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CLINICAL PRESENTATION OF RHEUMATOID
ARTHRITIS
A RECEARCH PRESENTED BY
THE STUDENT : YOSRA ASHRAF EL-ALFY
ID# : 9760249
PROJECT SUPERVISOR Dr.RAFIQ ABUSHAABAN
July.2001
AJMAN UNIVERSITY OF SCIENCE & TECHNOLOGY
ABU-DHABI BRANCH
UAE
Research for this project was carried out by me during the period of hospital
training –2 no.700315 (acadimic year 2000-2001)
Signed
Yosra Ashraf
Date:July.22 2001
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Rheumatoid Arthritis
Acknowledgement
ACKNOWLEDGMENT
Sincere gratitude were extended to project supervisor
Dr.Rafeeq Abushaaban from the pharmaceutics department, for the
continuous follow up, constructive criticism, valuable comments, support,
encouragement & fruitful accompaniment throughout the training &
presentation of this project.
The author wishes to express special gratitude & thanks to those
contributing in this revolutionary, distinctive and advanced Hospital
pharmacy training 2 ; namely Dr.Dana
Sallam and the staff of ALNOOR HOSPITAL.
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Rheumatoid Arthritis
CLINICAL PRESENTATIONS OF RHEUMATOID
ARTHRITIS
INDEX
Section
Page
Section l :
General Introduction
P.4
(( Drugs Used In The Treatment Of Rheumatoid Arthritis))
Section ll
(( Pharmaceutical care of Rheumatoid Arthritis))
2.1 patient counsling.
P.8
P.8
2.2 Chice of drug therapy.
P.10
In case of having other diseases
P.10
Section lll :
Discussion Of Clinical Cases About Rheumatoid Arthritis
P.15
Section lV :
Additional Practice Points
P.57
Pharmacoe-economics
P.58
Section V:
References
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P.60
GENERAL INTRODUCTION
GENERAL INTRODUCTION
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Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic disorder of immune regulation which is
characterized primarily by articular manifestations. Joint synovial linings demonstrate
progressive proliferative changes which often ultimately progress to destruction of the
joint space and underlying cartilage with loss of function of the articular unit.
Rheumatoid nodules may also form in subcutaneous tissues overlying easily
traumatized bone (such as upper extremity extensor surfaces) and may also be found
in other tissues and organs (lung, skeletal muscle, etc.) These nodules demonstrate
central paucicellular areas of eosinophilic necrosis which are flanked by rows, or
palisades of histiocytes and other inflammatory cells. The pathogenesis underlying the
formation of these nodules is not completely understood; they are noted in
approximately 25% of patients with RA.
Rheumatoid vasculitis is a well-described entity in RA patients, and can be a
serious threat to function and life, depending upon the size and location of the
involved vessels. Blindness, peripheral neuropathies, cerebrovascular accidents, and
skin ulceration with gangrene has been noted in these patients; this complication is
most often noted in patients with the highest rheumatoid titers.
In the laboratory, a diagnosis of rheumatoid arthritis is supported (in the proper
clinical context) by the identification of so-called Rh factor, an anti-self antibody
noted in over 80% of RA patients. Most of these antibodies are of the IgM subtype,
and show specificity for the Fc portion of the IgG molecule. These antibodies form
circulating complexes with their respective IgG antibodies; these complexes form
deposits in synovial membranes and are felt to contribute to the formation of the
typical synovitis and pannus of RA through the activation of complement in situ.
Similar activity in the extraarticular tissues (renal glomerulus, small systemic vessels,
etc) cause many of the disease manifestations in these regions. In the absence of
identifiable Rh factor in serum or synovial fluid, the diagnosis of "seronegative" RA
is made on a clinical basis, with the findings of symmetrical arthritis affecting three or
General Introduction
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Rheumatoid Arthritis
more areas and especially involving joints of the hand, typical radiologic findings of
RA (narrowing of the joint spaces, marginal erosions, and digit deviations or
subluxations), morning stiffness, and the identification of rheumatoid nodules (usually
not identified in absence of elevated Rh titer). The disease course of RA is variable,
with most cases of a chronic nature with periodic exacerbations. Death, if related to
RA, is usually due to complications of vasculitis and chronic vessel changes
(including amyloid depositions in vessel walls) and therapy-related complications
(infections secondary to chronic immunosuppression, or coagulopathy secondary to
NSAID overuse).
Progressive pseudorheumatoid arthritis of childhood (PPAC) is a rare
atuosomal recessive disorder, resembling rheumatoid arthritis, especially the
seronegative spondylo-arthropathies of childhood(1). However, there is no
inflammation of the joints and it has been demonstrated that the disorder is actually
due to a non inflammatory chondropathy affecting mainly the articular cartilage(1,2).
An early clinical diagnosis is difficult and it is the characteristic radiological features
which help in an early recognition of the disease. Three cases have been reported
from India earlier(3,5). We report here a case of PPAC presenting to us at the age of
11 years, who was diagnosed for the first time at our center on the basis of clinical
and radiological features. However, this patient was different from the other reported
cases in having prominent facial dysmorphism.
Goals Of RA Treatment :
The goal of management of RA are to:
1. Relieve pain and inflammation.
2. Prevent joint destruction.
3. Preserve or improve patient’s functional ability.
General Introduction
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Rheumatoid Arthritis
A table for NSAID’s with its daily adult doses used in the
treatment of Rheumatoid Arthritis :
DRUG
ADULT DAILY DOSE RANGE FOR RA.
Acetic acid :
Aceclofenac
100 mg in 2 doses
Diclofenac
75-150 mg in 3 doses
(or 100mg once daily sustained release)
Anthranilic acids
Mefenamic acids
1500 mg in 3 doses
Indole/Indene/derivatives
Acemetacin
60mg in 2 doses
Etodolac
200-600 mg in 2 doses
Indomethacin
50-200 mg in 3 doses
Sulindac
300-400 mg in 2 doses
Propionic acids
Fenbufen
600-1000 mg in 2 doses
Fenoprofen
2.4-3.2 g in 4 doses
Flurbiprofen
150-300 mg in 2-4 doses
Ibuprofen
1.2-3.2 g in 3-4 doses
Ketoprofen
150-300 mg in 3 doses
Naproxen
500-750 mg in 2 doses
Tiaprofenic acid
600-1200 mg in 3 doses
Butanone
Nabumetone
1-1.5 g in 1-2 doses
Oxicams
Meloxicam
15 mg in 1 dose
Piroxicam
20 mg in 1 or 2 doses
Tenoxicam
20 mg daily
Pyrazolidinediones
Phenylbutazone
Yosra Ashraf
300-400 mg in 3-4 doses
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Rheumatoid Arthritis
Azapropazone
1.2 g in 2-4 doses
Salicylates
Aspirin
3-6 g in 4-6 doses
Benorylate
4-8 g in 2-3 doses
Diflunisal
1.0 g in 2 doses
Other drugs used in the treatment of Rheumatoid
Arthritis
First line Treatment:
Analgesics
NSAID’s
Second Line Treatment:
Antimalarials
Gold (parenteral and oral)
Penicillamine
Salphasalazine
Third line Treatment:
Azathioprine
Methotrexate
Cyclophosphamide
Other Agents
Corticosteroids ( oral or parenteral )
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Section ll
2.1 Patient Counsling:
Patients with Rheumatoid Arthritis (RA) must be appropriately educated and
counselled as it is really vital point. Patient Education Only Part of a Good RA
Management Program as the patient should have a knowledge of the disease process,
the likely prognosis and the treaetment strategy.
Patient counsling should reinforce the need to comply with monitoring requirements,
the time delay before a response is seen, potential toxicity and action to take in the
events of adverse effects.
NSAID’s preparations should be taken with or after food, the patients should be
warned of potential adverse effects and what to do if these occur.
Non Drug Treatment :

Rest & Nutrition :
Complete bed rest is recommended for a short period during the most active ,painful
stage of severe diseaes. In less severe cases, the clinical pharmacist should prescribe a
regular rest.
An ordinary nutritious diet is generally sufficient. Rarely, patients have foodassociated exacerbations. Fish or plant oil supplements may partially releive the
symptoms because they can decrease production of prostaglandins.

Physiotherapy :
Physiotherapy is a vital part of treating RA in a patient, both in acute flares of disease
and in the chronic state.
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Rheumatoid Arthritis
Section ll
Heat, Cold & electrotherapy help to reduce pain and swelling, and a programme of
exercise strengthens joints to prevent disuse atrophy, mobilize joints to minimize
deformity and increase the range of movement and functions.
Occupational therapy educates patients to protect joints, improve function by means
of exercise and use of aids and appliances, and provide splints to rest and protect
joints.
Surgical techniques ranging from carpal tunnel decompression to major joint
replacement can be effective in relieving pain and restoring functions.
With more aggressive and effective drug treatments becoming available the frequency
of surgical intervention may reduce.
