Before you start:

We are going to talk about Behcets disease, Gout,

Spondyloarthropathy & Scleroderma.
This is supposed to be 2 lec.s but the dr. gave them as
one.
This lecture contains 60 mins of the dr. continuous
talking & 94 slides for the 1st 3 diseases & for the
scleroderma I couldnt get the slides(You dont need to
refer to the slides)
It is very easy lec. Although it is long, but it is full of
figures.

& as usual

Enjoy
Behcets disease

Behcets disease was not that important for someone that lives
in USA or Europe, but nowadays because of migration it is, but
for Middle East countries it is important, because all the time
we see patients with Behcets disease.

What is Behcets disease??

It is chronic relapsing systemic inflammatory disease, it has
certain characteristics that lead us to diagnose the patients as
having Behcets disease, for example if you see hemoptysis or
DVT in young patient, these are alarming signs for Behcets
disease.
Behcets diseases diagnosis is clinically because we dont have a
lab test that we rely on to diagnose it.
Behcets disease is epidemic in the middle east & in the far
east,, in Jordan, in the other Arab countries, Iran, Korea,
China & Japan.
It mostly affects young people (20-40 years) because it is
related to the immune system, & their immune system is
young, so it is more active, & it mostly affects MALES.
Its prevalence is (80-370)/100,000 in Turkey, (13-20) in
Saudi Arabia and Japan.
As a clinician you know that it is an autoimmune disease with
unknown cause, it may be genetically predisposed, some
physicians order blood test or genes test for their patients to
diagnose Behcets disease, but this is NOT true because 50% of
Behcets disease patients have HLA B51 positive, but this

doesnt mean anything because this is not from the criteria for
the diagnosis, because as we said the diagnosis is CLINICALLY.
As an autoimmune disease, what happens is that there is
aberrant immune response triggered by exposure to an agent
possibly infectious, this will lead to increase immune complexes
and Cytokines & Increased CD8/CD4 ratio with decrease CD4
suppressor subpopulations.
In a way or another, Behcets disease is related to blood
vessels; we dont know the exact mechanism but they are prone
to have venous thrombosis more than arterial although they are
not in hypercoagulability state, but what causes the thrombosis
is that their endothelial system is abnormal, they have
inflammation that cause activation of the endothelial system
with low activated protein C levels & vascular endothelial
growth factor levels are high & then we have thrombosis, so it
is a form of vasculitis which is seen with lymphocytic
infiltration of mucocutaneous lesion and neutrophilic infiltrate in
Pathergy Test ** explained later
The clinical manifestations in general vary
between people, some have mild disease &
others have very severe disease (males have
very bad disease)
Most important one is Oral Ulcers which
3

Oral ulcers in Behcets disease

are similar to the aphthous ulcers that affect normal people

but here in Behcets disease they are multiple, recurrent,
painful, deep, & larger than the ulcers in normal people their
size vary from few mms to few cms, they heal spontaneously
within 1-3 weeks & can be continuous, its criteria is recurrence
of ulcers more than 3 times per year & it is usually the first
manifestation of the disease and the last one to leave.
Genital ulcers 75% of Behcets
disease patients have genital ulcers,
typically they are painful & found on
the scrotum in males & on the vulva in
females (the females sometimes arent
aware of them, sometimes they are shy,
sometimes they describe them as itching

Genital ulcers

or discharge or something like that), the genital ulcers leave

scars but we didnt see scaring in the oral ulcers because the
blood supply to the oral mucosa is much better than here.
Coetaneous lesions
Acne like rash on the face & the back, can be mild or
extensive,
Pseudo folliculitis: when you look at the hair follicles, they
look as they are infected but actually they are NOT, or

sometimes without hair follicles you can see small papules

containing pus but they arent infected areas!
Erythema nodosum: painful nodules on the lower
extremities.
Superficial thrombophlebitis.
Pyoderma gangrenosum.
Nodules.
Palpable purpura.
Just the underlined cutaneous lesions are accepted as criteria for the clinical diagnosis.

Pathergy test
One of the clues for Behcets disease is that when we put an
IV line for the patient he will develop a reaction around the
site of the puncture in the form of erythematous papule or
pustule of 2 mm or more, whereas normally we dont have
such reactions, it is seen in (50-75) % of eastern patients &
(10-20) % of north European patients.

