Herpes Simplex Virus Pneumonia Research Articles

The Diagnosis and Management of Herpes Simplex Pneumonia in the Critical Care Setting: A Comprehensive Review.

Herpes simplex virus (HSV) belongs to the Herpesviridae family and is divided into two subtypes: HSV-1 and HSV-2. It is known that herpesviruses lie dormant in neural ganglion cells and are reactivated during times of stress, trauma, fever, and immunosuppression. While HSV primarily causes mucosal infections such as cold sores or upper respiratory tract manifestations, it can also lead to serious, life-threatening infections, particularly in immunocompromised patients. Although HSV is occasionally detected in airway samples from critically ill patients, true HSV pneumonia is rare. HSV pneumonia is thought to result from the aspiration of salivary secretions that can travel from the pharynx and tracheobronchial areas to the lungs. It can be difficult to diagnose, and the presence of HSV in respiratory specimens does not necessarily indicate true infection. Treatment with antiviral drugs such as acyclovir should be considered based on the clinical presentation, corroborative findings, and the presence of cytopathological changes in the bronchoalveolar specimen. The prognosis of HSV pneumonia is generally poor and early detection is critical for better outcomes. This review discusses the risk factors, clinical presentation, diagnosis, treatment, and prognosis of HSV pneumonia and emphasizes the importance of distinguishing between true infection and carrier status.

Risk Stratification for Herpes Simplex Virus Pneumonia Using Elastic Net Penalized Cox Proportional Hazard Algorithm with Enhanced Explainability.

Herpes simplex virus (HSV) pneumonia is a serious and often fatal respiratory tract infection that occurs in immunocompromised individuals. The early detection of accurate risk stratification is essential in identifying patients who are at high risk of mortality and may benefit from more aggressive treatment. In this study, we developed and validated a risk stratification model for HSV bronchopneumonia using an elastic net penalized Cox proportional hazard algorithm. We analyzed data from a cohort of 104 critically ill patients with HSV bronchopneumonia identified in Chang Gung Memorial Hospital, Linkou, Taiwan: one of the largest tertiary medical centers in the world. A total of 109 predictors, both clinical and laboratory, were identified in this process to develop a risk stratification model that could accurately predict mortality in patients with HSV bronchopneumonia. This model was able to differentiate the risk of death and predict mortality in patients with HSV bronchopneumonia compared to the APACHE II score in the early stage of ICU admissions. Both hazard ratio coefficient and selection frequency were used as the metrics to enhance the explainability of the informative predictors. Our findings suggest that the elastic net penalized Cox proportional hazard algorithm is a promising tool for risk stratification in patients with HSV bronchopneumonia and could be useful in identifying those at high risk of mortality.

Typical target lesion with a central blister in erythema multiforme major caused by drug allergy in a toddler

Erythema multiforme (EM) is an uncommon acute mucocutaneous illness with target lesions primarily on the face and limbs. Slow-onset hypersensitivity reactions to infections (including herpes simplex virus and mycoplasma pneumonia) and medicines (including antibiotics, anticonvulsants, and nonsteroidal anti-inflammatory drugs) cause EM. A 4-year-old male with EM after taking metamizole, ampicillin, cloxacillin, and an unknown puffer, the major developed lip sores and blisters on various places of his body. Dermatological examination revealed haemorrhagic crusts on the lips. On both hands and feet, typical target lesions with central blisters, purplish red in color, well-defined boundaries, round to oval in form, and variable size were seen. There were erythematous macules and genital oedema. A blood test revealed higher levels of leucocytes and CRP. Serological testing revealed no IgG, IgM, or anti-HSV1&2 antibodies. The X-ray of the chest was normal. Clinical improvement occurred after elimination of suspected drugs and intravenous dexamethasone, gentamicin, and paracetamol, oral cetirizine, fusidic acid 2% cream, 0.9% NaCl compress, and sterile gauze. The diagnosis of EM was established based on the presence of multiple typical target lesions with central blisters, symmetrical distribution on the extremities (dorsal surfaces of hands and feet), and involvement of lip and genital mucosal lesions after taking drugs. Negative IgG and IgM Anti HSV 1&2 test results lead to the diagnosis of drug allergy-related Erythema Multiforme Major.

COVID-associated pulmonary aspergillosis and herpes simplex virus pneumonia in a renal transplant recipient.

COVID-associated pulmonary aspergillosis and herpes simplex virus pneumonia in a renal transplant recipient.