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Rheumatoid Arthritis
Section ll
2.2 Choice of drug therapy :
The cyclooxygenase (COX)-2 inhibitors are a the better choice for such patients, since
they appear to have a lower risk of gastrointestinal toxicity. The improved safety of
these drugs should not be assumed to imply improved efficacy, however. No
nonsteroidal medication can alter the course of rheumatoid arthritis; they do not
change radiographic progression or slow joint destruction. For that reason, they
should be used as adjuncts, never as monotherapy.
NSAIDs has the following specific interactions:
DISEASE
DRUGS
STATE
USED
Hypertension
ACEI’s
INTERACTION
Aspirin and other NSAID’s have been reported to reduce the
hypotensive effects of ACEI’s via inhibition of PG synthesis.
Ca channel blockers
The antiplatelete effects of aspirin and Ca channel blockers
may be increased when they are used together.
Diuretics
They decrease the hypotensive effect of the diuretics as the
combination is generally contraindicated. The mechanism of
may be interference with the production of renal PG which is
required to mediate the action of the diuretics.
All other antihypertensives
Caution should be exercised when NSAID’s are given to
patient receiving antihypertensives as their effect is reduced.
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Rheumatoid Arthritis
Diabetes
Oral hypoglycemics
May increase the effects of sulphonylureas and
necessitate a reduction in their dose.
Mellitus
Insulin
Doses maybe reduced to avoid severe
hypoglycemia
Infections
Quinolones
Convulsions can occur due to interactions of
Ciprofloxacin mainly and antimicrobiales and
NSAID’s
Probenecid
Excretion of ketoprofen delayed (increased plasma
concentration).Salicylate antagonise the uricosuric
action of probenecid and sulphenpyrazone and
should not be given concurrently.
Epilepsy
Griseofolvin
Reduce aspirin blood levels and alter its absorption.
Metoclopramide
Enhances the absorption of paracetamol.
Sodium valproate
Prolonged use with aspirin may result in greater
than anticipated free levels of valproic acid with
accumulation to toxic levels.
Phenytoin
Azapropazone, ibuprofen and phenylbutazone can
inhibit the metabolism of phenytoin.
Inflammation
Cyclosporin
Causes renal deterioration with the use of
diclofenac. And also it causes nephrotoxicity.
Generally all
They decrease the blood salicylate concentration by
corticosteroids
increasing the glomerular filteration rate. Both drugs
are ulcerogenic.
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Rheumatoid Arthritis
Heart
Anticoagulants
Aspirin displaces coumarins from plasma protien
binding sites and thus potentiate their action.
diseases
Aspirin also tends to reduce plasma prothrombi
when taken in large doses. It decreases platelat
adhesiveness and cause occult bleeding.
Warfarin
NSAID’s may inhibit latelet function and enhance
the hypoprothrombinaemic effects of warfarin. The
mechanism is thought to be an intrensic effect on
coagulation or by displacement of the anticoagulant
from plasma protein binding sites.
Notes : ------------ All NSAID’s should be used with caution, or not at al, in patients on
anticoagulant therapy.
Alcohol
All NSAID’s
It increases blood loss due to aspirin’s damage to the
gastric mucosa.
Rheumatoid
Methotrexate
Can be displaced from plasma protein binding by
salicylates which also inhibit the renal tubular
Arthritis
excretion; methotrexate toxicity may be increased.
All NSAID’s can inhibit the renal PG synthesis
causing the toxicity.
NSAID’s + Aspirin
Aspirin in high doses can reduce Tenoxicam plasma
concentrations.
Phenylbutazone + Aspirin Phenylbutazone inhibits the uricosuria which usually
follows large doses of saicylate.
Bipolar
Lithium
depression
Diclofenac and indomethacin can reduce the renal
clearance of lithium resulting in clinically important
increases in steady-state plasma lithium
concentrations. This is occurs due to the reduction of
renal PG synthesis.
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Rheumatoid Arthritis
hyperlipidaemia Cholestyramine It reduces the bioavailability of diclofenac when the two
agenta are given together.
Colestipol
Appetite
Produces the same effect but smaller.
All NSAID’s Severe hypertension developed in a patient who took suppresssant
indomethacin shortly after ingesting an appetite suppressant
( Trimolets ) containing phenylpropanolamine. The mechanism was
explained by indomethacin – inhibition of PG synthesis evoking
enhanced sympathomimetics effects of phenylpropanolamine.
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Rheumatoid Arthritis
Section lll
CASE STUDY # l :
A 52-year-old female with a 21-year history of deforming polyarticular symmetrical
inflammatory arthritis predominantly involving the wrists and metacarpophalangeal
(MCP) joints, as well as the knees and ankle joints. She was referred to the arthritis
center by her primary care physician for evaluation and treatment. For the previous 6
months, the patient has had nodules around her hand joints, elbows, and over the
Achilles tendons. An ulcer that appeared over the right malleolus following minor
trauma 3 weeks previously had not healed following application of local dressings.
The patient is married and has no children. She is a social worker and lately it has been
difficult for her to work full time, drive her car, and take care of her house. She
smoked for 20 years but has recently stopped. She has been menopausal for 5 years
and has refused estrogen replacement therapy. The patient's mother fractured her hip at
age 72 years and the patient had a sister who died of breast cancer at age 55 years.
Examination showed extensive nodules over her hands, advanced ulnar deformity with
subluxed second and third MCP joints and small effusion in her knee joints that had
not been aspirated. Her leg ulcer did not show good granulation and was secondarily
infected. There was evidence of peripheral neuropathy up to the ankles bilaterally.
Small vasculitis lesions were present on her lower extremity, some of which had
necrotic areas. Her spleen was palpable and there was evidence of epigastric
tenderness on abdominal examination.
Laboratory evaluation showed that her hemoglobin level was 10.9 g/dL with
microcytosis and she had low serum iron. Her leukocyte count was 3200/micro-L with
evidence of neutropenia and a peripheral smear showed large, granular lymphocytes.
Platelet count was 450000/micro-L, erythrocyte sedimentation rate (ESR) was 72
mm/hr and rheumatoid factor was 1:1280. Her fasting blood glucose was 72 mg/dL,
blood urea nitrogen (BUN) was 38 mg/dL and serum creatinine was 2.1 mg/dL
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Rheumatoid Arthritis
Section lll
The patient's current medications include ibuprofen 800 mg 4 times per day,
hydroxychloroquine 200 mg twice daily, and prednisolone 5 mg per day. She had been
continuously on prednisolone at an average dose of 7.5 mg per day for the last 7 years.
Six months ago, she was tried on methotrexate but it caused severe stomatitis and
abnormal hepatic transaminases levels.
Part 1: ( See Q & A # 1 )
This patient has several features of progressive, active rheumatoid arthritis, including
active synovitis, elevated ESR, high rheumatoid factor and evidence of rheumatoid
nodules and vasculitis rash. Despite the use of a (NSAID), prednisolone, and
hydroxychloroquine, her disease has been progressive. Moreover, there are several
adverse effects that could be related to her therapy, namely microcytic anemia and
renal dysfunction. Her history of methotrexate toxicity and the strong family history of
osteoporosis with hip fracture also represent potential problems.
Part 2: Continuation of Case ( See Q & A # 2 )
The patient returned 3 weeks later and her leg ulcer looked clean. However, she had
new vasculitic lesions on her lower extremities and she complained of polydypsia and
polyuria. Her fasting blood sugar was 162 mg/dL, although her BUN and serum
creatinine had improved with values of 32 mg/dL and 1.6 mg/dL, respectively. The
patient, therefore, has not responded well to prednisolone and she has early signs of
iatrogenic diabetes mellitus.
Part 3: Continuation of Case ( See Q & A # 3 )
The patient is at risk of developing osteoporosis because of prolonged use of
corticosteroids, being menopausal without taking anti-osteoporosis measures, leading
a sedentary lifestyle and having a family history of hip fracture.
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Rheumatoid Arthritis
Section lll
Summary of the case study
Patient
Patient
Signs &
Laboratory
Details
History
Symptoms
Tests
* Female
21-year history of deforming
*Difficulty to work full time, drive
*Hb: 10.9 g/dL
*52 yrs old
polyarticular symmetrical
her car, and take care of her house.
(microcytosis) *low serum
inflammatory arthritis
*Polydypsia.
iron. *leukocyte count was
* a social worker
* smoked for 20
years but has recently
predominantly involving the
3200/micro-L (neutropenia
*Polyuria.
wrists, (MCP) joints, knees and
ankle joints. evaluation and
and a peripheral smear
( Signs of iatrogenic diabetes
mellitus).
showed large, granular
stopped
treatment was done. For the
*married and has no
previous 6 months, the patient has
count 450000/micro-L,
children
had nodules around her hand
*(ESR) was 72 mm/hr
joints, elbows, and over the
*RF was 1:1280.
