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REVIEW ARTICLE
Year : 2014  |  Volume : 5  |  Issue : 2  |  Page : 155-158

Steroid pulse therapies in dermatology


Department of Dermatology, SDM Medical College, Sattur, Dharwad, Karnataka, India

Date of Web Publication1-Jul-2014

Correspondence Address:
Gaurang Gupta
Department of Dermatology, OPD No. 10, SDM Medical College, Sattur, Dharwad - 580 009, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-9727.135756

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  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.

Keywords: Dexamethasone-cyclophosphamide pulse therapy, pulse therapy, steroid


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

How to cite this URL:
Gupta G, Jain A, Narayanasetty NK. Steroid pulse therapies in dermatology. Muller J Med Sci Res [serial online] 2014 [cited 2019 Sep 18];5:155-8. Available from: http://www.mjmsr.net/text.asp?2014/5/2/155/135756


  Introduction Top


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 Top

"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]"

Various modifications and modes are in use. Most commonly used corticosteroids in pulse therapies are methylprednisolone and dexamethasone. [6]


  Methylprednisolone Pulse Therapy Top


Methylprednisolone is an intermediate acting, potent, anti-inflammatory agent with a low tendency to induce sodium and water retention compared with hydrocortisone. It's biological half-life is 12-36 h, potency 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 Top


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]


  Administration of Pulse Therapy Top


Initially, the duration of infusion was 10-20 min. However, rapid infusions are known to be associated with a higher risk of hemodynamic abnormalities, now-a-days the corticosteroid preparation is dissolved in 150-200 ml of 5% dextrose and infused IV, slowly over 2-3 h. [8],[10]

Advantage of Corticosteroid as a Pulse Therapy

  1. An immediate profound anti-inflammatory effect is achieved and the toxicities seen with conventional 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],[9],[10]



  Mechanism of Action Top


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 Top


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.



  Laboratory Monitoring Top


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 Top


  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. Seizures, particularly in systemic lupus 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]
  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 Top


DCP Therapy is Divided into four Phases

1 st 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 are withdrawn, the patient is considered to have entered phase II. [26]

2 nd phase

Phase of remission while on therapy. DCP schedule is given for duration of 9 months.

3 rd phase

Monthly pulses are terminated and oral cyclophosphamide is continued for duration of 9 month.

4 th phase

Treatment is stopped and patients are followed-up for next 10 years.


  Modifications of DCP Therapy Top


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 Top


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 Top


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 Top


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 some sever and chronic disease of dermatology such as pemphigus, erythroderma, TEN/SJS etc.

 
  References Top

1.Bell PR, Briggs JD, Calman KC, Paton AM, Wood RF, Macpherson SG, et al. Reversal of acute clinical and experimental organ rejection using large doses of intravenous prednisolone. Lancet 1971;1:876-80.  Back to cited text no. 1
    
2.Kountz SL, Cohn R. Initial treatment of renal allografts with large intrarenal doses of immunosuppressive drugs. Lancet 1969;1:338-40.  Back to cited text no. 2
    
3.Cathcart ES, Idelson BA, Scheinberg MA, Couser WG. Beneficial effects of methylprednisolone "pulse" therapy in diffuse proliferative lupus nephritis. Lancet 1976;1:163-6.  Back to cited text no. 3
    
4.Pasricha JS, Srivastava G. Cure in pemphigus a possibility. Indian J Dermatol Venereol Leprol 1986;52:185-6.  Back to cited text no. 4
    
5.Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: Current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61:718-22.  Back to cited text no. 5
    
6.Laxler RM, Gazarian M. Pharmacology and drug therapy. In: Cassidy JT, Petty RE, Lindsley CB, Laxler RM, editors. Textbook of Pediatric Rheumatology. 5 th ed. Philadelphia: WB Saunders Company; 2005. p. 90-146.  Back to cited text no. 6
    
7.Schimmer BP, Parker KL. Adrenocorticotropic hormones; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman′s The Pharmacological Basis of Therapeutics. 11 th ed. New York: Mc Graw-Hill Professional; 2006. p. 1587-612.  Back to cited text no. 7
    
8.Novak E, Stubbs SS, Seckman CE, Hearron MS. Effects of a single large intravenous dose of methylprednisolone sodium succinate. Clin Pharmacol Ther 1970;11:711-7.  Back to cited text no. 8
    
