Assessment of the therapeutic benefit of oral prednisolone and common adjuvant therapy in stage II of randomized controlled trial study for management of pemphigus vulgaris.

BACKGROUND: Pemphigus is an autoimmune blistering mucocutaneous disorder. Common treatments include corticosteroids and immunosuppressive drugs. This study aimed to assess the therapeutic effects of oral prednisolone along with the common adjuvant therapy in pemphigus vulgaris. METHODS:   Eighty-seven patients with pemphigus vulgaris from the first stage of a previously randomized clinical trial were enrolled in the present non-blinded clinical trial. The patients were divided into four groups and treated accordingly with prednisolone alone (P; N = 23), prednisolone and azathioprine (P/A; N = 23), prednisolone and mycophenolate mofetil (P/M; N = 21), and prednisolone and cyclophosphamide (P/C; N = 20). These patients were followed-up for an extended one-year period. RESULTS: The primary localization of the recurrence occurred in the oral cavity of 7, 6, 2, and 5 patients in the P, P/A, P/M, and P/C groups, respectively. There was no significant difference between them (P = 0.40). The mean total dose of prednisolone administered in groups P, P/A, P/M, and P/C was accordingly 7.5, 8.4, 9.2, and 8.6 mg/day. Minor recurrence of the disease in the above-mentioned groups was observed in 7 (30.4%), 5 (21.7%), 6 (28.6%), and 7 (35.0%) of the patients, respectively. With regard to the minor recurrence of the disease, there was no significant difference among the four treatment groups (P = 0.80). CONCLUSION: Since in this follow-up study no therapeutic benefit of oral prednisolone and common adjuvant therapy was found in terms of the number of minor and major recurrences, the extent to which treatment of PV can be improved upon treatment with these agents remains to be elucidated.

Quality of life and psychological status of patients with pemphigus vulgaris using Dermatology Life Quality Index and General Health Questionnaires.

Pemphigus vulgaris with painful chronic blisters and/or erosions on skin and mucosa can impair quality of life (QOL). Therapeutic modalities in the long run can have additional negative impact. There are few studies that have focused on QOL of such patients except in treated cases. The aim of this study was to describe the effect of the disease per se on QOL before receiving treatment and evaluation of psychological status of the patients and its effect on their QOL. A total of 61 patients with newly diagnosed non-treated pemphigus vulgaris participated in the study. The Persian version of the Dermatology Life Quality Index (DLQI) questionnaire was used to evaluate their QOL and the 28-item General Health Questionnaire (GHQ-28) for their psychological status. In this study, the mean DLQI score was 10.9 ± 6.9. QOL was worse in patients with nasal and pharynx involvement, with positive Nikolsky sign, patients with severe skin involvement and those who showed the symptom of itching. There was a negative correlation between DLQI score and duration of the disease. More than 77% of patients experienced anxiety and depression with more impaired QOL. In conclusion, pemphigus vulgaris is responsible for great alteration in QOL, especially in its severe form. The disease in its initial stage may have greater impact on the QOL. The high probability of anxiety and depression in these patients and its negative effect on QOL should be taken into account in the management of these patients right from the start of the treatment.

Spectrum of autoimmune bullous diseases in Iran: a 10-year review.

BACKGROUND: Autoimmune bullous diseases (ABDs) are potentially devastating bullous dermatoses of the skin and mucosae characterized by the presence of tissue-bound and circulating antibodies directed against disease-specific target antigens. These diseases comprise two major subgroups of subepidermal autoimmune bullous disorders and pemphigus, based on the level of blister formation. Although they occur worldwide, the relative frequencies of different ABDs show wide geographical variation. Most epidemiological studies on ABDs have focused on single diseases or a group of diseases; published surveys studying the whole spectrum of diseases are scarce. OBJECTIVES: This study aimed to assess the relative frequencies of different ABDs in patients presenting to the Bullous Diseases Research Center, Tehran, Iran. METHODS: Medical files for all newly diagnosed patients with ABD presenting to the Center between March 1997 and February 2006 were examined. Patients with dermatitis herpetiformis were not included. RESULTS: A total of 1402 patients were diagnosed with ABD during the study period. Pemphigus vulgaris (PV) was the most common ABD (81.2%), followed by bullous pemphigoid (BP) (11.6%), pemphigus foliaceus (PF) (4.4%), pemphigoid gestationis (0.7%), mucous membrane pemphigoid (0.7%), epidermolysis bullosa acquisita (0.5%), linear immunoglobulin A (IgA) disease (0.4%), paraneoplastic pemphigus (0.2%), IgA pemphigus (0.2%), and pemphigus erythematosus (0.1%). The mean age at diagnosis and male : female ratio were 43.4 years and 1 : 1.39, 42.2 years and 1 : 1.34, and 59.4 years and 1 : 1.36 for PV, BP, and PF, respectively. CONCLUSIONS: Pemphigus vulgaris was the most frequent ABD according to our study; cases of PV outnumbered those of BP by a ratio of almost 8 : 1. This finding contrasts with those of studies conducted in Western European countries, in which BP predominates. There was a female predominance in most subtypes of ABD. Mean age at onset of PV and BP was lower than in Europe. In view of its large population of PV patients, Iran should be considered a suitable field for future clinical trials.

