This chronic blistering eruption is characterized by tense bullae, ranging up to several centimeters, occurring on erythematous skin. Occasionally, there are urticarial non-bullous lesions which may precede the blisters. This is a disease of the elderly and usually occurs on the lower abdomen, groin, and on the flexor surfaces of the arms and legs. The oral cavity is involved in 10-40%. There are periods of remissions and exacerbations but death is rare. There are several clinical variants described in the outline.
The pathologist must differentiate the bullous changes from other bullous disorders with eosinophils including arthropod bites, drug eruptions, dermatitis herpetiformis, and parasite infections. The most difficult distinction may be in the early urticarial, non-bullous phase where only eosinophilic spongiosis may be present. In these cases, distinction from early pemphigus vulgaris is critical. Direct immunofluorescence may be helpful.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Approximate incidence of 10 cases per million population.1
DISEASE ASSOCIATIONS CHARACTERIZATION Autoimmune diseases
Systemic lupus erythematosus
Primary biliary cirrhosis
PATHOGENESIS CHARACTERIZATION IgG Autoantibody
Directed against the bullous pemphigoid antigen present within the lamina lucida and hemidesmosomes of the basal keratinocytes
The antigen is composed of a 230 kd protein (BPAg1) within the hemidesmosomes and a transmembranous 180 kd protein (BPAg2)
Binding of the antibody leads to complement activation and recruitment of eosinophils and neutrophils.
CHARACTERIZATION General VARIANTS CHILDHOOD
Clin Exp Dermatol 1993;18:483-5.
J Am Acad Dermatol 1994;30:884-8.
Int J Dermatol 1991;30:339-42
J Am Acad Dermatol 1988;19:366-7.
The major clinical, histopathologic, and immunologic features of childhood BP are considered indistinguishable from adult BP
Mucous membrane involvement was more frequent than in the adult form and all infants 1 year of age or younger had marked palmoplantar and facial involvement
Systemic corticosteroid therapy (prednisolone 1-2 mg/kg per day) is the treatment of choice in childhood BP
- J Am Acad Dermatol. 2008 Jan;58(1):41-8. Abstract quote
BACKGROUND: Recent cases of infants with bullous pemphigoid (BP) prompted us to explore the clinical and laboratory features of childhood BP.
OBJECTIVES: We sought to explore the characteristics of infantile BP and compare them with childhood BP.
METHODS: All new consecutive cases of infantile BP referred to dermatologic departments in Israel during 2004 to 2006 were retrospectively reviewed. All reported cases in the English- and foreign-language medical literature were gathered and statistical analysis of all cases was performed.
RESULTS: Reports on infantile BP are rapidly increasing. Among 78 reported children with BP, 42 (53%) occurred in the first year of life. The incidence of infantile BP in Israel in the last years is 2.36:100,000/y. Predisposition for acral involvement is significantly higher in infantile BP than in childhood BP (79% vs 17%, P < .001), whereas genital involvement is very rare (5% vs 44%, P = .002). Laboratory parameters were not significantly different, except for a more frequent IgM deposition at the dermoepidermal junction in childhood BP (29% vs 10%, P = .042).
LIMITATIONS: Statistical analyses of published cases may not be representative and could be affected by possible reporting biases.
CONCLUSIONS: Infantile BP may not be as rare as commonly stated. Age-related differences in regional distribution of lesions in BP were demonstrated. No major differences regarding laboratory results, treatment, and prognosis were found.
Childhood bullous pemphigoid: a clinicopathologic study and review of the literature.
Fisler RE, Saeb M, Liang MG, Howard RM, McKee PH.
Am J Dermatopathol. 2003 Jun;25(3):183-9 Abstract quote
Bullous pemphigoid (BP) is an acquired bullous disorder that predominantly affects the elderly. It is rare in children but when it occurs, there is considerable clinical and histologic overlap with other acquired or congenital blistering disorders.
A definitive diagnosis of childhood BP requires direct immunofluorescence and, in some cases, characterization of the target antigen. Three cases of childhood BP are presented, with their histologic and immunofluorescence findings. The first was a 5-month-old male infant who presented with erythema and bullae of the palms and soles and was found to have linear deposition of IgG and C3 along the dermoepidermal junction on direct immunofluorescence (DIF).