Positive Pathergy test is one of the criteria for the diagnosis.

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Ocular lesions

**One of the most common causes of blindness in Japan is

Behcets disease**

They affect (25-75) % of the patients who may present with

*blurred vision,**uveitis; it isnt necessary to see redness to say
that this is uveitis because it is an inside inflammation, the
uveitis is episodic, bilateral, & may lead to blindness, ***retinal
vasculitis, ****optic neuritis and *****vascular occlusion.
The ocular manifestations require treatment including
immunosuppressants.

Differential diagnosis:
Common Oral ulcers
Inflammatory Bowl Diseases(Crohns & UC)
Rheumatic diseases such as SLE( can cause oral &
genital ulcers BUT they are painless, but if they have
secondary infection they will be painful)
Vasculitis
Drug reactions such as Methotrexate
Pemphigus and pemphigoid

How to diagnose??

Diagnostic criteria for Behcets disease

The major criterion is oral ulcers & the minors are genital

ulcers, eye lesions (whatever the lesion is), skin

manifestations (one of the four that we talked about
previously) & pathergy test

If we have 2 minors + 1 major = Behcets disease

This criteria is just a guideline, sometimes we diagnose
Behcets disease in patients who miss one criterion {such as one
who has oral ulcers, uveitis & DVT Behcets disease;
although DVT isnt counted as one of the criteria here}.

What is the treatment??

It is difficult to treat Behcets disease, we use Colchicine,
Thalidomide, Dapsone (here we dont have Thalidomide &
Dapsone), Methotrexate, Steroids & we treat according to
what organ is involved
Brain: it affects the venous system mostly, they may present
with stroke, headache, sagittal sinus or any sinus thrombosis
because the sinuses are abnormal.
Lung: in the pulmonary artery we have inflammation that will
lead to aneurysm; if it ruptures the patient will die {once
we had a patient who was 16 years old, we admitted him & he
died within few hours because of sudden gush of blood that led
to the rupture of the aneurysm.
7

The problem in Behcets disease involving the lung in the clinical

life that they present with acute shortness of breath & chest
pain, so we think of pulmonary embolism & give them
thrombolytic agents, & because they have aneurysm, you will
guarantee their death , such patients you should order chest
CT for him to rule out aneurysms.

Guidelines for the treatment:

For mucocutaneous lesions: topical steroid, colchicine,
thalidomide, Dapsone
For resistant lesions use *azathioprine, **methotrexate
For ocular disease :use local and systemic steroids &
immunosuppressant with azathioprine, cyclosporine,
methotrexate
Major organ involved CNS, Lungs and vasculitis: high dose
steroid and immunosuppressant drugs such as
cyclophosphamide, chlorambucil, interferon alpha, TNF
inhibitors, mycophenolate mofetil.
Superficial thrombophlebitis :low dose aspirin
DVT and PE : systemic anticoagulation and consider
immunosuppressant but as we said above concern with
anticoagulation the presence of aneurysms and the risk of
bleeding which can be fatal.

Prognosis and course

The disease is characterized by exacerbations and remissions,
it is worse in young adult males & if it involves CNS, eyes,
and large vessels (arterial or venous) it will carry the highest
morbidity and mortality but the prognosis seems to be
better with treatment

