38 research outputs found
Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus
Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus
Wieloogniskowe nowotwory skóry u chorych po przeszczepieniu nerki — opis przypadków i przeglÄ…d piÅ›miennictwa
Terapia immunosupresyjna stosowana po przeszczepieniu nerki ma immunomodulujący wpływ na układ odpornościowy, co bezpośrednio prowadzi do znamiennego wzrostu zachorowalności na nowotwory. Istotne jest, że nowotwory skóry w populacji chorych po przeszczepieniu narządów występują znacznie częściej wieloogniskowo oraz mają bardziej agresywny przebieg.
Zaprezentowano opis dwóch przypadków pacjentów po przeszczepieniu nerki, u których wystąpiły wieloogniskowe nowotwory skóry. Pierwszy z nich to przypadek 45-letniego pacjenta z wieloogniskowym czerniakiem, natomiast drugi dotyczy 67-letniego chorego, u którego rozwinęło się osiem ognisk raka skóry. Chorzy po transplantacji ze zdiagnozowanymi rakami skóry powinni być kontrolowani przez dermatologa co 6 miesięcy, natomiast z rozpoznanym czerniakiem co 3 miesiące ze względu na to, że kolejne ogniska nowotworów skóry pojawiają się w ciągu pierwszych 15 miesięcy od rozpoznania pierwotnego
The value of the pragmatic-explanatory continuum indicator summary wheel in an ongoing study: the bullous pemphigoid steroids and tetracyclines study
BACKGROUND: The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus. METHODS: Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial. RESULTS: The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the 'flexibility of the comparison intervention' and 'practitioner adherence' domains (SD = 13). The trial team appeared to disagree most on the 'eligibility criteria' (SD = 35) and 'participant compliance' (SD = 31) domains, although the large standard deviations were a result of a single outlier in the two domains. CONCLUSION: The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies. TRIAL REGISTRATION: Current Controlled Trials http://www.controlled-trials.com/ISRCTN13704604
Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial
Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids.Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids
Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial
Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids.
Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed.
Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001).
Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term
Interventions for Mucous Membrane Pemphigoid/Cicatricial Pemphigoid and Epidermolysis Bullosa Acquisita
n/