Signed Date:July.22 2001
Yosra Ashraf
1
Rheumatoid Arthritis

Acknowledgement
Yosra Ashraf
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Rheumatoid Arthritis

INDEX
Section Page
P.4
(( Pharmaceutical care of Rheumatoid Arthritis))
P.8
patient counsling.
P.8
Chice of drug therapy.
P.10
In case of having other diseases
P.10
Discussion Of Clinical Cases About Rheumatoid Arthritis
P.15
Additional Practice Points
P.57
Pharmacoe-economics
P.58
Yosra Ashraf
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Rheumatoid Arthritis

P.60
GENERAL INTRODUCTION
Yosra Ashraf
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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
Yosra Ashraf
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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.
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
Yosra Ashraf
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Rheumatoid Arthritis

Anthranilic acids
Mefenamic acids
Indole/Indene/derivatives
Acemetacin
Etodolac
Indomethacin
Sulindac
Propionic acids
Fenbufen
Fenoprofen
Flurbiprofen
Ibuprofen
Ketoprofen
Naproxen
Tiaprofenic acid
Butanone
Nabumetone
Oxicams
Meloxicam
Piroxicam
Tenoxicam
Pyrazolidinediones
Phenylbutazone
Yosra Ashraf
DRUG ADULT DAILY DOSE RANGE FOR RA.
Acetic acid :
Aceclofenac
Diclofenac
100 mg in 2 doses
75-150 mg in 3 doses
(or 100mg once daily sustained release)
1500 mg in 3 doses
60mg in 2 doses
200-600 mg in 2 doses
50-200 mg in 3 doses
300-400 mg in 2 doses
600-1000 mg in 2 doses
2.4-3.2 g in 4 doses
150-300 mg in 2-4 doses
1.2-3.2 g in 3-4 doses
150-300 mg in 3 doses
500-750 mg in 2 doses
600-1200 mg in 3 doses
1-1.5 g in 1-2 doses
15 mg in 1 dose
20 mg in 1 or 2 doses
20 mg daily
300-400 mg in 3-4 doses
7
Rheumatoid Arthritis

Azapropazone 1.2 g in 2-4 doses
Salicylates
Aspirin
Benorylate
Diflunisal
3-6 g in 4-6 doses
4-8 g in 2-3 doses
1.0 g in 2 doses
Yosra Ashraf
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Rheumatoid Arthritis

Section ll
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.

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 is a vital part of treating RA in a patient, both in acute flares of disease and in the chronic state.
Yosra Ashraf
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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.
Yosra Ashraf Rheumatoid Arthritis

Section ll
2.2
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.
DISEASE
STATE
DRUGS
USED
ACEI’s
INTERACTION
Aspirin and other NSAID’s have been reported to reduce the hypotensive effects of ACEI’s via inhibition of PG synthesis.
Diuretics may be increased when they are used together.
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. patient receiving antihypertensives as their effect is reduced.
Yosra Ashraf Rheumatoid Arthritis

Oral hypoglycemics
Insulin
May increase the effects of sulphonylureas and necessitate a reduction in their dose.
Doses maybe reduced to avoid severe hypoglycemia
Quinolones
Probenecid
Griseofolvin
Metoclopramide
Convulsions can occur due to interactions of
Ciprofloxacin mainly and antimicrobiales and
NSAID’s
Excretion of ketoprofen delayed (increased plasma concentration).Salicylate antagonise the uricosuric action of probenecid and sulphenpyrazone and should not be given concurrently.
Reduce aspirin blood levels and alter its absorption.
Enhances the absorption of paracetamol.
Sodium valproate
Phenytoin
Cyclosporin
Generally all corticosteroids
Prolonged use with aspirin may result in greater than anticipated free levels of valproic acid with accumulation to toxic levels.
Azapropazone, ibuprofen and phenylbutazone can inhibit the metabolism of phenytoin.
Causes renal deterioration with the use of diclofenac. And also it causes nephrotoxicity.
They decrease the blood salicylate concentration by increasing the glomerular filteration rate. Both drugs are ulcerogenic.
Yosra Ashraf Rheumatoid Arthritis

