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supersede recommendations made in the guidelines.
CLINICAL PRACTICE GUIDELINES
Use of
Corticosteroids in
General Practice
Endocrine and Metabolic
Society of Singapore
College of Physicians,
Singapore
SINGAPORE THORACIC SOCIETY
College of Surgeons,
Singapore
Gastroenterological Society
of Singapore
Dec 2006
MiNISTRY OF HEALTH
SINGAPORE
ISBN 978-981-05-7317-1
College of Family
Physicians, Singapore
Singapore Orthopaedic
Society
MOH Clinical Practice Guidelines 5/2006
Levels of evidence and grades of recommendation
Levels of Evidence
Level
1++
1+
12++
2+
23
4
Type of Evidence
High quality meta analyses, systematic reviews of RCTs, or RCTs with a
very low risk of bias
Well conducted meta analyses, systematic reviews of RCTs, or RCTs with
a low risk of bias
Meta analyses, systematic reviews of RCTs, or RCTs with a high risk of
bias
High quality systematic reviews of case-control or cohort studies
High quality case-control or cohort studies with a very low risk of
confounding, bias, or chance and a high probability that the relationship is
causal
Well conducted case control or cohort studies with a low risk of
confounding, bias, or chance and a moderate probability that the
relationship is causal
Case control or cohort studies with a high risk of confounding, bias, or
chance and a significant risk that the relationship is not causal
Non-analytic studies, e.g. case reports, case series
Expert opinion
Grades of recommendation
Grade
A
(evidence
levels 1++, 1+)
B
(evidence
levels 2++, 1++,
1+ )
C
(evidence
levels 2++, 2+)
D
(evidence
levels 2+, 3, 4)
GPP
(good practice
points)
Recommendation
At least one meta analysis, systematic review, or RCT rated as
1++, and directly applicable to the target population; or
A systematic review of RCTs or a body of evidence consisting
principally of studies rated as 1+, directly applicable to the target
population, and demonstrating overall consistency of results
A body of evidence including studies rated as 2++, directly
applicable to the target population, and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
A body of evidence including studies rated as 2+, directly
applicable to the target population and demonstrating overall
consistency of results; or
Extrapolated evidence from studies rated as 2++
Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
Recommended best practice based on the clinical experience of
the guideline development group
CLINICAL PRACTICE GUIDELINES
Use of Corticosteroids in
General Practice
MOH Clinical Practice Guidelines 5/2006
Published by Ministry of Health, Singapore
16 College Road,
College of Medicine Building
Singapore 169854
Printed by Craft Print International Limited
Copyright ” 2006 by Ministry of Health, Singapore
ISBN 978-981-05-7317-1
Available on the MOH website: http://www.moh.gov.sg/cpg
Statement of Intent
These guidelines are not intended to serve as a standard of medical care.
Standards of medical care are determined on the basis of all clinical data
available for an individual case and are subject to change as scientific
knowledge advances and patterns of care evolve.
The contents of this publication are guidelines to clinical practice, based on
the best available evidence at the time of development. Adherence to these
guidelines may not ensure a successful outcome in every case. These
guidelines should neither be construed as including all proper methods of
care, nor exclude other acceptable methods of care. Each physician is
ultimately responsible for the management of his/her unique patient, in the
light of the clinical data presented by the patient and the diagnostic and
treatment options available.
Foreword
Corticosteroids are very potent drugs that are known for their antiinflammatory,
anti-proliferative
and
immunosuppressive
effects.
Corticosteroids, often just called “steroids”, greatly improve symptoms and
provoke impressive results in number of conditions. However, there are also
side effects associated with their use. It is therefore important that these drugs
are used for evidence-based indications.
The MOH Clinical Practice Guidelines on Use of Corticosteroids in General
Practice incorporates the best available evidence from the scientific literature,
appraised by experts from many disciplines in an attempt to cover as wide as
possible indications on use of steroids in daily clinical practice. These
guidelines will highlight how these powerful drugs could have valuable effect
if administered within proper guidelines.
I hope this set of guidelines will assist all doctors, particularly primary care
physicians, in appropriate use of corticosteroids in their practice.
PROFESSOR K SATKU
DIRECTOR OF MEDICAL SERVICES
Contents
Executive summary of recommendations
Page
1
1.
Introduction
17
2.
Corticosteroid therapy in clinical practice
19
3.
Intranasal corticosteroid use in clinical practice
31
4.
Use of corticosteroid ear drops in clinical practice
33
5.
Corticosteroids and gastrointestinal conditions
34
6.
Use of corticosteroids in children
39
7.
Corticosteroid injections in joints and soft tissues
44
8.
Corticosteroids in rheumatological conditions
48
9.
Respiratory diseases
53
10.
Corticosteroids in dermatologic conditions
59
11.
Use of corticosteroids in ophthalmology
66
12.
Corticosteroids in other conditions
70
Clinical quality improvement
71
References
72
Self-assessment (MCQs)
100
Workgroup members
104
Executive summary of recommendations
Details of recommendations can be found in the main text at the pages indicated.
Corticosteroid therapy in clinical practice
D The baseline information on blood pressure, weight, growth curve (in
children), ophthalmic examination, tuberculosis screening, and levels of fasting
glucose, triglycerides and potassium levels, is required in patients in whom
steroids have to be started. Repeat ophthalmologic examinations should be
done every 6 monthly. The levels of triglycerides, fasting glucose and
potassium should be checked after one month of steroid therapy and thereafter,
every 3-4 monthly. Blood pressure and weight should be measured at every
visit. A history of adverse effects would be ideal at every visit (pg 21).
Grade D, Level 4
GPP Hepatitis B status should be checked in all patients in whom steroids
have to be started on long term basis (pg 21).
GPP
B In patients at risk of ischemic heart disease, myocardial infarction, angina,
coronary revascularization, heart failure, transient ischaemic attack or stroke, it
is best to avoid corticosteroids. However, if definitely indicated, dose should
be less than or equal to 7.5 mg prednisolone daily, and should be reduced over
time as deemed safe and efficacious (pg 23).
Grade B, Level 2++
D Use of corticosteroids should be carefully considered and preferably
restricted in obese patients as studies have linked corticosteroids with elevated
ratio of intra-abdominal to subcutaneous fat mass (pg 24).
Grade D, Level 3
B Blood sugar should be monitored before and after commencement of
corticosteroids as there is an increased risk of developing hyperglycaemia
when corticosteroids exceed the dose equivalent to 10 mg prednisolone per day
(pg 24).
Grade B, Level 2++
C Corticosteroids should be used in the lowest possible dose to avert longterm fracture risk. Even low doses of steroids equivalent to 2.5 mg
prednisolone per day could compromise bone integrity, and doses of 5 mg and
above are associated with increased long-term fracture risk (pg 24).
Grade C, Level 2+
1
B Calcium and vitamin D should be prescribed for patients receiving an
average of near-physiologic level of 5-7 mg prednisolone per day to avert
reduction in bone loss (pg 25).
Grade B, Level 1+
A The combination of bisphosphonates combined with vitamin D is the most
effective and is highly recommended for the treatment of glucocorticoidinduced osteoporosis (pg 25).
Grade A, Level 1+
D Tests of bone mineral density, particularly of the spine, should be done in
women who are above 50 years of age, and have received 6 months of
corticosteroids. (pg 25).
Grade D, Level 4
D In situations of wound repair, steroids should be avoided but if unavoidable,
should be used sparingly (pg 26).
Grade D, Level 4
D Changes in mental state, cognitive function and emotional responses in
patients on corticosteroids could be due to corticosteroids. As this is eminently
treatable, due care should be taken to monitor those with a predisposition to
mental disturbances, e.g. those with a family history of mental disturbances, a
past history of depression or alcoholism when prescribing corticosteroids to
these patients (pg 26).
Grade D, Level 3
A If corticosteroids are indicated for growing children, the regime should be
alternate-day, preferably topical, and used sparingly (pg 27).
Grade A, Level 1+
D In the elderly, dosage of steroids should be limited to 10 mg prednisolone
per day, not exceeding a year, as the elderly are more likely to be disabled by
complications of glaucoma and subcapsular cataract (pg 27).
Grade D, Level 3
D To decrease the risk of myopathy, particularly in the elderly, fluorinated
corticosteroid preparations like dexamethasone and triamcinolone should be
avoided and dose of prednisolone should not exceed 10 mg per day (pg 27).
Grade D, Level 3
2
GPP It is best to avoid the usage of high dose corticosteroids over a prolonged
duration (pg 28).
GPP
A Corticosteroids should be withdrawn by tapering the dose gradually. The
decision on tapering regime should be made on individually tailored basis
(page 29).
Grade A, Level 1+
D Prompt withdrawal with rapid tapering is required in the following instances
(pg 29):
x Steroid psychosis
x Herpes-induced corneal ulceration
x Uncontrolled hypertension
x Serious lumbar spine osteoporosis
x When therapeutic targets have been achieved or when the regime with
steroids proves inefficacious.
Grade D, Level 4
D It is unlikely that a tapering regime would be required in the following
patients (pg 29):
x those receiving any dose of corticosteroids for less than 3 weeks duration
x those on alternate-day therapy
x those given less than 10 mg prednisolone per day (day dose) for more than
a few weeks or at physiologic doses taken for less than 1 month.
Grade D, Level 3 & 4
A Withdrawal plans should be commenced by reducing the corticosteroids
from supraphysiologic to physiologic doses, which is equivalent to 5-7 mg of
prednisolone per day (or hydrocortisone at 15-20 mg per day). Subsequent
reduction has been suggested with conversion to hydrocortisone (because of
shorter half life) or alternate day prednisolone. During periods of stress or
injury, additional doses may be required to avert adrenal crises. The whole
process of withdrawal may last from 9 to 12 months (pg 30).
Grade A, Level 1+
Intranasal corticosteroid use in clinical practice
A Intranasal steroids are indicated in both adults and children with allergic
rhinitis, with no significant growth effects in children. However, there is no
definite recommendation for use in pregnancy (pg 32).
Grade A, Level 1++
3
A Intranasal steroids should not be given to children with upper respiratory
infections as intranasal steroids use neither provides symptomatic relief nor
decreases episodes of acute otitis media (pg 32).
Grade A, Level 1+
A Both oral and topical intranasal steroids may be used alone or in
combination with an antibiotic as steroid use along with antibiotic, leads to a
quicker resolution of otitis media with effusion in the short-term. However,
there is no definite recommendation for a long-term benefit with their use (pg
32).
Grade A, Level 1+ and 1++
Use of corticosteroid ear drops in clinical practice
A Either combination of steroid and acetic acid ear drops or steroids and
antibiotic ear drops may be used in the treatment of acute otitis externa (pg 33).
Grade A, Level 1++
A Steroid ear drops may be used in the treatment of eczematous otitis externa
as steroid use leads to improvement of otological symptoms, particularly
erythema, swelling and discharge (pg 33).
Grade A, Level 1+
Corticosteroids and gastrointestinal conditions
A Oral systemic and intravenous steroids are useful in inducing remission and
may be used in active ulcerative colitis (pg 34).
Grade A, Level 1++
A Budesonide, an oral topically acting steroid, is also useful and may be used
in active ulcerative colitis (pg 34).
Grade A, Level 1+
A Steroid enemas are useful in inducing remission in patients with distal colitis
and a useful adjunct in patients with left-sided colitis (pg 35).
Grade A, Level 1+
A Steroids should not be used in maintaining remission in ulcerative colitis
(pg 35).
Grade A, Level 1++
4
A Both systemic steroids and oral topically acting steroids (budesonide), either
alone or in combination, may be used in active Crohn’s disease (pg 35).
Grade A, Level 1++
A Steroids should not be used in maintaining remission in Crohn’s disease (pg
35).
Grade A, Level 1++
A Steroids are very useful and may be used in inducing remission and
preventing relapse in autoimmune hepatitis (pg 36).
Grade A, Level 1++
A Steroids may be used in the treatment of severe alcoholic hepatitis (pg 36).
Grade A, Level 1+
GPP Patients who are on steroids should have prophylaxis if they are also on
non-steroidal anti-inflammatory drugs or are elderly with a history of peptic
ulcer disease (pg 37).
GPP
A Patients who are known to be hepatitis B virus carriers and are receiving
chemotherapy with corticosteroids should also receive prophylaxis (pg 37).
Grade A, Level 1+
GPP Patient who are known to be hepatitis B virus carriers should be
considered for prophlylactic medication if they are to receive systemic steroids
for a duration of more than a week (pg 38).
GPP
GPP It is advisable to test all patients for hepatitis B if systemic long-term
steroids are being considered (pg 38).
GPP
A Based on present evidence, there is no need to specifically look for the
presence of hepatitis C before starting corticosteroid treatment in any medical
condition (pg 38).
Grade A, Level 1+
5
Use of corticosteroids in children
D Although children receiving long-term systemic corticosteroid therapy
should be screened for cataracts, this is unnecessary in children on inhaled
corticosteroids alone (pg 40).
Grade D, Level 3
A Systemic corticosteroids are NOT recommended in children with acute
bronchiolitis (pg 41).
Grade A, Level 1++
A Inhaled corticosteroids are NOT recommended in children with acute
respiratory syncytial viral bronchiolitis (pg 41).
Grade A, Level 1+
A Corticosteroids are recommended
laryngotracheobronchitis (pg 41).
for
the
treatment
of
acute
Grade A, Level 1++
A Nebulized budesonide, oral and parenteral dexamethasone have the same
effectiveness and may be used for treatment of laryngotracheobronchitis (pg
41).
Grade A, Level 1+
GPP For children with mild croup, a single dose of oral dexamethasone is an
effective treatment. Choice between oral and parentral dexamethasone is up to
the individual clinical setting (pg 42).
GPP
A Systemic corticosteroids are recommended for children with acute asthma
exacerbation (pg 42).
Grade A, Level 1++
A Inhaled corticosteroids are recommended for the treatment of children with
persistent asthma (pg 42).
