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CT scan showing an aortic wall thickening at the aortic bifurcation with a soft tissue cuff above the right common iliac artery consistent with endarteritis
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Background
Ustekinumab (Stelara®), a human monoclonal antibody targeting the p40-subunit of interleukin (IL)-12 and IL-23, is indicated for moderate to severe plaque psoriasis and psoriatic arthritis. In large multicenter, prospective trials assessing efficacy and safety of ustekinumab increased rates of severe infections have not been observed so...
Context in source publication
Context 1
... on the day of admission showed no signs of arth- ritis, joint effusion or empyema in the right ankle joint. However, edema and thickening of the aortic/right common iliac artery wall at the aortic bifurcation, consistent with an inflammatory vascular lesion, was noted ( Fig. 3a and b). Without an unambiguous focus (and prior to the CT scan) the patient had been started on an empiric antibiotic therapy with intravenous piperacillin/tazobactam (4.5 g every 8 h) and oral clari- thromycin (500 mg/d). The next day, the patient's condition improved. Blood cultures yielded growth of S. aureus (susceptible to methicillin, ...
Citations
... For ustekinumab, multiple cases of bacterial skin infections and Herpesviridae infections have been described in clinical trials and case reports (13)(14)(15). Herpesviridae infections were seen more frequently during the first 12 weeks of treatment with secukinumab compared with etanercept (16). ...
... To date, clinical trials have not reported an increased risk of bacterial skin infections in secukinumab and ustekinumab users (27,28). A single case report has described the occurrence of S. aureus bacteraemia with iliac artery endarteritis after the third dose of ustekinumab (14). Only a few case reports have been published on bacterial skin infections during TNF-α inhibitor therapy (29,30). ...
Genetic defects in interleukin-12/23/17 immunity are known to cause Staphylococcus aureus and herpesvirus skin infections. This study analysed spontaneous safety reports from the WHO Pharmacovigilance Center of bacterial skin or herpesvirus infections associated with secukinumab, ustekinumab and tumour necrosis factor-α inhibitors. Associations found in disproportionality analyses were expressed as reporting odds ratios (ROR). For bacterial skin infections, ustekinumab showed the strongest association (ROR 6.09; 95% confidence interval (95% CI) 5.44–6.81), and, among the tumour necrosis factor-α inhibitors, infliximab showed the strongest association (ROR 4.18; 95% CI 3.97–4.40). Risk was comparable between infliximab and secukinumab (ROR 3.51; 95% CI 3.00–4.09). Secukinumab showed the strongest association with herpes simplex infection (ROR 4.80; 95% CI 3.78–6.10). All biologics were equally associated with herpes zoster. Infliximab was the only biologic associated with cytomegalovirus infection (ROR 5.66; 95% CI 5.08–6.31) and had the strongest association with Epstein-Barr virus infection (ROR 6.90; 95% CI 6.03–7.90). All biologics evaluated were positively associated with bacterial skin infections, herpes simplex, and herpes zoster, compared with all other drugs in the WHO database for which individual case safety reports were collected. The possibility of under-reporting, reporting bias and difference in causality assessment between countries and reporters must be taken into account when interpreting the results of disproportionality analyses.
... For ustekinumab, multiple cases of bacterial skin infections and Herpesviridae infections have been described in clinical trials and case reports (13)(14)(15). Herpesviridae infections were seen more frequently during the first 12 weeks of treatment with secukinumab compared with etanercept (16). ...
... To date, clinical trials have not reported an increased risk of bacterial skin infections in secukinumab and ustekinumab users (27,28). A single case report has described the occurrence of S. aureus bacteraemia with iliac artery endarteritis after the third dose of ustekinumab (14). Only a few case reports have been published on bacterial skin infections during TNF-α inhibitor therapy (29,30). ...
Genetic defects in interleukin-12/23/17 immunity are known to cause Staphylococcus aureus and herpesvirus skin infections. This study analysed spontaneous safety reports from the WHO Pharmacovigilance Center of bacterial skin or herpesvirus infections associated with secukinumab, ustekinumab and tumour necrosis factor-α inhibitors. Associations found in disproportionality analyses were expressed as reporting odds ratios (ROR). For bacterial skin infections, ustekinumab showed the strongest association (ROR 6.09; 95% confidence interval (95% CI) 5.44-6.81), and, among the tumour necrosis factor-α inhibitors, infliximab showed the strongest association (ROR 4.18; 95% CI 3.97-4.40). Risk was comparable between infliximab and secukinumab (ROR 3.51; 95% CI 3.00-4.09). Secukinumab showed the strongest association with herpes simplex infection (ROR 4.80; 95% CI 3.78-6.10). All biologics were equally associated with herpes zoster. Infliximab was the only biologic associated with cytomegalovirus infection (ROR 5.66; 95% CI 5.08-6.31) and had the strongest association with Epstein-Barr virus infection (ROR 6.90; 95% CI 6.03-7.90). All biologics evaluated were positively associated with bacterial skin infections, herpes simplex, and herpes zoster, compared with all other drugs in the WHO database for which individual case safety reports were collected. The possibility of under-reporting, reporting bias and difference in causality assessment between countries and reporters must be taken into account when interpreting the results of disproportionality analyses.
