Download PHYSICAL EXAMINATION Admission (August 24, 2010)

LeeChuy, Katherine
Lee, Sidney Abert
Lerma, Daniel Joseph
Legaspi, Roberto Jose
Li, Henry Winston
Li, Kingbherly
Lichauco, Rafael
Lim, Imee Loren
Lim, Jason Morven
Lim, John Harold
Lim, Mary
Lim, Phoebe Ruth
Lim, Syndel Raina
Lipana, Kirk Andrew
Liu, Johanna
Llamas, Camilla Alay
•
•
•
•
•
•
•
•
•
•
•
•
•
Name: T. R.
Age: 60
Sex: M
Status: Married
Nationality: Filipino
Date of Birth: 12/10/1949
Place of Birth: Leyte
Religion: Roman Catholic
Educational attainment: High School Graduate
Occupation: retired; Grass cutter of Military Shrines Service
Current Address: Bataan
Informant: Patient, Wife, Niece, Nephew
Reliability: 70%
“Namamaga ang mga kasukasuan sa kamay,
tuhod, at bukong-bukong hanggang paa(swelling
of the hands, knees and ankle to feet)”
•
10 years PTA
4 months PTA
•
10 years history of recurrent monoarthritis
-No proper consult was done; self-medicated with
paracetamol 500mg + ibuprofen 200mg (Alaxan) &
paracetamol (Biogesic) 500mg
-denied steroid intake and aspirin
-pain free interval: 3 weeks initially, progressive shorter pain
free intervals
-frequency of drug intake 3 tabs/day: taken as needed,
initially TID
-efficacy: slight relief of pain
patient slipped and sustained an injury to the both hands and
wrist in an attempt to break his fall
• admitted at a local hospital in Bataan
• confined and was given unrecalled medications
• relieved from the pain
2 weeks PTA
-patient accidentally stepped on a sharp object and
cleaned the wound site with guava leaves and
betadine and then applied 500mg penicillin powder
-recurrence of joint pain and swelling of both hands,
knees, and feet; self-medicated with Mefenamic acid
500 mg and amoxicillin 500 mg which provided relief,
taken as needed
1 week PTA
-progression of joint pain and swelling of both wrist
and hands, knees, ankles and feet, graded 10/10
with limitation of movement these joints
ADMISSION (August 24, 2010)
• No major hospitalization, unrecalled immunizations
• No allergy, no previous transfusion
• (-) DM, PTB, Asthma, Cancer
Family History
•
not clear to the patient
Personal and Social History
•Non-smoker
•Alcoholic beverage drinker ( 2 bottles beer; 3x a week and occasional
gin drinker 2-3 bottles/week)
•Diet: mixed diet
•Denies illicit drug use
•
•
•
•
•
•
•
•
General: no fever, no weight loss, (-) anorexia, (-) weakness, (-) insomnia
HEENT: no blurring of vision, no eye redness, pain, itchiness, no excessive
lacrimation, no ear pain nor tinnitus, no ear discharge, no epistaxis, no nose
discharge, no anosmia, no obstruction nor sinusitis, no mouth sores, fissures,
bleeding, no dental carries, no throat irritation,
Pulmonary: no hemoptysis, no coughing, no dyspnea, no chest wall
abnormality
Gastrointestinal: no abdominal pain, no melena nor hematochezia, no
changes in bowel habits
Genitourinary: no hematuria, no dysuria, no urinary frequency, no hesitancy,
no incomplete voiding
Endocrine: no heat or cold intolerance, no polyphagia, no polydipsia, no
polyuria, no thyroid enlargement
Musculoskeletal: see HPI
Hematologic: no abnormal bleeding,easy bruising
PHYSICAL EXAMINATION
Admission (August 24, 2010)
August
General survey:
Conscious, Coherent, stretcher-borne not
in respiratory distress
General survey:
• conscious, coherent, ambulatory, not in
cardiorespiratory distress, normal speech,
appropriate thought process and content
and well-oriented as to time, place and
date.
