Transcript Rheumatology-6 PPt(modif).

-GOUT
-Pseudogout
Systemic sclerosis
A disease of Kings
Gout has been 
recognized from as early as
the 4th century BC.
Gout is an inflammatory 
arthritis associated with
Hyperuricemia and intraarticular sodium urate
crystals causing attacks of
painful inflammation in one
or more joints.
Acute gout
“Classic” – an obese, 
hypertensive man, age
30 to 50, frequent
imbiber of alcohol
(especially beer)
It is a true crystal deposition 
disease, defined as the
pathological reaction of the
joint or periarticular tissues
to the presence of
MonoSodium Urate
Monohydrate(MSUM)
crystals. It usually favoring
lower rather than upper
limbs especially first
metatarsophalangeal & small
joints of feet & hands.
There is progressive 
involvement of
proximal joints&
cartilages with bone
damage &
development of
secondary OA.
The prevalence of gout is increasing 
mainly in developed countries . It
increases with age with male to
female ratio of 10:1.
Primary gout is a male disease & is 
the most common cause of
inflammatory arthritis in men over
the age of 40. It rarely occurs before
young adulthood ( when it suggests
a specific enzyme defect),& seldom
in premenopausal females .
Secondary gout due to renal 
impairment or drug therapy
affects people over the age of 65
mainly & seen in women in
whom there is an increased
diuretic use. Serum uric acids
are higher in men than
women& positively correlate
with obesity , age&
ethnicity(being higher in
Newzealands).
Hyperuricemia is defined as 
serum uric acid >7.1 mg/dl .
95% of hyperuricemic 
subjects never develop gout.
Causes of primary gout: 1- 
90% of cases are
due to defective renal 
excretion of
uric acid( under execretors). 
2- 9% have intrinsic increased 
production of uric acid (overproducers).
3- 1% have specific inherited enzyme 
defect of purine synthesis & this is when
the age is below 25 years.& in patients
with urate stones.
Risk factors for gout include DM, HT& 
alcohol intake.
Secondary gout results from chronic 
hyperuricemia in patients with renal
impairment, drug therapy especially
aspirin, diuretics , cyclosporine& alcohol.
CLINICAL FEATURES
Clinically, gout may 
present as asymptomatic
hyperuricemia, acute
arthritis, chronic
arthritis, or chronic
tophaceous gout.
Attacks of pain are rapid in onset, 
waking the patient in early
morning. Single distal joint is often
affected(first metatarsal jointpodagra) , but eventually other
joints are affected. The pain is
associated with extreme tenderness
that the patient is unable to wear a
sock. The swelling is marked with
overlying shiny red skin. Complete
resolution of swelling & pain occur
in 5-14 days.
When the attacks subside; pruritus 
& desquamation of overlying skin is
common.
Some patients have only mild 
attacks lasting few days(petit
attacks). Other have one attack
fallowed by other one(cluster
attacks). Some patients have only
one attack & other have repeated
episodes with further deposition of
MSUM.
Eventually chronic pain & joint 
damage occur. White colored
tophaceous nodules are formed
at the extensor surface of
fingers, hand, feet, elbow&
sometimes helix of the ear.
These nodules may ulcerate &
rupture& associated with local
inflammation.
Renal stones occur in 10% of 
urate type in gout patients.
Progressive renal disease is
an important complication
of untreated chronic
tophaceous gout with
subsequent
glomerulosclerosis&
pyelonephritis.
INVESTIGATIONS 
Definitive diagnosis requires 
identification of MSUM
crystals in synovial fluid
from joint , bursa or tophus.
Synovial fluid reveals
increased viscosity &
turbidity ( > 90%
neutrophils).
Hyperuricemia is usually 
evident , but normal serum
uric acid does not exclude
gout (uric acid falls as part
of acute phase response in
acute gout ). 24 hour urine
collection for uric acid on
low purine diet reveals
overproducers.
Renal function test ,RBS, serum 
lipid profile, evaluation of HT,
CRP& ESR are all necessary
investigations.
X ray findings can be delayed 
until late in the disease, where
there is joint space narrowing,
gouty erosions(bony tophi),
sclerosis& OA changes.
MANAGEMENT OF 
GOUT: a fast acting
NSAIDs (naproxen,
diclofenac sodium,
indomethacin ) can give
rapid relief of the pain &
given as maintenance dose.
Oral colchicin( a potent 
neutrophils micro tubular
assembly) can be very effective
but associated with sever
vomiting & diarrhea(1 mg
loading dose then 0.5 mg 6
hourly) until symptoms abate.
Joint aspiration with or without
corticosteroid intraarticular
injection can sometimes
improve the symptoms.
Correction of 
predisposing factors of
gout like DM,
hyperlipidemia, HT, &
avoidance of diuretics&
treatment of obesity all
are necessary .
Hypouricemic drugs are 
indicated for recurrent attacks
of acute gout, tophi, evidence of
bone or joint damage , renal
disease& gout with high serum
uric acid. Allopurinol in a dose
of 100-300 mg daily is the usual
drug . It inhibits xanthine
oxidase & reduces the
conversion of hypoxanthine&
xanthine to uric acid.
.
Uricosuric drugs such 
as probenecid or
sulfinpyrazone can
achieve equivalent
reduction in serum uric
acid to Allopurinol.
Pseudogout It is 
an acute synovitis caused by
deposition of Calcium Pyro
Phosphate Dihydrate(CPPD)
in hyaline & fibro cartilage
of joints resulting in
chondrocalcinosis. It is the
most common cause of acute
monoarthritis in elderly
. Shedding of crystals into a 
joint precipitates acute
synovitis which resembles
gout, except that it is more
common in elderly females&
usually affects knee joint or
wrist. In young people it
may be associated with
hemochromatosis,
hyperparathyroidism, or
Wilson's disease.
