SATELLITE LESIONS: A NEW PROGNOSTIC SIGN FOR HIGH-RISK HERPES ZOSTER
el Hayderi, L., Bontems, S., Nikkels-Tassoudji, N., Arrese, J. E., Seidel, L., Meex, C., & Nikkels, A. F. (2015). Satellite lesions accompanying herpes zoster: A new prognostic sign for high-risk zoster. The British Journal of Dermatology, 172(6), 1530-1534.
Herpes zoster, or shingles, is a painful vesicular eruption caused by reactivation of varicella-zoster virus (Wilson, 2011). This condition affects almost one million individuals annually in the United States, with an estimated lifetime risk of 32% (Harpaz, Ortega-Sanchez, & Seward, 2008). Zoster classically affects a single dermatome but can occasionally present with satellite lesions (SLs) away from the primary site (Wilson, 2011). Previous reports have suggested that these SLs may represent hematogenous spread of the virus (Castronovo & Nikkels, 2012), but the overall clinical significance of these SLs has not been studied.
el Hayderi and colleagues conducted a prospective case series to determine if the presence of SLs in patients with herpes zoster was associated with severity of illness. The authors observed 120 patients from a tertiary care center with lesions suspicious for herpes zoster, over a period of 2.5 years. The diagnosis of zoster was made for each patient by immunohistochemistry using varicella-zoster virus-specific antibodies on a Tzanck smear and/or skin biopsy. Confirmed cases were examined for SLs, defined as small, isolated, nonclustered, varicella-like skin lesions at least 5 cm away from the primary dermatome. Relative risks (RRs) were calculated for multistage disease, multidermatomal disease, increased surface involvement, pain, systemic symptoms (fever, malaise, lymphadenopathy, and/or headache), underlying immunosuppression, and need for hospitalization.
There were 109 confirmed cases of herpes zoster, of which 23 patients (21%) had SLs. Immunocompromised patients had a 3.15-fold increased RR of having SLs and were more likely to have higher numbers of SLs compared with immunocompetent patients. SLs were usually located on the trunk and were not pruritic or painful. The presence of SLs significantly increased risk of systemic signs (RR = 2.08, 95% confidence interval [CI] [1.35, 3.30]), underlying immunosuppression (RR = 2.38, 95% CI [1.46, 3.87]), multistage zoster (RR = 3.30, 95% CI [1.96, 5.55]), multidermatomal zoster (RR = 10.6, 95% CI [4.72, 23.8]), increased surface involvement (RR = 3.27, 95% CI [1.89, 5.7]), and hospitalization (RR = 2.94, 95% CI [1.55, 5.58]).
REMARK: This study identifies SLs as a novel risk factor for high-risk herpes zoster infection. Interestingly, SLs have been thought to have no prognostic importance (Gnann & Whitley, 2002). One limitation of this study is possible overrepresentation of immunocompromised patients, given that patients were from a tertiary care center. Furthermore, it is unclear how the investigators conducted the full skin examination and whether this was standardized for all patients. Finally, although the presence of SLs may reflect severity at the time of initial presentation, the authors do not comment on long-term severity outcomes such as postherpetic neuralgia, length of hospital stay, or complications.
KEY POINT: Clinicians should be aware of the spectrum of herpes zoster infection. Full skin examinations should be conducted for all patients with herpes zoster, and the presence of SLs may identify high-risk patients.
RISK OF DEPRESSION IN WOMEN WITH PSORIASIS: A COHORT STUDY
Dommasch, E. D., Li, T., Okereke, O. I., Li, Y., Qureshi, A. A., & Cho, E. (2015). Risk of depression in women with psoriasis: A cohort study. The British Journal of Dermatology, 173(4), 975-980.
Psoriasis is a chronic inflammatory disease that can affect both the skin and joints and has a substantial impact on quality of life. There are multiple comorbidities associated with psoriasis including cardiovascular disease, obesity, and metabolic syndrome. Multiple cross-sectional and case-control studies have shown a significant association between psoriasis and clinical depression. It has been hypothesized that chronic systemic inflammation in diseases such as psoriasis is linked with depressive symptoms. A recent meta-analysis of 98 studies found 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).
Dommasch and colleagues conducted a large prospective inception cohort in the United States using data from the Nurses' Health Study. This is a multidecade cohort that collects data on a variety of health parameters at 2-year intervals. This study included 50,750 female registered nurses. Participants must have been depression free at the start of the study in 2000. Depression was defined as either self-reported physician-diagnosed depression or regular use of antidepressant medication. Psoriasis was defined as self-reported physician-diagnosed psoriasis and was collected retrospectively in 2008. Covariates included body mass index (BMI), physical activity, smoking, and chronic medical conditions. Their statistical analysis included descriptive statistics, t tests, and multivariate analysis using Cox proportional hazards.