• Vital Signs
– BP: (RUE) 170/100
(LUE) 170/100
– PR: 74 beats/minute
– RR: 17 cycles/minute
– Temperature (axillary): 37.2oC
Vital signs:
BP: 120/70
PR:88 regular
RR:22 cpm
Temp: 36.5 C
Anthropometric mesaurement
-Ht: 165.1 cm Wt: 65 kgs BMI: 23.9
•
Anthropometric measurement
-Ht: 165.1 cm Wt: 65 kgs BMI: 23.9
PHYSICAL EXAMINATION
Admission (August 24, 2010)
August 27, 2010
Skin
• Skin: Warm, moist skin, no
jaundice, no skin discoloration,
(+) tophi on the right wrist, right
dorsum of the hand, right elbow,
both feet, (+) ruptured tophi on
dorsum on the right foot and sole
of the left foot. (+)desquamation
and non-healing wound on the
medial calcaneal area of the left
foot
No rashes, petechiae, No palmar
erythema, no spider angioma
Nails without clubbing or
cyanosis.
Warm, dry skin, (+) scaling on the
right foot and ulcers on the sole
of the left foot
PHYSICAL EXAMINATION
Admission (August 24, 2010)
August 27, 2010
HEENT
Pale palpebral conjunctiva, slightly icteric
sclera, 3-4 mm ERTL
No tragal tenderness, No nasoaural
discharge, nasal septum midline, no
hoarseness
Supple neck, no palpable cervical lymph
nodes, trachea is midline thyroid not
enlarged
HEENT
Pale palpebral conjunctivae,
anicteric sclera, pupils ERTL 23mm, no exophthalmos, no tragal
tenderness, no aural discharge,
supple neck, no distended neck
veins, no palpable cervical lymph
nodes, thyroid gland not enlarged
PHYSICAL EXAMINATION
Admission (August 24, 2010)
August 27,2010
Respiratory
Symmetrical chest expansion
No retractions
Equal vocal and tactile fremiti
Resonant on percussion
(+) crackles on both lower lung fields
Respiratory
• Symmetrical chest expansion, no
subcostal retractions, unimpaired
tactile and vocal fremiti , resonant
upon percussion,(-) crackles on both
lower lung bases, no wheezes, no
rhonchi
PHYSICAL EXAMINATION
Admission (August 24, 2010)
August 27,2010
Cardiovascular
Adynamic precordium
Apex beat at 5th LICS MCS
No heaves and thrills
S1 > S2 at the apex, S2> S1 at the base
No murmurs
Cardiovascular
• Adynamic precordium, AB at 5th LICS
MCL, no heaves, no lifts, no thrills,
S1>S2 apex,S2>S1 base; Pulses were
full and equal in all extremities, no
cyanosis and clubbing
PHYSICAL EXAMINATION
Admission (August 24, 2010)
Gastrointestinal
August 27, 2010
Gastrointestinal
Inspection: Globular and symmetrical
Flabby abdomen, Abdominal
circumference: 98 cm, (+) shifting
dullness, (+) venous collaterals,
normoactive bowel sounds, no
palpable mass, no tenderness,
tympanitic all over, liver span 10 cm
MCL, Traubes space not obliterated, (-)
Murphy’s sign , DRE: smooth rectal
vault, no perianal tenderness, tight
sphincteric tone, no masses, prostate
not enlarge and greenish brown on
examining finger
Genitourinary
(-) CVA tenderness
DRE: greenish brown on examining finger
abdomen, No caput medusae,
inverted umbilicus, no visible
peristalsis, pulsation or mass
Auscultation: Normoactive bowel sound ,
No bruits
Percussion: tympanitic, Liver span 10 cm
along the Right MCL, Traube’s space
not obliterated, (-) shifting dullness
Palpation: Liver edge not palpable. No
mass, (-) succusion splash, (-) fluid
wave
Genitourinary
(-) CVA tenderness, kidneys not palpable
PHYSICAL EXAMINATION
Admission (August 24, 2010)
Musculoskeletal
Pulses full and equal, no cyanosis, (+)
bipedal edema, (+) swelling on wrist
to hands and ankle to foot, warm to
touch, (+) draining abscess measuring
1 X 1 cm on the sole of the left foot
August 27, 2010
Musculoskeletal
(+) swelling on both wrists and hands,
ankles and feet, warm to touch
Cervical spine, L&R shoulder, left elbow,
and L&R knee joints with full ROM
R elbow, L& R wrists, L&R MCPs, L&R
PIPs, L&R DIPs has limited ROM
No tenderness upon palpation.