Grade A, Level 1++
A Topical corticosteroids are recommended for children with moderate to
severe eczema. Topical corticosteroids results in improvement in disease
severity and reduces the risk of relapse (pg 43).
Grade A, Level 1+
6
GPP It is recommended that systemic corticosteroids in children (except short
courses or “bursts” which are not likely to cause side effects) should be used in
consultation with physicians with experience in its use and in monitoring for
side effects (pg 43).
GPP
Corticosteroid injections in joints and soft tissues
A Corticosteroid injections may have short-term benefits but may not be
sustained. The subacromial route is recommended for rotator cuff tendonitis
and intra-articular injection for adhesive capsulitis. Oral non-steroidal antiinflammatory drug therapy may be considered prior to injection therapy (pg
44).
Grade A, Level 1+
A Corticosteroid injections can provide short-term relief, and can be useful in
early treatment of lateral epicondylitis (Tennis Elbow) and medial epicondylitis
(Golfer’s elbow) (pg 44).
Grade A, Level 1+
D Corticosteroid injections can provide short-term relief, is useful and may be
used in early treatment of De Quervain’s Tenosynovitis (pg 45).
Grade D, Level 3
A Corticosteroid injections can provide short-term relief and may be used for
carpal tunnel syndrome (pg 45).
Grade A, Level 1++
D Recommended safe injection technique for carpal tunnel syndrome (pg 45):
x
x
x
25G needle at 30 degree angle insertion, approach skin ulnar to palmaris
longus tendon.
Withdraw needle if paresthesia experienced by patient.
Bulge in palm distal to transverse carpal ligament is indication of correct
placement of needle.
Grade D, Level 4
D Corticosteroid injections are highly effective and may be used as first line
therapy for long-term treatment of trigger finger and thumb (pg 45).
Grade D, Level 3
A Intra-articular corticosteroid injections provides short-term benefit and may
be used in relieving pain. Judicious use is advocated in acute exacerbation of
7
osteoarthritis. It may be combined with knee aspiration if effusion is present
(pg 46).
Grade A, Level 1+
GPP Regular use of intra-articular steroids is not recommended for
osteoarthritis of the knees in the general practice setting (pg 46).
GPP
A No benefit has been shown for the use of injection corticosteroid in
Archilles tendonitis and it is not recommended for this condition (pg 46).
Grade A, Level 1+
A Corticosteroid injections can provide short-term relief of symptoms to a
small degree and may be used in plantar fasciitis. Orthosis should be
prescribed for those patients who stand for long periods (pg 46).
Grade A, Level 1+
GPP There should be at least 6 weeks of interval between corticosteoid
injections, and up to a maximum of 3 doses are recommended in shoulder
conditions, lateral epicondylitis and trigger finger (pg 47).
GPP
GPP A single dose of corticosteoids is recommended in De Quervain
Tenosynovitis and carpal tunnel syndrome (pg 47).
GPP
Corticosteroids in rheumatological conditions
GPP There is no evidence for the use of systemic corticosteroids in
osteoarthritis. It should not be prescribed for the treatment of osteoarthritis (pg
48).
GPP
D In patients with acute gout affecting one or two joints, intra-articular
injection of a long-acting corticosteroid preparation, such as
methylprednisolone, triamcinolone acetonide or triamcinolone hexatonide, will
control symptoms within 1 to 2 days. It should be given only when the
diagnosis is confirmed and infection has been excluded. Patients with
polyarticular gout who have a suboptimal or delayed response to oral nonsteroidal anti-inflammatory drugs often benefit from adjunctive corticosteroid
injections into those joints with persistent synovitis (pg 49).
Grade D, Level 3
8
D Both intramuscular injection of corticosteroid (triamcinolone acetonide 40
mg - 60 mg once) and oral corticosteroid are effective and may be used in
acute attacks particularly in the patient with polyarticular gout. Prednisolone
can be started at a dose of 20 to 40 mg/day and tapered over 7 to 10 days. If
tapered too rapidly, a rebound flare-up of gout may occur (pg 49).
Grade D, Level 3
D Well conducted studies on the use of intra-articular or systemic
corticosteroids in acute attacks of pseudogout are lacking. However, clinical
experience suggests that a similar approach to that for the management of acute
gout may be effective in acute attacks of pseudogout (pg 49).
Grade D, Level 4
A Rheumatoid synovitis may be suppressed for three months or longer using
relatively insoluble microcrystalline corticosteroid preparations. Intra-articular
corticosteroid should be considered ancillary to rest, physical therapy, nonsteroidal anti-inflammatory agents, and disease modifying anti-rheumatic drugs.
No convincing evidence exists, that joint erosive changes are retarded (pg 49).
Grade A, Level 1+
A Systemic corticosteroids may thus be used in the management of rheumatoid
arthritis in two ways (pg 50):
(1) Short-term, low dose bridge therapy, aimed at controlling symptoms
during periods of active disease while awaiting the effects of newly started
single or combination disease modifying anti-rheumatic drugs (DMARDs).
(2) Moderate to longer-term low dose prednisolone (usually 10 mg or less)
given in addition to single or combination DMARDs if this treatment has
failed to control disease activity sufficiently.
Grade A, Level 1+
D Periodic intra-articular injection of corticosteroid can be of particular value
in the management of patients with oligoarticular disease or those with
controlled polyarticular disease but one or two persistently active inflamed
joints despite disease modifying anti-rheumatic drugs (pg 51).
Grade D, Level 4
D In general, systemic corticosteroids should be used judiciously in psoriatric
arthritis because of the risk of provoking a pustular flare in the skin on
withdrawal (pg 51).
Grade D, Level 3
9
A Intra- or peri-articular corticosteroid injections have been shown in small
randomized controlled trials to be effective and may be used for the pain of
sacroiliitis (pg 51).
Grade A, Level 1+
D There are no clinical studies evaluating the efficacy of intra-articular
corticosteroid on peripheral arthritis nor on the use of local corticosteroid
injections for the enthesitis of ankylosing spondylitis. Clinical experience
suggests that corticosteroid injections can be helpful in selected cases (pg 51).
Grade D, Level 4
D The use of systemic corticosteroids for axial disease is not supported by
evidence. These patients already have significant loss of bone density, which
can be exacerbated by steroid therapy (pg 52).
Grade D, Level 4
Respiratory diseases
A Inhaled steroids are the preferred treatment for patients with persistent
asthma symptoms at all levels of severity (pg 53).
Grade A, Level 1++
A Add-on therapy with another class of controller medication (e.g. long-acting
E2-agonist) is preferred to increasing the dose of inhaled corticosteroids (pg 53).
Grade A, Level 1++
B The risks of poorly controlled asthma should be weighed against the limited
risk of long-term inhaled corticosteroids (pg 53).
Grade B, Level 2++
D Inhaled corticosteroids should be started at a dose appropriate to the control
of Asthma (pg 54).
Grade D, Level 4
A Inhaled steroids should be given twice daily (pg 54).
Grade A, Level 1+
B The dose of inhaled steroids should be titrated slowly to the lowest dose that
can achieve effective asthma control. After adequate control has been achieved,
the inhaled corticosteroid dose should be gradually reduced by 25% every 3
months and titrated according to asthma control. Once the dose of
10
corticosteroids is less than 500 Pcg of beclomethasone diproponate or its
equivalent, then withdrawal of add-on therapy can be considered (pg 54).
Grade B, Level 1+
C Inhaled steroid regimen should not be changed in pregnancy (pg 54).
Grade C, Level 2++
A Systemic steroids should be given at least 5 days in acute exacerbations of
asthma that do not have rapid and sustained response to short-acting E2-agonist
therapy. Oral dosing is preferred over intravenous therapy. Intravenous
administration should only be considered in the critically ill or if the patient is
unable to tolerate oral medication. There is no need for tapering dose at the end
of a short course of oral prednisolone (up to 10 days) (pg 55).
Grade A, Level 1++
A The role of conventional doses of inhaled corticosteroids as adjunctive
therapy to systemic steroids in an acute exacerbation of asthma is limited (pg
55).
Grade A, Level 1++
A Combined inhaled corticosteroids with long-acting bronchodilators should
be considered in severe COPD patients with recurrent exacerbations or
symptoms (pg 56).
Grade A, Level 1++
A Long-term treatment with oral corticosteroids is not recommended in COPD
(pg 56).
Grade A, Level 1++
A Oral corticosteroids should be considered if patients experience a significant
increase in breathlessness that interferes with daily activities especially if the
baseline FEV1 is less than 50% of predicted. A dose of prednisolone of 30-40
mg/day for 7 to 14 days is recommended for acute exacerbations of COPD (pg
57).
Grade A, Level 1++
D Corticosteroids should not be used in the management of acute bronchitis
(pg 57).
Grade D, Level 4
11
D Corticosteroids should not be used in the treatment of lower respiratory tract
infections (pg 57).
Grade D, Level 4
A The routine use of corticosteroids should be avoided in the management of
pulmonary tuberculosis (pg 58).
Grade A, Level 1++
GPP The following respiratory disorders may require corticosteroid therapy
and patients with these conditions should be referred to a specialist respiratory
service (pg 58):
x Allergic bronchopulmonary aspergillosis
x Churg Strauss syndrome
x Eosinophilic pneumonia
x Sarcoidosis
x Pulmonary vasculitis
x Alveolar haemorrhage syndromes
x Pneumocystis carinii pneumonia with respiratory failure
x Interstitial lung disease
x Post-radiation pneumonitis
GPP
Corticosteroids in dermatologic conditions
A There is reasonable evidence from randomised controlled trials to support
the use of topical corticosteroids as the mainstay of treatment of atopic eczema
(pg 59).
Grade A, Level 1+
GPP Topical corticosteroids in treatment of psoriasis are best reserved for
localised sites such as hands, feet, flexures, genitalia, face and scalp (pg 59).
GPP
A Topical corticosteroids should not be used more than twice a day (pg 60).
Grade A, Level 1+
GPP It is not recommended to dilute and mix other types of creams with
topical corticosteroids in your practice (pg 61).
GPP
12
GPP In the presence of infected eczema, use of oral antibiotics is considered
as good practice (pg 61).
GPP
D To prevent side effects, the amount of topical corticosteroids used per week
and duration of use must be monitored and controlled. Adjunctive therapy
must be emphasized (pg 62).
Grade D, Level 3
GPP It is recommended that not more than 25 g of clobetasal propionate per
week be used in adults. All patients on clobetasol propionate should be
monitored closely for potential side effects (pg 62).
GPP
GPP For areas of the face and flexures it is best to confine use of topical
steroids to mild topical corticosteroids and less commonly to moderate to
potent topical corticosteroids for short periods of time (pg 62).
GPP
GPP When patient requests for repeat prescription of moderately potent and
super potent topical corticosteroids, clinical review must be done before
repeating the dose. Patient should be educated regarding the need to come for
clinical review before extending the duration by explaining the risk and
benefits of continuing steroids on long term basis (pg 62).
GPP
D Use of flourinated topical corticosteroids should be avoided on the face as
there is a high risk for complications like perioral dermatitis, rosacea-like
dermatitis, acneform lesions and facial hypotrichosis. Where indicated it
should be used for short period, under frequent and close review of patient's
condition. Longer usage should be in consultation with a specialist
dermatologist (pg 62).
Grade D, Level 4
GPP It is presently unknown whether topical corticosteroids are excreted in
breast milk. The general advice is to use topical corticosteroids with caution in
breastfeeding mothers and they are not to be used on the breast just prior to
breastfeeding (pg 63).
GPP
GPP In elderly patients, topical corticosteroids should be used for short
periods, intermittently and under close supervision (pg 63).
GPP
13
GPP Guidelines as for use in infants and young children should apply to the
elderly (pg 63).
GPP
GPP In general practice (or primary care), it is best to confine use of systemic
corticosteroids to dermatoses that are ‘short-lived’ or rapidly responsive (pg
64).
GPP
‘Short-lived dermatoses’ include acute allergic contact dermatitis (allergen withdrawn like hair dye allergy), certain cutaneous adverse drug exanthem and acute urticaria.
GPP Long-term systemic corticosteroids used in autoimmune bullous
dermatoses (like pemphigus vulgaris) or other autoimmune cutaneous disorder
(systemic lupus erythematosus, dermatomyositis) are best left to the purview of
the specialist (pg 64).
GPP
Use of corticosteroids in ophthalmology
GPP The role of steroid eye drops in the primary care setting is mainly in the
management of acute red eyes. Vision-threatening causes of red eyes – acute
glaucoma, iritis, keratitis and scleritis – should first be excluded with careful
history, visual acuity testing and examination for corneal clarity and pupillary
response (pg 66).
GPP
A Patients with vernal conjunctivitis (active papillae and/or follicles) could
benefit from topical corticosteroid during the acute phase to reduce the acute
inflammation and itch. Topical steroid should be stopped once the symptoms
have been relieved. The mainstay of treatment, however, is sodium
cromoglycate (mast cell stabilizer) eye drops (pg 66).
Grade A, Level 1+
D The use of topical steroid for the management of viral conjunctivitis in the
primary care setting is more controversial. While it certainly alleviates ocular
inflammation, it should be used when the presentation is typical and diagnosis
certain. Some conditions that mimic viral conjunctivitis (such as herpetic
epithelial keratitis and microbial keratitis) may be aggravated by the use of
steroid eye drops (pg 66).
Grade D, Level 3
14
GPP Symptoms of acute allergic conjunctivitis (characterized by conjunctival
chemosis) usually subside within 24 hours without treatment. Similarly,
episcleritis often subsides without treatment. The use of topical steroid may not
be necessary in these cases. Alternatives such as Antazoline eye drops may be
considered instead (pg 66).
GPP
GPP Infective keratitis (corneal ulcer) and herpetic keratitis can mimic viral
conjunctivitis. Topical steroids can worsen these conditions while masking the
symptoms and are contraindicated in these conditions (pg 67).
GPP
GPP Topical steroids are contraindicated in the presence of a history of
contact lens use or ocular trauma as microbial keratitis could be present and
aggravated by steroid use (pg 67).
