7. A chronic joint disorder in which there is
progressive softening and disintegration of
articular cartilage accompanied by new growth of
cartilage and bone at the joint margins
(osteophytes) and capsular fibrosis
16. Femoral neck buttressing
Tilt deformity ( flattening of head surface with
osteophyte at anteroinferior aspect)
Superior >medial migration
Secondary OA due to previous trauma or
inflammatory arthritis
17.
18. Erect weight-bearing AP film
Unicompartmental
Sharpening of tibial prominence
Loose bodies
Varus deformity
Patellar tooth sign – irregular anterior patellar
surface
38. Boutonniere deformity :
flexion deformity at PIP jt & hyperextension at
DIP
• Swan neck deformity :
combination of flexion at DIP
and extension at PIP
53. ◦ Rheumatoid arthritis is a synovial disease
-Osteoarthritis is a disease of the cartilage.
-Volar subluxation never in osteoarthritis
Normal joint
55. Most of the disability in RA is a result of the
INITIAL burden of disease
People get disabled because of:
◦ Inadequate control
◦ Lack of response
◦ Compliance
GOAL: control the disease early on!
68. Competitive inhibitor of dihydroorotate
dehydrogenase (rate-limiting enzyme in de novo
synthesis of pyrimidines)
Reduce lymphocyte proliferation
69. Oral
T ½ - 4 – 28 days due to EHC
Elimination hepatic
Action in one month
Avoid pregnancy for 2 years
74. • Complex protein molecules
• Created using molecular biology methods
• Produced in prokaryotic or eukaryotic cell cultures
75. TNF is a potent inflammatory cytokine
TNF is produced mainly by macrophages and
monocytes
TNF is a major contributor to the inflammatory and
destructive changes that occur in RA
Blockade of TNF results in a reduction in a
number of other pro-inflammatory cytokines (IL-1,
IL-6, & IL-8)
78. Potent anti-inflammatory drugs
Serious adverse effects with long-term use
To control the diaseas
Indications
◦ As a bridge to effective DMARD therapy
◦ Systemic complications (e.g. vasculitis)
79. Most common childhood chronic disease
causing disability.
About 7/100,00 newly diagnosed children
with JIA per year.
Prevalence about 1/1,000 children = 1,000
children in BC with JIA.
7 subtypes.
Disease begins at any time during childhood
or adolescence.
80. To be considered JIA, onset must occur before 16 years of age.
JIA is heterogeneous: the presentation of the disease and its
natural history vary among individuals and over time.
The disease is typically classified into categories based on the
symptoms displayed and their severity.
Systemic arthritis
Oligoarthritis
Rheumatoid-factor positive (RF+) polyarthritis
Rheumatoid-factor negative (RF-) polyarthritis
Enthesitis-related arthritis
Psoriatic arthritis
Undifferentiated
G.ahrq.gov/dmardsjia.cfm.
81.
82. Child under 16 years old
At least one joint with objective signs of arthritis:
› Swelling, or two of the following: pain with movement,
warmth of the joint, restricted movement, or tenderness
Duration of more than 6 weeks
Other causes have been excluded (ex. Infections, Lupus and other
connective tissue diseases, malignancies)
83. All kids with JIA have fevers.
All kids with JIA have rashes.
A child with joint pain (but no arthritis) must have JIA.
All arthritis is painful.
If a child has a positive rheumatoid factor, they must have
arthritis.
If x-rays are normal, there is no arthritis.
84. Heterogeneous group of diseases characterized by chronic
inflammatory processes involving the synovial
membrane, cartilage, and bone
The classification of JIA subgroups based on clinical and
laboratory characteristics including the number of affected joints
and the presence of autoimmune markers
Th1 cell-mediated disorder, driven by a population of T cells
producing inflammatory cytokines and chemokines
85. Joint pain, stiffness, and
swelling: These are the most
common symptoms of JRA,
but many children do not
recognize, or do not report,
pain. Stiffness and swelling
are likely to be more severe
in the morning.
Loss of joint function: Pain,
swelling, and stiffness may
impair joint function and
reduce range of motion.
Some children are able to
compensate in other ways
and display little, if any,
disability. Severe limitations
86. Limp: A limp may
indicate a
particularly severe
case of JRA,
although it also may
be due to other
problems that have
nothing to do with
arthritis, such as an
injury. In JRA, a
limp often signals
knee involvement.
87. Eye irritation, pain, and
redness: These
symptoms are signs of
eye inflammation. The
eyes may be sensitive
to light. In many cases,
however, eye
inflammation has no
symptoms. If the
inflammation is very
severe and not
reversed, it can
cause loss of vision.
The most common
types of eye
88. Recurrent fevers: Fever
is high and comes and
goes with no apparent
cause. Fever may
“spike” (go high) as
often as several times
in one day.
Rash: A light rash may
come and go without
explanation.
89. Myalgia (muscle
aches): This is
similar to that achy
feeling that comes
with the flu. It
usually affects
muscles throughout
the whole body, not
just one part.
90. Lymph node swelling. Swollen lymph nodes
are noticed most often in the neck and under
the jaw, above the clavicle, in the armpits, or
in the inguinal region.
Weight loss. This is common in children with
JRA. It may be due to the child’s simply not
feeling like eating.
91. Growth problems: Children
with JRA often grow more
slowly than average.
Growth may be unusually
fast or slow in an affected
joint, causing one arm or
leg to be longer than the
other. General growth
abnormalities may be
related to having a chronic
inflammatory condition such
as JRA or to the treatment,
especially glucocorticoids
93. The goals: eliminate active disease, normalize
joint function, preserve normal growth, prevent
long-term joint damage, and prevent patient
disability
The American College of Rheumatology Pediatric
30 criteria (ACR Pedi 30) defines improvement as
involving at least 3 of 6 core set variables, with no
more than 1 of the remaining variables worsening
by > 30%.
94. The 6 core set includes
◦ Physician global assessment
◦ active joint count
◦ number of joints with limited range of motion
◦ Inflammatory markers
◦ patient or parent assessments
95. Medication
s
Doses
(mg/kg)
Side effects
Aspirin 50-120 Stomack pain, vomiting,
gastrointestinal
bleedings, headache,
blood in the urine, fluid
retention, thinning and
scarring of the skin
(especially with
naproxen), stomach
ulcer (aspirin).
Ibuprofen 10-30
Tolmentin 10-15
Naproxen 5-20
97. Medication
s
Doses(weekly,
depending
from body
weight )
Side effects
Auranofin,
Ridaura,
Myochrysine
Solganol
20 kg – 10 mg
30 kg – 20 mg
40 kg – 30 mg
50 kg – 40 mg
> 50 kg – 50 mg
Skin rash,
mouth sores,
kidney
problems, a low
blood count or
anemia
104. Identify diagnostic criteria for gout
Identify 3 treatment goals for gout
Name the agents used to treat the acute flares of
gout and the chronic disease of gout
105. Prevalence increasing
May be signal for
unrecognized comorbidities :
( Not to point of searching)
Obesity (Duh!)
