Treatment Of Bullous Pemphigoid Research Articles

Potent topical and/or systemic corticosteroids are first-line treatment of bullous pemphigoid

Potent topical and/or systemic corticosteroids are first-line treatment of bullous pemphigoid

Epidural abscess as a side effect of an immunosuppressive therapy treatment for bullous pemphigoid

Epidural abscess as a side effect of an immunosuppressive therapy treatment for bullous pemphigoid

Fallberichte

Bullous pemphigoid (BP) is a cutaneous autoimmune disease predominantly affecting older patients which can cause death either due to severe clinical manifestations or due to the side effects of systemic immunosuppressive treatment. Topical treatment with corticosteroids is an established alternative to systemic treatment. However, prolonged application is accompanied by side effects such as skin atrophy. Recently, the immunomodulatory calcineurin antagonists tacrolimus and pimecrolimus have been introduced for topical treatment of skin diseases. Tacrolimus has been reported to be effective in several inflammatory skin disorders such as atopic dermatitis, psoriasis, lichen planus, lupus erythematosus and pyoderma gangraenosum. Efficacy has also been described in the topical treatment of BP in some cases. Here we present the case of a 89 year old patient with BP. He was treated with 0.1% tacrolimus ointment, which was able to control the disease. We briefly review the literature and discuss the potential role of tacrolimus as a novel option for the topical treatment of BP.

Correlation of clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA kit in bullous pemphigoid

Titres of circulating autoantibodies detected by indirect immunofluorescence (IIF) have been used for the diagnosis and evaluation of disease activity in bullous pemphigoid (BP). In BP, the major pathogenic epitope is known to be the non-collagenous extracellular domain (NC16A) of the 180-kDa transmembrane hemidesmosomal protein (BPAG2). Recently, an enzyme-linked immunosorbent assay (ELISA) kit using the NC16A domain recombinant protein (BP180 ELISA kit) has become commercially available to measure the quantities of pathogenic autoantibodies circulating in BP patients. To investigate the correlation of clinical severity and ELISA indices in BP. Fourteen patients with a typical form of BP and one refractory BP patient who died despite extensive treatment were included in this study. Antibody titres in sera from these patients were measured using BP180 ELISA kit and an analysis of ELISA indices with disease activity was performed. ELISA indices were significantly reduced after successful therapy, although IIF titres did not always show apparent correlations. In the patient with refractory BP, ELISA indices also showed a good correlation with disease course. ELISA indices measured using the BP180 ELISA kit were well correlated with the disease activity. This commercially available kit more closely followed disease activities than the IIF titres. The BP ELISA system may be a useful tool to evaluate the disease activity and to assess the effectiveness of the treatment of BP.

Topical class I corticosteroids in 10 patients with bullous pemphigoid: correlation of the outcome with the severity degree of the disease and review of the literature.

Treatment of bullous pemphigoid (BP) with systemic immunosuppressive agents, in particular with systemic corticosteroids, has many long-term side-effects. A dozen reports were published regarding the efficacy of topical corticosteroids in the treatment of bullous pemphigoid. To evaluate the efficacy of potent class I topical corticosteroids in relation to the affected body surface area (BSA) in patients with bullous pemphigoid and to review the literature. An open prospective trial with 10 patients with BP with measurement of the affected BSA. Treatment protocol consisted of three steps: potent class I topical corticosteroid treatment, systemic tetracyclines and systemic corticosteroids. Follow-up period was between 24 and 72 months. Our study suggests a correlation between the success rate of topical corticosteroid treatment and the body surface area initially affected: all patients with an affected BSA of less than 20% healed with topical treatment only. The patients with more than 40% affected BSA needed systemic treatment with steroids. Topical class I corticosteroids seem to be effective in healing lesions of BP, especially if less than 20% of the BSA is affected. This study comprises only 10 patients, making further studies necessary to draw definite conclusions.