Pemphigus and pregnancy: a 23-year experience.

BACKGROUND: Studies on the interaction of pemphigus and pregnancy are limited to case reports and small case series. Pregnancy is not rare in Iranian pemphigus patients due to lower age at onset of the disease. AIM: We sought to investigate the outcome of pregnancy and the course of pemphigus in pemphigus patients in a retrospective study. METHODS: The files of 779 pemphigus women younger than 50 presenting to our center from 1984 till 2006 were examined for any mention of pregnancy. Data related to outcome of pregnancy and the course of the disease were collected. RESULTS: Sixty-six patients with a history of pregnancy were identified. Forty-eight known pemphigus patients experienced one or more pregnancies during their disease (total pregnancy number: 52). The course of pemphigus was as follows in this group: 28 cases (54%) of exacerbation, 15 cases (31%) with no alteration, and 9 cases (17%) showing improvement. The rate of abortion was 9.6% (5 cases). In 18 cases, the disease had started during pregnancy, 2 of them (11%) ended in an abortion. Overall, postpartum flare was seen in 33 cases (47.1%). CONCLUSION: Pemphigus may be exacerbated during or after pregnancy, but often to a mild degree. Although the rate of stillbirth was not as high as previously reported, the rate of abortion was considerable. Pregnancy may have an uneventful course, especially in patients in clinical remission; nevertheless, careful monitoring of the high risk mother and fetus is mandatory.

Desmoglein ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris.

Anti-desmoglein 3 and 1 autoantibodies are involved in the pathogenesis of pemphigus diseases. Our objective was to assess the value of ELISA in the diagnosis of pemphigus and its correlation with the severity of pemphigus vulgaris. Based on clinical presentation and histopathologic confirmation for the diagnosis of the pemphigus, 38 patients took part in the study. Sera of the patients were tested by desmoglein 1 and desmoglein 3 ELISA. Also, direct immunofluorescence was performed for all patients which revealed positive results in 36 patients (94.7%). ELISA was positive in 37 of 38 pemphigus patients (Sensitivity: 97.3%). The relationship between desmoglein 1 index values and skin severity was statistically significant (p<0.05). Desmoglein 3 index values increased with oral severity although this was not statistically significant. Iranian patients similar to Indian patients had higher positive anti-desmoglein 1 autoantibodies. Desmoglein-ELISA test is appropriate in the diagnosis of pemphigus. Desmoglein 1 index value is statistically correlated with the severity of pemphigus vulgaris.

Nail changes in pemphigus vulgaris.

BACKGROUND: The frequency and types of nail changes in pemphigus vulgaris (PV) are unclear. Aim To determine the frequency and types of nail changes, and their correlation with the number of skin and periungual bullae. METHODS: Seventy-nine patients with PV, including 59 new patients and 20 patients in relapse, were entered into the study. Microscopic examination in potassium hydroxide and culture for fungus were performed on all clinically abnormal nails. RESULTS: Twenty-five (31.6%) of 79 patients showed nail changes, with paronychia (n = 8) and onychomadesis (n = 6) being the most common. One patient in relapse had onychomycosis. The frequency of nail changes in fingers affected by periungual bullae was significantly higher than in other fingers (P < 0.05). The number of nail changes was higher in patients with a larger number of skin bullae and in those with a longer duration of disease (P < 0.05). CONCLUSIONS: Nail changes in PV are common and related to the number of skin bullae and the presence of periungual bullae.

Role of thiopurine methyltransferase activity in the safety and efficacy of azathioprine in the treatment of pemphigus vulgaris.