Metabolic syndrome
DM
HTN
CV disease
Renal disease
106. ORGAN MEATS
WILD GAME
SEAFOOD
LENTILS
PEAS
ASPARAGUS
YEAST
BEER
Rich foods have a higher
concentration of protein. This could
cause major problems for a person
afflicted with gout.
107. Urate: end product of purine metabolism
Hyperuricemia: serum urate > urate solubility (>
6.8 mg/dl)
Gout: deposition of monosodium urate crystals
in tissues
108. Hyperuricemia caused by
Overproduction
Underexcretion
No Gout w/o crystal deposition
110. Purines are not
properly processed
in our body
Excreted through
kidneys and urine
Hyperuricemia-
build-up of uric acid
in body and joint
fluid
111. Asymptomatic hyperuricemia
Acute Flares of crystallization
Intervals between flares
Advanced Gout & Complications
112. Abrupt onset of severe joint inflammation, often
nocturnal;
Warmth, swelling, erythema, & pain;
Possibly fever
Untreated? Resolves in 3-10 days
90% 1st
attacks are monoarticular
50% are podagra
113. 90% of gout
patients eventually
have podagra : 1st
MTP joint
130. Transplant
Alcohol intake
Highest with beer
Not increased with wine
High BMI (obesity)
Diet high in meat & seafood
131. The Gold standard
Crystals intracellular during attacks
Needle & rod shapes
Strong negative birefringence
132.
133. Acute Gout: septic arthritis, pseudogout,
Reactive arthritis, acute rheumatic fever and other
crystalline arthropathies.
Chronic tophaceus gout: Rheumatoid Arthritis,
Pseudogout, seronegative spondyloarthropathies
and erosive osteoarthritis.
134. Similar Acute attacks
Different crystals under Micro;
Rhomboid, irregular in CPPD
135.
136. Both have polyarticular, symmetric arthritis
Tophi can be mistaken for RA nodules
137.
138. Diet is usually impractical, ineffective and rarely
adhered to in clinical practice.
Indications for pharmacological therapy includes:
inability to reverse secondary causes, tophaceus
gout, recurrent acute gout and nephrolithiasis.
139. 139
•Treat acute flare rapidly with anti-
inflammatory agent
•Initiate urate-lowering therapy to
achieve sUA <6
•Use concomitant anti-inflammatory
prophylaxis for up to 6 mo to prevent
mobilization flares
INITIATE
(acute flare)
RESOLVE
(urate-lowering therapy)
139
•Continue urate lowering therapy
to control flares and avoid crystal
deposition
•Prophylaxis use for at least 3-6
months until sUA normalizes
MAINTAIN
(treatment to control sUA)
140. Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation
Prevent disease progression
Lower serum urate to deplete total body urate pool
Correct metabolic cause
141. Control inflammation & pain & resolve the flare
Not a cure
Crystals remain in joints
Don’t try to lower serum urate during a flare
Choice of med not as critical as alacrity & duration
143. Colchicine- reduces pain, swelling, and
inflammation; pain subsides within 12 hrs and
relief occurs after 48 hrs
Prevent migration of neutrophils to joints
145. Colchicine :
Not as effective “late” in flare
Drug interaction : Statins, Macrolides,
Cyclosporine
Contraindicated in dialysis pt.s
Cautious use in : renal or liver dysfunction; active
infection, age > 70
146. The choice of pharmacologic agent depends on severity of the
attack
◦ Monotherapy for mild/moderate attack
◦ Combination therapy for severe attack or those refractory to
monotherapy
Acceptable combination therapy approaches include
◦ Colchicine and NSAIDS
◦ Oral steroids and colchicine
◦ Intra-articular steroids with all other modalities
Continue current therapy during flare
Patient education on signs of flare for self treatment
146Kanna D, et al. Arthritis Care Res (Hoboken). 2012 Oct;64(10):1447-61
147. Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation
Prevent disease progression
Lower serum urate to deplete total body urate
pool
Correct metabolic cause
148. Hyperuricemia ≠ Gout
Goal sUA < 6
Use prophylaxis for at least 3 months after
initiating gout therapy
Do not stop gout medication unless patient is
showing evidence of drug toxicity or adverse
reaction
Ask your friendly rheumatologist for help!
148
149. Colchicine : 0.5-1.0 mg/day
Low-dose NSAIDS
Both decrease freq & severity of flares
Prevent flares with start of urate-lowering RX
Best with 6 mos of concommitant RX
Won’t stop destructive aspects of gout
150. Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation
Prevent disease progression
Lower serum urate to deplete total body urate
pool
Correct metabolic cause
151. Lower urate to < 6 mg/dl : Depletes
Total body urate pool
Deposited crystals
RX is lifelong & continuous
MED choices :
Uricosuric agents
Xanthine oxidase inhibitor
152.
153.
154. Probenecid, (Losartan & fenofibrate for mild
disease)
Increased secretion of urate into urine
Reverses most common physiologic abnormality
in gout ( 90% pt.s are underexcretors)
155. Patients taking uricosuric agents are at risk for
urolithiasis. This can be decreased by ensuring
high urinary output and by adding sodium
bicarbonate 1 gram TID.
The available agents include: probenecid (1-2
g/day) and sulfinpyrazone (50-400 mg BID).
Dose should be increased to decrease uric acid <
6.0 mg/ml
156.
157. Allopurinol :
Blocks conversion of hypoxanthine to uric acid
Effective in overproducers
May be effective in underexcretors
Can work in pt.s with renal insufficiency
159. Oxypurinol, allopurinol metabolite, cleared by kidney and
accumulates in patients with renal failure
Oxypurinol inhibits xanthine oxidase
Increased oxypurinol related to risk of allopurinol
hypersensitivity syndrome
allopurinol oxypurinol
Xanthine
Oxidase
Stevens-
Johnson
Syndrome
Allopurinol
Hypersensitivity
Syndrome
Toxic Epidermal
Necrolysis
159
160. Allopurinol decreases uric acid in overproducers
and underexcreters; it is also indicated in patients
with a history of urolithiasis, tophaceus gout, renal
insufficiency and in prophylaxis of tumor lysis
syndrome.
161. Allopurinol: usual dose is 300 mg/day. Maximal
recommended dose is 800 mg/day.
In renal insufficiency dose should be decreased to
200 mg/day for creatinine clearance < 60ml/min
and to 100 mg/day if clearance < 30 ml/min).
162. Start with small doses of allopurinol to reduce the
risk of precipitating an acute gout attack.
Most common side effects are rash (2% of
patients) but rarely patients can develop
exfoliative dermatitis that can be lethal.
Chronic use of colchicine (0.6-1.2 mg/day) is used
as prophylaxis for acute attacks.
163. 2% of all allopurinol users develop cutaneous rash
Frequency of hypersensitivity 1 in 260
DRESS syndrome
◦ Drug Reaction, Eosinophilia, Systemic Symptoms
20% mortality rate
Life threatening toxicity: vasculitis, rash, eosinophilia,
hepatitis, progressive renal failure
Treatment: early recognition, withdrawal of drug,
supportive care
◦ Steroids, N-acetyl-cysteine, dialysis prn
Markel A. IMAJ, 2005.