PHYSICAL EXAMINATION
Admission (August 24,2010)
August 27, 2010
Neurologic Exam
Neurologic Exam
GCS 15 (E4V5M6)
Alert, oriented in three spheres
Intact cranial nerves
Cerebellar – can do FTNT and APST with
ease
MMT- 5/5 on all extremities
No sensory deficits
Refelexes: ++ on all extremities, (-)
Babinsky, nuchal rigidity, Brudzinki’s
and Kernig’s
• Mental status: Conscious,
awake, alert GCS 15
• Pupils 2-3mm, isocoric ERTL,
EOMs full and equal, no ptosis,
no nystagmus
• No facial asymmetry, can shrug
shoulders, can turn head against
resistance
• MMT: cannot be assessed
• No sensory deficits
• Reflexes:
• Superficial: (+) Gag and
corneal reflex
• Deep Tendon: not done
Physical Examination
Physical Examination
Physical Examination
Physical Examination
Physical Examination
Physical Examination
SALIENT FEATURES
SUBJECTIVE DATA
OBJECTIVE DATA
Age: 60
BP 170/100
(+) tophi on the right wrist, right dorsum
of the hand, right elbow, both feet, (+)
ruptured tophi on dorsum on the right
foot and sole of the left foot. (+)
desquamation and non-healing wound
on the medial calcaneal area of the left
foot
(+) swelling on the wrists and hands,
ankles and feet, which are warm to touch
(+) pale palpebral conjunctiva
DRE: greenish brown on examining finger
Sex: M
Swelling of joints of hands, feet and legs
Recurrent monoarthritis
Limitation of movements on the hands
and feet
Alcoholic beverage drinker
Upon admission
• Given Clindamycin 300mg q 6h
• Cold compress on affected areas, colchicine
(0.5 mg bid)
• Send wound discharge for Gram’s stain and
culture
COMPLETE BLOOD
COUNT
Hemoglobin
*8/23
UNIT
48
8/25, after transfusion of
5 ‘U’ PRBC
68
G/L
REFERENCE
RANGE
120-170
RBC
2.43
2.89
X 10^12/L
4.0-6.0
HCT
0.16
0.21
MCV
63.30
73.20
U^3
87 + - 5
MCH
19.7
23.60
Pg
29 + - 2
MCHC
30
32.3
g/dl
34 + - 2
RDW
23.00
29.30
MPV
5.30
6.00
fL
7.4 – 10.4
PLATELET
802
619
x 10^9 / L
150 – 450
WBC
19.8
10.40
x 10^9 / L
4.5 – 10.0
0.89
0.90
METAMYELOCYTES
0.01
-
BANDS
0.01
0.01
0.00 – 0.05
SEGMENTED
0.89
0.89
0.50 – 0.70
LYMPHOCYTES
0.06
0.09
0.20 – 0.40
MONOCYTES
-
-
0.00 – 0.07
EOSINOPHILS
0.03
0.01
0.00 – 0.05
BASOPHILS
-
-
0.00 – 0.01
Reticulocyte count
33
0.37-0.54
11.6 – 14.6
DIFFERENTIAL COUNT
NEUTROPHILS
0.50 – 0.70
x 10^-3 / L
5 - 15
8/23
8/25
8/26
8/28
9/01
Reference
Creatinine
2.86
2.29
2.21
2.08
1.82
BUN
65.70
Sodium
123
136.00
132.48
129.00
Potassium
4.96
4.47
4.21
3.36
iPO4
4.5
Ionized
Calcium
Fasting
Blood
Sugar
SGPT - ALT
1.66
1.42
1.37
1.32
0.5-1.2
mg/dl
8-23
mg/dL
137-147
mmol/L
3.8-5
mmol/L
2.3-4.7
mg/dL
1.12-1.32
mmol/L
70-110
mg/dL
36.91
3.8-5 U/L
Uric Acid
13
HbA1c
7.90
4-8.5
mg/dl
4.8-6.0 %
78.97
1.52
78.97
8/26
8/28
Reference
Total Cholesterol
119.78
150-250 mg/dL
Triglycerides
130.33
10-90 mg/dL
HDL
22.03
LDL
68.20
Total Protein
7.00
6-7.8 g/dL
Albumin
2.57
3.2-4.5 g/dL
Globulin
4.43
2.3-3.5 g/dL
VG Ratio
0.58
1-3
Intact PTH
8.2
15-65 pg/ml
ESR
38
0-13 MM After 1 Hr
COMPLETE BLOOD
COUNT
Hemoglobin
8/28
9/01
UNIT
117
105
G/L
REFERENCE
RANGE
120-170
RBC
4.56
4.16
X 10^12/L
4.0-6.0
HCT
0.36
0.33
MCV
79.80
79.80
U^3
87 + - 5
MCH
25.60
25.30
Pg
29 + - 2
MCHC
32.00
31.70
g/dl
34 + - 2
RDW
25.50
25.70
MPV
6.60
7.40
fL
7.4 – 10.4
