Post on 17-Jan-2016
description
LeeChuy, KatherineLee, Sidney Abert
Lerma, Daniel JosephLegaspi, Roberto Jose
Li, Henry WinstonLi, Kingbherly
Lichauco, RafaelLim, Imee Loren
Lim, Jason MorvenLim, John Harold
Lim, MaryLim, Phoebe RuthLim, Syndel Raina
Lipana, Kirk AndrewLiu, 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 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
4 months PTA • 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
-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
2 weeks PTA
1 week PTA -progression of joint pain and swelling of both wrist to hands, knees, ankles to feet, graded 10/10with 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)
General survey:Conscious, Coherent, stretcher-borne not
in respiratory distress
Vital signs:BP: 120/70PR:88 regularRR:22 cpmTemp: 36.5 C
Anthropometric mesaurement -Ht: 165.1 cm Wt: 65 kgs BMI: 23.9
August
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
• Anthropometric measurement -Ht: 165.1 cm Wt: 65 kgs BMI: 23.9
PHYSICAL EXAMINATION
Admission (August 24, 2010)Skin
Warm, dry skin, (+) scaling on the right foot and ulcers on the sole of the left foot
August 27, 2010
• 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. (+) ulcer on the medial calcaneal area of the left footNo rashes, petechiae, No palmar erythema, no spider angiomaNails without clubbing or cyanosis.
PHYSICAL EXAMINATION
Admission (August 24, 2010)HEENTPale palpebral conjunctiva, slightly icteric
sclera, 3-4 mm ERTLNo tragal tenderness, No nasoaural
discharge, nasal septum midline, no hoarseness
Supple neck, no palpable cervical lymph nodes, trachea is midline thyroid not enlarged
August 27, 2010
HEENTPale palpebral conjunctivae, anicteric sclera, pupils ERTL 2-3mm, 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)RespiratorySymmetrical chest expansionNo retractions Equal vocal and tactile fremiti Resonant on percussion(+) crackles on both lower lung fields
August 27,2010Respiratory• 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)
CardiovascularAdynamic precordiumApex beat at 5th LICS MCSNo heaves and thrillsS1 > S2 at the apex, S2> S1 at the baseNo murmurs
August 27,2010
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
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
August 27, 2010GastrointestinalInspection: Globular and symmetrical
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, 2010Musculoskeletal(+) swelling on both wrists and hands,
ankles and feet, warm to touchThe patient can move his head, shoulders,
elbows and knees with ease.
Can perform flexion, extensions and supination of the hands and elbows without difficulty.
No tenderness upon palpation.
PHYSICAL EXAMINATION
Admission (August 24,2010)Neurologic ExamGCS 15 (E4V5M6)Alert, oriented in three spheresIntact cranial nervesCerebellar – can do FTNT and APST with
easeMMT- 5/5 on all extremitiesNo sensory deficitsRefelexes: ++ on all extremities, (-)
Babinsky, nuchal rigidity, Brudzinki’s and Kernig’s
August 27, 2010Neurologic Exam
• 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: 5/5 all extremities• No sensory deficits• Can do FTNT, APST • Reflexes:
• Superficial: (+) Gag and corneal reflex
• Deep Tendon: (++) on all extremities
• No Babinski, nuchal rigidity, Brudzinski, Kernig’s
Physical Examination
Physical Examination
Physical Examination
Physical Examination
Physical Examination
Physical Examination
SUBJECTIVE DATA OBJECTIVE DATA
Age: 60
Sex: M
Swelling of joints of hands, feet and legs
Recurrent monoarthritis
Limitation of movements on the hands and feet
Alcoholic beverage drinker
