Year : 2007 | Volume
: 52 | Issue : 4 | Page : 188--191
Epidemiology of pemphigus in northeast Iran: A 10-year retrospective study
Zari Javidi1, Naser Tayyebi Meibodi2, Yalda Nahidi1,
1 Dermatology Department, Imam-Reza Hospital, MUMS, Mashhad, Iran
2 Pathology Department, Imam-Reza Hospital, MUMS, Mashhad, Iran
Naser Tayyebi Meibodi
Department of Pathology, Imam-Reza Educational Hospital, Mashhad University of Medical Sciences (MUMS), Mashhad
Pemphigus is an autoimmune blistering disease of the skin and mucous membranes with different reported epidemiological aspects from different countries. Aim: Our aim was to evaluate the epidemiological aspects of pemphigus in Mashhad city. This is the first report with regard to the characteristics of pemphigus in Khorasan province of Iran. Materials and Methods: In this cross-sectional study, all the patients with pemphigus, who were referred to the Dermatology Department of Imam Reza hospital of Mashhad, were examined over nine years, i.e., from May 1998 to March 2007. The data obtained through questionnaires, including age, sex, profession, mucosal or skin or the involvement of both, lag-time period between the onset of disease and the first presentation, gap between cutaneous and mucosal involvements, season of onset and family history, were analysed by using statistical tests of Chi square and Student«SQ»s t -test and the statistical software of SPSS. Results: In 178 patients with pemphigus, pemphigus vulgaris was the most common type (86.5%). Female to male ratio was 1.4. In pemphigus vulgaris patients, there was involvement of both the skin and mucosa in 64.3%, mucosal involvement in 14% and skin involvement in 21.7%. There was no mucosal involvement in patients with pemphigus foliaceus. Two patients (1.4%) had a positive family history. Summer was the most common season for the onset of the disease (37.5%). Most of the patients were housewives in the premenopausal age group. Conclusion: The results reveal a high incidence of pemphigus in northeast Iran with an incidence of 20 patients per year.
|How to cite this article:|
Javidi Z, Meibodi NT, Nahidi Y. Epidemiology of pemphigus in northeast Iran: A 10-year retrospective study.Indian J Dermatol 2007;52:188-191
|How to cite this URL:|
Javidi Z, Meibodi NT, Nahidi Y. Epidemiology of pemphigus in northeast Iran: A 10-year retrospective study. Indian J Dermatol [serial online] 2007 [cited 2020 Sep 23 ];52:188-191
Available from: http://www.e-ijd.org/text.asp?2007/52/4/188/37723
The word pemphigus comes from pemphix , a Greek word that means blister. Pemphigus is a life-threatening autoimmune bullous disease that involves the squamous epithelia and mucous membranes, manifesting as loose blisters and painful erosions. IgG autoantibodies cause intraepidermal blisters as a result of acantholysis. ,, In immunopathology, we can find circulating IgG acting against desmoglein I and III. ,,,
Clinically, several subtypes of pemphigus are recognized. Pemphigus vulgaris (PV) is the most common type accounting for approximately 80% of cases worldwide. Women are more likely to be affected than men and mean age of onset is approximately 4-6 decades.  Pemphigus vegetans, pemphigus foliaceus (PF), pemphigus erythematosus, paraneoplastic pemphigus, drug-induced pemphigus, fogo selvagem or endemic pemphigus foliaceus, IgA pemphigus and pemphigus herpetiformis are the other uncommon subtypes of this disease. ,
There are some reports available on the clinical and epidemiological characteristics of pemphigus in the north and south of Iran. Since no similar study was performed in northeast Iran, this retrospective study was undertaken to examine the epidemiology of pemphigus in Khorasan Razavi, northern Khorasan and southern Khorasan provinces.
Materials and Methods
This study was carried out at the dermatology ward of Imam-Reza Hospital, Mashhad, which is a referral center for patients with pemphigus. During a 10-year period (1997-2007), a total of 178 newly diagnosed cases of pemphigus were admitted. At first, all the cases were sampled for histopathologic examination; further, diagnosis was performed on the basis of clinical, histopathological and immunofluorescence patterns.
The files of all the patients were collected and the following data were recorded: clinical variant of disease, gender, occupation, age, age at the onset of disease, family history, geographic location of residence, site and extent of lesions and season of onset. Regarding extent of the lesions, we divided our cases into two groups: cases with more than 10% involvement were known as diffuse pemphigus and those with equal or less than 10% involvement were known as limited pemphigus.
At the end of this period, the collected data were analyzed by SPSS software (version 13) using Chi-square test, Student's t -test and Fisher's exact tests in addition to Pearson and Spearman's correlation coefficient with 95% confidence interval.