* patient's mother
fractured her hip at
age 72 years and the
patient had a sister
who died of breast
cancer at age 55
years.
lymphocytes). *Platelet
Achilles tendons. An ulcer that
FBS: 72 mg/dL, *blood urea
appeared over the right malleolus
nitrogen (BUN) was 38
following minor trauma 3 weeks
mg/dL
previously had not healed
following application of local
*serum creatinine was 2.1
dressings.
mg/dL.
menopausal for 5
years
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Rheumatoid Arthritis
Further
Diagnosis
Treatments
Comments
Investigations
No Further
*Active rheumatoid
*Ibuprofen 800 mg 4
**The physician must start
investigation
arthritis, including active
times per day.
giving her an anti-osteoporosis
written in the
synovitis, elevated ESR,
*Hydroxychloroquine therapy to protect her from
case
high rheumatoid factor and 200 mg twice daily.
having this disease as she is
extensive hand nodules
*Prednisolone 5 mg
menopause and takes
and vasculitis rash.
per day
corticosteroids.
*Advanced ulnar
( had been
**Methotrexate should be
deformity with subluxed
continuously on
avoided due to her susceptibility
second and third MCP
prednisolone at an
to its toxicity.
joints.
average dose of 7.5 mg
*Small effusion in knee
per day for the last 7
joints (not aspirated)
years).
*Peripheral neuropathy up
*She tried only
to the ankles bilaterally.
Methotrexate.
* Small vasculitis lesions
*Hydroxychloroquine.
were present on her lower
extremity, with necrotic
areas. *Spleen was
palpable. *Epigastric
tenderness.
Notes:** There are several adverse effects that could be related to her therapy, namely
microcytic anemia and renal dysfunction.
**Also she has history of methotrexate toxicity and the strong family history of
osteoporosis with hip fracture also represent potential problems.
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Rheumatoid Arthritis
Section lll
Questions And Comments About The Case Study
Q1: What would be the most appropriate strategy for managing the
patient's leg ulcer with vasculitis and neuropathy?
The other issues needing to be discussed are the periperal neuropathy, vasculitic skin
lesions, and neutropenia with splenomegaly. This constellation of findings in the
patient with longstanding RA should lead to a diagnosis of Felty's syndrome. Also of
interest is the reference to large granular lymphocytes. This particular variant of
Felty's syndrome may actually present earlier in the course of the disease.
Certainly it would be helpful to know the actual neutrophil count, as extremely low
counts increase the risk of systemic infection, especially in the patient on
glucocorticoids. If the absolute neutrophil count were as low as 500, consideration
should be given to using a course of granulocyte colony stimulating factor. Lithium
and testosterone have also been used, but controlled studies of these agents is very
limited.
Gold injections and penicillamine have both been reported to be beneficial in the
management of Felty's syndrome, although these agents have been used less frequently
since the addition of methotrexate to the armamentarian. To date I know of no
reference to the use of ARAVA or ENBREL in this setting, but would imagine a
benefit if the drugs were tolerated. Imuran has also been used in this setting, as well as
cytoxan, but the risk of bone marrow suppression would require extremely careful
monitoring of the patient.
Using IV Imunoglobulin is benificial
.Having diabetes
and taking Prednisolone will certainly interfere with
healing. So the doctor should use becaplermin to help start granulation tissue.
Her NSAID treatment should be stopped because of her renal dysfunction and
possible occult gastrointestinal bleed. She should be started on an anti-gastritis
regimen, such as PPI’s with an iron supplement for her anemia.
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Rheumatoid Arthritis
Section lll
To treat her leg ulcer, she needs to be on an antibiotic, such as cephalexin,
with local dressings applied.
The dose of oral prednisolone should be increased to 1 mg/kg daily for at least
seven to ten days and then lowered according to her progress.
Methotrexate cannot be used because of her renal dysfunction and past history
of methotrexate toxicity. She will continue her other medications, including
hydroxychloroquine.
Baseline tests for osteoporosis should be performed, including bone
densitometry measurements to determine the risk of fractures.
Measurements of thyroid function, serum calcium, serum phosphorus, 25hydroxyvitamin D and kidney function should be made.
If her bone density was found to be in the osteopenia range and the other tests
showed normal values, the patient should be started on calcium and vitamin D
at respective daily doses of 1500 mg and 400 units. The third generation
bisphosphonate alendronate would also be recommended.
An estrogen should not be given because of the patient's family history of
breast cancer. However, a "designer estrogen", such as Evista ® (raloxifene),
would be a good alternative if she is intolerant of alendronate. Like estrogen
replacement therapy, raloxifene increases bone mineral density but it is not
associated with endometrial changes or breast malignancy.
******************************************
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Rheumatoid Arthritis
Section lll
Q2: What would be the proper course of action now, given that the
patient still has progression of vasculitis as well as early signs of
iatrogenic diabetes mellitus?
A steroid-sparing, cytotoxic, immunosuppressive drug would be strongly
recommended.
At present, the best choice would be oral cyclophosphamide or the
antipyrimidine drug Arava® (leflunomide). which should be started at a low
dosage of 1 mg/kg/day because of the patient's neutropenia. This dosage could be
increased to a maximum of 2.5 mg/kg/day if her blood cell counts become more
stable. Close monitoring of blood cell counts would be required. The white cell
count should not be allowed to drop below 3000/mL and the neutrophil count
should not fall below 1000/mL. Cyclophosphamide dose should be decreased if
her counts drop and her CBC is monitoried closely.
low dose of oral prednisolone 5 to 10 mg daily would be recommended. The
patient's blood glucose should be monitored for the need to control her iatrogenic
diabetes mellitus.
If her hyperglycemia persists, insulin would be started and insulin dose will be
adjusted depending on her blood sugar levels.
*******************************************
Q#3: What would be the correct plan of action under these
circumstances?
Appropriate
intake
of
calcium(1200mg/day)
and
vitamin
D(400-
800units/day)would be required for cardiac/skeletal protection.
Do a baseline DEXA scan, with a repeat scan in 6 months to 1 year to insure a
therapeutic benefit.
*******************************************
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Rheumatoid Arthritis
Section lll
Case Study # 2
A lady 75-years old who has had Rheumatoid arthritis (RA) in her hands, wrist and
knees for several years. She has tried various NSAID’s in the past to obtain pain relief
and is currently taking Tenoxicam ( 10 mg ) and Prednisolone ( 7.5 mg each
morning ).
MrsX.B is admitted to the hospital feeling lethargic, tired and generally unwell .
Here blood test results conferm a low haemoglobin level, and endoscopy reveals a
bleeding gastric ulcer.
The patient is married and has 2 sons . She is smoker ( smokes 10 cigarettes per day ).
Her mother died 19 years ago due suffering from gastric tumor and osteoporosis.
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Rheumatoid Arthritis
Summary Of The Case Study
Patient
Patient
Signs &
Details
History
Symptom
Laboratory Tests
*Female.
(RA) in her hands, *Feeling lethargic.
*Blood test results:
*72 yrs old
wrist and knees for *Tired and
( low Hb levels ---Anaemia ).
* married and has 2
several years
generally unwell.
sons . She is smoker
(
smokes
10
cigarettes per day ).
* Her mother died 19
years
ago
suffering
gastric
due
from
tumor
and
osteoporosis.
Further
Diagnosis
Treatment
Comments
Investigations
*Endoscopy
*RA in her hands, wrist *Various NSAID’s in the The patient can take NSAID’s
reveals a bleeding and knees.
past to obtain pain relief which has more affinity to
gastric ulcer.
*Currentlytaking
* Active gastric ulcer.
COX-2
like
Nabumetone
Tenoxicam ( 10 mg ) and instead of stopping this type of
Prednisolone ( 7.5 mg therapy as the doctor did.
each
morning ).
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Rheumatoid Arthritis
Section lll
Questions And Comments About The Case Study
Q#1 : How should this patient managed ?
Corticosteroids are associated with many adverse effects including fluid and
electrolytes disturbances, hyperglycaemia, glycosuria, increased susceptibility to
infections, osteoporosis, cataracts, mood changes, and increased occurrence of peptic
ulcer. The increased risk of peptic ulceration associated with corticosteroids occures
for example with total doses of 1g prednisolone given over 30 days or less, with
patient receiving less than 15 mg prednisolone per day having a sinificantly decreased
rate of ulcer formation.
It would be inappropriate to routinely prescribe prophylaxis to all patients receiving
corticosteroids. However, in geriatrics taking NSAID’s it is important to prescribe a
prophylaxis therapy.
******************************
Q#2 : How should this patient be managed ?
It will be necessary to stop the NSAID’s because of the gastric bleed. The patient
should rest and receive simple analgesics regularly with intra-articular ateroids
injections in the affected joints. The patient should continue her prednisolone. In view
of the gastric bleed.
The patient must take PPI like omeprazole ( 20 mg daily ).
The patient blood result show an iron deficiency anemia ( low Hb, MCV, MCHC )
The patient should receive oral ferrous sulphate ( 200 mg 8-hourly ). After 10 days of
reticulocyte count should be taken to ensure that the iron is being absorbed and thus
the the patient’s anemia is being corrected. The patient Hb level should rise by 2 g
every 3 weeks.
