Fragrance contact allergy in Iran.

BACKGROUND: Fragrances are considered as one of the most common causes of allergic contact dermatitis. About 1-4% of the general population suffer from fragrance contact allergy (FCA). OBJECTIVES: To determine the frequency of FCA and its clinical relevance in a sample of Iranian patients with history of contact and/or atopic dermatitis from January 2004 to December 2008. METHODS: Standardized patch testing with 28-allergen screening series recommended by the German Contact Dermatitis Research Group and European Standard Series was used at six dermatological clinics in Iran. Fragrance allergens comprised of fragrance mix I (FM I), Myroxylon pereirae (MP; balsam of Peru), Lyral, turpentine and FM II. RESULTS: Fragrance contact allergy was detected in 7.2% of the patients. The frequency of positive reactions to FM I, MP and FM II were 3.7% (41/1105), 2.8% (32/1135) and 1.1% (3/267) respectively. 82.4% of the reactions to fragrance allergens were clinically relevant. The most common involved areas were hands (68.4%) and face (35.4%). Fragrance allergy predominantly affected women aged more than 40 years (P=0.008). Positive reaction to more than two allergens was significantly higher in FCA patients compared with other contact dermatitis patients (P<0.0001), and FM I, nickel and MP were the most frequent allergens in these patients. CONCLUSIONS: Despite less frequency of FCA in comparison with some European countries, its clinical relevance in Iranian patients seems to be high. It mostly affects the hands and the face predominantly in women aged more than 40 years.

Desmoglein 1 and 3 enzyme-linked immunosorbent assay in Iranian patients with pemphigus vulgaris: correlation with phenotype, severity, and disease activity.

BACKGROUND: Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder of the skin and mucosa characterized by the presence of autoantibodies against desmoglein3 (Dsg3). Some patients also have antibodies against desmoglein1 (Dsg1). The aims of this study were to evaluate the diagnostic value of Dsg enzyme-linked immunosorbent assay (ELISA) in Iranian PV patients, to assess its correlation with the clinical phenotype and severity of disease and to investigate the changes of these antibodies after treatment. METHODS: Seventy-three patients with PV (29 men, 44 women) presenting to the Pemphigus Research Unit at Razi Hospital, Tehran, Iran were enrolled. ELISAs were used to detect IgG autoantibodies reactive with the ectodomains of Dsg1 and Dsg3, and the correlation of antibodies with the clinical phenotype as well as oral and skin disease severity was assessed. In addition, the tests were repeated in 18 patients after treatment and the resulting remission. RESULTS: Anti-Dsg1 and anti-Dsg3 were detected in 56 (76.7%) and 69 (94.5%) patients, respectively. Anti-Dsg1 and anti-Dsg3 antibodies were present in 48 (94.1%) and 50 (98%) patients with mucocutaneous type, in 2 (12.5%) and 15 (93.7%) patients with mucosal type, and in 6 (100%) and 4 (66.7%) patients with cutaneous PV, respectively. The mean anti-Dsg1 index values were significantly higher in cutaneous and mucocutaneous phenotypes than mucosal PV (P < 0.001). The mean anti-Dsg3 index values were significantly lower in cutaneous and mucosal phenotypes than mucocutaneous PV (P < 0.01). The severity of skin lesions (but not oral lesions) was correlated with anti-Dsg1 antibody level (P < 0.001); on the other hand, the severity of oral lesions (P < 0.01) as well as skin lesions (P < 0.001) was significantly correlated with anti-Dsg3 antibody levels. Both anti-Dsg1 and anti-Dsg3 levels were significantly reduced after treatment and clinical remission (P < 0.001). CONCLUSION: Dsg ELISA is not only a sensitive tool for the diagnosis of PV, it can also serve as a predictive means for assessing the severity as well as for monitoring the disease activity. Although, in general, the clinical phenotype is related to the antibody profile, there are occasional cases with discordant phenotype and antibody profile. These discrepancies might be explained by genetic variations or the presence of possible minor antigens involved in the pathogenesis of pemphigus.

A randomized, double-blind, placebo-controlled clinical trial of itraconazole in the treatment of cutaneous leishmaniasis.

BACKGROUND: Several modalities have been used for the treatment of cutaneous leishmaniasis (CL) with various results. In vitro and in vivo studies have shown inhibitory effects of azole drugs on Leishmania parasites. OBJECTIVES: To evaluate the efficacy and tolerability of oral itraconazole in the treatment of CL caused by L. major. METHODS: A total of 200 patients with parasitologically confirmed CL with a duration of less than 45 days from a well known L. major endemic area were included in a randomized, double-blind, placebo-controlled clinical trial. The patients received either itraconazole 200 mg daily (100 patients) or placebo (100 patients) for 8 weeks. The primary outcome measures were clinical cure (complete re-epithelization of all lesions) and parasitological cure at the end of the treatment. RESULTS: Eighty-three patients in the itraconazole and 75 patients in the placebo group completed the treatment course. After 8 weeks of treatment, clinical cure was observed in 59% and 53% and parasitological cure was observed in 83% and 76% of patients in the itraconazole and placebo groups, respectively, which were not significantly different. There was no difference in the rate of adverse events. CONCLUSIONS: An 8-week course of oral itraconazole was not more effective than placebo in the treatment of CL.