Terkeltaub RA, in Primer on the Rheumatic Disease, 13th
ed. 2008.
163
164. Base choice on above considerations & whether
pt is an overproducer or underexcretor : Need to
get a 24-hr. urine for urate excretion:
< 700 --- underexcretor
(uricosuric)
> 700 --- overproducer
(allopurinol/ febuxostat)
165. Allopurinol Uricosuric
Issue in renal disease X X
Drug interactions X X
Potentially fatal hypersen-
sitivity syndrome X
Risk of nephrolithiasis X
Mutiple daily dosing X
167. Non-purine selective inhibitor of xanthine oxidase
Lowers serum uric acid levels more potently than allopurinol while having
minimal effects on other enzymes associated with purine and pyrimide
metabolism
Frequent adverse events reported in clinical trials liver function
abnormalities, nausea, arthralgias, and rash
Available as 40- and 80-mg tablets
Recommended starting dosage is 40 mg orally once daily. If serum uric
acid concentrations are not less than 6 mg/dL after two weeks, the dosage
can be increased to 80 mg orally once daily
Dosage adjustments are not needed in elderly patients or patients with mild
or moderate renal or hepatic impairment.
.
168. Therapeutic goal of urate-lowering therapy is
sUA <6.0 mg/dL
Urate lowering therapy indications:
◦ Recurrent gout attacks
◦ Tophi and/or radiographic changes on initial presentation
Address associated risk factors and
comorbidities – tailor to the individual
168
Zhang W, et al. Ann Rheum Dis. 2006; 65: 1312-1324.
168
169. Lifestyle Modification for all patients with gout
Xanthine Oxidase Inhibitor (XOI) first-line urate-lowering
pharmacologic therapy
Target sUA <6 at minimum, sUA <5 better
Starting dose of allopurinol should be 100mg, less in CKD with
titration above 300mg prn if needed (even in CKD)
Continue prophylaxis for 3 (no tophi) – 6 months (tophi) after
achieving target sUA
169Khanna D, et al. Arthritis Care Res . 2012 Oct;64(10):1431-46
170. Gout is chronic with 4 stages
Uncontrolled gout can lead to severe disease
Separate RX for flares & preventing
advancement
Many meds for flares
Treating the disease requires lowering urate
Get a 24-hr urine for urate excretion
171. Calcium pyrophosphate Crystal Deposition
Disease (CPPD) is the syndrome secondary to the
calcium pyrophosphate in articular tissues.
This includes: Chondrocalcinosis, Chronic CPPD
and Pseudogout.
172. Etiology: It is unknown, but can be secondary to
changes in the cartilage matrix or secondary to
elevated levels of calcium or inorganic
pyrophosphate.
Pathology: CPPD crystals are found in the joint
capsule and fibrocartilaginous structures. There is
neutrophil infiltration and erosions.
173.
174. Demographics: It is predominantly a disease of
the elderly, peak age 65 to 75 years old. It has
female predominance (F:M, 2-7:1).
Prevalence of chondrocalcinosis is 5 to 8% in the
general population.
176. Clinical Manifestations
Pseudogout: Usually presents with acute self-
limited attacks resembling acute gout. The knee
is involved in 50% of the cases, followed by the
wrist, shoulder, ankle, and elbow.
177. In 5% of patients gout can coexist with
pseudogout.
The diagnosis is confirmed with the synovial fluid
analysis and/or the presence of chondrocalcinosis
in the radiographs.
Acute Pseudogout primarily affects men.
178. Chondrocalcinosis: Generally is an incidental
finding in XRays.
Diagnostic Tests: Inflammatory cell count in the
synovial fluid. Rhomboidal or rodlike intracellular
crystals. Imaging studies reveal
chondrocalcinosis usually in the knee, but can be
seen in the radial joint, symphisis pubis and
intervertebral discs.
179. Chronic CPPD: predominately affects women; it is
a progressive, often symmetric, polyarthritis.
Usually affects the knees, wrists, 2nd and 3rd
MCP’s, hips, spine, shoulders, elbows and ankles.
Chronic CPPD differs from pseudogout in its
chronicity, involvement of the spine and MCP’s.
180. Differential Diagnosis: Includes septic arthritis,
gout, inflammatory OA, Rheumatoid Arthritis,
neuropathic arthritis and Hypertrofic
Osteoarthropathy.
181.
182. Therapy: It is similar to gout and includes
intrarticular corticosteroids. Colchicine can be
used in acute attacks and also in prophylaxis.
There is no specific treatment for chronic CPPD. It
is important to treat secondary causes and
colchicine could be helpful.
188. Spondyloarthropathies
Axial and Peripheral
AMOR criteria (1990)
ESSG criteria (1991)
Axial Spondyloarthritis
ASAS classification 2009
Ankylosing spondylitis
Prototype of axial spondylitidis
Modified New York criteria 1984
Peripheral Spondyloarthritis
ASAS classification 2010
Psoriatic arthritis
From Moll & Wright 1973 to CASPAR criteria 2006
Sieper et al. Ann Rheum Dis 2009;68:ii1-ii44
Taylor et al. Arthritis & Rheum 2006;54:2665-73
Van der Heijde et al. Ann Rheum Dis 2011;70:905-8
ESSG: European Spondyloarthropathy Study Group
ASAS: Assessment of Spondyloarthritis International Society
CASPAR: Classification criteria for psoriatic arthritis
Infliximab (IFX) and Golimumab (GLM)
indications
189. AS is a chronic, progressive immune-mediated inflammatory
disorder that results in ankylosis of the vertebral column and
sacroiliac joints1
The spine and sacroiliac joints are the common affected sites1
◦ Chronic spinal inflammation (spondylitis) can lead to fusion
of vertebrae (ankylosis)1
1
Taurog JD. et al. Harrison‘s Principles of Internal Medicine, 13 th Ed. 1994: 1664-67.
190. Normal interspace 2-5mm
B/L symmetric
Lower two third
Rosary bead appearance
Reactive sclerosis
Bony ankylosis
osteoporosis
SACROILITIS
199. • Mortality figures parallel RAMortality figures parallel RA6,7,86,7,8
““Rare”Rare”
““Not” a serious disease, functional limitation isNot” a serious disease, functional limitation is
mildmild
““Rarely shortens life”Rarely shortens life”
• Burden of disease significant in pain, sick leave, early retirementBurden of disease significant in pain, sick leave, early retirement3,4,53,4,5
• 0.1-0.9%0.1-0.9%1,21,2
11
Sieper J et al.Sieper J et al. Ann Rheum Dis.Ann Rheum Dis. 2002; 61 (suppl 3);iii8-18.2002; 61 (suppl 3);iii8-18.
22
Lawrence RC., Arthritis Rheum 1998; 41:778-99.Lawrence RC., Arthritis Rheum 1998; 41:778-99.
33
Zink A., et al.,Zink A., et al., J RheumatolJ Rheumatol 2000; 27:613-22.2000; 27:613-22.
44
Boonen A.Boonen A. Clin Exp RheumatolClin Exp Rheumatol. 2002;20(suppl 28):S23-S26.. 2002;20(suppl 28):S23-S26.