Management of Bullous Pemphigoid

In 1953, Lever differentiated bullous pemphigoid from autoimmune pemphigus. The natural course of bullous pemphigoid is relatively benign, with a disease-related mortality rate of 24% compared with around 70% in pemphigus. In spite of the introduction of systemic corticosteroids, the mortality rates in bullous pemphigoid have generally not improved and vary between 0% and 40%. Higher doses of systemic corticosteroids seem to be associated with higher mortality rates, which led to the addition of corticosteroid-sparing agents to the treatment of bullous pemphigoid. However, many of these modalities are also accompanied by severe adverse effects and have not led to a significant decrease in the mortality rate. In recent years, there has been a move toward less toxic treatment options for a disease that is usually self-limited. A systematic review of the literature found that treatment with lower doses of systemic corticosteroids and potent topical corticosteroids is effective and accompanied by less serious adverse effects, including death. No benefit of the addition of plasmapheresis or azathioprine to systemic corticosteroids has been shown. The treatment of bullous pemphigoid with tetracyclines and niacinamide (nicotinamide) is effective and accompanied by less serious adverse effects. However, more randomized controlled trials are needed to confirm these results and to determine the best treatment for bullous pemphigoid.

Role of intravenous immunoglobulin in the treatment of bullous pemphigoid: Analysis of current data

Background: Conventional therapy of severe bullous pemphigoid (BP) relies on the use of high-dose systemic corticosteroids with or without adjuvants, notably immunosuppressive agents. This approach can result in debilitating and potentially fatal side effects, hence the need to explore alternative therapies. Intravenous immunoglobulin (IVIg) therapy is emerging as one possibility. Objective: Our purpose was to determine whether any preliminary conclusion can be drawn about the potential for the use of IVIg to treat patients with severe BP. Methods: A literature search was done to identify reports, in English-language peer-reviewed journals, on the use of IVIg to treat patients with BP. Reports were examined for information on disease duration, severity, therapies used before and after IVIg, dose and frequency of IVIg administration, and its immediate and long-term effects. Results: Data on treatment of 17 patients indicated that 12 patients (70%) experienced a beneficial clinical response to IVIg. In 5 patients (30%) no clinical benefit was observed. A minimum dose of 2 g/kg per cycle at monthly intervals for 3 months has been the most common approach. However, this should not be perceived as a “standard dose” at the present time. In some patients the use of IVIg appears to permit a systemic corticosteroid-sparing effect. Longer use has achieved sustained clinical remission in some patients. Lack of response was observed in patients who received low-dose IVIg or who received a single infusion only. Minimal side effects in the form of headaches and nausea and vomiting were observed in some patients. Conclusion: The present experience consists only of open uncontrolled trials in a few patients and does not allow for definitive conclusions. However, at this time IVIg appears to be a promising agent for the treatment of BP, especially for patients who do not respond to conventional therapy. Adequate doses for longer periods may be required to induce and maintain sustained clinical remissions. Large-scale controlled studies with defined entry criteria, objectives, end points, and long-term follow-up are necessary to determine the specific role of IVIg in the overall management of BP. (J Am Acad Dermatol 10.1067/mjd.2000.112288)

The use of chlorambucil with prednisone in the treatment of pemphigus

Background: Chlorambucil is an alkylating agent that preferentially affects B cells over T cells and has been shown to be effective in the treatment of bullous pemphigoid. Objective: Our purpose was to determine whether chlorambucil is effective in the treatment of pemphigus. Methods: We retrospectively reviewed the medical records of 9 patients with pemphigus (7 with pemphigus vulgaris and 2 with pemphigus foliaceus) in whom therapy with other immunosuppressive regimens failed and who were subsequently treated with chlorambucil and prednisone. Results: There was clinical improvement in 6 of 9 patients and a decrease in indirect immunofluoresent antibody titers in 3 of the 5 patients who had titers drawn before and after treatment with chlorambucil. Three of the 9 patients failed treatment with chlorambucil, as evidenced by lack of improvement of lesions. Conclusion: Chlorambucil may be a potential adjuvant therapeutic approach with steroid-sparing effects in patients with pemphigus who have failed treatment with other immunosuppressive regimens. (J Am Acad Dermatol 2000;42:85-8.)

