Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Oct 6;2010(10):CD002292.
doi: 10.1002/14651858.CD002292.pub3.

Interventions for bullous pemphigoid

Gudula Kirtschig  1 , Philippa Middleton, Cathy Bennett, Dedee F Murrell, Fenella Wojnarowska, Nonhlanhla P Khumalo
Affiliations
Review

Interventions for bullous pemphigoid

Gudula Kirtschig et al. Cochrane Database Syst Rev. .

Update in

  • Interventions for bullous pemphigoid.
    Singh S, Kirtschig G, Anchan VN, Chi CC, Taghipour K, Boyle RJ, Murrell DF. Singh S, et al. Cochrane Database Syst Rev. 2023 Aug 11;8(8):CD002292. doi: 10.1002/14651858.CD002292.pub4. Cochrane Database Syst Rev. 2023. PMID: 37572360 Free PMC article. Review.

Abstract

Background: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the West. Oral steroids are the standard treatment.This is an update of the review published in 2005.

Objectives: To assess treatments for bullous pemphigoid.

Search strategy: In August 2010 we updated our searches of the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials), MEDLINE, EMBASE, and the Ongoing Trials registers.

Selection criteria: Randomised controlled trials of treatments for participants with immunofluorescence-confirmed bullous pemphigoid.

Data collection and analysis: At least two authors evaluated the studies for the inclusion criteria, and extracted data independently.

Main results: We included 10 randomised controlled trials (with a total of 1049 participants) of moderate to high risk of bias. All studies involved different comparisons, none had a placebo group. In 1 trial plasma exchange plus prednisone gave significantly better disease control at 1 month (0.3 mg/kg: RR 18.78, 95% CI 1.20 to 293.70) than prednisone alone (1.0 mg/kg: RR 1.79, 95% CI 1.11 to 2.90), while another trial showed no difference in disease control at 6 months.No differences in disease control were seen for different doses or formulations of prednisolone (one trial each), for azathioprine plus prednisone compared with prednisone alone (one trial), for prednisolone plus azathioprine compared with prednisolone plus plasma exchange (one trial), for prednisolone plus mycophenolate mofetil or plus azathioprine (one trial), for tetracycline plus nicotinamide compared with prednisolone (one trial). Chinese traditional medicine plus prednisone was not effective in one trial.There were no significant differences in healing in a comparison of a standard regimen of topical steroids (clobetasol) with a milder regimen (RR 1.00, 95% 0.97 to 1.03) in one trial. In another trial, clobetasol showed significantly more disease control than oral prednisolone in people with extensive and moderate disease (RR 1.09, 95% CI 1.02 to 1.17), with significantly reduced mortality and adverse events (RR 1.06, 95% CI 1.00 to 1.12).

