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Observation
February 2007

Clinical Response of Severe Mechanobullous Epidermolysis Bullosa Acquisita to Combined Treatment With Immunoadsorption and Rituximab (Anti-CD20 Monoclonal Antibodies)

Author Affiliations

Author Affiliations: Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität, Marburg (Drs Niedermeier, Eming, Pfütze, and Hertl and Ms Happel), Hautklinik und Poliklinik der Georg-August-Universität Göttingen, Göttingen (Drs Neumann and Reich), and Dermatologikum Hamburg, Hamburg (Dr Reich), Germany.

Arch Dermatol. 2007;143(2):192-198. doi:10.1001/archderm.143.2.192
Abstract

Background  Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disorder with mucocutaneous involvement, skin fragility, and tendency to scarring. The mechanobullous form of EBA has a chronic relapsing course and is difficult to treat. We describe herein the therapeutic response of 2 patients with recalcitrant mechanobullous EBA to combined treatment with immunoadsorption and rituximab, an anti-CD20 monoclonal antibody that induces depletion of B cells in vivo.

Observations  Two patients with mechanobullous EBA received combined treatment with immunoadsorption and rituximab, resulting in an almost complete clinical remission in one patient and stable disease in the other patient. In the patient with complete remission, prolonged B-cell depletion and clinical improvement with disappearance of mucocutaneous erosions paralleled the decline in titers of circulating anti–basement membrane zone autoantibodies. In the other patient, combined treatment with immunoadsorption and rituximab reduced the de novo appearance of blisters but did not lead to significant improvement of gingivitis, despite depleted B cells for 6 months that remained at 5% 12 months after the last administration of rituximab, as well as a reduction in autoantibody titers.

Conclusion  The patients' response suggests that combined treatment with immunoadsorption and rituximab may be a valuable adjuvant treatment regimen for severe mechanobullous EBA, which is in line with recently observed beneficial effects in inflammatory EBA.

Epidermolysis bullosa acquisita (EBA) is a chronic subepidermal bullous disease of the skin and mucous membranes characterized by the presence of autoantibodies against type VII collagen, a major component of anchoring fibrils. There is great diversity in the clinical presentation of the disease. At least 5 clinical subsets of EBA can be distinguished1: (1) classic mechanobullous presentation with spontaneous or trauma-induced blisters resembling hereditary dystrophic epidermolysis bullosa, (2) bullous pemphigoid–like presentation, (3) mucous membrane pemphigoid–like presentation, (4) Brunsting-Perry pemphigoid–like presentation, and (5) linear IgA bullous dermatosis–like disease. The classic form is especially difficult to treat. This form manifests as mechanobullous noninflammatory disease with an acral distribution and skin fragility over trauma-prone surfaces. The blisters and erosions heal with scarring and milia formation. The vesicles and tense bullae appear on noninflamed or atrophic skin, leading to erosions, crusts, scales, scars, scarring alopecia, cysts, milia, and nail dystrophy. In the more severe form, there can also be loss of nails, sclerosis of the hands and fingers, and esophageal stenosis,2,3 reminiscent of recessive dystrophic epidermolysis bullosa.1

The treatment of EBA is often a major therapeutic challenge. There are anecdotal reports of successful treatment with cyclosporine,46 colchicine,7,8 high- and low-dose intravenous immunoglobulins,9 plasmapheresis in conjunction with immunoglobulins,10 and extracorporeal photochemotherapy.11,12 Because of the rareness of the disease, controlled clinical therapeutic trials have not been performed, to our knowledge.

Immunoadsorption (IA) is used in antibody-mediated autoimmune disorders refractory to immunosuppressive therapy.1316 It is an effective adjuvant treatment to reduce circulating autoantibodies in patients in whom unacceptably high dosages of glucocorticosteroids are required for initial therapy or in whom the disease activity does not allow for sufficient tapering of the glucocorticosteroid dosage necessary to reduce adverse effects.

Rituximab is a genetically engineered chimeric monoclonal antibody consisting of a human IgG1 constant region with murine light- and heavy-chain variable regions that are specific for CD20, a molecule located on pre-B mature B lymphocytes and in most B-cell neoplasms.17,18 Rituximab was originally designed for the treatment of B-cell neoplasms; it is approved for the first-line treatment of diffuse large B-cell, CD20+, non-Hodgkin lymphoma, in combination with CHOP (cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone) or other anthracycline-based chemotherapy regimens. It has also been used to treat various refractory autoimmune diseases, including idiopathic thrombocytopenic purpura,19 autoimmune hemolytic anemia,20 rheumatoid arthritis,21 systemic lupus erythematosus,22,23 myasthenia gravis,24 Wegener granulomatosis,2527 Sjögren syndrome,28 dermatomyositis,29 and paraneoplastic pemphigus.3032 Rituximab has been recently approved for the treatment of rheumatoid arthritis by the Food and Drug Administration in combination with methotrexate in patients who are refractory to other disease-modifying antirheumatic drugs, including 1 therapy or more with tumor necrosis factor α inhibitors. There are case reports on the effect of rituximab treatment in refractory pemphigus3349 and a report on the use of rituximab in a patient with inflammatory bullous pemphigoid–like EBA.50 Herein, we describe 2 patients with mechanobullous EBA who were successfully treated with a combination of IA followed by rituximab.