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. (+) ulcer on the medial calcaneal area of the left foot(+) swelling on the wrists to hands, ankles to feet, which are warm to touchPresence of ulcers on medial calcaneal area of the left foot(+) pale palpebral conjunctivaDRE: greenish brown on examining finger
SALIENT FEATURES
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
*8/23 8/25, after transfusion of 5 ‘U’ PRBC
Hemoglobin 48 68
RBC 2.43 2.89
HCT 0.16 0.21
MCV 63.30 73.20
MCH 19.7 23.60
MCHC 30 32.3
RDW 23.00 29.30
MPV 5.30 6.00
PLATELET 802 619
WBC 19.8 10.40
DIFFERENTIAL COUNT
NEUTROPHILS 0.89 0.90
METAMYELOCYTES 0.01 -
BANDS 0.01 0.01
SEGMENTED 0.89 0.89
LYMPHOCYTES 0.06 0.09
MONOCYTES - -
EOSINOPHILS 0.03 0.01
BASOPHILS - -
Reticulocyte count 33
UNIT REFERENCE RANGE
G/L 120-170
X 10^12/L 4.0-6.0
0.37-0.54
U^3 87 + - 5
Pg 29 + - 2
g/dl 34 + - 2
11.6 – 14.6
fL 7.4 – 10.4
x 10^9 / L 150 – 450
x 10^9 / L 4.5 – 10.0
0.50 – 0.70
0.00 – 0.05
0.50 – 0.70
0.20 – 0.40
0.00 – 0.07
0.00 – 0.05
0.00 – 0.01
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 0.5-1.2 mg/dl
BUN 65.70 8-23 mg/dL
Sodium 123 136.00 132.48 129.00 137-147 mmol/L
Potassium 4.96 4.47 4.21 3.36 3.8-5 mmol/L
iPO4 4.5 2.3-4.7 mg/dL
Ionized Calcium
1.66 1.52 1.42 1.37 1.32 1.12-1.32 mmol/L
Fasting Blood Sugar
78.97 78.97 70-110 mg/dL
SGPT - ALT 36.91 3.8-5 U/L
Uric Acid 13 4-8.5 mg/dl
HbA1c 7.90 4.8-6.0 %
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
8/28 9/01 UNIT REFERENCE RANGE
Hemoglobin 117 105 G/L 120-170
RBC 4.56 4.16 X 10^12/L 4.0-6.0
HCT 0.36 0.33 0.37-0.54
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 11.6 – 14.6
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
DIFFERENTIAL COUNT
NEUTROPHILS 0.80 0.38 0.50 – 0.70
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
Reticulocyte count 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 findingsBoth 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:
CardiomegalyAtheromatous aorta
Anemia due to:Patient NSAID
GastropathyChronic Kidney
Disease
Hypochromic microcytic anemia
Hypochromic and microcytic anemia
(↓ iron)
Normocytic and normochromic
anemia (↓EPO)
(+) FECAL OCCULT BLOOD TEST + -
Chronic NSAID use(Alaxan-paracetamol+ibuprofen; Mefenamic acid)
+ -
Hct 16% <20-25% 20 to 30%
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 diabetesTable 3—Criteria for the diagnosis of diabetes1. 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 AssociationDiagnosis and Classification of Diabetes Mellitus, DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010
Patient 8/23 8/25 8/26 8/28 9/01 Reference
Fasting Blood Sugar
78.97 78.97 70-110 mg/dL
HbA1c 7.90 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 AssociationDiagnosis 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 nephrosc lerosis
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
Febuxostat: the evidence for its usein the treatment of
hyperuricemia and gout
Angelo L GaffoKenneth 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, placebo-controlled, 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
254Febuxostat 80 mg/d
254Febuxostat 120 mg/d
254Allopurinol 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 1.5-
2.0 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
• 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
1072 patients
Febuxostat 80 mg/d
Febuxostat 120 mg/d
Febuxostat 240 mg/d
PlaceboAllopurinol
300 mg/d or 100 mg/d
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
294Febuxostat
80 mg/d
294Febuxostat 120 mg/d
147Allopurinol
80 mg/d
Phase III - CONFIRMS
• Randomized, controlled, multicenter, double-blind
2269 patients
Febuxostat 40 mg/d
Febuxostat 80 mg/d
Allopurinol 200 or 300 mg/d
SUA <6mg/dL45%
SUA <6mg/dL 67%
SUA <6mg/dL 42%
Summary of evidence
Thank You!