Authors' conclusions: Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Higher dose prednisolone (1.25 mg/kg p/solone) versus lower dose prednisolone (0.75 mg/kg p/solone), Outcome 1 Disease control.
1.2
1.2. Analysis
Comparison 1 Higher dose prednisolone (1.25 mg/kg p/solone) versus lower dose prednisolone (0.75 mg/kg p/solone), Outcome 2 Mortality at day 51.
2.1
2.1. Analysis
Comparison 2 Methylprednisolone (mp/solone) versus prednisolone (p/solone), Outcome 1 Disease control ‐ number of blisters at day 10.
2.2
2.2. Analysis
Comparison 2 Methylprednisolone (mp/solone) versus prednisolone (p/solone), Outcome 2 Overall improvement.
2.3
2.3. Analysis
Comparison 2 Methylprednisolone (mp/solone) versus prednisolone (p/solone), Outcome 3 Disease control ‐ extent of erythema at day 10 (score out of 3).
2.4
2.4. Analysis
Comparison 2 Methylprednisolone (mp/solone) versus prednisolone (p/solone), Outcome 4 Quality of life ‐ extent of itching (score out of 3).
3.1
3.1. Analysis
Comparison 3 Prednisone + azathioprine (p/sone+azathio) versus prednisone (p/sone), Outcome 1 Disease control.
3.2
3.2. Analysis
Comparison 3 Prednisone + azathioprine (p/sone+azathio) versus prednisone (p/sone), Outcome 2 Mortality and severe adverse events at 6 months.
3.3
3.3. Analysis
Comparison 3 Prednisone + azathioprine (p/sone+azathio) versus prednisone (p/sone), Outcome 3 Mortality.
4.1
4.1. Analysis
Comparison 4 Prednisolone plus plasma exchange (p/solone+plas/x) versus prednisolone, Outcome 1 Disease control.
4.2
4.2. Analysis
Comparison 4 Prednisolone plus plasma exchange (p/solone+plas/x) versus prednisolone, Outcome 2 Disease control at 1 month ‐ cumulative steroid dose (g).
4.3
4.3. Analysis
Comparison 4 Prednisolone plus plasma exchange (p/solone+plas/x) versus prednisolone, Outcome 3 Mortality and severe adverse events at 6 months.
4.4
4.4. Analysis
Comparison 4 Prednisolone plus plasma exchange (p/solone+plas/x) versus prednisolone, Outcome 4 Mortality.
5.1
5.1. Analysis
Comparison 5 Prednisolone plus azathioprine (p/solone+azathio) versus prednisolone plus plasma exchange (p/solone+plas/x), Outcome 1 Disease control at 6 months.
5.2
5.2. Analysis
Comparison 5 Prednisolone plus azathioprine (p/solone+azathio) versus prednisolone plus plasma exchange (p/solone+plas/x), Outcome 2 Mortality at 6 months.
5.3
5.3. Analysis
Comparison 5 Prednisolone plus azathioprine (p/solone+azathio) versus prednisolone plus plasma exchange (p/solone+plas/x), Outcome 3 Mortality and adverse events at 6 months.
6.1
6.1. Analysis
Comparison 6 Nicotinamide plus tetracycline (nicot+tetracy) versus prednisone (p/sone), Outcome 1 Disease control.
6.2
6.2. Analysis
Comparison 6 Nicotinamide plus tetracycline (nicot+tetracy) versus prednisone (p/sone), Outcome 2 Mortality at 6 months.
7.1
7.1. Analysis
Comparison 7 Clobetasol propionate cream (clobetasol) versus oral prednisone (oral p/sone), Outcome 1 Disease control at day 21.
7.2
7.2. Analysis
Comparison 7 Clobetasol propionate cream (clobetasol) versus oral prednisone (oral p/sone), Outcome 2 Severe complications.
7.3
7.3. Analysis
Comparison 7 Clobetasol propionate cream (clobetasol) versus oral prednisone (oral p/sone), Outcome 3 Mortality at 1 year.
8.1
8.1. Analysis
Comparison 8 Mild regimen clobetasol propionate cream (mild clobetasol) regimen versus standard clobetasol propionate cream (stnd clobetasol) regimen, Outcome 1 Healing of skin lesions: complete (at day 21).
8.2
8.2. Analysis
Comparison 8 Mild regimen clobetasol propionate cream (mild clobetasol) regimen versus standard clobetasol propionate cream (stnd clobetasol) regimen, Outcome 2 Number of relapses.
8.3
8.3. Analysis
Comparison 8 Mild regimen clobetasol propionate cream (mild clobetasol) regimen versus standard clobetasol propionate cream (stnd clobetasol) regimen, Outcome 3 Mortality.
9.1
9.1. Analysis
Comparison 9 Jingui Shenqi Pill (JSP) 1# bid plus prednisone (JSP pill+p/sone) versus prednisone (p/sone) alone, Outcome 1 Healing at 4 weeks.
10.1
10.1. Analysis
Comparison 10 Azathioprine plus methylprednisolone (azathio+mp/solone) versus mycophenolate mofetil plus methylprednisolone (MMF+mp/solone), Outcome 1 Healing of lesions.
See this image and copyright information in PMC

