Transcript treatment for psoriatic arthritis

Medicine II –Module 4
Clinical Case: Psoriasis
Psoriatic Arthritis
Cellulitis
Mendoza, T., Mindanao, A., Miranda, M., Molina, M., Monzon, J., Morales, A.,
Musni, M., Nallas, A., Naval, A., Nepomuceno, J., Nerpiol, C., Ng, C., Ng, P., Niere, J.,
Millicent Tan Ong, MD
Helmar Soldevilla, MD
3C-MED
1
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
2
MEDICAL HISTORY
• 28 year old male, catholic, married,
tricycle driver, residing in Caloocan
City
• Chief Complaint:
3
History of Present Illness
7 Yrs
PTA
Diagnosed with Psoriasis based on the following:
• Flaky white scales on the scalp
• Pustules, papules  plaques topped with scales at the
back, trunk, upper and lower extremities and his face
• Punch biopsy: Psoriasis
Rx:
 Psoralen + Ultraviolet A (PUVA) therapy
 Methotrexate (2.5mg) at 12 hr intervals for three doses
each week
 Dermovate (unrecalled dose) with Petroleum Jelly and
LCD
 Hydroxizine (Iterax) for pruritus 3x/day prn
Full resolution of skin lesions
2 Yrs
PTA
• Recurrence of skin lesions
• Pain and swelling of all the digits of both hands
• Rx: Naproxen (550mg/tab) BID prn
• Asymmetric oligoarthritis polyarthritis involving the DIPs
and PIPs of both hands, BKJ
• Consult to Rheumatologist
• Rx: Celecoxib (unrecalled dose)
4
1 Yr PTA
• Pain and swelling on both knee joints (BKJ) limping
• Relieved by various unrecalled NSAIDs
1 month
PTA
• persistent swelling on BKJ with↑ pain (VAS 9/10)
1 week
PTA
• Non-radiating pain (VAS 7/10) on the low back, hips, and
BAJ
• More difficulty in ambulation
5 days
PTA
• Consult to Orthopedic Surgeon; diagnosed with BKJ
effusion & advised arthrocentesis
4 days
PTA
• Undocumented fever temporarily relieved by Cefuroxime
and Paracetamol (unrecalled dose)
• Consult at FEU Hospital: (X-Ray of leg: soft tissue
swelling)
• Advised admission but refused due to financial constraints
• Transferred to USTH for further evaluation & management
ADMISSION
5
Past Medical History
•
•
•
•
•
•
(-) DM
(-) HPN
(-) Joint surgery
(-) history of trauma
(-) Allergy
Diagnosed with dengue fever (2nd
year high school)
• Excision of cyst at the back (2007)
6
Family History
•
•
•
•
•
•
•
(+) Myocardial Infarction – father
(+) DM – father
(-) HPN
(-) stroke
(-) Psoriasis
(-) Cancer
(-) Arthritides
7
Personal & Social History
• Smoker: 0.6 pack years
• Occasional Alcoholic Beverage
Drinker
• Denies Illicit Drug Use
• 3 past sexual partners, all protected
• Tricycle driver
• No history of travel outside manila
8
Review of Systems
• No wt. loss, no loss of appetite
• No hearing loss, no nasal congestion,
no cough
• No dyspnea, orthopnea, cyanosis
• No chest pain, palpitations
• No abdominal pain, diarrhea,
constipation
• No dysuria, frequency, change in
character of urine
9
PHYSICAL EXAMINATION
General Survey
• Conscious, coherent, oriented as to time, place and
person, not in cardio-respiratory distress
Vital Signs
• BP 120/70 mmHg Wt: 70 kgs
• PR 83 bpm
Ht: 1.62 m
• RR 20 cpm
BMI : 26.5 kg/m2
• T° = 36.6 °C
Skin
(+) generalized erythema w/ multiple well- to
ill-defined papules and plaques topped
with whitish scales over the scalp, trunk
and extremities
(+) onychodystrophy, nail pitting, oil spots of
all nails of the hands and feet
10
HEENT
• Pink palpebral conjunctivae, anicteric sclerae, no nasoaural discharge, no tragal tenderness, moist buccal
mucosa, nonhyperemic PPW, tonsils not enlarged
Neck
• Supple neck, trachea midline, no palpable cervical lymph
nodes, thyroid gland not enlarged
Cardiovascular
• Adynamic precordium, AB at 5th LICS, MCL; no murmurs
• All pulses full and equal
Respiratory
• Symmetric chest expansion, no retractions, clear breath