METHODS
PATIENTS

Both patients had an unambiguous diagnosis of EBA according to the following clinical and laboratory diagnostic criteria: (1) cutaneous and mucosal superficial erosions and skin fragility with a tendency to scarring and cutaneous atrophy, (2) subepidermal loss of adherence as shown by histopathologic findings, (3) indirect immunofluorescence showing linear IgG fluorescence along the dermoepidermal junction and dermal IgG staining on skin substrate that was separated at the lamina lucida by incubation with 1M sodium chloride, and (4) detection of anti–collagen VII antibodies in the serum.

CLINICAL OUTCOME

To date, there is no consensus about uniform criteria to grade disease severity or to define remission in autoimmune bullous diseases. An autoimmune bullous skin disorder intensity score was established to assess disease activity and therapeutic response in individual patients (M.P., unpublished data, 2006). Briefly, the autoimmune bullous skin disorder intensity score consists of 3 components (skin, oral mucosa, and genital mucosa), representing the most commonly affected areas. Skin involvement was measured according to the type and extent of lesions. This score was designed for monitoring intraindividual therapeutic responses rather than comparing disease activity among individuals. Disease severity of the oral mucosa was graded on a scale from 0 (no disease activity in any of 11 defined sites of the oral mucosa) to 11 (maximum disease activity). Atrophic skin lesions that are typically found in mechanobullous EBA were not counted as lesions.

TREATMENT REGIMEN

Immunoadsorption was performed according to an established protocol.51 Briefly, IA was performed on 4 consecutive days using commercially available adsorbers (Globaffin; Fresenius Medical Care, Lexington, Mass), representing 1 treatment cycle. Each cycle was followed by a second cycle after a 4-week interval. During the entire IA treatment, patients continued receiving an immunosuppressive medication consisting of glucocorticosteroids and the glucocorticosteroid-sparing adjuvant agent mycophenolate mofetil (1 g 3 times daily).

After IA, rituximab was administered intravenously at a dose of 375 mg/m2 in body surface area during 4 to 6 hours once weekly for 4 consecutive weeks. The patient was pretreated with intravenous administration of 100 mg of prednisolone-21-hydrogen succinate, 4 mg of dimethindene maleate, and 50 mg of ranitidine hydrochloride. As an oral antipyretic agent, 500 mg of acetaminophen was given 2 hours before treatment.

IMMUNOLOGICAL FINDINGS

Both patients showed linear IgG and complement C3 deposits at the dermoepidermal junction of perilesional skin by direct immunofluorescence; anti–collagen VII IgG autoantibodies were detected by immunoblot analysis with recombinant protein of the immunodominant domain NC1 of collagen VII, produced in a baculovirus expression system (Ralf Müller, PhD, unpublished data, 2006). Anti–basement membrane zone antibodies were detected by indirect immunofluorescence analysis of patients' blood samples using epithelial cell surfaces of monkey esophagus as substrate and sodium split human skin. The count of peripheral blood B cells was investigated by flow cytometric analysis of peripheral blood mononuclear cells using a monoclonal antibody reacting with the pan-B CD19+ differentiation antigen (Department of Oncology and Hematology, University Hospitals of Marburg, Marburg).

REPORT OF CASES
PATIENT 1

A 67-year-old man had been diagnosed as having EBA 4 years previously. He had bullous and erosive lesions of the oral mucosa, esophagus, and nasopharynx. His hands, shanks, and feet showed tense blisters and erosions. On both feet, nail loss had occurred on most of the toes due to postinflammatory scarring (Figure 1A). The lesions on the soles significantly impaired walking. Before IA, he had already undergone several long-term immunosuppressive treatment regimens (Figure 2A). Because of unresponsiveness to these regimens, patient 1 received 2 treatment cycles of IA. After completion of IA, rituximab was administered during 4 weeks. Patient 1 subsequently received adjuvant immunosuppressive treatment with mycophenolate mofetil (3 g/d). The lesions on his hands improved slightly (Figure 1B), whereas the oral lesions and the lesions on his soles and feet showed no improvement. The patient's autoantibody titers were only marginally reduced (1:1600 before treatment and 1:800 after treatment). His peripheral B cells were completely depleted for 6 months and remained at 5% 12 months after the last administration of rituximab (Figure 1C).

