JAMDA 15 (2014) 955e956
JAMDA journal homepage: www.jamda.com
Letter to the Editor
Case Report: Herpes Simplex Esophagitis in a Frail Elderly Patient To the Editor: Frail older persons in nursing homes are at high risk for developing unusual infections.1e3 Herpes simplex esophagitis (HSE) is most commonly seen in immunocompromised individuals with conditions that debilitate the cellular immune system, such as malignancies, radiation, chemotherapy, transplantation, and AIDS.4 It is considered an AIDS-defining illness4 but is a rare clinical entity in the immunocompetent patient. Incidence by gender depends on age5,6; it has been predominantly described in young male patients (78% were 40 years or younger, and 76% were male). Overall, its incidence has been estimated from autopsies. A Japanese series of 1307 autopsies found an incidence of 1.8%.7 Case Report A 91-year-old Caucasian woman presented to the hospital for a 5-day history of dysphagia and odynophagia. She had a history of hypertension, coronary artery disease, hypothyroidism, and recurrent Clostridium difficile colitis. She had received epidural and knee steroid injections within 2 months of admission for spinal stenosis and osteoarthritis. Her recent hospitalizations include an admission 1 month earlier for hemoptysis due to bronchiectasis. Subsequently, she was readmitted 2 weeks later with hospital-acquired pneumonia. She also had a methicillin-resistant Staphylococcus urinary tract infection, treated with doxycycline. At the end of this hospitalization, she started complaining of odynophagia. She was discharged to a skilled nursing facility on ranitidine for presumed acid reflux, and then changed to omeprazole a few days later due to worsening symptoms. She subsequently had 2 episodes of melena, resulting in this hospitalization. Physical examination was relatively unremarkable. Oropharynx was without erythema, lip or oral blisters, or ulcers. There was no chest wall tenderness. Laboratory values showed a hematocrit of 25.4%, hemoglobin of 8.2 g/dL, white blood cell count of 10.7 103/ mL, with 82.2% neutrophils and 8.2% lymphocytes. The patient was started on intravenous (IV) pantoprazole for upper gastrointestinal bleeding. She underwent an upper endoscopy, which showed cratered and linear esophageal ulcers without bleeding and stigmata of recent bleeding. The patient was also started on sucralfate and viscous lidocaine in addition to pantoprazole. Doxycycline was discontinued. Esophageal biopsy showed esophageal squamous mucosa with acute and chronic inflammation, ulceration, and inflammatory/ necrotic debris with cytological features consistent with herpes simplex. Biopsies were negative for intestinal metaplasia, http://dx.doi.org/10.1016/j.jamda.2014.09.006 1525-8610/Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
malignancy, and fungal organisms. The immunocytochemistry for herpes simplex virus (HSV) type I and type II was strongly positive. The strong positivity of both HSV I and II likely indicates cross reactivity. Serology was sent during acute illness and found to be positive for HSV I and II. HSV I/II immunoglobulin (Ig)G was 86.2 (high) and HSV I/II IgM was 6.02 (high), confirming active infection. The patient was started on IV acyclovir. HIV serology and CD4 counts were not sent because the patient had no risk factors for HIV and her family declined testing. A convalescence serology 2 months later showed an IgM titer of 4.47 and IgG 61.6, specific for HSV type I. The patient was discharged on oral valacyclovir 6 days after admission, showing clinical improvement without signs of dysphagia, odynophagia, or bleeding. Discussion In the immunosuppressed person, HSE most likely occurs due to viral reactivation, whereas it is most commonly a primary infection in the immunocompetent.8 Factors such as stress, immunosuppression, heat exposure, and courses of corticosteroids9 have been proposed as triggers for herpes reactivation. Trauma to the esophageal mucosa from acid reflux,10 instrumentation, or nasogastric tube placement has been suggested as a risk factor for HSE. Epidemiological