Histopathologic examination revealed a subepidermal blister containing eosinophils. Type IV collagen was demonstrated along the floor of the blister cavity by a direct immunoperoxidase technique.
The second case was an 8-month-old female infant who presented with a blistering eruption of her palms and soles that then became widespread. Direct immunofluorescence showed linear IgG and C3 at the dermoepidermal junction, with laminin deposition at the base of the blister.
The third case was a 7-year-old female with bullae and erosions on the vulva and vaginal mucosa. A subepidermal blister was seen on microscopic examination whereas immunofluorescence demonstrated linear IgG and C3 deposition at the basement membrane zone (BMZ). A literature review uncovered 50 cases of childhood BP confirmed by direct or indirect immunofluorescence, or both, and often with evidence of autoantibodies against either the 180 kD or the 230 kD human bullous pemphigoid antigens (BP180 or BP230).
This review was used to delineate characteristics of childhood BP, including the newly proposed subtypes: infantile BP and childhood localized vulval BP. Infantile BP presents within the first year of life and is characterized by BP-like lesions on erythematous or normal acral skin. Localized vulval BP is a self-limited, nonscarring BP-like process that involves only the vulva. Both subtypes are normally self-limited and respond well to either topical or systemic steroids, if treatment is initiated before the disease becomes widespread.
Childhood bullous pemphigoid developed after the first vaccination
J Am Acad Dermatol 2001;44:348-50
In the last 5 years, 10 adult and 2 infantile BP cases with a close relation of vaccination have been reported
Anti-influenza vaccine, tetanus toxoid booster, and tetracoq vaccine were the possible causes of these cases
3.5-month-old BP case in whom the lesions developed 24 hours after the first tetracoq vaccine
Suggest that vaccination may be the triggering factor of BP of any age by stimulating the immune system with an unexplained mechanism
Vesicular pemphigoid Chronic eruption of small pruritic vesicles resembling dermatitis herpetiformis. Pemphigoid vegetans Resembles pemphigus vegetans with verrcuous vegetating lesions in intertriginous areas
May be asociated with ulcerative colitis
Polymorphic pemphigoid Combines features of dermatitis herpetiformis and bullous pemphigoid
Some cases may represent linear IgA disease
Pemphigoid nodularis Combines features of prurigo nodularis and bullous pemphigoid
May resolve with scarring
Variant with hyperkeratotic islands within areas of blisters called pemphigoid en cocarde.
Subacute prurigo variant of bullous pemphigoid: autoantibodies show the same specificity compared with classic bullous pemphigoid.
Schmidt E, Sitaru C, Schubert B, Wesselmann U, Kromminga A, Brocker EB, Zillikens D.
Department of Dermatology, University of Wurzburg, Josef-Schneider-Strasse 2, 97080 Wurzburg, Germany.
J Am Acad Dermatol 2002 Jul;47(1):133-6 Abstract quote
We describe a 76-year-old white woman with a 6-month history of intensive pruritus and excoriated papules resembling subacute prurigo. Histopathology showed signs of chronic dermatitis, whereas findings by direct and indirect immunofluorescence microscopy were compatible with bullous pemphigoid (BP).
The patient's serum contained IgG autoantibodies that recognized epitopes on both BP180 and BP230 by Western blot analysis of epidermal extracts. In addition, we found strong reactivity with recombinant NC16A, an immunodominant region of BP180 targeted in the majority of BP sera, whereas no antibodies against the keratinocyte-derived soluble BP180 ectodomain (LAD-1) or the recombinant intracellular domain of BP180 were detected. The patient's disease responded well to oral methylprednisolone and mycophenolate mofetil. Disease activity correlated with enzyme-linked immunosorbent assay reactivity of antibodies to BP180 but not with titers of antibodies to the dermoepidermal junction as determined by indirect immunofluorescence on salt-split skin.
Our findings suggest that the subacute prurigo form of BP is a true variant of BP.