Figure 1.
Patient 1. Partial clinical response of mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption (IA) and rituximab. A, The patient had blisters and erosions on his hands, feet, and oral mucosa. B, At 15 weeks after completion of combined treatment with IA and rituximab therapy, marked improvement of the lesions on the dorsal aspect of his hands was notable, while erosions of the oral mucosa remained largely unaffected. C, Data are shown before and at 15 weeks after combined treatment with IA and rituximab therapy. ABSIS indicates autoimmune bullous skin disorder intensity. The light gray arrows each indicate 1 treatment cycle of IA; black arrow, 1 treatment cycle of rituximab consisting of 375 mg/m2 body surface area weekly on 4 consecutive weeks.

Patient 1. Partial clinical response of mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption (IA) and rituximab. A, The patient had blisters and erosions on his hands, feet, and oral mucosa. B, At 15 weeks after completion of combined treatment with IA and rituximab therapy, marked improvement of the lesions on the dorsal aspect of his hands was notable, while erosions of the oral mucosa remained largely unaffected. C, Data are shown before and at 15 weeks after combined treatment with IA and rituximab therapy. ABSIS indicates autoimmune bullous skin disorder intensity. The light gray arrows each indicate 1 treatment cycle of IA; black arrow, 1 treatment cycle of rituximab consisting of 375 mg/m2 body surface area weekly on 4 consecutive weeks.

Figure 2.
Both patients received the following treatment regimens before combined treatment with immunoadsorption (IA) (1 treatment cycle on 4 consecutive days) and rituximab (375 mg/m2 in body surface area once weekly for 4 consecutive weeks) (arrows): extracorporeal photopheresis (ECP), dexamethasone sodium phosphate pulse (50-100 mg during 3 days every 5 weeks), cyclophosphamide pulse (500-600 mg/m2 every 4 weeks in patient 1 and an unknown dosage in patient 2), cyclosporine (3.5 mg/d per kg of body weight in patient 1 and 2.8-1.5 mg/d per kilogram in patient 2), dapsone (100 mg/d), leflunomide (20 mg/d), intravenous immunoglobulins (IVIG) (1-2 g/kg in patient 1 and 2 g/kg in patient 2), methotrexate (25 mg/wk in patient 1 and an unknown dosage in patient 2), azathioprine (1-2 mg/d per kilogram), and mycophenolate mofetil (1-3 g/d). The complete regimens are shown for patient 1 (A) and for patient 2 (B), who also received an unknown dosage of prednisolone.

Both patients received the following treatment regimens before combined treatment with immunoadsorption (IA) (1 treatment cycle on 4 consecutive days) and rituximab (375 mg/m2 in body surface area once weekly for 4 consecutive weeks) (arrows): extracorporeal photopheresis (ECP), dexamethasone sodium phosphate pulse (50-100 mg during 3 days every 5 weeks), cyclophosphamide pulse (500-600 mg/m2 every 4 weeks in patient 1 and an unknown dosage in patient 2), cyclosporine (3.5 mg/d per kg of body weight in patient 1 and 2.8-1.5 mg/d per kilogram in patient 2), dapsone (100 mg/d), leflunomide (20 mg/d), intravenous immunoglobulins (IVIG) (1-2 g/kg in patient 1 and 2 g/kg in patient 2), methotrexate (25 mg/wk in patient 1 and an unknown dosage in patient 2), azathioprine (1-2 mg/d per kilogram), and mycophenolate mofetil (1-3 g/d). The complete regimens are shown for patient 1 (A) and for patient 2 (B), who also received an unknown dosage of prednisolone.

PATIENT 2

A 42-year-old man who had been diagnosed as having EBA 9 years previously was admitted to the hospital because of a severe chronic course. He had blisters and skin fragility mainly on his trunk and forearms (Figure 3A). The oral mucosa had also been affected in a previous manifestation. To control the disease, he had undergone multiple immunosuppressive therapies (Figure 2B). Because of recalcitrant EBA, patient 2 received 2 treatment cycles of IA followed by rituximab infusions during 4 weeks and adjuvant immunosuppressive treatment with mycophenolate mofetil (3 g/d). The patient discontinued mycophenolate mofetil treatment after rituximab therapy. When he was seen 34 weeks later, his disease was well controlled, with few crusty erosions and atrophic lesions (Figure 3B). The clinical response was accompanied by a decline in titers of circulating autoantibodies (1:800 before treatment and 1:200 after treatment). Titers were below the detection limit at 34 weeks after rituximab therapy. Complete B-cell depletion persisted for at least 37 weeks (Figure 3C).