HERPES SIMPLEX VIRUS PNEUMONIA MASQUERADING AS DRUG-INDUCED PNEUMONITIS

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

HSV PNEUMONIA IN AN IMMUNOCOMPETENT PATIENT PROGRESSING TO ORGANIZING PNEUMONIA

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: HSV pneumonia has been rarely reported in immunocompetent patients. We report a case of a 75-year-old healthy female with intractable pneumonia diagnosed as HSV that progressed to organizing pneumonia CASE PRESENTATION: A 75-year-old female with a past medical history of Barrett's esophagus presented to the ER with a 3-week history of fatigue, fevers, and shortness of breath. She had no family history of autoimmune disorders, she moved from Iran 40 years ago and had no known exposure to TB. She denied smoking and had no pets or any other exposures. Labs showed leukocytosis of 14000 with neutrophilic and monocytic predominance, mild hyponatremia (132 meq/L), and a procalcitonin of 0.25 ng/ml. Chest X-ray revealed infiltrates in the right upper and lower lobes. She was started on ceftriaxone and azithromycin but continued to worsen. Antibiotics were broadened again without clinical response. Urine streptococcus, legionella antigen, B-D-glucan, Tuberculin skin test, HIV, histoplasma were all negative. Bronchoscopy was done on day 10 that revealed copious clear, yellow clear fluid in her proximal and distal airway and with similarly appearing fluid with mucus plugs on the BAL. Cultures from BAL including modified AFB for nocardia were unrevealing. Rheumatological workup including, ANA, ANCA, anti-CCP, Sjogren's antibody, myositis panel, HSP was also negative. Subsequent CT scan revealed worsening infiltrates and a right-sided pleural effusion, patient underwent thoracentesis, and cultures on pleural fluid were positive for HSV. The patient underwent a VATS biopsy (Day 22) that revealed organizing pneumonia with thickened alveoli and fibrinous plugs. HSV 1 IgG antibodies were also positive. She was started on steroids and acyclovir with significant improvement. DISCUSSION: HSV is known to infect the upper airway and can cause gingivostomatitis and pharyngitis. It can progress to pneumonitis or pneumonia in patients who are immunocompromised or mechanically ventilated. Only in rare cases does it manifest as clinically significant lower respiratory tract infections in immunocompetent individuals. Our patient had a biphasic illness, she was diagnosed based on the HSV culture on the pleural fluid, which has a specificity of 99%. Her second episode of respiratory failure with worsening infiltrates represented the development of organizing pneumonia that responded to steroids. The use of acyclovir in such patients is not supported by clinical trials and needs to be studied. Our patient finished a course of acyclovir and was treated with steroids for several weeks. CONCLUSIONS: HSV pneumonia should be considered as an etiology of intractable pneumonia when patients do not show clinical improvement on conventional therapy. This case also suggests that acute herpes infection can have serious complications like organizing pneumonia and further studies are needed to understand this association. REFERENCE #1: Mills B, Ratra A, El-Bakush A, Kambali S, Nugent K. Herpes Simplex Pneumonia in an Immunocompetent Patient With Progression to Organizing Pneumonia. J Investig Med High Impact Case Rep. 2014 Apr 9;2(2):2324709614530560. doi: 10.1177/2324709614530560. PMID: 26425602; PMCID: PMC4528890. REFERENCE #2: Martinez E, de Diego A, Paradis A, Perpiñá M, Hernandez M. Herpes simplex pneumonia in a young immunocompetent man. Eur Respir J. 1994 Jun;7(6):1185-8. PMID: 7925891. DISCLOSURES: No relevant relationships by Chahat Puri, source=Web Response No relevant relationships by Kyunghoon Rhee, source=Web Response No relevant relationships by Donald Slack, source=Web Response No relevant relationships by Jennifer Sullivan, source=Web Response No relevant relationships by Ari Zaiman, source=Web Response

HERPES SIMPLEX VIRUS PNEUMONITIS IN AN IMMUNOCOMPETENT, CRITICALLY ILL HOST

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pneumonitis due to herpes simplex virus is well reported in immunocompromised patients. It is extraordinarily uncommon in immunocompetent patients. CASE PRESENTATION: A 68 year old female with a history of chronic hypoxic respiratory failure on 2 Liters home oxygen presented to our facility with one day of dizziness and profound shortness of breath. At presentation, her oxygen saturation was 75%. A CT of the chest demonstrated significant bilateral diffuse infiltrates of ground glass appearance with consolidation. She was intubated and was transferred to the ICU. She had septic shock requiring vasopressors, and was started on community acquired pneumonia coverage with vancomycin, doxycycline, and ceftriaxone. She was extubated to high flow nasal canula and she was transferred to Step Down. On the floor, she failed to improve and required significant high flow nasal canula and bilevel positive airway pressure (BIPAP) support. A bronchoscopy was performed which showed that the lungs appeared normal. Cytopathology of bronchial washings showed positive staining for HSV-1. Transbronchial biopsy was also performed which demonstrated organizing pneumonia with focal nuclear atypia, findings suggestive of a viral pneumonitis. She was initiated on IV Acyclovir and was evaluated for immunocompromise, however, an extensive workup revealed no cause of compromise. She was noted to have perioral lesions consistent with herpes labialis which she reported started prior to her admission. She improved significantly after initiation of anti-viral therapy. DISCUSSION: Unfortunately, the signs and symptoms of herpes simplex pneumonitis are quite non specific, and in the intensive care setting, diagnosis can be obscured by positive HSV PCR on bronchial specimens in patients without HSV Pneumonitis. . A 2020 retrospective study showed that patients being treated for antibiotic-resistant ventilator associated pneumonia who were also found to have high levels of HSV DNA by PCR experienced a mortality benefit when treated with acyclovir. This finding suggests that HSV may be an underrepresented pathogen in immunocompetent hosts. Despite the vague nature of HSV pneumonitis, there are several features which can be suggestive. It should be considered in patients with disease resistant to antibacterial therapy, difficulty weaning from oxygen, and unexplained leukocytosis. Chest X-ray findings are nonspecific, but CT imaging usually shows ground glass opacities. CONCLUSIONS: Prior case reports have suggested that HSV pneumonitis in immunocompetent hosts occurs late in the course of illness and is associated with ventilator use. This case is significant as it represents HSV as a potential pathogen in immunocompetent patients at the onset of illness prior to initiation of invasive ventilation. REFERENCE #1: 1. Ishihara T, Yanagi H, Ozawa H, Takagi A. Severe herpes simplex virus pneumonia in an elderly, immunocompetent patient. BMJ Case Rep. 2018;2018:bcr2017224022. Published 2018 Jul 18. doi:10.1136/bcr-2017-224022 REFERENCE #2: 2. Schuierer L, Gebhard M, Ruf HG, et al. Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication. Crit Care. 2020;24(1):12. Published 2020 Jan 10. doi:10.1186/s13054-019-2701-5 REFERENCE #3: 3. Pandita A, Dannheim K, Madhuripan N, Ehsan A, Farmakiotis D. Acute Necrotizing Pneumonia from Herpes Simplex Virus. Am J Med. 2021;134(2):e121-e122. doi:10.1016/j.amjmed.2020.06.050 DISCLOSURES: No relevant relationships by Jacob Gelman, source=Web Response No relevant relationships by Lucas Hamrick, source=Web Response No relevant relationships by Allison Lastinger, source=Web Response