Anticoagulants
Warfarin
Aspirin displaces coumarins from plasma protien binding sites and thus potentiate their action.
Aspirin also tends to reduce plasma prothrombi when taken in large doses. It decreases platelat adhesiveness and cause occult bleeding.
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.
All NSAID’s It increases blood loss due to aspirin’s damage to the gastric mucosa.
Methotrexate Can be displaced from plasma protein binding by salicylates which also inhibit the renal tubular 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.
Lithium 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.
Yosra Ashraf Rheumatoid Arthritis

Cholestyramine It reduces the bioavailability of diclofenac when the two agenta are given together.
Colestipol 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.
Yosra Ashraf Rheumatoid Arthritis

Section lll
:
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
Yosra Ashraf 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.
Yosra Ashraf Rheumatoid Arthritis

Section lll
Patient
Details
Patient
History
Signs &
Symptoms
Laboratory
Tests
* Female
*52 yrs old
* a social worker
* smoked for 20 years but has recently stopped
*married and has no children
* 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.
21-year history of deforming polyarticular symmetrical inflammatory arthritis predominantly involving the wrists, (MCP) joints, knees and ankle joints. evaluation and treatment was done. 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.
*Difficulty to work full time, drive her car, and take care of her house.
*Polydypsia.
*Polyuria.
( Signs of iatrogenic diabetes mellitus). menopausal for 5 years
*Hb: 10.9 g/dL
(microcytosis) *low serum iron. *leukocyte count was
3200/micro-L (neutropenia and a peripheral smear showed large, granular lymphocytes). *Platelet count 450000/micro-L,
*(ESR) was 72 mm/hr
*RF was 1:1280.
FBS: 72 mg/dL, *blood urea nitrogen (BUN) was 38 mg/dL
*serum creatinine was 2.1 mg/dL.
Yosra Ashraf Rheumatoid Arthritis

Further
Investigations
Diagnosis Treatments Comments
No Further investigation written in the case
*Active rheumatoid arthritis, including active
*Ibuprofen 800 mg 4 times per day.
**The physician must start giving her an anti-osteoporosis synovitis, elevated ESR, *Hydroxychloroquine high rheumatoid factor and 200 mg twice daily. extensive hand nodules and vasculitis rash.
*Prednisolone 5 mg per day therapy to protect her from having this disease as she is menopause and takes corticosteroids.
*Advanced ulnar deformity with subluxed second and third MCP joints.
*Small effusion in knee joints (not aspirated)
*Peripheral neuropathy up to the ankles bilaterally.
*She tried only
Methotrexate.
*Hydroxychloroquine.
* Small vasculitis lesions were present on her lower extremity, with necrotic areas. *Spleen was palpable. *Epigastric tenderness.
( had been continuously on
**Methotrexate should be avoided due to her susceptibility prednisolone at an average dose of 7.5 mg to its toxicity.
per day for the last 7 years).
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.
Yosra Ashraf Rheumatoid Arthritis

Section lll
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.
Yosra Ashraf 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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Yosra Ashraf 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.
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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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Yosra Ashraf Rheumatoid Arthritis

Section lll
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.
Yosra Ashraf Rheumatoid Arthritis

Patient
Details
Patient
History
Signs &
Symptom
Laboratory Tests
*Female.
*72 yrs old wrist and knees for
* married and has 2 several years
*Tired and generally unwell. sons . She is smoker
(RA) in her hands, *Feeling lethargic.
( smokes 10 cigarettes per day ).
*Blood test results:
( low Hb levels ---Anaemia ).
* Her mother died 19 years ago due suffering from gastric tumor and osteoporosis.
Further
Investigations
Diagnosis Treatment Comments
*Endoscopy reveals a bleeding and knees. gastric ulcer.
*RA in her hands, wrist
* Active gastric ulcer.
*Various NSAID’s in the The patient can take NSAID’s past to obtain pain relief
*Currentlytaking which has more affinity to
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 ).
Yosra Ashraf Rheumatoid Arthritis