Figure 3.
Patient 2. Marked clinical response of mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption (IA) and rituximab. A, The patient had extensive blisters and erosions on his trunk and hands. Top inset, Detail of fresh erosions on the trunk. Bottom inset, Detail of fresh lesion on the index finger of the right hand. B, At 8 months after completion of combined IA and rituximab therapy, the patient had almost complete clinical remission, with postinflammatory atrophic hyperpigmentations on his chest and a few crusty erosions. Top inset, Detail of healed erosions and remaining scars. C, The data are shown before and at 34 weeks after combined treatment with IA and rituximab. ABSIS indicates autoimmune bullous skin disorder intensity. The light gray arrows each indicate 1 treatment cycle of IA; black arrow, 1 treatment cycle of rituximab consisting of 375 mg/m2 body surface area weekly on 4 consecutive weeks.

Patient 2. Marked clinical response of mechanobullous epidermolysis bullosa acquisita to combined treatment with immunoadsorption (IA) and rituximab. A, The patient had extensive blisters and erosions on his trunk and hands. Top inset, Detail of fresh erosions on the trunk. Bottom inset, Detail of fresh lesion on the index finger of the right hand. B, At 8 months after completion of combined IA and rituximab therapy, the patient had almost complete clinical remission, with postinflammatory atrophic hyperpigmentations on his chest and a few crusty erosions. Top inset, Detail of healed erosions and remaining scars. C, The data are shown before and at 34 weeks after combined treatment with IA and rituximab. ABSIS indicates autoimmune bullous skin disorder intensity. The light gray arrows each indicate 1 treatment cycle of IA; black arrow, 1 treatment cycle of rituximab consisting of 375 mg/m2 body surface area weekly on 4 consecutive weeks.

COMMENT

Epidermolysis bullosa acquisita is a chronic subepidermal blistering disease associated with humoral autoimmunity to type VII collagen, an integral part of anchoring fibrils that are important components of the dermoepidermal junction. The pathogenic relevance of collagen VII–specific autoantibodies in EBA has been recently shown in an animal model.52 Epidermolysis bullosa acquisita is refractory to many immunosuppressive treatments. At present, no controlled clinical therapeutic studies exist for this disease, to our knowledge. In a recent systematic review of the literature, it was stated that definitive conclusions for the treatment of EBA53 cannot be drawn. The bullous pemphigoid–like inflammatory presentation of EBA seems to be more responsive to immunosuppression than the classic mechanobullous form,1 which has been reported to be refractory to systemic corticosteroids, oral azathioprine, methotrexate, and cyclophosphamide.9,54 Immunoadsorption has increasingly been used to decrease autoantibody levels in autoimmune disorders refractory to established immunosuppressive agents. Reports on the successful use of IA in systemic lupus erythematosus,14 Sjögren syndrome,13 severe bullous pemphigoid,16 and diseases of the pemphigus group15,55 have been published. For patients with severe pemphigus, a treatment protocol was recently published that induced prolonged clinical improvement of mucosal and cutaneous lesions and was accompanied by a dramatic reduction in serum IgG autoantibodies.51 Therefore, IA may be an efficient technique to rapidly remove circulating autoantibodies as the pathogenic agent in EBA. In the previous study,51 the use of an adsorber system (Globaffin) as an adjuvant treatment in 4 patients with pemphigus vulgaris and in 2 patients with pemphigus foliaceus was investigated. The peptide matrix of the adsorber binds to IgG and circulating immune complexes with high affinity and with lower affinity to IgA and IgM. Its binding characteristics are similar to those of protein A Sepharose.56 In the IA study,51 all 6 treated patients tolerated IA well and showed no symptoms of allergic reactions or cardiovascular dysfunction; the adsorber system effectively reduced anti–desmoglein 1 and desmoglein 3–reactive IgG by a mean of 50% to 70% per IA cycle consisting of 4 consecutive IA treatments. In an earlier study by Schmidt et al,55 5 patients with severe pemphigus were treated with IA using Staphylococcus aureus protein A columns. The treatment schedule consisted of IA treatment on 3 consecutive days; a fourth IA treatment was given on day 8, followed by up to 19 IA treatments during intervals of 1 to 4 weeks. Protein A IA effectively reduced anti–desmoglein 1 and desmoglein 3 IgG by a mean of 76%, correlating with a good clinical response in all patients.55 In a study by Lüftl et al,15 a tryptophan-linked polyvinylalcohol adsorber system was applied. Three patients with acute onset and 6 patients with recalcitrant pemphigus received 2 IA treatments each during 3 days, followed by an intravenous prednisolone pulse. The tryptophan-linked polyvinylalcohol adsorber led to a 30% decrease in desmoglein-reactive autoantibodies, which was accompanied by significant clinical improvement. Findings from these studies, as well as other case reports,57,58 suggest that IA is an efficacious and safe treatment for severe and therapy-resistant bullous autoimmune disorders.