sounds on all lung fields, no crackles, no wheezes
Abdomen
• Flat abdomen, NABS, soft, nontender, no masses
11
Musculoskeletal
Hand
• (+) sausage-shaped 2nd and 4th digit
of the right hand & 4th & 5th digits of
the (L) hand
• (+) Flexion contracture of the DIPs
of the 2nd, 4th and 5th digits of the (R)
hand & 5th digit of the (L) hand
• (+) tender, swollen, erythematous
DIPs and PIPs of the 2nd, 4th and 5th
digits of the ® hand and DIP of the
4th and 5th digit of the (L) hand
• All Active Range of Motion (AROM)
of bilateral hands are within normal
limits EXCEPT:
(R )
DIP
PIP
2nd digit
45-45°
0-30°
(L)
DIP
PIP
4th digit
45-45°
0-45°
4th digit
0-45°
0-45°
5th digit
30-30°
0-50°
5th digit
50-50°
0-40°
(L) hand
(R) hand
Passive Range of Motion (PROM) not assessed due to tenderness of the affected joints
12
BKJ
• (+) swelling, warmth,
tenderness
• PROM within normal limits
AROM
(R)
(L)
BKJ
0-100°
0-125°
Legs
• swollen, warm, tender,
erythematous (R) leg
Limb Girth Measurement
RIGHT
LEFT
DIFFERENCE
3 inches
40.5 cm
38 cm
2.5 cm
6 inches
40.5 cm
37.5 cm
3 cm
9 inches
30.5 cm
28 cm
2.5 cm
Landmark: Medial Tibial Plateau
13
SALIENT FEATURES
Pertinent (+)
•
•
•
•
•
•
•
•
•
28 y/o male
History of Psoriasis
Asymmetric oligoarthritis polyarthritis of the
affected DIPs and PIPs of both hands, BKJ, and
(BAJ)
(+) Flexion contracture of the DIPs of the affected
digits
(+) sausage-shaped digits
Limited AROM of the affected joints
BKJ effusion
swollen, warm, tender, erythematous (R) leg
Undocumented fever
14
SALIENT FEATURES
Pertinent (-)
• No history of morning stiffness of
joints
• No hx of bacterial infection or serious
chronic illness
• No hx of infection before onset of
arthritis
• No family history of arthritides
15
Course in the Ward
Upon admission: Arthrocentesis
• Aspirated knee: 42cc (R) knee, 18cc (L)
• Gram stain = no microorganisms
1st hospital day
• Cefazolin 1g/IV every 8 hours
• Dolcet tablet (pain)
• Paracetamol (temperature exceeding 38.0⁰C)
2nd hospital day
• Dermatology; advised to continue using Dove Extrasensitive Soap
and Petroleum Jelly
• Advised to have regular leg exercises (improve mobility)
• Noted to have febrile episodes and tender, warm swelling of (R) leg
• Medications still continued
4th hospital day, decrease swelling of (R) leg, afebrile
6th hospital day, started on Cloxacillin 500mg/cap, 1 capsule every 6 hours
16
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
17
DIFFERENTIAL
DIAGNOSES
3C-MED
18
MUSCULOSKELETAL
COMPLAINT
NONARTICULAR
HISTORY & PE
ARTICULAR
INFLAMMATION
•TENDONITIS
•BURSITIS
•MYOFASCIAL
PAIN
MINIMAL:
OSTEOARTHRITIS
PRESENT:
•MONOARTHRITIS
•PAUCIARTHRITIS
•POLYARTHRITIS
19
ARTICULAR
INFLAMMATORY
MONOARTHRITIS
Gout
Septic Arthritis
PAUCIARTHRITIS
PROMINENT
SPINE
INVOLVEMENT:
Ankylosing
Spondylitis
Psoriatic arthritis
POLYARTHRITIS
MINIMAL SPINE
INVOLVEMENT:
Rheumatoid
arthritis
SLE
20
Harrison’s Principles of Internal Medicine 17th edition
21
PSORIATIC
ARTHRITIS
SEPTIC
ARTHRITIS
REACTIVE
ARTHRITIS
GOUT
RHEUMATOID
ARTHRITIS
Nature
Inflammatory
Arthritis
Infectious
Acute nonpurulent
arthritis
Metabolic Disease
Autoimmune
Disease
Process
Inflamed synovium
with less
hyperplasia and
cellularity than in
RA
Direct invasion of
joint space by
various
microorganisms,
including bacteria,
viruses,
mycobacteria, and
fungi
Acute, nonpurulent
arthritis occurs after
infection
Inflammatory
reaction to
microcrystal of
sodium urate
Chronic
inflammation of
synovial
membranes w/
secondary erosion
of adjacent
cartilage and bone
Cause
genetic and
environmental
factors, immunemediated
Bacterial Infection
(Gnococcal,
Nongonococcal),
Fungi, Virus
Shigella (S.