9.Gallant C, Kenny P. Oral glucocorticoids and their complications. A review. J Am Acad Dermatol 1986;14:161-77.  Back to cited text no. 9
    
10.Miura M, Ohki H, Yoshiba S, Ueda H, Sugaya A, Satoh M, et al. Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease. Arch Dis Child 2005;90:1096-7.  Back to cited text no. 10
    
11.Buttgereit F, Saag KG, Cutolo M, da Silva JA, Bijlsma JW. The molecular basis for the effectiveness, toxicity, and resistance to glucocorticoids: Focus on the treatment of rheumatoid arthritis. Scand J Rheumatol 2005;34:14-21.  Back to cited text no. 11
    
12.Smith MD, Ahern MJ, Roberts-Thomson PJ, Youssef PP. Similar effects of pulse corticosteroid and tumor necrosis factor alpha blockade in rheumatoid arthritis: Comment on the article by Taylor et al. Arthritis Rheum 2001;44:245-6.  Back to cited text no. 12
    
13.Sinha A, Bagga A. Pulse steroid therapy. Indian J Pediatr 2008;75:1057-66.  Back to cited text no. 13
    
14.Mittal R, Sudha S, Murugan S, Adikrishnan, Shobana S, Anandan S. Pulse therapy in dermatology. Sri Ramachandra J Med 2007;1:44-6.  Back to cited text no. 14
    
15.Baethge BA, Lidsky MD, Goldberg JW. A study of adverse effects of high-dose intravenous (pulse) methylprednisolone therapy in patients with rheumatic disease. Ann Pharmacother 1992;26:316-20.  Back to cited text no. 15
    
16.Klein-Gitelman MS, Pachman LM. Intravenous corticosteroids: Adverse reactions are more variable than expected in children. J Rheumatol 1998;25:1995-2002.  Back to cited text no. 16
    
17.Kang I, Park SH. Infectious complications in SLE after immunosuppressive therapies. Curr Opin Rheumatol 2003;15:528-34.  Back to cited text no. 17
    
18.Kanwar AJ, Kaur S, Dhar S, Ghosh S. Hiccup - A side-effect of pulse therapy. Dermatology 1993;187:279.  Back to cited text no. 18
    
19.Dhar S, Kanwar AJ. Facial flushing - A side effect of pulse therapy. Dermatology 1994;188:332.  Back to cited text no. 19
    
20.Appelhans M, Bonsmann G, Orge C, Bröcker EB. Dexamethasone-cyclophosphamide pulse therapy in bullous autoimmune dermatoses. Hautarzt 1993;44:143-7.  Back to cited text no. 20
    
21.Kar BR, Handa S, Dogra S, Kumar B. Placebo-controlled oral pulse prednisolone therapy in alopecia areata. J Am Acad Dermatol 2005;52:287-90.  Back to cited text no. 21
    
22.Efentaki P, Altenburg A, Haerting J, Zouboulis CC. Medium-dose prednisolone pulse therapy in alopecia areata. Dermatoendocrinol 2009;1:310-3.  Back to cited text no. 22
    
23.Minocha YC, Sood VK, Singh D, Minocha KB. Topical corticosteroid pulse therapy in psoriasis. Indian J Dermatol Venereol Leprol 1991;57:307-8.  Back to cited text no. 23
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24.Pasricha JS. Pulse therapy as a cure for autoimmune diseases. Indian J Dermatol Venereol Leprol 2003;69:323-8.  Back to cited text no. 24
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25.Valia AR, Ramesh V, Jerajani HR, Fernandez RJ. Blistering disorder. In: Valia RG, Valia AR, editors. IADVL Textbook of Dermatology. 3 rd ed. Mumbai: Bhalani Publication House; 2008. p. 1087-152.  Back to cited text no. 25
    
26.Rao PN, Lakshmi TS. Pulse therapy and its modifications in pemphigus: A six year study. Indian J Dermatol Venereol Leprol 2003;69:329-33.  Back to cited text no. 26
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  In this article
Abstract
Introduction
Definition
Methylprednisolo...
Dexamethasone Pu...
Administration o...
Mechanism of Action
Uses of Corticos...
Laboratory Monit...
Contraindication...
DCP Therapy
Modifications of...
DCP Therapy in C...
DCP Therapy in S...
Conclusion
References

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