RESEARCH HIGHLIGHTS Research Highlights Jennifer Tran, Patrick Fleming, Cathryn Sibbald

SATELLITE LESIONS: A NEW PROGNOSTIC SIGN FOR systemic symptoms (fever, malaise, lymphadenopathy, HIGH-RISK HERPES ZOSTER and/or headache), underlying immunosuppression, and el Hayderi, L., Bontems, S., Nikkels-Tassoudji, N., Arrese, J. E., Seidel, L., need for hospitalization. Meex, C., & Nikkels, A. F. (2015). Satellite lesions accompanying herpes zoster: A new prognostic sign for high-risk zoster. The British Journal There were 109 confirmed cases of herpes zoster, of of Dermatology, 172(6), 1530Y1534. which 23 patients (21%) had SLs. Immunocompromised patients had a 3.15-fold increased RR of having SLs and erpes zoster, or shingles, is a painful vesicular were more likely to have higher numbers of SLs compared eruption caused by reactivation of varicella-zoster with immunocompetent patients. SLs were usually located virus (Wilson, 2011). This condition affects almost on the trunk and were not pruritic or painful. The pres- oneH million individuals annually in the United States, with ence of SLs significantly increased risk of systemic signs an estimated lifetime risk of 32% (Harpaz, Ortega-Sanchez, (RR = 2.08, 95% confidence interval [CI] [1.35, 3.30]), & Seward, 2008). Zoster classically affects a single der- underlying immunosuppression (RR = 2.38, 95% CI matome but can occasionally present with satellite lesions [1.46, 3.87]), multistage zoster (RR = 3.30, 95% CI [1.96, (SLs) away from the primary site (Wilson, 2011). Pre- 5.55]), multidermatomal zoster (RR = 10.6, 95% CI [4.72, vious reports have suggested that these SLs may represent 23.8]), increased surface involvement (RR = 3.27, 95% CI hematogenous spread of the virus (Castronovo & Nikkels, [1.89, 5.7]), and hospitalization (RR = 2.94, 95% CI 2012), but the overall clinical significance of these SLs [1.55, 5.58]). has not been studied. REMARK: This study identifies SLs as a novel risk el Hayderi and colleagues conducted a prospective case factor for high-risk herpes zoster infection. Interestingly, series to determine if the presence of SLs in patients with SLs have been thought to have no prognostic importance herpes zoster was associated with severity of illness. The (Gnann & Whitley, 2002). One limitation of this study is authors observed 120 patients from a tertiary care center possible overrepresentation of immunocompromised pa- with lesions suspicious for herpes zoster, over a period tients, given that patients were from a tertiary care center. of 2.5 years. The diagnosis of zoster was made for each Furthermore, it is unclear how the investigators conducted patient by immunohistochemistry using varicella-zoster the full skin examination and whether this was standard- virus-specific antibodies on a Tzanck smear and/or skin ized for all patients. Finally, although the presence of SLs biopsy. Confirmed cases were examined for SLs, defined may reflect severity at the time of initial presentation, the as small, isolated, nonclustered, varicella-like skin lesions authors do not comment on long-term severity outcomes at least 5 cm away from the primary dermatome. Relative such as postherpetic neuralgia, length of hospital stay, or risks (RRs) were calculated for multistage disease, multi- complications. dermatomal disease, increased surface involvement, pain, KEY POINT: Clinicians should be aware of the spec- trum of herpes zoster infection. Full skin examinations Jennifer Tran, MD, Dermatology Centre, Sunnybrook Health should be conducted for all patients with herpes zoster, Sciences Centre, University of Toronto, Toronto, Ontario, Canada. and the presence of SLs may identify high-risk patients. Patrick Fleming, MD, MSc, Dermatology Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Cathryn Sibbald, BScPhm, MD, Dermatology Centre, Sunnybrook RISK OF DEPRESSION IN WOMEN WITH PSORIASIS: A Health Sciences Centre, University of Toronto, Toronto, Ontario, COHORT STUDY Canada. Dommasch,E.D.,Li,T.,Okereke,O.I.,Li,Y.,Qureshi,A.A.,&Cho,E.(2015). The authors declare no conflict of interest. Risk of depression in women with psoriasis: A cohort study. The British Journal of Dermatology, 173(4), 975Y980. Correspondence concerning this article should be addressed to Jennifer Tran, MD, Dermatology Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Suite M1-700, soriasis is a chronic inflammatory disease that can Toronto, ON M4N 3M5, Canada. affect both the skin and joints and has a substantial E-mail: [email protected] impact on quality of life. There are multiple comor- DOI: 10.1097/JDN.0000000000000213 biditiesP associated with psoriasis including cardiovascular