PLATELET
450
268
x 10^9 / L
150 – 450
WBC
8.50
6.9
x 10^9 / L
4.5 – 10.0
0.80
0.38
METAMYELOCYTES
-
-
BANDS
-
-
0.00 – 0.05
SEGMENTED
0.80
0.38
0.50 – 0.70
LYMPHOCYTES
0.13
0.52
0.20 – 0.40
MONOCYTES
-
-
0.00 – 0.07
EOSINOPHILS
0.07
0.10
0.00 – 0.05
BASOPHILS
-
-
0.00 – 0.01
0.37-0.54
11.6 – 14.6
DIFFERENTIAL COUNT
NEUTROPHILS
Reticulocyte count
0.50 – 0.70
x 10^-3 / L
5 - 15
Other Ancillary procedures:
• Fecal occult blood test – (+)
• ECG – Sinus rhythm with left ventricular
hypertrophy
• Urinalysis: albumin- negative, sugar –
negative, RBC-0-2/hpf, Pus cell-1-4/hpf
X-ray of the left foot
September 1, 2010
X-ray of the right foot
September 1, 2010
X-ray of the left foot
September 1, 2010
Official X-ray findings
Both feet
• Multiple erosive and lytic changes involving the tarsal,
metatarsal, and phalangeal bones in both sides, with evidence
of narrowing of the joint spaces.
• Calcaneal spurs are noted.
• One notes evidence of soft tissue swelling, with soft tissue
lucencies, which may be due to abscess formation. .
• Sclerotic changes are also noted involving the tarsocalcaneal
articulating surfaces on the right side.
• One notes of decreased bone density.
• Impression:
• Above findings consider the possibility of Osteomyelitis.
• The possibility of Gouty arthritis is not entirely ruled out.
Chest X-ray
Official X-ray findings
• Lung fields are clear.
• There is increase in the transverse diameter of
the heart.
• Aorta is calcified.
• Diaphragm & sinuses are intact.
• Impression:
Cardiomegaly
Atheromatous aorta
Anemia due to:
NSAID
Gastropathy
Chronic Kidney
Disease
Hypochromic and
microcytic anemia
(↓ iron)
Normocytic and
normochromic
anemia
(↓EPO)
(+) FECAL OCCULT
BLOOD TEST
+
-
Chronic NSAID use
(Alaxan-paracetamol+ibuprofen;
Mefenamic acid)
+
-
<20-25%
20 to 30%
Patient
Hypochromic microcytic
anemia
Hct 16%
Hawkey CJ. Non-steroidal anti-inflammatory drug gastropathy: causes and treatment. Scand J Gastroenterol Suppl. 1996;220:124-7.
CATHERINE S. SNIVELY, M.D.,et.al. Chronic Kidney Disease: Prevention and Treatment of Common Complications. Am Fam Physician. 2004 Nov 15;70(10):1921-1928.
ADA Criteria for the diagnosis of diabetes
Table 3—Criteria for the diagnosis of diabetes
1. A1C ≥ 6.5%. The test should be performed in a laboratory using a method that is
NGSP certified and standardized to the DCCT assay.*
OR
2. FPG ≥ 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8
h.*
OR
3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be
performed as described by the World Health Organization, using a glucose load
containing the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a
random plasma glucose ≥ 200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by
repeat testing.
American Diabetes Association
Diagnosis and Classification of Diabetes Mellitus, DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010
Patient
8/23
Fasting
78.97
Blood Sugar
HbA1c
7.90
8/25
8/26
78.97
8/28
9/01
Reference
70-110
mg/dL
4.8-6.0 %
In the setting of an elevated Hba1C but “nondiabetic” FPG, the likelihood of
greater postprandial glucose levels or increased glycation rates for a given
degree of hyperglycemia may be present.