OBJECTIVE: To evaluate the relationship between thiopurine methyltransferase (TPMT) activity and the safety and efficacy of azathioprine sodium in the treatment of pemphigus vulgaris. DESIGN: Cross-sectional study. SETTING: Referral university hospital for autoimmune blistering diseases. PARTICIPANTS: One hundred thirty-nine patients with pemphigus vulgaris treated with azathioprine. Intervention The TPMT activity in red blood cells was measured using high-performance liquid chromatography. Main Outcome Measure Severe adverse effects were defined as those judged serious enough that azathioprine therapy be discontinued in 139 patients treated with azathioprine. To evaluate the relationship of clinical response and TPMT concentration in 52 patients who had been treated with a combination of prednisolone and azathioprine only for at least 1 year were included in the study, and the clinical response was considered favorable if there was no recurrence of pemphigus vulgaris in the first year of treatment. RESULTS: The median activity of TPMT was 44.7 ng/mL/h (interquartile range, 28.7 ng/mL/h). Eleven patients (7.9%) had low TPMT activity (TPMT-HL), 127 patients (91.4%) had normal TPMT activity (TPMT-HH), and 1 patient (0.7%) had supranormal enzyme activity; TPMT activity was noted in all patients. Serious adverse effects occurred in 14 patients (10.1%). There was no relationship between development of adverse effects and TPMT activity (P = .29). Eleven patients with low TMPT activity had been treated with azathioprine for a mean (SD) of 10.2 (4.1) months. Only 1 patient exhibited serious adverse effects. The TPMT enzyme activity was not different in 28 patients with unfavorable clinical response compared with 24 patients with favorable clinical response (P = .09). Conclusion Larger prospective studies are needed to determine the clinical relevance of TPMT activity and to determine accurate azathioprine dosing guidelines based on TPMT activity.

Impact of smoking on pemphigus.

BACKGROUND: A positive history of smoking is less common in patients with pemphigus than in healthy subjects. The aim of this case-control study was to compare the remission rate and clinical locations involved in smokers and nonsmokers with pemphigus vulgaris. METHODS: Seventy patients with pemphigus vulgaris, treated with a uniform protocol, were enrolled. The sites of involvement, average time needed for disease control, and number of relapses were compared in smokers and nonsmokers. At the end of the first and second years of treatment, the rate of remission was compared in the two groups. RESULTS: Ten of the patients were current cigarette smokers, but the other 60 (85.7%) had no history of smoking. There was no difference in the rate of cutaneous or mucosal involvement between smokers and nonsmokers. The predominant subtype was the mucocutaneous type in both groups. Smokers with pemphigus vulgaris achieved partial remission more frequently than nonsmokers at the end of the first year of treatment. The number of patients in remission at the end of the second year of therapy was significantly higher for smokers with pemphigus than for nonsmokers. The main reason for disease activity in both groups was recurrence. CONCLUSIONS: Cigarette smoking may not affect the rate of cutaneous or mucosal involvement in pemphigus; however, the data indicate that remission may be achieved sooner in pemphigus patients who smoke.

Treatment of pemphigus vulgaris with mycophenolate mofetil as a steroid-sparing agent.

Pemphigus vulgaris is a rare autoimmune blistering disease. Estimation of the incidence in Iran is one patient per 100,000 of the population per year. Mycophenolate mofetil is an immunosuppressive drug and successful treatment of pemphigus vulgaris and bullous pemphigoid has been reported with it, in combination with high dose prednisone, or as monotherapy. The present study describes our experience of the adjuvant use of mycophenolate mofetil in the management of 31 patients with pemphigus vulgaris as an initial treatment. We evaluated the efficacy and safety of mycophenolate mofetil combined with prednisolone in this cohort. We also assessed the relationship between the demographic indices/disease severity factors, and the failure of this treatment. In this study, mycophenolate mofetil was of definite benefit in 21 cases (67.7%). Generalized forms; patients with higher sum of the clinical scores at presentation; severe involvement of the groin; chest; face and limbs and those who had nail dystrophy also appeared to have poorer responses. When we excluded patients with generalized forms, only four patients were included in the failure group and the response rate reached 83.3%. It can be concluded that, except for generalized diseases, mycophenolate mofetil can be used safely and effectively in patients with pemphigus vulgaris as a first line, steroid sparing agent.

