Gout and Behcets

8/18/2019 Gout and Behcets

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يم

الرح

الرحن

بسم

Before you start:

We are going to talk about Behc et’s 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 1 st 3 diseases & for the

sclero derma I couldn’t get the slides(You don’t need to

refer to the slides)

It is very easy lec. Although it is long, but it is full of

figures.

& as usual… Enjoy

Behcet’s 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 Behcet’s disease.

ehcet’s disease


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What is Behcet’s disease??

It is chronic relapsing systemic inflammatory disease, it has

certain characteristics that lead us to diagnose the patients as

having Behcet’s disease, for example if you see hemoptysis or

DVT in young patient , these are alarming signs for Behcet’s

disease.

Behcet’s disease’s diagnosis is clinically because we don’t have a

lab test that we rely on to diagnose it.

Behcet’s 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 Behcet’s disease, but this is NOT true because 50% of

Behcet’s disease patients have HLA B51 positive, but this


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doesn’t 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 isaberrant 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, Behcet’s disease is related to blood

vessels; we don’t 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 ¹ Oral Ulcers whichOral ulcers in Behcet’s disease


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are similar to the aphthous ulcers that affect normal people

but here in Behcet’s 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.

² Genital ulcers »» 75% of Behcet’s

disease patients have genital ulcers,typically they are painful & found on

the scrotum in males & on the vulva in

females (the females sometimes aren’t

aware of them, sometimes they are shy,

sometimes they describe them as itching

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

scars but we didn’t see scaring in the oral ulcers because the

blood supply to the oral mucosa is much better than here.

³ 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

enital ulcers


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sometimes without hair follicles you can see small papules

containing pus but they aren’t infected areas!

Erythema nodosum: painful nodules on the lower

extremities.

Superficial thrombophlebitis.

Pyoderma gangrenosum.

Nodules.

Palpable purpura.

⁴

Pathergy test »»

One of the clues for Behcet’s 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 don’t 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

Behcet’s disease **

Just the underlined cutaneous lesions are accepted as criteria for the clinical diagnosis.


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The major criterion is oral ulcers & the minors are¹genital

ulcers

,²eye lesions

(whatever the lesion is),³skin

manifestations

(one of the four that we talked about

previously) &⁴pathergy test

…

If we have 2 minors 1 major = Behcet’s disease

»» This criteria is just a guideline, sometimes we diagnose

Behcet’s disease in patients wh o miss one criterion {such as one

who has oral ulcers, uveitis & DVT »» Behcet’s disease;

although DVT isn’t counted as one of the criteria here}.

What is the treatment??

It is difficult to treat Behcet’s disease, we use Colchicine,

Thalidomide, Dapsone (here we don’t have Thalidomide &

Dapsone), Methotrexate, Steroids & we treat according towhat 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.


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The problem in Behcet’s 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: ¹topical steroid, ²colchicine,

³thalidomide, ⁴ Dapsone

For resistant lesions use *azathioprine, **methotrexate

For ocular disease :use ¹local and systemic steroids &

²immunosuppressant with azathioprine, cyclosporine,

methotrexate

Major organ involved CNS, Lungs and vasculitis: ¹high dose

steroid and ²immunosuppressant drugs such as

cyclophosphamide, chlorambucil, interferon alpha, TNF

inhibitors, mycophenolate mofetil.

Superficial thrombophlebitis :low dose aspirin

DVT and PE : ¹systemic anticoagulation and consider

²immunosuppressant but as we said above concern with

anticoagulation the presence of aneurysms and the risk of

bleeding which can be fatal.


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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


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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

can’t 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 Ny han’s syndrome } or exogenous) or undersecretion of

Gout


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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 he’ll have hyperuri cemia because of

undersecretion) but we need hyperuricemia for prolonged time

to trigger Gout, for example patients with acute renal failure

don’t 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 can’t 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 & thusincreased 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

4. Thiazide

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 don’t 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.

These are important especially in males

who are using them & come to you

with ankle or knee recurrent pain


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Stages of Gout:

1) Prolonged asymptomatic undiagnosed Gout.

2)

Intermittent Gout: Attacks of severe pain that are selfaborted 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 don’t 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

don’t see Gout in the shoulder or the hip.