flexneri),
Salmonella,
Yersinia,
Deposition of MSU
in joint and
connective tissue
tophi
Unknown
Sex
M=W
M>F
Enteric: M = W
Venereal: M > W
M>F
M=F
postmenopausal
F 3X > M
Age
20-30- y/o
50-60 y/o
> 65 y/o
18 – 40 y/o
Middle age to
elderly men and
post menopausal
women
4th – 5th decade of
life
Clinical
Presentation
Oligoarthritis,
PolyArthritis, Axial
Arthritis
Subacute or
Chronic
monoarthritis,
Acute Polyarticular
Isolated transient
monoarthritis
Acute Arthritis
Chronic
Polyarthritis
Symmetry
Asymmetric/
Symmetric
Asymmetric
Viral - Symmetric
Asymmetric
Symmetric
Symmetric
22
PSORIATIC
ARTHRITIS
SEPTIC
ARTHRITIS
REACTIVE
ARTHRITIS
GOUT
RHEUMATOID
ARTHRITIS
No. of joints
Oligoarticular /
Polyarticular
Monoarticular or
Polyarticular
Monoarticular
Mono / oligoarticular
Initially : mono
Subsequent: poly
Polyarticular
Most common
joint affected
DIP
Knee, Hip, Shoulder,
Ankle, Wrists
Joints of lower
extremities (Knee,
Ankle)
MTP joint of big toe
PIP and MCP joints
Progression
and Duration
Erosive disease
develops,
progressive disease
w/ deformity and
disability
Acute, additive w/
involvement of new
joints in a few days
to 1-2 weeks
Occasionally isolated
attacks lasting days
up to 2 weeks
Often chronic with
remissions and
exacerbations
Swelling
Dactylitis (>30%),
Enthesitis,
Tenosynovitis
Diffuse swelling of
a solitary finger or
toe, Dactylitis or
sausage-finger,
Tenidinitis and
fasciitis
Present within and
around the involved
joint
Synovial tissue in
joints or tendon
sheaths
Stiffness
Morning stiffness
Limitations of
motion
reduced range of
motion
Present
Prominent, often for
an hour or more in
the morning, also
after inactivity
marked limitation of
both active and
passive ranges of
motion
Patient cannot walk
without support
Motion is limited
primarily by pain
Motion limited by
pain
23
PSORIATIC
ARTHRITIS
SEPTIC
ARTHRITIS
REACTIVE
ARTHRITIS
GOUT
RHEUMATOID
ARTHRITIS
Generalized
Symptoms
Silver or grey scaly
spots on the scalp,
elbows, knees etc,
Lifting or pitting of
fingernails/toenails
Redness and pain
in the eye
Fever, arthralgias
of multiple joints,
and multiple skin
lesions
Fatigue, malaise,
fever and weight
loss
Fever may be
present
Weakness, fatigue,
weight loss, and
low fever are
common,
lymphadenopathy
and splenomegaly
Radiologic feature
Classic pencil-cup
deformity, marginal
erosions w/
adjacent bony
proliferation
(whiskering), smalljoint ankylosis,
osteolysis of
phalangeal and
matecarpal bone,
periostitis
Soft-tissue
swelling, jointspace widening,
displacement of
tissue planes by
distended capsule
Absent or confined
to juxtaarticular
osteoporosis,
marginal erosions
and loss of joint
space, Periostitis w.
reactive new bone
formation, spurs at
the inseertion of
plantar fascia
Cystic changes well
defined erosion
with sclerotic
margins (often
overhanging bony
edges)
Soft tissue masses
characterized radio
features of
advanced chronic
tophaceous gout
Soft tissue swelling
and joint effusion
Juxta articular
osteopenia
loss of articular
cartilage
Bone erosion
Associated
deformities
Pencil-cup
deformity
Telescoping of
fingers/ Operaglass deformity
Heberden’s node
Bouchard’s node
Swan node
deformity,
Boutonniere
deformity, Baker’s
cyst
Extraarticular
Manifestations
Psoriatic skin
lesions
Conjunctivitis
Uric acids
nephrolithiasis
Rheumatoid
nodules
Rheumatoid
vasculitis
Pleuropulmonary
manifestations
Caplan’s & Felty’s
syndrome
Urogenital lesions
Conjunctivitis
Keratoderma
blenorrhagica
Circinate Balanitis
24
CLINICAL IMPRESSION:
PSORIATIC ARTHRITIS
3C-MED
25
An inflammatory arthritis that
characteristically occurs in a patient
with psoriasis.