Immune response measured in human volunteers vaccinated with autoclaved Leishmania major vaccine mixed with low dose of BCG.

The immune responses induced against Leishmania antigens in volunteers who were vaccinated in a double-blind, randomized field efficacy trial of a preparation of autoclaved Leishmania major (ALM) mixed with a low dose of Bacille Calmette-Guerin vaccine (BCG) who developed either a cutaneous leishmaniasis (CL) lesion due to exposure to infected sandfly bite(s) or did not develop a lesion during the course of the trial were studied and compared with those of non-vaccinated controls. Blood samples were also assayed from different groups including volunteers with history of CL and volunteers with previous positive or negative leishmanin skin test (LST) without a history of CL. The vaccinated volunteers had received a single dose of either ALM mixed with a low dose of BCG or the same dose of BCG alone. The LST and in vitro proliferative response (stimulation index, SI), interferon gamma (IFN-gamma) production and, in a few cases, interleukin (IL)-4 production of peripheral blood mononuclear cells to soluble Leishmania antigens were measured. The results indicated that volunteers who developed CL in the vaccine arm showed a slightly higher SI than cases who received BCG alone. Volunteers with history of CL and volunteers with positive LST demonstrated the strongest proliferation indices and IFN-gamma production. The data suggest that a single dose of ALM + BCG induces a weak Th1 response in vaccinated volunteers that is far lower than that in volunteers with prior subclinical infection or volunteers with history of CL, who are presumed to be immune.

Itraconazole pulse therapy improves the quality of life of patients with toenail onychomycosis.

BACKGROUND: Toenail onychomycosis is a common disease that can have serious adverse effects on the quality of life (QOL) of patients. AIM: To evaluate the impact of itraconazole pulse therapy on the QOL of patients with toenail onychomycosis. METHODS: A total of 20 patients with disto-lateral subungual toenail onychomycosis were treated with itraconazole 200 mg twice daily for 1 week every 4 weeks for 12 weeks. The patients were asked to complete a QOL questionnaire before treatment and on the last follow-up visit (week 48). A score of 0-4 was given according to the five possible responses to each question and these were summed to give the final score of the patient. The mean of the final scores of the patients before and after treatment were compared using the Wilcoxon matched-pairs test. RESULTS: At 48 weeks after commencing treatment, 14 patients (70%) responded to treatment (nine patients were cured with almost totally clear toenails and five patients improved), and 16 patients (80%) were mycologically cured (negative KOH smear and culture). The mean of the QOL scores of the patients before treatment was 18.0+/-7.8, which reduced to 13.1+/-11.3 after treatment (two-tailed, p=0.009). CONCLUSION: Itraconazole pulse therapy is an effective treatment and can improve the QOL of patients with toenail onychomycosis.

Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated leprosy patients, a randomised, placebo-controlled trial.

OBJECTIVE: to evaluate immunotherapy as a means of improving peripheral blood flow in chronic leprosy patients. DESIGN: this was a double-blind, randomised, placebo-controlled, clinical trial. MATERIALS: heat-killed Mycobacterium vaccae 1mg plus 0.02 microg Tuberculin protein per 0.1 ml dose in borate buffer, with saline as placebo. Those studied were 92 long-treated residents of a leprosy centre in Iran, 10 of their healthy children and 10 staff members. Evaluation employed the Perimed PF2, Laser-Doppler Flowmeter, a platinum skin thermistor, and a thermal sensibility tester. METHODS: single intradermal injections of test or placebo were given to 103 patients 18 months before the blinded evaluation. Fingerpulp blood flux was measured in controlled conditions and vasomotor reflexes and skin sensation to touch, pain and heat were evaluated in 45 and 47 patients in the placebo and M. vaccae groups, respectively, and in 20 healthy control persons. RESULTS: Laser-Doppler flux, skin temperature, vasomotor reflexes and sensation were impaired in leprosy patients. Immunotherapy improved (p < 0.05) Laser-Doppler flux, skin temperature and temperature sensation. CONCLUSIONS: immunotherapy, given 18 months earlier, significantly improved blood flow and temperature sensation, in fully-treated, chronic, leprosy patients. The same principles might be employed in other conditions of reduced peripheral blood flow.

Successful treatment of ocular leishmaniasis.

PURPOSE: To report successful treatment of a case of ocular leishmaniasis with combined stibogluconate and allupurinol. METHOD: A 32-year-old physician developed a non-tender reddish chalazion like lesion in his right lower lid, associated with conjunctivitis and nodular episcleritis. Biopsy of the lesion in his eyelid and conjunctiva disclosed a dense inflammatory response including histiocytes containing typical leishmania organisms. RESULT: Therapy with stibogluconate, both intralesional and intramuscular, was initiated with some improvement. However recurrence of the lesion occurred. Systemic retreatment with combined stibogluconate and allupurinol led to complete healing of the lesion. CONCLUSION: Ocular leishmaniasis is a rare and potentially blinding disorder. Combined stibogluconate and allupurinol may be an effective therapy in such cases.

