Case Report Chemotherapy 2013;59:385–386 DOI: 10.1159/000360616
Received: September 25, 2013 Accepted after revision: February 13, 2014 Published online: May 13, 2014
Human Herpesvirus 6 Encephalitis Simulating Brain Metastases in a Patient with Advanced Small-Cell Lung Cancer Patrizia Mordenti a Elena Zaffignani a Paolo Immovilli b Elisabetta Nobili a Luigi Cavanna a a
Dipartimento Oncologia-Ematologia and b Unità Operativa di Neurologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy
Abstract Background: The brain is a frequent site of metastases in small-cell lung cancer. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Case: A man with small-cell lung cancer developed a human herpesvirus 6 (HHV-6) meningoencephalitis with neurological symptoms that simulated brain involvement from the lung cancer. HHV-6 is a T cell lymphotropic virus which may be pathogenic in the immunocompromised host. HHV-6 remains latent after the first infection, and when the immune system is compromised it can reactivate. The treatment of HHV-6 infection is highly specific and the drugs recommended are the two antivirals, ganciclovir or foscarnet. Conclusion: In cancer patients neurologic symptoms are usually due to brain metastases. This case shows that in a cancer patient any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are effective. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0009–3157/14/0595–0385$39.50/0 E-Mail [email protected] www.karger.com/che
Introduction
Small-cell lung cancer represents 20–30% of all lung cancer [1] and the brain is a frequent site of metastases. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Our patient developed a human herpesvirus 6 (HHV-6) meningoencephalitis simulating brain involvement from the lung cancer. Discovered in 1986, HHV-6 is the sixth herpesvirus in patients with lymphoproliferative diseases [2]. Acute HHV-6 infection is rare in immunocompetent adults [3] and can manifest as a mononucleosis-like illness with a negative test for cytomegalovirus and EpsteinBarr virus. Case Report In November 2008, a 61-year-old man presented with a productive cough, dyspnea, fatigue and weight loss. He had a history of smoking 400 packs/year, aortocoronary bypass with aortic and mitral valvular substitution, diabetes and hypertension. The only physical alteration was hepatomegaly. Ultrasonography of the abdomen revealed bilateral hepatic metastases. A computed tomography (CT) scan of the chest demonstrated giant mediastinal lymph node metastases. Colonoscopy and esophagogastroduodenoscopy were negative. The ultrasonography-guided hepatic fine-
Patrizia Mordenti Dipartimento Oncologia-Ematologia Ospedale Guglielmo da Saliceto Via Taverna 49, IT–29121 Piacenza (Italy) E-Mail p.mordenti @ ausl.pc.it
Downloaded by: University of Tokyo 157.82.153.40 - 6/5/2015 10:26:39 AM
Key Words Human herpesvirus 6 · Encephalitis · Small-cell lung cancer
needle biopsy was positive for metastases of small-cell lung cancer with an intense and diffuse immunoreactivity for TTF1. In December 2008, chemotherapy with carboplatin (AUC5 day 1 of every 21) and etoposide (100 mg/m2 days 1–3 of every 21) was started. At this time the patient presented multiple lipothymic events and confusion, but a CT scan of the brain was negative. Since the electroencephalographic test revealed an abnormal activity, a lumbar puncture was done. The virological features on liquor showed an encephalitis caused by HHV-6, so intravenous antiviral therapy with gancyclovir was started and the patient’s conditions rapidly improved. In February 2009, a new lumbar puncture was negative and the neurologic exam was quite normal, so the chemotherapy was restarted and continued for six cycles. In June 2009, a total body CT scan revealed complete response. In September 2009, the patient relapsed and we restarted chemotherapy with carboplatin and etoposide but stopped after two cycles due to clinical impairment and hepatic failure. The patient died due to disease progression in December 2009, 13 months after diagnosis.