Evaluation of the safety and efficacy of potential topical corticosteroid in the treatment of bullous pemphigoid

Evaluation of the safety and efficacy of potential topical corticosteroid in the treatment of bullous pemphigoid

Tetracycline and nicotinamide in treatment of bullous pemphigoid

Tetracycline and nicotinamide in treatment of bullous pemphigoid

Prospective study of treatment of bullous pemphigoid with class I topical corticosteroid

Prospective study of treatment of bullous pemphigoid with class I topical corticosteroid

Bullous pemphigoid after prosthetic vascular graft placement

The use of prosthetic material to create vascular access in patients undergoing hemodialysis is a commonly performed procedure in the United States. 1 Hirth RA Turenne MN Woods JD Young EW Port FK Pauly MV et al. Predictors of type of vascular access in hemodialysis patients. JAMA. 1996; 276: 1303-1308 Crossref PubMed Scopus (0) Google Scholar Infection, either in the immediate postoperative period or as a late sequela, continues to be a serious complication of this operation. The determination of whether a prosthetic vascular graft is infected can, at times, be challenging. We describe a patient in whom bullous pemphigoid developed after prosthetic graft placement. Although this patient's presentation was indistinguishable from that of a prosthetic graft infection, the treatment of bullous pemphigoid and that of graft infection differ significantly.

A Highly Sensitive Enzyme-Linked Immunosorbent Assay for the Detection of Circulating Anti-BP180 Autoantibodies in Patients with Bullous Pemphigoid

The BP180 antigen, a component of the epidermal anchoring complex, has been identified as one of the major antigenic targets of autoantibodies associated with the blistering skin disease, bullous pemphigoid. Our research group has recently demonstrated that reactivity of bullous pemphigoid autoantibodies to the BP180 ectodomain is almost entirely restricted to a set of four antigenic sites clustered within the membrane-proximal noncollagenous stretch (NC16A). Using a passive transfer mouse model, antibodies to the corresponding noncollagenous region of murine BP180 were shown to trigger an inflammatory subepidermal blistering disease that closely mimics bullous pemphigoid. We now report the development of an enzyme-linked immunoabsorbent assay system that is extremely sensitive in detecting disease-specific autoantibodies in the sera of bullous pemphigoid patients. The target antigen in this assay is a recombinant form of the BP180 NC16A domain that contains all four of the well-defined bullous pemphigoid-associated antigenic sites. Of 50 randomly selected bullous pemphigoid sera tested, 47 (94%) were positive in this assay, whereas no specific reactivity was detected in any of the 107 controls. Interestingly, all three of the bullous pemphigoid sera that were negative in this assay had been obtained from patients who were already undergoing treatment. The NC16A enzyme-linked immunosorbent assay is more sensitive than any of the standard techniques for detecting circulating bullous pemphigoid autoantibodies, including other enzyme-linked immunosorbent assays, immunoblotting, and indirect immunofluorescence. Finally, the NC16A enzyme-linked immunosorbent assay provides immunologic information that cannot be obtained from direct immunofluorescence studies of skin biopsies, and that may well be relevant in the diagnosis and treatment of bullous pemphigoid.

Treatment of bullous pemphigoid with dapsone: Retrospective study of thirty-six cases

Bullous pemphigoid (BP) 1 is usually responsive to high-dose systemic steroid therapy. 2 However, side effects from steroid use can often be more severe than the disease itself. 3 This has lea to the search for alternative treatments. 4-9 Dapsone has been widely used because of its antiinflammatory effects 1° and is effective in dermatitis herpetiformis (DH) 11 and linear IgA disease. 12 Its effects are less certain in epidermolysis bullosa acquisita and blistering diseases of the BP group. I3 We therefore undertook a study of the effect of dapsone on BP.

Nicotinamide and Tetracycline Therapy of Bullous Pemphigoid

The combination of nicotinamide and tetracycline has been anecdotally reported to be effective in the treatment of bullous pemphigoid. We conducted a randomized, open-labeled trial comparing the combination of 500 mg of nicotinamide, three times daily, and 500 mg of tetracycline four times daily, with prednisone therapy in 20 patients with bullous pemphigoid. The study was divided between an 8-week acute phase with fixed drug dosages and a 10-month follow-up phase in which study medications were tapered based on patient response. Eighteen of 20 patients enrolled in the study were treated, two patients were unavailable for follow-up. Twelve patients were treated with the combination of nicotinamide and tetracycline and six patients were treated with prednisone. There were five complete responses, five partial responses, one nonresponder, and one patient with disease progression in the nicotinamide and tetracycline group compared with one complete response and five partial responses in the prednisone group. There were no statistically significant differences in response parameters between the two groups. All five patients in the nicotinamide and tetracycline group receiving long-term follow-up remained disease free during medication tapering, while three patients in the prednisone group had repeated disease flare-ups with steroid tapering. Adverse effects in the nicotinamide and tetracycline group included gastrointestinal upset (two patients) and transient renal failure (one patient). In the prednisone group, there was one occurrence each of hypertension, erosive gastritis, multiple decubitus ulcers, osteomyelitis, deep venous thrombosis, and death related to sepsis. Two patients required insulin therapy for hyperglycemia. The combination of nicotinamide and tetracycline appears to be a useful alternative to systemic steroids in the treatment of bullous pemphigoid.