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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: ¹Acute onset ²Severe

pain ³Erythema ⁴ Very tender 5May be febrile 6Resolve in (3-

10) days.

out in the DIP Typical Gout of 2 joints the 1 st MTP& the ankle oint

Tephaceous gout of uric acid deposits & if we

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


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Very severe chronic neglected gout withTophi hands and olecranon bursa

Olecranon bursitis

Soft tissue swelling because

of Tophi with large erosions involving

DIPs, with hanging edges

Soft tissue swelling & erosionsaround 1st MTP, this may taketime (years) to develop


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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 aren’t very dangerous diseases, they

cause severe pain but they won’t 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 won’t affect the inflammation.

»»You should know the NSAID’s 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 ¹ GI problems such as :abdominal

pain, diarrhea & nausea &, it also may cause

² myelosuppression, ³ azospermia and ⁴ infertility, IV

Colchicine is very toxic to bone marrow so it isn’t

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

doesn’t affect the serum uric acid lev el.

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 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


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Before chemotherapy

Renal insufficiency GFR


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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 aren’t important” Dr. said

Pseudogout associations:

Hyperparathyroidism

Familial hypercalciuric hypercalcemia

Hemochromatosis

Hemosiderosis

Hypophosphatasia

Hypomagnesemia

HypothyroidismGout

Neuropathic joints

Aging

Amyloidosis

Trauma

Again… MoOoOoOoOoOve to the next disease

Chondrocalcinosis: typical picture of pseudogout


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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.

Spondylarthropathies


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Reactive Arthritis

Reiter’s syndrome

Enteropathic Arthritis: In Ulcerative collitis and Crohn’s

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.

Almost the same

syndrome


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Usually the patients are young (


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Nonveretebral symptoms in the Spondyloarthropathies:

Asymmetric peripheral arthritis.

Arthritis of the whole digits

Arthritis of the toe IP joints

Achilles tenosynovitis: typically they’ll 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.

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

Recurrent irits leads to theirregularity of the pupil because ofthe adhesions between the lens & the

iris (s nechiae).


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Inflammation of the

sacroiliac joint in its early

stage on the right, then itwill 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.


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Reiter’s syndrome

: It has many similarities with ankylosing

spondylitis but with infectious triggers (such as ¹urethritis,

²cervicitis, or ³infectious diarrhea), often they are associated

with sacroiliitis & enthesopathy, balanitis (genital ulcers), oral

ulcers & keratodermia, & it is seronegative asymmetric

arthritis.

Plantar fasciitis, sometimes wehave calcaneal s ur & erosion

Lung fibrosis in ankylosing spondylitis patients

Triggers for reactive

arthritis


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Heel tendonitis in Reiter’s syndrome

Pustules, we should think carefully of suchatients in order not to miss the dia nosis

Keratoderma Blenorrhagica

Pustules +Kertaoderma Blenorrhagica


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Balanitis

Tongue lesions

Palate erosions

Conjunctivitis

Nail dystrophy seen in

Reiter's syndrome &

psoriasis

Asymmetrical Sacroiliitis

Plantar periostitis


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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

Affecting DIPs,PIPs,

sausage digit & NO rash


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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.

Nail dystrophy &

arthritis

Nail pitting

Dactylitis

Swelling, joint

destruction, Erosions in

DIPs, PIPs, MCPs

Pencil in a cup changes

Severe changes in DIPs, less

in PIPs & minimal in MTPs


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»» 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 isn’t 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 lastMoOoOoOoOoOoOve

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 don’t 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. Raynaud’s 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 can’t ,

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 you’ll

lose them.

5.

Pulmonary hypertension: presented with dyspnea.


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6.

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

scleroderma.

Raynaud’s phenomenon

Reversible skin color changes from white to blue to red, 1 st 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 isn’t 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 Raynaud’s : ¹vasculitis, ²hyperviscosity,

³polycythemia, & if we have ⁴ compression on blood vessels or on

sympathetic & parasympathetic systems.

Complications: ¹hypertension, ²high renin, ³microangiopathic

hemolytic anemia, & ⁴ thrombocytopenia.


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CREST : it is a form of scleroderma that is characterized by

calcinosis, Raynaud’s 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}.

:reatment

, fortunately 2/3 of theo effective treatment for the skin N *

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


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

inhibitors to patients who have high creatinine level).

& Finally

The End

د

ب

ت

Done by:

Group B

Kawther A. Al alem

Documents

Gout and Behcets