Authors: David D’Arienzo, Kailas Rumjahn Gryte, Francisco Noya, Veronique D. Morinville
Categories: Gastroenterology, Case Report
Source: JPGN Reports
Patients on immunosuppression, including inflammatory bowel disease patients on anti-tumor necrosis factor therapies, are at increased risk of severe varicella and herpes zoster infections. Although varicella vaccine-related herpes zoster reactivation is a rare complication, physicians must remain vigilant about this diagnosis, particularly in those on immunosuppressive medications. Here, we report a case of a patient with Crohn disease, on only adalimumab immunosuppression, who developed varicella vaccine-related disseminated herpes zoster with meningitis, over 15 years after immunization.
Immunization status for vaccine-preventable illnesses is reviewed in inflammatory bowel disease (IBD) patients at diagnosis and before initiation of biological therapies to evaluate risk for developing serious infections (1). It has recently been reported that adult IBD patients could safely receive live attenuated herpes zoster (HZ) vaccination even while on biologic therapy to reduce risk of clinical HZ (2), and some literature suggests pediatric IBD patients may safely receive varicella zoster virus (VZV) vaccination despite being on immunosuppression including biologics (3). Live vaccines are not risk-free; however, and rare but important reactivations of vaccine strains have been described (4,5). We herein describe a teenager with Crohn’s disease, vaccinated at 1 year of age, who developed disseminated vaccine-strain HZ virus infection while on maintenance adalimumab.
A 16-year-old boy with Crohn’s disease presented to the emergency department (ED) with a 2-day history of severe left neck and left shoulder pain. He had been diagnosed with Crohn’s colitis at age 12, in full clinical remission on adalimumab 40 mg subcutaneous every 2 weeks for almost 2 years (0.73 mg/kg/dose; adalimumab level 14.3 μg/mL (therapeutic range 5–20 μg/mL) 5 months before presentation on same maintenance dosing). As he was otherwise well, with no skin/ local findings, he was discharged from the ED with a prescription for naproxen for suspected musculoskeletal pain. Three days later, he returned to the ED with persistent severe left neck and shoulder pain, and new vesicular lesions following the C5–C6 dermatomes (Fig. 1). He was diagnosed with localized HZ infection and admitted to hospital for pain control and intravenous (IV) antiviral treatment.
FIGURE 1. Painful, vesicular rash involving left C5–C6 dermatomes, on second presentation to emergency room.
The patient did not have a history of VZV infection, nor had he been exposed to anyone with varicella or HZ in prior weeks. As per the vaccination schedule at the time, he had received a single dose of VZV live attenuated vaccine at 12 months of age. At IBD diagnosis, a varicella zoster IgG titer was negative by enzyme immunoassay. He had appropriate IgG antibody responses to measles and mumps vaccines, while rubella IgG antibody levels were grey zone.
In hospital, he developed diffuse, vesicular lesions involving multiple dermatomes, over the trunk and all extremities, compatible with disseminated HZ. He also developed headache, photophobia, and neck stiffness. A lumbar puncture was performed, confirming the presence of varicella virus in cerebrospinal fluid. Results are summarized in Table 1.
The patient received 14 days of IV acyclovir followed by a 6-month course of prophylactic oral valacyclovir. One dose of adalimumab was held during hospitalization. A repeat colonoscopy before discharge revealed endoscopic remission of colon and terminal ileum and only chronic inactive colitis on histology. By the time of discharge, the patient was completely asymptomatic and back to baseline status.
A sample taken from a skin lesion subsequently confirmed vaccine-strain VZV infection.
The patient and the parents of the child in question are aware of this case report and have provided their consent. They provided Figure 1 for publication.
As gastroenterologists typically become IBD patients’ primary care providers after diagnosis, they must remain familiar with indications, benefits, and potential risks of vaccinations (1). They must also remain familiar with risks and presentations of potential infections in their immunocompromised patients.