55
Gran JT, et al.Gran JT, et al. Br J RheumatolBr J Rheumatol. 1997;36:766-771.. 1997;36:766-771.
66
Wolfe F., et al. Arthritis Rheum. 1994 Apr;37(4):481-94.Wolfe F., et al. Arthritis Rheum. 1994 Apr;37(4):481-94.
77
Myllykangas-Luosujarvi R, et al.Myllykangas-Luosujarvi R, et al. Br J Rheumatol.Br J Rheumatol. 1998;37:688-690.1998;37:688-690.
88
Khan MA, et al.Khan MA, et al. J Rheumatol.J Rheumatol. 1981;8:86-90.1981;8:86-90.
99
Braun J., Pincus T., Clin Exp Rheumatol. 2002; 20(6 Suppl 28):S16-22.Braun J., Pincus T., Clin Exp Rheumatol. 2002; 20(6 Suppl 28):S16-22.
200. The incidence of AS may be underestimated
due to unreported cases1
HLA-B27 gene is associated with AS6
Age of onset typically between 15 and 35
years1,2,3
2-3 times more frequent in men than in women6
1
The Spondylitis Association of America. Available at: www.spondylitis.org. Accessed December
2,2004. 61(suppl 3);iii8–18. 6
Khan MA. Ann Intern Med. 2002;136:896–907.
201. Axial manifestations:
• Chronic low back pain
• With or without buttock pain
• Inflammatory characteristics:
– Occurs at night (second part)
– Sleep disturbance
– Morning stiffness
• Limited lumbar motion
• Onset before age of 40 years
Sengupta R & Stone MA.
Inflammatory back
pain (IBP) =
Characteristic symptom
MRI sacro-iliac joint
202. AS: Characteristic Pathologic FeaturesAS: Characteristic Pathologic Features
Sieper J. Arthritis Res Ther 2009;11:208
Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035
• Chronic inflammation in:
– Axial structures (sacroiliac joint, spine, anterior chest
wall, shoulder and hip)
– Possibly large peripheral joints, mainly at the lower limbs
(oligoarthritis)
– Entheses (enthesitis)
• Bone formation particularly in the axial joints
203. Most striking feature of AS = New bone
formation in the spine with:
Spinal syndesmophytes
Ankylosis
Both can be seen on conventional
radiography
Bamboo spine and
bilateral sacroiliitis
X-ray showing
syndesmophytes
Even in patients with longer-
standing disease, syndesmophytes
are present in ~ 50% patients and
a smaller percentage will develop
ankylosis
Sieper J. Arthritis Res Ther 2009;11:208
207. The first abnormality to appear in
swollen joints associated with
spondyloarthropathies is an enthesitis2
Likelihood of erosions is higher
for digits with dactylitis than
those without1
1
Brockbank. Ann Rheum Dis 2005;62:188-90;
2
McGonagle et al. The Lancet 1998;352.
208. EAM Prevalence in AS
Patients (%)
Anterior uveitis 30-50
IBD 5-10
Subclinical inflammation of the gut 25-49
Cardiac abnormalities
Conduction disturbances
Aortic insufficiency
1-33
1-10
Psoriasis 10-20
Renal abnormalities 10-35
Lung abnormalities
Airways disease
Interstitial abnormalities
Emphysema
40-88
82
47-65
9-35
Bone abnormalities
Osteoporosis
Osteopenia
11-18
39-59
Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035
Terminal ileitis
Anterior uveitis
Cardiac
abnormalities
209. Bad QoL1
◦ Pain
◦ Sleep problems
◦ Fatigue
◦ Loss of mobility and
dependency
◦ Loss of social life
Effect employability1
Higher rate of mortality2
High socio-economic consequences
AS=23.7 years
90.2
83.1
62.4
54.1
0
20
40
60
80
100
Stiffness Pain Fatigue Poor
SleepN=175
AS mean duration: 23.7 yr
PercentageofPatients(%)
1
210. Adapted from Feldtkeller E et al. Rheumatol Int 2003;23:61–66
Sengupta R & Stone MA. Nat Clin Pract Rheumatol 2007;3:496-503
First symptoms
First diagnosis
Age in years
Males (n=920)
Females (n=476)
0
0 10 20 30 40 50 60 70
20
40
80
60
100
PercentageofPatients(%)
Average delay in diagnosis: 8.8
years
B27(+) 8.5 vs B27(-) 11.4
Delay Worse clinical outcomes contributing to both physical and
work-related disability
211. Modified New York Criteria for AS1
◦ Low back pain > 3 months (improved by exercise and not relieved by
rest)
◦ Limitation of lumbar spinal motion in sagittal and frontal planes
◦ Chest expansion decreased relative to normal
◦ Bilateral sacroilitis grade 2-4 or unilateral sacroilitis grade 3 or 4
Detection of sacroilitis via X-ray or MRI1
◦ MRI can be used for earlier detection of inflammation (enthesitis) at
other sites.
There is no specific laboratory test for AS1
◦ ESR and CRP can indicate inflammation
50-70% of active AS patients will have increased ESR and CRP2
◦ Rheumatoid factor is not associated with AS
◦ HLA-B27
1
Khan M, Ankylosing Spondylitis-the facts; 2002:Oxford University Press:94-98.
2
Sieper J, et al. Ann Rheum Dis. 2002;61(Suppl 8).
212. Diagnostic Standard for AS: Modified NYDiagnostic Standard for AS: Modified NY
Classification Criteria (1984)Classification Criteria (1984)11
• Clinical components:
– Low back pain and stiffness for more than 3 months which
improves with exercise, but is not relieved by rest
– Limitation of motion of the lumbar spine in both the sagittal
and frontal planes
– Limitation of chest expansion relative to normal values
correlated for age and sex
• Radiological component:
– Sacroiliitis Grade >2 bilaterally or Grade 3-4 unilaterally
Definite AS if the radiological criterion is associated with at least one clinical
criterion2
Probable AS if three clinical criteria present or radiologic criteria present
without clinical criteria2
1
Linden VD et al. Arthritis Rheum 1984;27:361-368
2
Rudwaleit M et al. Arthritis Rheum 2005;52:1000-1008
• Old criteria
• Defined before TNF blockers
• Sacroiliitis detectable by X-ray occurs
lately
• No magnetic resonance imaging (MRI)
• Used for clinical trial
213. Adapted from Rudwaleit M et al. Arthritis Rheum 2005;52:1000-1008
Brandt HC et al. Ann Rheum Dis 2007;66:1479-84
Time (years)
Back Pain
Syndesmophytes
Radiographic stage
(Ankylosing Spondylitis)
Back Pain
Radiographic
sacroiliitis
Modified NY criteria (1984)
Diagnostic Standard for AS: Modified NYDiagnostic Standard for AS: Modified NY
Classification Criteria (1984) (Cont’d)Classification Criteria (1984) (Cont’d)
The greatest problem in the management of AS was the lack of effective
treatments. In recent years, NSAIDs and TNF-blockers have been shown to
have good efficacy in the treatment of AS.