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Copyright © 2016 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited. RESEARCH HIGHLIGHTS disease, obesity, and metabolic syndrome. Multiple cross- had other skin disorders. However, a validation study did sectional and case-control studies have shown a signifi- find 93% accuracy for self-reported psoriasis within this cant association between psoriasis and clinical depression. cohort. It has been hypothesized that chronic systemic inflamma- KEY POINT: This study reinforces the importance for tion in diseases such as psoriasis is linked with depressive clinicians to consider the mental health of their patients symptoms. A recent meta-analysis of 98 studies found with psoriasis. that risk of depression in patients with psoriasis was significantly elevated (odds ratio = 1.57, 95% CI [1.40, 1.76]; Dowlatshahi, Wakkee, Arends, & Nijsten, 2014). ADVERSE EVENTS RESULTING IN WITHDRAWAL OF Dommasch and colleagues conducted a large prospec- BIOLOGIC THERAPY IN CANADA Kim, W. B., Marinas, J. E., Qiang, J., Shahbaz, A., Greaves, S., & Yeung, J. (2015). tive inception cohort in the United States using data from Adverse events resulting in withdrawal of biologic therapy for the Nurses’ Health Study. This is a multidecade cohort psoriasis in real-world clinical practice: A Canadian multicenter retrospective study. Journal of the American Academy of Dermatology, that collects data on a variety of health parameters at 73(2), 237Y241. 2-year intervals. This study included 50,750 female registered nurses. Participants must have been depression free iologic therapies are the most effective treatments at the start of the study in 2000. Depression was defined for psoriasis, and tumor necrosis factor-! antagonists as either self-reported physician-diagnosed depression or and IL12-23 inhibitors are commonly prescribed regular use of antidepressant medication. Psoriasis was toB patients who have failed other agents. Clinical trial data defined as self-reported physician-diagnosed psoriasis and describe a low incidence of adverse events, with the main was collected retrospectively in 2008. Covariates included concerns including infection, tuberculosis activation, and body mass index (BMI), physical activity, smoking, and a possible increased risk of malignancy (Mansouri & chronic medical conditions. Their statistical analysis in- Goldenberg, 2015). However, there is a lack of real-word cluded descriptive statistics, t tests, and multivariate analy- data on side effects, and information about safety outside sis using Cox proportional hazards. constrained trial settings can help clinicians to better inform During the study period, there were 5,300 new cases of patients considering these treatments. depression among the 50,750 participants. Nine hundred Kim and colleagues conducted a multicenter retrospec- thirty participants had psoriasis. After adjusting for tive chart review of patients with psoriasis at two aca- age, BMI, physical activity, smoking, and chronic disease, demic hospitals in Toronto, Canada, from September 2005 the RR of depression (self-reported or use of antide- to September 2014. Patients were included if they were pressants) was 1.29 (95% CI [1.10, 1.52]). The adjusted 18 years or older and being treated with etanercept, in- RR of depression in women with psoriatic arthritis was fliximab, adalimumab, or ustekinumab. even higher at 1.52 (95% CI [1.06, 2.19]) in the multi- Three hundred ninety-eight patients were analyzed, variate model. including 545 different biologic treatment courses as REMARK: This is a large inception cohort with long- 117 patients received more than one biologic. The most term prospective data. There was a 29% higher risk of common biologic prescribed was ustekinumab (n =176), newly diagnosed depression in female patients with psoria- followed by etanercept (n = 175), adalimumab (n = sis compared with the general population when control- 134), and infliximab (n = 60). Most patients were men ling or adjusting for age, BMI, physical activity, and chronic (62.4%), with a mean duration of psoriasis of 19.4 years. medical conditions. In psoriatic arthritis, the adjusted risk Comorbidities included psoriatic arthritis (38.1%), hy- was 52%. There is growing recognition of the risk of co- pertension (18.4%), dyslipidemia (12.1%), and diabetes morbidities in patients with psoriasis and psoriatic arthri- (10.6%). Other systemic agents were taken concomitantly tis, and that risk includes depression. This study appears in 20% of patients (n = 79). to support recently published evidence-based Canadian The overall incidence of discontinuation from adverse clinical guidelines that recommend routine screening for effects was 4% (n = 22), with an incidence rate of 1.97/ depression in patients with psoriasis and psoriatic arthritis 100 patient-years (95% CI [1.32, 2.94]). The highest inci- (Roubille et al., 2015). dence was seen with infliximab (15%, n =9),andthe There are several limitations to this study. The Nurses’ lowest was seen with etanercept (2.3%, n = 4). Unique Health Study includes registered nurses who have close agent-specific events that led to discontinuation included follow-up and have a higher level of education compared infusion reactions in 8.3% of patients on infliximab with the general population, which may reduce the ex- (n = 5) and injection site reactions in 1.71% of patients ternal validity. As well, it is unclear if these results also on etanercept (n = 3). Infections led to withdrawal in five apply to male psoriasis patients, although cross-sectional patients, three of which were taking adalimumab and one data suggest that there is a high risk of depression in these each on infliximab and ustekinumab. Malignancies were patients as well. A dermatologist did not examine par- detected in two patients on ustekinumab and one patient ticipants in this study so it is possible that some may have each on etanercept and infliximab.