Update of

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Beissert 2007 {published data only}
    1. Beissert S, Werfel T, Frieling U, Böhm M, Sticherling M, Stadler R, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Archives of Dermatology 2007;143(12):1536‐42. - PubMed
Burton 1978 {published data only}
    1. Burton JL, Harman RR, Peachy RD, Warin RP. Azathioprine plus prednisone in treatment of pemphigoid. British Medical Journal 1978;2:1190‐1. - PMC - PubMed
Dreno 1993 {published data only}
    1. Dreno B, Sassolas B, Lacour P, Montpoint S, Lota I, Giordano F, et al. Methylprednisolone versus prednisolone methylsulfobenzoate in pemphigoid: A comparative multicenter study. Annales de Dermatologie et de Vénéréologie 1993;120:518‐21. - PubMed
Fivenson 1994 {published data only}
    1. Fivenson DP, Breneman DL, Rosen GB, Hersh CS, Cardone S, Mutasim D. Nicotinamide and tetracycline therapy of bullous pemphigoid. Archives of Dermatology 1994;130(6):753‐8. - PubMed
Guillaume 1993 {published data only}
    1. Guillaume JC, Vaillant L, Bernard P, Picard C, Prost C, Labeille B, et al. Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid. Archives of Dermatology 1993;129(1):49‐53. - PubMed
Joly 2002 {published data only}
    1. Joly P, Benichou J, Lok C, Hellot MF, Saiag P, Trancrede‐Bohin E, et al. Prediction of survival for patients with bullous pemphigoid. A prospective study. Archives of Dermatology 2005;141:691‐98. - PubMed
    1. Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, et al. A comparison of oral and topical corticosteroids in patients with bullous pemphigoid. New England Journal of Medicine 2002;346(5):321‐7. - PubMed
Joly 2009 {published data only}
    1. Joly P. Personal communication. Email communication clarifying the published report. 30 January 2010.
    1. Joly P, Roujeau JC, Benichou J, Delaporte E, D'Incan M, Dreno B, et al. A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: A multicenter randomized study. Journal of Investigative Dermatology 2009;129(7):1681‐7. - PubMed
Liu 2006 {published data only}
    1. Liu BG, Li ZY, Du M. Effects of Jingui Shenqi Pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients. Chinese Journal of Integrated Traditional and Western Medicine 2006;26(10):881‐4. - PubMed
Morel 1984 {published data only}
    1. Morel P, Guillaume JC. Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day versus 1.25 mg/kg/day. A multicenter randomized study. Annales de Dermatologie et de Vénéréologie 1984;111(10):925‐8. - PubMed
Roujeau 1984 {published data only}
    1. Roujeau JC, Guillaume JC, Morel P, Crickx B, Dalle E, Doutre MS, et al. Plasma exchange in bullous pemphigoid. Lancet 1984;2(8401):486‐8. - PubMed

References to ongoing studies

ACTRN12607000104459 {published data only}
    1. ACTRN12607000104459. Rituximab in the adjuvant treatment of bullous pemphigoid: A prospective open‐label pilot study in three patients to study remission of disease with rituximab. http://www.anzctr.org.au/ACTRN12607000104459.aspx (accessed 27 July 2010).
ISRCTN13704604 {published data only}
    1. ISRCTN13704604. A randomised controlled trial to compare the safety and effectiveness of doxycycline (200 mg/day) with prednisolone (0.5 mg/kg/day) for initial treatment of bullous pemphigoid. http://www.controlled‐trials.com/ISRCTN13704604/Bullous+Pemphigoid (accessed 20 April 2009). - PubMed
NCT00286325 {published data only}
    1. NCT00286325. Rituximab in the treatment of patients with bullous pemphigoid. http://www.clinicaltrials.gov/ct2/show/NCT00286325 (accessed 20 April 2009).
NCT00472030 {published data only}
    1. NCT00472030. An open label case series on the effects of Xolair (Omalizumab) in bullous pemphigoid. http://clinicaltrials.gov/show/NCT00472030 (accessed 20 April 2009).
NCT00525616 {published data only}
    1. NCT00525616. Assessment of rituximab efficiency and tolerance in treatment of bullous pemphigoid. http://www.clinicaltrials.gov/show/NCT00525616 (accessed 20 April 2009).
NCT00802243 {published data only}
    1. NCT00802243. Leflunomide associated with topical corticosteroids for bullous pemphigoid. An open prospective study. http://clinicaltrials.gov/show/NCT00802243 (accessed 20 April 2009).
NCT00809822 {published data only}
    1. NCT00809822. NPB‐01 (intravenous immunoglobulin) therapy for patients with bullous pemphigoid unresponsive to corticosteroids: Randomized, double‐blind, placebo control, parallel assignment study (phase II). http://clinicaltrials.gov/show/NCT00809822 (accessed 20 April 2009).

