Levamisole toxicity mimicking autoimmune disease.

BACKGROUND: Levamisole is present as a contaminant or additive in most cocaine sold in the United States. Cases of agranulocytosis attributed to levamisole-tainted cocaine have been widely described. A vasculopathic reaction to levamisole has also been reported; however, diagnostic features such as antineutrophil cytoplasmic antibody (ANCA) and additional autoimmune marker positivity are not well recognized. As such, many patients are given a misdiagnosis, prompting aggressive and often unnecessary treatment. OBJECTIVE: We hope to educate practitioners about the clinical and laboratory features of levamisole-induced vasculopathy to ensure accurate diagnosis and management. METHODS: This was a case series. RESULTS: Six patients were admitted with purpuric lesions and vasculitic changes on biopsy specimen; 5 of them were given the diagnosis of and treated for autoimmune conditions before their true diagnosis was revealed. All patients had ANCA positivity, and 4 had additional abnormalities in autoimmune markers. All patients reported recent cocaine abuse, and were ultimately given the diagnosis of levamisole-induced vasculopathy. LIMITATIONS: This observational study is limited by sample size. CONCLUSIONS: Patients presenting with purpuric lesions with ANCA positivity should be assessed for cocaine exposure. It is important to recognize that levamisole may not only induce ANCA positivity but also other autoimmune marker abnormalities. Patients can often be treated with less aggressive therapeutic strategies than what is used for primary ANCA-associated vasculitides.

The association between physical activity and the risk of incident psoriasis.

OBJECTIVE: To examine the association between total physical activity, walking, and vigorous exercise and the incidence of psoriasis in women. DESIGN: Cohort study. SETTING: The Nurses' Health Study II, a cohort of 116,430 women aged 27 to 44 years in 1991. PARTICIPANTS: The study population included 86,655 US female nurses who reported whether they had ever been diagnosed as having psoriasis and who completed detailed physical activity questionnaires in 1991, 1997, and 2001. We excluded participants with a history of psoriasis prior to 1991. MAIN OUTCOME MEASURES: Risk of psoriasis by quintile of physical activity as measured by a metabolic equivalent task score. RESULTS: We documented 1026 incident psoriasis cases during 1,195,703 person-years of follow-up (14 years, 1991-2005). After adjusting for age, smoking, and alcohol use, increasing physical activity was inversely associated with the risk of psoriasis. The most physically active quintile of women had a lower multivariate relative risk (RR) of psoriasis (0.72 [95% CI, 0.59-0.89; P < .001 for trend]) compared with the least active quintile. Vigorous physical activity (≥6 metabolic equivalents) was associated with a reduced risk of psoriasis (multivariate RR for the highest quintile, 0.66 [95% CI, 0.54-0.81; P < .001 for trend]); this association remained significant after adjusting for body mass index (RR, 0.73 [95% CI, 0.60-0.90; P = .009 for trend]). Walking was not associated with psoriasis risk. In a subset of 550 confirmed psoriasis cases, we observed a similarly reduced risk of psoriasis associated with vigorous physical activity (multivariate RR for the highest quintile, 0.64 [95% CI, 0.48-0.86; P = .03 for trend]). CONCLUSION: In this study of US women, vigorous physical activity is independently associated with a reduced risk of incident psoriasis.

Comparative effectiveness of topical calcineurin inhibitors in adult patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by extreme pruritis and lichenified papules and plaques that may begin in or persist into adulthood. Topical corticosteroids are first-line prescription therapy for AD; they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus were approved by the US FDA in 2000 and 2001, respectively, as second-line topical therapy for AD. This review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD. Tacrolimus was found to be as effective as class III-V topical corticosteroids for AD of the trunk and extremities, and more effective than low-potency class VI or VII corticosteroids for AD of the face or neck. Pimecrolimus was less effective than both tacrolimus and low-potency topical corticosteroids for moderate to severe AD. The short-term safety studies found that, compared with topical corticosteroid-treated adults, patients treated with topical calcineurin inhibitors had an increased frequency of application-site reactions, an equivalent infection risk, and a decreased risk of skin atrophy. The long-term safety of topical calcineurin inhibitors remains under investigation. Currently published studies that evaluated the comparative cost and quality-of-life effects compared tacrolimus with less potent topical corticosteroids despite the availability of equivalent potency corticosteroids. Further cost and quality-of-life studies are needed that compare topical calcineurin inhibitors with stronger classes of topical corticosteroids over longer time periods. The available clinical trials data do not suggest an efficacy advantage for topical calcineurin inhibitors over topical corticosteroids in adults with AD of the trunk and extremities, and there is not yet adequate evidence to support topical calcineurin inhibitors as first-line therapy for adult AD.

