Autoimmune bullous diseases are systemic disorders with autoantibodies that result in blisters. Aim of this study was to indicate the spectrum and treatment modalities of five types of bullous disorders most prevalent in the south of Iran: pemphigus vulgaris (PV), pemphigus foliaceus (PF), epidermolysis bullousa aquisita (EBA), bullous pemphigoid (BP), and pemphigoid gestationis (PG). Patients with PV, PF, BP, EBA, and PG were included in this study. The data regarding the age, sex, and the treatment used for PV, PF, and BP were recorded and analyzed in our center, a tertiary referral center. T-test and Mann-Whitney test for independent samples were used for the analysis of parametric and nonparametric variables, respectively. Chi-square test was used for frequencies. Of the 441 patients included in this study, 82.9% had PV, 4.7% PF, 8.5% BP, 1.5% EBA, and 1.3% PG. 93.5% of patients with PV, 95.3% with PF, and 100% with patients with BP were treated and responded to first line therapies with one or two medications.The most frequent autoimmune bullous disease was PV, followed by PF. For PV and PF, combination of prednisolone and azathioprine was the most frequent first line medication. In the patients with BP, prednisolone monotherapy was the most frequent one. Only a minority of patients with PV and PF needed the third or fourth medications.</p

Farideh Jowkar

Maryam Sadat Sadati

Mohammad Amin Agah

Samar Tavana

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246 ACTA DERMATOVENEROLOGICA CROATICAEpidemiology of Autoimmune Bullous Diseases and Therapeutic Modalities During a 10 Year Period in IranFarideh Jowkar1, Maryam Sadat Sadati1, Samar Tavana2,  Mohammad Amin Agah21Dermatology Center, Shiraz University of Medical Sciences; 2 Shiraz University of  Medical Sciences; Molecular dermatology research center, Shiraz University of  Medical Sciences, Shiraz, Iran.Corresponding author: Maryam Sadat Sadati, MDMolecular Dermatology Research Center Dermatology DepartmentShahid Faghihi Hospital Zand streetShirazIranmsadati63@yahoo.comReceived: May 31, 2013Accepted: September 1, 2014Acta Dermatovenerol Croat                       2014;22(4):246-249            ORIGINAL SCIENTIFIC ARTICLESuMMArY Autoimmune bullous diseases are systemic disorders with auto-antibodies that result in blisters. Aim of this study was to indicate the spectrum and treatment modalities of five types of bullous disorders most prevalent in the south of Iran: pemphigus vulgaris (PV), pemphigus foliaceus (PF), epider-molysis bullousa aquisita (EBA), bullous pemphigoid (BP), and pemphigoid gestationis (PG). Patients with PV, PF, BP, EBA, and PG were included in this study. The data regarding the age, sex, and the treatment used for PV, PF, and BP were recorded and analyzed in our center, a tertiary referral center. T-test and Mann-Whitney test for independent samples were used for the analysis of parametric and nonparametric variables, respectively. Chi-square test was used for frequencies. Of the 441 patients included in this study, 82.9% had PV, 4.7% PF, 8.5% BP, 1.5% EBA, and 1.3% PG. 93.5% of patients with PV, 95.3% with PF, and 100% with patients with BP were treated and responded to first line therapies with one or two medications.The most frequent autoimmune bullous disease was PV, followed by PF. For PV and PF, combination of prednisolone and azathioprine was the most frequent first line medication. In the patients with BP, prednisolone monotherapy was the most frequent one. Only a minority of patients with PV and PF needed the third or fourth medications.KEYworDS: pemphigus vulgaris; pemphigus foliaceus; bullous pemphigoid; treatmentInTroDuCTIonAutoimmune bullous disorders (ABD) are a group of systemic disorders with autoantibodies that result in intraepidermal and subepidermal blisters (1). They need serious medical care, otherwise they have rela-tively high mortality (2,3).Limited research has been done worldwide on the epidemiology and treatment of ABD. In particular, only a small number of epidemiological studies are available about epidemic spectrum and treatment of various types of ABD in Iran. The aim of this study was to indicate the spectrum of five types of most prevalent bullous disorders in the south of Iran. We also determined the frequency of different types of ABD treatment.PATIEnTS AnD METhoDSDuring a 10 year period, the records of all the new patients admitted with bullous disease at Shiraz Uni-versity of Medical Sciences (SUMS) dermatology cen-ter were evaluated. This is the