HISTOLOGICAL TYPES CHARACTERIZATION General
Subepidermal bulla with eosinophils and a lesser degree of neutrophils
Eosinophilic spongiosis may be present on the periphery of lesions but also in early urticarial, non-bullous lesions
If the blister is older, re-epithelialization of the base may occur, mimicking an intraepidermal blister
Generalized pruritic eruption with suprabasal acantholysis preceeding the development of bullous pemphigoid
María A.Barnadas1, Ramón M.Pujol1, RománCurell2, XavierMatías-Guiu2 and AgustínAlomar1
Departments of 1Dermatology and 2Pathology, Hospital de la Sta. Creu i St. Pau, Barcelona, Spain
J Cutan Pathol 2000;27 (2), 96-98 Abstract quote
We report a patient who presented with a papular pruritic eruption of a 3-month duration that histologically showed suprabasal acantholysis accompanied of an eosinophilic inflammatory infiltrate that was consistent with the diagnosis of Grover's disease. Later, erythematous plaques and vesicles appeared which showed a histopathological pattern of eosinophilic spongiosis.
The direct immunofluorescence (DIF) study showed linear IgG and C¢3 at the dermal epidermal junction which was consistent with the diagnosis of bullous pemphigoid. No anti-intercellular deposits of immunoglobulin G (IgG) or C¢3 were observed.
We consider that suprabasal acantholysis may represent the early phase of bullous pemphigoid.
Pemphigoid nodularis associated with autoantibodies to the NC16A domain of BP180 and a hyperproliferative integrin profile
Marianne Schachter, MD
Joaquin C. Brieva, MD
Jonathan C. R. Jones, PhD
Detlef Zillikens, MD
Christian Skrobek, MD
Lawrence S. Chan, MD
Chicago, Illinois, and Wuerzburg, Germany
J Am Acad Dermatol 2001;45:747-54 Abstract quote
Pemphigoid nodularis, a rare variant of bullous pemphigoid, has clinical features resembling prurigo nodularis, with blisters arising from normal-appearing or nodular skin. The fine antigenic epitope of the autoantibodies and the mechanism accounting for the nodular phenotype has not been delineated.
We describe a patient with pemphigoid nodularis that fulfilled the criteria of bullous pemphigoid by histopathologic examination and direct and indirect immunofluorescence studies. Immunopathologic examination also revealed in situ deposition and circulating autoantibodies of all IgG subclasses, except IgG3, and both light chains to the patient's skin basement membrane. By immunoblotting, the patient's IgG autoantibodies labeled BP180, BP230, and an unidentified 150-kd epidermal protein and mapped the BP180 epitope to the MCW-1, region 2 of the NC16A domain. The nodular plaque skin showed expression of -6 and -1 integrin subunits, mediators of matrix-cell signaling and proliferation, at the basal and the suprabasal epidermis, a pattern found in psoriasis, which is the prototype of hyperproliferative dermatoses.
CHARACTERIZATION Special stains Immunoperoxidase Direct immunofluorescence (DIF)
Linear IgG and C3 staining at the dermoepidermal junction
IgM and IgA are present in 20% of cases
The salt split skin technique localizes the immunoreactants to the epidermal side of the blister
A predominant IgG4 subclass may be responsible for false-negative direct immunofluorescence in bullous pemphigoid.
Buschman KE, Seraly M, Thong HY, Deng JS, Draviam RP, Abernethy JL.
Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA and the Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA.
J Cutan Pathol 2002 May;29(5):282-6 Abstract quote
BACKGROUND: Bullous pemphigoid (BP) is an immune-mediated blistering disease, usually characterized immunopathologically by the linear deposition of IgG and C3 along the basement membrane zone (BMZ) of skin. However, positive deposition of C3 but negative staining for IgG on direct immunofluorescence (DIF) studies has been noted in some patients.
METHODS: Twelve patients known to have BP but with absence of staining for IgG were included in this study. Frozen sections of skin specimens from the 12 patients were subjected to IgG DIF, as well as a sandwich double antibody method of staining for IgG, IgG subclasses, and light chains. Enzyme-linked immunosorbent assay (ELISA) using commercially available human IgG subclasses was used to analyze the subclass restriction of FITC-labeled antihuman IgG conjugates.
RESULTS: Of the 12 skin specimens with positive C3 and negative IgG on DIF, nine were positive for IgG with the double antibody sandwich method. In addition, all 12 specimens had positive linear staining for the subclass IgG4 along the BMZ with this method. There was no IgG light chain restriction. Two commercially obtained antihuman IgG conjugates, both commonly used in our laboratory for DIF testing, were analyzed for separate IgG subclass specificity by ELISA. Both conjugates showed high reactivity to IgG1 and IgG3 with less reactivity to IgG2 and IgG4.