214. Adapted from Rudwaleit M et al. Arthritis Rheum 2005;52:1000-1008
Time (years)
Back Pain
IBP
MRI active sacroiliitis
Back Pain
Syndesmophytes
Radiographic stage
(Ankylosing Spondylitis)
Pre-radiographic stage
(Axial undifferentiated SpA)
Back Pain
Radiographic
sacroiliitis
Modified NY criteria (1984)
Diagnostic Standard for AS: Modified NYDiagnostic Standard for AS: Modified NY
Classification Criteria (1984) (Cont’d)Classification Criteria (1984) (Cont’d)
• Recent application of MRI techniques has demonstrated (and confirmed) that ongoing
active (“acute”) inflammation in fact does occur in the sacroiliac joints and/or spine
prior to the appearance of changes detectable radiographically
• The presence and absence of radiographic sacroiliitis in patients with SpA represent
different stages of a single disease continuum
215. In patients with back pain ≥3 months and age at onset <45 years
Sacroiliitis* on imaging
plus
≥1SpA feature**
HLA-B27
plus
≥2 other SpA features**
**SpA features:
•Inflammatory back pain
•Arthritis
•Enthesitis (heel)
•Uveitis
•Dactylitis
•Psoriasis
•Crohn’s disease/ulcerative colitis
•Good response to NSAIDs
•Family history for SpA
•HLA-B27
•Elevated CRP
*Sacroiliitis on imaging:
•Active (acute) inflammation on
MRI highly suggestive of
sacroiliitis associated with SpA
or
•Definite radiographic sacroiliitis
according to modified New York
criteria
Rudwaleit M et al. Ann Rheum Dis 2009;68(6):770-6
OR
216. Patients will be categorized as an ASAS 20 responder if the patient
achieves the following:
◦ >20% improvement from baseline and absolute baseline
improvement of >10 (on a 0-100mm scale) in at least 3 of the
following 4 domains:
Patient global assessment
Spinal pain
Function (BASFI)
Inflammation
Average of the last 2 BASDAI questions concerning level and
duration of morning stiffness
◦ No deterioration from baseline (>20% and absolute change of at
least 10 on a 0-100 mm scale) in the potential remaining domain
Anderson JJ, et al. Arthritis Rheum. 2001;44(8):1876–1886.
217. Chronic progressive, inflammatory disorder of the joints and skin1
◦ Characterized by osteolysis and bony proliferation1
◦ Clinical manifestations include dactylitis, enthesitis,
osteoperiostitis, large joint oligoarthritis, arthritis mutilans,
sacroiliitis, spondylitis, and distal interphalangeal arthritis1
PsA is one of a group of disorders known as the
spondyloarthropathies2
Males and females are equally affected3
PsA can range from mild nondestructive disease to a severely
rapid and destructive arthropathy3
◦ Usually Rheumatoid Factor negative3
Radiographic damage can be noted in up to 47% of patients at a
median interval of two years despite clinical improvement with
standard DMARD therapy4
1
Taylor WJ. Curr Opin Rheumatol. 2002;14:98–103.
2
Mease P. Curr Opin Rheumatol. 2004;16:366–370.
3
Brockbank J, et al. Exp Opin Invest Drugs. 2000;9:1511–1522.
4
Kane D, et al. Rheumatology. 2003;42:1460–1468.
218. Spondyloarthritis (SpA)
The prevalence of SpA is comparable to that of RA (0.5–1.9%)1,2
Psoriasis (Pso)
Psoriasis affects 2% of population
7% to 42% of patients with Pso will develop arthritis3
Psoriatic Arthritis
A chronic and inflammatory arthritis in association with skin psoriasis4
Usually rheumatoid factor (RF) negative and ACPA negative5
◦ Distinct from RA
Psoriatic Arthritis is classified as one of the subtypes of spondyloarthropathies
◦ Characterized by synovitis, enthesitis, dactylitis, spondylitis, skin and nail psoriasis4
1
Rudwaleit M et al. Ann Rheum Dis 2004;63:535-543; 2
Braun J et al. Scand J Rheumatol 2005;34:178-90;
3
Fitzgerald “Psoriatic Arthritis” in Kelley’s Textbook of Rheumatology, 2009;
4
Mease et al. Ann Rheum Dis 2011;70(Suppl 1):i77–i84. doi:10.1136/ard.2010.140582;
5
Pasquetti et al. Rheumatology 2009;48:315–325
Juvenile SpA
Reactive
arthritis
Arthritis
associated with
IBD
PsA
Undifferentiated
SpA (uSpA)
Ankylosing
spondylitis (AS)
RA: Rheumatoid arthritis
219. Affects men & women equally
Occurs in 4-6% up to 30% of patients with known
psoriasis
◦ 60 – 70%: Skin psoriasis first
◦ 15%: Psoriatic arthritis first
◦ 15%: Skin and arthritis diagnosed at same time
220. Prevalence of psoriasis in the general
population: 0.1-2.8%.
Prevalence of psoriasis in arthritis patients:
2.6-7.0%.
Prevalence of arthritis in the general
population: 2-3%.
Prevalence of arthritis in psoriatic patients: 6-
42%.
Epidemiological Evidence
221. Morning stiffness lasting >30 min in 50% of patients1
Ridging, pitting of nails, onycholysis – up 90% of patients vs
nail changes in only 40% of psoriasis cases2,3
Patients may present with less joint tenderness than is usually
seen in RA1
Dactylitis may be noted in >40% of patients2,4
Eye inflammation (conjunctivitis, iritis, or uveitis) — 7–33% of
cases; uveitis shows a greater tendency to be bilateral and
chronic when compared to AS2
Distal extremity swelling with pitting edema has been reported
in 20% of patients as the first isolated manifestation of PsA5
1
Gladman DD. In: Up To Date. Available at: www.uptodate.com. Accessed December 3, 2004.
2
Taurog JD. In: Harrison's Online McGrawHill. Available at: http://www3.accessmedicine.com/popup.aspx?
aID=94996&print=yes. Accessed January 2,2005.
3
Gladman DD. Rheum Dis Clin N Amer. 1998;24:829–844.
4
Veale D, et al. Br J Rheumatol. 1994;33:133–38.
5
Cantini F, et al. Clin Exp Rheumatol. 2001;19:291–296.