Clinically, it is similar 
to OA & management is
similar to gout but
aspiration of synovial
fluid& intra-articular
corticosteroid injections
are mandatory
treatment options.
Systemic sclerosis
Thick skin of fingers and hands
(limited scleroderma)
Morphea
calcinosis
Previously called 
SCLERODERMA, is a
generalized disorder of
connective tissue affecting the
skin, internal organs &
vasculature. This distinguishes
it from localized scleroderma
syndromes , such as morphea,
that do not involve internal
organs& are rarely associated
with vasospasm( Raynaud's
disease).
The clinical hallmark is the 
presence of sclerodactyly in
combination with Raynaud's
phenomenon or digital
ischemia. The peak age of
onset is the 4th& 5th decades
of life with prevalence of 1020/ million population & 4:1
female :male ratio. It is rare
in children.
It is subdivided into diffuse 
cutaneous systemic
sclerosis(DCSS)& limited
cutaneous systemic
sclerosis(LCSS).
LCSS is phenotypically grouped 
into the CREST
syndrome(Calcinosis,
Raynaud's, Esophageal
involvement, Sclerodactyly,
Telangiectasia).
ETIOLOGY & PATHOGENESIS 
:the etiology is unknown with
no genetic , geographical or
racial associations.
Environmental factors are
important in isolated cases, such
as exposure to silica dust, vinyl
chloride, hypoxyresins&
trichloroethylene. Bleomycin
which is a cytotoxic drug can
cause a similar picture.
Early in the disease, there is 
infiltration of T-lymphocytes&
fibroblast activation with increased
type 1-collagen production resulting
in symmetrical thickening ,
tightening & indurations of
skin(sclerodactyly). In addition,
there is an arteriolar narrowing &
vessel wall inflammation with
release of vasoconstrictors& platelet
activation resulting in further
ischemia.
DIAGNOSIS systemic sclerosis is a 
clinical diagnosis, based on the
presence of sclerodactyly(finger
pulp atrophy), beaking of
nails(pseudoclubbing),atrophic
nails,& telangiectasia(nail- fold
capillaries . Most patients have
positive ANA. 30% of diffuse type
have antibodies to topoisomerase(scl-70)& 10% of LCSS
have antibodies to centromere.

Raynaud's 
phenomenon is
common& may be
the first clinical
picture *
*cutaneous features: 
initially there is non
pitting edema of fingers&
tendon sheaths, then the
skin becomes shiny, taut&
distal skin creases
disappear with
involvement of the
nose(peaked nose)& lips.
. Skin involvement distal to 
elbow& knee ( apart from
face) is classified as LCSS or
CREST. Involvement
proximal to knee & elbow &
on the trunk is classified as
DCSS. There may be skin
ulceration over pressure
areas & pulp atrophy at
finger tips.
Scleroderma sine 
scleroderma: skin is not
affected, patients present
with pulmonary fibrosis,
renal crisis, cardiac failure
or malabsorption.
MSK features*: arthralgia, 
morning stiffness, muscle
weakness& wasting due to
myositis.
GIT* : smooth muscle 
atrophy& fibrosis in the
lower two third of
esophagus lead to acid
reflex & esoghagitis which
should be treated with
proton pump inhibitors.
Dysphagia &
odynophagia may occur.
Involvement of stomach 
causes early satiety& outlet
obstruction . watermelon
stomach ( antral vascular
ectasia) may cause occult
upper GIT bleeding & this
occurs in 20% of patients.
. Small intestine 
involvement leads to
malabsorption, bacterial
overgrowth ,pain &
constipation. Autonomic
neuropathy may cause
dilated small & large
bowel & pseudo
obstruction.
Cardiopulmonary 
diseases*: pulmonary
involvement is a major
cause of morbidity &
mortality. Fibrosing
alveolitis occurs mainly in
diffuse disease &
associated with positive
anti topo-isomerase -1.
Pulmonary hypertension occurs 
in limited than diffuse type&
characterized by progressive
dyspnea, right sided heart
failure, angina& associated with
digital ischemia. Treatment
includes vasodilators,
continuous infusion of
epoprostenol, oral endothelin-1
antagonist bosentan& heartlung transplantation.
Renal features*: one of the main 
causes of death is hypertensive renal
crises which characterized by
malignant hypertension & renal
failure. Treatment is usually with
ACE inhibitors even in the presence
of renal impairment. It is more
common in topo-isomerase -1
positive diffuse type. Some
clinicians use prophylactic ACE
inhibitors to prevent this
complication.
Causes of anemia in 
scleroderma:
1-iron deficiency from chronic 
oesophigitis
2-folate &vitaminB-12 
deficiency from malabsorption
3- anemia of chronic disease 
4-microangiopathic hemolytic 
anemia
MANAGEMENT& 
PROGNOSIS :5 years survival
is approximately 70%.
Risk factors at presentation that 
associated with poor prognosis
include old age, DCSS type,
protein urea, high ESR, low gas
transfer factor for carbon
monoxide(TLCO) & pulmonary
HT.
Avoidance of peripheral cold 
exposure is important. Infection of
ulcerated skin should be treated
with heavy dose of antibiotics& for
long time because the drug poorly
penetrate the infected skin. e.g.
flucloxacillin 500 mg 6 hourly.
Calcium antagonists( nifedipine, 
amlodipine)& angiotensin 2
receptor antagonists(valsartan) may
be effective for Raynaud's disease.
For digital ischemia, 
intermittent infusion of
epoprostenol may be helpful.
Corticosteroids & cytotoxic
drugs are indicated for patients
with myositis or alveolitis. Dpencillamine is effective for skin
lesions. No agent has been
shown to arrest or improve skin
lesions.