In contrast to the IA protocols by Schmidt et al55 and by Frost et al,58 we do not favor frequent and successive use of IA. In our view, IA represents an efficacious method that rapidly removes circulating autoantibodies as the pathogenic agent in blistering autoimmune disorders like pemphigus or EBA. However, for sustained remission of the disease, sufficient immunosuppressive treatment after IA is important to prevent rebounding autoantibody synthesis by autoreactive B cells and long-lived plasma cells. To achieve long-term arrest of production of pathogenic antibodies, we administer rituximab according to an established protocol previously used in patients with pemphigus and the inflammatory form of EBA.3341,43,4549

Rituximab is administered by slow infusion during several hours. The standard regimen consists of 4 infusions (1 course) of rituximab with a dose of 375 mg/m2 at weekly intervals following premedication with an analgesic (such as acetaminophen) and an antihistamine or a corticosteroid. Systemic infusion reactions are frequently observed in patients with lymphoma, probably owing to a high load of abnormal B cells.59,60 Approximately 50% of patients treated with rituximab experience infusion-related adverse reactions, including cytokine release syndrome. These are accompanied by hypotension and bronchospasm in about 10% of patients. Severe cytokine release syndrome has been reported to occur mostly in patients with lymphoma60,61; however, a few patients have been described who were treated for indications other than lymphoma. A common feature was development of severe reactions during the first infusion, particularly dyspnoe, hypoxia, or severe bronchospasm.60 In autoimmune diseases, these adverse reactions seem to be less of a problem. A pricking sensation in the throat that occurs 30 to 60 minutes after the start of the infusion is a common feature and has been interpreted as penetration of rituximab into the Waldeyer ring.21 The absence of normal B cells for several months has not been associated with a significant increase in infectious risk.62 Total IgG levels and antitetanus titers are unaffected, whereas IgM levels are reduced to the lower end of the normal range with rituximab therapy.63

In patients with pemphigus treated with rituximab, treatment is generally well tolerated. Most adverse reactions occur during the first infusion and consist of occasional dyspnea, nausea, fever, chills, and hypotension.60 These reactions usually diminish with subsequent infusions and can be well controlled by premedication with acetaminophen and antihistamines. However, case reports exist of patients with pemphigus or other autoimmune bullous diseases that describe serious adverse effects, such as pneumonia, septic arthritis,33 sepsis,40 fatal Pneumocystis carinii pneumonia,35 deep venous thrombosis,50 and hypogammaglobulinemia.43

Based on previous observations in patients with recalcitrant pemphigus vulgaris,51 the suppression of de novo autoantibody production may be critical for a prolonged clinical remission of EBA. In support of this, patient 2 in our study with mechanobullous EBA who was recalcitrant to various immunosuppressive treatments (Figure 2) showed a remarkable clinical response to combined treatment with IA and rituximab. Although reaching complete B-cell depletion, patient 1 did not similarly benefit from the combined treatment, but we believe that both treatments contributed to the patient's improvement. In the short term, IA decreased the pathologic circulating autoantibodies, and long-term treatment with rituximab led to clinical remission. We believe that the lack of detectable antibodies to collagen VII in patient 2 reflects the excellent clinical response to combined treatment with IA and rituximab and indicates that spontaneous remission was not responsible for the improvement of EBA.

To our knowledge, this is the first publication on successful therapeutic control of the mechanobullous form of EBA by combined treatment with IA and rituximab. It is known from the literature that the NC1 domain of type VII collagen constitutes the major immunodominant epitopes that are targeted by most EBA serum samples.6466 In recent studies,52,67 the pathogenicity of autoantibodies to the NC1 domain of collagen VII was shown in animal models. Therefore, it is likely that circulating antibodies against the NC1 domain of collagen VII may correlate with the disease activity of patients with EBA. Based on the good response in patient 2 and the stable disease in patient 1, the combination of IA and rituximab treatment may be a novel therapeutic option for patients with severe long-standing refractory EBA.

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Article Information

Correspondence: Andrea Niedermeier, MD, Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen und Marburg, Philipps-Universität, Deutschhausstrasse 9, 35037 Marburg, Germany (a-niedermeier@web.de).

Financial Disclosure: None reported.

Accepted for Publication: July 19, 2006.

