Autoimmune bullous diseases (ABD) are a group of diseases caused by autoantibodies against the dermoepidermal junction and desmosome, cleaving the skin and mucous membrane. The clinical forms and the prevalence seem to be different from one continent to another.

Since 1984, patients with bullous disease have been seen in our ABD Research Center. In a study from March 1997 to February 2006, 1402 cases of ABD were seen in our center. At this time, the population of Iran was approximately 72.5 million with 8 million in Tehran. Pemphigus vulgaris (PV) was the most frequent ABD at 81.2% (95% confidence interval [CI] 79%–83.1%); followed by 11.6% bullous pemphigoid (95% CI 10.05%–13.4%) and 4.4% pemphigus foliaceus (95% CI 3.5%–5.6%). Much rarer were pemphigoid gestationis 0.7% (95% CI 0.4%–1.3%), mucous membrane pemphigoid 0.7% (95% CI 0.4%–1.3%), epidermolysis bullosa acquisita 0.5% (95% CI 0.2%–1.1%), linear IgA disease 0.4% (95% CI 0.2%–1%), paraneoplastic pemphigus 0.2% (95% CI 0.04%–0.67%), IgA pemphigus 0.2% (95% CI 0.04%–0.67%), and pemphigus erythematosus 0.1% (95% CI 0%–0.45%). Our center is the major referral center for ABDs in Iran.

Patients with pemphigus were registered using a predefined computer-based data chart and saved into an electronic database. They were followed at the Pemphigus Research Unit regularly, and the database was updated subsequently. The diagnosis was based on clinical manifestations, the histologic pattern, and direct immunofluorescence (DIF). The analysis of the database, performed in 2007, showed 1782 cases of pemphigus. The male/female ratio was 1:1.44. The mean age was 42 ± 19 years with 95% CI of 41.9 to 43.1. Familial pemphigus were found in 1.5% (95% CI 1%–1.4%) and juvenile pemphigus in 2.7% (95% CI 2%–3.6%) of the cohort.

The major clinical form of the disease was PV observed in 1606 patients (91.1%, CI 1.4). PV has different phenotypes: (1) the mucous membrane alone phenotype was seen in 19%; (2) skin and mucous membrane together phenotypes in 69%; (3) the skin alone phenotype in 12%.

The other clinical forms of the disease were: pemphigus foliaceus, which was seen in 7% (95% CI 5%–9%); pemphigus vegetans 2.6% (95% CI 1.7%–3.5%); and a few cases of drug-induced pemphigus, paraneoplastic pemphigus, and IgA pemphigus.

Our group studied the frequency of HLA class II alleles (DRB, DQA1, and DQB1) and haplotypes in 52 Iranian non-Jewish patients with PV and in 180 normal individuals as the control group. The results of our study showed that 36.5% of the patients with PV carry the HLA-DRB1∗04, DQA1∗ 0301, DQB1∗0302 haplotype versus 5.5% in the control group ( P <.0001). In the patients, 25% carry the HLA-DRB1∗1401, DQA1∗0104, DQB1∗0502 haplotype versus 4.4% in the control group ( P <.0001). Ashkenazi Jewish PV carry the DRB1∗040, DQB1∗0302 haplotype. Our findings suggest that the susceptibility complex of PV histocompatibility class II alleles in non-Jewish Iranians patients with PV is the same as the Ashkenazi Jewish PV. A previous study reported the same finding and concluded that they probably derive from the same ancestor.

In a study done in 2005, the prevalence of pemphigus in Iran was found to be about 30 per 100,000 inhabitants. The incidence per 100,000 inhabitants per year was 1.6 in Tehran and 1 for Iran. An average of 4 new cases per week are seen in the ABD Research Center in Tehran.

Our treatment strategy is to start prednisolone, an indispensable drug for pemphigus, plus cytotoxic drugs. Prednisolone is started at 2 mg per kg of body weight per day (total dose not going over 120 mg/d). Then, as soon as no new blisters appear and the lesions are dried, the total dose is reduced by one-third. Then every 3 days or every other day, the dose of prednisolone is reduced by 5 mg to reach 30 mg per day. Then prednisolone is gradually tapered by 1.25 mg per week to reach 15 mg per day, and then every 2 weeks to reach 7.5 or 5 mg per day. After 6 months, if DIF and enzyme-linked immunosorbent assay (ELISA) are negative, the dose of prednisolone is reduced to 2.5 mg and then the treatment is stopped.

In addition to steroid, a cytotoxic drug is added to the regimen. Azathioprine was shown to be efficient. We start our patients at 2.5 mg per kg per day, or mycophenolate mofetil 2 g per day. Thiopurine S -methyltransferase activity is not measured routinely before using azathioprine (not available in Iran). Mycophenolate mofetil is a more expensive drug than azathioprine, and some patients cannot afford it, but it is a very efficient drug in some patients and is well tolerated If azathioprine has side effects, or is not efficient, it is changed to mycophenolate mofetil, or vice versa . If azathioprine and mycophenolate are not effective, the patients is switched to oral cyclophosphamide 100 mg/d for 3 to 6 months. Oral cyclophosphamide has important side effects in treatment of long duration, especially in young patients. If cyclophosphamide is not efficient, rituximab (anti-CD20 antibody) or IVIg is used but they are expensive and few patients can afford these drugs.

In cases of complete remission, if the disease is dependent on steroids, more than 15 mg prednisolone daily, other drugs, including dapsone, methotrexate gold are tried. They sometimes seem efficient, although there is no evidence.

Some patients on a minimum dose of 5 to 7.5 mg/d of prednisolone relapse frequently, but localized to the face or head, and always in the same place. These patients receive triamcinolone acetonide intralesionally every week diluted as 20 mg/mL in lidocaine. As pemphigus foliaceus, can also be severe, this is treated in the same way as PV. In pregnant patients, the starting dose of prednisolone is 30 mg per day, plus application 15 g of corticosteroid on normal skin when the disease is severe. In juvenile patients, we prefer prednisolone plus dapsone. If the disease is severe and does not respond, azathioprine or mycophenolate mofetil is used.

In conclusion, early treatment and adequate drugs adapted for each patient are the mainstay of treatment. It is worthwhile reaching the minimum possible level of corticosteroid whenever possible. Patient education and prevention of relapses and complications are essential. The patient must avoid triggers (stress being the most important), infections especially herpes simplex, and drugs and vaccinations that induce pemphigus. Possibly avoidance of some food and toxic substances are also important in the management of these patients.

Pemphigus seems to be more frequent in Iran, with a more severe phenotype and younger patients. Multicenter studies are warranted to find the best and most cost-effective treatment.