**5 year survival is 80%.

& Now

MoOoOoOoOoOve to the next disease

Gout
Gout in acute attacks cause severe pain (worse than the
infections pain), the cause is the tissue deposition of Mono
Sodium Urate (MSU) crystals due to super saturation of the
ECF with the MSU.
Hyperuricemia is a prerequisite for Gout meaning that you
cant get Gout without the presence of hyperuricemia
before, normally before puberty the uric acid level is very low
(2-3 mg) in both males & females, on puberty the level will
jump & in males will be more than females {in males >7mg &
in females >6mg}, the females level of uric acid will be less
than males till the menopause.
Only (15-20) % of patients who have hyperuricemia will
develop Gout.
Uric acid is an end product of purine metabolism, but human do
not have enzyme Uricase to convert it to allantoin (highly
soluble) to be secreted, the problem in hyperuricemia is either
overproduction(endogenous {in certain syndromes that are very
rare, they have positive family history & some mental problems
such as Nyhans syndrome} or exogenous) or undersecretion of
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uric acid (the problem is in the kidney & even if we have mild
renal impairment the uric acid excretion will be affected, renal
impairment counts for 90% of Gout patient, the idea here is
that the kidney has different threshold for uric acid excretion,
meaning that if we have 2 persons, the 1st excrete 900 mg of
uric acid in 24 hours when the serum uric acid level is 7 mg,
but the second one needs it to be 10 or 11 to excrete the
same amount, so hell have hyperuricemia because of
undersecretion) but we need hyperuricemia for prolonged time
to trigger Gout, for example patients with acute renal failure
dont develop Gout but they do in chronic renal failure.
The higher the level of uric acid & the longer the period
with hyperuricemia, the higher the risk to develop Gout.
The typical presentation for Gout is a male patient who is
30 or above years old, hypertensive, & on diuretics, he has
mild renal impairment, & now he is complaining of pain & he
gives you a history of prior similar pain (attacks of very
severe pain that can awakens him from sleep & he describes
it as someone had hit him with a hummer!! But indeed
there is no trauma).
Gout is a disease of adult men with peak in 5th decade, it is
very rare before puberty and in premenopausal women, &
family history may contribute in 20% of patients (such as in

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some rheumatologic diseases,, btw Gout & rheumatoid

arthritis cant be presented together).
90% of Gout patients are primary (idiopathic).
Acquired causes of overproduction:
1. Excess dietary purine consumption.
2. Accelerated ATP degradation: alcohol abuse, glycogen
storage diseases.
3. Myeloproliferative and Lymphoproliferative disorders
both causing increased nucleotide turnover, such as
*someone with chronic myelocytic leukemia, he is prone
to develop Gout because he has too much cell
destruction that will lead to increase uric acid level
** or someone with tumor lysis syndrome, with
chemotherapy he will have cell destruction & thus
increased uric acid level the treatment for these is
rehydration & allopurinol, because if these left with this
sharp & rapid increase in uric acid level, they will
develop Acute Renal Failure.
Acquired causes of underexcretion:
1. Renal disease
2. Poly cystic kidney disease
3. Hyperparathyroidism
4. Hypothyroidism
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5. Hypertension, especially those who are using diuretics.

Drugs cause underexcretion:
1. Cyclosporine
2. Alcohol
3. Nicotinic acid

These are important especially in males

who are using them & come to you

4. Thiazide

with ankle or knee recurrent pain

5. Lasix(furosemide)
6. Ethambutol

7. Aspirin (low dose), because aspirin will compete with uric

acid excretion & thus causes hyperuricemia.
8. Pyrazinamide: anti TB drug.
Alcohol mechanism of hyperuricemia: Not that important
because usually we dont ask about it in the exams, but we
may ask about it this year!! dr. said
Increases lactic acid production which reduces renal
excretion of urate.
Increases Urate synthesis because of increased ATP
degradation.
Beer also contains purine guanosine.

13

Stages of Gout:
1) Prolonged asymptomatic undiagnosed Gout.
2) Intermittent Gout: Attacks of severe pain that are self
aborted within 7-10 days.
3) Chronic tophaceous Gout: they have deposits of uric acid
outside, common site is the ears.

Clinical manifestations of Gout:

Recurrent Gouty Arthritis (articular and
periarticular).
Tophi
Uric acid urinary calculi: the uric acid crystals may be
prerequisite for a stone, so patients with recurrent
renal stones & hyperuricemia we should treat
hyperuricemia even if they dont have Gout yet.
Interstitial nephropathy with renal function
impairment if the uric acid level is very high.
Crystals are strongly related to the temperature, when the
temperature is low they tend more to deposit, so we see the
crystals more in the distal joints such as DIP & MTP but we
dont see Gout in the shoulder or the hip.

14

Gout in the DIP

Typical Gout of 2 joints the 1st MTP

& the ankle joint

Podegra is the Gout of the big toe (1st MTP joint) mainly;
the big toe has a lot of diseases such as RA, osteoarthritis,
trauma, congenital anomalies, Gout, pseudo gout & infection.
It has several characteristics such as: Acute onset Severe
pain Erythema Very tender 5May be febrile 6Resolve in (310) days.