Author Contributions: Dr Niedermeier had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Niedermeier, Eming, Pfütze, and Hertl. Acquisition of data: Niedermeier, Eming, Pfütze, and Happel. Analysis and interpretation of data: Niedermeier, Neumann, Happel, Reich, and Hertl. Drafting of the manuscript: Niedermeier, Pfütze, and Hertl. Critical revision of the manuscript for important intellectual content: Niedermeier, Eming, Neumann, Happel, Reich, and Hertl. Obtained funding: Hertl. Administrative, technical, and material support: Niedermeier, Eming, Pfütze, Happel, and Reich. Study supervision: Neumann and Hertl.

Funding/Support: This study was supported in part by grants 2004.120.1 from the Wilhelm-Sander-Stiftung (Dr Hertl) and He1602/8-1; 82 from the Deutsche Forschungsgemeinschaft (Dr Hertl).

References
1.
Hallel-Halevy  DNadelman  CChen  MWoodley  DT Epidermolysis bullosa acquisita: update and review. Clin Dermatol 2001;19712- 718
PubMedArticle
2.
Stewart  MIWoodley  DTBriggaman  RA Epidermolysis bullosa acquisita and associated symptomatic esophageal webs. Arch Dermatol 1991;127373- 377
PubMedArticle
3.
Harman  KEWhittam  LRWakelin  SHBlack  MM Severe, refractory epidermolysis bullosa acquisita complicated by an oesophageal stricture responding to intravenous immune globulin. Br J Dermatol 1998;1391126- 1127
PubMedArticle
4.
Khatri  MLBenghazeil  MShafi  M Epidermolysis bullosa acquisita responsive to cyclosporin therapy. J Eur Acad Dermatol Venereol 2001;15182- 184
PubMedArticle
5.
Burger  JGmur  JBruckner-Tuderman  L Epidermolysis bullosa acquisita, a rare late complication of allogeneic bone marrow transplantation? Bone Marrow Transplant 1992;9139- 141
PubMed
6.
Maize  JC  JrCohen  JB Cyclosporine controls epidermolysis bullosa acquisita co-occurring with acquired factor VIII deficiency. Int J Dermatol 2005;44692- 694
PubMedArticle
7.
Cunningham  BBKirchmann  TTWoodley  D Colchicine for epidermolysis bullosa acquisita. J Am Acad Dermatol 1996;34781- 784
PubMedArticle
8.
Arora  KPSachdeva  BSingh  NBhattacharya  SN Remission of recalcitrant epidermolysis bullosa acquisita (EBA) with colchicine monotherapy. J Dermatol 2005;32114- 119
PubMed
9.
Kofler  HWambacher-Gasser  BTopar  G  et al.  Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita. J Am Acad Dermatol 1997;36331- 335
PubMedArticle
10.
Engineer  LAhmed  AR Emerging treatment for epidermolysis bullosa acquisita. J Am Acad Dermatol 2001;44818- 828
PubMedArticle
11.
Gordon  KBChan  LSWoodley  DT Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy. Br J Dermatol 1997;136415- 420
PubMedArticle
12.
Bloching  MDippel  EJovanovic  SHess  MZouboulis  CC Manifestation der Epidermolysis bullosa acquisita (EBA) im HNO-Gebiet. HNO 1999;47497- 501
PubMedArticle
13.
Bohm  MDorner  TKnebel  FBruns  AJochmann  NBaumann  G Longlasting effects of immunoadsorption in severe Sjogren's syndrome [letter]. Ann Rheum Dis 2004;63214- 215
PubMedArticle
14.
Stummvoll  GHAringer  MSmolen  JS  et al.  IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study. Ann Rheum Dis 2005;641015- 1021
PubMedArticle
15.
Luftl  MStauber  AMainka  AKlingel  RSchuler  GHertl  M Successful removal of pathogenic autoantibodies in pemphigus by immunoadsorption with a tryptophan-linked polyvinylalcohol adsorber. Br J Dermatol 2003;149598- 605
PubMedArticle
16.
Herrero-Gonzalez  JESitaru  CKlinker  EBrocker  EBZillikens  D Successful adjuvant treatment of severe bullous pemphigoid by tryptophan immunoadsorption. Clin Exp Dermatol 2005;30519- 522
PubMedArticle
17.
Tedder  TFEngel  P CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today 1994;15450- 454
PubMedArticle
18.
Gottenberg  JEGuillevin  LLambotte  O  et al.  Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases. Ann Rheum Dis 2005;64913- 920
PubMedArticle
19.
Koulova  LAlexandrescu  DDutcher  JPO’Boyle  KPEapen  SWiernik  PH Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): report of three cases. Am J Hematol 2005;7849- 54
PubMedArticle
20.
Shanafelt  TDMadueme  HLWolf  RCTefferi  A Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc 2003;781340- 1346