data suggest an increased susceptibility to infections in the elderly.11 This susceptibility is attributed to malnutrition, age-associated physiological and anatomical changes, and immunosenescence.11,12 In our case, we attribute her frailty, aging with immunosenescence, corticosteroid use, and recent severe illness as the underlying immunosuppressive factors. The typical presentation of HSE has an acute onset of odynophagia, dysphagia, or heartburn. Retrosternal chest pain also is common.5,6,8 Symptoms at presentation are found to be similar regardless of immune status.13 Fever, upper respiratory symptoms, or oral herpetic lesions can be present as a prodrome.6 From a case series previously published, the incidences of symptoms were odynophagia (76.3%), heartburn (50.0%), fever (44.7%), dysphagia (21.1%), myalgia (21.1%), and weight loss (13.2%). The most common endoscopic findings consist of multiple discrete or coalescent small ulcers. The distal esophagus is the most frequently involved segment (64%), but diffuse involvement is the usual presentation.6 The endoscopic differential diagnosis of HSE includes reflux or drug-induced esophagitis in the immunocompetent14 and cytomegalovirus in the immunocompromised.15 Candidiasis also can occur as a secondary esophageal infection with HSE.8 Methods that support the diagnosis of HSE include histopathology, viral culture, immunohistochemical staining, and polymerase chain reaction (PCR). Serology can be useful if seroconversion is present for diagnosing primary infection. Histological findings seen in HSE are not specific, as can be seen with cytomegalovirus or herpes zoster16; therefore, immunohistochemistry,
956
Letter to the Editor / JAMDA 15 (2014) 955e956
culture, or PCR are important for HSV confirmation. Biopsy specimens should be obtained from the edges of the ulcers to obtain a better yield.14 HSE course can vary from a self-limited asymptomatic to an acute disease with complications such as gastrointestinal bleeding or perforation. In the immunocompetent patient with HSE, the complication rate of gastrointestinal bleeding5,17e19 and perforation20 is 5.8% and 1.8%, respectively. Acyclovir is an established treatment for HSE in the immunocompromised patient. Observational studies of acyclovir treatment in immunocompetent patients with HSE have not shown benefit in those with mild symptoms, although it could benefit those with severe symptoms by reducing healing time11 and complication rates.18 However, in elderly patients with impaired immunity, HSE may not be a self-limiting disease and would therefore require antiviral treatment. In conclusion, this is the first documented presentation of HSE in an elderly frail patient older than 90 years. HSE should be considered in the differential diagnosis of frail elderly patients presenting with acute esophagitis, as illustrated by our case.21,22 Esophagogastroduodenoscopy should be performed promptly, as early diagnosis and treatment can potentially prevent the development of severe complications, such as perforation or gastrointestinal bleeding. References 1. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 2. Le Reste JY, Nabbe P, Manceau B, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc 2013;14:319e325. 3. Rougé Bugat ME, Cestac P, Oustric S, et al. Detecting frailty in primary care: A major challenge for primary care physicians. J Am Med Dir Assoc 2012;13: 669e672. 4. Genereau T, Lortholary O, Bouchaud O, et al. Herpes simplex esophagitis in patients with AIDS: Report of 34 cases. Clin Infect Dis 1996;22:926e931. 5. Kato S, Yamamoto R, Yoshimitsu S, et al. Herpes simplex esophagitis in the immunocompetent host. Dis Esophagus 2005;18:340e344. 6. Ramanathan J, Rammouni M, Baran J Jr, Khatib R. Herpes simplex virus esophagitis in the immunocompetent host: An overview. Am J Gastroenterol 2000;95:2171e2176. 7. Itoh T, Takahashi T, Kusaka K, et al. Herpes simplex esophagitis from 1307 autopsy cases. J Gastroenterol Hepatol 2003;18:1407e1411. 8. Bando T, Matsushita M, Kitano M, Okazaki K. Herpes simplex esophagitis in the elderly. Dig Endosc 2009;21:205e207.
