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REVIEW ARTICLE

Steroid pulse therapies in dermatology

Gaurang Gupta, Ambuj Jain, Naveen Kikkeri Narayanasetty

ABSTRACT
Steroids pulse therapies are used in inflammatory and autoimmune conditions as they are cumulatively less toxic. Pulse therapy is
the administration of supra therapeutic administration of steroids in intermittent manner. This form of therapy has given excellent
treatment response with very few side-effects. Various modifications of steroid pulse therapies have been tried in pemphigus, alopecia,
vitiligo etc., successfully.
Key Words: Dexamethasone-cyclophosphamide pulse therapy, pulse therapy, steroid

Introduction hydrocortisone. It’s biological half-life is 12-36 h, potency

Pulse therapy means the administration of large
(suprapharmacologic) doses of drugs in an intermittent
manner to enhance the therapeutic effects and
reduce the side-effects.[1] The first reported use of
pulse administration of corticosteroids is attributed to
Kountz and Cohn who used it to prevent renal graft
rejection in 1973.[2] It was later used for treatment of
lupus nephritis in 1976 and in steroid resistant nephritic
syndrome.[3] In India, Pasricha and Srivastava introduced
dexamethasone-cyclophosphamide pulse (DCP) therapy
for the pemphigus group of disorders in 1981.[4]
Definition
“Pulse therapy refers to discontinuous intravenous (IV)
infusion of high doses of the medication, arbitrarily
defined as treatment with more than 250 mg prednisone
or its equivalent per day, for one or more days.[5]”
1.25 times compared with prednisolone.[7]
Dosage
Methylprednisolone is administered at a dose of
20-30 mg/kg (500-1000 mg/m 2) per pulse up to a
maximum dose of 1 g.[8]
Dexamethasone Pulse Therapy
It is a fluoridated glucocorticoid, is a long acting agent
half-life of 36-72 h. It is 6.7 times more potent than
prednisolone, has negligible mineralocorticoid effect
with almost no sodium retaining tendency and a small
equipotent volume.[9]
Dosage
Dexamethasone is administered at a dose of 4-5 mg/kg
(100-200 mg) per pulse.[8]

Various modifications and modes are in use. Most Administration of Pulse Therapy
commonly used corticosteroids in pulse therapies are Initially, the duration of infusion was 10-20 min. However,
methylprednisolone and dexamethasone.[6] rapid infusions are known to be associated with a higher
risk of hemodynamic abnormalities, now-a-days the
Methylprednisolone Pulse Therapy corticosteroid preparation is dissolved in 150-200 ml of
Methylprednisolone is an intermediate acting, potent, 5% dextrose and infused IV, slowly over 2-3 h.[8,10]
anti-inflammatory agent with a low tendency to
induce sodium and water retention compared with Advantage of Corticosteroid as a Pulse Therapy
1. An immediate profound anti-inflammatory effect is
Access this article online
achieved and the toxicities seen with conventional
Quick Response Code
Website:
Department of Dermatology, SDM Medical College, Sattur, Dharwad,
www.mjmsr.net
Karnataka, India
Address of correspondence: Dr. Gaurang Gupta, Department of
DOI: Dermatology, OPD No. 10, SDM Medical College, Sattur,
10.4103/0975-9727.135756 Dharwad - 580 009, Karnataka, India.
E-mail: manavgups@gmail.com