Discussion
HHV-6 is today recognized as a T cell lymphotropic virus with high affinity for CD4 lymphocytes [4]; it has two variants that may be pathogenic in the immunocompromised host. After the first infection, HHV-6 remains latent unless the immune system is compromised, at which time the virus can reactivate [5]. In the immunocompetent host this persistent infection is generally not clinically relevant and, since the disease closely resembles mononucleosis, Epstein-Barr virus and/or cytomegalovirus infection should be excluded. HHV-6 reactivation oc-
curs in 33–48% of patients undergoing hematopoietic stem cell transplantation [5]. Treatment of HHV-6 infection varies according to the clinical presenting symptoms and the therapy is usually unnecessary in primary infection in immunocompetent hosts. The treatment of HHV6 infection is highly specific and based on the use of antiviral drugs. The drugs recommended are ganciclovir or foscarnet [6], with ganciclovir reported to be beneficial against HHV-6 reactivation in patients undergoing stem cell transplantation. HHV-6 encephalitis is reported in different settings of patients such as immunocompetent and immunocompromised hosts, adults and children, with different clinical evolution despite the same antiviral therapies [3, 5, 6]. In cancer patients, the neurologic symptoms are usually due to brain metastases. However, other diseases, such as viral encephalitis or electrolyte imbalances, can cause neurological impairment similar to that seen in the presence of brain metastases. We conclude that even in a cancer patient, any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are different and both effective for the specific pathology. In fact, the evidence of a curable infectious disease allowed us to eradicate the encephalitis with an appropriate and highly specific antiviral therapy. In this way, our patient was able to resume chemotherapy, achieve a good response and greatly improve his quality of life.
References
386
3 Akashi K, Eizuru Y, Sumiyoshi Y, et al: Brief report: severe infectious mononucleosis-like syndrome and primary human herpesvirus 6 infection in an adult. N Engl J Med 1993;329: 168–171. 4 Lusso P, Ensoli B, Markham PD, et al: Productive dual infection of human CD4 + T lymphocytes by HIV-1 and HHV-6. Nature 1989;337:370–373.
Chemotherapy 2013;59:385–386 DOI: 10.1159/000360616
5 Kadakia MP, Rybka WB, Stewart JA, et al: Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation. Blood 1996; 87: 5341– 5354. 6 Yoshikawa T: Human herpesvirus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol 2004;124:421–432.
Mordenti /Zaffignani /Immovilli /Nobili / Cavanna
Downloaded by: University of Tokyo 157.82.153.40 - 6/5/2015 10:26:39 AM
1 Crabb SJ, Bradbury J, Nolan L, et al: A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer. Chemotherapy 2012;58:257–263. 2 Salahuddin SZ, Ablashi DV, Markham PD, et al: Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986;234:596–601.
Received: September 25, 2013 Accepted after revision: February 13, 2014 Published online: May 13, 2014
Human Herpesvirus 6 Encephalitis Simulating Brain Metastases in a Patient with Advanced Small-Cell Lung Cancer Patrizia Mordenti a Elena Zaffignani a Paolo Immovilli b Elisabetta Nobili a Luigi Cavanna a a
Dipartimento Oncologia-Ematologia and b Unità Operativa di Neurologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy
Abstract Background: The brain is a frequent site of metastases in small-cell lung cancer. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Case: A man with small-cell lung cancer developed a human herpesvirus 6 (HHV-6) meningoencephalitis with neurological symptoms that simulated brain involvement from the lung cancer. HHV-6 is a T cell lymphotropic virus which may be pathogenic in the immunocompromised host. HHV-6 remains latent after the first infection, and when the immune system is compromised it can reactivate. The treatment of HHV-6 infection is highly specific and the drugs recommended are the two antivirals, ganciclovir or foscarnet. Conclusion: In cancer patients neurologic symptoms are usually due to brain metastases. This case shows that in a cancer patient any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are effective. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0009–3157/14/0595–0385$39.50/0 E-Mail [email protected] www.karger.com/che
Introduction
Small-cell lung cancer represents 20–30% of all lung cancer [1] and the brain is a frequent site of metastases. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Our patient developed a human herpesvirus 6 (HHV-6) meningoencephalitis simulating brain involvement from the lung cancer. Discovered in 1986, HHV-6 is the sixth herpesvirus in patients with lymphoproliferative diseases [2]. Acute HHV-6 infection is rare in immunocompetent adults [3] and can manifest as a mononucleosis-like illness with a negative test for cytomegalovirus and EpsteinBarr virus. Case Report In November 2008, a 61-year-old man presented with a productive cough, dyspnea, fatigue and weight loss. He had a history of smoking 400 packs/year, aortocoronary bypass with aortic and mitral valvular substitution, diabetes and hypertension. The only physical alteration was hepatomegaly. Ultrasonography of the abdomen revealed bilateral hepatic metastases. A computed tomography (CT) scan of the chest demonstrated giant mediastinal lymph node metastases. Colonoscopy and esophagogastroduodenoscopy were negative. The ultrasonography-guided hepatic fine-