9. Jetté-Côté I, Ouellette D, Béliveau C, Mitchell A. Total dysphagia after short course of systemic corticotherapy: Herpes simplex virus esophagitis. World J Gastroenterol 2013;19:5178e5181. 10. DiPalma JA, Brady CE III. Herpes simplex esophagitis in a nonimmunosuppressed host with gastroesophageal reflux. Gastrointest Endosc 1984;30:24e25. 11. Dewan SK, Zheng SB, Xia S, et al. Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl) 2012;125:3325e3331. 12. Halter J, Ouslander J, Tinnety M, et al. Hazzard’s Geriatric Medicine and Gerontology. New York, NY: McGraw Hill; 2009. 13. Canalejo E, Garcia Duran F, Cabello N, Garcia Martinez J. Herpes esophagitis in healthy adults and adolescents. Report of 3 cases and review of the literature. Medicine 2010;89:204e210. 14. Higuchi D, Sugawa C, Shah SH, et al. Etiology, treatment, and outcome of esophageal ulcers: A 10-year experience in an urban emergency hospital. J Gastrointest Surg 2003;7:836e842. 15. Wilcox CM, Schwartz DA, Clark WS. Esophageal ulceration in human immunodeficiency virus infection: Causes, response to therapy and long term outcome. Ann Intern Med 1995;123:143e149. 16. Lavery A, Coyle W. Herpes simplex virus and the alimentary tract. Curr Gastroenterol Rep 2008;10:417e423. 17. Kurahara K, Aoyagi K, Nakamura S, et al. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: A case report and review of the literature. Am J Gastroenterol 1998;93:2239e2240. 18. Chien RN, Chen PC, Lin PY, Wu CS. Herpes esophagitis: A cause of upper gastrointestinal bleeding in an immunocompetent patient. J Formos Med Assoc 1992;91:1112e1114. 19. Nagri S, Hwang R, Anand S, Kurz J. Herpes simplex esophagitis presenting as acute necrotizing esophagitis (‘‘black esophagus’’) in an immunocompetent patient. Endoscopy 2007;39:E169. 20. Cronstedt JL, Bouchama A, Hainau B, et al. Spontaneous esophageal perforation in herpes simplex esophagitis. Am J Gastroenterol 1992;87:124e127. 21. Messinger-Rapport BJ, Cruz-Oliver DM, Thomas DR, Morley JE. Clinical update on nursing home medicine: 2012. J Am Med Dir Assoc 2012;13:581e594. 22. Morley JE. Developing novel therapeutic approaches to frailty. Curr Pharm Des 2009;15:3384e3395.
Julio Noda, MD Shannon Devlin, BS Gerald M. Mahon, MD Division of Geriatric Medicine Department of Internal Medicine Saint Louis University School of Medicine St Louis, Missouri Weigang Zhu, MD Department of Pathology DesPeres Hospital St Louis, Missouri
JAMDA journal homepage: www.jamda.com
Letter to the Editor
Case Report: Herpes Simplex Esophagitis in a Frail Elderly Patient To the Editor: Frail older persons in nursing homes are at high risk for developing unusual infections.1e3 Herpes simplex esophagitis (HSE) is most commonly seen in immunocompromised individuals with conditions that debilitate the cellular immune system, such as malignancies, radiation, chemotherapy, transplantation, and AIDS.4 It is considered an AIDS-defining illness4 but is a rare clinical entity in the immunocompetent patient. Incidence by gender depends on age5,6; it has been predominantly described in young male patients (78% were 40 years or younger, and 76% were male). Overall, its incidence has been estimated from autopsies. A Japanese series of 1307 autopsies found an incidence of 1.8%.7 Case Report A 91-year-old Caucasian woman presented to the hospital for a 5-day history of dysphagia and odynophagia. She had a history of hypertension, coronary artery disease, hypothyroidism, and recurrent Clostridium difficile colitis. She had received epidural and knee steroid injections within 2 months of admission for spinal stenosis and osteoarthritis. Her recent hospitalizations include an admission 1 month earlier for hemoptysis due to bronchiectasis. Subsequently, she was readmitted 2 weeks later with hospital-acquired pneumonia. She also had a methicillin-resistant Staphylococcus urinary tract infection, treated with doxycycline. At the end of this hospitalization, she started complaining of odynophagia. She was discharged to a skilled nursing facility on ranitidine for presumed acid reflux, and then changed to omeprazole a few days later due to worsening symptoms. She subsequently had 2 episodes of melena, resulting in this hospitalization. Physical examination was relatively unremarkable. Oropharynx was without erythema, lip or oral blisters, or ulcers. There was no chest wall tenderness. Laboratory values showed a hematocrit of 25.4%, hemoglobin of 8.2 g/dL, white