Tephaceous gout of uric acid deposits & if we

have sample from one of them we will see
needle like deposits as in the figure on the left

15

Very severe chronic neglected gout with

Olecranon bursitis

Tophi hands and olecranon bursa

Soft tissue swelling because

Soft tissue swelling & erosions

of Tophi with large erosions involving

around 1st MTP, this may take

time (years) to develop

DIPs, with hanging edges

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Differential diagnosis:
Pseudogout
Septic arthritis: the most dangerous one, it may lead
to death
Reactive arthritis
Other inflammatory arthritis
pseudogout & Gout arent very dangerous diseases, they
cause severe pain but they wont kill patients, in such patients
we do aspiration by needle, & the best diagnostic method is by
doing synovial fluid analysis.
Management of acute Gout:
NSAIDs: such as ibuprofen (800mg), diclofenac,
COX2 inhibitors, indomethacin (most effective one),
& naproxen (500mg) at full dose, we use all NSAIDs
except paracetamol because it may kill the pain but
it wont affect the inflammation.
You should know the NSAIDs toxicity &
contraindications.
Steroids: are used for acute management if we want
to have fast results & if NSAIDs & colchicine use are
not warranted, they are given orally(such as
prednisolone 20-40 mg daily for 5-7 days), intra
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articular, IM & IV(if unable to take it orally) ,

Intra-articular injection of triamcinolone is fastest
way to get relief ,at the same time can get synovial
fluid for analysis
Always make sure that no infection coexists.
Colchicine: ( 0.6-1mg) here in Jordan we have 1mg
dose tablets, it is limited because of its toxicity,
main side effects are GI problems such as :abdominal
pain, diarrhea & nausea &, it also may cause
myelosuppression, azospermia and infertility, IV
Colchicine is very toxic to bone marrow so it isnt
used anymore,& if the patient has renal impairment
you should adjust it for your patient.
Prophylaxis:
By prophylaxis we need to bring serum uric acid level into
subnormal, usually we use allopurinol(its problem that it cause
severe hypersensitivity reaction & it can affect the kidney &
the liver), sometimes we use NSAIDs & colchicine, here
colchicine problem is that it abort the attack if we have but it
doesnt affect the serum uric acid level.
Indications for prophylaxis:
Recurrent attacks of Gout
Renal stones
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 Tophaceous Gout
Chronic gout with joint damage and erosions
Hyperuricemia uric acid > 12mg/dl
24 hour urine excretion of >1100 mg uric acid
We use Probencid (Uricose uric acid), that leads to the
excretion of the uric acid in the urine we give it in certain
patients who are:
1-age <60
2-Creatinine clearance >50ml/min
3-24 hour urine of uric acid < 700mg(under excretion)
4-No history of renal stone
Also we have new drugs that are similar in their mechanism to
the Uricase enzyme that converts the uric acid to allantoin
that is excreted in the urine & it is found normally in animals
not in humans, of course it is very expensive drug & not
available in Jordan.
Allopurinol (xanthene oxidase inhibitor):
*We use it in hyperuricemia with the following conditions:
Urinary uric acid >1000mg
Uric acid nephropathy
Nephrolithiasis
19

Before chemotherapy
Renal insufficiency GFR<50
Allergy to Uricosuric agents
**Average dose is 300mg.
*** In renal impairment you should use lower dose.
****It may precipitate acute gout when first used
*****Side effects can be very serious range from dyspepsia,
headache, diarrhea & rash to more severe including fever,
eosinophilia, interstitial nephritis, hepatitis, vasculitis, acute
renal failure, toxic epidermal necrolysis, & hypersensitivity
syndrome.

Other crystals arthropathies:

*Pseudogout:
Deposition of calcium pyrophosphate dehydrate crystals, it is
very difficult to differentiate between gout &pseudogout
clinically but you may differentiate by looking at the crystals
under the microscope, & usually gout is associated with
pseudogout, & those who have gout are at risk to develop
pseudogout.