Controlled Trial of Azathioprine and Plasma Exchange in Addition to Prednisolone in the Treatment of Bullous Pemphigoid

Bullous pemphigoid is usually treated with systemic corticosteroids. Side effects are common in elderly patients, justifying the search for adjuvant therapy. This randomized, multicentric unblind study was designed to assess the efficacy of azathioprine or plasma exchange when added to conventional doses of prednisolone. One hundred patients with active disease entered the study. They were randomly allocated to receive 28 days of treatment with oral prednisolone sodium metasulfobenzoate (1 mg/kg per day) either alone or in combination with oral azathioprine (100 to 150 mg/d) or four large-volume plasma exchanges. After 28 days, the prednisolone doses were progressively decreased according to the same strict regimen in the three groups (in combination with oral azathioprine in group 2). The clinical results were evaluable in 98 of the 100 patients included in the study. There was no appreciable difference in the percentages of complete remission of the disease in the three therapeutic groups at 28 days (71%, 80%, and 71%, respectively) or at 6 months (42%, 39%, and 29%, respectively). Severe complications were more often observed among patients receiving azathioprine. At 6 months, 14 of 98 patients had died, without any differences noted among the three study groups. We conclude that neither azathioprine nor plasma exchange is effective enough to be used routinely as an adjuvant to corticosteroids in the management of bullous pemphigoid.

Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid

Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid

Adjuvant Therapy for Bullous Pemphigoid: No Benefit

Classic teaching recommends the addition of an immunosuppressive agent, such as azathioprine, to systemic corticosteroids as the initial treatment of bullous pemphigoid. To date only two controlled studies have looked at adjuvant therapy in the treatment of this disease: one found azathioprine to be steroid-sparing, and the other found the same benefit with plasma exchange. However, neither study was …

The use of chlorambucil in the treatment of bullous pemphigoid

Twenty-six patients with bullous pemphigoid were treated with a combination of chlorambucil and a systemic corticosteroid; 23 completed treatment. The corticosteroid requirement during therapy was reduced by 50% compared with that reported for corticosteroid and azathioprine, and the mean total duration of therapy was only 5 months. The side effects of chlorambucil have not been significant, but in 30% of the patients a mild transient thrombocytopenia developed. In one patient a more significant marrow suppression developed. Despite complete recovery, chlorambucil treatment was discontinued in this patient. There was no evidence that either the disease treated in this way or the treatment itself had an adverse effect on survival during therapy or for the mean follow-up period of 36 months. Patients who responded less well to treatment tended to be younger, and their disease was more severe in that a higher dosage was required for initial control. Patients in whom thrombocytopenia developed were older and had lower pretreatment platelet levels.

Vesiculo‐bullous mucocutaneous disease: benign mucous membrane and bullous pemphigoid

Bullous pemphigoid (BP) and benign mucous membrane pemphigoid (BMMP) are autoimmune diseases characterised by subepithelial bulla formation and showing substantial overlap in clinical signs and symptoms. BP principally involves skin and BMMP the oral mucosa and eyes. The gingiva are affected in 90% of cases of BMMP and buccal mucosa and palate in up to 30%. Lesions may heal with scarring. Extension into the pharynx and esophagus causes sore throat and dysphagia. Severe ocular involvement may cause blindness. Bulla formation is attributed to complement activation, following IgG binding to the basement membrane zone, with subsequent polymorphonuclear leukocyte accumulation. The target antigen in BP is a 180-230 kD protein associated with the basilar membrane of basal keratinocytes. The gene encoding the BP antigen has been partially cloned. It is likely that the same antigen is involved in BMMP, but the mechanism of scarring is not understood. Treatment of BP and BMMP includes systemic steroid and azathioprine therapy and topical steroids.