During the 10-year study period (1997-2007), 178 patients were admitted in dermatology ward. In 35 cases, the questionnaires were incomplete and only age, sex and pemphigus variant were distinguished. Other 143 questionnaires were complete in all aspects. The female to male ratio was 1.4 (74 men, 104 women) for all cases with pemphigus. The age group of cases ranged from 7 to 90 years with a mean of 41.66 ± 17.69 in men and 40.82 ± 14.21 in women. There was no significant difference between the mean ages of men and women ( P = 0.734).
Pemphigus vulgaris was the most common clinical variant diagnosed in 64 (41.6%) male patients and 90 (58.4%) female patients, followed by pemphigus foliaceus in 23 (12.9%) patients and pemphigus vegetans in 1 (0.6%) patient. Pemphigus erythematosus, drug-induced and paraneoplastic, was not found. The mean of the ages of patients suffering from pemphigus vulgaris was 40.64 ± 16.04. Student's t -test did not show a significant difference between the mean ages of men and women ( P = 0.994). The mean interval between the first onset of disease and the first visit was 5.09 ± 14.07 months.
The age of cases with pemphigus foliaceus ranged from 24 to 65 years with a mean of 44.39 ± 13.3. Male to female ratio was 1.2 (10 men, 13 women). Student's t -test did not show significant difference between the mean age in men and women in this group ( P = 0.226). Mean interval between the first onset of disease and the first visit was 18.5 ± 24.75 months. There was no correlation between the mean age of patients with pemphigus vulgaris and pemphigus foliaceus ( P = 0.287).
Only one patient, aged 49 years, suffered from pemphigus vegetans.
Majority of cases with pemphigus vulgaris and foliaceus were in the age group of 30-40 years (53.4%); 60% lived in urban areas and 40% in rural areas. Fisher's exact test did not confirm any relation between the geographic location of residence and pemphigus variant ( P = 1). From the patients with pemphigus vulgaris, 21.7% had only cutaneous involvement, 14% had only mucosal involvement and 64.3% had both cutaneous and mucosal involvement. The most common site of mucosal involvement was oral mucosa in 96.5% of patients, oral/conjunctival mucosa in 2.6% and oral/genital mucosal in 0.9%. Age and sex did not have any relation with the involvement site with regard to Pearson and Spearman's correlation test ( P = 0.419, r = 0.106).
The maximum and minimum intervals between cutaneous and mucosal involvement was 10 years and 1 day, respectively. This interval was equal or less than 2 months in 65.2% of cases (15.2% had simultaneous cutaneous and mucosal involvement) and more than 2 months in 34.8%.
Pemphigus foliaceus cases had only dermal involvement. Two patients (1.4%) had positive family history; both of them had pemphigus vulgaris.
The first manifestations of pemphigus occurred in summer (35.7%), followed by autumn (24.5%), spring (21%) and winter (18.8%). Among them, 14% of the patients were government employees; 18.9%, workers; 17.5%, farmers and 49.7%, housewives. The occupation of the patients and pemphigus variant did not correlate ( P = 0.135).
Among women, 34% of the patients were in the menopausal age group. With regard to the abovementioned division 42.7% of patients had limited and 57.3% had diffuse disease. Although there was no relation between pemphigus variant and extent of the lesions ( P = 0.136), the relative morbidity risk of PV was significantly higher than PF (Risk estimate = 1.386, CI= 95%).
Pemphigus is an intraepithelial immunobullous disorder that involves cutaneous and mucosal surfaces with a worldwide distribution. Based on the site of epidermal split, pemphigus is divided to two major types: vulgaris and foliaceus. These two major types divided to subtypes as vegetans and erythematosus.