GPP
A Prolonged application of steroidal eye drops can cause elevation of the
intraocular pressure. This effect has also been demonstrated in children. The
frequency, severity and time-course of the response may be higher in children.
Thus special care must be taken when prescribing steroid eye drops for
children (pg 67).
Grade A, Level 1+
A Being asymptomatic, steroid-induced ocular hypertension may go
undetected for months, resulting in steroid induced glaucoma. Intraocular
pressure should be monitored regularly if steroid eye drops are being used for
long duration (pg 67).
Grade A, Level 1+
D Without intraocular pressure monitoring, steroidal eye drops should not be
used beyond 1 week (pg 67).
Grade D, Level 3 & 4
GPP Patients should be counseled prior to the start of long-term systemic
steroid regarding cataract formation. These are easily diagnosed as fairly dense
central opacities of the pupillary red reflex. Decision to continue or cease
systemic steroid therapy is largely dependant on the primary disease status for
which the steroid was started – cataract can be dealt with surgically with very
high success rates. Routine eye screening for presence of cataract is important
especially for patients in the amblyogenic age group (10 years old or younger),
or when the patient develops visual symptoms (pg 68).
GPP
15
C Prolonged high-dose steroid is known to be associated with central serous
chorio-retinopathy, a condition characterised by single or multiple subretinal
fluid blebs. The patient presents with micropsia (diminished image size) and/or
metamorphopsia (distortion of image). If confirmed by an ophthalmologist,
systemic steroid should be reduced, replaced and discontinued wherever
possible (pg 68).
Grade C, Level 2+
D Patients who require periocular steroid treatment for longer than 4 weeks
would require monitoring of intraocular pressure (pg 68).
Grade D, Level 3
Corticosteroids in other conditions
D Adrenaline is the treatment of choice in anaphylaxis. Corticosteroids are not
helpful acutely but potentially might prevent recurrent or protracted
anaphylaxis (pg 70).
Grade D, Level 4
A Corticosteroids are not recommended for the treatment of Bell's palsy (pg
70).
Grade A, Level 1+
16
1
Introduction
1.1
Background information
These clinical practice guidelines on the use of corticosteroids (also
referred to as steroids in these guidelines) are the result of a series of
dialogue and feedback sessions between the Ministry of Health and
the College of Family Physicians, Singapore. The prescription and
dispensing of steroids in all forms, whether topical or systemic
administration, form a major part of the daily clinical practice of all
doctors in the country.
While steroids are useful in conferring a positive therapeutic response
to many medical conditions in the short-term, long-term usage and
administration of steroids pose many potential hazards to patients and
can lead to medium to adverse effects, some of which can be lifethreatening.
1.2
Development of guidelines
Due to the vast diversity of medical conditions that may be helped by
steroid treatment, our committee was formed with specialists from
many disciplines, such as respiratory medicine, dermatology,
ophthalmology, otorhinolaryngology, rheumatology, gastroenterology,
endocrinology, orthopaedics, paediatrics and family medicine. Our
committee attempted to cover as wide as possible a spectrum of
possible indications and use of steroids in daily clinical practice. The
list of medical conditions covered is by no means exhaustive. The
medical conditions are grouped by medical and surgical disciplines
authored by the respective expert specialists in our panel.
As steroids have been in existence and widely used for a very long
time, much of the evidence to support our recommendations is
gleaned from good clinical practice principles. Where possible, our
expert committee has based its recommendations on supporting
evidence from the scientific literature.
1.3
Objectives
This book is not intended to be a list of dos and don’ts. We are fully
mindful and cognizant of the professionalism of our fellow medical
17
colleagues and would defer to their final assessment and clinical
judgment of their patients’ conditions and the necessary treatments for
the best clinical outcomes. It is our earnest desire and hope that our
fellow colleagues will find this book a useful clinical tool in aiding
them to make better informed and safer clinical decisions when
prescribing steroids to their patients, especially those requiring longterm therapy.
1.4
Review of guidelines
Evidence-based clinical practice guidelines are only as current as the
evidence that supports them. Users must keep in mind that new
evidence could supercede recommendations in these guidelines. The
workgroup advises that these guidelines be scheduled for review 3
years after publication, or when new evidence appears that requires
updating of the recommendations.
1.5
Economic benefits
Steroids have been in existence for a very long time and have the
benefit of being very low cost to most patients, especially in the case
of oral prednisolone. The value of inhaled steroids in reducing the
frequency of recurrent asthmatic attacks, in lengthening the remission
periods, and in reducing the frequency of hospitalizations is well
documented. Our committee feels that as a class of drugs, steroids
represent a low cost therapy to patients who have clinical indications
requiring its use. Due to the vast diversity of preparations involved, it
is beyond the scope and scale of this committee to ascertain which of
the brand or type of steroid is most cost effective and cost beneficial
to the patient. The physician is thus advised to use the most
appropriate and economical preparation available to manage his or her
patient.
18
2
Corticosteroid Therapy in Clinical Practice
2.1
General introduction
The use of corticosteroids started some 50 years ago. Being very
powerful anti-inflammatory agents, they were described as impressive
drugs as they not only improved certain clinical conditions, but also
confered a subjective sense of well-being. These drugs were widely
used but sometimes without strong indications. Most of the uses of
corticosteroids have been in the fields of rheumatology, orthopaedics,
dermatology, oncology, respiratory medicine, otorhinolaryngology
(ENT) and ophthalmology. Endocrinology utilizes corticosteroids for
hypoadrenalism and tapering regimes in hypothalamic-pituitaryadrenal axis suppression.
While powerful as anti-inflammatory agents, these medications have a
host of systemic effects which are deleterious to the patient. Hence,
care should be exercised in the indications, route of administration and
duration of treatment. Drug interactions as well as disease states per se
are modifiers in the response and could result in the enhancement of
side effects.
The latest development towards greater safety of corticosteroids usage
with preservation of full efficacy is channeled at the glucocorticoid
receptor so that reduced potency in side effects is possible. These new
insights may pave the way for novel, safer therapies that retain the
efficacy of currently prescribed steroids.1
Until then we will have to prescribe sensibly and rationalize the
indications, dose, duration and preparation of the right steroid to the
right purpose.
2.2
Corticosteroid potencies and preparations:
Steroids can be prescribed as:
x
x
x
x
x
Topical steroids
Intranasal steroids
Steroid ear and eye drops
Intra-articular steroid injections
Oral steroids
19
Relative potencies of corticosteroids 2,3
Corticosteroids
AntiPharmainflammatory cological
Potency
Cortisone
Hydrocortisone
Prednisone
Prednisolone
Triamcinolone
Methylprednisolone
Betamethasone
Dexamethasone
0.8
1
3.5
4
5
5
25
30
25
20
5
5
4
4
0.6
0.75
Half-life
Salt
Hypothalamic(min) retention
pituitaryadrenal axis
suppression
30
2
1
90
2
1
60
1
4
20
1
4
300
0
4
180
0
100-300
0
100-300
0
17+
Factors in successful corticosteroid therapy4,5
Monitoring
Counseling
x
x
x
x
x
x
x
x
x
x
x
x
Recognising
complications
x
x
x
x
x
Glucose concentration (serum and urine)
Electrolytes (serum and urine),
Ophthalmologic examination
Stool tests for occult blood
Growth and development (children and adolescents)
Take food with medication
Never discontinue medication on your own
Gradual reduction is usually necessary
Carry or wear MEDIK AWAS
Dosage increases may be necessary at times of increased stress
(surgery or emergency)
Be aware of potential side effects (visual effects, bruising,
delayed wound healing)
What to do if a dose is missed:
- If dose is every other day, take in the morning if remembered
that morning, if not skip that day. Take the next morning, and
then skip the following day.
- If dose is daily: take as soon as possible. But skip if almost
time for next dose. Never double doses.
Early in therapy and essentially unavoidable are insomnia,
enhanced appetite, weight gain
Delayed and insidious: cataracts, atherosclerosis
Rare and unpredictable: psychosis, glaucoma, pancreatitis
Complications are common in patients with underlying risk
factors: hypertension, diabetes mellitus, peptic ulcer disease
Long-term intense treatment leads to Cushingoid habitus,
hypothalamic-pituitary-adrenal suppression, impaired wound
healing
20
2.3
Principles of corticosteroid therapy
Guidelines for pharmacologic administration of corticosteroids 6
1.
2.
3.
4.
5.
6.
7.
2.4
Initiate only if there is published evidence of objective
therapeutic benefit
Use only after other specific therapies fail
Identify a specific therapeutic objective
Use objective criteria of response
Administer sufficient steroid for a sufficient time to achieve the
desired response
Administer steroids for no longer than is necessary to achieve the
desired response
Terminate if objective therapeutic benefit is not observed when
expected, if complications arise or if maximum benefit has been
achieved.
Adverse effects of corticosteroids in various
formulations for systemic and local use
As adverse effects of steroids are related to its dose and duration, it is
essential to have a strong indication before commencing on steroids.
Besides the older, nonetheless relevant studies of rheumatoid
arthritis7-9 patients exhibiting adverse events, notably increased
mortality, a recent study has also demonstrated that patients with
steroids by prescription had a significant increase in subsequent
cardiovascular events.10
D The baseline information on blood pressure, weight, growth curve
(in children), ophthalmic examination, tuberculosis screening, and
levels of fasting glucose, triglycerides and potassium levels, is
required in patients in whom steroids have to be started. Repeat
ophthalmologic examinations should be done every 6 monthly. The
levels of triglycerides, fasting glucose and potassium should be
checked after one month of steroid therapy and thereafter, every 3-4
monthly. Blood pressure and weight should be measured at every visit.
A history of adverse effects would be ideal at every visit.11,12
Grade D, Level 4
GPP Hepatitis B status should be checked in all patients in whom
steroids have to be started on long term basis.
GPP
21
The following side effects are correlated with duration, potency and
dosage of steroids used. As the more vulnerable are at extremes of life,
the young and elderly merit special attention.
A) Iatrogenic or factitious Cushing’s syndrome
Iatrogenic Cushing’s syndrome is caused by the administration of
excessive amounts of a synthetic glucocorticoid (which includes
prednisolone, prednisone, dexamethasone), and rarely by ACTH. It is
the commonest cause of Cushing’s syndrome and is also referred to as
ACTH-independent. It can be occasionally caused by megestrol
acetate which has intrinsic glucocorticoid activity.
Features of iatrogenic Cushing’s syndrome as opposed to natural
Cushing’s syndrome are as follows:
More common in iatrogenic Cushing’s syndrome
x Traditional stigmata of central obesity
x Supraclavicular fat pads
x Moon facies
x Plethora
x Easy bruising
x Thin skin
x Striae
x Myopathy
x Muscle weakness (proximal)
x Poor wound healing
x Depression
x Psychosis
x Osteoporosis13
x Increased incidence of infection
Less common in iatrogenic Cushing’s syndrome
x Hypertension
x Hypokalemia
x Hirsutism or virilism
Virtually unique to iatrogenic Cushing’s syndrome
x Benign intracranial hypertension
x Glaucoma
22
x
x
x
x
Posterior subcapsular cataract14
Pancreatitis
Aseptic necrosis of bone
Panniculitis
The most striking laboratory result to distinguish iatrogenic Cushing’s
syndrome from ACTH-dependent Cushing’s syndrome is a low
plasma cortisol coupled with low ACTH levels after cessation of
steroids in Iatrogenic Cushing’s syndrome.
To avert the onset or to minimise the effects of iatrogenic Cushing’s
syndrome, glucocorticoids with little or no mineralocorticoid activity
(i.e. hydrocortisone, prednisone, prednisolone, methylprednisolone,
triamcinolone, betamethasone, and dexamethasone) could be used as
opposed to mineralocorticoids like fludrocortisone.
The only
naturally-occuring glucocorticoids are cortisol and cortisone. The
mode of administration could play a significant role in the onset and
evolution of adverse effects.
B) Corticosteroids and macrovascular disease
B In patients at risk of ischemic heart disease, myocardial infarction,
angina, coronary revascularization, heart failure, transient ischaemic
attack or stroke, it is best to avoid corticosteroids. However, if
definitely indicated, dose should be less than or equal to 7.5 mg
prednisolone daily, and should be reduced over time as deemed safe
and efficacious.
Grade B, Level 2++
Exogeneous corticosteroids in excess can contribute to the
development of hypertension, insulin resistance, hyperglycaemia,
weight gain, hyperhomocysteinemia and atherosclerosis.10,15
Increased rates of all cardiovascular events were found in those who
were prescribed 7.5 mg prednisolone or more per day compared to
those with non-steroid prescription, the adjusted risk ratio being 2.56.
For individual outcomes of congestive heart failure, acute myocardial
infarction, stroke and transient ischaemic attacks and all-cause
mortality, it was noted that those who were prescribed high dose
corticosteroids had significantly increased risk (relative risk: 3.72,
3.26, 1.73, and 7.41 respectively).10
23
Current usage of corticosteroids was associated with increased risk of
heart failure (relative risk 2.66) and mild increase in transient
ischaemic attacks (odds ratio 1.2) but not stroke.15
There was an increased risk of arteriosclerosis in patients with
rheumatoid arthritis receiving long-term corticosteroids therapy,
shown by a 3-fold increase in the incidence of lower limb
calcifications.16
D Use of corticosteroids should be carefully considered and
preferably restricted in obese patients as studies have linked
corticosteroids with elevated ratio of intra-abdominal to subcutaneous
fat mass.17,18
Grade D, Level 3
C) Corticosteroids and hyperglycemia
B Blood sugar should be monitored before and after commencement
of corticosteroids as there is an increased risk of developing
hyperglycaemia when steroids exceed the dose equivalent to 10 mg
prednisolone per day.
