Treatment of bullous pemphigoid with low-dose oral cyclophosphamide: a case series of 20 patients

Background Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. Objective To assess the cl...

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Published in	Journal of the European Academy of Dermatology and Venereology Vol. 28; no. 6; pp. 814 - 818
Main Authors	Gual, A., Iranzo, P., Mascaró Jr, J.M.
Format	Journal Article
Language	English
Published	England Blackwell Publishing Ltd 01.06.2014
Subjects	Administration, Oral Aged Aged, 80 and over Cyclophosphamide - administration & dosage Female Humans Immunosuppressive Agents - administration & dosage Male Pemphigoid, Bullous - drug therapy Retrospective Studies
Online Access	Get full text
ISSN	0926-9959 1468-3083 1468-3083
DOI	10.1111/jdv.12155

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Abstract	Background Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. Objective To assess the clinical efficacy and safety of low‐dose oral cyclophosphamide (CFM) (50–100 mg/day) in patients with refractory bullous pemphigoid. Methods We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain. Results Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. Conclusions In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low‐dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate‐to‐severe bullous pemphigoid.
AbstractList	Background Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. Objective To assess the clinical efficacy and safety of low‐dose oral cyclophosphamide (CFM) (50–100 mg/day) in patients with refractory bullous pemphigoid. Methods We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain. Results Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. Conclusions In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low‐dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate‐to‐severe bullous pemphigoid. Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid. We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain. Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid. Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality.BACKGROUNDCyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality.To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid.OBJECTIVETo assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid.We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain.METHODSWe conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain.Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy.RESULTSComplete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy.In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid.CONCLUSIONSIn our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid. Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid. We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clinic of Barcelona, Spain. Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid.
Author	Mascaró Jr, J.M. Gual, A. Iranzo, P.
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/23581830$$D View this record in MEDLINE/PubMed
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References	Guillaume JC, Vaillant L, Bernard P et al. Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid. Arch Dermatol 1993; 129: 49-53. Langan SM, Smeeth L, Hubbard R et al. Bullous pemphigoid and pemphigus vulgaris incidence and mortality in the UK: population based cohort study. BMJ 2008; 58: 41-48. Beissert S, Werfel T, Frieling U et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Arch Dermatol 2007; 143: 1536-1542. Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol 2012; 30: 78-83. Di Zenzo G, Marazza G, Borradori L. Bullous pemphigoid: physiopathology, clinical features and management. Adv Dermatol 2007; 23: 257-258. Cortés B, Marazza G, Naldi L et al. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol 2011; 165: 368-374. Munyangango EM, Le Roux-Villet C, Doan S et al. Oral cyclophosphamide without corticosteroids to treat mucous membrane pemphigoid. Br J Dermatol 2013; 168: 381-390. Jung M, Kippes W, Messer G et al. Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence. J Am Acad Dermatol 1999; 41: 266-268. Gual A, Mascaró JM Jr, Rojas-Farreras S et al. Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical center. J Eur Acad Dermatol Venereol 2012; Dec 22. doi: 10.1111/jdv.12065. [Epub ahead of print]. Joly P, Baricault S, Sparsa A et al. Incidence and mortality of bullous pemphigoid in France. J Invest Dermatol 2012; 132: 1998-2004. Venning VA, Taghipour K, Mohd Mustapa MF et al. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. Br J Dermatol, 2012; 167: 1200-1214. Perini P, Calabrese M, Rinaldj L, Gallo P. Cyclophosphamide-based combination therapies for autoimmunity. Neurol Sci 2008; 29: S233-S234. Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 2009; 6: 638-647. Dawe RS, Naidoo DK, Ferguson J. Severe bullous pemphigoid responsive to pulsed intravenous dexamethasone and oral cyclophosphamide. Br J Dermatol 1997; 137: 826-827. García-Romero MT, Werth VP. Randomized controlled trials needed for bullous pemphigoid interventions. Arch Dermatol 2012; 148: 243-246. Kjellman P, Eriksson H, Berg P. A retrospective analysis of patients with bullous pemphigoid treated with methotrexate. Arch Dermatol 2008; 144: 612-616. Olszewska M, Kolacinska-Strasz Z, Sulej J et al. Efficacy and safety of cyclophosphamide, azathioprine, and cyclosporine (ciclosporin) as adjuvant drugs in pemphigus vulgaris. Am J Clin Dermatol 2007; 8: 85-92. Taïeb A, Klene C, Maleville J. Immediate treatment of bullous pemhigus with a corticosteroid-cyclophosphamide combination. Ann Dermatol Venereol 1986; 113: 1223-1229. 1997; 137 2012; 132 1993; 129 1986; 113 2012; 167 2012 2007; 143 2008; 29 2008; 58 2007; 8 2013; 168 1999; 41 2009; 6 2012; 148 2008; 144 2007; 23 2011; 165 2012; 30 e_1_2_6_10_1 e_1_2_6_9_1 e_1_2_6_8_1 e_1_2_6_19_1 e_1_2_6_5_1 Taïeb A (e_1_2_6_18_1) 1986; 113 e_1_2_6_4_1 e_1_2_6_7_1 Langan SM (e_1_2_6_3_1) 2008; 58 e_1_2_6_6_1 e_1_2_6_13_1 e_1_2_6_14_1 e_1_2_6_11_1 e_1_2_6_2_1 e_1_2_6_12_1 e_1_2_6_17_1 e_1_2_6_15_1 e_1_2_6_16_1
References_xml	– reference: Cortés B, Marazza G, Naldi L et al. Mortality of bullous pemphigoid in Switzerland: a prospective study. Br J Dermatol 2011; 165: 368-374. – reference: Venning VA, Taghipour K, Mohd Mustapa MF et al. British Association of Dermatologists' guidelines for the management of bullous pemphigoid 2012. Br J Dermatol, 2012; 167: 1200-1214. – reference: García-Romero MT, Werth VP. Randomized controlled trials needed for bullous pemphigoid interventions. Arch Dermatol 2012; 148: 243-246. – reference: Jung M, Kippes W, Messer G et al. Increased risk of bullous pemphigoid in male and very old patients: a population-based study on incidence. J Am Acad Dermatol 1999; 41: 266-268. – reference: Taïeb A, Klene C, Maleville J. Immediate treatment of bullous pemhigus with a corticosteroid-cyclophosphamide combination. Ann Dermatol Venereol 1986; 113: 1223-1229. – reference: Beissert S, Werfel T, Frieling U et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Arch Dermatol 2007; 143: 1536-1542. – reference: Olszewska M, Kolacinska-Strasz Z, Sulej J et al. Efficacy and safety of cyclophosphamide, azathioprine, and cyclosporine (ciclosporin) as adjuvant drugs in pemphigus vulgaris. Am J Clin Dermatol 2007; 8: 85-92. – reference: Gual A, Mascaró JM Jr, Rojas-Farreras S et al. Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical center. J Eur Acad Dermatol Venereol 2012; Dec 22. doi: 10.1111/jdv.12065. [Epub ahead of print]. – reference: Kjellman P, Eriksson H, Berg P. A retrospective analysis of patients with bullous pemphigoid treated with methotrexate. Arch Dermatol 2008; 144: 612-616. – reference: Joly P, Baricault S, Sparsa A et al. Incidence and mortality of bullous pemphigoid in France. J Invest Dermatol 2012; 132: 1998-2004. – reference: Emadi A, Jones RJ, Brodsky RA. Cyclophosphamide and cancer: golden anniversary. Nat Rev Clin Oncol 2009; 6: 638-647. – reference: Munyangango EM, Le Roux-Villet C, Doan S et al. Oral cyclophosphamide without corticosteroids to treat mucous membrane pemphigoid. Br J Dermatol 2013; 168: 381-390. – reference: Di Zenzo G, Marazza G, Borradori L. Bullous pemphigoid: physiopathology, clinical features and management. Adv Dermatol 2007; 23: 257-258. – reference: Perini P, Calabrese M, Rinaldj L, Gallo P. Cyclophosphamide-based combination therapies for autoimmunity. Neurol Sci 2008; 29: S233-S234. – reference: Dawe RS, Naidoo DK, Ferguson J. Severe bullous pemphigoid responsive to pulsed intravenous dexamethasone and oral cyclophosphamide. Br J Dermatol 1997; 137: 826-827. – reference: Langan SM, Smeeth L, Hubbard R et al. Bullous pemphigoid and pemphigus vulgaris incidence and mortality in the UK: population based cohort study. BMJ 2008; 58: 41-48. – reference: Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol 2012; 30: 78-83. – reference: Guillaume JC, Vaillant L, Bernard P et al. Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid. 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Snippet	Background Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published... Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of...
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SubjectTerms	Administration, Oral Aged Aged, 80 and over Cyclophosphamide - administration & dosage Female Humans Immunosuppressive Agents - administration & dosage Male Pemphigoid, Bullous - drug therapy Retrospective Studies
Title	Treatment of bullous pemphigoid with low-dose oral cyclophosphamide: a case series of 20 patients
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