Muller Journal of Medical Science and Research | Vol 5 | Issue 2 | Jul - Dec 2014 155
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Gupta, et al.: Pulse therapy
high dose oral therapy are low. Faster clinical
recovery from symptoms than with oral therapy, the
clinical improvement is seen to last about 3 weeks
after one pulse.
2. No prolonged suppressive effect on the hypothalamic-
pituitary axis.[8-10]
Mechanism of Action
Glucocorticoids exert a variety of immunosuppressive,
anti-inflammatory and anti-allergic effects. They mediate
their actions through genomic and non-genomic
methods.[7] Buttgereit et al. have postulated 3 “modules”
of glucocorticoid effect on cells resulting from different
concentrations:[11]
1. Low concentrations mediate effects via genomic
events.
2. Medium concentrations bind to cell surface receptors,
which activate cross membrane signal transmission
for genomic and non-genomic intracellular events.
3. At very large concentrations steroids dissolve in
the cell membrane resulting in greater membrane
stability and reduced non-genomic cell function.
Overall, effects of corticosteroid pulses appear to include
down regulation of activation of immune cells and pro-
inflammatory cytokine production. These effects are
qualitatively similar to those seen with anti-tumor necrosis
factor-alpha therapy.[12]
Uses of Corticosteroid Pulse Therapy
The dermatological disorders in which corticosteroid
pulse therapy has been advocated are:[13]
1. Pemphigus vulgaris.
2. Bullous dermatitis herpetiformis.
3. Severe psoriasis.
4. Alopecia totalis.
Infrequently used in the therapy of:
1. Severe Steven-Johnson syndrome (SJS).
2. Pyoderma gangrenosum.
3. Vitiligo with rapidly progressive disease.
4. Exfoliative dermatitis.
Others:[14]
1. Autoimmune blistering disorder.
2. Systemic sclerosis.
3. Systemic lupus erythematosus.
4. Dermatomyositis.
5. Toxic epidermal necrolysis (TEN).
6. Lichen planus.
7. Alopecia areata.
8. Sarcoidosis.
9. Systemic vasculitis.
156 Muller Journal of Medical Science and Research | Vol 5 | Issue 2 | Jul - Dec 2014
Laboratory Monitoring
Before Starting the Therapy
As a routine, it is mandatory to admit every patient
enrolled for pulse therapy. Hemogram, serum electrolytes,
renal and liver function tests, blood sugar (including
hemoglobin A1c), urine microscopic examination, chest
X-ray, electrocardiogram and pregnancy test are some
of the preliminary laboratory tests to be done at the first
visit. Blood sugar, serum electrolytes, urine microscopic
examination, body weight and blood pressure should be
monitored at baseline and at each visit of the patient.[14]
During and Following Therapy
Careful record of heart rate, respiratory rate and blood
pressure every 15-30 min should be maintained. If an
arrhythmia is suspected, the infusion is discontinued; an
electro cardiogram and blood levels of sodium, potassium,
calcium and magnesium are obtained and abnormalities
are rectified. Careful screening for occurrence or
exacerbation of infections should be done. Estimate blood
levels of sugar and electrolytes every other day.[13]
Contraindication in Pulse Therapy
1. Systemic infections, fungal sepsis, uncontrolled
hypertension and hypersensitivity to the steroid
preparation.[13]
2. Absolutely contraindicated in pregnant, lactating and
unmarried patients.[14]
Adverse Effects
The most significant serious effects in children are:
1. Increased blood pressure in already hypertensive
children during and after the infusion.
2. S e i z u r e s , p a r t i c u l a r l y i n s y s t e m i c l u p u s
erythematosus, which may be related to rapid flux
in electrolytes.
3. Anaphylactic shock after even one prior infusion,
usually associated with the succinate ester of
methylprednisolone.[15]
Common side-effects are:
1. Abnormal behavior, mood alteration, hyperactivity,
psychosis, disorientation, sleep disturbances are
common acute adverse effects, being seen in about
10% patients.[16]
2. Hyperglycemia, hypokalemia and infections. Higher
cumulative doses of methylprednisolone (>5 g)
confer a higher risk of infection.[17]
Side-effects peculiar to pulse therapy include:
1. Hiccups.[18]
2. Facial flushing.[19]
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Gupta, et al.: Pulse therapy
3. Diarrhea,
4. Weakness,