blood cell count of 10.7 103/ mL, with 82.2% neutrophils and 8.2% lymphocytes. The patient was started on intravenous (IV) pantoprazole for upper gastrointestinal bleeding. She underwent an upper endoscopy, which showed cratered and linear esophageal ulcers without bleeding and stigmata of recent bleeding. The patient was also started on sucralfate and viscous lidocaine in addition to pantoprazole. Doxycycline was discontinued. Esophageal biopsy showed esophageal squamous mucosa with acute and chronic inflammation, ulceration, and inflammatory/ necrotic debris with cytological features consistent with herpes simplex. Biopsies were negative for intestinal metaplasia, http://dx.doi.org/10.1016/j.jamda.2014.09.006 1525-8610/Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
malignancy, and fungal organisms. The immunocytochemistry for herpes simplex virus (HSV) type I and type II was strongly positive. The strong positivity of both HSV I and II likely indicates cross reactivity. Serology was sent during acute illness and found to be positive for HSV I and II. HSV I/II immunoglobulin (Ig)G was 86.2 (high) and HSV I/II IgM was 6.02 (high), confirming active infection. The patient was started on IV acyclovir. HIV serology and CD4 counts were not sent because the patient had no risk factors for HIV and her family declined testing. A convalescence serology 2 months later showed an IgM titer of 4.47 and IgG 61.6, specific for HSV type I. The patient was discharged on oral valacyclovir 6 days after admission, showing clinical improvement without signs of dysphagia, odynophagia, or bleeding. Discussion In the immunosuppressed person, HSE most likely occurs due to viral reactivation, whereas it is most commonly a primary infection in the immunocompetent.8 Factors such as stress, immunosuppression, heat exposure, and courses of corticosteroids9 have been proposed as triggers for herpes reactivation. Trauma to the esophageal mucosa from acid reflux,10 instrumentation, or nasogastric tube placement has been suggested as a risk factor for HSE. Epidemiological data suggest an increased susceptibility to infections in the elderly.11 This susceptibility is attributed to malnutrition, age-associated physiological and anatomical changes, and immunosenescence.11,12 In our case, we attribute her frailty, aging with immunosenescence, corticosteroid use, and recent severe illness as the underlying immunosuppressive factors. The typical presentation of HSE has an acute onset of odynophagia, dysphagia, or heartburn. Retrosternal chest pain also is common.5,6,8 Symptoms at presentation are found to be similar regardless of immune status.13 Fever, upper respiratory symptoms, or oral herpetic lesions can be present as a prodrome.6 From a case series previously published, the incidences of symptoms were odynophagia (76.3%), heartburn (50.0%), fever (44.7%), dysphagia (21.1%), myalgia (21.1%), and weight loss (13.2%). The most common endoscopic findings consist of multiple discrete or coalescent small ulcers. The distal esophagus is the most frequently involved segment (64%), but diffuse involvement is the usual presentation.6 The endoscopic differential diagnosis of HSE includes reflux or drug-induced esophagitis in the immunocompetent14 and cytomegalovirus in the immunocompromised.15 Candidiasis also can occur as a secondary esophageal infection with HSE.8 Methods that support the diagnosis of HSE include histopathology, viral culture, immunohistochemical staining, and polymerase chain reaction (PCR). Serology can be useful if seroconversion is present for diagnosing primary infection. Histological findings seen in HSE are not specific, as can be seen with cytomegalovirus or herpes zoster16; therefore, immunohistochemistry,
956
Letter to the Editor / JAMDA 15 (2014) 955e956