CONCLUSION: These results suggest that the following factors contribute to false-negative staining for IgG on DIF in some BP patients: (i): subthreshold IgG in skin specimens; (ii) limited reactivity of commercial antihuman IgG conjugates to the IgG4 subclass; and (iii) decreased sensitivity of DIF compared with double antibody methods for the detection of IgG. The use of sandwich double antibody immunofluorescence methods to test for IgG and/or IgG subclasses may be helpful in definitively diagnosing BP in patients with negative IgG and positive C3 staining on DIF.
Indirect immunofluorescence (IIF)
There are circulating IgG anti-basement membrane antibodies in the serum of 60-80% of patients
However, the titer does not correlate with the course of the disease.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
- Prediction of survival for patients with bullous pemphigoid: a prospective study.
Joly P, Benichou J, Lok C, Hellot MF, Saiag P, Tancrede-Bohin E, Sassolas B, Labeille B, Doutre MS, Gorin I, Pauwels C, Chosidow O, Caux F, Esteve E, Dutronc Y, Sigal M, Prost C, Maillard H, Guillaume JC, Roujeau JC.
Department of Dermatology, Institut National de la Sante et de la Recherche Medicale U 519, University of Rouen, Rouen, France.
Arch Dermatol. 2005 Jun;141(6):691-8. Abstract quote
OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP).
DESIGN: Prospective study of patients with BP included in a randomized, controlled trial.
SETTING: Twenty dermatology departments in France.Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples).
MAIN OUTCOME MEASURES: The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids.
RESULTS: Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample.
CONCLUSIONS: The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.
Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age.
Rzany B, Partscht K, Jung M, Kippes W, Mecking D, Baima B, Prudlo C, Pawelczyk B, Messmer EM, Schuhmann M, Sinkgraven R, Buchner L, Budinger L, Pfeiffer C, Sticherling M, Hertl M, Kaiser HW, Meurer M, Zillikens D, Messer G.
Department of Dermatology, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Mannheim, Germany.
Arch Dermatol 2002 Jul;138(7):903-8 Abstract quote
BACKGROUND: Although bullous pemphigoid (BP) is the most frequent autoimmune bullous disease and is associated with a considerable case-fatality rate, little is known about factors that influence its prognosis.
OBJECTIVE: To identify prognostic factors for lethal outcome in the first year after the initial hospitalization in patients with BP.
DESIGN: A multicenter retrospective cohort study.
SETTING: Seven dermatologic university hospitals in Germany.
PARTICIPANTS: A total of 369 patients diagnosed as having BP between January 1, 1987, and December 31, 1997.
STATISTICS: Univariate (Kaplan-Meier) and multivariate (Cox regression) analysis.
RESULTS: Of the 369 patients with BP, 209 (57%) died, 106 (29%) within the first year after hospitalization. Fifty-four percent were women. The mean +/- SD age at entry was 77.3 +/- 11.1 years. The patients with BP were followed up to 10.5 years, with a median time of 1.8 years to death or interview (25th and 75th quartiles, 0.5 and 4.0 years). The major risk factors for lethal outcome in the first year after hospitalization were an increased age, with a multivariate risk estimate of 3.2 (95% confidence interval [CI], 1.9-5.2) for age greater than 80.4 years (median); a daily glucocorticosteroid dosage of more than 37 mg (75th quartile) at discharge, with a multivariate risk estimate of 2.5 (95% CI, 1.5-4.3); serum albumin levels of 3.6 g/dL or less (25th quartile), with a multivariate risk estimate of 2.6 (95% CI, 1.5-4.4); and an erythrocyte sedimentation rate greater than 30 mm/h (75th quartile), with a multivariate risk estimate of 1.7 (95% CI, 1.1-2.8).
CONCLUSIONS: There is a considerable case-fatality rate in patients with BP. Older patients who require a higher dosage of oral glucocorticosteroids at hospital discharge and who have low serum albumin levels are at greater risk of death within the first year after hospitalization. These prognostic factors should be considered in the care of patients with BP as well as in the design of future clinical trials.
TREATMENT Corticosteroids are mainstay of therapy
Steroid sparing medications include:
GENERAL A Systematic Review of Treatments for Bullous Pemphigoid
Nonhlanhla P. Khumalo, MD; Dedeé F. Murrell, MD; Fenella Wojnarowska, MD; Gudula Kirtschig, MD
Arch Dermatol. 2002;138:385-389 Abstract quote
To assess the effectiveness of treatments for bullous pemphigoid.