PubMedArticle
21.
Edwards  JCLeandro  MJCambridge  G B lymphocyte depletion therapy with rituximab in rheumatoid arthritis. Rheum Dis Clin North Am 2004;30393- 403
PubMedArticle
22.
Looney  RJAnolik  JSanz  I Treatment of SLE with anti-CD20 monoclonal antibody. Curr Dir Autoimmun 2005;8193- 205
PubMed
23.
Eisenberg  R SLE: rituximab in lupus. Arthritis Res Ther 2003;5157- 159
PubMedArticle
24.
Wylam  MEAnderson  PMKuntz  NLRodriguez  V Successful treatment of refractory myasthenia gravis using rituximab: a pediatric case report. J Pediatr 2003;143674- 677
PubMedArticle
25.
Sneller  MC Rituximab and Wegener's granulomatosis: are B cells a target in vasculitis treatment? Arthritis Rheum 2005;521- 5
PubMedArticle
26.
Kallenbach  MDuan  HRing  T Rituximab induced remission in a patient with Wegener's granulomatosis. Nephron Clin Pract 2005;99c92- c96
PubMedArticle
27.
Ferraro  AJDay  CJDrayson  MTSavage  CO Effective therapeutic use of rituximab in refractory Wegener's granulomatosis. Nephrol Dial Transplant 2005;20622- 625
PubMedArticle
28.
Ahmadi-Simab  KLamprecht  PNolle  BAi  MGross  WL Successful treatment of refractory anterior scleritis in primary Sjogren's syndrome with rituximab. Ann Rheum Dis 2005;641087- 1088
PubMedArticle
29.
Levine  TD Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 2005;52601- 607
PubMedArticle
30.
Heizmann  MItin  PWernli  MBorradori  LBargetzi  MJ Successful treatment of paraneoplastic pemphigus in follicular NHL with rituximab: report of a case and review of treatment for paraneoplastic pemphigus in NHL and CLL. Am J Hematol 2001;66142- 144
PubMedArticle
31.
Borradori  LLombardi  TSamson  JGirardet  CSaurat  JHHugli  A Anti-CD20 monoclonal antibody (rituximab) for refractory erosive stomatitis secondary to CD20+ follicular lymphoma–associated paraneoplastic pemphigus. Arch Dermatol 2001;137269- 272
PubMed
32.
Schadlow  MBAnhalt  GJSinha  AA Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus. J Drugs Dermatol 2003;2564- 567
PubMed
33.
Dupuy  AViguier  MBedane  C  et al.  Treatment of refractory pemphigus vulgaris with rituximab (anti-CD20 monoclonal antibody). Arch Dermatol 2004;14091- 96
PubMedArticle
34.
Wenzel  JBauer  RBieber  TTuting  T Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple immunosuppressants. Acta Derm Venereol 2005;85185- 186
PubMed
35.
Morrison  LH Therapy of refractory pemphigus vulgaris with monoclonal anti-CD20 antibody (rituximab). J Am Acad Dermatol 2004;51817- 819
PubMedArticle
36.
Goebeler  MHerzog  SBrocker  EBZillikens  D Rapid response of treatment-resistant pemphigus foliaceus to the anti-CD20 antibody rituximab. Br J Dermatol 2003;149899- 901
PubMedArticle
37.
Virgolini  LMarzocchi  V Anti-CD20 monoclonal antibody (rituximab) in the treatment of autoimmune diseases: successful result in refractory pemphigus vulgaris: report of a case. Haematologica 2003;88ELT24
PubMed
38.
Cooper  HLHealy  ETheaker  JMFriedmann  PS Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (rituximab). Clin Exp Dermatol 2003;28366- 368
PubMedArticle
39.
Herrmann  GHunzelmann  NEngert  A Treatment of pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab). Br J Dermatol 2003;148602- 603
PubMedArticle
40.
Salopek  TGLogsetty  STredget  EE Anti-CD20 chimeric monoclonal antibody (rituximab) for the treatment of recalcitrant, life-threatening pemphigus vulgaris with implications in the pathogenesis of the disorder. J Am Acad Dermatol 2002;47785- 788
PubMedArticle
41.
Arin  MJEngert  AKrieg  THunzelmann  N Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus. Br J Dermatol 2005;153620- 625
PubMedArticle
42.
Belgi  ASAzeez  MHoyle  CWilliams  RE Response of pemphigus vulgaris to anti-CD20 antibody therapy (rituximab) may be delayed [letter]. Clin Exp Dermatol 2006;31143
PubMedArticle
43.
Schmidt  EHerzog  SBrocker  EBZillikens  DGoebeler  M Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab. Br J Dermatol 2005;153449- 451
PubMedArticle
44.
Kong  HHProse  NSWare  REHall  RP  III Successful treatment of refractory childhood pemphigus vulgaris with anti-CD20 monoclonal antibody (rituximab). Pediatr Dermatol 2005;22461- 464