Grade B, Level 2++
There is 1.8-fold risk of developing diabetes de novo even at doses
lower than 10 mg prednisolone per day.19 Patients with a family
history of diabetes mellitus or who have the metabolic syndrome,
must be carefully assessed for the need for oral hypoglycaemic drug
therapy as reversibility with reduced dosing of steroids is a
possibility.19-22
D) Corticosteroids and bone mineral density
C Corticosteroids should be used in the lowest possible dose to avert
long-term fracture risk. Even low doses of steroids equivalent to 2.5
mg prednisolone per day could compromise bone integrity, and doses
of 5 mg and above are associated with increased long-term fracture
risk.23-25
Grade C, Level 2+
If steroids are required for prolonged periods, the dose should be
limited to 15-20 mg prednisolone per day to avert osteonecrosis (of
24
heads of femur and humerus). The risk of osteonecrosis is greater with
higher doses of corticosteroids. Osteonecrosis can also occur with
lower doses given for long duration and after intra-articular
corticosteroids.27
It has been suggested that corticosteroid-induced
contributes to the high fracture rate in these patients.
myopathy
Fractures may occur in 30-50% of patients on chronic corticosteroid
therapy. Bone loss is fastest in the first 6 months of therapy and
persists at a lower rate thereafter.28
A retrospective cohort study showed significantly increased risk of
non-vertebral, hip, forearm and vertebral fractures (relative risk: 1.33,
1.61, 1.09, and 2.60 respectively) in patients treated with
corticosteroids as compared to controls. Fracture risk may decrease
rapidly after cessation of steroids.23
A meta-analysis of seven prospective cohort studies found that prior
use or current use of corticosteroids was associated with increased
fracture risk.25
B Calcium and vitamin D should be prescribed for patients receiving
an average of near-physiologic level of 5-7 mg prednisolone per day
to avert reduction in bone loss.29
Grade B, Level 1+
There is a fracture risk of 34-58% in patients receiving prolonged
prednisolone at 6.5 mg to 8.6 mg per day. In a study of those receiving
an average dose of 5.6 mg per day, reduction in bone mineral density
of 2% and 0.9% of the lumber spine and trochanter respectively was
preventable with vitamin D supplementation.30
A The combination of bisphosphonates combined with vitamin D is
the most effective and is highly recommended for the treatment of
glucocorticoid-induced osteoporosis.30
Grade A, Level 1+
D Tests of bone mineral density, particularly of the spine, should be
done in women who are above 50 years of age, and have received 6
months of corticosteroid.31,32
Grade D, Level 4
25
E) Corticosteroids and wound healing
D In situations of wound repair, steroids should be avoided but if
unavoidable, should be used sparingly.
Grade D, Level 4
Corticosteroids delay healing of wounds by inhibiting inflammation,
collagen synthesis and cross-linking of collagen fibres, hence
affecting the structural integrity of wounds. The problem is likely to
be compounded if there is hyperglycaemia.33,34
F) Corticosteroids and central nervous system effects
D Changes in mental state, cognitive function and emotional
responses in patients on corticosteroids could be due to corticosteroids.
As this is eminently treatable, due care should be taken to monitor
those with a predisposition to mental disturbances, e.g. those with a
family history of mental disturbances, a past history of depression or
alcoholism when prescribing corticosteroids to these patients.35-43
Grade D, Level 3
It is commonly reported that 50% of patients with either natural or
iatrogenic Cushing’s syndrome have psychiatric illness, depression
being the most common.
At a daily dose of prednisone of 15 mg per day, mood disorders have
been observed in rheumatoid arthritis patients.
High dose of corticosteroids taken for ocular symptoms produced
hypomanic symptoms in 30% and depressive symptoms in 10% of
patients within a one-week period.36
A study of corticosteroid treated multiple sclerosis patients revealed
increased risk of hypomanic and manic symptoms in those with a
family history of depression or alcoholism.40
Partial memory loss was observed in patients receiving steroid doses
between 5 mg and 40 mg prednisolone per day for 1 year or more. In
some patients, effects were evident after three months of therapy.41
26
Chronic exposure to excess corticosteroids can lead to cerebral
atrophy. There had been only partial reversal following decrease or
cessation of steroids use, hence it is best to keep steroids to low doses,
if they are definitely required.44
G) Special considerations
Adverse effects in children
A If corticosteroids are indicated for growing children, the regime
should be alternate-day, preferably topical, and used sparingly.
Grade A, Level 1+
Inhaled corticosteroids (supposedly short-lived) have been associated
with significant side effects, like growth retardation in children and
reduction of bone markers in adolescents.45,46
Intranasal corticosteroids have been linked to Cushing’s syndrome.47
Intra-articular and intradermal steroids were reported to have caused
Cushing’s syndrome in 3 children.48
Adverse effects in elderly patients
D In the elderly, dosage of steroids should be limited to 10 mg
prednisolone per day, not exceeding a year, as the elderly are more
likely to be disabled by complications of glaucoma and subcapsular
cataract.49
Grade D, Level 3
Cushingoid facies occur exclusively at doses equal to or exceeding 7.5
mg prednisolone daily.
D To decrease the risk of myopathy, particularly in the elderly,
fluorinated corticosteroid preparations like dexamethasone and
triamcinolone should be avoided and dose of prednisolone should not
exceed 10 mg per day.50
Grade D, Level 3
Myopathy is a dose-dependent effect that could develop within one
month, particularly with fluorinated preparations. It is a potentially
reversible condition with reduction or cessation of dose.
27
Elderly patients who are vulnerable to memory decline may
experience aggravated and accelerated memory decline due to
corticosteroids.51-53 Loss of brain volume may be reversed following
eucortisolism.54
2.5
Endocrine effects and withdrawal after discontinuation
of corticosteroids
GPP It is best to avoid the usage of high dose corticosteroids over a
prolonged duration.
GPP
This is due to hypothalamic-pituitary-adrenal axis suppression and the
adverse effects of corticosteroids, coupled with the difficulty in tailing
off these medications for the following reasons55-58:
1.
2.
3.
4.
5.
The illness may relapse.
Hypothalamic-pituitary-adrenal axis suppression may last for
more than 6 months.
Non-specific withdrawal may develop even when doses are at
physiological replacement level.
Psychological dependence occurs resulting in anxiety and panic
with activation of sympathoadrenal system.59
The weaning off process even when hypothalamic-pituitaryadrenal axis is normal (using criteria of stimulated cortisol with
insulin tolerance test or co-syntropin) or when dose of
corticosteroids are at physiological levels, could be associated
with symptoms of anorexia, weight loss, nausea, emesis, fatigue,
myalgias, arthralgias, headaches, abdominal pain, postural
hypotension, fever and skin desquamation. This appears to be
indicative of “physical dependence on supraphysiological levels
of glucocorticoids”. This is also described as the corticosteroid
withdrawal syndrome. Its underlying basis is postulated to be the
hyposecretion of corticotrophin-releasing factor due to
hypoactivity of central corticotrophin releasing hormone neurons,
with possible disturbance of vasopressin and oxytocin neurons.
28
Withdrawal of corticosteroids
A Corticosteroids should be withdrawn by tapering the dose gradually.
The decision on tapering regime should be made on individually
tailored basis.60
Grade A, Level 1+
There is insufficient evidence to support any particular regimen at this
point of time.60
Inter-individual differences for drug absorption and clearance
contribute to the difficulty in advocating any particular regime. Even
non-oral forms i.e. topical, intra-articular, intranasal, have been
demonstrated to cause hypothalamic-pituitary-adrenal axis
suppression if used in supraphysiological doses. Withdrawal plans are
based on the dual goal of avoiding adverse effects of prolonged
steroid therapy while avoiding the potential consequences of adrenal
insufficiency.
D Prompt withdrawal with rapid tapering is required in the following
instances61:
x Steroid psychosis
x Herpes-induced corneal ulceration
x Uncontrolled hypertension
x Serious lumbar spine osteoporosis
x When therapeutic targets have been achieved or when the regime
with steroids proves inefficacious.
Grade D, Level 4
D It is unlikely that a tapering regime would be required in the
following patients56,57:
x those receiving any dose of corticosteroids for less than 3 weeks
duration62,63
x those on alternate-day therapy52
x those given less than 10 mg prednisolone per day (day dose) for
more than a few weeks63 or at physiologic doses taken for less
than 1 month.58
Grade D, Level 3 & 4
Studies revealed that there is no correlation of hypothalamic-pituitaryadrenal axis suppression with duration, dose or level of early
cortisol.64,65
29
A Withdrawal plans should be commenced by reducing the
corticosteroids from supraphysiologic to physiologic doses, which is
equivalent to 5-7 mg of prednisolone per day (or hydrocortisone at 1520 mg per day). Subsequent reduction has been suggested with
conversion to hydrocortisone (because of shorter half life) or alternate
day prednisolone.66 During periods of stress or injury, additional doses
may be required to avert adrenal crises. The whole process of
withdrawal may last from 9 to 12 months.
Grade A, Level 1+
Testing the hypothalamic-pituitary-adrenal axis integrity would
involve plasma cortisol at 0800 hour, low dose or high dose Cosyntropin testing,61 and/or the gold standard insulin tolerance test60,66
in a hospital setting. Issues of sensitivity and specificity relate to such
tests.61 In lieu of further testing, an alternative approach would be to
continue a gradual taper from the level of physiologic replacement.67
30
3
Intranasal Corticosteroid Use in Clinical
Practice
Randomised controlled trials showed significant improvement in nasal
obstruction, nasal discharge, nasal itch, post-nasal drip and total nasal
symptoms in patients on intranasal corticosteroids compared to
patients on oral H1 receptor antagonists. There was no difference in
eye symptoms between the 2 groups.68
Randomised controlled trials showed no difference in the comparative
efficacy of the various intranasal steroids.69
There is a multitude of studies comparing the use of intranasal
steroids. Meta-analysis suggests that the efficacy of intranasal steroids
is better compared with that of oral antihistamine.
Administration of budesonide aqueous nasal spray for 6 weeks had no
measurable suppressive effects on hypothalamic-pituitary-adrenal axis
function in children aged 2 to 5 years old.70
Fluticasone propionate aqueous nasal spray administered for one year
had no effects on growth velocity in children aged 3.5 to 9 years old
with allergic rhinitis.71
Mometasone furoate aqueous nasal spray administered for one year in
children aged 3 to 9 years old with perennial allergic rhinitis had no
effect on growth velocity, with no evidence of hypothalamic-pituitaryadrenal axis suppression at any time point.72
The data suggest that intranasal steroids are relatively safe in children.
In a study of long-term use of up to one year, a multicentre, placebocontrolled, double blinded study did not show any effect on growth or
the hypothalamic-pituitary-adrenal axis. Table 1 (page 32) shows the
ages and safety doses.72
An 8-week course of fluticasone propionate aqueous nasal spray did
not affect maternal cortisol levels, foetal growth or pregnancy
outcomes.73
There is not much data on the use of steroids in pregnancy.
Triamcinolone has been found to be teratogenic and thus is to be
avoided in pregnancy. Recently a study of one nasal steroid did not
show an impact on pregnancy as referenced above.73
31
A randomised controlled trial showed symptomatic relief of nasal
symptoms after 12 weeks of treatment with fluticasone propionate
nasal drops but no objective change in polyp size in bilateral nasal
polyposis in adults.74
There is data to show that nasal polyps can be reduced by intranasal
steroids as a single modality of treatment. The above study showed
symptomatic relief but no objective reduction of polyp size. There is
also no conclusive data that nasal steroids are helpful in the presence
of sinusitis.
A Intranasal steroids are indicated in both adults and children with
allergic rhinitis, with no significant growth effects in children.
However, there is no definite recommendation for use in pregnancy.
Grade A, Level 1++
Table 1
Intranasal
steroids
Fluticasone
propionate
Mometasone
fuorate
Beclomethasone
dipropionate
Triamcinalone
acetonide
Commonly used intranasal steroids
Adult
dosage*
(ȝg/day)
Maximum
number of
sprays
per day
Child’s age
above which
use of steroids
is approved
(years)
Child
dosage
(ȝg/day)
Maximum
number of
sprays
per day
200
4
4
100
2
200
4
2
100
2
200
10
6
100
5
220
4
4
110
2
* adult dosage is for those who are >12 years of age.
(Source: Prescription drug information from package inserts)
A Intranasal steroids should not be given to children with upper
respiratory infections as intranasal steroids use neither provides
symptomatic relief nor decreases episodes of acute otitis media.75
Grade A, Level 1+
A Both oral and topical intranasal steroids may be used alone or in
combination with an antibiotic as steroid use along with antibiotic,
leads to a quicker resolution of otitis media with effusion in the shortterm. However, there is no definite recommendation for a long-term
benefit with their use.76,77
Grade A, Level 1+ and 1++
32
4
Use of Corticosteroid Ear Drops in Clinical
Practice
A randomized controlled trial showed that ear drops containing
corticosteroids were more effective than acetic ear drops in the
treatment of acute otitis externa (cure at day 14). Steroid and acetic or
steroid and antibiotic ear drops are equally effective.78
There is a paucity of data with randomized control studies to compare
the efficacy of steroids in acute ear infections. In the above study, the
ear preparations containing corticosteroids were more effective than
acetic acid ear drops in the treatment of acute otitis externa. It is
noteworthy that steroid and acetic acid or steroid and antibiotic ear
drops are equally effective.
A Either combination of steroid and acetic acid ear drops or steroids
and antibiotic ear drops may be used in the treatment of acute otitis
externa.
Grade A, Level 1++
A Steroid ear drops may be used in the treatment of eczematous otitis
externa as steroid use leads to improvement of otological symptoms,
particularly erythema, swelling and discharge.79
Grade A, Level 1+
A randomized controlled trial showed that five-day treatment with
antihistamine or corticosteroid, in addition to antibiotic, did not
improve acute otitis media outcomes. Antihistamine use during an
acute episode of otitis media should be avoided.80
33
5
5.1
Corticosteroids and Gastrointestinal Conditions
Introduction
Corticosteroids are useful in very few specific gastrointestinal and
hepatic conditions. These include inflammatory bowel diseases
(ulcerative colitis, Crohn’s disease), autoimmune hepatitis, severe
alcoholic hepatitis, and certain other rare conditions like collagenous
sprue/eosinophlic gastroenteritis, which will not be further discussed
here. In other conditions like vasculitis, or other drug-induced
problems, the decision to use steroids is on a case-to-case basis.