The Cochrane Library search strategy was used to identify randomized controlled trials from MEDLINE and EMBASE, from their inception to September 30, 2001. All randomized controlled trials on interventions for bullous pemphigoid, confirmed by immunofluorescence studies, were included.
We found 6 randomized controlled trials with a total of 293 patients. Two trials, one comparing prednisolone, 0.75 mg/kg per day, with prednisolone, 1.25 mg/kg per day, and the other comparing methylprednisolone with prednisolone, did not find any significant difference in effectiveness. The higher dose of prednisolone, however, was associated with more severe adverse effects. Combination treatments of prednisone with azathioprine in one trial and of prednisolone with plasma exchange in another were useful in halving the corticosteroid dose required (mean SD, 0.52 0.28 mg/kg in the plasma exchangetreated group vs 0.97 0.33 mg/kg in the prednisolone onlytreated group). However, a fifth trial, including all 3 treatment groups (prednisolone alone, prednisolone and azathioprine, and prednisolone and plasma exchange), failed to confirm the benefit of combination treatment over prednisolone alone. A trial of 20 patients, comparing prednisone with tetracycline and niacinamide, found no statistically significant difference in response between the 2 groups, but the prednisone-treated group had more serious adverse effects.
There is inadequate evidence for a recommendation of a specific treatment for bullous pemphigoid, and there is a need for larger randomized controlled trials with adequate power. Starting doses of prednisolone greater than 0.75 mg/kg per day do not seem to give additional benefit, and it seems that lower doses may be adequate for disease control. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and niacinamide seems useful, although this needs further validation.
Comparison Between Intravenous Immunoglobulin and Conventional Immunosuppressive Therapy Regimens in Patients With Severe Oral Pemphigoid Effects on Disease Progression in Patients Nonresponsive to Dapsone Therapy
A. Razzaque Ahmed, MD, DMSc; José E. Colón, DMD
Arch Dermatol. 2001;137:1181-1189 Abstract quote
Mucous membrane pemphigoid has a wide clinical spectrum. The clinical context was to determine whether pemphigoid disease that initiates in the oral cavity progresses to involve other mucosae and to determine the influence of systemic therapy on such progression.
To determine the clinical outcomes and disease progression in patients with oral pemphigoid for whom dapsone therapy was impossible.
Retrospective analysis of a cohort of 20 patients with immunopathologic-proven oral pemphigoid studied between September 1, 1994, and October 31, 2000. Twelve patients received conventional therapy that consisted of a combination of oral prednisone with an immunosuppressive agent. Eight patients in whom such therapy was contraindicated received intravenous immunoglobulin therapy. Patients were followed up for 33 to 62 months (mean follow-up, 47.5 months).
Patients were treated in an ambulatory tertiary medical care facility of a university-affiliated hospital.
The 20 patients had pemphigoid disease limited to the oral cavity only at the initial clinical presentation and when enrolled in the study.
Main Outcome Measures
The following variables were compared between the 2 groups of patients: (1) duration of treatment, (2) frequency of relapses, (3) induction of remission, (4) adverse effects of therapy, (5) extra oral involvement, and (6) quality of life.
Using the aforementioned factors, the group treated with intravenous immunoglobulin had statistically significant shorter treatment duration, fewer relapses, higher remission rate, fewer adverse effects, no extraoral involvement, and a better quality of life compared with the group who received conventional therapy.
Intravenous immunoglobulin is a safe and effective modality to treat mucous membrane pemphigoid. It seems to be a good option for patients who cannot be treated with dapsone and in whom conventional therapy is contraindicated or results in the development of serious adverse effects. In patients with progressive mucous membrane pemphigoid, intravenous immunoglobulin therapy may arrest disease progression.
Intravenous immunoglobulin therapy for patients with bullous pemphigoid unresponsive to conventional immunosuppressive treatment
A. Razzaque Ahmed, MD
J Am Acad Dermatol 2001;45:825-35 Abstract quote
Background: Up to 24% of patients with bullous pemphigoid (BP) do not respond to conventional therapy consisting of oral prednisone alone or combined with corticosteroid-sparing immunosuppressive agents (ISAs). They cannot sustain a prolonged clinical remission and continue to have relapses.