Section lll
Q#1 :
?
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.
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Q#2
?
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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Yosra Ashraf Rheumatoid Arthritis

Section lll
Q#3 :
?
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
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Yosra Ashraf Rheumatoid Arthritis

Section lll
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 Rheumatoid Arthritis

Section lll
Patient
Details
Patient History Signs &
Symptoms
Laboratory Tests
*Male.
*Age: 51 years old.
* social drinker.
*He is not married and lives with his father who is suffering from hypertension.
*Rheumatoid
Arthritis 2 years ago.
*Severe pain.
*Morning stiffness.
*Decreased activity .
Further
Investigation s
Diagnosis Treatment
No Laboratory
Tests are found in this case
Comments
No Further
Investigations
*Rrheumatoid Arthritis getting worsen.
found in this case
*Diclofenac ( 50 mg three times a day ) .
*Sulphasalazine ( 1.5 g twice a day ).
The phicision must check for the presence of 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 Rheumatoid Arthritis

Section lll
Q#1:
?
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.
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Q#2:
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.
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Yosra Ashraf Rheumatoid Arthritis

Section lll
Q#3:
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.
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Q#4:
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 be continued until the neutrophil count has reached and can be maintained at more than 1.5 *10
9
/L.
Yosra Ashraf Rheumatoid Arthritis

Section lll
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.
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 infection. Two biopsies are procured from the right colon; one is sent for
Yosra Ashraf Rheumatoid Arthritis

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.
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.
NECROTIZING LEUKOCYTOCLASTIC SMALL VESSEL VASCULITIS OF
THE COLON, OF PROBABLE AUTOIMMUNE ETIOLOGY
Yosra Ashraf Rheumatoid Arthritis

Section lll
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 anti-
Smith 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 phenomenon. Although most commonly found to involve the small venules of the
Yosra Ashraf Rheumatoid Arthritis

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 Rheumatoid Arthritis

Section lll
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. severe joint deformities in **hematocrit of 23.9.
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 Rheumatoid Arthritis

Sectio n lll
Further
Investigations
Diagnosis
Treatment
Comments
* Rectal Exam.
*Coumadin and The physician must
NECROTIZING
* Colonoscopy . *Hydrocortisone (100 mg reduce the dose of
LEUKOCYTOCLASTI
* Two biopsies are every 8 hours) for her joint steroids taken to
C SMALL VESSEL procured from the disease.
minimize the side effects
VASCULITIS OF THE right colon . * chronic administration of as the steroids are used
COLON, OF
*Examination of
PROBABLE systemic steroids. only in severe cases where it is life
AUTOIMMUNE the submucosa.
threatening .
ETIOLOGY WITH
THE PRESENCE OF
ACTIVE RA.
Yosra Ashraf Rheumatoid Arthritis

Section lll
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 Rheumatoid Arthritis

: diet-controlled hyercholesterolemia; Family members deny prior diabetes, hypertension, seizure disorder, autoimmune disease or neurological disease.
Section lll
: hysterectomy in 1986 and a hernia repair in 1992.
s: None.
: Prednisone 5 mg a day, Plaquenil 200 mg a day, Reglan, Ritalin,
Paxil,and,Premarin.
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.
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
.
B.P. 150/100 ; pulse 78 ; temperature 98.2 ; respirations were regular at 20.
:
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 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.
: Exam reveals a regular rhythm with normal rate and good S1 and S2. There is no significant murmur and no rub.
Exam reveals lung fields are clear to auscultation
: 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 Rheumatoid Arthritis

: Examination reveals hyperpigmentation on the distal extremities and small subcutaneous nodules on the extensor surfaces of the forearms.
: No signs of clubbing, cyanosis, or edema.
Section lll
Mental-Status
: 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.
Are normal
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.
Revealed withdrawal of all four extremities to noxious stimuli.
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 Rheumatoid Arthritis