Additional references

Adam 1992
    1. Adam BA. Bullous diseases in Malaysia: Epidemiological and natural history. International Journal of Dermatology 1992;31(1):42‐5. - PubMed
Ahmed 1977
    1. Ahmed AR, Maize JC, Provost TT. Bullous pemphigoid: Clinical and immunologic follow‐up after successful treatment. Archives of Dermatology 1977;113(8):1043‐6. - PubMed
Bernard 1995
    1. Bernard P, Vaillant L, Labeille B, Bedane C, Arbeille B, Denoeux JP, et al. Incidence and distribution of subepidermal autoimmune bullous skin diseases in three French regions. Bullous Diseases French Study Group. Archives of Dermatology 1995;131(1):48‐52. - PubMed
Colbert 2004
    1. Colbert RL, Allen DM, Eastwood D, Fairley JA. Mortality rate of bullous pemphigoid in a US medical center. Journal of Investigative Dermatology 2004;122(5):1091‐5. - PubMed
Garg 1994
    1. Garg V, Jusko WJ. Bioavailability and reversible metabolism of prednisone and prednisolone in man. Biopharmaceutics and Drug Disposition 1994;15(2):163‐72. - PubMed
Gudi 2005
    1. Gudi VS, White MI, Cruickshank N, Herriot R, Edwards SL, Nimmo F, et al. Annual incidence and mortality of bullous pemphigoid in the Grampian Region of North‐east Scotland. British Journal of Dermatology 2005;153(2):424‐7. - PubMed
Hadi 1988
    1. Hadi SM, Barnetson RS, Gawkrodger DJ, Saxena U, Bird P, Merrett TG. Clinical, histological and immunological studies in 50 patients with bullous pemphigoid. Dermatologica 1988;176(1):6‐17. - PubMed
Hertl 2008
    1. Hertl M, Zillikens D, Borradori L, Bruckner‐Tuderman L, Burckhard H, Eming R, et al. Recommendations for the use of rituximab (anti‐CD20 antibody) in the treatment of autoimmune bullous skin diseases. Journal der Deutschen Dermatologischen Gesellschaft 2008;6(5):366‐373. [DOI: 10.1111/j.1610‐0387.2007.06602.x] - PubMed
Higgins 2008
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. Available from www.cochrane‐handbook.org.
Jadad 1996
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12. - PubMed
Jin 1993
    1. Jin P, Shao C, Ye G. Chronic bullous dermatoses in China. International Journal of Dermatology 1993;32(2):89‐92. - PubMed
Joly 2010
    1. Joly P, et al. Personal communication. Email communication clarifying the published report. 30 January 2010.
Kirtschig 1994
    1. Kirtschig G, Wojnarowska F, Marsden RA, Edwards S, Bhogal B, Black MM. Acquired bullous disease of childhood: Re‐evaluation of diagnosis by indirect immunofluorescence examination on 1 M NaCl split skin and immunoblotting. British Journal of Dermatology 1994;130(5):610‐6. - PubMed
Lebrun‐Vignes 1999
    1. Lebrun‐Vignes B, Roujeau JC, Bernard P, Delaporte E, Joly P, Prost C, et al. Prednisone is more effective than prednisolone metasulfobenzoate in the treatment of bullous pemphigoid. Archives of Dermatology 1999;135(1):89‐90. - PubMed
Lever 1953
    1. Lever WF. Pemphigus. Medicine 1953;32(1):1‐123. - PubMed
Logan 1987
    1. Logan RA, Bhogal B, Das AK, McKee PM, Black MM. Localization of bullous pemphigoid antibody ‐ An indirect immunofluorescence study of 228 cases using a split‐skin technique. British Journal of Dermatology 1987;117(4):471‐8. - PubMed
Morrison 1990
    1. Morrison LH, Diaz L, Anhalt GJ. Bullous pemphigoid. In: Wojnarowska F, Briggaman RN (Editors) editor(s). Management of blistering diseases. London: Chapman and Hall Medical, 1990:63‐82.
Nemeth 1991