5. Generalized swelling and weight gain,
6. Joint and muscle pains.[20]
7. Arrhythmias and shock.
Mini Pulse Corticosteroid Therapy
Oral betamethasone has been given at a dose of 10 mg
once weekly; 10 mg of betamethasone is spilt in two
equal doses on two consecutive days a week. It is used
in following skin disease with variable success:[14]
1. Vitiligo.
2. Lichen planus.
3. Alopecia areata.
Prednisolone Pulse Therapy
1. Few studies show significant improvement with oral
prednisolone pulse therapy in alopecia areata. It is
given 200 mg once weekly.[21]
2. 100 mg IV prednisolone pulse therapy on three
consecutive days at 1 month intervals in alopecia
areata.[22]
Topical Corticosteroid Pulse Therapy
Topical corticosteroid pulse therapy comprises of
intermittent use of superpotent corticosteroids. Prolonged
continuous therapy with such agents in patients with
psoriasis results in certain side-effects e.g., telangiectasis,
cutaneous atrophy, hypothalamic-pituitary-adrenal (HPA)
axis suppression and tachyphylaxis, whereas intermittent
therapy may achieve beneficial effects for maintenance
of remissions with an advantage of diminishing the side-
effects and total cost of medication.
Clobetasol propionate (0.05%), weekly topical treatment
with three consecutive applications at 12 h intervals is
used mainly in psoriasis.[23]
DCP Therapy
DCP Therapy is Divided into four Phases
1st phase
Dexamethasone 100 mg in 5% dextrose as a slow IV
infusion over 2 h for three consecutive days along with
cyclophosphamide 500 mg infusion on one of the days
is instituted.[24] DCPs are repeated every 28 days until no
new lesions appear between pulses. Cyclophosphamide
50 mg/day is given orally on the remaining days. During
this phase, the patient may develop recurrences in
between the DCPs and conventional doses of oral
corticosteroids can be given to achieve quicker clinical
recovery.[25] After the skin and mucous membrane lesions
have subsided completely and the additional medications
Muller Journal of Medical Science and Research | Vol 5 | Issue 2 | Jul - Dec 2014
are withdrawn, the patient is considered to have entered
phase II.[26]
2nd phase
Phase of remission while on therapy. DCP schedule is
given for duration of 9 months.
3rd phase
Monthly pulses are terminated and oral cyclophosphamide
is continued for duration of 9 month.
4th phase
Treatment is stopped and patients are followed-up for
next 10 years.
Modifications of DCP Therapy
There are following modifications of DCP therapy
Dexamethasone Azathioprine Pulse Therapy
Cyclophosphamide is known to cause oligo/azoospermia
and amenorrhea. For unmarried patients who have not
completed their family, cyclophosphamide was replaced
by 50 mg of azathioprine daily during the first three
phases.[26]
Dexamethasone Methotrexate Pulse Therapy
Cyclophosphamide was replaced by 7.5 mg of
methotrexate weekly given orally, during the first three
phases of pulse therapy.[26]
DCP Therapy in Children
DCP therapy can be given to patients of all ages but the
doses have to be reduced to half for children below the
age of 12 years.[24]
DCP Therapy in Systemic Diseases
Diabetic patients need to be given 10 units of soluble
insulin for every 500 ml bottle of 5% dextrose dissolved
in the same drip. In addition, patient’s regular treatment
for diabetes mellitus is continued. Similarly patients
having concomitant diseases such as hypertension and
tuberculosis must receive the respective medication.[14]
If there is serious infection the pulse may be delayed
for a week or two until the infection is under control.[13]
Conclusion
Steroid as an intermittent pulse therapy is much safer
than daily administration. HPA axis suppression is one
of the serious side-effects of long-term steroid therapy.
It can be easily avoid by steroid pulse therapy. Now-a-
days this mode of therapy is very frequently in use in
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Gupta, et al.: Pulse therapy
some sever and chronic disease of dermatology such
as pemphigus, erythroderma, TEN/SJS etc.
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How to cite this article: Gupta G, Jain A, Narayanasetty NK. Steroid
pulse therapies in dermatology. Muller J Med Sci Res 2014;5:155-8.
Source of Support: Nil, Conflict of Interest: None declared.