Herpes Simplex Virus Type 1 Pneumonia-A Review.

Pneumonia due to herpes simplex virus (HSV) is uncommon but can be seen in immunocompromised patients and has been associated with poor prognosis in this population. The aim was to study the results, outcome and mortality of HSV pneumonia in immunocompromised patients and patients receiving mechanical ventilation. Furthermore, it has been unclear whether to initiate prophylactic treatment with acyclovir or not. We have conducted a literature search using the keywords herpes simplex pneumonia, critically ill patients and intensive care unit for identification of relevant publications. HSV pneumonia can cause severe infection or even death in immunocompromised patients and critically ill patients. A clear diagnosis of HSV pneumonia can be difficult to establish. Respiratory condition may improve after initiation of acyclovir but data is scarce. HSV pneumonia should be considered in the immunocompromised patient and/or the intensive care patient who continues to deteriorate despite appropriate treatment. The value of prophylactic treatment with acyclovir is unproven but should be considered.

Routine testing for herpes simplex virus in bronchoalveolar lavage specimens is unwarranted

Herpes simplex virus (HSV) infections of the lung are rare, but HSV is occasionally detected in bronchoalveolar lavage (BAL) specimens. We assessed whether routinely performing HSV PCR tests in BAL specimens is warranted. HSV was detected in 7% (52/722) of BALs. In 47% of HSV-positive patients a typical respiratory virus or pathologic microorganism was identified. Oral HSV reactivation was identified in 27%; however,anti-HSV therapy was initiated in just three patients following the positive HSV test. Patients undergoing BAL for transplant surveillance received anti-HSV prophylaxis more often than those with acute respiratory failure, but both groups did not differ significantly in terms of patient outcome or co-infections. No patient was diagnosed with HSV pneumonia. These findings suggest that positive HSV PCR results in BAL specimens most commonly represents contamination from oral HSV reactivation, and that HSV PCR should be ordered selectively, rather than routinely, as part of a test panel.