major tertiary referral 247ACTA DERMATOVENEROLOGICA CROATICAJowkar et al. Acta Dermatovenerol CroatAutoimmune bullous diseases in Iran 2014;22(4):246-249center for dermatologic diseases in the south of Iran. Private dermatologists also refer new bullous disorder patients to our tertiary center for better management and follow up. The diagnosis was made based on the clinical presentation, histopathology, and direct im-munofluorescence. Five diseases were included in our study: pemphi-gus vulgaris (PV), pemphigus foliaceus (PF), epider-molysis bullousa aquisita (EBA), bullous pemphigoid (BP), and pemphigoid gestationis (PG). The data re-garding the age, sex, and the treatment used for PV, PF, and BP were recorded and analyzed.The SPSS statistical package was used for analysis. T-test and Mann-Whitney test for independent sam-ples were used for all parametric and nonparametric variables analysis, respectively. Chi-square test was used for qualitative variables. In all statistical tests, P<0.05 was considered significant.rESulTSAbout 6400 patients with various dermatologic diseases were admitted during the 10 year period of the study. A total number of 441 patients with auto-immune bullous disorders were included. 369 cases were diagnosed as PV (82.9% of the total cases). Table 1 shows characteristics of different bullous diseases including the number, frequency, mean age, median age, age range, and sex ratio.We studied different medical treatments used in our center for treating PV, PF, and BP. Out of the 369 cases of PV, there were only 311 patients with avail-able treatment data. The frequency of the 1st, 2nd and 3rd line therapies for the cases are shown in Table 2 and 3.93.5% of patients with PV, 95.3% with PF, and 100% of patients with BP responded to the 1st line therapies of one or two medications. 6.5% of patients with PV and 4.7% with PF needed the 2nd and 3rd line therapies in order to control the disease.DISCuSSIonABDs are rare blistering diseases affecting the skin and mucosa. Their clinical and epidemiologic features vary according to geographic location and ethnic background. Few surveys have been done to describe the spectrum of ABD in our region. The SUMS dermatology center is the referral center for dermatology diseases for southern Iran, with about 6.5 million inhabitants in this area. Epidemiology441 ABD cases were included in the study. PV ac-counted for the majority of cases (83.67%), followed by BP, PF, EBA, and PG. PV outnumbered other ABD cases; this finding is similar to studies conducted in most of the world, except Latin American counties, Mali, Tunisia and Finland: in these regions, other bul-lous diseases such as fogo selvagem, PF, and pemphi-gus erythematosus predominate (3-8).Patients with PV and PF were predominantly men. This is in contrast to what has been noted in Germany, Kuwait, Switzerland, and the UK (9-12); studies from India, Saudi Arabia, Bangladesh, and China found the same predominance (13-16). Patients with BP were predominantly women, in line with previous studies (2,10,11). However, studies from China and Germany found that patients with BP were predominantly men (15,16). On the other hand, patients with EBA were also predominantly women in our study, as in Kuwait (11), but a study of north of Iran reports a male pre-dominance (3).The mean ages were 45.8 years for PV, 40.4 years for EBA, and 50.7 years for PF. The mean ages for PV and EBA are similar to what was found in the stud-ies in the north of Iran, Saudi Arabia, and Singapore (3,13,17). PF mean age is relatively close to Korea and Japan, where the disease presented in the sixth and seventh decades (18,19). The mean age of patients with PG was 27.3 years, which is younger than that of the study from Sao Paulo (30.3 years) (20).M : F ratio Age range (years) Median of age (years) Mean ± SD of age at onset (years) % of patients No. of patients Autoimmune bullous disease   1.1 : 1 21-89 44 45.8 ± 16.2 83.67 369 Pemphigus vulgaris 1.1 : 1 22-75 51 50.7 ± 17.35 4.76 21 Pemphigus foliaceus 1 : 1.23 21-90 65 64.1 ± 17.70 8.61 38  Bullous pemphigoid 1 : 1.2 17-69 41 40.4 ± 17.82 1.58 7 Epidermolysis bullousa aquisitaAll were females 19-35 27 27.3 ± 5.32 1.36 6 Pemphigoid gestationis Table 1. The frequency and epidemiology of autoimmune bullous disease during a 10 year period248 ACTA DERMATOVENEROLOGICA CROATICATable 3. The frequency of 2nd and 3rd line therapies for autoimmune disease in resistant casesBP was the second most common ABD in this study, PV being the most common. The