Use of Steroid in Rheumatology by Dr. Chit Soe

1. Dr. Chit Soe
Associate Professor
Consultant Physician & Rheumatologist
Use of Steroid in Rheumatology

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Long Term Steroid
• The millennium brings with it the 50th
anniversary
of Hench’s discovery that corticosteroids might
be used to treat rheumatoid arthritis.
• Attitudes towards such use have waxed and
waned since then.
• Initial hope that steroids might dramatically alter
the long term course of the disorder gave way to
a recognition of serious adverse effects, that
accompany high dose treatment.
• The use of low dose corticosteroids in arthritis
remains highly controversial.

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• A recent survey in general practice found
that 1.4% of patients aged over 54 were
using corticosteroids at a mean dose of
8mg daily
• Although rheumatologists claim to use
less the audit had found use (as great as
80%).

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Reasons
• in an attempt to modify the progression of
structural disease.
• “bridge” to suppress inflammation while
other disease modifying drugs take effect
or
• to combat acute flares of the disease

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Clinical Courses of RA
Adapted from: Henderson, Edwards, Pettipher. Mechanisms and Models in Rheumatoid Arthritis.
© 1995 Academic Press Limited.
Chronic Progressive
Chronic
Intermittent
Acute Onset
Time
DieseaseActivity/FunctionalImpairment

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Th1 cell
IFN -γ
TNF-α
IL-2
Activated Th1 Cell in Rheumatoid
Arthritis
Smith JB, Haynes MK. Ann Intern Med. 2002;136:908-922
Feldmann M, Brennan FM, Maini RN. Annu Rev Immunol. 1996;14:397-440.

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Regulation of Gene
Expression by
Glucocorticoids• Following ligand binding, HSP90 and several
other of the associated proteins dissociate,
and the GR is directed into the nucleus
where it can interact with specific DNA
sequences within the regulatory regions of
affected genes.
• These short DNA sequences that are
recognized by the activated glucocorticoid
receptor are termed glucocorticoid-
responsive elements (GREs)
• and provide specificity to the induction of
gene transcription by glucocorticoids.
• The currently acknowledged consensus GRE
DNA sequence is GGTACAnnnTGTTCT,

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Improve symptom
• A Dutch trial comparing prednisolone 10 mg
daily with placebo as an adjunct to
intramuscular gold reported clinical
improvement in both groups over 12 weeks;
• this was greatest among those trearted with
prednisolone.
• The Arthritis and Rheumatism Council trial
randomised 128 patients to prednisolone 7.5
mg daily or placebo in additon to non-
steroidal and disease modifying agents.
• Symptomatic benefit was maintained for only
6-9 months of the two year follow up.

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Meta-analysis
• A meta-analysis of the effectiveness of low dose
corticosteroidsa in rheumatoid arthritis based on
9 of 34 studies identified in a rigorous search
strategy
• compared the effectiveness of prednisolone to
either placebo or active drug controls (aspirin,
chloroquine, or deflazacort).
• Although corticosteroids tended to be better at
reducing the number of tender or swollen joints
and the number of erythrocyte sedimentation
rate, these differences were not significant.

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Retard Erosion!!
• Whether corticosteroids attenuate the
progression of erosive damage is also
unresolved.
• In the Arthritis and Rheumatism Council
study showed prednisolone had a
pronounced and significant (p<0.004)
effect on the development of hand
erosions in patients with rheumatoid
arthritis of less than two year’s duration.

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• Gotzsche and Johansen report a further
meta-analysis comparing prednisolone at
a dose of 2.5-15 mg daily with palacebo or
non-steroidal anti-inflammatory drugs
• They show that at these dose
prednisolone is much more effective than
non-steroidal drugs at improving joint
tenderness, pain, and grip strength.

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Concern
• To the practising rheumatologist the great
disincentive to using short term low dose
prednisolone is not concern about lack of
anti-aiflammatory effect
• but the worry that stepping treatment
down may be difficult, with the
consequence
• that the patient is exposed to the risk of

13. CPT
Corticosteroid Pulse Therapy

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Corticosteroid Pusle Therapy in Active
Rheumatiod Arthritis
By Bas L.A.M. Weusten, Johannes
W.G.Jacobs, and Johnnes W.J.Bijisma• In an attempt to reduce the frequent and
potentially servere side effects of long-term
oral steroid therahy, the intermittent
intravenous administration of high doses of
corticosteroids (corticosteroid pulse therapy,
CPT) was introduced.
• CPT was reported to be effective against renal
allograft rejection.