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REMARK: Overall, this study provides valuable data KEY POINT: Biologics have a favorable safety profile, to help inform patients about the risks of biologic treat- with low rates of adverse events requiring withdrawal ments. Biologics appeared to maintain a very favorable of therapy. side effect profile in a real-world Canadian setting, with low rates of adverse events requiring withdrawal of ther- REFERENCES apy. These Canadian rates are congruent with safety data Castronovo, C., & Nikkels, A. F. (2012). Chronic herpes zoster duplex from larger multicontinental registries (Papp et al., 2015). bilateralis. Acta Dermato-Venereologica, 92, 148Y151. Knowledge of the specificity of infusion and injection site Dowlatshahi, E. A., Wakkee, M., Arends, L. R., & Nijsten, T. (2014). The prevalence and odds of depressive symptoms and clinical depression in reactions to infliximab and etanercept may aid in initial psoriasis patients: A systematic review and meta-analysis. The Journal or subsequent therapy selection. Of particular note, the of Investigative Dermatology, 134, 1542Y1551. Gnann, J. W. Jr., & Whitley, R. J. (2002). Clinical practice. Herpes zoster. risk of infections requiring withdrawal of therapy, although The New England Journal of Medicine, 347, 340Y346. small, emphasizes the importance of ongoing practices Harpaz, R., Ortega-Sanchez, I. R., & Seward, J. F. (2008). Prevention of to prevent and detect infections in patients receiving herpes zoster: recommendations of the Advisory Committee on Immu- nization Practices (ACIP) [MMWR Recomm Rep. 57(RR-5)]. Retrieved these therapies. from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e0515a1. The main advantage of this study is the real-world htm?s_cid=rr57e0515_e setting, in which patients may have more comorbidities Mansouri, Y., & Goldenberg, G. (2015). Biologic safety in psoriasis: Review of long-term safety data. The Journal of Clinical and Aesthetic Derma- and less stringent therapy restrictions or monitoring com- tology, 8(2), 30Y42. pared with clinical trials. However, there are limitations, Papp, K., Gottlieb, A. B., Naldi, L., Pariser, D., Ho, V., Goyal, K., I Krueger, G. (2015). Safety surveillance for ustekinumab and other psoriasis including possible incomplete data capture because of treatments from the Psoriasis Longitudinal Assessment and Registry reviewing charts retrospectively. Another limitation is (PSOLAR). Journal of Drugs in Dermatology, 14(7), 706Y714. the relatively short follow-up time that may not capture Roubille, C., Richer, V., Starnino, T., McCourt, C., McFarlane, A., Fleming, P., I Haraoui, B. (2015). Evidence-based recommendations for the manage- the risk of side effects with a longer latency period, such ment of comorbidities in rheumatoid arthritis, psoriasis, and psoriatic as malignancies. For this purpose, ongoing surveillance of arthritis: Expert opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative. The Journal of Rheumatology, 42,1767Y1780. larger multicontinental registries remains an important Wilson, J. F. (2011). In the clinic. Herpes zoster. Annals of Internal Medicine, activity. 154,ITC31YITC315.

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