HERPES SIMPLEX VIRUS MASQUERADING AS AN ENDOBRONCHIAL LESION

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Herpes simplex virus (HSV) endobronchial lesions are rarely observed. Case reports describe partially or fully obstructing masses in both immunocompetent and immunocompromised patients. Diagnosis requires both visualization and histological evidence in the absence of malignancy. CASE PRESENTATION: A 68 year-old immunocompetent female with a history of oxygen dependent chronic obstructive pulmonary disease presented to the emergency department for dyspnea and cough. Chest x-ray showed atelectasis of the right lung fields with mediastinal shift towards the right and suggested an underlying pleural effusion. Computed tomography of the chest revealed a large right pleural effusion with near complete atelectasis of the right lung and suspicion for a mass in the right lower lobe. The patient required intubation for hypoxemic respiratory failure and was treated for septic shock and pneumonia. A small bore chest tube was placed and subsequent fluid analysis was consistent with empyema. Culture results were treated with appropriate antibiotics. A bedside bronchoscopy was performed for worsening copious secretions and found a partially obstructing endobronchial lesion in the right posterior basal segment. Biopsy and bronchial lavage washings were sent for analysis. While awaiting results the patient was extubated and improving. Bronchoscopy results yielded HSV-1. The patient was started on acyclovir and made a full recovery. DISCUSSION: To our knowledge all reported endobronchial HSV mass lesions have resulted in HSV pneumonia requiring antiviral treatment. Interestingly, our patient improved clinically prior to positive HSV polymerase chain reaction results and was extubated. Most likely the endobronchial lesion led to post-obstructive pneumonia and eventual empyema. What is truly unique is that the herpetic pseudotumor did not appear to result in a viral pneumonia but instead was the nidus for superimposed secondary bacterial infection. We did initiate acyclovir for one week but the severity of our findings were questioned. Studies have looked at HSV’s presence in upper and lower respiratory tract and have found it is not an uncommon finding. As of yet there is not a clear understanding of its pathogenicity. CONCLUSIONS: HSV is a rare cause of endobronchial mass lesions in immunocompetent adults. The clinical significance of this finding is not fully understood at this time and requires further investigation. *HCA Disclaimer “This research was supported (in whole or part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this presentation represent those of the author and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.” Reference #1: Odani, K., Tachibana, M., Tamashima, R., & Tsutsumi, Y. (2019). Herpes Simplex Virus Pneumonia: Importance of Aspiration Etiology. Case Reports in Pathology, 2019, 1-3. doi:10.1155/2019/7623576 Reference #2: Simoons-Smit, A., Kraan, E., Beishuizen, A., Schijndel, R. S., & Vandenbroucke-Grauls, C. (2006). Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clinical Microbiology and Infection, 12(11), 1050-1059. doi:10.1111/j.1469-0691.2006.01475.x Reference #3: Dantas, G. C., Shoji, H., Hoelz, C., Funari, M. B., & Szarf, G. (2017). Herpes simplex lesion mimicking left upper lobe bronchial tumour. Thorax, 73(1), 94-95. doi:10.1136/thoraxjnl-2017-210026 DISCLOSURES: No relevant relationships Added 05/29/2020 by Leonard Hamera, source=Web Response, value=Grant/Research Support Removed 05/29/2020 by Leonard Hamera, source=Web Response No relevant relationships by Jeffrey Jordan, source=Web Response No relevant relationships by Gaurav Shah, source=Web Response

36-YEAR-OLD MAN WITH ACUTE INFLUENZA AND SECONDARY BACTERIAL PNEUMONIA COMPLICATED BY HERPES VIRUS INFECTION

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Herpes Simplex Virus (HSV) pneumonia is rare in immunocompetent individuals. It has been described in young to middle aged patients with flu-like symptoms [1]. It should be suspected in patients with clinical deterioration despite antimicrobial therapy [2]. Diagnosis is made by PCR, culture, cytopathology and response to acyclovir therapy. Active infection is controversial since HSV-1 is commonly identified in the respiratory tract mucosa of critically ill patients [1-3]. CASE PRESENTATION: Patient is a 36 year-old male with history of bronchial asthma presented to an outside hospital with acute onset dyspnea, productive cough and worsening of hemoptysis for one week prior to admission. Exposures include sand blasting and cotton processing. He presented with fever, bilateral pulmonary infiltrates, and respiratory failure that required intubation with mechanical ventilation. Multifocal consolidative changes with air bronchograms and ground glass opacities were seen on CT Chest. Influenza A/H1 was diagnosed by PCR and treated with oseltamivir as well as antibacterial antibiotics for superimposed bacterial infection. Initial bronchoscopy with BAL did not show fungal or bacterial growth. Autoimmune panel and HIV were negative. Despite appropriate antibiotic coverage, he failed he failed to improve. On hospital day 7, he developed fever and a rash. His antibiotics were changed to vancomycin and meropenem. Repeat bronchoscopy was performed. Erythematous bronchial mucosa with mucopurulent exudate were seen. BAL cultures were negative for bacteria, fungi or PJP. DFA was positive for HSV1 with a positive viral culture. Antibiotics were discontinued, and he was started on acyclovir. Patient’s ventilator requirements decreased and chest imaging improved. He was successfully extubated on day 16th DISCUSSION: Pathogenic mechanisms for HSV pneumonia include stress induced by mechanical ventilation, systemic inflammation and respiratory distress which contribute to viral reactivation in the lower respiratory tract [1-3]. Chronic lung disease can also be an important factor as illustrated in our case. There are no established diagnostic criteria for HSV pneumonia and guidelines on its treatment with acyclovir are sparse. HSV diagnosis is a challenge, and it should be considered after excluding other infection sources, inflammatory and autoimmune causes. CONCLUSIONS: HSV pneumonia can be suspected in patients with prolonged mechanical ventilation. It requires a high index of suspicion. HSV pneumonia is associated with worse outcomes and longer hospital stays. Reference #1: Ishihara T, Yanagi H, Ozawa H, et al. Case report: Severe herpes simplex virus pneumonia in an elderly, immunocompetent patient. BMJ Case Rep (2018) 18 July 2018: 1- 4. Reference #2: Linssen CF, Jacobs JA, Stelma FF, et al. Herpes simplex virus load in bronchoalveolar lavage fluid is related to poor outcome in critically ill patients. Intensive Care Med 2008;34:2202–9. Reference #3: Simoons-Smit AM, Kraan EM, Beishuizen A, et al. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander? Clin Microbiol Infect 2006;12:1050–9. DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Barbara Mantilla, source=Web Response No relevant relationships by Arunee Motes, source=Web Response No relevant relationships by Victor Test, source=Web Response No relevant relationships by Myrian Vinan Vega, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