Varicella-zoster virus causes two distinct varicella and HZ (4). Varicella occurs due to primary VZV infection and presents as a generalized, pruritic, vesicular rash, often associated with prodromal symptoms such as fever and malaise. Following primary infection, VZV establishes latency. Disseminated VZV infection involves spread to other organs including respiratory, neurologic (meningitis, encephalitis, acute cerebellar ataxia), hematologic, ocular, renal, and hepatic complications. Herpes zoster results from VZV reactivation and manifests as a painful, vesicular rash, typically localized to a primary dermatome, often proceeded by neuropathic pain (4). Immunosuppressed patients that develop HZ are at increased risk of viremia, which may result in cutaneous or visceral dissemination (4).
Primary VZV infection and HZ reactivation represent potentially very serious illnesses in IBD, with IBD status by itself is being a risk factor for HZ compared to the general population (2), and increased risk of HZ in any immunocompromised patient on anti-tumor necrosis factor (TNF)-α therapy (6,7). A recent case of VZV meningitis from an HZ reactivation in a 40-year-old Crohn’s patient on both anti-TNFα and corticosteroids highlighted the risk for this severe opportunistic infection in IBD (7). The fact that our patient presented while in remission, after two years of maintenance adalimumab at 40 mg Q2 weekly rather than during the initial higher-dose induction regimen, makes it a particularly concerning scenario.
The incidence of HZ in vaccinated children is 79% lower than in unvaccinated children (8). However, vaccinating against varicella does not confer absolute protection, nor is it without risks. Live attenuated VZV vaccine can establish latency and reactivate to cause HZ (4). A 2011 review identified rare cases of disseminated HZ secondary to vaccine-strain VZV and vaccine-strain VZV reactivation resulting in meningitis or encephalitis, 19 months to 8 years after vaccination (5).
Varicella zoster vaccine is recommended for healthy children in a two-dose regimen. European recommendations suggest giving 2 doses of VZV vaccine for seronegative immunocompetent IBD patients, finishing at least 3 weeks before immunomodulators (1). Herpes zoster vaccine is recommended in immunocompetent individuals over 50 years of age. Comfort in vaccinating IBD patients has increased, with retrospective publications reporting lesser rates of HZ in HZ-vaccinated patients, and safe outcomes even in those immunosuppressed at the time of vaccination (2,8). In one series, 59 IBD patients on anti-TNFα therapy (median age 64.9 years) safely received HZ vaccination without development of HZ, leading to the question of whether even younger IBD adults should receive HZ vaccination (2).
An increasing percentage of pediatric IBD patients have never had wild-type varicella infection, having received VZV vaccination. What made our case unique was the timing of disseminated HZ post VZV vaccination and in relation to IBD therapies. At IBD diagnosis in December 2015, the patient had not been revaccinated due to the need for rapid immunosuppression, and uncertainty of actual risk for varicella despite negative VZV IgG. The issue of what could be done to prevent such a case remains a key consideration. The medical literature has evolved since this patient’s presentation, with increasing comfort level with immunizing immunosuppressed patients. VZV vaccination is now reported to be safe and well tolerated in patients with IBD, on immunosuppression, and ensuring immunoreactivity by laboratory markers may be a reasonable approach to deciding if an additional dose of the VZV vaccine should be given (10). Given our patient had a negative VZV IgG, despite receiving the vaccine previously, the patient might have benefited from another dose of VZV vaccine at some point even while on immunosuppression. The more recent literature supporting use of VZV vaccine in immunocompromised IBD patients should prompt pediatric gastroenterologists to re-discuss vaccination options with non-protected patients. Additionally, the more recent availability of nonlive-adjuvanted HZ vaccine, although currently only approved in adults >50 years old, may eventually become a feasible safer alternative for younger immunosuppressed patients who have concerns about receiving live-attenuated virus.
To our knowledge, this is the first report of a varicella vaccine-strain HZ disseminated infection including meningitis in a pediatric Crohn’s patient, on only adalimumab maintenance, presenting more than 15 years after immunization. Optimizing protection against vaccine-preventable illnesses is a key concern in IBD patients, even while on immunosuppression. Vaccine-related complications; however, should always be considered in IBD patients on immunosuppressant medications, regardless of the time interval between symptom onset and immunization date.