222. Helliwell PS & Taylor WJ. Ann Rheum Dis 2005;64(2:ii)3-8
Fitzgerald “Psoriatic Arthritis” in Kelley’s Textbook of Rheumatology, 2009
*Low levels of RF and ACPA can be found in 5-16% of patients; **To a lesser degree than in RA
***Spinal disease occurs in 40-70% of PsA patients
223. 1
Gladman D et al. Arth & Rheum 2007;56:840; 2
Kane. D et al. Rheum 2003;42:1460-1468
3
Gladman D et al. Ann Rheum Dis 2005;64:188–190; 4
Lawry M. Dermatol Ther 2007;20:60-
67
Enthesopathy (38%)2
Dactyilitis (48%)3
DIP involvement (39%)2
Back involvement (50%)1
Nail psoriasis (80%)4, 5
SkinInvolvement
In nearly 70% of patients,
cutaneous lesions precede
the onset of joint pain, in
20% arthropathy starts
before skin manifestations,
and in 10% both are
concurrent. 6
DIP: Distal interphalangeal
224. Pso patients6-8
• Psychosocial burden
• Reactive depression
• Higher suicidal ideation
• Alcoholism
Metabolic Syndrome3-5
• Hyperlipidemia
• Hypertension
• Insulin resistent
• Diabetes
• Obesity
⇒ Higher risk of
Cardiovascular disease (CVD)
Ocular inflammation1
(Iritis/Uveitis/ Episcleritis)
IBD2
1
Qieiro et al. Semin Arth Rheum 2002;31:264; 2
Scarpa et al. J Rheum 2000;27:1241; 3
Mallbris et al. Curr Rheum Rep 2006;8:355;
4
Neimann et al. J Am Acad Derm 2006;55:829; 5
Tam et al. 2008;47:718; 6
Kimball et al. Am J Clin Dermatol 2005;6:383-392;
7
Naldi et al. Br J Dermatol 1992;127:212-217; 8
Mrowietz U et al. Arch Dermatol Res 2006;298(7):309-319
225. D a c t y lit is E n t h e s it is
P s o r ia t ic A r t h r it is
Ritchlin C. J Rheumatol. 2006;33:1435–1438.
Helliwell PS. J Rheumatol. 2006;33:1439–1441.
226. ACR Slide Collection on the Rheumatic Diseases; 3rd
edition. 1994.
1
Brockbank J, et al. Ann Rheum Dis. 2005;64:188–190.
2
Veale D, et al. Br J Rheumatol. 1994;33:133–38.
• Diffuse swelling of a digit may be acute, with painful
inflammatory changes, or chronic wherein the digit remains
swollen despite the disappearance of acute inflammation1
• Also referred to as
“sausage digit”1
• Recognized as one
of the cardinal
features of PsA,
occurring in up
to 40% of patients1,2
• Feet most commonly
affected1
• Dactylitis involved
digits show more
radiographic damage1
227. Entheses are the regions at
which a tendon, ligament, or
joint capsule attaches to
bone1
Inflammation at the
entheses is called enthesitis
and is a hallmark feature of
PsA1,2
Pathogenesis of enthesitis
has yet to be fully
elucidated2
Isolated peripheral
enthesitis may be the only
rheumatologic sign of PsA
in a subset of patients3
1
McGonagle D. Ann Rheum Dis. 2005;64(Suppl II):ii58–ii60.
2
Anandarajah AP, et al. Curr Opin Rheumatol. 2004;16:338–343.
3
Salvarani C. J Rheumatol. 1997;24:1106–1140.
235. Distal asymmetric distribution
Ray pattern
Soft tissue swelling( sausage/spindle)
Preserved bone density
Marginal erosions
Fluffy periosteitis
236. Pencil in cup deformity
Mouse ear sign
Arthritis mutilans
Nonmarginal syndesmophytes
Bilateral asymmetric involvenent of SI joint
237. Including 5 clinical patterns:
◦ Asymmetric mono-/oligoarthritis (~30% [range 12-70%])1-4
◦ Symmetric polyarthritis (~45% [range 15-65%])1-4
◦ Distal interphalangeal (DIP) joint involvement (~5%)1
◦ Axial (spondylitis and Sacroiliitis) (HLA-B27) (~5%)1,3
◦ Arthritis Mutilans (<5%)1,3
References see notes
• However patterns may change over time and are therefore not useful for
classification 5
HLA: Human leucocytes antigen
238. McHugh et al. Rheum 2003;42:778-783
Clinical subgroups at baseline and follow-up:
Monoarthritis Monoarthritis
Oligoarthritis Oligoarthritis
DIP DIP
Polyarthritis Polyarthritis
Spondyloarthritis Spondyloarthritis
Mutilans Mutilans
No clinical evidence of
joint disease
239. Inflammatory articular disease (joint, spine, or
entheseal)
With ≥3 points from following categories:
− Psoriasis: current (2), history (1), family history (1)
− Nail dystrophy (1)
− Negative rheumatoid factor (1)
− Dactylitis: current (1), history (1) recorded by a
rheumatologist
− Radiographs: (hand/foot) evidence of juxta-articular new
bone formation
Specificity 98.7%, Sensitivity 91.4%
Taylor et al. Arthritis & Rheum 2006;54: 2665-73
240. Spondyloarthropathies
Axial and Peripheral
AMOR criteria (1990)
ESSG criteria (1991)
Axial Spondyloarthritis
ASAS classification 2009
Ankylosing spondylitis
Prototype of axial spondylitidis
Modified New York criteria 1984
Peripheral Spondyloarthritis
ASAS classification 2010
Psoriatic arthritis
From Moll & Wright 1973 to CASPAR criteria 2006
Sieper et al. Ann Rheum Dis 2009;68:ii1-ii44
Taylor et al. Arthritis & Rheum 2006;54:2665-73
Van der Heijde et al. Ann Rheum Dis 2011;70:905-8
ESSG: European Spondyloarthropathy Study Group
ASAS: Assessment of Spondyloarthritis International Society
CASPAR: Classification criteria for psoriatic arthritis
Infliximab (IFX) and Golimumab (GLM)
indications
242. Reactive Arthritis
◦ LE arthritis
◦ 1-4 weeks after an
infection
◦ Infectious agents:
Shigella
Salmonella
Yersinia
Campylobacter
Chlamydia
◦ Triad: urethritis,
conjunctivitis, arthritis
◦ Keratoderma
Blennorhagicum
Inflammatory Bowel
Disease Associated
◦ Crohn’s
◦ LE distribution
AAFP
243. Bare area erosions
Terminal tuft erosions
Ray pattern
Irregular periosteal bone apposition
Feet more severely affected than hands’
Severe bone destruction without regional
osteoporosis
Subluxations
245. Psoriatic Arthritis Response Criteria (PsARC)Psoriatic Arthritis Response Criteria (PsARC)
Clegg D.O. et al. Arthritis Rheum 1996;39:2013.
Clinical assessment of joint improvement, no skin
assessment
Improvement in at least 2 of 4 criteria,
one of which must be tender or swollen-joint score
◦ Physician global assessment (> 1 unit)
◦ Patient global assessment (> 1 unit)
◦ Tender-joint score (> 30%)
◦ Swollen-joint score (> 30%)
No worsening in any criterion
246. Urethritis, conjunctivitis, arthritis
Lower extremity
Osteoporosis/soft tissue swelling
Uniform joint space loss
Marginal erosion/periosteitis
Asymmetric broad based nonmarginal
syndesmophytes
Bilateral asymmetric involvenent of SI joint
249. Wave like hyperostosis
Flowing ossification
>4 contiguous vertebras
Thoracic spine
ossified anterior
longitudinal ligament
Normal SI joint
Normal disc space
250. Calcification of cartilage, synovium, capsule,
tendon or ligaments
More than one joint exclusive of the intervertebral
disks.
