Validity of noninvasive markers of methotrexate-induced hepatotoxicity: a retrospective cohort study.

BACKGROUND: Methotrexate is a cost-effective systemic treatment for moderate-to-severe psoriasis, but the perceived risk of associated liver fibrosis prevents optimal use. Procollagen III aminoterminal propeptide (PIIINP) is a widely adopted noninvasive biomarker of liver fibrosis; however, its clinical utility is narrow owing to limited evidence of performance and the need for serial measurement. The Enhanced Liver Fibrosis (ELF) assay is a validated biomarker of liver fibrosis. OBJECTIVES: To evaluate the diagnostic accuracy of the ELF test compared with PIIINP for the diagnosis of liver fibrosis in a cohort of patients with psoriasis treated with methotrexate. METHODS: A retrospective cohort study comparing the diagnostic accuracy of PIIINP and ELF in detecting liver fibrosis in patients treated with methotrexate. Liver biopsy was the reference standard. RESULTS: Twenty-seven patients were identified and included in the study. The diagnostic accuracies [area under the receiver operating curve (AUROC)] of serial PIIINP and serial ELF were 0·589 [95% confidence interval (CI) 0·379-0·800] and 0·643 (95% CI 0·391-0·895), respectively, for mild fibrosis; and 0·576 (95% CI 0·237-0·916) and 0·674 (95% CI 0·421-0·927) for at least moderate fibrosis. The AUROC values for single PIIINP and single ELF were 0·582 (95% CI 0·363-0·801) and 0·693 (95% CI 0·482-0·904), respectively, for mild fibrosis; and 0·667 (95% CI 0·363-0·971) and 0·806 (95% CI 0·564-1·000) for at least moderate fibrosis. CONCLUSIONS: This pilot study suggests that ELF may be at least equivalent or possibly superior to PIIINP in the detection of liver fibrosis in patients with psoriasis treated with methotrexate, and supports further investigations into the performance of ELF in this clinical setting.

Evaluating the use of the interferon-γ response to Mycobacterium tuberculosis-specific antigens in patients with psoriasis prior to antitumour necrosis factor-α therapy: a prospective head-to-head cross-sectional study.

BACKGROUND: Targeted biological therapies have transformed the treatment of chronic inflammatory disease. However, reactivation of latent tuberculosis infection (LTBI) is a significant risk with the use of antitumour necrosis factor (anti-TNF)-α therapy and screening is mandatory prior to treatment. The tuberculin skin test (TST) may be difficult to interpret in patients with inflammatory disease or receiving immunosuppressive therapies. OBJECTIVES: The aim of this study was to evaluate and compare the QuantiFERON(®) -TB Gold In-Tube (QFR) and T-SPOT.TB (TSTB) interferon-γ-release assays (IGRA) against the TST in a cohort of patients commencing anti-TNF-α therapies for chronic inflammatory disease. METHODS: A prospective cross-sectional study was undertaken at a London tertiary referral centre. Demographic data collected included TB risk factors. TST, QFR and TSTB were performed in all patients. RESULTS: Seventy patients with chronic plaque psoriasis were included in the study. Agreement between QFR and TSTB, excluding indeterminate results, was 89% (κ = 0.567), between QFR and TST 85% (κ= 0.313) and 81% (κ = 0.244) between TSTB and TST. There was no significant association with concomitant immunosuppression and either TST or IGRA results. Seven patients received chemoprophylaxis for LTBI diagnosed after clinical risk assessment together with positive TST and/or IGRA. Three patients had positive results in all three tests. CONCLUSIONS: While there was moderate overall agreement between QFR and TSTB and fair correlation between TST, QFR and TSTB, there were a number of discordant results, suggesting that a three-pronged approach using TST, QFR and TSTB may be of additional benefit.

A prospective case-controlled cohort study of endothelial function in patients with moderate to severe psoriasis.

