Case Presentation: An 85-year-old female with a history of non-Hodgkin’s B-cell lymphoma on Ibrutinib is brought into the emergency department (ED) by ambulance for generalized, progressive weakness and recurrent falls. She was recently diagnosed with herpes zoster 2 weeks prior, on her right upper extremity and denies being started on any medication. She complained of poor appetite, fevers and chills with worsening pain in her right upper extremity and purulent discharge from both of her eyes. Her temperature was 38.9°C, heart rate 112 respiratory rate 32, blood pressure 112/84. Physical exam was notable for, a diffuse vesicular rash in different stages of healing involving her conjunctival bilaterally with conjuctival injection. The right upper extremity had confluent lesions and large bullae. Her Brudzinski sign was negative. Labs revealed a white count of 11.2 109/L, elevated lactate 2.4 mM and creatinine of 1.2 mg/dL (increased from a baseline of 0.6). The CSF cultures were positive for varicella-zoster virus, confirming meningitis. The diagnosis of disseminated herpes zoster with secondary manifestations of zoster opthalmicus was made. She was treated with IV acyclovir, ophthalmic ointment ganciclovir and erythromycin.

Discussion: Herpes Zoster is an opportunistic reactivation of herpes varicella that occurs when the immunity of previous inoculation or native immune response decreases. Immunocompromised states secondary to advanced age are the most important risk factors.1 The rate of complications is also significantly higher in immunocompromised patients.2 One of the feared complications of this disease is disseminated herpes. This occurs in 2% of the general population and about 15%-30% of cases in immunocompromised patients.3 As seen in this patient, she was diagnosed with Herpes Zoster maintaining her Ibrutinib therapy and denies receiving antiviral therapy. The ibrutinib therapy for her Non-Hodgkin’s Lymphoma was the proposed mechanism for reactivation and dissemination, however, a CT chest, abdomen and pelvis with a blood smear was conducted to ensure no underlying malignancy or recurrence was detected. This case highlights the importance of considering prophylactic treatments in an immunosuppressed state, for both T and B-cell modifying immunotherapies. Ibrutinib is an oral, irreversible inhibitor of both Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Blocking ITK blunts type-2 T-helper (Th2) cells responses after T-cell receptor stimulation.4 This mechanism leads to an immunosuppressed state. The risk of opportunistic infections in patients treated with inhibitors of the BCR pathway has only recently begun to be defined with 3 case reports of disseminated zoster identified using Ibrutinib in CLL.5 Currently, people on BCR inhibitors are risk stratified individually to determine if prophylactic treatment is necessary.

Conclusions: Disseminated Varicella Zoster carries a high morbidity and mortality in the immunocompromised. Currently, the association between opportunistic infections and BCR inhibitors is starting to be defined. There are no current recommendations of the use of antiviral prophylaxis in individuals undergoing BCR inhibitor therapy. Clinicians should be aware of the risk of opportunistic infections and individually stratify targeted therapies based on individual risk. Further studies evaluating the use of prophylactic antivirals or microbials in BCR-inhibitor therapies is warranted.

IMAGE 1: Figure 1: Right Upper Extremity