AN UNUSUAL CASE OF HERPES SIMPLEX VIRUS PNEUMONIA WITH NECROTIC AND CAVITARY CHANGES

SESSION TITLE: Global Case Report Posters SESSION TYPE: Global Case Reports PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Herpes simplex virus (HSV) pneumonia can occur in both immunocompromised and immunocompetent patients. Ground glass opacities, consolidation, and pleural effusions are observed in HSV pneumonia. Neither necrosis nor cavitation has been reported in areas of parenchymal disease. We describe a case of HSV pneumonia with unusual multiple cavitary and necrotic changes. CASE PRESENTATION: A 63-year-old woman was referred to us on January 15, 2019. She had been managed as a case of community-acquired pneumonia for 15 days at another hospital but had been progressed to respiratory failure. On January 2, chest CT scan showed peribronchial and subpleural patchy consolidation, and multiple small nodules in both lungs. She was intubated on January 4. She had a medical history of hypertension. She was newly diagnosed with diabetes at admission. Upon admission, broad spectrum antibiotics were administered but she did not improve. On January 23, chest CT showed progressive necrotic and cavitary changes in areas of consolidation and small nodules in both lungs. Bilateral pleural effusion was also increased with multiple necrotic lymph nodes. Bronchoscopy on the same day showed scattered whitish plaque-like lesions, especially on both lower lobe bronchi. Biopsy showed ulceration, necrotic inflammatory exudate, extensive squamous metaplasia and several multinucleated epithelial cells containing intranuclear inclusions, consistent with HSV or varicella-zoster virus infection. Immunohistochemical staining showed a positive reaction to HSV. Viral serology, PCR, and viral, bacterial, and fungal cultures with bronchial aspirate showed negative results. Acyclovir therapy was started on January 24. Percutaneous catheter drainage was performed for left exudative pleural effusion. The patient improved slowly; a CT scan on February 12 showed overall improvement. She was moved to the general ward after being weaned off mechanical ventilation on February 14. DISCUSSION: HSV pneumonitis cannot be diagnosed based on imaging alone; evidence of viral cytopathic effect on cytologic and/or histopathologic specimens with confirmation of HSV infection via culture, PCR, or immunohistochemical staining is required. Detection of histological hallmarks of HSV infection, such as multinucleated cells with ground glass intranuclear changes and Cowdry type A intranuclear inclusion bodies, is specific for true lower respiratory tract infections rather than a carrier state, especially in critically ill patients. In this case, we could confirm HSV pneumonia by typical endobronchial lesions, histopathologic findings, immunohistochemical staining, and overall improvement on follow-up chest CT with acyclovir therapy. CONCLUSIONS: To our knowledge, this is the first reported case of HSV pneumonia with multiple cavitary and necrotic changes in areas of consolidation and nodules. Reference #1: Chong S, Kim TS, Cho EY. Herpes simplex virus pneumonia: high-resolution CT findings. Br J Radiol 2010; 83:585–589. Reference #2: Aquino SL, Dunagan DP, Chiles C, Haponik EF. Herpes simplex virus 1 pneumonia: patterns on CT scans and conventional chest radiographs. J Comput Assist Tomogr 1998; 22(5):795-800. Reference #3: Simoons-Smit AM, Kraan EM, Beishuizen A, Strack van Schijndel AJ, Vandenbroucke-Grauls CM. Herpes simplex virus type 1 and respiratory disease in critically-ill patients: real pathogen or innocent bystander? Clin Microbiol Infect 2006; 12:1050–1059 DISCLOSURES: No relevant relationships by Cheol-Woo Kim, source=Web Response No relevant relationships by Hong Lyeol Lee, source=Web Response

THORACIC CENTRAL VEIN OCCLUSION CAUSING LUNG COLLAPSE IN A PATIENT ON VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION

SESSION TITLE: Clinical Conundrums in ECMO SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/20/2019 1:00 PM - 2:00 PM INTRODUCTION: Thoracic central vein occlusion (TCVO) is a feared complication in hemodialysis (HD) patients. Superior vena cava (SVC) obstruction impeding thoracic venous flow to the right atrium (RA) results in upper body and facial edema. We describe a case of TCVO in a patient on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) associated with azygous vein (AV) distension causing right mainstem (RMS) bronchus compression and lung collapse. CASE PRESENTATION: A 56-year-old woman with Hodgkin’s lymphoma was admitted with acute respiratory distress syndrome and herpes simplex pneumonia. Despite lung protective ventilation and paralysis, she remained hypoxemic. She progressed to refractory shock in the setting of severely reduced cardiac function and sepsis. VA-ECMO using a femoral configuration was initiated. Two days after ECMO cannulation, she developed arm and facial edema as well as collapse of the right lung (Figure 1). A bronchoscopy showed RMS bronchus occlusion by an extrinsic structure. Endobronchial ultrasound showed a vascular structure at the carina obstructing the RMS consistent with a severely distended AV. The ECMO configuration was changed to facilitate dual caval drainage. The SVC was drained via a 14-French (Fr) cannula, the inferior vena cava (IVC) was drained via a 25-Fr cannula, and oxygenated blood was returned to the patient via femoral artery cannulation. The addition of the dedicated SVC drainage cannula resulted in improvement in edema and AV distention, and thus extrinsic compression of the RMS resolved (Figure 2). The patient improved and was weaned off ECMO. Later, a stent was placed in the SVC with durable resolution of the obstruction. DISCUSSION: A common VA-ECMO technique is insertion of a venous cannula in the IVC or RA for drainage and an arterial cannula in the femoral artery for return of pressurized oxygenated blood to the patient. In our patient, femoral access in the setting of underlying SVC obstruction led to inadequate drainage of the upper half of the body causing venous hypertension with upper extremity, torso and face edema, similar to TCVO described in HD patients. AV distension led to RMS bronchus compression and caused right lung collapse. This complication has not previously been described. By changing the ECMO configuration to dual caval drainage, the SVC obstruction was bypassed and drainage of the upper half of the body could be achieved. CONCLUSIONS: ECMO is a life-saving therapy in patients with refractory cardiorespiratory failure that can be associated with severe complications. Consideration of different cannula configurations depending on the patient’s anatomy is important since placement of these catheters is associated with morbidity (1). SVC obstruction causing inadequate drainage of the upper half of the body in patients on VA-ECMO is rarely seen, and resulting AV distension leading to RMS bronchus compression is rarer still. Reference #1: 1. Zangrillo A, Landoni G, et al. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc 2013;15:172-8. DISCLOSURES: No relevant relationships by Seema Amin, source=Web Response No relevant relationships by Haval Chweich, source=Web Response No relevant relationships by Erik Garpestad, source=Web Response Consultant relationship with Abiomed Please note: $1001 - $5000 Added 03/14/2019 by John Reich, source=Web Response, value=Consulting fee

Herpes simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host: Burden and predictors

To evaluate burden and predictors of HSV pneumonia among immunocompromised patients not undergoing invasive mechanical ventilation according to a tailored diagnostic algorithm. This prospective, observational study included immunocompromised adults with pneumonia non-responding to empirical antibiotic therapy. Bronchoalveolar lavage (BAL) specimens were cultured for bacteria, mycobacteria and fungi. Real-time PCR for Herpesviruses and other microorganisms were performed on BAL and other specimens. Cytological examination of BAL samples was carried out for identification of intranuclear inclusion bodies and immunohistochemical staining for HSV. We enrolled 45 patients (mean age 64.6 years) from January 2015 to June 2016. Nineteen (42.2%) cases tested positive for HSV-1 PCR on BAL. According to our definitions, 11 (24.4%) patients had HSV-1 pneumonia with viral loads ranging between 103 copies/mL and 107 copies/mL. HSV-1 positive throat swab (OR 85.2, 95% CI 5.83-1245.1, P < 0.001) and solid organ transplant (SOT) (OR 53.3, 95% CI 1.37-2072.8, P < 0.03) as underlying condition were found to be independently associated with HSV pneumonia by multivariable analysis. HSV pneumonia turned out to be relatively common and should be investigated especially in individuals with HSV positive throat swab and SOT. Interventional studies are needed to assess the real clinical impact of HSV pneumonia in immunocompromised patients.

Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-δ Syndrome.

The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is important for multiple stages of herpesvirus replication including virus entry, replication, latency, and reactivation. Recently, patients with gain-of-function mutations in the p110δ-catalytic subunit of PI3K or in the p85-regulatory subunit of PI3K have been reported. These patients have constitutively active PI3K with hyperactivation of Akt. They present with lymphoproliferation and often have infections, particularly recurrent respiratory infections and/or severe virus infections. The most frequent virus infections are due to Epstein–Barr virus (EBV) and cytomegalovirus (CMV); patients often present with persistent EBV and/or CMV viremia, EBV lymphoproliferative disease, or CMV lymphadenitis. No patients have been reported with CMV pneumonia, colitis, or retinitis. Other herpesvirus infections have included herpes simplex pneumonia, recurrent zoster, and varicella after vaccination with the varicella vaccine. Additional viral infections have included adenovirus viremia, severe warts, and extensive Molluscum contagiosum virus infection. The increased susceptibility to virus infections in these patients is likely due to a reduced number of long-lived memory CD8 T cells and an increased number of terminally differentiated effector CD8 T cells.

Isolated herpes simplex virus pneumonia in children

Disseminated herpes simplex virus (HSV) infection is a well recognized condition in infants and children. However, the diagnosis of isolated HSV pneumonia, without evidence of other organ involvement, in this population is rare. We present a case series of isolated HSV pneumonia in four patients, all of which survived this acute illness with normal neurological outcome. Clinical features, diagnostic approaches, intensive care management, and antiviral drug therapy are reviewed.