20

**Deposition of Basic calcium phosphate:

Affect old females (80s & after), it causes what is called
Milwaukee shoulder & knee (destruction to these joints), these
crystals need electron microscope to be detected.
** Other crystal arthropathies arent important Dr. said
Pseudogout associations:
Hyperparathyroidism
Familial hypercalciuric hypercalcemia
Hemochromatosis
Hemosiderosis
Hypophosphatasia
Hypomagnesemia
Hypothyroidism
Chondrocalcinosis: typical

Gout
Neuropathic joints

picture of pseudogout

Aging
Amyloidosis
Trauma

Again

MoOoOoOoOoOve to the next disease

21

Spondylarthropathies
Common characteristics between the diseases in this group
are:
Inflammatory axial spine involvement
Asymmetrical peripheral arthritis (in RA we have
symmetrical peripheral arthritis)
Enthesopathy: means affecting the site of the insertion
of the tendon, in RA it affects the joint itself.
Inflammatory eye disease
Mucocutaneous features
Rheumatoid factor negative(in RA the rheumatoid
factor positive)
High frequency of HLA B27 AG
Familial aggregation: as other rheumatic diseases.
Examples:
Ankylosing Spondylitis
Psoriatic Arthritis: mimic RA as well as ankylosing
spondylitis.

22

 Reactive Arthritis

Almost the same

Reiters syndrome

syndrome

Enteropathic Arthritis: In Ulcerative collitis and Crohns

disease
Juvenile Ankylosing Spondylitis it will be deleted soon, we
still put it just to remember that it may affect children.

HLA B27 association is

more in Ankylosing
spondylitis(>90%), Look at
the figure beside >>>

In ankylosing spondylitis we have typical inflammatory back pain,

it is different from the disc pain that this pain will be relieved
on movement & exacerbated by rest especially at night & when
they awake in the morning they will have morning stiffness, but
during the day with movement the pain will decrease.
** The other thing that causes night pain is some malignancies
such as multiple myeloma, because we have lytic lesions so it is
something serious that cause night pain.
23

Usually the patients are young (<40), & the pain duration is
longer than 3 months.
This is the criteria for diagnosis, it may be changed soon:

The patient will become

Flat lumber spine, loss of lordosis, he

one piece.

uses the hips for binding

24

The stages of the disease in the last one he seems better because he had hip replacement.

Nonveretebral symptoms in the Spondyloarthropathies:

Asymmetric peripheral arthritis.
Arthritis of the whole digits
Arthritis of the toe IP joints
Achilles tenosynovitis: typically theyll have pain in the
Achilles tendon that may lead to its rupture.
Plantar fasciitis.
Costochondritis: presentation is chest pain because of
the inflammation of the joint with the sternum
Iritis: they have eye inflammation.
Mucocutaneous lesions.
Recurrent irits leads to the
irregularity of the pupil because of
the adhesions between the lens & the
iris (synechiae).

25

Inflammation of the
sacroiliac joint in its early
stage on the right, then it
will be completely fused as
in the left figure

Disc peripheral calcification

in the right figure & later
the vertebrae will be square
like shape & longitudinal
ligament calcification

Bamboo spine: the spine is one

piece because of the fusion of all
the vertebrae together, & the
ossification follow the contour of
the intervertebral discs.

26

Lung fibrosis in ankylosing

Plantar fasciitis, sometimes we

spondylitis patients

have calcaneal spur & erosion

Reiters syndrome:

It has many similarities with ankylosing

spondylitis but with infectious triggers (such as urethritis,

cervicitis, or infectious diarrhea), often they are associated
with sacroiliitis & enthesopathy, balanitis (genital ulcers), oral
ulcers & keratodermia, & it is seronegative asymmetric
arthritis.

Triggers for reactive

arthritis

27

Pustules, we should think carefully of such

Heel tendonitis in Reiters syndrome

patients in order not to miss the diagnosis

Pustules +Kertaoderma Blenorrhagica

Keratoderma Blenorrhagica

28

Balanitis

Nail dystrophy seen in

Palate erosions

Tongue lesions

Asymmetrical Sacroiliitis

Reiter's syndrome &

psoriasis

29

Conjunctivitis

Plantar periostitis

Psoriatic arthritis:
It is a syndrome that mimics
ankylosing spondylitis without
peripheral arthritis, it may
presents with just sacroiliitis
without anything else, or it may
present as asymmetrical arthritis
especially with large joints like
spondylarthropathy or it may be
presented with sausage digit, or nail changes.