Section lll
Patient History Patient Details Signs &
Symptoms
Laboratory Tests
*60 year old Hispanic
*Past Medical History: *Raised bilateral rash on
*ANA of 1:160.
female.
* The patient lived alone in Corpus Christi, Texas until the onset of this illness. She had been
Diet-controlled hyercholesterolemia; diabetes,hypertension, seizure disorder, autoimmune disease or her feet and lower extremities with residual hyperpigmentation.
* worsening cognitive difficulty.
*Homogeneous pattern with an elevated ESR 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 chills.
Yosra Ashraf Rheumatoid Arthritis

Section lll
Further
Investigations
Diagnosis Treatment Comments
* Various NSAID’s and
*B.P. 150/100 hyperpigmentation
* Pulse 78 on the distal immunosuppressive
therapy.
* Temperature 98.2 ;
extremities and
*Prednisone 5 mg a
*Respirations were
small day. regular at 20.
*Plaquenil 200 mg a
* HEENT subcutaneous
*CVS check
* Abdominal nodules on the extensor surfaces day. *Reglan.
* Ritalin.
*Paxil. examination.
*Premarin.
*Skin examination of the forearms.
( pigmentation).
*Chest examination.
*Extremities examination.
* Neurological examination.( some abnormality in attention
Yosra Ashraf Rheumatoid Arthritis

Section lll
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
Juvenile rheumatoid arthritis, which responded to hydroxychlorine, previously had been present at age 16.
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 Rheumatoid Arthritis

Section lll
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 P-
ANCAs negative, anti-DNA Ab negative, and calcium 8.5 mg/dl.
There are palisades of histiocytes surrounding a central area of eosinophilic fibrinoid degeneration. The surrounding fat lobules are atrophic
Juvenile rheumatoid arthritis (Juvenile chronic arthritis).
Yosra Ashraf Rheumatoid Arthritis

Section lll
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 nodules in rheumatoid factor-negative patients have been reported but appear to be rare.
Yosra Ashraf
Section lll
Rheumatoid Arthritis

Patient Details
* Female.
*31-year-old.
Patient History
*Juvenile rheumatoid arthritis since age 16.
Signs &
Symptoms
Laboratory Tests
*Asymptomatic lesions on WBCs 6.4 x 109/L,( with 51% her arms of five months neutrophils, 27% lymphs, 8% duration. monos, 12% eosinophils, and
*Morning stiffness in her
1% basophils),
ESR: 11 mm/hr, hands, elbows, and knees.
*Ten pound weight loss
RF<20 IU/ml,
ACI: 36.8 U/L, HLA-B27 since the birth of her son in
*Urinalysis normal,
April, 2000.
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
Diagnosis Treatment Comments
*Skin biopsies .
*Physical Examination.
* Histography.
*Juvenile rheumatoid arthritis .
*plaquenil 200 mg. twice daily.
*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
Yosra Ashraf Rheumatoid Arthritis

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.
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.
Yosra Ashraf Rheumatoid Arthritis

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.
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.
Yosra Ashraf Rheumatoid Arthritis

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 the spine,lateral-view showing
Fig. 3. X-ray pelvis–broad femoral epiphysis and symphysis pubis.
platyspondyly with tongue like projection of the vertebrae anteriorly
.
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 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
Yosra Ashraf Rheumatoid Arthritis

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.
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.
Yosra Ashraf Rheumatoid Arthritis