Herpes Simplex Pneumonia in an Immunocompetent Patient With Progression to Organizing Pneumonia

Background. Organizing pneumonia is an uncommon diffuse interstitial lung disease that affects the terminal and respiratory bronchioles, alveolar ducts, and alveoli. Most cases are idiopathic, but some are associated with infections. We present an uncommon case of organizing pneumonia associated with herpes simplex virus-1 (HSV-1). Case. A 39-year-old man with hypertension presented with dyspnea, fever, and productive cough for 2 weeks. He was treated for 5 days for acute bronchitis as an outpatient with no improvement. His examination revealed mild respiratory distress, O2 saturation 92% on room air, and right sided crackles. Labs included a white blood cell count of 19 300/µL. His chest x-ray showed bilateral infiltrates greater on the right. Bronchoalveolar lavage was positive for HSV-1; transbronchial biopsies showed focal pneumonitis with plentiful intra-alveolar macrophages. His respiratory status progressively deteriorated, and he was intubated for mechanical ventilation. He received 10 days of intravenous (IV) antibiotics and 14 days of IV acyclovir. He was readmitted 10 days later with worsening symptoms and was intubated for respiratory failure. His CT chest showed diffuse, patchy consolidation of both lungs, right more than left. Open lung biopsy showed extensive organizing pneumonia, diffuse alveolar damage, intra-alveolar macrophages, and pleural fibrosis; he was treated with IV corticosteroids. He was extubated after 10 days; within 2 weeks his chest x-ray was markedly improved. Discussion. Organizing pneumonia is usually idiopathic; infection is one of the secondary causes. To our knowledge this is only the second reported case associated with HSV. This association may have important pathogenic and therapeutic implications.

Haploidentical TCRab Depleted Hematopoietic Cell Transplantation Leads To Rapid Immune Reconstitution and Promising Clinical Outcome In Adults

Immunomagnetic TCRab-depletion and reduced intensity conditioning (RIC) for haploidentical hematopoietic cell transplantation (HHCT) has been reported to result in improved immune reconstitution and clinical outcome in children. We here report the first clinical results in 10 adult patients. HHCT using TCRab-depleted grafts was performed in 7 men and 3 women (median age at transplantation 35 years, range 21-68 years). Patients were treated for ALL (n=1), AML (n=5), CLL (n=1), NHL (n=2) or SAA (n=1). Disease status prior transplantation was CR in two patients, minimal residual disease but cytologic CR in 1 patient, conditioning out of aplasia after salvage chemotherapie in 4 patients, and active disease in 3 patients. Haploidentical donors were parents (n=3), siblings (n=4) and children (n=3). Seven patients were treated with HHCT due to relapse after first (n=6) or second (n=1) allogeneic HCT. In 3 patients, HHCT was performed as primary transplantation. Conditioning regimen was myeloablative (12 Gy TBI/high dose cyclophosphamide) in 1 patient and reduced intensity conditioning (fludarabine/clofarabine, thiotepa, melphalan) in the remaining 9 patients. All conditioning regimens included ATG and mycophenolate mofetil as postgrafting immunosuppression until day +30. Patients received a median of 6.18 x 106 (range 3.4-20.4 x106) CD34+,5.92 x 106 (range 2.26-14.84) CD3+and 36.77 x 106 (range 15.75-51.84) CD56+ cells per kilogram body weight. TCRab-depletion of the grafts was a median of 4.5 logs with 0.38 104 TCRab+ CD3+ (range 0.06-1.17) cells per kilogram body weight in the graft. Median engraftment of neutrophils (> 500/µl) and thrombocytes (> 25.000/µl) occurred on days 12 (range day 8-15) and 14 (range day 10-23), respectively, with one patient not achieving thrombocyte engraftment until death. Patients were followed for a median of 276 days after HHCT (range 41-723 days). To date, 6 patients remain alive and in CR (60%). Four patients died due to viral infections (n=4, 40%) at a median of 92 days after HHCT (range 41-100 days) comprising adenovirus viremia, varicella zoster virus encephalitis, respiratory syncytial virus pneumonia and herpes simplex virus pneumonia. One patient also suffered from severe graft versus host disease (GvHD) of the liver. Acute GvHD ≥II occurred in a total of 5 patients with development of chronic GvHD not being observed. None of the patients experienced relapse of the underlying hematologic disease, the non-relapse mortality was 40%. Median overall and disease free survival were not reached during the observation period. Immune reconstitution was studied by flow cytometry at least every week for a median follow-up of 122 days after transplantation (range 25-558 days). Detailed information on immune reconstitution data is provided in the table. Median T cell (CD3+) engraftment (> 200/µl) occurred on day 42 (range 21-397 days). Two patients did not reach > 200/µl CD3+ cells until death. Engraftment of CD4+ T cells > 200/µl was only achieved in 3 patients during the observation period. Our data indicate that in comparison to approaches applying CD34 selected or CD3/CD19 depleted grafts, depletion of TCRab T cells in HHCT might lead to more rapid immune reconstitution. A prospective study evaluating the role of TCRab depletion in HHCT in adults is presently ongoing.TablePeripheral cell counts of leukocyte subsets.NK cellsT cellsT helper cellsCytotoxic T cellsB cellsCD56+ CD16+ CD3-CD3+CD3+ CD4+CD3+ CD8+CD19+Day 30 (median [/µl])435283121range [/µl]113-6425-1,6550-2922-5090-212Day 60 (median [/µl])43345754342213range [/µl]188-5041-1,3670-1750-3680-556Day 100 (median [/µl])3197493982range [/µl]118-1,2230-2,2920-2290-1,28919-344Peak (median [/µl])466416186221309range [/µl]134-2,6505-4,5293-7872-4,0291-3,065Day Peak (median [day])5262596263range [days]19-33725-3978-55825-34419-344 Disclosures:No relevant conflicts of interest to declare.