Harrison’s Internal Medicine 17th edition
A form of arthritis that occurs in
patients with psoriasis with the
hallmarks of an "inflammatory"
arthritis, including joint pain,
erythema, and swelling, often with
prominent stiffness.
Mease, P., Menter, A. (2005) , Psoriatic Arthritis: Understanding Its Pathophysiology and
Improving Its Diagnosis and Management. Retrieved from:
26
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
27
EPIDEMIOLOGY
• 5-30% prevalence of PsA among
individuals with psoriasis
• 60 – 70% psoriasis precedes joint disease
• 15 – 20% psoriasis and PsA appear within
1 yr of each other
• 15-20%arthritis precedes the onset of
psoriasis
• M=F
• 2 peaks in onset:
– 20 – 30 y/o
– 50 – 60 y/o
Harrison’s Principles of Internal Medicine 17th edition
Feldman, Pearce, Epidemiology, Clinical manifestations, and Diagnosis of Psoriasis;
28
May 13, 2009
PATHOPHYSIOLOGY
3C-MED
29
Psoriasis
• VIDEO HYPERLINK
30
31
32
CLINICAL FEATURES
3C-MED
33
CLINICAL FEATURES
• pain and stiffness in the affected joints
– morning stiffness lasting more than 30 minutes
– stiffness accentuated with prolonged
immobility
– alleviated by physical activity
• On PE :
– stress pain
– joint line tenderness
– effusions in the affected joints
• asymmetric distribution
• The distal interphalangeal joints and spine
affected in 40 to 50 % percent of cases
Gladman,D. (2008), Clinical Manifestations of Psoriatic Arthritis,
34
Clinical Features
• Unique to Psoriatic Arthritis:
– DIP joint involvement
– Nail changes
– Dactylitis
– Enthesitis
– Spondylitis Lytic and periarticular new
bone formation x-ray features
– Iritis or Uveatis
Mease, P., Menter, A. (2005) , Psoriatic Arthritis: Understanding Its Pathophysiology and Improving Its Diagnosis and Management.
Retrieved from: http://cme.medscape.com/viewarticle/509053
35
CLINICAL FEATURES
• SCHEME OF WRIGHT AND MOLL
–
–
–
–
–
ARTHRITIS OF DIP JOINTS
ASYMMETRIC OLIGOARTHRITIS
SYMMETRIC POLYARTHRITIS
AXIAL INVOLVEMENT
ARTHRITIS MUTILANS
• OLIGOARTHRITIS
• POLYARTHRITIS
• AXIAL ARTHRITIS
Harrison’s Principles of Internal Medicine 17th edition
36
Psoriatic Arthritis
Distal Interphalangeal
joint arthritis
• Occurs in 15 % of
cases
• Nail changes also
seen
Harrison’s Internal Medicine 17th edition
37
Psoriatic Arthritis
Asymmetric
Oligoarthritis
• Involves the knee or any
large joint with a few small
joints in the fingers and toes
– Metarsophalangeal
– Proximal interphalengeal
– Distal interphalengeal
•
Dactylis
– Sausage shaped digits due to
inflammation of the flexor tendons and
synovium and pitting edema of the
distal extremities may be observed
Harrison’s Internal Medicine 17th edition
38
Psoriatic Arthritis
Symmetric polyarthritis
• Affects the Hands, wrists,
knees, and feet
symmetrically
– Proximal interphalangeal joints
– Metacarpophalangeal joints
• Peripheral joints are less
tender compared to RA
Harrison’s Internal Medicine 17th edition
39
Psoriatic Arthritis
Axial Arthropathy
• Spine and sacroiliac
joints
Harrison’s Internal Medicine 17th edition
40
Psoriatic Arthritis
Arthritis mutilans
• Widespread shortening
or telescoping of digits
due to osteolysis of the
phalanges and
metacarpals
• coexisting with
ankylosis and
contractures in other
digits
• opera-glass deformity
or pencil-in-cup
radiographic findings
• Fever
Harrison’s Internal Medicine 17th edition