*********************************
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Rheumatoid Arthritis
Section lll
Q#3 : Would topical NSAID’s be of any use to this patient ?
The effeciency of topical NSAID’s remains poorly defined mainly because of the
difficulty in measuring response. The topical preparations are expensive when
compaired to rubifacients.
Topical NSAID’s are designed to present a high concentration of the locally applied
agent to the joints with minimal systemic effects. The topical NSAID’s have been
associated with fewer side effects than systemic NSAID’s
***********************************
Yosra Ashraf
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Rheumatoid Arthritis
Section lll
Case Study # 3
A 51 years old male, was diagnosed to have rheumatoid arthritis ( RA) 2 years ago by
his general practitioner (GP). He has been reasonably well controlled on diclofenac
( 50 mg three times a day ) and salphasalazine ( 1.5 g twice a day ).
In the last few weeks his RA has shown increased signs of activity with worsening
morning stiffness.
The patient is a social drinker . He is not married and lives with his father who is
suffering from hypertension.
Yosra Ashraf
26
Rheumatoid Arthritis
Section lll
Summary Of The Case Study
Patient
Patient History
Signs &
Details
Laboratory Tests
Symptoms
No Laboratory
*Male.
*Rheumatoid
*Severe pain.
*Age: 51 years old.
Arthritis
*Morning stiffness.
Tests are found in
*Decreased activity.
this case
2 years
ago.
*social drinker.
*He is not married
and lives with his
father who is suffering
from hypertension.
Further
Diagnosis
Treatment
Comments
*Rrheumatoid Arthritis
*Diclofenac ( 50 mg three times
The phicision must check
getting worsen.
a day ) .
for the presence of
Investigation
s
No Further
Investigations
found in this
case
*Sulphasalazine ( 1.5 g twice a
day ).
leucopenia, neutropenia &
thrombocytopenia which
may occur in the first 3-6
months of sulphasalazine
treatment to avoid GIT
intolerance,and other side
effects like rash.
Yosra Ashraf
27
Rheumatoid Arthritis
Section lll
Questions And Comments About The Case Study
Q#1: What are the treatment options for this patient ?
As this patient has had response to sulphasalazine and is experiencing no particular
problems with its use, there is a good argument for the co-prescription of a second
DMARD. Methotrexate is more effective than other DMARD such as gold and
hydroxychloroquine, and has low discontinuation rate. There seems little to be gained
by stopping sulphasalazine, and the addition of a DMARD with a different site and
mode of action may give an additive or even synergistic effect. The combination of
sulphasalazine and methotrexate has been shown to be effective and well tolerated.
***************************************
Q#2: What baseline data should be collected if
methotrexate therapy were to be commenced ?
Before starting Methotrexate therapy a full blood count should be taken, serum
albumin and the renal and liver functions due to the risk of liver damage with
methotrexate therapy. Methotexate should be avoided as much as possible if the
patient is alcoholic. Also this drug should be avoided in case of having
abnormal lver function or evidence of chronic viral hepatitis.
**************************************************
Yosra Ashraf
28
Rheumatoid Arthritis
Section lll
Q#3: How is Methotrexate initiated and when should a
response to methotrexate be expected ?
Methotrexate should be initiated at a dose of ( 7.5mg in one day each week ).
Mr.P.B should be counseled to take this on the same day and preferably at the same
time to avoid potentially serious administration errors. Folic Acid possibly at the dose
of (5mg twice a week ) and not on the methotrexate day, should also be started to
reduce the severity of side effects. At 4-8 weekly intervals,the dose should be
increased by 2.5 mg per week depending on patient tolerance. As Mr P.B is on
sulphasalazine it maybe appropriate to aim for a maximum maintenance dose of
( 15mg weekly rather than 20 to 25 mg ). The patient could expect to see some
improvement in symptoms 4-6 weks after the addition of methotrexate. The maximal
response would be after 3 months, depending on how quickly the dose was increased.
*************************************
Q#4: What treatment options are there to correct low
WBCs count that can be associated with methotrexate?
Leucovorin rescue is useful as the first line treatment. It is used to diminish the
toxicity and counteract the folic acid antagonistic action of methotrexate. The dosage
depends on the severity of the leucopenia. In general, up to 150 mg is usually given in
individual doses over 12-24 hrs by IM injection, IV bolus or infusion. Measures to
ensure prompt excretion of methotrexate are also important, and include alkalinization
of urine to above pH 7.0 an dmaintenance of increased urine output. In cases where
leucopenia is severe, treatment with granulocyte colony-stimulating factor may be
required. It can include marked increase in peripheral blood neutrophil counts within
24 hrs of administration. A SC dose of 5 microgram/Kg/day may be given and should
Yosra Ashraf
29
Rheumatoid Arthritis
be continued until the neutrophil count has reached and can be maintained at more
than 1.5 *10 9/L.
Section lll
Case Study # 4
PATIENT HISTORY:
The patient is a 52 year old woman with a recent history of myocardial infarction, and
a long standing history of rheumatoid arthritis with severe joint deformities in both
hands, including a gangrenous left fifth digit. She also has a history of multiple deep
venous thromboses of the lower extremities. A vague history of possible systemic
lupus erythematosus is also reported (constituting a possible mixed connective tissue
disorder). She is on multiple medications, including Coumadin and hydrocortisone
(100 mg every 8 hours) for her joint disease. The patient has a long history The
patient has a long history of borderline adrenal gland insufficiency,, which is likely a
result of the chronic administration of systemic steroids. She presents to the hospital
with complaints of fatigue and is noted to be anemic on complete blood count, which
reveals a hemoglobin of 8.1 with a hematocrit of 23.9. A rectal exam is guaiac
positive for blood. The patient is scheduled for colonoscopy to evaluate the source of
the gastrointestinal bleeding.
COLONOSCOPIC FINDINGS:
Colonoscopy demonstrates diffuse vascular nti-inf lesions from the level of the midtransverse colon to the cecum. Multiple diffuse vascular lesions are noted in the right
hemicolon, including the cecum, ascending colon and proximal transverse colon.
Although no active bleeding is noted at the time of colonoscopy, these lesions are
thought to represent the most probable source of the heme positivity in the stool.
Etiologies which are considered for the lesions evaluated endoscopically include
vasculitis, arteriovenous malformations, angiodysplasia, or lesions of cytomegalovirus
Yosra Ashraf
30
Rheumatoid Arthritis
infection. Two biopsies are procured from the right colon; one is sent for
histopathologic study, and the second is sent for CMV studies. CMV is not detected in
these subsequent studies.
Section lll
GROSS DESCRIPTION:
The specimen is received in formalin and consists of an irregularly shaped fragment
of tan-pink mucosal tissue measuring 0.1 cm in greatest dimension.
Microscopic Discripyions :
The biopsy specimen consists of a portion of cecal mucosa with a portion of
underlying submucosa with several larger submucosal vessels. Examination of the
surface of the biopsy demonstrates colonic epithelium with goblet cells and
moderately distorted crypts. Some areas of the lamina propria are expanded by a
moderate number of lymphoid cells with admixed plasma cells. Other areas of the
lamina propria demonstrate focal hemorrhage, and collections of neutrophils and
probable fragments of nuclear debris. Examination of the submucosa reveals edema
and numerous small vessels which display varying amounts of neutrophilic infiltration
and destruction of the vascular wall. Some of the vessels demonstrate tortuosity and
occlusion by a combination of neutrophils, thrombosis, nuclear debris, and
eosinophilic necrosis of the vessel wall. In the deepest portion of the biopsy, a
thickened, tortuous, moderately fibrotic vessel is noted, suggesting a chronic
vasculitic/inflammatory process.
FINAL DIAGNOSIS:
NECROTIZING LEUKOCYTOCLASTIC SMALL VESSEL VASCULITIS OF
THE COLON, OF PROBABLE AUTOIMMUNE ETIOLOGY
Yosra Ashraf
31
Rheumatoid Arthritis
Section lll
Contributor’s Note:
Systemic lupus erythematosus (SLE) is an autoimmune disorder seen predominantly
in women of childbearing age (approximately 9:1 male:female ratio), in which there is
a primary defect in the discrimination of self versus non-self antigens by the immune
system. Various antibodies with self-directed specificity have been described and are
considered diagnostic of SLE when in combination and in the appropriate clinical
setting. Clinically, SLE commonly manifests in a myriad of systemic abnormalities,
including skin rashes, polyarticular arthritis and myalgias, renal dysfunction, weight
loss with fatigue, coagulation and other hematologic abnormalities, serositis involving
heart and lungs, and localized or systemic vasculitides (as mentioned above). At least
one group has correlated the rise in the serum of complement split products with
increased risk of small vessel vasculitis in SLE patients (Abramson et al).