    1. Nemeth AJ, Klein AO, Gould EW, Schachner LA. Childhood bullous pemphigoid. Clinical and immunologic features, treatment, and prognosis. Archives of Dermatology 1991;127(3):378‐86. - PubMed
Orange 1989
    1. Orange AP, Joost T. Pemphigoid in children. Pediatric Dermatology 1989;6(4):267‐74. - PubMed
Parker 2008
    1. Parker SR, Dyson S, Brisman S, Pennie M, Swerlick RA, Khan R, et al. Mortality of bullous pemphigoid: An evaluation of 223 patients and comparison with the mortality in the general population in the United States. Journal of the American Academy of Dermatology 2008;59(4):582‐8. - PubMed
Person 1977
    1. Person JR, Rogers RS. Bullous and cicatricial pemphigoid: Clinical, pathological, and immunologic collerations. Mayo Clinic Proceedings 1977;52:54‐66. - PubMed
Reguiaï 2009
    1. Reguiaï Z, Tchen T, Perceau G, Bernard P. Efficacy of rituximab in a case of refractory bullous pemphigoid [Efficacite du rituximab dans une pemphigoide bulleuse en echec therapeutique.]. Annales de dermatologie et de Vénéréologie 2009;136(5):431‐4. [PUBMED: 19442800] - PubMed
Rollin 1993
    1. Rollin C, Chosidow O, Diquet B, Dutreuil C, Herson S, Revuz J, et al. Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone. European Journal of Clinical Pharmacology 1993;44(4):395‐9. - PubMed
Roujeau 1998
    1. Roujeau JC, Lok C, Bastuji‐Garin S, Mhalla S, Enginger V, Bernard P. High risk of death in elderly patients with extensive bullous pemphigoid. Archives of Dermatology 1998;134(4):465‐9. - PubMed
Savin 1979
    1. Savin JA. The events leading to the death of patients with pemphigus and pemphigoid. British Journal of Dermatology 1979;101(5):521‐34. - PubMed
Savin 1987
    1. Savin JA. Death in bullous pemphigoid. Clinics in Dermatology 1987;5(1):52‐9. - PubMed
Tham 1998
    1. Tham SN, Thirumoorthy T, Rajan VS. Bullous pemphigoid: Clinico‐epidemiological study of patients seen at a Singapore skin hospital. Australasian Journal of Dermatology 1998;25(2):68‐72. - PubMed
Venning 1992
    1. Venning VA, Wojnarowska F. Lack of predictive factors for the clinical course of bullous pemphigoid. Journal of the American Academy of Dermatology 1992;26(4):585‐9. - PubMed
Wojnarowska 1998
    1. Wojnarowska F, Eady RAJ, Burge SM. Bullous pemphigoid. In: Champion RH, Burton JL, Burns DA, Breathnach SM editor(s). Textbook of Dermatology. 6. Vol. 3, Oxford: Blackwell Science Ltd, 1998:1866‐73.
Wojnarowska 2002
    1. Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP. Guidelines for the management of bullous pemphigoid. British Journal of Dermatology 2002;147(2):214‐221. - PubMed
Zillikens 1995
    1. Zillikens D, Wever S, Roth A, Weidenthaler‐Barth B, Hashimoto T, Bröcker EB. Incidence of autoimmune subepidermal blistering dermatoses in a region of central Germany (Comment). Archives of Dermatology 1995;131(1):48‐52. - PubMed
Zimmermann 1999
    1. Zimmermann R, Faure M, Claudy A. Prospective study of treatment of bullous pemphigoid by a class I topical corticosteroid. Annales de Dermatologie et de Vénéréologie 1999;126(1):13‐6. - PubMed

References to other published versions of this review

Khumalo 2002
    1. Khumalo NP, Murrell DF, Wojnarowska F, Kirtschig G. A systematic review of treatments for bullous pemphigoid. Archives of Dermatology 2002;138(3):385‐9. - PubMed
Khumalo 2005
    1. Khumalo N, Kirtschig G, Middleton P, Hollis S, Wojnarowska F, Murrell DF. Interventions for bullous pemphigoid. Cochrane Database of Systematic Reviews 2005, Issue 3. [DOI: 10.1002/14651858.CD002292.pub3] - DOI - PubMed

MeSH terms