Corticosteroids are “double-edged swords” and while useful, have
potential dangers especially with prolonged use. Other than the well
known systemic side effects of corticosteroids, specific effects in the
gastrointestinal tract include an increased incidence of complications
of peptic ulcer disease and reactivation of hepatitis B.
5.2
Beneficial effects of corticosteroids
5.2.1 Corticosteroids and inflammatory bowel disease
A Oral systemic and intravenous steroids are useful in inducing
remission and may be used in active ulcerative colitis.81-83
Grade A, Level 1++
In severe ulcerative colitis, intravenous steroids should be used
initially. In mild to moderate cases, patients can be started on oral
doses. The doses should be kept at maximum therapeutic levels for at
least 2 weeks or until clinical remission occurs before tapering.
A Budesonide, an oral topically acting steroid, is also useful and may
be used in active ulcerative colitis.84,85
Grade A, Level 1+
Budesonide is an oral non-systemic corticosteroid with only 10%
systemic bioavailability. It is effective in patients with extensive
ulcerative colitis as compared to patients with only left-sided colitis. It
is, however, less effective than systemic corticosteroids.
34
A Steroid enemas are useful in inducing remission in patients with
distal colitis and a useful adjunct in patients with left-sided colitis.86
Grade A, Level 1+
Enemas are useful in inducing remission in patients with distal
colitis/proctitis. They are also useful adjuncts in inducing remission
with more extensive colitis. They have less systemic side effects
compared to systemic steroids. However, steroid enemas have been
found to be less efficacious than topical aminosalicylates.
A Steroids should not be used in maintaining remission in ulcerative
colitis.81,87,88
Grade A, Level 1++
While steroids are useful in inducing remissions, large scale studies
have found no evidence that these drugs can prolong remission.
Patients in remission should be taken off steroids. Patients who are
steroid dependent and cannot be tailed off should be given an
alternative drug.
5.2.2
Corticosteroids in Crohn’s disease
A Both systemic steroids and oral topically acting steroids
(budesonide), either alone or in combination, may be used in active
Crohn’s disease.89-93
Grade A, Level 1++
In active Crohn’s disease, steroids are useful in bringing the disease
into remission. Most patients attain remission in 10 to 12 weeks.
Budesonide is more effective for patients with disease involving the
terminal ileum and ascending colon. While budesonide is not as
effective as systemic steroids, it has considerably less side effects.
A Steroids should not be used in maintaining remission in Crohn’s
disease.89,90,94-96
Grade A, Level 1++
Steroids have not been found to be useful in maintaining remission in
Crohn’s disease. Patients continued on steroids do not have a lower
incidence of relapse as compared to patients without steroids. Patients
35
who do not respond to steroids or relapse soon after should be started
on alternative treatments.
5.2.3 Corticosteroids and liver disease
Autoimmune hepatitis
A Steroids are very useful and may be used in inducing remission and
preventing relapse in autoimmune hepatitis.97-99
Grade A, Level 1++
This is a condition more common in females and characterized by the
presence of hepatitis in the presence of hypergammaglobulinemia and
autoantibodies. Prednisolone induces remission in the majority of
patients but 80% relapse after cessation of treatment. These patients
will benefit from continuous low dose prednisolone.
Alcoholic liver disease
A Steroids may be used in the treatment of severe alcoholic
hepatitis.100-103
Grade A, Level 1+
Severe alcoholic hepatitis is a serious condition with a mortality of
60% in the first 4 weeks after diagnosis. Steroids are used to suppress
the activated immune response. While controversial, recent metaanalyses have found an improvement in the short-term mortality in
patients with severe alcoholic hepatitis. However, they should be used
in the absence of renal failure, active infections and gastrointestinal
bleeding - complications commonly associated with this condition.
5.3
Problems with steroids
5.3.1 Corticosteroids and peptic ulcer disease
Corticosteroids do not increase the incidence of gastric and duodenal
ulcer.104-106
Steroids with the use of non-steroidal anti-inflammatory drugs
(NSAIDs) increase the incidence of peptic ulcer disease.107
36
Patients on steroids complain of dyspepsia more often than those
without. However, large scale studies while showing a trend towards a
higher incidence of peptic ulcer disease, have not shown any statistical
significance between those with and those without steroids. This
indicates that it is unnecessary to practice preventive anti-ulcer
treatment to all patients receiving steroids. There is, however, a higher
incidence of peptic ulceration in patients who use both steroids and
NSAIDs.
Steroids do not increase the incidence of peptic ulcer complicationsbleeding and perforation.104
There is some evidence that steroid usage results in a higher incidence
of peptic ulcer perforation in the elderly.108,109
Steroids when used together with NSAIDs, result in a higher
incidence of peptic ulcer complications.108,109
While there is a trend showing a higher incidence of complications for
the usage of steroids alone, it is not statistically significant. However,
the usage of NSAIDs and steroids together more than doubles the
risks of complications. Patients on such combination should receive
preventive anti-ulcer medication.
GPP Patients who are on steroids should have prophylaxis if they are
also on non-steroidal anti-inflammatory drugs or are elderly with a
history of peptic ulcer disease.
GPP
5.3.2 Corticosteroids and Hepatitis B and C (HBV
and HCV)
The usage of corticosteroids can lead to reactivation of quiescent
hepatitis B infection or recurrent flares. This can result in fulminant
hepatitis.110-113
A Patients who are known to be hepatitis B virus carriers and are
receiving chemotherapy with corticosteroids should also receive
prophylaxis.114-116
Grade A, Level 1+
37
GPP Patient who are known to be hepatitis B virus carriers should be
considered for prophlylactic medication if they are to receive systemic
steroids for a duration of more than a week.
GPP
GPP It is advisable to test all patients for hepatitis B if systemic
long-term steroids are being considered.
GPP
Initial studies had demonstrated the effectiveness of steroids for
treating chronic active hepatitis in non-hepatitis B patients.
Subsequent studies on patients who are hepatitis B virus carriers have
either shown no added effects or worse outcome in those treated with
long-term steroids. There is an increase in hepatitis B virus DNA
levels with the use of steroids and its subsequent cessation can lead to
a flare of the condition. It is therefore not advisable to start patients
with hepatitis B virus on long-term systemic steroids. Studies have
also shown that the hepatitis B virus DNA levels especially in eantigen positive individuals rise exponentially in 2 weeks. It is
therefore advisable to consider prophylaxis in patients who are to take
systemic steroids for more than a week.
More recent studies have shown that when used in combination with
other chemotherapeutic drugs for malignancy, hepatitis-related flares
are common. This usually occurs when the doses are being tailed
down. Patients on such therapy should also receive prophylactic
antivirals.
The usage of corticosteroids has neither beneficial nor deleterious
effects in patients with hepatitis C.117-119
Hepatitis C is sometimes associated with autoimmune phenomena
which might require the use of steroids. Moreover, there is an overlap
in the diagnosis of hepatitis C and autoimmune hepatitis. This might
necessitate the use of corticosteroids. Unlike hepatitis B, reviews have
not found sufficient evidence of any beneficial or deleterious effects
with the use of corticosteroids in this condition.
A Based on present evidence, there is no need to specifically look for
the presence of hepatitis C before starting corticosteroid treatment in
any medical condition.
Grade A, Level 1+
38
6
6.1
Use of Corticosteroids in Children
Introduction
6.1.1 Special considerations in the paediatric patient
The side effects of systemic corticosteroids in adults and children are
well known, whereas topical corticosteroids are generally thought to
be safe. However, physicians should remember that this safety profile
has been demonstrated when corticosteroids are used at recommended
doses. Topical corticosteroids may not be as innocuous if used at
higher than recommended doses in children. Issues with inhaled
corticosteroids will be discussed here.
6.1.2 Growth
The paediatric age is the time of growth. Growth retardation is a side
effect of treatment with systemic corticosteroids.120,121 The longer the
treatment, the more severe the impairment. The data for inhaled
steroids is not as clear-cut. However, it should be remembered that
substantial symptomatic improvement occurs in asthmatic children
treated with inhaled corticosteroids.
Normal final adult height is achieved with low dose inhaled
corticosteroids.122,123
There may be some reduction in growth velocity in the first year of
therapy but this tends not to be sustained during subsequent years.
Moderate doses of beclomethasone and fluticasone in children with
mild to moderate asthma caused a slight decrease in linear growth
velocity (1.51 cm/year and 0.43 cm/year, respectively) when followed
up for 54 weeks.124
The effect of moderate and high doses of inhaled corticosteroids when
given for >54 weeks on final adult height remains unknown.
6.1.3
Cataracts
There is no evidence that inhaled corticosteroid therapy causes
posterior subcapsular cataract formation, even if treatment is for as
long as 3 to 6 years.125,126
39
D Although children receiving long-term systemic corticosteroid
therapy should be screened for cataracts, this is unnecessary in
children on inhaled corticosteroids alone.
Grade D, Level 3
6.1.4 Effect on bone metabolism
At recommended doses, inhaled corticosteroids have no adverse
effects on bone density in children.127
Children aged 6 to 14 years treated with fluticasone propionate had
normal increases in lumbar spine and femoral neck bone mineral
densities.
6.1.5
Suppression of adrenal function
Low to moderate dose inhaled corticosteroids do not cause adrenal
suppression.128
Low dose budesonide aqueous spray in children aged 2 to 5 years also
does not result in adverse effect on the hypothalamic-pitutary-adrenal
axis.70
However, acute adrenal insufficiency has been reported in children
receiving high doses (>500 ug/day) of fluticasone propionate.129
6.1.6 Neuropsychological disturbances
Low doses of inhaled corticosteroids do not cause neuropsychological
and behavioural changes in children.123,130
However, small case series have shown that moderate doses of
budesonide can cause aggressiveness, hyperanxiety, mood changes
and excitability in children.131
Oral prednisolone at a dose of 2 mg/kg/day for 5 days in children with
asthma exacerbations was more likely to cause changes in behaviour
(aggression and anxiety) than a dose of 1 mg/kg/day.132
40
6.2
Use of corticosteroids in the paediatric patient
Corticosteroids are used for many medical indications in children.
These include diseases of the respiratory tract, skin and autoimmune
conditions. There is overlap with the use in adults, but there are
medical conditions unique to the paediatric age group. These will be
discussed here.
6.2.1 Acute bronchiolitis
Acute bronchiolitis occurs in children less than 2 years of age. It is
characterized by upper respiratory tract symptoms progressing on to
tachypnoea, crepitations and wheezing.
A Systemic corticosteroids are NOT recommended in children with
acute bronchiolitis.133
Grade A, Level 1++
A Inhaled corticosteroids are NOT recommended in children with
acute respiratory syncytial viral bronchiolitis.134
Grade A, Level 1+
No benefits were found in either length of stay in hospitalized patients
or in clinical score in patients seen at the emergency department.
6.2.2 Acute laryngotracheobronchitis
Acute laryngotracheobronchitis (ALTB or croup) occurs in children
less than 6 years old, typically between the ages of 1 to 2 years. They
have symptoms of an upper respiratory tract infection with the gradual
onset of stridor. The commonest aetiological agent is parainfluenza
virus.
A Corticosteroids are recommended for the treatment of acute
laryngotracheobronchitis.135
Grade A, Level 1++
A Nebulized budesonide, oral and parenteral dexamethasone have the
same effectiveness and
laryngotracheobronchitis.136
may
be
used
for
treatment
of
Grade A, Level 1+
41
Treatment with oral dexamethasone or nebulised budesonide resulted
in relieving symptoms, fewer return visits, fewer readmissions and
shorter length of stay for hospitalized patients.
GPP For children with mild croup, a single dose of oral
dexamethasone is an effective treatment. Choice between oral and
parentral dexamethasone is up to the individual clinical setting.
GPP
6.2.3
Asthma
Corticosteroids are used in acute asthma exacerbations (systemic) as
well as for maintenance therapy (inhaled) in patients with persistent
asthma.
A Systemic corticosteroids are recommended for children with acute
asthma exacerbation.137
Grade A, Level 1++
Both oral prednisolone and intravenous steroids have been shown to
be effective in acute asthma, resulting in earlier discharge, shorter
length of stay and less chance of relapse. There is insufficient
evidence to support the use of early inhaled corticosteroids in the
treatment of acute asthma exacerbations.138
A Inhaled corticosteroids are recommended for the treatment of
children with persistent asthma.139,140
Grade A, Level 1++
Inhaled corticosteroids resulted in improvements in FEV1 (forced
expiratory volume in the first second), morning peak flow values,
reduction in rescue ȕ2-agonist use and reduction in need for rescue
prednisolone. Physicians should refer to the global initiative for
asthma (GINA) guidelines (www.ginasthma.org) for more
information.
6.2.4 Eczema
Eczema is a chronic inflammatory skin disease which affects about 15
to 20% of children in Singapore. It causes not only medical
complications but can also adversely affect the quality of life of child
42
and parent. Eczema commonly begins at a young age (usually infancy)
and runs a course of exacerbations and remissions.
A Topical corticosteroids are recommended for children with
moderate to severe eczema. Topical corticosteroids results in
improvement in disease severity and reduces the risk of relapse.141,142
Grade A, Level 1+
In two studies looking at children 2 to 14 years old, treatment was
well tolerated with no visible signs of skin atrophy. Treatment should
be in conjunction with adjunctive therapy such as emollients and antihistamines as necessary.
6.2.5 Systemic corticosteroids
GPP It is recommended that systemic corticosteroids in children
(except short courses or “bursts” which are not likely to cause side
effects) should be used in consultation with physicians with
experience in its use and in monitoring for side effects.
GPP
43
7
Corticosteroid Injections in Joints and Soft
Tissues
Corticosteroids are used for injection into
1. joints
2. bursae
3. soft tissues
Aseptic technique is important. The presence of infection must be
excluded before corticosteroid injections.