During the study period, there were 5,300 new cases of depression among the 50,750 participants. Nine hundred thirty participants had psoriasis. After adjusting for age, BMI, physical activity, smoking, and chronic disease, the RR of depression (self-reported or use of antidepressants) was 1.29 (95% CI [1.10, 1.52]). The adjusted RR of depression in women with psoriatic arthritis was even higher at 1.52 (95% CI [1.06, 2.19]) in the multivariate model.
REMARK: This is a large inception cohort with long-term prospective data. There was a 29% higher risk of newly diagnosed depression in female patients with psoriasis compared with the general population when controlling or adjusting for age, BMI, physical activity, and chronic medical conditions. In psoriatic arthritis, the adjusted risk was 52%. There is growing recognition of the risk of comorbidities in patients with psoriasis and psoriatic arthritis, and that risk includes depression. This study appears to support recently published evidence-based Canadian clinical guidelines that recommend routine screening for depression in patients with psoriasis and psoriatic arthritis (Roubille et al., 2015).
There are several limitations to this study. The Nurses' Health Study includes registered nurses who have close follow-up and have a higher level of education compared with the general population, which may reduce the external validity. As well, it is unclear if these results also apply to male psoriasis patients, although cross-sectional data suggest that there is a high risk of depression in these patients as well. A dermatologist did not examine participants in this study so it is possible that some may have had other skin disorders. However, a validation study did find 93% accuracy for self-reported psoriasis within this cohort.
KEY POINT: This study reinforces the importance for clinicians to consider the mental health of their patients with psoriasis.
ADVERSE EVENTS RESULTING IN WITHDRAWAL OF BIOLOGIC THERAPY IN CANADA
Kim, W. B., Marinas, J. E., Qiang, J., Shahbaz, A., Greaves, S., & Yeung, J. (2015). Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: A Canadian multicenter retrospective study. Journal of the American Academy of Dermatology, 73(2), 237-241.
Biologic therapies are the most effective treatments for psoriasis, and tumor necrosis factor-[alpha] antagonists and IL12-23 inhibitors are commonly prescribed to patients who have failed other agents. Clinical trial data describe a low incidence of adverse events, with the main concerns including infection, tuberculosis activation, and a possible increased risk of malignancy (Mansouri & Goldenberg, 2015). However, there is a lack of real-word data on side effects, and information about safety outside constrained trial settings can help clinicians to better inform patients considering these treatments.
Kim and colleagues conducted a multicenter retrospective chart review of patients with psoriasis at two academic hospitals in Toronto, Canada, from September 2005 to September 2014. Patients were included if they were 18 years or older and being treated with etanercept, infliximab, adalimumab, or ustekinumab.
Three hundred ninety-eight patients were analyzed, including 545 different biologic treatment courses as 117 patients received more than one biologic. The most common biologic prescribed was ustekinumab (n = 176), followed by etanercept (n = 175), adalimumab (n = 134), and infliximab (n = 60). Most patients were men (62.4%), with a mean duration of psoriasis of 19.4 years. Comorbidities included psoriatic arthritis (38.1%), hypertension (18.4%), dyslipidemia (12.1%), and diabetes (10.6%). Other systemic agents were taken concomitantly in 20% of patients (n = 79).
The overall incidence of discontinuation from adverse effects was 4% (n = 22), with an incidence rate of 1.97/100 patient-years (95% CI [1.32, 2.94]). The highest incidence was seen with infliximab (15%, n = 9), and the lowest was seen with etanercept (2.3%, n = 4). Unique agent-specific events that led to discontinuation included infusion reactions in 8.3% of patients on infliximab (n = 5) and injection site reactions in 1.71% of patients on etanercept (n = 3). Infections led to withdrawal in five patients, three of which were taking adalimumab and one each on infliximab and ustekinumab. Malignancies were detected in two patients on ustekinumab and one patient each on etanercept and infliximab.
REMARK: Overall, this study provides valuable data to help inform patients about the risks of biologic treatments. Biologics appeared to maintain a very favorable side effect profile in a real-world Canadian setting, with low rates of adverse events requiring withdrawal of therapy. These Canadian rates are congruent with safety data from larger multicontinental registries (Papp et al., 2015). Knowledge of the specificity of infusion and injection site reactions to infliximab and etanercept may aid in initial or subsequent therapy selection. Of particular note, the risk of infections requiring withdrawal of therapy, although small, emphasizes the importance of ongoing practices to prevent and detect infections in patients receiving these therapies.
The main advantage of this study is the real-world setting, in which patients may have more comorbidities and less stringent therapy restrictions or monitoring compared with clinical trials. However, there are limitations, including possible incomplete data capture because of reviewing charts retrospectively. Another limitation is the relatively short follow-up time that may not capture the risk of side effects with a longer latency period, such as malignancies. For this purpose, ongoing surveillance of larger multicontinental registries remains an important activity.
KEY POINT: Biologics have a favorable safety profile, with low rates of adverse events requiring withdrawal of therapy.
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