As a group, the self-directed immunoglobulins in SLE are referred to as anti-nuclear
antibodies (ANA), noted in greater than 95% of SLE cases. Major subtypes include
anti-double stranded DNA antibody (directed towards ds DNA in patient cells, with
their subsequent destruction); anti-Smith (directed against core proteins in the small
nuclear ribosomal complex); anti-histone antibodies, and anti-ribonucleoprotein
antibodies (U1RNP). Although these and other antibodies can be seen in other
autoimmune disorders (such as systemic sclerosis and Sjögren’s syndrome), the
combination of the proper clinical features with the presence of anti-ds DNA and antiSmith antibody is considered virtually diagnostic of SLE. The course of the disease is
variable, with a usual chronic course that tends to respond to
nti-inflammatory
therapy in the event of periods of disease exacerbation. If patients with SLE succumb
to their disease, the most common causes of death are renal failure and infections
(often secondary to long term immunosuppressive therapy).
Secondary vasculitides in patients with primary autoimmune disorders, such as
systemic lupus erythematosus and rheumatoid arthritis, are a well-recognized
Yosra Ashraf
32
Rheumatoid Arthritis
phenomenon. Although most commonly found to involve the small venules of the
skin and subcutaneous tissue, a more severe systemic vasculitis, clinically
indistinguishable from the polyarteritis nodosa group (PAN) can be seen. These
Section lll
variants are characterized by an often necrotizing leukocytoclastic vasculitis of
systemic small to medium-sized muscular arteries which can affect any system or
region. As in classic PAN, however, renal, musculoskeletal, and gastrointestinal
arteries are most commonly involved. The presentation of the case described above is
unusually florid, with diffuse vascular changes by endoscopy in the right colon,
gangrenous changes in a digit (which may represent either severe Raynaud’s
phenomenon, as noted in many SLE patients, or localized vasculitis with attendant
thrombosis of the vessels supplying the digit), a history of deep venous thromboses,
and coronary artery disease (which may or may not be related to the patient’s
autoimmune
disease).
Further
immunologic
studies
of
patient
sera
and
immunofluorescence microscopy of biopsy specimens from involved sites would have
been of great interest in the further evaluation of this case, but clinical factors
precluded such investigation.
Yosra Ashraf
33
Rheumatoid Arthritis
Section lll
Summary OF The Case Study
Patient
Details
Patient history
Signs &
Symptoms
Laboratory Tests
* 52 year old
*Myocardial infarction.
*Gastrointestinal
*Complete blood count, which
*woman.
*Long standing history of
bleeding.
reveals a :
rheumatoid arthritis with
* Fatigue.
**hemoglobin of 8.1.
**hematocrit of 23.9.
severe joint deformities in
both hands, including a
gangrenous left fifth digit.
*Multiple deep venous
thromboses of the lower
extremities.
*A vague history of possible
systemic lupus
erythematosus
*Long history of borderline
adrenal gland insufficiency,
Yosra Ashraf
34
Rheumatoid Arthritis
Section lll
Further
Investigations
* Rectal Exam.
* Colonoscopy.
* Two biopsies are
procured from the
right colon.
*Examination of
the submucosa.
Treatment
Diagnosis
NECROTIZING
LEUKOCYTOCLASTI
C SMALL VESSEL
VASCULITIS OF THE
COLON, OF
Comments
*Coumadin and
The physician must
*Hydrocortisone (100 mg
reduce the dose of
every 8 hours) for her joint
steroids taken to
disease.
minimize the side effects
* chronic administration of
as the steroids are used
systemic steroids.
only in severe cases
PROBABLE
where it is life
AUTOIMMUNE
threatening .
ETIOLOGY WITH
THE PRESENCE OF
ACTIVE RA.
Yosra Ashraf
35
Rheumatoid Arthritis
Section lll
Case Study # 5
History
The patient is a 60 year old Hispanic female with a recent diagnosis of Rheumatoid
Arthritis, brought to this tertiary care referral center by her daughters who reported a 2
month history of worsening cognitive difficulty and decreased arousal since the
patient fell from a chair.
Two and a half years ago the patient began to lose weight. She initially experienced a
rapid loss of weight from 160 to 130 pounds, but has continued to lose weight to the
point where she now weighs 116 pounds. About nine months ago, her daughters
noticed a raised bilateral rash on her feet and lower extremities with residual
hyperpigmentation of her feet and the distal portion of her legs. Six months prior to
her current presentation, she developed joint pains and subcutaneous nodules.
Diagnostic evaluation at that time revealed a Rheumatoid Factor titer of 1:1260 and
an ANA of 1:160, homogeneous pattern with an elevated ESR. She was diagnosed
with Rheumatoid Arthritis and has since been treated with regimens of non-steroidal
medications and immunosuppresive therapy. At the time of evaluation her current
regimen was Plaquenil and Prednisone.
Four months earlier she was noted by her Rheumatologist to experience gait
difficulties with "falling episodes". During this time, she is also noted to have
occasional fever and chills. A diagnosis of Diabetes Mellitus was presumed secondary
to steroid therapy. A remote reference to a diagnosis of Felty's is also mentioned in
progress notes reviewed during this time frame. Two months prior to presentation, she
fell from a chair and has had rapid progressive decline in mental status since that time.
The family denies prior significant illnesses or disease.
Yosra Ashraf
36
Rheumatoid Arthritis
Past Medical History : diet-controlled hyercholesterolemia; Family members
deny prior diabetes, hypertension, seizure disorder, autoimmune disease or
neurological disease.
Section lll
Past Surgical History: hysterectomy in 1986 and a hernia repair in 1992.
Allergies:None.
Medications: Prednisone 5 mg a day, Plaquenil 200 mg a day, Reglan, Ritalin,
Paxil,and,Premarin.
Social History: The patient lived alone in Corpus Christi, Texas until the onset
of this illness. She had been divorced for 30 years with two adult daughters and two
adult
sons.
She
does
not
smoke
or
consume
alcoholic
beverages.
Family History: positive for Diabetes Mellitus-type II in one son and a history
of joint pains in one of the daughters; her ex-husband is deceased secondary to gastric
cancer
PhysicalExamination
B.P. B.P. 150/100 ; pulse 78 ; temperature 98.2 ; respirations were regular at 20.
General: This is a thin Hispanic female lying in bed without signs of respiratory
compromise or signs of pain or discomfort. She is intermittently responsive to verbal
stimuli.
HEENT: HEENT exam reveals anicteric sclera with no conjunctival erythema.
There are no oral mucosal lesions and the oropharynx is clear noting a palatine torus.
The neck examination shows no JVD, no bruits, and no lymphadenopathy or
thyromegaly.
Cardiovascular: Exam reveals a regular rhythm with normal rate and good S1
and
S2.
Chest:
There
Exam
is
reveals
no
significant
lung
fields
murmur
are
clear
and
to
no
rub.
auscultation
Abdomen: Soft, non tender with bowel sounds present in all four quadrants; there
is no evidence of hepatosplenomegaly; there is a PEG in place which is clean, dry and
without evidence of induration, erythema, or exudate.
Yosra Ashraf
37
Rheumatoid Arthritis
Skin: Examination reveals hyperpigmentation on the distal extremities and small
subcutaneous
nodules
on
the
extensor
surfaces
of
the
forearms.
Extremities: No signs of clubbing, cyanosis, or edema.
Section lll
Neurological-Examination
Mental-Status
Attention: intermittently alert and responsive to verbal stimuli; she was not
oriented to place or time; speech is whispered, sparse, and slow; spontaneous speech
is limited; comprehends simple commands but not complex commands, she could
perform simple repeats; a full MMSE score was not available but she was reported to
be unable to perform memory operations, write a sentence, perform constructional
tasks, and did not name objects. She had evidence of ideomotor apraxias.
Cranial nerve function: Are normal.
Motor-Examination:
Tone was moderately increased in both lower extremities and increased in the upper
extremities with tone in the left arm markedly increased. Muscle bulk revealed
moderate atrophy of all extremity muscles with wasting of the small intrinsics of the
hand.
Sensory-Examination:
Revealed
withdrawal
of
all
four
extremities
to
noxious
stimuli.
Reflexes:
Brisk on the right and there was a mild jaw jerk. Toes were downgoing on the right
but upgoing on the left with Babinski examination. There was a bilateral palmomental
reflex and a snout reflex but no evidence of glabellar or rooting reflex.
Yosra Ashraf
38
Rheumatoid Arthritis
Section lll
Summary Of The Case Study
Patient History
Patient Details
Signs &
Symptoms
*60 year old Hispanic
*Past Medical History:
*Raised bilateral rash on
female.
Diet-controlled
her feet and lower
* The patient lived alone
hyercholesterolemia;
extremities with residual
in Corpus Christi, Texas
diabetes,hypertension,
hyperpigmentation.
until the onset of this
seizure disorder,
* worsening cognitive
illness. She had been
autoimmune disease or
difficulty.
divorced for 30 years
neurological disease.