... The levels of these cytokines, along with others derived from TH 17 cells, in skin lesions as well as in peripheral blood have been shown to be elevated in psoriasis patients as compared to their healthy counterparts [5]. IL-17 has also been shown to act on dermal fibroblasts in stromal tissue leading to the production of proinflammatory cytokines that promote the expression of keratin 17, which is the only keratin that has been found in the lesions of psoriasis patients [6]. ...
Psoriasis is a chronic, inflammatory, autoimmune disease characterized by red, dry, itchy, and scaly patches of abnormal skin growth on the elbows, knees, and/or scalp, which can negatively impact a patient's quality of life and activities of daily living. Both genetic predispositions and environmental factors, which can vary in susceptibility and effect, including infection, stress, medications, and cold temperatures, can lead to the onset of psoriasis and progression of the condition. This review aims to highlight recent advances in understanding the pathophysiology of psoriasis and provide insight into the importance of vaccinations and their role in reducing the risk of infection in psoriasis patients. Vaccination has been shown to reduce the risk of infection in psoriasis patients and those with other autoimmune diseases. Still, vaccination remains limited among autoimmune disease patients. Awareness of the benefits of vaccination needs to be raised among healthcare professionals due to the overarching impact on these patients' lives. The focus of this literature review is to examine the existing data to determine whether vaccination is beneficial for psoriasis patients. Herein, we primarily focus on influenza, pneumococcal, and herpes zoster vaccines and whether immunization benefits or adversely affects psoriasis patients. Overall, we found that most psoriasis and vaccine literature support immunization of this patient population, particularly with non-live attenuated vaccines; however, more studies are needed to fully develop a vaccine recommendation schedule for psoriasis patients.
... -Psoriasis: MSSA bacteremia, endophthalmitis, and osteomyelitis in a patient with diabetes treated with the interleukin-17A inhibitor, secukinumab [33], Staphylococcus aureus bacteremia with iliac artery endarteritis in a patient receiving ustekinumab [34], Nocardia farcinica bacteremia in a patient on long term prednisolone and etanercept [35], one case of urinary sepsis in an observational retrospective study including 102 patients with plaque-type psoriasis receiving etanercept [36]. -Hidradenitis suppurativa: fatal pneumococcal sepsis in a patient treated with infliximab [37], Gemella morbillorum bacteremia after infliximab therapy [38], one case of bacteremia in a parallel randomized trial of adalimumab including 154 adult patients [39]. ...
In patients who develop sepsis, whether due to primary, secondary or metastatic lesions, the skin is frequently affected. However, there are unresolved aspects regarding the general clinical manifestations in the skin or the prognosis and/or therapeutic implications. The main challenge in the approach to sepsis is its early diagnosis and management. In this review, we address the sepsis–skin relationship and the potential impact of early dermatological intervention on the septic patient through ten basic questions. We found little evidence of the participation of the dermatologist in sepsis alert programs. There are early skin changes that may alert clinicians on a possible sepsis, such as skin mottling or variations in acral skin temperature. In addition, the skin is an accessible and highly cost-effective tissue for etiological studies of some forms of sepsis (e.g., meningococcal purpura) and its involvement defines the prognosis of certain patients (e.g., infective endocarditis).
... This may lead to increased susceptibility to infection or inability to control infection. In both adult and pediatric patients with inflammatory conditions, biologics have been associated with an increased risk of infections including tuberculosis (reactivation and disseminated disease), invasive fungal infections, severe bacterial and viral infections and more rarely opportunistic infections [36][37][38][39][40][41][42][43][44][45][46][47]. Biologics are often given concomitantly with other immunosuppressive agents, which, in combination with the underlying inflammatory condition, add to the cumulative risk of infection. ...
Introduction: More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appear to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants.
Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant.
Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.
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Biologics target various pathways to modify immunologic activity. Biologic use to treat pediatric patients continues to expand; but limited data exist regarding infectious complications of these agents, especially for newer agents. Infectious events reported in the literature for pediatric patients indicate that a variety of bacterial, mycobacterial, viral, and fungal infections can occur. Further pediatric-specific reports are needed to fill knowledge gaps in the complications related to these agents.