Pemphigus vulgaris in Iran: a clinical study of 140 cases.

BACKGROUND: Pemphigus vulgaris (PV) is a rare autoimmune blistering disease of the skin and mucous membranes. It varies in its clinical profile and epidemiologic characteristics in different parts of the world. OBJECTIVE: To determine the clinical features of PV in Iran in a prospective manner. METHODS: The study included 140 patients with newly registered PV attending our dermatology clinic between January 2003 and June 2004. RESULTS The mean age at the onset of the disease was 41.5 +/- 15.7 years, with a female to male ratio of 1.59 : 1. At presentation to our clinic, both skin and mucosal involvement was observed in 95 patients (67.9%). Cutaneous lesions without the involvement of the mucous membranes were seen in nine patients (6.4%), and exclusive mucosal involvement was present in 36 patients (25.7%). The most common initial localization of the disease was the oral cavity, which was involved in 93 patients (77.5%). The most frequent cutaneous and mucosal sites involved were the thorax and oral cavity, respectively. CONCLUSION: Although minor differences were noted, the results of this study are in relatively good agreement with the literature with regard to the age, gender, and initial presentation of PV in Iran. Some skin sites, such as the scalp, thorax, and axilla, may be more commonly affected in men. Patients with initial mucosal lesions were significantly younger than those with initial cutaneous involvement. Mucosal lesions other than the oral mucosa may be more common than previously thought.

Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris.

BACKGROUND: Pemphigus is a severe autoimmune blistering disease affecting the skin and mucosa. Mortality is high in the absence of treatment. Nowadays, treatment is based mainly on corticosteroids and cytotoxic drugs; however, because of the rarity of the disease worldwide, there is not yet a standard treatment based on randomized controlled trials, and the treatment used is based mainly on the experience of experts. OBJECTIVE: The aim of this study was to compare the efficacy and safety of 4 treatment regimens for pemphigus vulgaris: prednisolone alone, prednisolone plus azathioprine, prednisolone plus mycophenolate mofetil, and prednisolone plus intravenous cyclophosphamide pulse therapy. METHODS: One hundred twenty new cases of pemphigus vulgaris were enrolled. These patients were randomly allocated into 1 of 4 treatment groups (each comprising 30 patients) and received prednisolone (P), prednisolone and azathioprine (P/A), prednisolone and mycophenolate mofetil (P/MM), and prednisolone and intravenous cyclophosphamide pulse therapy (P/PC). They were followed up for 1 year at the Pemphigus Research Unit. RESULTS: In groups P, P/A, P/MM, and P/PC, 23 (76.5%), 24 (80%), 21 (70%), and 22 (73.3%) of the patients, respectively, followed the regimen for the full 1-year period. The mean total dose of prednisolone administered in groups P, P/A, P/MM, and P/PC was 11631 mg (standard deviation [SD] = 7742), 7712 mg (SD = 955), 9798 mg (SD = 3995), and 8276 mg (SD = 810), respectively. The mean total dose of prednisolone in group P (prednisolone alone) was 11,631 mg, The mean total dose of prednisolone in the 3 cytotoxic groups was 8652 mg. By using analysis of variance, the difference was statistically significant (P = .047). In the cytotoxic groups, there was a significant difference between the P/A and P/MM groups (P = .007), but not between P/A and P/PC (P = .971), and P/MM and P/PC (P = .670). Side effects were not significantly different among the 4 groups. LIMITATIONS: Larger sample sizes and blind design are suggested for future studies. CONCLUSION: The efficacy of prednisolone is enhanced when it is combined with a cytotoxic drug. The most efficacious cytotoxic drug to reduce steroid was found to be azathioprine, followed by cyclophosphamide (pulse therapy), and mycophenolate mofetil.

KID syndrome.

KID syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We have described a 4-year-old girl who is treated with bland emollients and topical keratolytics such as urea and surprisingly observed marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think that along with urgent ophthalmologic and otolaryngologic measures, simple topical therapies may improve skin condition in KID syndrome precluding the possible hazards of systemic retinoid therapy.

Bilateral cutaneous leishmaniasis of upper eyelids: a case report.

An 11-year-old girl presented with a 6-month history of bilateral upper eyelid erythema, induration, and blepharitis resistant to conventional antibiotic therapy. The lesions gradually progressed to symmetrical ulcerative nodules within 3 months. Cutaneous smear and biopsy revealed numerous amastigotes in macrophage cells. Therapy with systemic pentavalent antimonial resulted in successful healing of lesions. We conclude that cutaneous leishmaniasis must be kept in mind in the differential diagnosis of bilateral chronic eyelid swelling in endemic regions of the world.