*Weight loss.
with two adult daughters
*Past Surgical History:
*Joint pains.
and two adult sons.
hysterectomy in 1986
* Gait difficulties with
and a hernia repair in
falling episodes.
1992
* Occasional fever and
Laboratory Tests
*ANA of 1:160.
*Homogeneous pattern with an
elevated ESR
chills.
Yosra Ashraf
39
Rheumatoid Arthritis
Section lll
Further
Investigations
*B.P. 150/100
Diagnosis
* Temperature 98.2 ;
extremities and
*Prednisone 5 mg a
small
day.
subcutaneous
* HEENT
*CVS check
*Skin examination
the dose of Prednisolone to
7.5 mg instead of 5 mg to
achieve the best reduction of
*Plaquenil 200 mg a
joint destruction rate.
day. *Reglan.
nodules on the
* Ritalin.
extensor surfaces
*Paxil.
* Abdominal
examination.
immunosuppressive
therapy.
*Respirations were
regular at 20.
Comments
hyperpigmentation * Various NSAID’s and The physician must increase
on the distal
* Pulse 78
Treatment
of the forearms.
*Premarin.
( pigmentation).
*Chest examination.
*Extremities
examination.
* Neurological
examination.( some
abnormality in attention
Yosra Ashraf
40
Rheumatoid Arthritis
Section lll
Case Study # 6
History
M.S., 31-year-old woman presented to the Charles C. Harris Skin and Cancer Pavilion
in October, 2000, with asymptomatic lesions on her arms of five months duration. She
had been evaluated by a rheumatologist and a dermatologist who performed skin
biopsies and laboratory studies. On review of systems, she reported morning stiffness
in her hands, elbows, and knees, with improvement after 30 minutes. She also
reported a ten pound weight loss since the birth of her son in April, 2000. She denied
fever, malaise, headaches, visual difficulties, or other problems.
She was treated with plaquenil 200 mg. twice daily. At a one-month follow-up
examination, the lesions resolved although her joint symptoms persisted
Diagnosis:
Juvenile rheumatoid arthritis, which responded to hydroxychlorine, previously had
been present at age 16.
Physical Examination:
Flesh-colored, subcutaneous nodules ranging from 0.2 to 1.0-cm in diameter were
distributed linearly along the biceps and tendons of the medial aspects of the upper
arms. There was generalized fat wasting with zygomatic, temporal, and blood vessel
prominence. There was also buccal fat pad atrophy. There were no mucosal lesions or
pain on ocular moveme
Yosra Ashraf
41
Rheumatoid Arthritis
Section lll
Laboratory Tests
White-cell count 6.4 x 109/L, with 51% neutrophils, 27% lymphs, 8% monos, 12%
eosinophils, and 1% basophils, erythrocyte sedimentation rate 11 mm/hr, rheumatoid
factor <20 IU/ml, angiotensin converting enzyme 36.8 U/L, HLA-B27 negative,
urinalysis normal, serum protein electrophoresis with a total protein 6.3 g/dl, albumin
3.27 g/dl, and normal globulin indices, antinuclear antibody negative, C- and PANCAs negative, anti-DNA Ab negative, and calcium 8.5 mg/dl.
Histopathology:
There are palisades of histiocytes surrounding a central area of eosinophilic fibrinoid
degeneration. The surrounding fat lobules are atrophic
Diagnosis:
Juvenile rheumatoid arthritis (Juvenile chronic arthritis).
Yosra Ashraf
42
Rheumatoid Arthritis
Section lll
Comments:
Juvenile rheumatoid arthritis, known as juvenile chronic arthritis in Europe, is the
most common rheumatic disease in children. Criteria for diagnosis include age of
onset less than 16 years, disease duration greater than six weeks, arthritis, and
exclusion of other forms of juvenile arthritis. Juvenile rheumatoid arthritis is
subdivided into pauciarticular (less than five joints involved), polyarticular (five or
greater joints involved), and systemic (arthritis, fever and rash) forms.
Skin manifestations of juvenile rheumatoid arthritis include amyloiosis which occurs
in one to ten percent of all subtypes. Ninety percent of systemic-onset juvenile
rheumatoid arthritis is characterized by an evanescent salmon-covered eruption that
occurs on the trunk and thighs and which is concurrent with fever. The eruption may
be elicited by scratching, ie, the Koebner phenomenon. A variant of juvenile
rheumatoid arthritis with onset in young adulthood is adult Still's disease, which
occurs at ages 16 to 35, is characterized by multi-system involvement and an
evanescent, salmon-pink, macular and papular eruption, and is accompanied by fever.
The eruption occurs on the trunk and proximal extremities and may be elicited by the
Koebner phenomenon.
The skin manifestations of rheumatoid arthritis include rheumatoid nodules,
rheumatoid papules, rheumatoid neutrophilic dermatitis, and vasculitis. Rheumatoid
nodules are subcutaneous nodules that occur in 20 percent of rheumatoid patients with
positive rheumatoid factors, and rarely in seronegative patients. The nodules generally
correlate with disease activity. Rheumatoid nodulosis (multiple, widespread nodules)
is a separate entity that occurs mostly in men with a low-grade fever and mild
synovitis. Nodules develop most commonly on pressure areas, such as the elbows,
joints, ischial and sacral prominences, along tendons, and the occiput. In general,
nodules regress with treatment as the rheumatoid arthritis improves. Rheumatoid
Yosra Ashraf
43
Rheumatoid Arthritis
nodules in rheumatoid factor-negative patients have been reported but appear to be
rare.
Section lll
Summary Of The Case Study
Patient Details
Patient History
Signs &
Symptoms
Laboratory Tests
* Female.
*Juvenile rheumatoid
*Asymptomatic lesions on
WBCs 6.4 x 109/L,( with 51%
*31-year-old.
arthritis since age 16.
her arms of five months
neutrophils, 27% lymphs, 8%
duration.
monos, 12% eosinophils, and
*Morning stiffness in her
1% basophils),
hands, elbows, and knees.
*Ten pound weight loss
since the birth of her son in
April, 2000.
ESR: 11 mm/hr,
RF<20 IU/ml,
ACI: 36.8 U/L, HLA-B27
*Urinalysis normal,
SPE: with (t p 6.3 g/d), albumin
* She denied fever, malaise, 3.27 g/dl, and normal globulin
headaches,visualdifficulties. indices, antinuclear antibody
negative, C- and P-ANCAs
negative, anti-DNA Ab
negative, and calcium 8.5
mg/dl.
Further
Investigations
Yosra Ashraf
Diagnosis
Treatment
44
Comments
Rheumatoid Arthritis
*Skin biopsies.
*Juvenile rheumatoid
arthritis.
*plaquenil 200 mg. twice
*Physical Examination.
daily.
* Histography.
*Hydroxychlorine.
The physician must check
for the liver, kidney, and
vision function and
efficiency and do the slitlamp examination routinely
to check for uveitis while
using plaquenil.
Section lll
Case Study # 7
Case Report:
An 11-year-old girl, was brought with the complaints of progressively worsening
stiffness and restriction of movements of all joints, associated with increasing
difficulty in walking, and inability to close hands into a fist. She was the product of a
non-consanguineous marriage; her mother was 24 years and father 30 years old. She
was the second of three sibs, all of whom were normal. There was no history of a
similar illness in any family member.. She developed normally both physically and
mentally till the age of 3 years, when she was noted to walk with her right leg and
foot turned outwards. Within a year she developed knock knees as well. She also had
complaints of being tired easily following exertion, difficulty in getting up from the
squatting position and climbing stairs. The difficulty appeared to be related to the
developing abnormality of the joints as well as to muscular weakness. At age five
years she developed increasing stiffness of her joints which progressed to a marked
restriction of movements of many of her joints namely elbows, wrists, small joints of
hands and feet, hip, knee, ankle and neck at the time of presentation. There was no
history of fever, joint pains or fractures.
She had been worked up elsewhere, and been given provisional diagnoses of rheumatoid arthritis, rickets, mucopolysaccharidosis and metaphyseal dysplasia; treatments
received were high doses of Vitamin D, anti-inflammatory drugs and steroids at
different points of time, without any significant relief.
Yosra Ashraf
45
Rheumatoid Arthritis
On examination, she was thin built, height was 120 centimetres falling below the 5th
centile for her age, upper segment was 60 centimeres (upper segment = lower
segment) and arm span-125 centimaetres (more than height). Vitals were within
normal limits. She had a dysmorphic face with a mild depression of the nasal bridge,
flattened nose, everted nostrils, hypoplastic maxilla and a prominent pouting mouth,
giving a leonine appearance (Fig. 1). There were no corneal opacities.
Facial appearance of
the child with RA
Examination of the musculoskeletal system examination showed widening of the
elbows, wrists, knees and interphalangeal joints of the hands and feet. Movements of
all joints were restricted, including neck and spine (with loss of lumbar lordosis),
shoulder, elbow, wrist, knee, ankle and small joints of hands and feet, the restriction
being maximum in the distal joints as compared to the proximal joints. The widening
and fixed flexion deformity of the metacarpophalangeal and interphalangeal joints of
the hands gave the hands a claw like appearance. There was also coxa-vara and genu
valgum. There were no bony deformities or pain or tenderness of any of the joints.