41
CLINICAL FEATURES
Articular features:
• DACTYLITIS
• ENTHESITIS
• TENOSYNOVITIS
• “TELESCOPING”/SHORTENING OF DIGITS
• BACK AND NECK PAIN AND STIFFNESS
• NAIL CHANGES:
– PITTING, HORIZONTAL RIDGING,
ONYCHOLYSIS, YELLOWISH DISCOLORATION
OF NAIL MARGINS, DYSTROPHIC
HYPERKERATOSIS, COMBINATION
42
Nail Changes
• Pitting
• Horizontal
ridging
• Onycholysis
• Discoloration of
nail margins
• Dystrophic
hyperkeratosis
Nail pitting
Onycholysis
Onychodystrophy
Harrison’s Internal Medicine 17th edition
43
Dactylitis
Involvement of the distal and proximal
interphalangeal joints, together with
tendon sheath involvement, may give the
digit a sausage shape
Enthesitis
Inflammation at the sites of ligamentous and
tendinous insertions
Harrison’s Internal Medicine 17th edition
44
The Classification Criteria for Psoriatic
Arthritis (CASPAR)
• Presence of musculoskeletal inflammation (an
inflammatory arthritis, enthesitis, or back pain);
PLUS any three of the following:
• Skin psoriasis (present, previously present by history,
or a family history of psoriasis if the patient is not
affected)
• Nail lesions (onycholysis, pitting, and hyperkeratosis )
• Dactylitis (present or past)
• Negative rheumatoid factor
• Juxtaarticular bone formation on radiographs
These criteria have now been tested in psoriatic
arthritis and were both sensitive (91.4%) and
specific (98.7 %)
Taylor W, Gladman D, Helliwell P, etal. CASPAR Study Group. Classification criteria for psoriatic arthritis:
development of new criteria from a large international study. Arthritis Rheum. 2006 Aug;54(8):2665-45
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
46
DIAGNOSTIC WORK-UPS
3C-MED
47
• NO diagnostic laboratory tests
• ↑ESR and ↑ CRP
• Extensive psoriasis = uric acid may
be elevated
• Check for gout
• Test for HLA-B27
48
Reference
8/27/09
Hgb
120-170 d/L
105
Hct
RBC
0.37-0.54
Reference
4-6x 10^12/L
0.32
8/27/09
4.03
WBC
Hgb
Neutrophil
4.5-10x 10^9/L
120-170 d/L
0.50-0.70
8.60
105
0.70
Segs
Hct
Bands
0.50-0.70
0.37-0.54
0.70
0.32
Lympho
Plt
Mono
0.20-0.40
150-450x 10^9/L
0-0.07
0.30
552
Eos
MCV
0-0.05
87
+/-5 U^3
79.60
Plt
RDW
MCV
150-450x 10^9/L
25.90
87 +/-5 U^3
552
13.40
79.60
MCH
29+/-2 pg
26.0
MCHC
34+/-2 g/dL
32.70
RDW
25.90
13.40
49
Reference
8/27/09
BUN
9-23
6.9
Crea
0.5-0.2
0.76
AST-SGOT
0-32
27.3
ALT-SGPT
0-31
41.2
50
Urinalysis 8/27/09
Color
Transparency
pH
Dark yellow
Clear
8
Spec gravity
albumin
Sugar
1.015
Negative
negative
Hyaline cast
Granular cast
RBC
Pus cells
0-3/hpf
0-2/hpf
Bacteria few
Squamous cells
Few
51
• Check for rheumatoid factor for coincident
occurrence of rheumatoid arthritis
• Check for autoantibodies
• Sudden onset is assoc. with HIV so check
for HIV disease
• Nail scrapings – fungal cultures to rule out
fungal infection
• Gram stain and blood culture for bacterial
infection
Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology 5th ed
52
Synovial Fluid Analysis
Fluid Group
Color
Clarity
Viscosity
Mucin Clot
Cells/mm3
% of WBC
that are
PML
Normal
Pale yellow
Transparent
High
Good (<200)
<25%
Group 1 (Non
inflammatory)
Yellow or
straw
Transparent
High
Good
<2,000
<25%
Group II
(Moderately
inflammatory
Yellow or
Straw
Transparent
to opaque,
slightly
cloudy
Variably
decreased
Fair to
poor
3,00050,000
>70%
Group III (Highly
inflammatory,
septic)
Variable;
yellow-gray,
purulent
Opaque, cloudy