7.1
Upper limb conditions
7.1.1 Shoulder conditions including rotator cuff
tendonitis and adhesive capsulitis
A Corticosteroid injections may have short-term benefits but may
not be sustained. The subacromial route is recommended for rotator
cuff tendonitis and intra-articular injection for adhesive capsulitis.
Oral non-steroidal anti-inflammatory drug (NSAID) therapy may be
considered prior to injection therapy.143-145
Grade A, Level 1+
7.1.2 Lateral epicondylitis (Tennis Elbow) and
medial epicondylitis (Golfer’s elbow)
A Corticosteroid injections can provide short-term relief, and can be
useful in early treatment of lateral epicondylitis (Tennis Elbow) and
medial epicondylitis (Golfer’s elbow).146-148
Grade A, Level 1+
Possible adverse effects include subcutaneous necrosis with local skin
atrophy, and post-injection pain.4,5
44
7.1.3 De Quervain’s Tenosynovitis
D Corticosteroid injections can provide short-term relief, is useful
and may be used in early treatment of De Quervain’s Tenosynovitis.
Grade D, Level 3
It is most effective in patients that present early with a short history.
Injections may be coupled with splinting.149,150
Possible adverse effects include local discomfort, local flare, bruising,
superifical radial nerve neuropraxia, and local subcutaneous fat
atrophy.149,150
7.1.4 Carpal tunnel syndrome
A Corticosteroid injections can provide short-term relief and may be
used for carpal tunnel syndrome.
Grade A, Level 1++
It is most effective in early presentation with short history and
minimal neurological deficit. One study found this modality not
superior to oral NSAIDs with splinting.151
One possible complication is intra-neural injection of the median
nerve.
D Recommended safe injection technique for carpal tunnel
syndrome:152
x 25G needle at 30 degree angle insertion, approach skin ulnar to
palmaris longus tendon.
x Withdraw needle if paresthesia experienced by patient.
x Bulge in palm distal to transverse carpal ligament is indication of
correct placement of needle.
Grade D, Level 4
7.1.5 Trigger finger
D Corticosteroid injections are highly effective and may be used as
first line therapy for long-term treatment of trigger finger and
thumb.153,154
Grade D, Level 3
45
True intra-sheath injection confers no advantage compared to
subcutaneous injection over the annular pulley.155
7.2
Lower limb conditions
7.2.1 Osteoarthritis of the knee
A Intra-articular corticosteroid injections provides short-term
benefit and may be used in relieving pain.156,157 Judicious use is
advocated in acute exacerbation of osteoarthritis. It may be combined
with knee aspiration if effusion is present.
Grade A, Level 1+
The incidence of septic arthritis resulting from intra-articular injection
corticosteroids has ranged from 1:14,000 to 1:50,000.158-160
We suggest the use of this modality in the community setting with
caution.
GPP Regular use of intra-articular steroids is not recommended for
osteoarthritis of the knees in the general practice setting.
GPP
7.2.2 Achilles tendinitis
A No benefit has been shown for the use of injection corticosteroid
in Archilles tendonitis and it is not recommended for this condition.161
Grade A, Level 1+
There have been many animal studies showing the deleterious effects
of steroids on tendon healing, as well as case reports162-169 of Achilles
tendon rupture after injection corticosteroid. As there is no benefit
shown in the use of this modality in Achilles tendinitis, coupled with
the attendant risks, we strongly advise against any use of injection
corticosteroid therapy in this condition.
7.2.3 Plantar fasciitis
A Corticosteroid injections can provide short-term relief of
symptoms to a small degree and may be used in plantar fasciitis.
46
Orthosis should be prescribed for those patients who stand for long
periods.170
Grade A, Level 1+
Table 2
Table of dosages of steroid medication that have
been used and are provided for information
Shoulder
Condition*
Hydrocortisone
25-50 mg143
Triamcinolone
10-40
mg143,145
Dexamethasone
2-3 mg143
Methylprednisolone 40-80 mg143
Lignocaine 1%
Up to 10
mls172
Lateral
De Quervain’s Carpal
Epicondylitis* Tenosynovitis† Tunnel
syndrome†
25 mg146,147
25-50 mg150
25-50
mg176,177
175
10-20
30 mg
30 mg176,178
mg146,147,174
1.5-3 mg146,147 20 mg146,147,173 15-40 mg149
15-40
mg151
0.5-2
0.5-2
1-2
ml146,147,173
ml149,150,175
mls151,176-178
Trigger Osteoarthritis Plantar
Finger* of the Knee Fasciitis171
-
50 mg156,181
-
10-20
mg154
-
20-40 mg
5-10 mg182
0.5
mls155
156,179,180
40-80 mg158,180 40 mg183
-
1-2 mls182,183
* GPP There should be at least 6 weeks of interval between
corticosteoid injections, and up to a maximum of 3 doses are
recommended in shoulder conditions, lateral epicondylitis and trigger
finger.
GPP
†
GPP A single dose of corticosteoids is recommended in De
Quervain’s Tenosynovitis and carpal tunnel syndrome.
GPP
7.3
Trigger point injections
Although steroid injections are done frequently for trigger points,
effectiveness is not supported by studies.
47
8
8.1
Corticosteroids in Rheumatological Conditions
Osteoarthritis
8.1.1
Intra-articular corticosteroids
Knee
Intra-articular corticosteroids in osteoarthritis of knees was discussed
in Chapter 7.
Carpometacarpal joint of the thumb
One small double-blind randomized controlled trial showed no
clinical benefit was gained from intra-articular injection of
triamcinolone hexacetonide to the carpometacarpal joint of the thumb
in moderate to severe osteoarthritis compared with placebo
injection.184
Hip
There is no robust evidence to support the efficacy of steroid injection
for hip osteoarthritis.185,186
8.1.2
Systemic corticosteroids
GPP There is no evidence for the use of systemic corticosteroids in
osteoarthritis. It should not be prescribed for the treatment of
osteoarthritis.
GPP
8.2
Gout
In the management of acute attacks of gout, corticosteroids may be
used in patients with renal insufficiency or who for other reasons
cannot tolerate non-steroidal anti-inflammatory drugs (NSAIDs) or
colchicine.
48
8.2.1
Intra-articular corticosteroid
D In patients with acute gout affecting one or two joints, intraarticular injection of a long-acting corticosteroid preparation, such as
methylprednisolone, triamcinolone acetonide or triamcinolone
hexatonide, will control symptoms within 1 to 2 days.160,187-189 It
should be given only when the diagnosis is confirmed and infection
has been excluded. Patients with polyarticular gout who have a
suboptimal or delayed response to oral non-steroidal antiinflammatory drugs often benefit from adjunctive corticosteroid
injections into those joints with persistent synovitis.189
Grade D, Level 3
8.2.2
Systemic corticosteroid
D Both intramuscular injection of corticosteroid (triamcinolone
acetonide 40 mg - 60 mg once) and oral corticosteroid are effective
and may be used in acute attacks particularly in the patient with
polyarticular gout.189-191 Prednisolone can be started at a dose of 20 to
40 mg/day and tapered over 7 to 10 days. If tapered too rapidly, a
rebound flare-up of gout may occur.
Grade D, Level 3
8.3
Pseudogout
D Well conducted studies on the use of intra-articular or systemic
corticosteroids in acute attacks of pseudogout are lacking.160,192
However, clinical experience suggests that a similar approach to that
for the management of acute gout may be effective in acute attacks of
pseudogout.193
Grade D, Level 4
8.4
Rheumatoid arthritis
8.4.1 Intra-articular corticosteroids
A Rheumatoid synovitis may be suppressed for three months or
longer using relatively insoluble microcrystalline corticosteroid
preparations.194-197 Intra-articular corticosteroid should be considered
ancillary to rest, physical therapy, non-steroidal anti-inflammatory
agents, and disease modifying anti-rheumatic drugs. No convincing
evidence exists, that joint erosive changes are retarded.
Grade A, Level 1+
49
8.4.2
Systemic corticosteroids
Prednisolone in low doses (not exceeding 15 mg daily) may be used
intermittently in patients with rheumatoid arthritis, particularly if the
disease cannot be controlled by other means.198
Based on the limited data available, moderate-term low dose
prednisolone (not exceeding 15 mg per day) treatment of rheumatoid
arthritis appears to be superior to placebo and comparable to treatment
with aspirin or chloroquine in improving several common rheumatoid
arthritis disease activity measures.199
Studies conducted more recently have corroborated findings from
older trials that corticosteroids decrease the progression of rheumatoid
arthritis as detected radiographically.200-202
A Systemic corticosteroids may thus be used in the management of
rheumatoid arthritis in two ways198,199:
(1) Short-term, low dose bridge therapy, aimed at controlling
symptoms during periods of active disease while awaiting the
effects of newly started single or combination disease modifying
anti-rheumatic drugs (DMARDs).
(2) Moderate to longer-term low dose prednisolone (usually 10 mg or
less) given in addition to single or combination DMARDs if this
treatment has failed to control disease activity sufficiently.
Grade A, Level 1+
The benefits of low dose systemic corticosteroids, however, should
always be weighed against their adverse effects. For long-term disease
control, the corticosteroid dosage should be kept to a minimum. For
the majority of patients with rheumatoid arthritis, this means less than
10 mg of prednisolone per day.203
50
8.5
Psoriatric arthritis
8.5.1
Intra-articular corticosteroids
D Periodic intra-articular injection of corticosteroid can be of
particular value in the management of patients with oligoarticular
disease or those with controlled polyarticular disease but one or two
persistently active inflamed joints despite disease modifying antirheumatic drugs.204
Grade D, Level 4
8.5.2
Systemic corticosteroids
D In general, systemic corticosteroids should be used judiciously in
psoriatric arthritis because of the risk of provoking a pustular flare in
the skin on withdrawal.205
Grade D, Level 3
8.6
Ankylosing spondylitis
8.6.1
Intra-articular corticosteroids
Sacro-iliac joint
A Intra- or peri-articular corticosteroid injections have been shown in
small randomized controlled trials to be effective and may be used for
the pain of sacroiliitis.206-208
Grade A, Level 1+
Peripheral joints and entheses
D There are no clinical studies evaluating the efficacy of intraarticular corticosteroid on peripheral arthritis nor on the use of local
corticosteroid injections for the enthesitis of ankylosing spondylitis.
Clinical experience suggests that corticosteroid injections can be
helpful in selected cases.209
Grade D, Level 4
51
8.6.2
Systemic corticosteroids
D The use of systemic corticosteroids for axial disease is not
supported by evidence.209 These patients already have significant loss
of bone density, which can be exacerbated by steroid therapy.
Grade D, Level 4
8.7
Connective tissue diseases
Corticosteroid therapy is widely used in the management of
connective tissue diseases such as systemic lupus erythematosus,
polymyositis/dermatomyositis and systemic vasculitis. Corticosteroids
can been used as intravenous pulses to obtain rapid control of disease
activity in ill patients. More often varying dosages of oral
prednisolone are used depending on the disease condition, its
manifestations and disease activity. Based on pathophysiologic and
pharmacokinetic data, standardization of the terms such as "low" or
"high" dose has been recently proposed to minimize problems in
interpretation of these generally used terms.210 As there are specific
indications for corticosteroids in these multi-systemic disorders, they
are best managed in, or co-managed with, a specialist practice.
52
9
9.1
Respiratory Diseases
Asthma
9.1.1
Long-term asthma management
Corticosteroids are the most effective anti-inflammatory treatment for
asthma. They reduce airway inflammation and hyper-responsiveness.
This results in improved lung function and quality of life as well as
reduced symptoms and exacerbations.211-213 The therapeutic index and
safety profile of even high dose inhaled steroids is clearly better than
oral steroids.214 Common side effects with inhaled preparations are
oral candidiasis and dysphonia. The range of inhaled steroids
available differs in delivery devices, potency and bioavailability.
A Inhaled steroids are the preferred treatment for patients with
persistent asthma symptoms at all levels of severity.215,216
Grade A, Level 1++
The dose response curve of inhaled steroids is relatively flat in mild to
moderate asthma. This has been proven for outcome measures such as
symptoms, lung function and airway responsiveness.215,217,218
Therefore, escalating to high dose inhaled corticosteroids provides
limited further benefit in terms of asthma control but increases risk of
side effects.
A Add-on therapy with another class of controller medication (e.g.
long-acting E2-agonist) is preferred to increasing the dose of inhaled
corticosteroids.219
Grade A, Level 1++
Long-term treatment with high doses of inhaled corticosteroids may
be associated with skin thinning, easy bruising and adrenal
suppression.220,221 There is no evidence of conventional doses of
inhaled corticosteroids affecting bone mineral density or vertebral
fracture risk.222
B The risks of poorly controlled asthma should be weighed against
the limited risk of long-term inhaled corticosteroids.220-222
Grade B, Level 2++
53
D Inhaled corticosteroids should be started at a dose appropriate to
the control of asthma.223
Grade D, Level 4
A Inhaled steroids should be given twice daily.224
Grade A, Level 1+
B The dose of inhaled steroids should be titrated slowly to the lowest
dose that can achieve effective asthma control.225,226 After adequate
control has been achieved, the inhaled corticosteroid dose should be
gradually reduced by 25% every 3 months and titrated according to
asthma control. Once the dose of corticosteroids is less than 500 Pg of
beclomethasone diproponate or its equivalent, then withdrawal of addon therapy can be considered.223
Grade B, Level 1+
9.1.2
Asthma management in pregnancy
The clinical course of asthma can change in pregnancy and needs to
be carefully monitored. Poorly-controlled asthma has an adverse
effect on the fetus and can result in maternal complications like preeclampsia and hyperemesis. The overall perinatal prognosis in wellmanaged asthma in pregnancy is comparable to that of children born
to women without asthma.227 However, there may be an increased risk
of oral clefts in exposure to steroids in the first trimester.228 Using
steroids in pregnancy is justified even if their safety is not
unequivocally proven when the benefits outweigh the risks. Therefore,
well-controlled asthmatics should remain on their current treatment
regimen of inhaled corticosteroids during pregnancy if control is
acceptable.229
C Inhaled steroid regimen should not be changed in pregnancy.