ratio of PV to BP was 9.7:1, which is close to the results from studies in the north of Iran, Kuwait, and China (11,15). The median age for BP was 65 years, which is similar to the results of the study of the north of Iran (59.4 years) (3). EBA was observed in 1.5% of patients, and PG ac-counted for 1.3% of patients. Both estimates are high-er than what was reported in the north of Iran (0.5% and 0.7%, respectively) (3). TreatmentsPrednisolone with the dosage of 0.5 to 1.5 mg/kg is the first line medication that is used for ABD, and steroid sparing agents are added in an attempt to taper corticosteroids. For PV and PF, the combina-tion of prednisolone and azathioprine was the most frequent first line medication with 68% and 47.6%, respectively. It was followed by monotherapy with prednisolone accounting for 18.6% and 38% in PV and PF, respectively.In the BP group, prednisolone monotherapy (50%) was the most frequent medication, followed by pred-nisolone in combination with azathioprine (26.3%). Dapsone was used more frequently (23.6%) in BP pa-tients compared to PV and PF (1.2% and 9.5%, respec-tively). Prednisolone in combination with mycophe-nolate mofetil (1.2%) or cyclosporine (0.9%) was used as the first line therapy in a minority of PV cases.The patients who did not respond to the first line medications were treated with the 2nd and 3rd line therapies. None of BP cases required the third line medication. Only a minority of PF patients (4.7%) needed the addition of the third medication, in which only the combination of prednisolone, azathioprine, and mycophenolate mofetil was used. In the PV group, the most commonly used third line medications were dapsone (2.9%), mycopheno-late mofetil (1.6%), or cyclosporine (0.9%). The combi-nation of prednisolone with mycophenolate mofetil and tacrolimus was used in 0.3% of patients, which was similar to the frequency of using the combina-tion of prednisolone with cyclophosphamide and dapson (0.3%).Only 0.3% of PV cases received the four drug com-bination of prednisolone, azathioprine, mycopheno-late mofetil, and dapson.The more frequent use of the third and fourth medications in PV may imply the more severe nature of PV. In the study performed in Germany, more than 50% of patients with PV received prednisolone as the first medication and azathioprine was added in 81% of cases, which is close to our results. In that study, azathioprine was added in 69% of patients with BP, which is higher than the findings of our study (26.3%). Immunosuppressive agents that were used as alter-native were similar to those used in our center (21).ConCluSIonThe present study was carried out in a tertiary re-ferral center. Although most of ABD cases are referred to tertiary centers, the milder cases might be man-aged in an outpatient setting and would not have been included in this study. Due to the retrospective nature of this study, we could not determine the ex-act time of the patients’ response to the medications.Dx/drug% (No.)Prednisolone Dapsone Prednisonlone+cyclosporinePrednisolone+azathioprinePrednisolone+ MMPrednisolone+ dapsonePV (291) 18.6% (58) – 0.9% (3) 68% (212) 4.5% (14) 1.2% (4)PF (20) 38% (8) – – 47.6% (10) – 9.5% (2)BP (38) 50% (19) 5.2% (2) – 26.3% (10) – 18.4% (7)DX: disease; PV: pemphigus vulgaris; PF: pemphigus foliaceus; BP: bullous pemphigoid; MM: mycophenolate mofetilTable 2. The frequency of the first line therapies in autoimmune bullous disease in our centerDx/drug % (No.)Prednisolone+ azathioprine+ dapsonePrednisolone+ azathioprine+ MMPrednisolone+ azathioprine+ cyclosporinePrednisoloe+ MM+tacrolimusPrednisolone+ cyclophospmide+ dapsonePrednisolone+ azathioprine+ MM+dapsonePV (20) 2.9% (9) 1.6% (5) 0.9% (3) 0.3% (1) 0.3% (1) 0.3% (1)PF (1) – 4.7% (1) – – – –DX: disease; PV: pemphigus vulgaris; PF: pemphigus foliaceus; MM: mycophenolate mofetilJowkar et al. Acta Dermatovenerol CroatAutoimmune bullous diseases in Iran 2014;22(4):246-249249ACTA DERMATOVENEROLOGICA CROATICAreferences1.  Olasz EB, Yancey KB. Bullous pemphigoid and related subepidermal autoimmune blistering di-seases. Curr Dir Autoimmun 2008;10:141-66. 2.  Langan SM, Smeeth L, Hubbard R, Fleming KM, Smith CJP, West J. Bullous pemphigoid and pem-phigus vulgaris—incidence and mortality in the UK: population based cohort study. BMJ 2008;337: 160-163. 3.  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Epidemiology of Autoimmune Bullous Diseases and Therapeutic Modalities During a 10 Year Period in Iran

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