Low
Poor
50,000100,000
(usually
<100,000)
>75%, close
to 100%
Group IV
(Hemorrhagic)
Red
Opaque
High
Good
Up to normal
count in
blood
May be the
same as
normal blood
53
RADIOGRAPHIC
IMAGING
3C-MED
54
Pencil-in-cup
deformity
• DIP involvement – “pencil-in-cup”
deformity
http://www.hopkins-arthritis.org/arthritis-info/psoriatic-arthritis/diagnosis.html
55
ArthritisAnkylosis
Mutilans
Pencil-in-cup
deformity
Gladman, D. (2009). Clinical manifestations and diagnosis of psoriatic arthritis. Retrieved September 07,
2009 from http://www.uptodate.com/online/content/topic.do?topicKey=spondylo/2133&view=print
56
• Asymmetric sacroiliiitis
57
• spondylitis
• Severe cervical spine involvement but
relative sparing of thoracolumbar spine
58
Active
Inflammation
Active sacroiliitis
T1-weighted image
Short tau inversion
recovery (STIR) image
Magnetic resonance imaging in psoriatic arthritis: a review of the literature. Retrieved from http://arthritisresearch.com/content/8/2/207/figure/F6
59
MANAGEMENT AND
TREATMENT
3C-MED
60
Treatment Plan
Management
Goals
Pharmacologic
Relieve pain
•NSAIDS
•Analgesics
Non-Pharmacologic
•Paraffin bath
•Splinting
Note
Treat secondary infections prior to administration of immunosuppressive agents
Control Psoriatic
Arthritis
Management of
Psoriatic Lesions
•Biologics
•DMARDS
•Rehabilitation
•Lifestyle Modification
•Topical
•Systemic
•Phototherapy (PUV-A)
•Tar Compounds
61
PAIN MANAGEMENT
62
Tramadol
 Used to manage moderate to
moderately severe pain
 Mechanism of Action: centrally acting
analgesic that binds to μ-opioid
receptor and additionally inhibits reuptake of Norephinephrine and
Serotonin
 Adverse Effects: anaphylactoid
reactions, seizures
 Drug Interactions:
 Carbamazepine – inc. metabolism
 Quinidine – inc. Levels of tramadol
 Avoid in patients taking SSRI’s and MAO
inhibitors
63
According to a study published in the
American Journal of Surgery:
– Combination tramadol/paracetamol have
faster onset, longer duration, and greater
pain relief than tramadol or paracetamol
alone
64
Treatment of Psoriatic Arthritis
DMARDS
Drug
MOA
Dose
Toxicity
Drug Interaction
Methotrexate
•dihydrofolate
reductase inhibitor
•Oral
•15 – 25
mg/wk
Renal
dysfunction,
Nausea, and
Mucosal
Ulcers
concentration w/
hydroxychloroquine
Cyclosporine
•Calcineurin
inhibitor
•Oral
•3-5
mg/kg/day
•2 doses
Nephrotoxicity
toxicity with
diltiazem, K sparing
diuretics and CYP3A
inhibitors
•SC
•50 mg/wk
Macrophage
dependent
infections,
activation of
latent TB
Etanercept
BIOLOGICS
•Anti-TNF-α
Infliximab
•Anti-TNF-α
•IV
•3-5 mg/kg
every 8
wks.
Adalimumab
•Anti-TNF-α
•SC
•40 mg
every other
human antichimeric antibodies
with MTX
clearance with MTX
65
TREATMENT FOR
PSORIATIC ARTHRITIS
66
Etanercept
• Decreases the activity of TNF
• Often used with methotrexate
• Mechanism of Action: binds two
molecules of TNF (α and β) and
prevents them from binding to
cellular receptors
• Adverse Effects: risk of serious
infections, neurologic and
hematologic events, increased
malignant potential, latent TB
activation
67
– The effectiveness of etanercept, a fusion protein directed
against TNF-alpha, in the treatment of psoriatic arthritis
is comparable to that of the antibodies. To achieve a
marked improvement of the cutaneous manifestations,
high doses (50 mg twice weekly) are usually used in the
first 12 weeks.