Gait was waddling and because of stiffness of all joints, like a puppet.
Examination of central nervous system showed normal higher functions with IQ 90.
Cranial nerves were normal. There was wasting of all muscles of hands and feet; tone
and power could not be tested properly in view of the stiffness of all the joints. The
deep tendon jerks were normal. Other neurological parameters were normal.
Abdominal examina-tion did not reveal any hepatosplenomegaly, and the
cardiovascular and respiratory systems were unreamarkable.
Yosra Ashraf
46
Rheumatoid Arthritis
Investigations revealed: Serum calcium 10.2 mg/dl, phosphorus 3.2 mg/dl, and
alkaline phosphatase 12.0 KA units. Urine for muco-polysaccharidosis was negative.
CPK was 115 units/1, and rheumatoid factor and antinuclear antibodies were
negative. ESR was 9 mm fall in first hour by Westergren method.
On skeletal survey, X-ray Chest and skull were normal. X-ray thoracolumbar spine
(anteroposterior and lateral view) showed reduced height of the lumbar vertebral
bodies. There was anterior erosion of the vertebral body, with a tongue like projection
of the vertebra anteriorly. The intervertebral disc space was normal (Fig. 2). The
femoral epiphysis appeared broad, with widened symphysis pubis on pelvic X-ray
(Fig.3). There was metaphyscal and epiphyseal widening with irregularity of the
epiphyseal margins on hand X-rays.
Fig.2.
X-ray
of
spine,lateral-view
the
showing
Fig. 3. X-ray pelvis–broad femoral epiphysis
and symphysis pubis.
platyspondyly with tongue
like
projection
of
the
vertebrae anteriorly
.Comments
PPAC is an autosomal recessive dis-order(6); the gene has been localised recently to
chromosome 6q22(7,8). The etiopatho-genesis is not clear, but it has been shown to
be primarily a disorder of the articular cartilage. Histological studies show a peculiar
nest like clustering of the chondrocytes in the resting and growth cartilage(1). Various
treatment modalities have been tried, but none have proven effective till date. The
disease is relentlessly progressive and leads to severe difficulties in ambulation and
Yosra Ashraf
47
Rheumatoid Arthritis
activities of daily living. No reports are available on the ultimate outcome of these
patients since this is a relatively new disease.
Slowly progressive restriction of move-ments of all the joints starting between 3-8
years age, associated with widening of the joints but no pain or tenderness, should
raise the suspicion of PPAC. However, it is an uncommon condition not widely
Section lll
known, and frequently misdiagnosed. Spranger et al.(1) in their five cases reported
that one patient was given various diagnoses including rheumatoid arthritis,
polymyositis, endochondral dysosto-sis and Morquio disease, while another received
the diagnosis of endochondral dysostosis. Our patient also reported to us with
diagnoses of rickets, rheumatoid arthritis and MPS having been made elsewhere.
Normal calcium, phosphorus and alkaline phospaha-tase, and absence of
characteristic changes of rickets on X-rays of wrists and ankles excluded rickets,
while a normal ESR, negative rheu-matoid factor, absence of fever, pain and
tenderness ruled out rheumatoid arthritis. In view of the coarse facial features, short
stature and skeletal abnormalities and normal IQ, Morquio disease was a likely
possibility and a skeletal survey was ordered to look for bony changes of MPS.
The X-rays however showed up the pathognomonic changes of PPAC(9,10). In view
of the difficulty in early clinical diagnosis of the disease, it is imperative that
radiologists be familiar with radiographic features of the disease in order to avoid
needless investigations and trials of medication. The characteristic radiographic
features are narrow joint space with wide metaphyses and flat epiphyses. Femoral
heads are enlarged and acetabulae are irregular. Platyspondyly with erosion of end
plates is present. This condition mimics juvenile rheumatoid arthritis but bony
changes show joint space narrowing, over-growth of epiphyses and osteopenia, which
are not seen in PPAV. This condition should also be differentiated from
spondyloepiphyseal dysplasia congenita, in which the extremities are normal; from
spondyloepiphyseal dysplasia tarda, where the patient has a characteristic dorsal
hump and spondylo-metaphyseal dysplasia in which epiphyses are not affected and
joint stiffness is not present.
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Rheumatoid Arthritis
Though our patient showed all the classic clinical and radiological features of PPAC,
the facial dysmorphism was misleading. Such facies have not been reported in
association with PPAC earlier. Another hitherto un-reported feature in our patient was
the arm span being greater than the height. A reduction of measured standing height
may occur due to flexion deformities at the hips; however the flexion at the hips was
around 10 degrees and does not explain the marked difference of 5 cm between arm
span and standing height.
Section lll
Summary Of The Case Study
Patient Details
Patient
History
Signs &
Symptoms
* 11-year-old girl
* She was the product
of a nonconsanguineous
marriage; her mother
was 24 years and father
30 years old. She was
the second of three sibs,
all of whom were
normal.
*Thin built.
*Height was 120 cm.
*walk with her right
leg and foot turned
outwards.Then she
developed knock
knees and
complaints of being
tired easily.
*Worsening stiffness and
restriction of movements
of all joints.
*Increasing difficulty in
walking.
*Inability to close hands
into a fist.
Further
Investigations
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Diagnosis
Treatment
49
Laboratory
Tests
Serum calcium 10.2 mg/dl,
phosphorus 3.2 mg/dl, and
alkaline phosphatase 12.0 KA
units. Urine for mucopolysaccharidosis
was
negative. CPK was 115
units/1, and rheumatoid factor
and antinuclear antibodies
were negative. ESR was 9
mm fall in first hour by
Westergren method.
Comments
Rheumatoid Arthritis
*Physical examination.
*Musculoskeletal
system examination.
*Examination of central
nervous system,
abdominal and
respiratory examination.
*X-ray Chest and skull
were normal. X-ray
thoracolumbar spine
showed reduced height
of the lumbar vertebral
bodies.
The physician must
*Rheuma-toid arthritis,
*Vitamin D.
*Rickets.
*Anti-inflammatory
*Mucopolysaccharidosis. drugs.
*Metaphyseal dysplasia.
*Steroids.
change the therapy to
the second line
treatment instead of
having drugs which is
ineffective in this case
with keeping the dose
of vitamin D and
stopping the steroids.
Section lll
Case Study # 8
HISTORY:
This is a 7 year old girl lives with her parents who has had polyarticular JRA for over
a year. Most recent management has been with prednisone, methotrexate and tolectin.
The symptoms improved with little evidence of ongoing synovitis. A mass in the left
bicipital area was first noticed at the age of 7 years and 9 months.
PHYSICAL EXAM:
The mass was firm, located in the antero-medial aspect of the left upper arm and was
difficult to separate from the biceps. It did not transilluminate. Shoulder ROM was
full.
SONOGRAM AND XRAYS:
The sonogram showed a solid soft tissue mass which was fairly homogeneous in
echo-genicity, and well defined with minimal vascularity. No connection with the
shoulder joint was observed. MRI with gadolinium showed a mixed density collection
which appeared to have a narrow connection with the shoulder joint. An arthrogram
50
Yosra Ashraf
Rheumatoid Arthritis
of the left shoulder joint demonstrated extension of dye down the bicipital groove and
into the mass in the upper arm. The mass was more palpable after the arthrogram. We
concluded that the mass was a synovial cyst due to chronic synovitis.
FOLLOW-UP:
The synovial cyst has resolved spontaneously and has not recurred over 3-months
follow-up.
Section lll
Summary Of The Case Study
Patient
Details
Patient
History
*7 year old
*Has had
*Girl.
polyarticular JRA for
* Lives with her
over a year.
parents.
*Mass in the left
Signs &
Symptoms
* Just to check for the
improvement.
Laboratory Tests
No Laboratory
Tests Are Found
bicipital area.
Further
Investigations
Diagnosis
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Treatment
51
Comments
Rheumatoid Arthritis
*Physical
examination.
SYNOVIAL
* SONOGRAM .
CYST OF THE
*XRAYS.
SHOULDER
*MRI with
JOINT IN THE
gadolinium.
BICIPITAL
*Prednisone.
The physician must pay
* Methotrexate.
attention to the strength and
*Tolectin
frequency of methotrexate
dosing to avoid pulmonary
toxicity.
AREA IN
JUVENILE
RHEUMATOID
ARTHRITIS.
Section lll
Case Study # 9
Mrs. A.H is a 58 year old with a long history of severe RA. She presents to the
rheumatology clinic with severe pain in her left foot. On examination, three toes were
found to be discolored, and appeared ischemic. A large ulcer was also found on the
heel of the same foot. She was diagnosed as having rheumatoid vasculitis
**********************************
.