Grade C, Level 2++
9.1.3
Management of acute exacerbations of
asthma
Systemic corticosteroids speed up resolution of acute exacerbations of
asthma if there is no lasting response to initial short acting E2-agonist
therapy. Early use of oral corticosteroids is associated with a decrease
in hospital admission, relapse rate and E2-agonist use.230,231 Doses
54
higher than 0.5 to 1 mg/kg/day of prednisolone or 400 mg/day of
hydrocortisone offer no therapeutic advantage.232 Oral steroids are as
effective as intravenous steroids and are both less invasive and less
expensive.233
A Systemic steroids should be given at least 5 days in acute
exacerbations of asthma that do not have rapid and sustained response
to short-acting E2-agonist therapy. Oral dosing is preferred over
intravenous therapy. Intravenous administration should only be
considered in the critically ill or if the patient is unable to tolerate oral
medication. There is no need for tapering dose at the end of a short
course of oral prednisolone (up to 10 days).234
Grade A, Level 1++
The optimal increase in maintenance inhaled corticosteroids in an
acute exacerbation is not well defined. Increase of inhaled steroids
early in an acute attack (e.g. as part of an asthma action plan) reduces
hospital admission.138 High dose inhaled corticosteroids and E2agonists provide greater bronchodilation than E2-agonist alone.235
However, there is insufficient evidence that inhaled corticosteroids
provide additional benefit when used in combination with systemic
steroids in acute exacerbations of asthma.236 Inhaled corticosteroids
should be continued or started as part of the chronic asthma
management plan.237
A The role of conventional doses of inhaled corticosteroids as
adjunctive therapy to systemic steroids in an acute exacerbation of
asthma is limited.
Grade A, Level 1++
9.2
Chronic obstructive pulmonary disease (COPD)
9.2.1 Management of stable COPD
The therapeutic effects of both oral and inhaled corticosteroids in
COPD are less clear than in asthma and prescription should be limited
to specific indications.238 Patients who have a significant
bronchodilator response on spirometry (200 ml and 12% increase in
FEV1) may be more likely to respond to long-term inhaled
corticosteroids.239 Reversibility tests with a trial of oral corticosteroids
do not predict response to inhaled corticosteroids and should not be
55
used to identify who will benefit from inhaled corticosteroids.240
Inhaled corticosteroids do not have a clinically significant effect on
the long-term decline of FEV1 in COPD.241 However, long-term
inhaled corticosteroid therapy reduces the rate of acute exacerbations
and improves quality of life.242 Therefore, inhaled corticosteroids are
appropriate for symptomatic patients with FEV1 less than 50% of
predicted and repeated exacerbations requiring antibiotics or oral
corticosteroids (e.g. three episodes in the preceding 3 years).238
Furthermore, in patients with moderate to severe COPD,
discontinuation of inhaled corticosteroids may lead to an increase in
exacerbations and deterioration in quality of life.243 Combination
therapy of long-acting E2-agonists and inhaled corticosteroids have
been shown to reduce reliever use and severe exacerbations compared
to placebo in severe COPD.244
A Combined inhaled corticosteroids with long-acting bronchodilators
should be considered in severe COPD patients with recurrent
exacerbations or symptoms.
Grade A, Level 1++
There is a lack of substantial benefit in the long-term use of oral
corticosteroids in COPD. This should be weighed against considerable
side effects including steroid myopathy, which can worsen the
patient’s functional status and worsen respiratory failure.245
A Long-term treatment with oral corticosteroids is not recommended
in COPD.
Grade A, Level 1++
9.2.2 Management of exacerbations of COPD
Systemic corticosteroids increase the rate of lung function
improvement over the first 72 hours of an acute COPD exacerbation.
It also shortens recovery time and reduces treatment failure.246
Therapy beyond 14 days has not been shown to result in greater
efficacy and increases the risk of side effects.247
56
A Oral corticosteroids should be considered if patients experience a
significant increase in breathlessness that interferes with daily
activities especially if the baseline FEV1 is less than 50% of predicted.
A dose of prednisolone of 30-40 mg/day for 7 to 14 days is
recommended for acute exacerbations of COPD.
Grade A, Level 1++
9.3
Respiratory infections
9.3.1
Acute bronchitis
Acute bronchitis is defined as a syndrome of cough lasting less than 23 weeks that may be associated with sputum production as well as
other respiratory or constitutional symptoms. There is no data for the
use of inhaled or oral corticosteroids in the treatment of bronchial
hyper-responsiveness caused by acute bronchitis. Symptomatic
treatment with short-acting inhaled bronchodilators and anti-tussives
may be more appropriate for patients with persistent and troublesome
cough.248,249
D Corticosteroids should not be used in the management of acute
bronchitis.249
Grade D, Level 4
9.3.2
Lower respiratory tract infections
There is no data for the outpatient management of lower respiratory
tract infections like bronchiolitis or pneumonia with adjunctive
corticosteroid therapy. Appropriate anti-microbial therapy should be
administered expeditiously.250
D Corticosteroids should not be used in the treatment of lower
respiratory tract infections.
Grade D, Level 4
9.3.3
Pulmonary tuberculosis
Adjunctive therapy with corticosteroids in pulmonary tuberculosis
may hasten radiological resolution of lung infiltrates.251 However,
there is no appreciable effect on the rate of sputum conversion.251
There is also no benefit of corticosteroid use in tuberculous pleurisy in
both clinical and radiological outcomes.252 There is a role for
57
corticosteroids in the management of paradoxical reactions to
tuberculosis anti-microbial therapy as well as in the treatment of
extra-pulmonary tuberculosis with pericarditis or meningitis.253 These
conditions should be managed under specialist care.
A The routine use of corticosteroids should be avoided in the
management of pulmonary tuberculosis.
Grade A, Level 1++
9.4.
Other respiratory diseases
GPP The following respiratory disorders may require corticosteroid
therapy and patients with these conditions should be referred to a
specialist respiratory service:
x Allergic bronchopulmonary aspergillosis
x Churg Strauss syndrome
x Eosinophilic pneumonia
x Sarcoidosis
x Pulmonary vasculitis
x Alveolar haemorrhage syndromes
x Pneumocystis carinii pneumonia with respiratory failure
x Interstitial lung disease
x Post-radiation pneumonitis
GPP
58
10
10.1
10.2
Corticosteroids in Dermatologic Conditions
General principles
x
Accurate diagnosis, understanding and recognition of the steroidresponsive dermatoses is an important skill all practitioners need
to acquire before using topical corticosteroids.
x
Indications, risk, benefits, alternatives and associated adjunct
therapies of topical corticosteroids are essential before
prescribing.
x
Topical corticosteroids are effective and safe if used with
discretion.
x
Understanding of the relative and absolute contraindications for
topical corticosteroids like skin infections are critical for safe use
of topical corticosteroids.
x
The principle of reviewing the patient before repeating the
prescription is good clinical practice for safe and effective use of
topical corticosteroids.
Indications
Topical corticosteroids are potent and effective local antiinflammatory and anti-proliferative medications available for the
treatment of inflammatory skin and mucosal disorders.
Topical corticosteroids are useful in the treatment of steroidresponsive dermatoses, namely eczema/dermatitis, psoriasis, lichen
planus, pityriasis rosea, drug eruptions, and lupus erythematoses.
A There is reasonable evidence from randomised controlled trials to
support the use of topical corticosteroids as the mainstay of treatment
of atopic eczema.254
Grade A, Level 1+
GPP Topical corticosteroids in treatment of psoriasis are best
reserved for localised sites such as hands, feet, flexures, genitalia, face
and scalp.
GPP
59
Intralesional corticosteroids are used in the therapy of prurigo,
lichenifed eczema, alopecia areata, granuloma annulare and keloids.
Topical corticosteroids are contraindicated in the presence of skin
infection (viral, bacterial, fungal, parasitic) ulceration and known
hypersensitivity to the steroid or its vehicle.
10.3
Uses
Topical corticosteroids are available in many strengths and their
potencies have been ranked in the Stughton-Cornell Classification
(USA system) which is originally based on an assay of each
corticosteroid’s ability to cause vasoconstriction.
The steroid
potencies range from Class 1 super potent steroids like clobetasal
propionate to Class 7 mildest 1% hydrocortisone.
In the British National Formulary, the potencies range from Class 1
super potent to Class 4 (see Table 4 page 65).
Topical steroids are available in creams, ointments, lotions, solutions,
foams and gel.
The potency of topical corticosteroids is directly related to the
beneficial effects and side effects.
The finger-tip unit (the amount of ointment/cream expressed from a
tube from distal skin crease to tip of index finger) is a readily
understandable measure for patients and doctors.255
Fluticasone propionate, mometasone furoate, prednicarbate and
hydrocortisone aceponate are associated with few side effects despite
their potencies. However, improved benefit/risk ratio remains to be
proven.256
Topical corticosteroids are often used in twice daily application.
There is no data supporting that more frequent application leads to a
better or faster resolution of lesions.142
A Topical corticosteroids should not be used more than twice a
day.254,257,258
Grade A, Level 1+
60
There is evidence in some situations that once a day application of
topical corticosteroids gives as effective result as twice daily
application.254
There is some evidence to suggest the benefit of using intermittent
(twice weekly) topical corticosteroids to prevent relapses of atopic
eczema. There is no evidence of skin thinning after 4 months of
intermittent use of a potent topical corticosteroids.142
There is no randomised controlled trials evidence to support the
notion that diluting topical corticosteroids reduces adverse effects
while maintaining efficacy in patients with atopic eczema.254
GPP It is not recommended to dilute and mix other types of creams
with topical corticosteroids in your practice.
GPP
There is no randomised controlled trial evidence of improved
efficiency with the use of topical corticosteroids plus antibiotics
(fusidic acid or gentamicin) as compared to plain topical
corticosteroids in patients with infected atopic eczema.254
GPP In the presence of infected eczema, use of oral antibiotics is
considered as good practice.
GPP
10.4
Safety and side effects
Hypothalamic-pituitary-adrenal (HPA) axis suppression has been
demonstrated in some patients with super potent topical
corticosteroids.
There are rare cases of iatrogenic Cushing’s syndrome in patients
treated (including self treatment) with super potent topical
corticosteroids. However, clinically significant effects seldom result
from minor degrees of adrenal suppression that occur with the use of
super potent topical corticosteroids.256
The increased skin surface to body mass ratio in infants and small
children makes them more susceptible to hypothalamic-pituitaryadrenal axis suppression.256
61
Local cutaneous side effects of epidermal atrophy, skin fragility,
dermal atrophy, striae, purpura, telengectasia and dryness do occur
when topical corticosteroids are used in excessive amount or
prolonged duration.256
D To prevent side effects, the amount of topical corticosteroids used
per week and duration of use must be monitored and controlled.
Adjunctive therapy must be emphasized.259
Grade D, Level 3
Adults applying a potent steroid in excess of 50 to 100 g weekly and
10-20 g in small children run the risk of hypothalamic-pituitaryadrenal axis suppression.
GPP It is recommended that not more than 25 g of clobetasal
propionate per week be used in adults. All patients on clobetasol
propionate should be monitored closely for potential side effects.
GPP
Applying potent topical corticosteroids under occlusion increases
absorption, efficacy and risk to hypothalamic-pituitary-adrenal axis
suppression.
GPP For areas of the face and flexures it is best to confine use of
topical steroids to mild topical corticosteroids and less commonly to
moderate to potent topical corticosteroids for short periods of time.
GPP
GPP When patient requests for repeat prescription of moderately
potent and super potent topical corticosteroids, clinical review must be
done before repeating the dose. Patient should be educated regarding
the need to come for clinical review before extending the duration by
explaining the risk and benefits of continuing steroids on long term
basis.
GPP
D Use of flourinated topical corticosteroids should be avoided on the
face as there is a high risk for complications like perioral dermatitis,
rosacea-like dermatitis, acneform lesions and facial hypotrichosis.
Where indicated it should be used for short period, under frequent
62
and close review of patient's condition. Longer usage should be in
consultation with a specialist dermatologist.260,261
Grade D, Level 4
Generic topical corticosteroids are not necessarily equal in efficacy to
branded products due mainly to differences in vehicle.262
10.5
Topical corticosteroids in pregnancy and lactation
Appropriate human studies using topical corticosteroids in pregnancy
have never been performed.
Most topical corticosteroids are rated by the US Food and Drug
Administration as Category C drugs which indicates that caution must
be exercised while using them and these should be used only if the
benefits outweigh any risk to the foetus.
Numerous studies of pregnant patients taking systemic corticosteroids
throughout pregnancy show no increase in the incidence of foetal
abnormalities.
GPP It is presently unknown whether topical corticosteroids are
excreted in breast milk. The general advice is to use topical
corticosteroids with caution in breastfeeding mothers and they are not
to be used on the breast just prior to breastfeeding.
GPP
10.6
Topical corticosteroids in geriatric use
Elderly patients have thinner skin (both epidermal and dermal atrophy)
and are at greater risk to the adverse effects of topical corticosteroids.
GPP In elderly patients, topical corticosteroids should be used for
short periods, intermittently and under close supervision.
GPP
GPP Guidelines as for use in infants and young children should
apply to the elderly.
GPP
63
10.7
Systemic corticosteroid use in general practice
Systemic corticosteroids are potent and effective anti-inflammatory
agents in acute, severe inflammatory dermatoses.
GPP In general practice (or primary care), it is best to confine use of
systemic corticosteroids to dermatoses that are ‘short-lived’ or rapidly
responsive.
GPP
‘Short-lived dermatoses’ include acute allergic contact dermatitis
(allergen withdrawn - like hair dye allergy), certain cutaneous adverse
drug exanthem and acute urticaria.