Patterns of arthritis in Psoriasis:

Spondylitis
DIP joint arthritis
Oligoarticular asymmetrical arthritis
Polyarticular symmetric arthritis
Arthritis mutilans

Rash, nail dystrophy & arthritis

Sausage digit & Rash

Affecting DIPs,PIPs,
sausage digit & NO rash
30

Nail dystrophy &

arthritis

Nail pitting

Pencil in a cup changes

Swelling, joint

Dactylitis

Severe changes in DIPs, less

in PIPs & minimal in MTPs

destruction, Erosions in
DIPs, PIPs, MCPs

Treatment

(very similar to the RA treatment):

NSAIDs to treat the symptoms.

Physical therapy, stretching & exercises to preserve spine
and joints function.
Maintain good posture
Sulfasalazine, Methotrexate.
Anti TNF drugs.
Prevent eye complications by early recognition and
treatment.

31

 if the disease is mild, you need just simple treatment for

them.
You should be aware of the association with the following
diseases:
Inflammatory bowel disease
Aortitis, aortic regurgitation (in 1% of ankylosing
spondylitis), because the aorta is a connective tissue so it
may be included in the disease.
Inflammatory eye disease
Pulmonary fibrosis in 1% of ankylosing spondylitis patients,
but it isnt significant to cause symptoms for the
patients, if we have respiratory symptoms such as dyspnea
this is because restrictive lung disease.
Severe reactive arthritis and HIV.

& the last MoOoOoOoOoOoOve to

Scleroderma
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Multi systemic disease with a problem in the endothelium &

fibroblast changes that leads to damage of small arteries &
then peripheral ischemia which is a factor in having skin fibrosis.
Unfortunately we dont have effective treatment for the skin;
we just have treatments for other major problems with the
scleroderma.
It is rare disease in adults & children, it is more in females.
Clinical features:
1. Raynauds phenomenon: we see it in all connective tissue
disease but it is very severe here.
2. Skin changes: the skin is adherent to the underlying
structures, you try to pinch the skin up but you cant,
almost overall the body, & it may have hypo
&hyperpigmentation, it looks like that you put pepper &
salt on the skin.
3. Esophageal fibrosis that lead to esophageal dismotility,
reflux, heartburn & even carcinoma.
4. Interstitial lung disease: it is significant here & affects the
lower parts, they need here aggressive treatment or youll
lose them.
5. Pulmonary hypertension: presented with dyspnea.

33

6. Renal crisis: in the 1st 5 years after the diagnosis of

scleroderma.

Raynauds phenomenon:
Reversible skin color changes from white to blue to red, 1st we
have severe vasospasm so no blood flow so white color, then
ischemia so blue color, then flushing so red color,, it is caused
by coldness & emotional stress, & it isnt necessary that
Raynaud will affect all the fingers, it may affect just 2 or 3
fingers with the least affection to the thumb, the major
problem in Raynaud that it may end up with necrosis.
Other causes of Raynauds: vasculitis, hyperviscosity,
polycythemia, & if we have compression on blood vessels or on
sympathetic & parasympathetic systems.
Complications: hypertension, high renin, microangiopathic
hemolytic anemia, & thrombocytopenia.

34

CREST:

it is a form of scleroderma that is characterized by

calcinosis, Raynauds phenomenon, sclerodactyle(deformed rigid

fingers), telangiectasia, & sometimes they develop superinfection
that is recognized by pus coming out of it & we should use
antibiotics to treat them

Diagnosis: clinical picture

+ ANA (+ve) +

anticentromere

antibodies (+ve) {especially in CREST}.

Treatment:
*No effective treatment for the skin, fortunately 2/3 of the
skin manifestations will improve gradually by themselves.
**Treat hypertension (you should keep the BP 120/80).
***Treat reflux (by PPI).
****For Raynaud sometimes we use Ca channel blockers.
*****Treat pulmonary hypertension (which is difficult to be
treated) but they now use Viagra to treat it, avoid steroids
because it may trigger renal crisis.
****** Treat renal crisis (hypertension with renal impairment):
ACE inhibitors, even the creatinine level is very high give ACE

35

inhibitors (this is the only condition in which we give ACE

inhibitors to patients who have high creatinine level).

& Finally

The End

Done by:

Kawther A. Al-alem
Group B8

36