Crystals aspirated from joints showing absent or
weakly positive birefringence
Joint-space narrowing, sclerosis, cyst formation
Bony fragmentation, and osteophytosis
261. Recurrent attacks of rheumatic fever
Deforning nonerosive peripheral arthropathy
Normal joint space
Juxta articular osteoporosis
Soft tissue swelling
Ulnar drifting
Flexion at MCP
262. Joint pain, swelling, and limitation of motion
3-5 th decade male
Knee> hip
Multiple intraarticular calcified nodules, uniform
in size
Laminated to stippled appearance
Promote early degenarative disease
Chondrosarcoma in 5%
272. Resorption of distal tuft
Retraction of fingertips <20%
Soft tissue calcification
Disuse osteoporosis
Joints may be normal or erosive
arthropathy
292. OA
RA
CPPD
Ankylosing spondylitis
Pigmented villonodular synovotis
Synovial osteochondromatosis
293. AS
IBD
PSORIASIS
REITER’S SYNDROME
OA
INFECTION
294. Certain questions to be answered
1). It is a monoarticular / pauci/ polyarticular
involvement
2). It is synovial or chondropathic
3).if polyarticular, specific distribution and
pattern
4). Sacroiliac and CVJ etc.
5). Clinical presentation (history)
295. Any monoarticular synovial jt. Involvement is
assumed to be infective unless proved
otherwise.
Any monoarticular chondropathic jt. is
considered as degenerative.
Polyarticular jt. Involvement s/o inflammatory
noninfective etiology.
296. Synovial arthropathy:
1). Periarticular osteopenia
2). Jt. Space effusion (soft tissue)
3). Erosions
4). Loss of jt. space (late feature)
297. D/D of synovial arthritis
Infection- >3month---tuberculous
acute onset— pyogenic
RA
Seronegative spondyloarthritis
GOUT
301. PSO RIASIS
REITER'S
RA; SLE
NEURO PATHIC
ALIG NM ENT
O A
CPPD
G O UT
PRESERVED
SUBCHO NDRAL
Pyogenic
G ENERALIZED
CT disorders
JUXTAARTICULAR
RA
LO ST
BO NY
M INERALISATIO N
O A
CPPD
HEM O CHRO .
CARTILAG E
SPACE LO SS
PIP
RA
CPPD
DIP
O A ; REITER'S
PSO RIASIS
DISTRIBUTIO N
INCREASED
PSO RIASIS
REITER'S
DECREASED
SCLERO DERM A
DERM ATO M YO
G ENERALISED LO CALISED
RA
G O UT
SO FT TISSUE
ARTHRITIS
RA
JRA
NFECTIVE
HEMOPHILIA
SLE
RA
JRA
HEMOPHILIA
INFECTIVE
SLE
302. ARTHRITS
Erosive Erosive+ Productive NO Erosion/
Productive Productive
RA Psoriasis OA SLE
Gout Reiter, AS DISH Dermatomyositis
Erosive OA JRA, Neuropathic
Notes de l'éditeur
Destructive effects of TNF
TNF triggers multiple destructive effects in RA. In part, it stimulates osteoclasts to resorb bone, ultimately resulting in bone erosions visible on x-ray.1 TNF also induces the proliferation of synoviocytes, which in turn produces inflammation due to the release of inflammatory mediators.2,3 As depicted here, inflammation not only causes pain and swelling but also has been shown to precede joint damage.2,4 Chondrocytes are a third target of TNF activation, producing collegenase that degrades cartilage and eventually causes joint space narrowing.1,5
In addition to these effects, TNF plays an early role in the inflammatory process by stimulating activation of T cells by foreign antigens.2,3 TNF also induces expression of adhesion molecules, thereby promoting the migration of macrophages and lymphocytes into the synovium.5
References: 1. Goronzy JJ, Weyand CM. Rheumatoid arthritis: epidemiology, pathology, and pathogenesis. In: Klippel JH, ed. Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation; 1997:155-174. 2. Carpenter AB. Immunology and inflammation. In: Wegener ST, ed. Clinical Care in the Rheumatic Diseases. Atlanta, Ga: American College of Rheumatology; 1996:9-14. 3. Albani S, Carson DA. Etiology and pathogenesis of rheumatoid arthritis. In: Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. Vol 1. 13th ed. Baltimore, Md: Williams & Wilkins; 1997:979-992. 4. McGonagle D, Conaghan PG, O&apos;Connor P, et al. The relationship between synovitis and bone changes in early untreated rheumatoid arthritis: a controlled magnetic resonance imaging study. Arthritis Rheum. 1999;42:1706-1711. 5. Rosenberg AE. Skeletal system and soft tissue tumors. In: Cotran RS, ed. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, Pa: W.B. Saunders Company; 1994:1213-1271.
Characteristics of JIA
To be considered JIA, onset must occur before 16 years of age.
JIA is heterogeneous: the presentation of the disease and its natural history vary among individuals and over time.
The disease is typically classified into categories based on the symptoms displayed and their severity:
- Systemic arthritis
- Oligoarthritis
- Rheumatoid-factor positive (RF+) polyarthritis
- Rheumatoid-factor negative (RF-) polyarthritis
- Enthesitis-related arthritis (inflammation of tendons and ligaments at the site of connection to bone)
- Psoriatic arthritis
- Undifferentiated
References:
Goldmuntz EA, White PH. Juvenile idiopathic arthritis: a review for the pediatrician. Pediatr Rev 2005;27(4):e24-25. PMID: 16581950.
http://www.ncbi.nlm.nih.gov/pubmed?term=16581950
Kemper A, Coeytaux R, Sanders G, et al. Disease-Modifying Antirheumatic Drugs (DMARDs) in Children With Juvenile Idiopathic Arthritis (JIA). Comparative Effectiveness Review No. 28 (Prepared by the Duke Evidence-based Practice Center under Contract No. HHSA 290-2007-10066-I). Rockville, MD: Agency for Healthcare Research and Quality; September 2011. AHRQ Publication No. 11-EHC039-EF. Available at www.effectivehealthcare.ahrq.gov/dmardsjia.cfm.
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Perceptions about AS are still wrong today. Physicians diagnose AS late, because they think it is rare, not a serious disease and that patients don’t die as a result of the disease. Patients often seek care late for the same reasons.
Pictures are from the CRI website (http://www.cri-net.com/) and are free for use
IRM des sacro-iliaques – Rehaussement du signal après injection de gadolinium témoignant de l’existence d’une sacro-iliite droite (spondylarthrite ankylosante débutante)
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2 first Pictures come from following website: http://www.rheumatologie-berlin.de/probability/early.php?m_id=9&s_id=91, the third one from the CRI website (http://www.cri-net.com/)
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Dactylitis=painfull swelling of the whole digit caused by inflammation
Pictures from the CRI website (http://www.cri-net.com/)
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Currently, there is a long delay, from 5 to 10 years, between the first occurrence of AS symptoms and a diagnosis of AS. Two major reasons can be named for such a delay:
There is certainly a low awareness of AS among nonrheumatologists and it can be seen as a major challenge for any physician in primary care to think of and to identify patients with inflammatory spine disease among the large group of patients with chronic back pain, most often of another origin.
