HERPES SIMPLEX VIRUS PNEUMONIA MASQUERADING AS DRUG-INDUCED PNEUMONITIS

ABSTRACT

TOPIC Chest Infections TYPE Fellow Case Reports INTRODUCTION: Drug induced pneumonitis is a major cause of adverse events during cancer therapy, and has become increasingly common with the use of immune-checkpoint inhibitor (ICI) therapy. Due to its rarity, ICI pneumonitis is a diagnosis of exclusion, and infection and malignancy must be ruled out. While multiple types of infection are typically assessed for, Herpes Simplex Virus (HSV) pneumonia is often not considered. We report the case of a 75 year old man with non-small cell lung cancer (NSCLC) on pembrolizumab who died despite aggressive treatment for a presumed ICI pneumonitis, and was found on autopsy to have had HSV pneumonia. CASE PRESENTATION A 75 year old man with NSCLC presented to hospital with two days of dyspnea. The patient was being treated with a multi-drug chemotherapy regimen, including pembrolizumab. His last cycle was five days prior to admission. On admission, he was found to be hypoxic, saturating 70% on room air, with course bilateral crackles, and extensive bilateral ground glass opacities on chest CT. He did not have leukocytosis. Multiple infectious studies, including COVID-19, CMV, respiratory viral panel, legionella, mycoplasma, beta-D glucan, and galactomannan were negative. ICI pneumonitis was highest on the differential, and the patient was therefore started on solumedrol. After two days of no improvement, the solumedrol was increased and infliximab was added. The patient's respiratory status continued to worsen, and he was ultimately intubated. The patient underwent bronchoscopy once intubated, however, he expired before the studies resulted. Autopsy revealed a severe HSV pneumonia. DISCUSSION: ICI pneumonitis occurs in approximately 5% of patients treated with PD(L)-1 inhibitors, of which approximately 25% of cases are graded as severe or life-threatening. While the vast majority of patients with non-severe disease are successfully treated by withholding the ICI alone or in conjunction with glucocorticoids, those with more severe disease may require additional immunosuppression, and a small number of these patients die despite treatment. Due to its rarity, ICI pneumonitis is a diagnosis of exclusion, and diagnoses such as infection and malignancy should always be ruled out. The fact that its radiographic presentation is so heterogenous, with patterns as variable as those seen with COP, NSIP, HP, and AIP/ARDS, makes it all the more difficult to diagnose. HSV pneumonia is known to infrequently cause pneumonia in severely immunocompromised patients. A prospective observational study conducted in 2018 on immunocompromised adults with pneumonia not responding to empiric antibiotic therapy found it to be much more common than expected, with 42% of patients testing positive for HSV-1 on BAL, and 24% meeting criteria for HSV pneumonia. CONCLUSIONS: HSV pneumonia should be more frequently considered in immunocompromised patients suspected of having an ICI pneumonitis. REFERENCE #1 Nishino M, et al. Drug-related pneumonitis in the era of precision cancer therapy. JCO Precision Oncology. 2017 May 26;1 1-12. REFERENCE #2 Naidoo J, et al. Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clinical Oncology. 2017 Mar;35 (7) 709-717. REFERENCE #3 Luzzati R, et al. Herpex simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host burden and predictors. J Infect. 2019 Feb;78 (2) 127-133. DISCLOSURES No relevant relationships by Jeffrey Ordner, source=Web Response No relevant relationships by Ariella Pratzer, source=Web Response No relevant relationships by Mark Sloane, source=Web Response No relevant relationships by Kristen Thomas, source=Web Response No relevant relationships by Karen Yang, source=Web Response