American Diabetes Association
Diagnosis and Classification of Diabetes Mellitus, DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010
Pending procedures
• Wound CS
-to determine etiology of the lesion as well as
the sensitivity or susceptibility of the
pathogen to antibiotics
Polarized light microscopy of
specimen collected
September 2, 2010
Final Diagnosis
• Ruptured tophi on the right foot with
secondary bacterial infection with
osteomyelitis
• Acute gouty arthritis on top of chronic
tophaceous gout
• Anemia secondary to occult GI bleeding
probably due to NSAID gastropathy
• Chronic kidney disease secondary to gouty
nephropathy and hypertensive nephrosclerosis
Management
Date
Medications/ Treatments
Frequency
8/24/10
Clindamycin 300 mg/ cap
Q6h
8/24/10 – 9/1/10
Cold compress on affected area
TID
8/25/10
Mupirocin ointment on affected area
TID
8/26/10 –
8/29/10
Ciprofloxacin 250 mg/tab
BID
8/29/10 -9/3/10
Amlodipine 10 mg/tab
OD
8/29/10
Omeprazole 40 mg/ tab
OD
8/29/10
Paracetamol 500 mg/tab T >38.5
Q4h
8/29/10
Bisoprolol 2.5 mg/ tab
OD
8/29/10
Aminoleban 1 sachet in 1 glass water
BID
8/29/10
Sultamicillin 350 mg/ tab
OD
9/1/10
Colchicine 0.5 mg/ tab
OD
9/1/10
Apply ice compress 10-15 min over affected joints
Q1h
9/3/10
Amlodipine 10 mg tab in am
BID
9/3/10
Amlodipine 5 mg tab in pm
Clindamycin
• reversibly binds to the 50S ribosomal subunits preventing
peptide bond formation thus inhibiting protein synthesis
• 600 mg-1.8g/d q6-8h PO
• Indicated for streptococci, S. aureus, and Bacteroides spp.
• GIT: diarrhea, pseudomembranous colitis, nausea, vomiting;
HEPATIC: elevation of liver enzymes; CVS: hypotension;
HEMATOLOGIC: eosinophilia; neutropenia, granulocytopenia,
thrombocytopenia; LOCAL: sterile abscess at injection site;
RENAL: renal dysfunction; MUSCULOSKELETAL: polyarthritis;
OTHERS: hypersensitivity reactions
• Diarrhea and any inflammatory bowel disease,
hypersensitivity to clindamycin or any component
Mupirocin ointment
• inhibits bacterial protein synthesis by reversibly and
specifically binding to bacterial isoleucyl transfer RNA
synthetase
• Apply 3x/d for 10 d
• Skin infection
• DERMATOLOGIC: polyethylene glycol {PEG} vehicle
may irritate broken skin or mucous membranes. Less
frequent incidence: skin burning, stinging, pain,
itching, rash and dry skin
• Hypersensitivity to mupirocin or any component,
e.g., PEG
Amlodipine
• acts primarily on peripheral vascular beds and have little
effect on cardiac muscle contraction or AV conduction
• block the voltage dependent calcium channel inhibiting the
availability of intracellular calcium to interact with the myosin
complex of smooth muscles. This action leads to relaxation of
the smooth muscle allowing a decrease in peripheral
resistance which leads to BP lowering
• 5-10 mg daily
• Hypertension, angina
• CNS: headaches; CVS: postural dizziness, palpitation,
tachycardia, ankle edema; DERMATOLOGIC: rash; OTHERS:
flushing and fatigue
• hypotensive and hypersensitive to the drug and in instances
of MI with heart failure or poor LV function.
Omeprazole
• Irreversibly inhibits gastric parietal cell proton pump (H+-K+
ATPase, inhibit gastric acid secretion, both basal and
stimulated
• 20-40 mg/d as single dose after breakfast for 4-8 wk PO
• Reflux esophagiti, acid-peptic ulcer disease, Zollinger-Ellison
syndrome
• CNS: reversible confusional states, agitation, depression,
hallucination; GIT: nausea, diarrhea, abdominal colic;
Hematologic: agranulocytosis, pancytopenia,
thrombocytopenia; Dermatologic : erythematous skin rashes,
erythema multiforme, exfoliative dermatitis; Renal: interstitial
nephritis, hematuria, glycosuria; Others: hypoglycemia,
alopecia, blurred vision, arthralgia.
