarged in size, 16 cm, normal parenchyma, no
focal mass or cyst
 Spleen is enlarged in size, 13 cm, no focal area of
abnormal density
Bone marrow
 ASPIRATE
Hematological findings are suggestive of infective
process. No abnormal infiltrates seen in the material
examined
 Trephine biopsy
normocellular, preserved architecture,
normoblastic erythropoiesis, hyperplastic myelopoieses,
prominent plasma cells: consistent with aspirate
findings
 BM routine cultures, fungal c/s, cultures for AFB and
Brucella were all negative.
FEVER
INFECTIONS
Tuberculosis (esp extra
pulmonary)
Brucellosis
Abdominal/pelvic abscess
Infective endocarditis
Osteomyelitis
Leptospirosis
HIV
MALIGNANCY
Lymphoma
Leukemia
Metastatic cancers
ARTHRITIS
AUTOIMMUNE DISORDERS
Systemic lupus
eryhthematosis
Rheumatoid arthritis
Vasculitis
Reiter’s syndrome
Rheumatic fever
Fever and Arthritis
Infections
Tuberculosis
Brucellosis
Infective endocarditis
HIV
Autoimmune disorders
SLE
RA
Vasculitis
Reactive arthritis
RF
PUO
 A temperature greater than 38.3 C, more than 3 weeks
duration, and failure to reach a diagnosis despite 1
week of inpatient investigation.
Possible Diagnosis ?
 Fever in the absence of any evidence for infection or
malignancy, along with arthralgias/arthiritis, High TLC
count, and high ESR/CRP… lead us to the possible
diagnosis of
Adult Onset Still’s disease.
YAMAGUCHI CRITERIA
Major Criteria
Minor Criteria
Exclusion Criteria
Temperature > 39ºC for
>1 week
Sore throat
Infection ,especially sepsis
Leukocytosis >
10,000/mm ( 80%
granulocytes)
Lymphadenopathy and/or
Epstein-Barr infection
Typical Rash
splenomegaly
Malignancy
Abnormal liver function
studies, particularly
elevations in AST ALT LDH
Inflammatory diseases
Arthralgia's
> 2weeks
Negative tests for ANA and
AOSD should be considered if rheumatoid
5 criteria (2 factor
of which being major) are met once
malignancies, infectious diseases and rheumatic diseases have been excluded.
 She was given Tab Prednisolone 1mg/kg. The fever
settled on the very next day of starting the steroids.
 Steroids were continued for two months, after that Tab
Methotrexate 10mg/week was added as steroid sparing
agent and prednisolone was tapered off very slowly.
Date
TLC
Neutros
Hb
PLT
Hct
24/8/14
19.8
94%
11.9
308
29.8
23/11/14
14.8
80%
13.1
320
30.6
9/12/14
15.3
81%
12.5
277
32
27/1/15
13.2
79%
13.3
208
30.6
Date
ESR
3/8/14
79
24/814
13
23/11/14
9
9/12/14
2
27/1/15
7