A closer look at chemotherapy-induced flagellate dermatitis.

Background: Flagellate dermatitis (FD) is a rare skin rash, which may occur following the administration of antineoplastic agents. It has been reported following the administration of bleomycin, docetaxel, trastuzumab, cisplatin, bendamustine and doxorubicin. We provide a summary of the epidemiology, aetiology, pathophysiology, and distribution of chemotherapy-induced FD. Methods: PubMed was searched using ((flagellat*) AND (Dermat*)) OR ((Flagellat*) AND (Erythema)). The search yielded 206 publications, out of which 54 individual case reports were identified which fulfilled our inclusion criteria. Statistical analysis was performed where appropriate. Results: Female patients were slightly more likely to develop FD compared to males. In the majority of cases FD appeared on the upper and lower limbs and pruritus was an accompanying feature in 51% of cases. Most cases developed after the first cycle of chemotherapy and females were statistically more likely to present within the first 72 hr (p <0.05). Skin biopsies were taken in 41% of cases and this was not statistically associated with the patient's gender, (p = 0.651), presentation within 72 hr (p = 0.076) or cancer diagnosis. Chemotherapy was stopped in 62% of patients and was associated with female gender (p = 0.0098). Most patients who received treatment were managed with topical steroids. Time for rash resolution ranged from a few weeks to four months following the discontinuation of the causative drug. Conclusion: FD is a rare adverse skin effect of chemotherapeutic treatment, most commonly presenting on the upper and lower limbs of patients following their first cycle of chemotherapy. Early presentation is more common in females leading to increased likelihood of stopping chemotherapy. Biopsy findings poorly correlate with disease severity. Continuation of chemotherapy treatment in combination with topical steroids may not adversely affect rash resolution.

Cardiac device implantation and device usage in Fabry and hypertrophic cardiomyopathy.

BACKGROUND: Fabry disease (FD) is a treatable X-linked condition leading to progressive cardiac disease, arrhythmia and premature death. We aimed to increase awareness of the arrhythmogenicity of Fabry cardiomyopathy, by comparing device usage in patients with Fabry cardiomyopathy and sarcomeric HCM. All Fabry patients with an implantable cardioverter defibrillator (ICD) implanted in the UK over a 17 year period were included. A comparator group of HCM patients, with primary prevention ICD implantation, were captured from a regional registry database. RESULTS: Indications for ICD in FD varied with 72% implanted for primary prevention based on multiple potential risk factors. In FD and HCM primary prevention devices, arrhythmia occurred more frequently in FD over shorter follow-up (HR 4.2, p < 0.001). VT requiring therapy was more common in FD (HR 4.5, p = 0.002). Immediate shock therapy for sustained VT was also more common (HR 2.5, p < 0.001). There was a greater burden of AF needing anticoagulation and NSVT in FD (AF: HR 6.2, p = 0.004, NSVT: HR 3.1, p < 0.001). CONCLUSION: This study demonstrates arrhythmia burden and ICD usage in FD is high, suggesting that Fabry cardiomyopathy may be more 'arrhythmogenic' than previously thought. Existing risk models cannot be mutually applicable and further research is needed to provide clarity in managing Fabry patients with cardiac involvement.

Five-minute heart rate variability can predict obstructive angiographic coronary disease.

OBJECTIVE: Obstructive coronary artery disease (CAD) is evident in only half of patients referred for diagnostic angiography. Five-minute heart rate variability (HRV) is a non-invasive marker for autonomic control of the vasculature, which this study hypothesised could risk-stratify cardiac patients and reduce unnecessary angiograms. DESIGN: A prospective observational study (the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study). SETTING: Three cardiac centres in Melbourne, Australia. PATIENTS: 470 consecutive patients undergoing elective angiography (with predominantly normal cardiac rhythm), regardless of co-morbidity. MAIN OUTCOME MEASURES: The presence of obstructive CAD (≥50% stenosis) on angiography. RESULTS: Patients with obstructive CAD had significantly reduced HRV, particularly in the low frequency (LF) range (median 180 vs 267 ms(2) without CAD; p<0.001). There was a linear trend with the severity of CAD; median LF power (IQR) in patients with normal coronaries was 275 (612), with minor coronary irregularities 255 (400), single-vessel CAD 212 (396) and more severe disease 170 (327) ms(2); p value for trend 0.003. There was a similar reduction in LF power regardless of the anatomical location of coronary stenoses. Comparing patients with LF less than 250 and 250 ms(2) or greater, the adjusted OR for obstructive CAD using multivariate regression was 2.42, 95% CI 1.33 to 4.38 (p=0.004). No interactions were noted in subgroup analysis and HRV added to risk prediction irrespective of the baseline Framingham risk (p<0.0001). CONCLUSION: Low HRV is strongly predictive of angiographic coronary disease regardless of other co-morbidities and is clinically useful as a risk predictor in patients with sinus rhythm. CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/show/NCT00403351 www.armcad.com.