Complicated Secondary Pneumonia after Swine-Origin Influenza A Virus Infection in an Immunocompetent Patient

The pandemic of the swine-origin influenza A virus (S-OIV) in 2009 demonstrated severe viral pneumonia followed by acute respiratory distress syndrome (ARDS). Although ARDS would be caused by the influenza virus pneumonia itself, it has remained unclear whether other respiratory viral or bacterial infections coexist with S-OIV pneumonia. We report an immunocompetent patient with methicillin-resistant Staphylococcus aureus (MRSA) and Herpes simplex virus (HSV) pneumonia secondary to S-OIV infection. A 57-year-old man previously without major medical illness was admitted to our hospital with severe pneumonia accompanied by ARDS due to S-OIV. In his clinical course, anti-influenza treatment was not effective. Sputum culture revealed the presence of MRSA, and HSV was isolated in broncho-alveoler lavage (BAL) fluid. Administration of an antiviral agent (acyclovir), an antibacterial agent (linezolid), and a corticosteroid (methylprednisolone) successfully improved the pneumonia and ARDS. HSV pneumonia can scarcely be seen in healthy people. However recently it has been recognized as a ventilator-associated pneumonia. Although coexistence of Streptococcus pneumoniae and MRSA was reported in S-OIV pneumonia, secondary viral infection has not been reported. The present report is the first patient with HSV pneumonia secondary to S-OIV infection. We propose that a possibility of hidden HSV pneumonia should be taken into consideration in patients with prolonged severe pneumonia due to influenza infection.

Renal transplant with bronchiolitis obliterans organizing pneumonia (BOOP) attributable to tacrolimus and herpes simplex virus (HSV) pneumonia

BackgroundSolid organ transplants (SOTs) may be complicated by a wide variety of infectious and noninfectious pulmonary disorders. Transplant patients receive immunosuppressive drugs to prevent rejection, but these drugs also predispose them to infection. Because immunosuppressive therapy impairs T-lymphocyte function, ie, cell-mediated immunity, such therapy, not surprisingly, predisposes patients to intracellular pulmonary pathogens. Community-acquired pneumonia (CAP) in patients with SOT usually involves one of the common typical or atypical bacterial CAP pathogens infecting immunocompetent hosts. The most frequent intracellular CAP pathogens in SOTs during immunosuppressive therapy are viral, eg, cytomegalovirus (CMV), respiratory syncytial virus (RSV), and herpes simplex virus (HSV). In addition, intracellular fungal pathogens are also common in patients with SOTs during immunosuppressive therapy, eg, Pneumocystis (carinii) jiroveci pneumonia (PCP). In addition, a variety of noninfectious disorders are not uncommon in patients with SOTs, including bronchiolitis obliterans organizing pneumonia (BOOP). Bronchiolitis obliterans organizing pneumonia may be associated with a variety of infectious agents, or may be attributable to drugs, including some immunosuppressive agents. MethodsThe clinical approach to CAP in patients with SOTs may be based on the appearance of the chest x-ray (CXR) or chest computed tomography scan, combined with the degree of hypoxemia (ie, the A-a gradient). Patients with SOTs and with a normal or nearly normal CXR and a high degree of hypoxemia (A-a gradient, >35) most often have an early viral pneumonia, eg, CMV or early PCP. If the CXR reveals bilateral patchy interstitial infiltrates and severe hypoxemia, the differential diagnosis is limited to moderate or severe viral pneumonia or PCP. Patients with SOTs and presenting with diffuse infiltrates and mild to moderate hypoxemia (A-a gradient, <35) are usually prone to noninfectious disorders, eg, congestive heart failure, pulmonary embolism, or drug-induced pneumonias. In patients with SOTs and CAP with focal or lobar infiltrates, the distribution of pathogens is the same as in immunocompetent hosts, ie, either a bacterial or atypical CAP pathogen. Case Report and ConclusionA renal transplant patient developed bilateral patchy interstitial infiltrates with severe hypoxemia during hospitalization. The most likely differential diagnostic possibilities included PCP and BOOP. Bronchoalveolar lavage was performed to rule out PCP, and indicated cytopathic effects diagnostic of HSV pneumonia. Lung biopsy pathology confirmed the diagnosis of BOOP. In reviewing the patient’s medications, we surmised that tacrolimus may have caused BOOP. The tacrolimus was discontinued, and the patient received acyclovir for HSV pneumonia.