Prediction of survival for patients with bullous pemphigoid: a prospective study. [Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day versus 1.25 mg/kg/day. A multicenter randomized study]. [Methylprednisolone versus prednisolone methylsulfobenzoate in pemphigoid: a comparative multicenter study]. Controlled trial of azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous pemphigoid. [Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients]. A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study. Nicotinamide and tetracycline therapy of bullous pemphigoid. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid.
To identify the prognostic factors of bullous pemphigoid (BP).
                Prospective study of patients with BP included in a randomized, controlled trial.
                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).
                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.
                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.
                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. Systemic corticosteroids for the treatment of bullous pemphigoid are an accepted therapeutic measure among dermatologists. Nevertheless, the best initial dosage is still unknown. The purpose of the present study was to compare the efficacy and safety of two dosages of prednisolone used as a single therapeutic agent: 0.75 mg/kg/day versus 1.25 mg/kg/day for three weeks. Fifty patients with bullous pemphigoid confirmed by direct cutaneous immunofluorescence were included in this study in different centers. They were randomly assigned to one of two groups: 24 patients were treated with prednisolone 0.75 mg/kg/day (group I) and 22 patients were treated with 1.25 mg/kg/day (group II). Four patients had to be excluded from this study. The low and high dosage prednisolone groups do not show a statistically significant difference from each other after 51 days. At day 21, 58 p. 100 of the patients in group I were disease-free, and 64 p. 100 in group II. At day 51, after a slow decrease of prednisolone therapy (half of the initial dosage per day), 33 p. 100 of the patients in group I were still free of skin lesions, and 55 p. 100 in group II. Bullous pemphigoid is a bullous skin disease associated with basal membrane antibodies. At present, the first treatment of these lesions is with corticosteroids. In this randomized study we compared the clinical results obtained with methylprednisolone (MePr) in 28 patients and with prednisolone methylsulfobenzoate (MsPr) in 29 patients. Both drugs were administered orally in daily doses of 1 to 1.5 mg/kg bodyweight. Three clinical data were examined: the number of bullous lesions, the intensity of pruritus and the extent of erythema after 5 then 10 days of treatment. After 10 days, the number of bullous lesions had decreased by 83 p. 100 with MePr and by 78 p. 100 with MsPr, and the decrease of pruritus had been significantly more pronounced in the MePr group than in the Ms group (p < 0.05). There had been no difference between treatments in the regression of erythema. Altogether, good results were obtained in 22/28 patients under MsPr (78.6 p. 100) and 18/29 patients under MePr (62.1 p. 100). This raises the question of the value of pharmacokinetic studies not only with these two corticosteroids, but also with prednisone which seems to be better absorbed. 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. To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients.
                Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01).
                JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid. Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome. 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. To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of bullous pemphigoid.
                A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with bullous pemphigoid undergoing different treatments.
                Thirteen departments of dermatology in Germany.
                Patients with bullous pemphigoid (n = 73) as evidenced by clinical lesions suggestive of bullous pemphigoid, signs of subepidermal blistering on histologic analysis of skin biopsy specimens, linear deposition of IgG and C3 along the dermoepidermal junction, and deposition of autoantibodies at the blister roof in split-skin analysis.
                Treatment with oral methylprednisolone plus azathioprine (azathioprine group) or oral methylprednisolone plus mycophenolate mofetil (mycophenolate mofetil group).
                The cumulative total methylprednisolone doses and rates of remission. Secondary outcome measures were safety profiles and duration of remission.
                In 38 of 38 patients in the azathioprine group (100%), complete remission was achieved after a mean +/- SD of 23.8 +/- 18.9 days vs 42.0 +/- 55.3 days for 35 of 35 patients in the mycophenolate mofetil group (100%). In the azathioprine group, the median +/- SD total cumulative methylprednisolone dose used was 4967.0 +/- 12 190.7 mg vs 5754.0 +/- 9692.8 mg in the mycophenolate mofetil group. Nine of 38 patients in the azathioprine group (24%) experienced grade 3 or 4 adverse effects vs 6 of 35 patients in the mycophenolate mofetil group (17%). Azathioprine therapy induced significantly elevated liver function test results compared with mycophenolate mofetil (P < .001). Importantly, patients in the azathioprine group showed significantly higher toxicity grades for aspartate aminotransferase (P = .03), alanine aminotransferase (P = .03), and gamma-glutamyltransferase (P = .01) than did those in the mycophenolate mofetil group.
                Mycophenolate mofetil or azathioprine demonstrate similar efficacy during treatment of bullous pemphigoid, and similar cumulative corticosteroid doses were given in both treatment arms to control disease. However, mycophenolate mofetil showed a significantly lower liver toxicity profile than azathioprine therapy.
Very potent topical steroids are effective and safe treatments for BP, but their use in extensive disease may be limited by side-effects and practical factors. Milder regimens (using lower doses of steroids) are safe and effective in moderate BP. Starting doses of prednisolone greater than 0.75 mg/kg/day do not give additional benefit, lower doses may be adequate to control disease and reduce the incidence and severity of adverse reactions. The effectiveness of adding plasma exchange, azathioprine or mycophenolate mofetil to corticosteroids, and combination treatment with tetracycline and nicotinamide needs further investigation.