Objective: Fifteen patients with recurrent BP who had experienced several significant side effects resulting from conventional therapy were treated with intravenous immunoglobulin (IVIg) therapy.
Methods: A preliminary dose-finding study tested 7 additional patients to ascertain the optimal IVIg dose of 2 gm/kg per cycle. Objective parameters to determine clinical outcomes were recorded before and after IVIg therapy: doses of prednisone and ISAs, their duration, side effects, clinical course, frequency of relapses and recurrence, response to therapy, number of hospitalizations, total days hospitalized, and quality of life. Results: While receiving IVIg as monotherapy, all study subjects achieved a sustained clinical remission. A statistically significant difference was noted in all the variables studied before and after IVIg therapy. IVIg had a corticosteroid-sparing effect and improved quality of life and did not produce any serious side effects.
Conclusion: IVIg appears to be an effective alternative in treating patients with severe BP whose disease is nonresponsive to conventional therapy. IVIg may be particularly useful, if treatment is begun early, in patients who are at risk of experiencing serious or potentially fatal side effects from conventional immunosuppressive therapy. After clinical control is achieved, IVIg therapy should be gradually withdrawn and not abruptly discontinued. (.)
Arch Dermatol 2000;136:1204-1205
Novel immunomodulatory agent used in preventing organ transplantation and treating rheumatoid arthritis
Two patients where standard steroid therapy treatment failed and both refused corticosteroid sparing therapy-both responded with initial doses of 20 mg/d allowing tapering of steroids
Converted into active metabolite A771726, a malononitrilamide, which inhibits:
Dihydro-orotate dehydrogenase, a mitochondrial enzyme critical for de novo synthesis of pyrimidines-critical for proper function of T and B lymphocytes and this drug inhibits cytotoxic T cells and the synthesis of antibodies
Lymphocyte tyrosine kinase activity upon mitogen stimulation or activation of the interleukin 2 receptor
Tumor necrosis factor-activated nuclear factor kappa B-dependent gene expression
A comparison of oral and topical corticosteroids in patients with bullous pemphigoid.
Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, Vaillant L, D'Incan M, Plantin P, Bedane C, Young P, Bernard P; The Bullous Diseases French Study Group.
Department of Dermatology and Biostatistics, INSERM Unite 519, University of Rouen, Rouen, France.
N Engl J Med 2002 Jan 31;346(5):321-7 Abstract quote
BACKGROUND: Bullous pemphigoid is the most common autoimmune blistering skin disease of the elderly. Because elderly people have low tolerance for standard regimens of oral corticosteroids, we studied whether highly potent topical corticosteroids could decrease mortality while controlling disease.
METHODS: A total of 341 patients with bullous pemphigoid were enrolled in a randomized, multicenter trial and stratified according to the severity of their disease (moderate or extensive). Patients were randomly assigned to receive either topical clobetasol propionate cream (40 g per day) or oral prednisone (0.5 mg per kilogram of body weight per day for those with moderate disease and 1 mg per kilogram per day for those with extensive disease). The primary end point was overall survival.
RESULTS: Among the 188 patients with extensive bullous pemphigoid, topical corticosteroids were superior to oral prednisone (P=0.02). The one-year survival rate was 76 percent in the topical-corticosteroid group and 58 percent in the oral-prednisone group. Disease was controlled at three weeks in 92 of the 93 patients in the topical-corticosteroid group (99 percent) and 86 of the 95 patients in the oral-prednisone group (91 percent, P=0.02). Severe complications occurred in 27 of the 93 patients in the topical-corticosteroid group (29 percent) and in 51 of the 95 patients in the oral-prednisone group (54 percent, P=0.006). Among the 153 patients with moderate bullous pemphigoid, there were no significant differences between the topical-corticosteroid group and the oral-prednisone group in terms of overall survival, the rate of control at three weeks, or the incidence of severe complications.
CONCLUSIONS: Topical corticosteroid therapy is effective for both moderate and severe bullous pemphigoid and is superior to oral corticosteroid therapy for extensive disease.
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Salt split skin assay-Normal skin incubated with 1M NaCl which separates the epidermis from dermis. The epidermal half contains the upper lamina lucida, hemidesmosomes, and BP antigen. The dermal half contains laminin 5, lamina densa, and anchoring fibrils.
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