(b) Radiographic sacroiliitis grade 2 bilaterally or grade 3 or 4 unilaterally is usually a requirement for making the diagnosis of AS according to the modified New York criteria.
However, radiographic changes indicate chronic changes and damage of the bone and are the consequence of inflammation and not active inflammation itself. Since AS is a slowly progressing disease as far as radiographic changes are concerned, definite sacroiliitis on plain radiographs appears relatively late, frequently taking several years of continuous or relapsing inflammation
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Sensitivity 82.9%, specificity 84.4%; n=649 patients with chronic back pain and age at onset &lt;45 yrs.
Imaging arm (sacroiliitis) alone has a sensitivity of 66.2% and a specificity of 97.3%. ** Note: Elevated CRP is considered
a SpA feature in the context of chronic back pain
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Since the BASDAI and BASFI alone do not give a complete disease measurement assessment of the AS patient, the ASAS response criteria was developed. In essence, this combines aspects of the BASDAI and BASFI into one criteria.
ABSTRACT from A&R article follows:
Objective. To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo controlled clinical trials of nonsteroidal anti-inflammatory drugs (NSAIDs).
Methods. Patient data from 5 short-term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple items in the 5 outcome domains for AS treatment: physical function, pain, spinal mobility, patient global assessment, and inflammation. At least one measure per domain was responsive (standardized response mean of &gt;0.5), except for the spinal mobility domain, which was omitted from the criteria. We developed and tested candidate improvement criteria in a random two-thirds subset from the 3 largest trials and used the remaining one-third for validation. These 3 largest trials included 923 patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of &lt;25%. Results. Candidate definitions were changes in single domains and in multiple measure indices, as well as combinations of improvements in multiple domains. Worsening in a domain was defined as a change for the worse of &gt;20% and a net change for the worse of &gt;10 units on a scale of 0–100. Partial remission (for comparison purposes) was defined as an end-of-trial value of &lt;20/100 in each of the 4 domains. Among 20 candidate criteria, change of &gt;20% and &gt;10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; x2 5 36.4, P &lt; 0.001). Results were confirmed in the validation subset. Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement rates using this criterion were 49% for NSAID-treated patients and 24% for placebo-treated patients. Conclusion. Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy-to-use measure of short-term improvement in AS.
PsA is one of a group of disorders known as the spondyloarthropathies. PsA is a chronic, progressive inflammatory disorder affecting the joints and skin characterized by osteolysis and bony proliferation. C
PsA can range from mild and non-destructive in nature to a severely rapid and destructive arthropathy. Radiographic damage can be noted in up to 47% of patients at a median interval of two years despite clinical improvement on standard DMARD therapy.
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Signs and symptoms of PsA in include morning stiffness lasting &gt;30 minutes in 50% of patients, nail involvement in up to 90% of patients (as compared to 40% of psoriasis patients). Patients may present with joint deformity and less pain than is usually seen in RA. Dactylitis may be noted in &gt;40% of patients, eye inflammation in 7-33% of cases. Finally, distal extremity swelling with pitting edema has been reported in 20% of patients as the first isolated manifestation of PsA.
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Medical Review: No Slide: 5/68
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########### Presentation updated on Wednesday, 4 August, 2010 ###########
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Medical Review: No Slide: 5/68
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Two important features of PsA that cause significant problems for PsA patetients. Data to be shared later will show significant benefit of anti-tnf therapy in this regard.
Dactylitis is characterized by swelling of a digit and may be acute with painful inflammatory changes, or chronic changes where the digit remains swollen despite the disappearance of acute inflammation. Digits with dactylitis are referred to as sausage digits. Dactylitis is recognized as one of the cardinal features of PsA, occurring in up to 40% of patients. Feet are most commonly affected. Dactylitis-involved digits show more radiographic damage.
Shown here is psoriasis involving the first, third and fourth toes accompanied by PsA of the interphalangeal joints of the third and fourth toes and dactylitis. The “sausage shape” of these toes is caused by soft-tissue swelling.
Entheses are the regions at which a tendon, ligament, or joint capsule attaches to bone. The entheses act to dissipate biomechanical stress and are subjected to repeated microtraumas. Inflammation at the entheses is called enthesitis and is a hallmark feature of PsA. The pathogenesis of enthesitis has yet to be fully elucidated. Isolated peripheral enthesitis may be the only rheumatologic sign of PsA in a subset of patients.
Psoriatic arthritis is an inflammatory disease, the manifestations of which may include:
Inflammatory arthritis which over time typically progresses to involve greater numbers of joints and can result in joint damage in over 40% of patients
Psoriasis
Diffuse swelling of the fingers and toes known as dactylitis
Enthesitis, which is the inflammation of the point of insertion of tendons, ligaments or joint capsules into bone. Shown here is swelling in the ankle region resulting from the inflammation of the Achilles tendon at the point of insertion into the heel. This is a common site of enthesopathy.
1Moll JMH, Wright V. Psoriatic arthritis. Semin Arthritis Rheum 1973;3:55-78
2Gladman DD et al. Q J Med. 1987;62(238):127-41
3Torre Alonso JC et al. Br J Rheumatol. 1991;30(4):245-50
4Helliwell PS & Taylor WJ, Ann Rheum Dis 2005;64:3-8
5 Gladman et al. Derm therapy 2009;22:40-55
It is important to note that since the original Moll and Wright publication of 1973, the proportion of each subgroup has been changed. The symmetric polyarthritis in the original publication was only 15% and now was shown to be the predominant group. The last 3 bullet points are as in Moll&Wright’s ref.
Helliwell & Taylor, ARD, 2005: Fig.1 shows different distributions of Sym. PolyA and Asym. OligoA according to different references.
For a recent review on SUBTYPES of PsA, PsA classification and a suggestion for a NEW classification, check out Coates & Helliwell, Clinical Rheumatology, July 2008.
Ref1973 Moll1987 Gladman1991 Torre
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DIP&lt;5%DIP involvement
found in all groups-----------------------------------------------------------------------------------------------------------------------------
Arth. Mutilans5%4%
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Symmetric Arth.15% (= PolyA?)30.5% sym PolyA*37% OligoA
+ 36% PolyA
No differentiation
------------------------------------------------------------------------------------------------between symA and
Asymmetric Arth.&gt;70% OligoA28% Asym. OligoAasymA.
+ MonoA+ 30.5% asym PolyA*
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Ankyl.Arth.5%23% SpondA
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HLA-B27Not mentionedNot mentioned
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associated with SpondA
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*Torre, 1991, talks about 61% PolyA, with equal repartition of sym.A and asymA.
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Juxtaarticular: The prefix &quot;juxta-&quot; comes from the Latin preposition meaning near, nearby, close.
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########## Presentation updated on Monday, 16 March, 2009 by KAB3 ##########
########### Presentation updated on Wednesday, 4 August, 2010 ###########
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Triad = Reiter’s syndrome
KB = hyperkeratotic lesions on the palms of hands and soles of feet
NSAIDS first for mild disease
DMARDS for &gt;5 jt involvement – start w/ MTX, then add LEF, then add TNF a inh.