68
Infliximab
• Chimeric IgGК monoclonal antibody
composed of human and murine regions
• Often used with methotrexate
• MOA: Neutralizes cytokines by binding
specifically to TNF-α
• Adverse Effects: serious infections,
hepatotoxicity, hematologic events,
hypersensitivity reactions, neurologic
events, potential for increased
malignancies, latent TB infection
69
– Infliximab and adalimumab are
therapeutic antibodies directed against
TNF-alpha that are highly effective
against psoriasis vulgaris and psoriatic
arthritis.
70
• The clinical and radiographic efficacy
of adalimumab demonstrated during
short-term treatment was sustained
during long-term treatment.
Adalimumab has a favourable risk–
benefit profile in patients with PsA.
71
Adalimumab
• Recombinant monoclonal antibody
• Mechanism of Action: binds to TNF-α
receptor sites, thus inhibiting
endogenous TNF-α activity
• Adverse Effects: serious infections,
neurologic events, potential for
increased malignancies,
hypersensitivity reactions,
hematologic events, latent TB
infection
72
• “Tumor necrosis factor (TNF)-alpha inhibitors (infliximab,
adalimumab, and etanercept) used in immune-mediated
inflammatory diseases such as rheumatoid arthritis, Crohn's
disease, or psoriatic arthritis have the potential to increase the
risk of infectious complications. Pulmonary infections are one of
the most frequent complications associated with the use of TNF
inhibitors.”
73
Treatment Plan
Management
Goals
Pharmacologic
Relieve pain
•NSAIDS
•Analgesics
Non-Pharmacologic
•Paraffin bath
•Splinting
Note
Treat secondary infections prior to administration of immunosuppressive agents
Control Psoriatic
Arthritis
Management of
Psoriatic Lesions
•Biologics
•DMARDS
•Rehabilitation
•Lifestyle Modification
•Topical
•Systemic
•Phototherapy (PUV-A)
•Tar Compounds
74
TREATMENT FOR
PSORIASIS
75
Alefacept
• Usually for plaque psoriasis
• Immunosuppressive dimeric fusion protein
• Consists of extracellular CD2 binding
portion of human leukocyte function
• MOA: Interferes with lymphocyte activation
resulting in the reduction in subsets of CD2
lymphocyte and circulating CD4 and CD8
lymphocyte counts
• Administration: IM
• Warnings: Lymphopenia, increased
malignancies and serious infections
Basic and Clinical Pharmacology, 10th Ed
Harrison’s Principles of Internal Medicine, 17th Ed
76
Efalizumab
• Usually for SEVERE psoriasis
• Immunosuppresive recombinant humanized
anti CD11a monoclonal antibody
• MOA: Binding to CD11a inhiits the interaction
of LFA-1 on all lymphocutes with intercellular
adhesion molecule inhibiting activation,
adhesion and migration of T-Lymphocytes into
skin
• Administration: SC injection
• Warnings: Serious infections, potential
increased malignancy, thrombocytopenia,
hemolytic anema and worsening of psoriasis
* Should not be given with other immunosuppresive
medication
Basic and Clinical Pharmacology, 10th Ed
Harrison’s Principles of Internal Medicine, 17th Ed
77
Cyclosporine
• Immunosuppresive agent
– Calcineurin inhibitor
• MOA:Form a complex with cyclophilin that
inhibits the cysoplasmic phosphatase,
calcineurin, which is necessary for
activation of T-cell specific transcription
factor
• Adverse effects: Renal dysfunction,
hypertension, hyperkalemia,
hyperuricemia, hypomagnesemia,
hyperlipidemia, increased risk of
malignancies
*reported to benefit Psoriatic arthritis
Basic and Clinical Pharmacology, 10th Ed
Harrison’s Principles of Internal Medicine, 17th Ed
78
Methotrexate
• Antimetabolite
• MOA: Inhibition of dihydrofolate reductase, an
enzme important in the production of
thymidine and purines
– May interfere with actions of interleukin-1
– May also simulate increased release of
adenosine, and endogenous anti-inflammatory
autocoid
– May stimulate apoptosis and death of activated T
Lymphocytes
• Administration: Oral
• Adverse effects: Hepatotoxicity, pulmonary
toxicity, pancytopenia, potential for increased
malignancies , ulcerative stomatitis, nausea,
diarrhea, teratogenecity
Basic and Clinical Pharmacology, 10
th
Ed
Harrison’s Principles of Internal Medicine, 17th Ed
79
Acitretin
• Effective in psoriasis (especially pustular forms)
• Metabolite of etretinate , an aromatic retinoid
• Retinoids include natural compounds and
synthetic derivatives of retinol that exhibit vitamin
A activity
• Because vitamin A affects normal epithelial
differentiation, it was investigated as a treatment for
cutaneous disorders
• Administration: Oral
• Adverse Effects: teratogenecity, osteophyte
formation, hyperlipidemia, flare of inflammatory
bowel disease, hepatotoxicity and depression
*Ethanol should be strictly avoided during treatment and for 2
months after discontinuing therapy
Basic and Clinical Pharmacology, 10th Ed
Harrison’s Principles of Internal Medicine, 17th Ed
80
Psoralen with Ultraviolet Light
(PUVA)
• Topically applied or systemically
administered psoralens are combined
with UV-A
• Psoralens
– Tricyclic furocouramins
– intercalated into DNA exposed to UV-A
form adducts with pyrimidine
basesform DNA crosslinksdecrease
DNA synthesisimprovement of psoriasis
• Adverse Effects: skin dryness, actinic
keratoses, increased risk of skin cancer
81
– Psoriasis is a very troublesome disease with a high
economic impact. The patient has an increased risk of
cardiovascular diseases and their complications.