Patrizia Mordenti Dipartimento Oncologia-Ematologia Ospedale Guglielmo da Saliceto Via Taverna 49, IT–29121 Piacenza (Italy) E-Mail p.mordenti @ ausl.pc.it
Downloaded by: University of Tokyo 157.82.153.40 - 6/5/2015 10:26:39 AM
Key Words Human herpesvirus 6 · Encephalitis · Small-cell lung cancer
needle biopsy was positive for metastases of small-cell lung cancer with an intense and diffuse immunoreactivity for TTF1. In December 2008, chemotherapy with carboplatin (AUC5 day 1 of every 21) and etoposide (100 mg/m2 days 1–3 of every 21) was started. At this time the patient presented multiple lipothymic events and confusion, but a CT scan of the brain was negative. Since the electroencephalographic test revealed an abnormal activity, a lumbar puncture was done. The virological features on liquor showed an encephalitis caused by HHV-6, so intravenous antiviral therapy with gancyclovir was started and the patient’s conditions rapidly improved. In February 2009, a new lumbar puncture was negative and the neurologic exam was quite normal, so the chemotherapy was restarted and continued for six cycles. In June 2009, a total body CT scan revealed complete response. In September 2009, the patient relapsed and we restarted chemotherapy with carboplatin and etoposide but stopped after two cycles due to clinical impairment and hepatic failure. The patient died due to disease progression in December 2009, 13 months after diagnosis.
Discussion
HHV-6 is today recognized as a T cell lymphotropic virus with high affinity for CD4 lymphocytes [4]; it has two variants that may be pathogenic in the immunocompromised host. After the first infection, HHV-6 remains latent unless the immune system is compromised, at which time the virus can reactivate [5]. In the immunocompetent host this persistent infection is generally not clinically relevant and, since the disease closely resembles mononucleosis, Epstein-Barr virus and/or cytomegalovirus infection should be excluded. HHV-6 reactivation oc-
curs in 33–48% of patients undergoing hematopoietic stem cell transplantation [5]. Treatment of HHV-6 infection varies according to the clinical presenting symptoms and the therapy is usually unnecessary in primary infection in immunocompetent hosts. The treatment of HHV6 infection is highly specific and based on the use of antiviral drugs. The drugs recommended are ganciclovir or foscarnet [6], with ganciclovir reported to be beneficial against HHV-6 reactivation in patients undergoing stem cell transplantation. HHV-6 encephalitis is reported in different settings of patients such as immunocompetent and immunocompromised hosts, adults and children, with different clinical evolution despite the same antiviral therapies [3, 5, 6]. In cancer patients, the neurologic symptoms are usually due to brain metastases. However, other diseases, such as viral encephalitis or electrolyte imbalances, can cause neurological impairment similar to that seen in the presence of brain metastases. We conclude that even in a cancer patient, any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are different and both effective for the specific pathology. In fact, the evidence of a curable infectious disease allowed us to eradicate the encephalitis with an appropriate and highly specific antiviral therapy. In this way, our patient was able to resume chemotherapy, achieve a good response and greatly improve his quality of life.
References
386
3 Akashi K, Eizuru Y, Sumiyoshi Y, et al: Brief report: severe infectious mononucleosis-like syndrome and primary human herpesvirus 6 infection in an adult. N Engl J Med 1993;329: 168–171. 4 Lusso P, Ensoli B, Markham PD, et al: Productive dual infection of human CD4 + T lymphocytes by HIV-1 and HHV-6. Nature 1989;337:370–373.
Chemotherapy 2013;59:385–386 DOI: 10.1159/000360616
5 Kadakia MP, Rybka WB, Stewart JA, et al: Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation. Blood 1996; 87: 5341– 5354. 6 Yoshikawa T: Human herpesvirus 6 infection in hematopoietic stem cell transplant patients. Br J Haematol 2004;124:421–432.
Mordenti /Zaffignani /Immovilli /Nobili / Cavanna
Downloaded by: University of Tokyo 157.82.153.40 - 6/5/2015 10:26:39 AM
1 Crabb SJ, Bradbury J, Nolan L, et al: A phase I clinical trial of irinotecan and carboplatin in patients with extensive stage small cell lung cancer. Chemotherapy 2012;58:257–263. 2 Salahuddin SZ, Ablashi DV, Markham PD, et al: Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 1986;234:596–601.