BACKGROUND: There is well-documented evidence that patients with moderate and severe psoriasis have a significantly increased risk of cardiovascular disease (CVD). While this risk can, at least in part, be attributed to the high prevalence of traditional risk factors in the population with psoriasis, some epidemiological evidence suggests it may be independent of these. OBJECTIVES: This prospective, case-controlled study investigates whether psoriasis is a risk factor for CVD using two, validated, sensitive markers of CVD, endothelial dysfunction and high-sensitivity C-reactive protein (hsCRP). METHODS: Patients were recruited from a tertiary referral psoriasis clinic and exclusion criteria included established CVD and/or conventional risks for CVD. Preclinical CVD was assessed using flow-mediated brachial artery dilatation, which measures endothelial dysfunction, and hsCRP, a serological marker of atherosclerosis. RESULTS: Sixty-four patients (22%) out of a total of 285 consecutive patients attending the severe psoriasis clinic were entered into the study. One hundred and sixty-one (56%) were excluded following identification of cardiovascular risk; 39 of the 161 (24%) had at least two cardiovascular risk factors. A further 16 (6%) patients were excluded because of established CVD. No statistically significant difference in endothelial dysfunction was observed between patients with psoriasis (n = 60) and healthy controls (n = 117) (P = 0·508). The hsCRP level was, however, significantly elevated in the psoriasis group (2·828 mg L(-1), SEM 0·219; controls 0·728 mg L(-1), SEM 0·142; P < 0·05). CONCLUSION: This large, investigative study is the first to assess endothelial function in patients with psoriasis after exclusion of traditional risk factors for CVD. These data suggest that psoriasis per se is not a risk factor for CVD and that elevated hsCRP is possibly independent of atheroma risk. There was a high prevalence of traditional risk factors in our population with severe psoriasis.

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation.

BACKGROUND: Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis. OBJECTIVES: To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly). METHODS: All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve >or= 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12. Results Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported. CONCLUSIONS: Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.

Intrauterine diagnosis of hydrothorax in a fetus who had a combination chylothorax and pulmonary sequestration after delivery.

Congenital hydrothorax was diagnosed prenatally by transabdominal ultrasonography. Five fetal thoracentesis procedures were performed and biochemical analyses of the fluids were done. After delivery a combination chylothorax and extralobar pulmonary sequestration was demonstrated in the infant. We believe this to be the first case report of this combination investigated prenatally. We suggest that investigators perform biochemical analyses on fetal pleural fluid removed in cases with a single diagnosis. Perhaps by comparing those data with the data reported here, a biochemical marker can be identified that will be useful in distinguishing these two conditions in utero.

Comparison of transvaginal sonography with endometrial biopsy in asymptomatic postmenopausal women.

The purpose of this study was to compare TVS with endometrial biopsy as a screening technique in asymptomatic postmenopausal women. Asymptomatic postmenopausal women were recruited by newspaper advertisement. Each study patient was subjected to pelvic examination and TVS followed by endometrial biopsy. Patients with suspected endometrial abnormalities by TVS (normal by endometrial biopsy) were evaluated further with hysteroscopy with biopsy or D&C or both. Eight patients were identified as having abnormalities by TVS, only one of whom had abnormalities by initial endometrial biopsy. Two patients were identified as having abnormalities by endometrial biopsy and normal by TVS. Further evaluation of the seven patients identified as having abnormalities by TVS (normal by endometrial biopsy) documented all seven patients as having abnormalities. The total yield of abnormalities with TVS was 16% (eight of 50 patients). The total yield of abnormalities with endometrial biopsy was 6% (three of 50 patients). The sensitivity of TVS in identifying endometrial abnormalities was 80% (eight of 10), while endometrial biopsy was only 30% (three of 10). TVS was more sensitive in detecting endometrial abnormalities, including endometrial hyperplasia, than was endometrial biopsy. The use of endometrial biopsy as a screening technique in asymptomatic postmenopausal patients is questioned.

Osteogenesis imperfecta and associated hearing loss in five kindreds.

We examined audiometric data of 30 medically confirmed cases of osteogenesis imperfecta, evaluating pure tone threshold and impedance data to determine the prevalence, type, and degree of hearing loss in five kindreds. Nineteen of the 30 individuals evaluated had normal hearing bilaterally, while 11 had hearing losses of various types and degrees. The results of pure tone testing, tympanometry, and acoustic reflex measurements suggest no clearly established pattern of hearing loss in this population. However, the presence of air-bone gaps and absent acoustic reflexes during the first and second decades support the findings of others, indicating that conductive hearing loss is most prevalent in younger individuals with osteogenesis imperfecta.