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• Later reports showed that patients with
idiopathic glomerulomephritis and
glomerulonephritis associated with
systemic lupus erythematous respond
well to this from of treatment.
• In the course of the past decade,CPT
also has been used to treat
rheumatoid arthritis (RA).

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Different Regimens
(For Acute Flare Up)
• Many studies of the efficacy of (different
regimens of) CPT in RA have been
performed
• 1,000 mg of methylprednisolone
intravenously in 10 RA patients once a month
for 6 consecutive months
• Tender joint counts, walking time, and grip
strength improvement were still apparent
more than 7 months after the last
corticosteriod infusion.
• CPT did not influence the progression of erosions
followed radiologically

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• Forster et al reported long-lasting clinical
improvement in their RA patients after a
regimen of
• 1,000 mg of methylprednisolone given on 3
alternate days and 1,000 mg intravenously
on 3 consecutive days
• The benefit lasted more than 1 year
• erythrocyte sedimentation rate and C-
reactive protein level, was of shorter
duration (about 2 weeks)
• whereas methylpredisolone is metabolized
and excreted within a few days

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CPT IN CONJUNTION
WITH DISEASE-MODIFYING
ANTIRHEUMATIC DRUG
THERAPY
(Bridging)
• Neumann et al investigated the
possibility of maintaining the clinical
improvement induced by intiating
(new) diseasemodifying antirheumatic
drug (DMARD) therapy
concomitantaly.
• They found that a regimen of 3
*1,000mg methylpredisolone
intravenously on alternate days,

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• If started simultaneously with a new DMARD,
was able to bridge the gap between the start
and effect of at least two different DMARDs: D-
penicillamine and sulphasalazine.
• In 1988, a similar effect of CPT in conjunction
with sodium aurothiomalate was
demonstrated.
• In contrast, we found that CPT (3x1,000 mg
methylperdnisolone) is unable to bridge the
gap between the start and the effect of
azathioprine.

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COMPARISON OF THE
EFFICACY OF DIFFERENT
REGIMENS OF CPT
• After intial reports on the efficacy of high-dose
intravenous CPT, several investigators studied
the effects of reduced doses of methylpred-
nisolone.
• Radia and Frust compared the efficacies of a
single dose of 1,000 mg of methylprednisolone
given intravenously,
• 320 mg of methylprednisolone administered
intravenously,
• and 320 mg of methylprednisolone given
intramuscularly.

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• Shipley et al claimed a significantly better
response to a single intravenous 1,000-
mg dose of methylprednisolone than to
500 mg and 40 mg.
• Dexamethasone (200 mg),given via an
intravenous infusion on alternate days
over a 5-day period was also tried.

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• They found that 85% of patients treated
with 1,000 mg of methylprednisolone
considered the therapy worthwhile,
• compared with only half the patients
receiving lower dosages.
• Several authors have compared high-dose
oral prednisolone with intravenous
methylprednisolone.

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• In conclusion, different regimens of CPT are of
clinical benefit for patients with severe,
intractable RA.
• As for bridging the gap between the start and
effect of a newly introduced DMARD, the effect
of low-dose or oral CPT has not been proved,
• Recommended regimens consisting of three
1,000-mg doses of methylprednisolone.

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SIDE EFFECTS OF CPT
• sudden death, infections, hypersensitivity,
osteonecrosis of the femoral head, and
multiple other complications

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ON
• Flattening or
deformity of the
femoral head was
assumed to be
possible ON, but only
when seen in
conjunction with a
normal joint space
was it considered
incontrovertible ON.

