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A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.

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Background and Purpose— The computed tomography angiographic spot sign refers to contrast leakage within intracerebral hemorrhage (ICH). It has been proposed as a surrogate radiological marker for ICH growth. We conducted a meta-analysis to study the accuracy of the spot sign for predicting ICH growth and mortality. Methods— PubMed, Medline, conference proceedings, and article references in English up to June 2017 were searched for studies reporting “computed tomography angiography” and “spot sign” or “intracerebral hemorrhage” and “spot sign.” Each study was ranked on 27 criteria resulting in a quality rating score. Bivariate random effect meta-analysis was used to calculate positive and negative likelihood ratios and area under summary receiver operating characteristics curve for ICH growth and mortality. Hematoma growth was defined using the change in ≥6 mL or ≥33% increase in volume. Results— There were 26 studies describing 5085 patients, including 15 studies not used in previous meta-analyses. Positive likelihood ratio and negative likelihood ratio for ICH growth were 4.85 (95% CI, 3.85–6.02; I 2 =76.1%) and 0.49 (95% CI, 0.40–0.58) and mortality were 4.65 (95% CI, 3.67–5.90) and 0.55 (95% CI, 0.40–0.69), respectively. For ICH growth, the pooled sensitivity was 0.57 (95% CI, 0.49–0.64) and pooled false positive rate was 0.12 (95% CI, 0.09–0.14). The post-test probability of ICH growth was 0.57. The area under the curve for ICH growth and mortality was 0.86 and 0.87 (CIs are not provided in bivariate method). Meta-regression showed sensitivity of the test to decline significantly with subsequent year of publication (β=−0.148; 95% CI, −0.295 to −0.001; P =0.05). Higher quality assessment is associated with lower false positive rate (β=−0.074; 95% CI, −0.126 to −0.022; P =0.006). Conclusions— The high area under the curve potentially suggests that the spot sign can predict hematoma growth and mortality. Caution is recommended in its application given the heterogeneity across studies, which is appropriate given the data.