culture, or PCR are important for HSV confirmation. Biopsy specimens should be obtained from the edges of the ulcers to obtain a better yield.14 HSE course can vary from a self-limited asymptomatic to an acute disease with complications such as gastrointestinal bleeding or perforation. In the immunocompetent patient with HSE, the complication rate of gastrointestinal bleeding5,17e19 and perforation20 is 5.8% and 1.8%, respectively. Acyclovir is an established treatment for HSE in the immunocompromised patient. Observational studies of acyclovir treatment in immunocompetent patients with HSE have not shown benefit in those with mild symptoms, although it could benefit those with severe symptoms by reducing healing time11 and complication rates.18 However, in elderly patients with impaired immunity, HSE may not be a self-limiting disease and would therefore require antiviral treatment. In conclusion, this is the first documented presentation of HSE in an elderly frail patient older than 90 years. HSE should be considered in the differential diagnosis of frail elderly patients presenting with acute esophagitis, as illustrated by our case.21,22 Esophagogastroduodenoscopy should be performed promptly, as early diagnosis and treatment can potentially prevent the development of severe complications, such as perforation or gastrointestinal bleeding. References 1. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: A call to action. J Am Med Dir Assoc 2013;14:392e397. 2. Le Reste JY, Nabbe P, Manceau B, et al. The European General Practice Research Network presents a comprehensive definition of multimorbidity in family medicine and long term care, following a systematic review of relevant literature. J Am Med Dir Assoc 2013;14:319e325. 3. Rougé Bugat ME, Cestac P, Oustric S, et al. Detecting frailty in primary care: A major challenge for primary care physicians. J Am Med Dir Assoc 2012;13: 669e672. 4. Genereau T, Lortholary O, Bouchaud O, et al. Herpes simplex esophagitis in patients with AIDS: Report of 34 cases. Clin Infect Dis 1996;22:926e931. 5. Kato S, Yamamoto R, Yoshimitsu S, et al. Herpes simplex esophagitis in the immunocompetent host. Dis Esophagus 2005;18:340e344. 6. Ramanathan J, Rammouni M, Baran J Jr, Khatib R. Herpes simplex virus esophagitis in the immunocompetent host: An overview. Am J Gastroenterol 2000;95:2171e2176. 7. Itoh T, Takahashi T, Kusaka K, et al. Herpes simplex esophagitis from 1307 autopsy cases. J Gastroenterol Hepatol 2003;18:1407e1411. 8. Bando T, Matsushita M, Kitano M, Okazaki K. Herpes simplex esophagitis in the elderly. Dig Endosc 2009;21:205e207.
9. Jetté-Côté I, Ouellette D, Béliveau C, Mitchell A. Total dysphagia after short course of systemic corticotherapy: Herpes simplex virus esophagitis. World J Gastroenterol 2013;19:5178e5181. 10. DiPalma JA, Brady CE III. Herpes simplex esophagitis in a nonimmunosuppressed host with gastroesophageal reflux. Gastrointest Endosc 1984;30:24e25. 11. Dewan SK, Zheng SB, Xia S, et al. Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl) 2012;125:3325e3331. 12. Halter J, Ouslander J, Tinnety M, et al. Hazzard’s Geriatric Medicine and Gerontology. New York, NY: McGraw Hill; 2009. 13. Canalejo E, Garcia Duran F, Cabello N, Garcia Martinez J. Herpes esophagitis in healthy adults and adolescents. Report of 3 cases and review of the literature. Medicine 2010;89:204e210. 14. Higuchi D, Sugawa C, Shah SH, et al. Etiology, treatment, and outcome of esophageal ulcers: A 10-year experience in an urban emergency hospital. J Gastrointest Surg 2003;7:836e842. 15. Wilcox CM, Schwartz DA, Clark WS. Esophageal ulceration in human immunodeficiency virus infection: Causes, response to therapy and long term outcome. Ann Intern Med 1995;123:143e149. 16. Lavery A, Coyle W. Herpes simplex virus and the alimentary tract. Curr Gastroenterol Rep 2008;10:417e423. 17. Kurahara K, Aoyagi K, Nakamura S, et al. Treatment of herpes simplex esophagitis in an immunocompetent patient with intravenous acyclovir: A case report and review of the literature. Am J Gastroenterol 1998;93:2239e2240. 18. Chien RN, Chen PC, Lin PY, Wu CS. Herpes esophagitis: A cause of upper gastrointestinal bleeding in an immunocompetent patient. J Formos Med Assoc 1992;91:1112e1114. 19. Nagri S, Hwang R, Anand S, Kurz J. Herpes simplex esophagitis presenting as acute necrotizing esophagitis (‘‘black esophagus’’) in an immunocompetent patient. Endoscopy 2007;39:E169. 20. Cronstedt JL, Bouchama A, Hainau B, et al. Spontaneous esophageal perforation in herpes simplex esophagitis. Am J Gastroenterol 1992;87:124e127. 21. Messinger-Rapport BJ, Cruz-Oliver DM, Thomas DR, Morley JE. Clinical update on nursing home medicine: 2012. J Am Med Dir Assoc 2012;13:581e594. 22. Morley JE. Developing novel therapeutic approaches to frailty. Curr Pharm Des 2009;15:3384e3395.
Julio Noda, MD Shannon Devlin, BS Gerald M. Mahon, MD Division of Geriatric Medicine Department of Internal Medicine Saint Louis University School of Medicine St Louis, Missouri Weigang Zhu, MD Department of Pathology DesPeres Hospital St Louis, Missouri