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Short-term Complications
Attributable to CPT
(n=90)Increase in diastolic blood pressure
(> 10 mm Hg) 44
(51%)
Hyperglycemia (> 6.0 mmol/L) or
glucosuria 14 (16%)
Facial flushing 12 (14%)
Headache 10 (12%)
Bitter taste 9 (10%)
Vertigo 5 (6%)
Palpitations/tachycardia 5(6%)
Urinary tract infections 4 (5%)
Euphoria 4 (5%)
Tiredness/malasie 2(2%)
Insomnia 2 (2%)
Erythema/urticaria 2 (2%)
Jitteriness/fear 2 (2%)
Hypokalemia 2 (2%)

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Long term
• TB
• Osteoporosis

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• (9) Systemic steroid therapy may have an
important early
• role in establishing control of synovitis or
bridging disease
• control between different DMARD
therapies but long-term
• use is not justified. (grade of
recommendation B)

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• When using corticosteroids
• in RA, osteoporosis prevention should always be
considered
• following the National Osteoporosis Society/RCP
guidelines [92].
• The recent NICE technology appraisal for the secondary
• prevention of osteoporosis [94] gives clear guidance on
treatment
• thresholds after fragility fracture and is due to report
shortly on
• primary prevention.

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Recent Developments in the
Therapy of patients with
Severe Systemic Lupus
Erythematosus
Dimitrios T.Boumpas,M.D.Long-term follow-up of patients
participation in these controlled trials
suggest that toxicity is low and benefit
outweigh the risk.

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EBM
• The Cochrane Controlled Trial Registry,
MEDLINE, and EMBASE were searched for
RCTs of treatment for DPLN.
• All available RCTs of patients with biopsy-
proven DPLN were included, and data were
extracted for overall mortality, end-stage renal
disease, doubling of serum creatinine level,
relapse, major infection, herpes zoster infection,
ovarian failure, malignancy, and bladder toxicity.

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• Twenty-five of 920 articles identified were
eligible RCTs and were included.
• The majority compared cyclophosphamide
or azathioprine plus steroids versus
steroids alone.
• cyclophosphamide combined with steroids
remains the best option to preserve renal
function

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Other Use
• Systemic use also in
– Vasculitis
– Dermatomyositis
• Local Injection
– Joint-(RA, OA, Gout)
– Soft tissue- (Painful arc,
tennis elbow, carpal
tunnel)
• Local application
– Psoriasis

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Equivalent doses of steroid.
This table takes no account of
mineralocorticoid activity effects, nor
dose it take account of variations in
duration of action (BNF)
Prednisolone 5 mg
= Betamethasone 750 microgram
= Cortisone acetate 25 mg
= Deflazacort 6 mg
= Dexamethasone 750 micrograms
= hydrocortisone 20 mg
= Methylprednisolone 4 mg
= Triamicinolone 4 mg
= methasone 750 micrograms
= hydrocortisone 20 mg
= Methylprednisolone 4 mg
= Triamicinolone 4 mg

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• The relatively high mineralocorticoid activity of
cortisone and hydrocortisone, and the
resulting fluid retention, make them unsuitable
for disease suppression on a long-term basis.
• However, they can be used for adrenal
replacement therapy
• hydrocortisone is preferred because cortisone
requires conversion in the liver to
hydrocortisone.

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• Betamethasone and dexamethasone
have very high gluococorticoid activity in
conjunction with insignificant
mineralocorticoid activity.
• This makes them particularly suitable for
high-dose therapy in conditions where
fluid retention would be a disadvantage
(e.g. cerebral oedema).

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STEROID
TREATMENT CARD
• I am a patient on STEROID treatment which
must not be stopped suddenly.
• If you have been taking this medicine for more
than three weeks, the dose should be reduced
gradually when you stop taking steroids unless
your doctor says otherwise.

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• Read the patient information leaflet given with
the medicine.
Always carry this card with you and show it to
anyone who treats you (for example a doctor,
nurse, pharamacist or dentist).
• For one year after you stop the treatment,
you must mention that you have taken
steriods.
•
If you become ill, or if you come into contact
with anyone who has an infectious disease,
consult your doctor promptly. If you have
never had chickenpox, you should avoid
close contact with people who have
chickenpox or shingles. If you do come into
contact with chickenpox, see your doctor
urgently.

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Summary
• Steroid reduce symptoms
• Steroid reduce disease progression
• Low dose long term- methylprednisolone 7.5-
15mg / OD CM
• Pulse- methylprednisolone 1000mg in 100 ml
NS in 1 hr alternate day for 3 dose
• Beware of side effects
• Educate to use steroid card

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