• Hypersensitivity to the drug, gastric malignancy
Paracetamol
• It is a para-aminophenol derivative with analgesic and
antipyretic properties 325-650 mg (6-12 mg/kg) q4h, PO; max
dose 4g/d
• Symptomatic treatment of mild to moderate pain and/or fever
• CNS: stupor, coma, euphoria; CVS: hypotension;
DERMATOLOGIC: pruritus, urticaria; GIT: hepatic dysfunction,
jaundice; GIT disturbances, nausea, vomiting; HEMATOLOGIC:
leukopenia, thrombocytopenia, pancytopenia,
methemogobinemia; RESPIRATORY: dyspnea, asthma; GUT:
dysuria, interstitial nephritis and renal papillary necrosis
• Prolonged administration is contraindicated in patients with
anemia or cardiac, pulmonary, hepatic or renal disease.
Hypersensitivity to paracetamol or any of its component
Bisoprolol
• Bisoprolol produces negative chronotropic effect
and minimal change in stroke volume
• 5-10 mg PO once daily up to a max of 20 mg daily
• Hypertension, angina, heart failure
• CVS: bradycardia, AV block, sinus arrest, peripheral
vasoconstriction, heart failure; RESPIRATORY:
bronchospasm; OPHTHALMOLOGIC: decreased
tearproduction; OTHERS: fatigue
• Asthma and obstructive airway disease, Heart failure,
second or third degree heart block, cardiogenic
shock
Aminoleban
• 150 g/day (3 sachets/day)
• Dietary supplement esp for patient w/ liver
impairment. Nutritional support to patients
w/ chronic liver disease esp those w/ hepatic
encephalopathy
• Diarrhea & nausea
• Hypersensitivity
Sultamicillin
• inhibits β-lactamases in penicillin-resistant
microorganisms and it acts against sensitive
organisms during the stage of active multiplication by
inhibiting biosynthesis of cell wall mucopeptide
• 375-750 mg bid
• Respiratory tract infections, otitis media, UTI
• Diarrhea, nausea, vomiting, rashes, pruritus, blood
dyscrasias, superinfections, dizziness, dyspnoea.
Potentially Fatal: Anaphylaxis
• Hypersensitivity
Colchicine
• mild anti-inflammatory drug with no analgesic effects.
• inhibiting microtubule polymerization by binding microtubule protein
subunits and preventing their aggregation, thus disrupting membranedependent functions as chemotaxis and phagocytosis, which are cardinal
events in the inflammatory response to precipitated crystals. It has no
effect on the serum uric acid levels orits renal excretion
• 500 mcg tab taken orally hourly until pain and inflammation subside, to a
maximum cumulative dose of 6.0 mg
• Acute attacks of gout and other crystal induced arthritis
• GIT: nausea, vomiting, diarrhea and abdominal pain in up to 80% of
patients undergoing rapid colchinization; hepatotoxicity, hemorrhagic
colitis with overdose or with liver or renal disease; HEMATOLOGIC: aplastic
anemia, bone marrow suppression; CNS: peripheral neuritis; colchicine
induced-myopathy and polyneuropathy with prolonged use;
DERMATOLOGIC: alopecia, rash; OTHERS: anorexia, azoospermia, renal
dysfunction with overdose or with liver or renal disease.
• Hypersensitivity to colchicine or any components Serious renal,
gastrointestinal, hepatic or cardiac disorders Blood dyscrasia
Febuxostat: the evidence for its use
in the treatment of
hyperuricemia and gout
Angelo L Gaffo
Kenneth G Saag
Core Evidence 2009:4;25–36
Objective
• Review the clinical evidence of effectiveness
of febuxostat (TEI-3420, or TMX-67) on
outcomes and its potential for clinical
management of hyperuricemia and gout.
Methods
• Phases II and III
evidence
• Literature searches
– PubMed
– Cochrane database
– American College of
Rheumatology
– European League
Against Rheumatism
• (?) Inclusion exclusion
criteria not mentioned
Febuxostat
• Orally administered, nonpurine selective
inhibitor of xanthine oxidase.