Additionally, one out of five patients develops psoriatic
arthritis.
– MTX and the TNF-alpha antagonists are effective against
the cutaneous manifestations of psoriasis.
82
• Topical Management of Psoriasis
– Polytar shampoo
– Topical corticoids
– Petroleum Jelly
– Vitamin D analogues (cacipotriol,
tacalcitol)
– Other skin care products
83
– Topical corticoids of strength classes II and III have a
favorable risk/benefit profile when properly used and are
also very effective against itching, from which about twothirds of patients suffer.
– A combined preparation consisting of the vitamin D3
analogue calcipotriol together with a corticoid of
intermediate strength, which was studied in a controlled
trial over a study interval of an entire year, is very
effective and is often used as first-line treatment.
84
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
85
COMPLICATION
3C-MED
86
Psoriasis
Psoriatic
Arthritis
Risk Factors:
• Immunocompromised
due to meds
• Auspitz sign – break in
skin integrity
Cellulitis
87
Psoriasis
Immunocompromised
patient due to
medications
Indigenous flora
colonizing the skin
 Staphylococcus
aureus
 Streptococcus
pyogenes
Exogenous bacteria
Auspitz sign
Break in the skin integrity
Bacteria gains access to
the epidermis
Acute inflammation of the
dermis and subcutaneous
tissue
Cellulitis
Harrison’s Principles of Internal Medicine 17th ed.
88
Cellulitis
• At the involved site
– Localized pain
– Erythema
– Swelling
– Warmth
– Borders are not
sharply demarcated
• Fever and chills
• Malaise
Harrison’s Principles of Internal Medicine 17th ed.
89
Primary Treatment for Cellulitis
• Nafcillin or oxacillin, 2 g IV q4 – 6h
– Beta Lactam Antibiotics
– MOA: interferes with the
transpeptidation reaction of bacterial
cell wall synthesis
– Indications: Susceptible infections due
to penicillinase-producing
staphylococci.
– AE: hypersensitivity
– DI: May be antagonized by tetracycline.
Potentiated by probenicid.
90
Alternative Treatment for Cellulitis
• Cefazolin 1 g IV q8
– MOA: inhibits cell wall synthesis
– Indications: Respiratory, GIT, GUT, otic
and bone, skin, soft tissue and post-op
infections, bacteremia, septicemia,
endocarditis, surgical prophylaxis
– AE: Shock, hypersensitivity reaction,
granulocytopenia, eosinophilia or
thrombocytopenia, GI disturbances,
CNS effects
– DI: Aminoglycosides, potent diuretics,
probenecid
91
OBJECTIVES
• To present a case of a 28 y/o male
with Psoriatic Arthritis (PsA)
• Differential Diagnoses
• Psoriatic Arthritis
– Epidemiology
– Pathophysiology
– Clinical Features
• Approach to a Patient with PsA
• Complications, Outcome and
Prognosis of PsA
92
Summary Slide
• A case of a 28 y/o male patient with PsA
• Psoriatic Arthritis
• Approach to a Patient with asymmetric
polyarthritis
• Management of Psoriatic Arthritis
• Complications of Psoriasis - Cellulitis
93
THANK YOU!
94