Section lll
Patient Details
* 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.
Patient
History
*walk with her right leg and foot turned outwards.Then she developed knock knees and complaints of being tired easily.
Signs &
Symptoms
*Worsening stiffness and restriction of movements of all joints.
*Increasing difficulty in walking.
*Inability to close hands into a fist.
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.
Further
Investigations
Diagnosis
Treatment Comments
*Physical examination. The physician must
*Rheuma-toid arthritis, *Vitamin D.
*Musculoskeletal change the therapy to
*Rickets. *Anti-inflammatory system examination.
*Examination of central *Mucopolysaccharidosis. drugs. the second line nervous system, *Metaphyseal dysplasia.
*Steroids.
treatment instead of abdominal and having drugs which is respiratory examination.
*X -ray Chest and skull were normal. X -ray thoracolumbar spine showed reduced height ineffective in this case with keeping the dose of vitamin D and stopping the steroids.
of the lumbar vertebral bodies.
Section lll
Yosra Ashraf Rheumatoid Arthritis

:
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.
:
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 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.
:
The synovial cyst has resolved spontaneously and has not recurred over 3-months follow-up.
Section lll
Yosra Ashraf Rheumatoid Arthritis

Patient
Details
*7 year old
*Girl.
* Lives with her parents.
Patient
History
Signs &
Symptoms
Laboratory Tests
*Has had polyarticular JRA for
* Just to check for the improvement.
No Laboratory
Tests Are Found over a year.
*Mass in the left bicipital area.
Further
Investigations
Diagnosis Treatment Comments
*Physical examination.
* SONOGRAM .
*XRAYS.
*MRI with gadolinium.
SYNOVIAL
CYST OF THE
SHOULDER
JOINT IN THE
BICIPITAL
AREA IN
JUVENILE
RHEUMATOID
ARTHRITIS.
*Prednisone.
* Methotrexate.
*Tolectin
The physician must pay attention to the strength and frequency of methotrexate dosing to avoid pulmonary toxicity.
Section lll
Yosra Ashraf Rheumatoid Arthritis

Patient
Details
*Female.
* 58 year sold.
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
**********************************
.
Patient
History
*Long history of severe Rheumatoid
Arthritis.
Signs &
Symptoms
*Severe pain in her left foot.
Laboratory Tests
No Laboratory
Tests Are Written
Further
Investigations
Diagnosis
* Normal foot examination.
*Rheumatoid vasculitis.
Treatment Comments
Treatment and comments are suggested in the questions & answers
Section lll
Yosra Ashraf Rheumatoid Arthritis

Q#1:
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 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:
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.
Yosra Ashraf Rheumatoid Arthritis

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:
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 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
Yosra Ashraf
Rheumatoid Arthritis

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 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
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
Yosra Ashraf Rheumatoid Arthritis

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
Section lll
Patient Details Patient
History
Signs &
Symptoms
Laboratory Tests
Yosra Ashraf Rheumatoid Arthritis

*Female.
* 60 years old
*Married.
*Had a history of chronic
Rheumatoid
Arhritis.
*She felt a clunk in her elbow.
*Difficulty in moving her elbow without
No Laboratory Tests
Are Found discomfort.
Further
Investigations
Diagnosis Treatment Comments
* Radiography.
* fluoroscopy.
*Ulnar nerve irritation.
* Chronic
Rheumatoid
Arthritis.
*Left total elbow arthroplasty.
( and on the other side also ).
* Closed reduction was attempted under anesthesia and fluoroscopy.
* Open reduction was attempted after
No medication are mentioned in this case so comments will be difficult on the surgical procedure
.
But the physician can use in this case the 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
Yosra Ashraf 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
Yosra Ashraf Rheumatoid Arthritis

Outcomes research is concerned with evaluating the effe cts of medical intervention on clinical, economic and humanistic measures .
To determine the marginal effect of including a minor, yet common, gastrointestinal
(GI) side effect in a cost effectiveness analysis of NSAID therapy.
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
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
Yosra Ashraf Rheumatoid Arthritis

initial ($64 or $71) and subsequent ($64) prescriptions for NSAID therapy, pharmacological treatment of side effects ($79), and physician office visits ($50).
Percent reduction in dyspepsia, average cost per OA patient treated.
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.
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.
Yosra Ashraf Rheumatoid Arthritis

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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Yosra Ashraf Rheumatoid Arthritis