Summary Of The Case Study
Patient
Details
Patient
History
Signs &
Symptoms
Laboratory Tests
*Female.
*Long history of
*Severe pain in her left
* 58 year sold.
severe Rheumatoid
foot.
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52
No Laboratory
Tests Are Written
Rheumatoid Arthritis
Arthritis.
Further
Investigations
Diagnosis
* Normal foot
*Rheumatoid
examination.
vasculitis.
Treatment
Comments
Treatment and comments are suggested
in the questions & answers
Section lll
Questions And Comments About The Case Study
Q#1: What is the role of Cyclophosphamide and
methylprednisolone in the management of this patient?
Cyclophosphamide and methylprednisolone have been used effectively in rheumatoid
vasculitis for their potent immunosuppressive actions. Regimens do vary, but
intravenous pulses every 4 to 6 weeks are often used in rheumatology centers.
Methylprednisolone at a dose of ( 500 mg to 1 g over an hour or more to prevent
cardiac arrhythmia or ischemia ) gives a rapid and intense anti-inflammatory action
as well as immunosuppressive activity. .Once the condition improves, oral steroids
may be considered. Such a improvement may be seen by monitoring laboratory
indices such as ESR, renal function and urine protein content. Cyclophosphamide ( a
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Rheumatoid Arthritis
cytotoxic agent ) may either be given as a slow IV bouls foe a short IV infusion, at a
dosage range of 7.5 to 12.5 mg/kg depending on the patient’s condition and renal
function. Patient usually tolerate cyclophosphamide well although prophylactic
antiemetics should be given and the possibility of fertility suppression should be
discussed with patients.
*************************************
Q#2: What precautions should be taken with
cyclophosphamide?
Prior to administration of cyclophosphamide, patients should have a full blood count,
urea and electrolytes, and creatinine measured. Also, a full medical examination
should be carried out to exclude intercurrent illness or evidence of infection.
Section lll
A high fluid intake ( at least 2.5 L on the infusion day ) should be maintained to
reduce the risk of haemorrhagic cystitis, possibly with the edition of IV fluids.
Mesna ( Uromitexan ) is sometimes also given, although there is little clinical
evidence
that
it
is
needed
with
such
moderate
doses.
Extravasationof
cyclophosphamide unlikely to be serious if infusion is promptly discontinued, and
ward staff should be familiar with the extravasation procedure.
*********************************
Q#3: What other treatment options are available for this
patient?
Administration of Epoprostenol or Iloprost has been used in rheumatoid vasculitis to
improve vasculitic ulcers and reduce peripheral ischemia. Neither is license in this
condition, and iloprost is available only no a named patient basis at present. Both are
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Rheumatoid Arthritis
forms of prostacyclin wich is a potent vasodilator and inhibitor of platelete
aggregation. These are given either as IV infusions over 8 to 12 hours for 3 to 6 days
or, in severe peripheral ischemia, as a continuous 24 hou infusion for up to 5 days.
Infusion rates are titrated according to patient response and tolerance. Pulse and blood
pressure should be monitored regularly at first as hypotension occurs (withhold any
medication that might potentiate this , eg. Nifedipine ).
Section lll
Case Study # 10
Clinical Problem
This is the radiograph of a 60 year old married lady with chronic rheumatoid arthritis
who presented to us with problems 4 weeks after left total elbow arthroplasty. She had
a similar procedure performed on the opposite side without problem. One week after
this surgery she felt a “clunk” in her elbow and then had difficulty moving it without
discomfort. Radiographs showed the elbow had dislocated. A closed reduction was
performed, but 2 weeks later the dislocation recurred. Open reduction and a soft tissue
reconstruction was performed at that time. Now the elbow is again dislocated, swollen
and painful on all motion – she keeps it in a splint at all times. Her lateral elbow
incision is relatively calm, but the sutures are still in place. She has had two surgeries
and one manipulation in less than one month. Her exam indicates ulnar nerve
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Rheumatoid Arthritis
irritation,
but
she
is
otherwise
neurovascularly
intact.
Our concerns included: the patient’s loss of elbow function, wound status,
neurovascular status, risks of revision of cemented prosthesis in soft rheumatoid bone,
incisional approaches.
Pre-operative Radiograph
Section lll
Management
Closed reduction was attempted under anesthesia and fluoroscopy. This could not be
accomplished.
Open reduction was attempted after ulnar nerve dissection through a new
posteriormedial approach. A stable reduction could not be achieved. Revision to
constrained total elbow was accomplished with minor penetrations of ulna and
humerus in process of cement removal. Post operative range was 0-135 degrees.
Neurovascular status intact.
Post operative radiograph
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Rheumatoid Arthritis
Section lll
Summary Of The Case Study
Patient Details
Patient
History
*Had a history of
*Female.
* 60 years old
chronic
Signs &
Symptoms
Laboratory Tests
*She felt a clunk in her
No Laboratory Tests
Are Found
elbow.
Rheumatoid
*Married.
Arhritis.
*Difficulty in moving
her elbow without
discomfort.
Further
Investigations
Yosra Ashraf
Diagnosis
Treatment
57
Comments
Rheumatoid Arthritis
* Radiography.
*Ulnar nerve
*Left total elbow
* fluoroscopy.
irritation.
arthroplasty.
* Chronic
( and on the other
Rheumatoid
side also ).
Arthritis.
* Closed reduction
was attempted under
anesthesia and
No medication
are mentioned
in this case so
comments will
be difficult on
the surgical
procedure
.
fluoroscopy.
But the physician can
* Open reduction
use in this case the
was attempted after
steroid therapy to reduce
ulnar nerve
pain and inflammation
dissection through a
inducedafter the surgery
new posteriormedial
as the case is severe.
approach.
Section lV
Important additional practice points :
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Rheumatoid Arthritis
Treatment of RA should begin as soon as possible, as there is evidence that most
patients will develop bone erosions within the first 2 years of their disease. Such
early treatment maybe realized by the use of early arthritis clinics in which
patients are seen within 2 weeks of referral from their general practitioner.
There is a new gene therapy for Rheumatic diseases.
Patients with RA may be highly susceptible to TB.
Starting RA treatment early saves money quickly.
People setting in smoking places and women are at risk for developing
Rheumatoid Arthritis.
Patient education only part of a good RA management program.
Multiple DMARD therapy may offer advantages over single-drug regimens.
An episode of depression can have a life-long influence on RA pain and disability
.
Section V
Pharmacoeconomics
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Rheumatoid Arthritis
Pharmacoeconomics is the science of demonstrating the
balance between costs and consequences of drug therapy.
Outcomes research is concerned with evaluating the effects of medical intervention on
clinical, economic and humanistic measures.
Pharmacoeconomics of NSAIDs: Beyond Bleeds
OBJECTIVE:
To determine the marginal effect of including a minor, yet common, gastrointestinal
(GI) side effect in a cost effectiveness analysis of NSAID therapy.
DESIGN:
Base economic model of cost effectiveness analysis (CEA) developed using data from
a randomized controlled trial of two formulations of an NSAID therapy (conventional
versus extended release etodolac) for the treatment of osteoarthritis (OA) of the knee.
Section
INTERVENTIONS:
Patients were randomized to receive either conventional or extended release etodolac
with primary endpoints evaluated at four weeks. Cost effectiveness was calculated
from a managed care perspective as dollars spent per OA patient treated, focusing on
the marginal dollar value of reduced side effects. Costs included in the analysis were
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Rheumatoid Arthritis
initial ($64 or $71) and subsequent ($64) prescriptions for NSAID therapy,
pharmacological treatment of side effects ($79), and physician office visits ($50).
MAIN OUTCOME MEASURES:
Percent reduction in dyspepsia, average cost per OA patient treated.
RESULTS:
Reduced instances of dyspepsia, a common side effect of NSAID therapy, from 20%
to 8% resulted in an estimated marginal cost savings to the insurer of $14 per patient
switched from conventional to extended release etodolac. In addition, there were cost
savings to the patient in terms of reduced out-of-pocket expenses. A more favorable
side-effect profile also may assist in improving patient compliance.
CONCLUSION:
The marginal effect of including common GI side effects in a CEA of NSAIDs may
have important economic implications for managed care providers. While ulceration
and bleeds are the most serious and costly side effects associated with NSAID
therapy, it is important to consider other positive and negative outcomes associated
with therapy when performing a pharmacoeconomic evaluation.
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Rheumatoid Arthritis
BIBLIOGARPHY :
1. Internet.
2. Clinical Pharmacy & Therapeutics.
Roger Walker _ Edwards
3. British National Formulary ( BNF ).
4. Basia & Clinical Pharmacology.
Betram G. Katzung
5. Lippen Cotts.
6. Clinical Drug Data.
7. The Merck Mannual
8. The Pharmacological Bases Of Therapeutics
Alfred Goodman Gilman.
9. Medical Journals:
British Journal of Reumatology.
Scandinavian journal of Rheumatology.
Drug Safety ( reprint ).

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