Age-group differences in medial cortex activity associated with thinking about self-relevant agendas.

In this functional magnetic resonance imaging (fMRI) study, we compared young and older adults' brain activity as they thought about motivationally self-relevant agendas (hopes and aspirations, duties and obligations) and concrete control items (e.g., shape of USA). Young adults' activity replicated a double dissociation (M. K. Johnson et al., 2006): An area of medial frontal gyrus/anterior cingulate cortex was most active during hopes and aspirations trials, and an area of medial posterior cortex-primarily posterior cingulate-was most active during duties and obligations trials. Compared with young adults, older adults showed attenuated responses in medial cortex, especially in medial prefrontal cortex, with both less activity during self-relevant trials and less deactivation during control trials. The fMRI data, together with post-scan reports and the behavioral literature on age-group differences in motivational orientation, suggest that the differences in medial cortex seen in this study reflect young and older adults' focus on different information during motivationally self-relevant thought. Differences also may be related to an age-associated deficit in controlled cognitive processes that are engaged by complex self-reflection and mediated by prefrontal cortex.

Multivoxel pattern analysis reveals increased memory targeting and reduced use of retrieved details during single-agenda source monitoring.

We used multivoxel pattern analysis (MVPA) of functional MRI (fMRI) data to gain insight into how subjects' retrieval agendas influence source memory judgments (was item X studied using source Y?). In Experiment 1, we used a single-agenda test where subjects judged whether items were studied with the targeted source or not. In Experiment 2, we used a multiagenda test where subjects judged whether items were studied using the targeted source, studied using a different source, or nonstudied. To evaluate the differences between single- and multiagenda source monitoring, we trained a classifier to detect source-specific fMRI activity at study, and then we applied the classifier to data from the test phase. We focused on trials where the targeted source and the actual source differed, so we could use MVPA to track neural activity associated with both the targeted source and the actual source. Our results indicate that single-agenda monitoring was associated with increased focus on the targeted source (as evidenced by increased targeted-source activity, relative to baseline) and reduced use of information relating to the actual, nontarget source. In the multiagenda experiment, high levels of actual-source activity were associated with increased correct rejections, suggesting that subjects were using recollection of actual-source information to avoid source memory errors. In the single-agenda experiment, there were comparable levels of actual-source activity (suggesting that recollection was taking place), but the relationship between actual-source activity and behavior was absent (suggesting that subjects were failing to make proper use of this information).

Neuroimaging evidence for agenda-dependent monitoring of different features during short-term source memory tests.

A short-term source monitoring procedure with functional magnetic resonance imaging assessed neural activity when participants made judgments about the format of 1 of 4 studied items (picture, word), the encoding task performed (cost, place), or whether an item was old or new. The results support findings from long-term memory studies showing that left anterior ventrolateral prefrontal cortex (PFC) is engaged when people make source attributions about reflectively generated information (cognitive operations, conceptual features). The findings also point to a role for right lateral PFC in attention to perceptual features and/or familiarity in making source decisions. Activity in posterior regions also differed depending on what was evaluated. These results provide neuroimaging evidence for theoretical approaches emphasizing that agendas influence which features are monitored during remembering (e.g., M. K. Johnson, S. Hashtroudi, & D. S. Lindsay, 1993). They also support the hypothesis that some of the activity in left lateral PFC and posterior regions associated with remembering specific information is not unique to long-term memory but rather is associated with agenda-driven source monitoring processes common to working memory and long-term memory.