• Binds to a channel in the molybdenum center
of the enzyme, leading to a very stable and
long-lived enzyme-inhibitor interactions with
both oxidized and reduced forms of the
enzyme
Phase II data
• 28-day, multicenter, double-blind, placebocontrolled, dose response clinical trial
• Determine safety and efficacy of once daily
febuxostat
– 40, 80, 120 mg
• Inclusion: patients with American College of
Rheumatology criteria-defined gout aged 23-80y/o
• Exclusion: absence of kidney dysfunction or taking
drugs known to affect serum urate (aspirin or
diuretics)
Phase II data
• Cases of reduction seen in as early as 7 days after
start of treatment
• Dose-dependent effect
• Incidence of gout flares, due to sudden removal and
mobilization of uric acid crystals from the tissues
– Despite pretreatment with colchicine
• Diarrhea, abdominal pain
• Abnormal liver function tests
– 40mg (14%), 80mg (8%), 120mg (8%)
Other Phase II data
• Reductions on tophi volume (by MRI)
• Good tolerance in allopurinol-intolerant patient
• 3 month colchicine prophylaxis in patients starting
with febuxostat
• Diarrhea, GI motility disorders, headache, abnormal
liver function tests, hyperlipidemia
• Japan (128 patients)
– reduced SUA regardless of underexcretors or
overproducers
– Safe and well tolerated
– Abnormal liver function tests and gout flares
Phase III data
•
•
•
•
FACT
APEX
EXCEL
CONFIRMS
Phase III data - FACT
• Febuxostat versus Allopurinol Controlled Trial (FACT)
• Randomized, double-blind, 52-week, multicenter
– Febuxostat 80 and 120 mg/day dose
– Allopurinol 300 mg/day fixed dose
• Inclusion: adult patients with American College of
Rheumatology-defined gout and SUA at least 8.0
mg/dL
• Exclusion: kidney dysfunction, concomitant drugs
known to affect serum urate, BMI >50, active liver
disease, pregnancy, use of prednisone >10 mg/d, or
alcohol abuse
Phase III data - FACT
• Primary endpoint – SUA of 6.0 mg/dL
• Clinical endpoint – reduction in tophus area,
change in number of tophi, and proportion of
patients requiring treatment for acute gout
flares
• Prophylaxis with colchicine or naproxen during
a 2-week washout period
Phase III data - FACT
762 patients
254
Febuxostat 80 mg/d
254
Febuxostat 120 mg/d
254
Allopurinol 80 mg/d
Discontinued
88 (34%)
Discontinued
98 (39%)
Discontinued
66 (26%)
Losses to follow-up, adverse events, and gout flares
Phase III data - FACT
Primary endpoint
Febuxostat 80 mg/d
Febuxostat 120 mg/d
Allopurinol 300 mg/d
53%
62%
21%
Phase III data - FACT
• Rates of total advers events and serious
adverse events were similar
• Liver function test abnormalitis (4-5%),
diarrhea (3%), headaches (1-3%)
• 4 patients in febuxostat group died
– Cardiovascular events
– Considered unrelated to administration of study
medications
Phase III data - APEX
• Allopurinol and Placebo-Controlled, Efficacy Study of
Febuxostat (APEX)
• Additional patients with mild to moderate renal
dysfunction (creatinine 2.0 mg/dL)
– Febuxostat at 80, 120, 240 mg/d
– Allopurinol 300 mg/d (crea 1.5mg/dL), 100 mg/d (crea 1.52.0 mg/dL)
• Inclusion: 18-85 y/o, American College of
Rheumatology-defined gout, SUA ≥8.0 mg/dL,
creatinine up to 2.0 mg/dL
• Exclusion: intolerances to allopurinol, colchicine,
naproxen, history of renal calculi, heavy alcohol
intake, baseline transaminases ≥1.5 upper limit of
normal
Phase III data - APEX
1072 patients
Febuxostat
80 mg/d
Febuxostat
120 mg/d
Febuxostat
240 mg/d
Allopurinol
300 mg/d or
100 mg/d
Placebo
• More gout flares in febuxostat 120 and 240
mg/d arm in first 8 weeks
• Similar rates in 8-28 weeks
• Diarrhea, liver function test abnormalities
Phase III - EXCEL
• Open-label phase III extension of FACT
• Continue evaluation response to treatment
• Allopurinol compared to febuxostat failed to
achieve continuous reduction of SUA 6.0
mg/dL
735 patients
294
Febuxostat
80 mg/d
294
Febuxostat
120 mg/d
147
Allopurinol
80 mg/d
Phase III - CONFIRMS
• Randomized, controlled, multicenter, doubleblind
2269 patients
Febuxostat
40 mg/d
Febuxostat
80 mg/d
Allopurinol
200 or 300 mg/d
SUA <6mg/dL
45%
SUA <6mg/dL
67%
SUA <6mg/dL
42%
Summary of evidence
Thank You!