PubMedArticle
45.
Niedermeier  AWörl  PBarth  SSchuler  GHertl  M Delayed response of oral pemphigus vulgaris to rituximab treatment. Eur J Dermatol 2006;16266- 270
PubMed
46.
Esposito  MCapriotti  EGiunta  ABianchi  LChimenti  S Long-lasting remission of pemphigus vulgaris treated with rituximab. Acta Derm Venereol 2006;8687- 89
PubMed
47.
Pitarch  GSanchez-Carazo  JLPardo  JTorrijos  ARoche  EFortea  JM Treatment of severe refractory pemphigus vulgaris with rituximab [in Spanish]. Actas Dermosifiliogr 2006;9748- 51
PubMedArticle
48.
Barnadas  MRoe  EBrunet  S  et al.  Therapy of paraneoplastic pemphigus with rituximab: a case report and review of literature. J Eur Acad Dermatol Venereol 2006;2069- 74
PubMedArticle
49.
Cecchi  RGasperini  U Severe pemphigus vulgaris treated with rituximab (Mabthera). J Dermatol 2005;32862- 864
PubMed
50.
Schmidt  EBenoit  SBrocker  EBZillikens  DGoebeler  M Successful adjuvant treatment of recalcitrant epidermolysis bullosa acquisita with anti-CD20 antibody rituximab. Arch Dermatol 2006;142147- 150
PubMed
51.
Eming  RRech  JBarth  S  et al.  Prolonged clinical remission of patients with severe pemphigus upon rapid removal of desmoglein-reactive autoantibodies by immunoadsorption. Dermatology 2006;212177- 187
PubMedArticle
52.
Sitaru  CMihai  SOtto  C  et al.  Induction of dermal-epidermal separation in mice by passive transfer of antibodies specific to type VII collagen. J Clin Invest 2005;115870- 878
PubMedArticle
53.
Kirtschig  GMurrell  DWojnarowska  FKhumalo  N Interventions for mucous membrane pemphigoid/cicatricial pemphigoid and epidermolysis bullosa acquisita: a systematic literature review. Arch Dermatol 2002;138380- 384
PubMed
54.
Chen  MHallel-Halevy  DNadelman  CWoodley  D Epidermolysis bullosa acquisita. Hertl  Med.Autoimmune Diseases of the Skin. Wien, Germany Springer-Verlag2005;109- 132
55.
Schmidt  EKlinker  EOpitz  A  et al.  Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus. Br J Dermatol 2003;1481222- 1229
PubMedArticle
56.
Ronspeck  WBrinckmann  REgner  R  et al.  Peptide based adsorbers for therapeutic immunoadsorption. Ther Apher Dial 2003;791- 97
PubMedArticle
57.
Ogata  KYasuda  KMatsushita  MKodama  H Successful treatment of adolescent pemphigus vulgaris by immunoadsorption method. J Dermatol 1999;26236- 239
PubMed
58.
Frost  NMesser  GFierlbeck  GRisler  TLytton  SD Treatment of pemphigus vulgaris with protein A immunoadsorption: case report of long-term history showing favorable outcome. Ann N Y Acad Sci 2005;1051591- 596
PubMedArticle
59.
Plosker  GLFiggitt  DP Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Drugs 2003;63803- 843
PubMedArticle
60.
Arin  MJHunzelmann  N Anti–B-cell–directed immunotherapy (rituximab) in the treatment of refractory pemphigus: an update. Eur J Dermatol 2005;15224- 230
PubMed
61.
Winkler  UJensen  MManzke  OSchultz  HDihl  VEngert  A Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999;942217- 2224
PubMed
62.
McLaughlin  PGrillo-Lopez  AJLink  BK  et al.  Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;162825- 2833
PubMed
63.
Looney  RJ B cell–targeted therapy in diseases other than rheumatoid arthritis. J Rheumatol Suppl 2005;7325- 30
PubMed
64.
Gammon  WRMurrell  DFJenison  MW  et al.  Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain. J Invest Dermatol 1993;100618- 622
PubMedArticle
65.
Lapiere  JCWoodley  DTParente  MG  et al.  Epitope mapping of type VII collagen: identification of discrete peptide sequences recognized by sera from patients with acquired epidermolysis bullosa. J Clin Invest 1993;921831- 1839
PubMedArticle
66.
Jones  DAHunt  SW  IIIPrisayanh  PSBriggaman  RAGammon  WR Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the noncollagenous (NC1) domain. J Invest Dermatol 1995;104231- 235
PubMedArticle
67.
Woodley  DTChang  CSaadat  PRam  RLiu  ZChen  M Evidence that anti–type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita. J Invest Dermatol 2005;124958- 964
PubMedArticle
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