Pemphigus: analysis of 1209 cases.

BACKGROUND: Pemphigus is a rare and chronic life-threatening disease. The clinical picture varies in reports from different regions of the world. OBJECTIVE: To define the clinical forms of pemphigus in a large cohort of patients. METHODS: Prospective analysis of 1209 patients diagnosed and followed at the Pemphigus Research Unit, Tehran University for Medical Sciences, from 1984 to 2003. RESULTS: The mean age at onset was 42 years with a female to male ratio of 1.5/1. The most frequent form was pemphigus vulgaris. In pemphigus vulgaris, patients' mucous membrane involvement alone was observed in 18%, skin involvement alone in 12%, and both in 70%. Pemphigus foliaceus was observed in 7% of the patients. Most complications were iatrogenic. CONCLUSION: In Iran, pemphigus vulgaris is the most frequent form of pemphigus. Females are more prone to the disease. The incidence of pemphigus in Tehran is approximately 1.6 per 100,000/year, and in Iran 1.0 per 100,000/year. The age of onset was lower than classically reported. Death occurred in 6.2% of the patients. In pemphigus vulgaris, the mucosal and skin form together had a worse prognosis than the other clinical forms.

Topical calcipotriol therapy in nail psoriasis: a study of 24 cases.

There are few reports regarding the treatment of nail psoriasis with topical calcipotriol. We undertook a case series study to evaluate the efficacy and safety of calcipotriol ointment (50 microg/g) in the treatment of nail psoriasis in 24 patients. This study involved 19 women and 5 men with nail psoriasis referred to Dermatology clinics of Razi hospital. The duration of trial was from October 2002 to September 2004. Informed consent was obtained from all patients before entering into the study. The patients applied calcipotriol ointment to the affected nails twice daily without occlusion for 3 months. Patients were seen by two academic dermatologists initially, after 2 weeks, and then at monthly intervals. The efficacy and safety were clinically assessed and any side effect was recorded. Patients who showed 50 percent or greater reduction in the baseline subungual thickness in at least one nail were considered to be responders and were offered continuation of therapy for an additional 2 months. After discontinuation of therapy, followup visits were performed at 1 and 2 months. After 3 months of therapy, fourteen patients showed significant clinical improvement, two of them were completely free from nail lesions after 5 months. Calcipotriol was particularly effective in subungual hyperkeratosis, onycholysis, and discoloration. In four patients fingertip tenderness and in one case the pain of involved distal phalanx were significantly reduced. No clinical response was observed in four patients. Only two cases showed adverse reactions. Topical Calcipotriol is an effective treatment for nail psoriasis and can be considered to be a safe topical treatment in chronic cases; its high tolerability allows prolonged usage without severe side effects.

Assessment of histologic criteria in the diagnosis of mycosis fungoides.

BACKGROUND: The histologic diagnosis of early mycosis fungoides (MF) can be difficult to establish in many instances because the subtle changes observed in patches of MF are also present in many inflammatory dermatoses. METHODS: To assess the frequency and significance of many of these histologic parameters, we retrospectively reviewed 50 slides from patients with documented MF in patch, plaque, and tumor stages. The diagnosis of MF was unequivocally established either by the progression of patients to advanced stages of the disease or by indubitable histologic findings. In the second phase of the study, we compared the histologic parameters observed in 24 patch stage MF patients with those in 24 non-MF patients. The non-MF group were patients whose pathologic pattern was suspicious for MF, but who definitely did not have MF on clinical grounds. The two groups were matched by histologic pattern. Two different observers evaluated the slides and the intensities of 32 histologic parameters were graded on a four-point scale to minimize the subjective variability in the histologic reports. RESULTS: On univariate analysis, the following parameters achieved significance in distinguishing MF from non-MF: Pautrier's microabscesses, haloed lymphocytes, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted lymphocytes in the epidermis and dermis, absence of dyskeratosis, and papillary dermal fibrosis. None of these features proved to have additional discriminating power on multivariate analysis. CONCLUSIONS: The efficacy of single histologic features in the diagnosis of early MF is generally poor and, to discriminate MF from its inflammatory simulators, a combination of cytologic and architectural features must be used.