Validation of the diagnostic criteria for atopic dermatitis.

OBJECTIVE: To validate the accuracy of newly proposed diagnostic criteria for atopic dermatitis (AD). DESIGN: Double-blind, cross-sectional study comparing the achievement of new criteria with the diagnosis of a dermatologist. SETTING: A private, general dermatology, outpatient clinic. PATIENTS: A sample of 416 consecutive patients attending the clinic within 2 months (146 males and 270 females), consisting of 60 patients with AD and 356 control patients with other skin diseases. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of proposed criteria in the diagnosis of AD. RESULTS: Sensitivity, specificity, and positive and negative predictive values of proposed diagnostic criteria for AD were 10.0% (95% confidence interval [CI], 4.1%-21.2%), 98.3% (95% CI, 96.2%-99.3%), 50.0% (95% CI, 22.3%-77.7%), and 86.6% (95% CI, 82.8%-89.7%), respectively. CONCLUSIONS: These diagnostic criteria for AD are highly specific and are suitable for clinical trials. However, they may not achieve enough sensitivity to be useful for large, population-based epidemiological studies or for routine clinical practice, at least in Iran.

A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran.

BACKGROUND: A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to human transmission) cutaneous leishmaniasis in a randomised double-blind trial in Bam, Iran. METHODS: 3637 schoolchildren, aged 6-15 years, with no history of cutaneous leishmaniasis and no response to a leishmanin skin test, were randomly assigned to receive 1 mg ALM mixed with BCG (n = 1839), or BCG alone (n = 1798). Safety of the vaccine and the incidence of confirmed cases of cutaneous leishmaniasis were followed up for 2 years. FINDINGS: Side-effects were those usually associated with BCG vaccination, but tended to persist longer in the ALM + BCG group. After exclusion of four cases occurring within 80 days of vaccination (one in the ALM + BCG group and three in the BCG group), the 2-year incidence of cutaneous leishmaniasis did not differ significantly between vaccine and BCG groups: 2.8% vs 3.3%, respectively (total cases 112). A sex-stratified analysis showed that in boys the vaccine conferred a protective efficacy of 18% and 78% for the first and second years, respectively--a crude 2-year overall protection of 55% (95% CI 19-75%, p < 0.01). In the first 9 months after vaccination, there was a non-significant excess of cases in the ALM + BCG group (25 vs 16), whereas the incidence of cutaneous leishmaniasis thereafter was significantly reduced in the ALM + BCG group (27 vs 44, p < 0.05). INTERPRETATION: A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test. The exact reason for the apparent protective effect of the vaccine in boys is unknown, and may be a chance finding. However, since boys are more exposed to the infection, which is indicated by higher disease prevalence in boys in this study population, the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies. Booster injections or alternative adjuvants should be tried to improve the potential efficacy of this vaccine.

Granuloma faciale: successful treatment of nine cases with a combination of cryotherapy and intralesional corticosteroid injection.

BACKGROUND: Granuloma faciale is a rare disorder characterized by asymptomatic papules, nodules, and plaques on the face. Although the exact pathogenesis of this disease in unclear, it is considered a variant of leukocytoclastic vasculitis confined to the skin. Several medical and surgical methods have been used to treat it with variable results. CASE REPORTS: We report nine cases of granuloma faciale treated with a combination of cryotherapy with liquid nitrogen and intralesional injection of corticosteroids. RESULTS: The lesions cleared completely in all of the patients without any side-effects. No recurrences have been observed. CONCLUSIONS: Cryotherapy with liquid nitrogen, followed by intralesional injection of corticosteroids, is a safe and effective method to treat granuloma faciale.

Identical MHC markers in non-Jewish Iranian and Ashkenazi Jewish patients with pemphigus vulgaris: possible common central Asian ancestral origin.

Previous studies showed that almost all Ashkenazi Jewish patients with pemphigus vulgaris carried the extended haplotype [HLA-B38, SC21, DRB1*0402, DQB1*0302] or [HLA-B35, SC31, DRB1*0402, DQB1*0302] or class II fragments of them. Non-Jewish patients carried [HLA-B55, SB45, DRB1*1401, DQB1*0503] or its class II fragments. In the present study of 20 Iranian patients with pemphigus vulgaris, 17 were found to carry DRB1*0402, DQB1*0302 haplotypes, also found among normal Iranian haplotypes and the same as that of the Jews. These findings suggest that the pemphigus MHC susceptibility gene among Iranians derived from the same ancestor as that in the Ashkenazim. The ancient Jews were under Persian domination from 500 B.C. until 300 B.C. and in the 8th century A.D., a Tataric people living in the kingdom of Khazar on the Western shore of the Caspian Sea and the Northern shore of the Black Sea, near Persia, converted to Judaism, providing possible opportunities for gene mixing in two populations that are distinct and separate today.