Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This ...Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher’ s exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1 12 (DR12) (11.2% vs 2.5% , pc < 0.01) and the haplotype DRB1 12/DQB1 0301/04/09/010 (11.2% vs 2.5% , p < 0.001, pc < 0.05), and a lower frequency of DRB1 0301/04 (DR17) (11.8% vs 25.8% , pc < 0.01) and the haplotype DRB1 03/DQB1 02DRB1 0301/ DQB1 0201/02/03 (11.2% vs 24.6% , pc < 0.0001) in patients compared with controls. HLADR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.展开更多
Hyperimmunoglobulin E syndrome (HIES) is a rare immunode-ficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cas...Hyperimmunoglobulin E syndrome (HIES) is a rare immunode-ficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.展开更多
Background: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-α , has been shown to be effective for moderate to severe psoriasis, but there are few data published on its ...Background: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-α , has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant resistant disease or in combination with other antipsoriatic therapies. Objectives: To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease. Methods: All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period. Results: Twenty three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5 ± 6.7, mean ± SD, n = 22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two). Conclusions: Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.展开更多
文摘Lichen sclerosus (LS) is considered to have an immunogenetic background. Several small studies, using serological typing, have reported that HLA-DR11, DR12, and DQ7 were increased in LS, with DR17 less frequent. This study aimed to validate and detect new HLA-DR and DQ associations with LS in females and its characteristic clinical parameters. The cases, 187 female LS patients, and 354 healthy controls were all UK North Europeans. PCR-sequence specific primers method was applied to genotype the HLA-DR, DQ polymorphisms that correspond to 17 serologically defined DR and seven DQ antigens. Statistical analysis was performed with two-tailed Fisher’ s exact test with Bonferroni adjustment (p value after Bonferrroni adjustment, Pc). We found increased frequency of DRB1 12 (DR12) (11.2% vs 2.5% , pc < 0.01) and the haplotype DRB1 12/DQB1 0301/04/09/010 (11.2% vs 2.5% , p < 0.001, pc < 0.05), and a lower frequency of DRB1 0301/04 (DR17) (11.8% vs 25.8% , pc < 0.01) and the haplotype DRB1 03/DQB1 02DRB1 0301/ DQB1 0201/02/03 (11.2% vs 24.6% , pc < 0.0001) in patients compared with controls. HLADR and DQ antigens were not associated with time of onset of disease, site of involvement, structural changes of genitals, and response to treatment with potent topical steroids. In conclusion, HLA-DR and DQ antigens or their haplotypes appear to be involved in both susceptibility to and protection from LS.
文摘Hyperimmunoglobulin E syndrome (HIES) is a rare immunode-ficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.
文摘Background: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-α , has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant resistant disease or in combination with other antipsoriatic therapies. Objectives: To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease. Methods: All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period. Results: Twenty three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5 ± 6.7, mean ± SD, n = 22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two). Conclusions: Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.