The incidence of pemphigus is reported between 0.5 to 1.62/10 5 /year in literatures. , This figure is 0.5 to 1.62 in developed countries, 1.68-2.7 in Israel, 0.67 in Shiraz, 1.6 in Tehran and 1/10 5 /year over the whole of Iran. ,,, A recent article mentioned that eight new cases of pemphigus are annually reported in Greece.  This is substantially less than our findings (20 new cases/year). This can be due to genetic and ethnic differences. A high incidence of pemphigus in some ethnic groups, namely, Ashkenazi Jews, Mediterraneans and Japanese has been shown to be strongly related to several HLA-class II genes (e.g., DR4, DrW6, DqW3, DQw8 and DQwl), DRw14 and DQB1. , These are a base for T-lymphocytes to recognize desmoglein III peptides.  Among patients with pemphigus vulgaris, 1.4% had a positive family history. A previous study conducted by Shams and colleagues in Tehran, which is the largest study on 1209 pemphigus patients in Iran, support this finding (1.5%).  Female to male ratio was 1.4. This was lower than the reports from Greece (2.25),  Tehran (1.5),  Tunisia (4.1),  Mali (4),  Italy (2.2),  Kuwait (1.7),  South Africa (1.5),  Croatia (2)  and higher than India (1.16),  Mediterranean beach of Turkey (1.35),  Bangladesh (1.3)  and Shiraz city (1.22).  Only in Saudi Arabia, a greater number of men were affected by this disorder with a male to female ratio of 2.2.  In northern America, Finland, Malaysia, England, France, Bulgaria and south eastern America morbidity rate was the same in the case of both men and women. ,, In total, we observed female dominance in majority of the literature. It can be due to more severe manifestations of disease in women or their higher referral to medical centers.  As mentioned above, 66% of women were in premenopausal ages; this is clearly higher as compared with 32% in northern Greece.  The age of onset is 4-6 decades. In middle Asia and Africa, the age of onset is significantly lower with unknown reasons. The mean age of onset was 41.17 ± 15.7. Previous studies in Africa (46 years), Saudi Arabia (43.1 years), Mali (46.7 years) and Turkey (43 years) show similar results.  Further, the results of Shams study were similar to our findings (42 years).  In our study, the mean ages of men and women were 41.66 ± 17.69 and 40.82 ± 14.21, respectively. There was no significant difference between the mean age of women and men, as supported by the study conducted by Tsankov, which reports a mean age of 54.31 ± 3.94 in women and 40.82 ± 14.21 in men.
Similar to a Turkish article, the mean age of patients with pemphigus foliaceus was higher than patients with pemphigus vulgaris,  but it was not significant. Although pemphigus vulgaris mainly affected middle-aged people, it was reported in 3-year-old and 89-year-old patients in some references.  With regard to our range of patients, we can conclude that pemphigus is expected to occur in patients with all age groups.
A study performed in Bulgaria demonstrated that about half of patients (45.94%) were workers.  Excessive heat of the work-place, anxiety and psychological stress may act as a trigger in these patients. However, in our study, majority of cases were housewives because of social and cultural differences.
Pemphigus vulgaris is the most common type accounting for approximately 80% of cases worldwide.  Higher prevalence of pemphigus vulgaris compared with other variants is reported from Shiraz city,  Turkey,  Saudi Arabia,  Bulgaria,  France,  Greece,  India,  Bangladesh,  Kuwait,  Italy  and Gilan province.  On the other hand, pemphigus erythematosus is more prevalent in Finland and pemphigus foliaceus is the dominant variant in Brazil,  South Africa, Mali, Tunisia.  We did not have these two variants in our cases. Therefore, the preponderance of pemphigus vulgaris in Caucasians and Europeans and the predominance of pemphigus foliaceus in Negros  demonstrates that the genetic and ethnic background has an important impact on the disease variant.
In this study, the total morbidity rate of mucosal involvement was 78.3% and majority of cases suffered from both cutaneous and mucosal involvement similar to Shams and colleagues study.  Despite of our study and a recent report from Bangladesh, the prevalence of oral lesions in pemphigus foliaceus patients was 0.6% as given in Shams report and 25% as given in an Indian article,  thereby confirming that mucosal involvement is not a reliable criteria for the clinical differentiation of pemphigus foliaceus and pemphigus vulgaris.
The mean interval between the onset of mucosal and dermal involvement was less than 2 months in around half of our cases. This interval was 6-9 months in India and 5-12 months in Croatia. 
The mean interval between the first onset of disease and the first visit was significantly higher in pemphigus foliaceus patients. Since our cases with pemphigus foliaceus had no mucosal involvement, we can state that the presence of mucosal lesions in patients with pemphigus vulgaris have lead to an early visit to medical centers. These findings are supported by a study conducted in Turkey. 
The exacerbation of disease in summer is reported from India and South Africa.  A study in Greece confirmed that high temperature and exposure to the sunshine can increase the relapsing risk.  Hashimoto showed that excessive heat can increase pemphigus vulgaris antigen expression in the epiderm. , Further, the study by Tsankov demonstrated that the onset of clinical manifestations predominantly occurred in spring and summer and the heat of the sun rays can provoke the disease.  In our study the onset of the disease in the majority of cases was in summer. However, pemphigus onset was often in the winter in Shiraz.  In Gilan province, there was no relationship between the prevalence of the disease and the seasons. 
The results of our study demonstrate that pemphigus vulgaris is the most common variant in northeast Iran, particularly among young housewives. The most common presentation of the disease was both cutaneous and mucosal involvement and majority of them occurred in summer.
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