GPP Long-term systemic corticosteroids used in autoimmune
bullous dermatoses (like pemphigus vulgaris) or other autoimmune
cutaneous disorder (systemic lupus erythematosus, dermatomyositis)
are best left to the purview of the specialist.
GPP
There is no evidence to support the benefit of long-term oral
corticosteroids in conditions like atopic eczema, hand eczema, discoid
eczema or chronic urticaria.
Systemic corticosteroids are of limited or no benefit but risk
destabilisation of the condition in the management of psoriasis.
Withdrawal of systemic steroids is a well recognised cause of
erythrodermic and generalized pustular psoriasis.
64
Table 4
Topical corticosteroid preparation
potencies
Class 1
Very potent (up to 600 times as hydrocortisone)
x Clobetasol propionate
x Betamethasone dipropionate
Class 2
Potent (150 to 100 times as potent as hydrocortisone)
x Betamethasone valerate
x Betamethasone dipropionate
x Diflucortolone valerate
x Fluticasone valerate
x Hydrocortisone 17-butyrate
x Mometasone furoate
x Methylprednisolone aceponate
Class 3
Moderate (2 to 25 times as potent as hydrocortisone)
x Aclometasone dipropionate
x Clobetasone butyrate
x Fluocinolone acetonide
x Triamcinolone acetonide
Class 4
x
x
Mild
Hydrocortisone 0.5 - 2.5%
(Source: British National Formulary)
65
11
11.1
Use of Corticosteroids in Ophthalmology
Steroid eye drops in the primary care setting
11.1.1 Indications
GPP The role of steroid eye drops in the primary care setting is
mainly in the management of acute red eyes. Vision-threatening
causes of red eyes – acute glaucoma, iritis, keratitis and scleritis –
should first be excluded with careful history, visual acuity testing and
examination for corneal clarity and pupillary response.
GPP
A Patients with vernal conjunctivitis (active papillae and/or follicles)
could benefit from topical corticosteroid during the acute phase to
reduce the acute inflammation and itch. Topical steroid should be
stopped once the symptoms have been relieved. The mainstay of
treatment, however, is sodium cromoglycate (mast cell stabilizer) eye
drops.263
Grade A, Level 1+
D The use of topical steroid for the management of viral
conjunctivitis in the primary care setting is more controversial. While
it certainly alleviates ocular inflammation264, it should be used when
the presentation is typical and diagnosis certain. Some conditions that
mimic viral conjunctivitis (such as herpetic epithelial keratitis265 and
microbial keratitis) may be aggravated by the use of steroid eye drops.
Grade D, Level 3
GPP Symptoms of acute allergic conjunctivitis (characterized by
conjunctival chemosis) usually subside within 24 hours without
treatment. Similarly, episcleritis often subsides without treatment. The
use of topical steroid may not be necessary in these cases. Alternatives
such as antazoline eye drops may be considered instead.
GPP
66
11.1.2
Contraindications
GPP Infective keratitis (corneal ulcer) and herpetic keratitis can
mimic viral conjunctivitis. Topical steroids can worsen these
conditions while masking the symptoms and are contraindicated in
these conditions.
GPP
GPP Topical steroids are contraindicated in the presence of a history
of contact lens use or ocular trauma as microbial keratitis could be
present and aggravated by steroid use.
GPP
11.1.3 Side effects of steroid eye drops
A Prolonged application of steroidal eye drops can cause elevation of
the intraocular pressure.266-271 This effect has also been demonstrated
in children.272,273 The frequency, severity and time-course of the
response may be higher in children.272 Thus special care must be
taken when prescribing steroid eye drops for children.
Grade A, Level 1+
A Being asymptomatic, steroid-induced ocular hypertension may go
undetected for months, resulting in steroid induced glaucoma.
Intraocular pressure should be monitored regularly if steroid eye drops
are being used for long duration.266-271
Grade A, Level 1+
D Without intraocular pressure monitoring, steroidal eye drops should
not be used beyond 1 week.266,274
Grade D, Level 3 & 4
Long-term use of steroidal eye drops can cause steroid-induced
cataracts.275
11.1.4 Types of steroid eye drops
Gutte Betamethasone and Gutte Dexamethasone are the mainstay of
steroidal eye drops. Gutte Prednisolone acetate 1% penetrates the eye
much better making it the most efficacious steroidal eye drop
available. Gutte Fluorometholone does not penetrate the eye well.
67
Therefore it is least likely to cause steroid-induced glaucoma.276 It is
a useful and safe ocular surface anti-inflammatory agent, but does not
treat intraocular inflammation. Some new steroidal preparations such
as Lotemax® and Vexol® may have less effect on the intraocular
pressure.
11.2
Ocular side effects of systemic steroid therapy
Long-term systemic steroid is known to cause bilateral posterior
subcapsular cataracts.270,277
GPP Patients should be counseled prior to the start of long-term
systemic steroid regarding cataract formation. These are easily
diagnosed as fairly dense central opacities of the pupillary red reflex.
Decision to continue or cease systemic steroid therapy is largely
dependant on the primary disease status for which the steroid was
started – cataract can be dealt with surgically with very high success
rates. Routine eye screening for presence of cataract is important
especially for patients in the amblyogenic age group (10 years old or
younger), or when the patient develops visual symptoms.
GPP
C Prolonged high-dose steroid is known to be associated with central
serous chorio-retinopathy,278-280 a condition characterised by single or
multiple subretinal fluid blebs. The patient presents with micropsia
(diminished image size) and/or metamorphopsia (distortion of image).
If confirmed by an ophthalmologist, systemic steroid should be
reduced, replaced and discontinued wherever possible.
Grade C, Level 2+
Glaucoma secondary to systemic steroid usage is uncommon.281-283
11.3
Ocular side effects of peri-ocular steroid therapy
Topical steroid application around the eye,284-287 intralesional steroid
injection288 and inhalational steroids289,290 are known to cause steroidinduced glaucoma.
D Patients who require periocular steroid treatment for longer than 4
weeks would require monitoring of intraocular pressure.
Grade D, Level 3
68
11.4
Systemic steroids for ophthalmic conditions
Systemic steroids may be required for the following ophthalmic
conditions:
1. Uveitis
2. Scleritis
3. Optic neuritis
4. Thyroid eye disease
These conditions are usually diagnosed and managed by the
ophthalmologist. Please refer to the earlier chapters for the guidelines
on systemic steroid usage for other conditions.
69
12
12.1
Corticosteroids in Other Conditions
Anaphylaxis
D Adrenaline is the treatment of choice in anaphylaxis.
Corticosteroids are not helpful acutely but potentially might prevent
recurrent or protracted anaphylaxis.291,292
Grade D, Level 4
12.2
Bell's palsy (idiopathic facial paralysis)
A Corticosteroids are not recommended for the treatment of Bell's
palsy.293
Grade A, Level 1+
Evidence from randomized controlled trials does not show significant
benefit from treating Bell's palsy with corticosteroids.293 More
randomized controlled trials with a greater number of patients are
needed to determine reliably whether there is real benefit (or harm)
from the use of corticosteroid therapy in patients with Bell's palsy.
70
Clinical Quality Improvement
The following clinical quality improvement parameters,
recommendations in these guidelines, are proposed:
based
on
Asthma
1.
Proportion of patients with persistent asthma symptoms using inhaled
corticosteroids. (Page 53, 9.1.1)
2.
Proportion of patients with an acute exacerbation given systemic
corticosteroids. (Page 55, 9.1.3)
COPD
1.
Proportion of COPD patients with an FEV1 < 50% predicted with
repeated exacerbations who are prescribed inhaled corticosteroids. (Page
56, 9.2.1)
Allergic Rhinitis
1. Proportion of children and adults with allergic rhinitis prescribed with
intranasal steroids (Page 32)
Atopic Dermatitis
1.
Avoidance of flourinated steroids on face for more than 2 weeks. (Page
62)
71
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Self-assessment (MCQs)
After reading the Clinical Practice Guidelines, you can claim one CME point
under Category III (Self-Study) of the SMC Online CME System. Before you
login to claim the CME point, we encourage you to evaluate whether you have
mastered the key points in the Guidelines by completing this set of MCQs. This
is an extension of the learning process and is not intended to “judge” your
knowledge and is not compulsory. The answers can be found at the end of the
questionnaire.
Instruction: Choose the best (one) answer for each question.
1.
Which of the following steroids has the largest potency to suppress the
hypothalamic-pituitary-adrenal axis?
A)
B)
C)
D)
2.
Iatrogenic Cushing’s syndrome can be diagnosed by the following after
cessation of steroids for 1 week:
A)
B)
C)
D)
3.
Prednisolone
Dexamethasone
Hydrocortisone
Triamcinolone
high plasma cortisol and a high plasma ACTH
low plasma cortisol and high plasma ACTH
low plasma cortisol and a low plasma ACTH
none of the above
Regarding effect of glucocorticoids on bone architecture, all are true
except
A) Bone integrity could be compromised at doses above 7.5 mg
B) Osteonecrosis occurs at doses equivalent to 5 mg of prednisolone for
period of 3 months
C) Fracture risk decreases rapidly after cessation of corticosteroids
D) Bisphonates and vitamin D are given in steroid-induced osteoporosis
100
4.
Intranasal steroids use in children have been shown not to affect the
hypothalamic-pituitary-adrenal axis up to
A)
B)
C)
D)
5.
3 months
6 months
9 months
12 years
A 2-year-old develops stridor over 2 days and this is associated with a
barking cough. The best treatment option is
A)
B)
C)
D)
E)
oral prednisolone at a dose of 2 mg/kg for 3 days.
single dose of oral dexamethasone.
inhaled budesonide 500 μg for 5 days.
prescribe beclomethasone 200 μg bd via MDI for 1 month.
nebulised salbutamol tds for 5 days.
6. A 45-year-old lady presents with numbness of both hands, worse at night
and early morning, improving with activity in the day. Clinically, her
symptoms and signs are suggestive of carpal tunnel syndrome, with no
motor involvement (in particular, thenar wasting). Treatment modalities
can include the following:
A) Trial of night splinting
B) Activity modification
C) Corticosteroid injection of 25 mg of hydrocortisone with 1 ml of 1%
lignocaine into the carpal tunnel
D) All of the above
7.
A 30-year-old female presents with signs and symptoms of De Quervain’s
Tenosynovitis. She is currently breastfeeding. She has been given a trial of
splinting with little improvement. You, as the treating doctor, decide to
give a local injection of corticosteroid/lignocaine admixture. The
following are common complications except:
A)
B)
C)
D)
Superficial radial nerve neuropraxia
Local fat atrophy
Local flare
Tendon rupture
101
8.
In the primary care setting without intraocular pressure monitoring, steroid
eye drops is considered unsafe beyond
A)
B)
C)
D)
1 day
1 week
1 month
1 year
102
Answer:
1.
B
(pg 20)
2.
C
(pg 23)
3.
B
(pg 24)
4.
D
(pg 31)
5.
B
(pg 42)
6.
D
(pg 45)
7.
D
(pg 45)
8.
B
(pg 67)
103
Workgroup Members
The members of the workgroup, who were appointed in their personal
professional capacity, are:
Chairman
Dr Tan See Leng
Senior Vice President
International Operations
Parkway Holdings Limited, Singapore
Group CEO
Pantai Hospitals, Malaysia
Members
A/Prof Chng Hiok Hee
Head of Rheumatology
Allergy & Immunology
Tan Tock Seng Hospital
A/Prof Goh Lee Gan
Department of COFM
Faculty of Medicine
National University of Singapore
Dr Chong Siong Eng, Roland
Roland Chong Gastroenterology
& Medical Clinic Pte Ltd
Gleneagles Medical Centre
Dr Lim Fong Seng
Director of Medical Affairs
National Healthcare Group
Polyclinics
Dr Anantham Devanand
Associate consultant
Department of Respiratory and
Critical Care Medicine
Singapore General Hospital
Dr Lim Tock Han
Director
The Eye Institute
National Healthcare Group
A/Prof Philip Eng
Head, Department of Respiratory
Medicine & Critical Care
Singapore General Hospital
104
Dr Lim Yi-Jia
Registrar
Department of Orthopaedics
Changi General Hospital
Dr Low Cheng Ooi
Chief of Orthopaedic Surgery
& Senior Consultant
Changi General Hospital
Dr Shek Pei-Chi, Lynette
Consultant Paediatrician
Children’s Medical Institute
National University Hospital
Dr Tay Ee Guan
Director
Medical Manpower Dept
Singapore Health Services
A/Prof Tan Kim Siang, Luke
Chief, Department of Otolaryngology
National University Hospital
Dr T Thirumoorthy
Director & Senior Consultant
Department of Dermatology
Singapore General Hospital
Dr Tan Siang Hui, Colin
Registrar
The Eye Institute
Tan Tock Seng Hospital
Dr Yeoh Swee Inn
Yeoh Swee Inn Endocrine
& Medical Clinic Pte Ltd
Subsidiary editors
Dr Pwee Keng Ho
Assistant Director (Health Technology Assessment)
Health Services Research & Evaluation Division
Ministry of Health
Dr Rajni Gupta
Clinical Guidelines & Technology Assessment Executive
Health Services Research & Evaluation Division
Ministry of Health
105
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CLINICAL PRACTICE GUIDELINES
Use of
Corticosteroids in
General Practice
Endocrine and Metabolic
Society of Singapore
College of Physicians,
Singapore
SINGAPORE THORACIC SOCIETY
College of Surgeons,
Singapore
Gastroenterological Society
of Singapore
Dec 2006
MiNISTRY OF HEALTH
SINGAPORE
ISBN 978-981-05-7317-1
College of Family
Physicians, Singapore
Singapore Orthopaedic
Society
MOH Clinical Practice Guidelines 5/2006
MiNISTRY OF HEALTH
SINGAPORE
College of Physicians,
Singapore
College of Family
Physicians, Singapore
Endocrine and Metabolic
Society of Singapore
Singapore Orthopaedic
Society
SINGAPORE THORACIC SOCIETY
College of Surgeons,
Singapore
Gastroenterological Society
of Singapore