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Disseminated varicella-zoster virus involving the esophagus and stomach
AT THE FOCAL POINT Massimo Raimondo, MD, Associate Editor for Focal Points
Disseminated varicella-zoster virus involving the esophagus and stomach
A 58-year-old man who had an autologous stem cell transplant for transformed follicular lymphoma presented to our hospital with a 5-day history of severe epigastric pain. Three weeks before admission, he was presumed to have Pneumocystis jiroveci pneumonia; he began treatment with trimethoprim-sulfamethoxazole and prednisone while lenalidomide was discontinued. At admission, translucent, dome-shaped papules, many of which had a hemorrhagic crateriform center, in different stages of healing were noted over his entire body (A). The results of initial laboratory testing and cross-sectional imaging were unremarkable. Subsequently, an upper endoscopy was performed and revealed a solitary, 2-mm, raised, erythematous ulcer with heaped-up borders in the mid-esophagus (B). A biopsy was done. A similar ulcer was found in the gastric body. Biopsy specimens from the ulcer edge stained strongly positive for varicella-zoster virus (C, varicella immunostain, orig. mag. 200). The same was true of a skin biopsy specimen obtained the following day.
1282 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5 : 2015
Despite empiric acyclovir treatment, the patient developed hepatitis, pancreatitis, and hypoxic respiratory failure. He died 2 days later from septic shock. DISCLOSURE All authors disclosed no financial relationships relevant to this publication. Chad Cornish, MD, Division of Gastroenterology and Hepatology, Elizabeth Urban, MD, PhD, Department of Internal Medicine, Christa Whitney-Miller, MD, Department of Pathology and Laboratory Medicine, Kira Mayo, MD, Department of Dermatology, George Philips, MD, Division of Digestive Diseases, Emory University Hospital, Atlanta, Georgia, USA http://dx.doi.org/10.1016/j.gie.2014.11.045
www.giejournal.org
At the Focal Point
Commentary Etymology of herpes is from the Greek: herpein, to creep, as it crept up in the case above. Varicella has a characteristic vesicular appearance caused by an enveloped linear, dsDNA varicella-zoster virus (VZV). Like other herpes viruses, it causes a primary infection (varicella or chickenpox) with seroconversion and subsequent lifelong latency (during which no antigens are expressed on the infected cell, to evade the immune system), primarily but not exclusively in sensory ganglias of cranial, dorsal root, and the autonomic nervous system. Reactivation causes localized neurologic disease with associated skin eruptions (herpes zoster or shingles; Greek: zoster, girdle or warrior’s belt; and shingles, translation in old French). In a severely immunosuppressed host, a disseminated VZV infection can occur. VZV is transmitted by droplets and by direct contact with the contents of the vesicles and is highly contagious. Virus shedding starts 2 days before onset of the rash. In immune-competent hosts, the lesions crust by 7 to 10 days and are no longer considered infectious. The development of new lesions more than a week after presentation suggests immunodeficiency. The incubation period is 11 to 20 days. Primary VZV infection occurring in adolescence and adult life (especially in hematopoietic stem cell transplant recipients, solid-organ transplant recipients, and patients receiving immunosuppression therapy) often is associated with more severe and life-threatening disease including visceral adverse events such as pneumonitis, encephalitis, hepatitis, and pancreatitis, with the most common cause of death from respiratory failure. In hematopoietic stem cell transplants, the recipient’s immune system can recover after successful engraftment. In solid-organ transplant, the recipient’s immune system never recovers its full potential because of lifelong immunosuppression therapy. In transplant patients, reactivation of VZV typically occurs later than in infection with cytomegalovirus or herpes simplex virus. VZV infection is the most common viral disease after hematopoietic stem cell transplantation (incidence 17%-50%), with a median interval of 3 to 6 months. In the majority of cases, cutaneous manifestations precede those of abdominal organ dissemination, making early diagnosis more likely and allowing prompt treatment to diminish mortality (9%-55%). In most cases, latent VZV is reactivated from the dorsal root ganglia, which share the afferent sympathetic fibers that supply the liver, pancreas, GI mucosa, and lungs. The evidence in the past decade suggests that the involvement of the GI system may be the rule rather than the exception and that the enteric nervous system can be a primary site of reactivation, with no cutaneous involvement. Because the clinical course is not uniform, it can be challenging to diagnose disseminated VZV. Severe abdominal pain is one of the most important symptoms and might be the only symptom of VZV infection in an immunosuppressed patient. An EGD with a biopsy of visible lesions can lead to prompt diagnosis. Real-time polymerase chain reaction assay and direct fluorescent antibody testing identify VZV from an array of clinical specimens. These methods are rapid and less expensive, compared with a culture. Enzyme-linked immunosorbent assay determines susceptibility to varicella and the need for immunization. Of interest, we came across a case report of VZV esophageal ulcer causing fistulization to bronchus in a patient with AIDS. Gastroenterologists and hepatologists can relate to and learn from this case because we are involved in caring for the inflammatory bowel disease (IBD) and liver transplant population. The Second European Evidence-Based Consensus on the Prevention of Opportunistic Infections in IBD 2014 recommended checking patient’s immunity with titers for measles, mumps, rubella, and varicella, regardless of their immunization or infection history. If patients are not immune, then live vaccine should be used at least 3 to 6 weeks before use of immunomodulators or biologics. Live vaccines must be avoided for at least 3 months after immunosuppressive therapy has been stopped (a month in case of steroids). Similar strong recommendations were made by the American Association for the Study of Liver Diseases at the 2014 annual meeting, for therapy before liver transplantation. Many immunosuppressed patients are unable to mount protective immune responses, especially in the setting of underlying diseases (eg, renal or hepatic insufficiency), allograft rejection, and immunosuppression therapy after transplantation. Therefore, an adequate vaccine response cannot be assumed. We thank the authors for sharing this case and for reminding us that prevention is better than cure or perhaps at least an attempt at prevention. Bhaumik Brahmbhatt, MD Fellow in Gastroenterology and Hepatology Mayo Clinic Florida Massimo Raimondo, MD Associate Editor for Focal Points
www.giejournal.org
Volume 81, No. 5 : 2015 GASTROINTESTINAL ENDOSCOPY 1283
Disseminated varicella-zoster virus involving the esophagus and stomach
A 58-year-old man who had an autologous stem cell transplant for transformed follicular lymphoma presented to our hospital with a 5-day history of severe epigastric pain. Three weeks before admission, he was presumed to have Pneumocystis jiroveci pneumonia; he began treatment with trimethoprim-sulfamethoxazole and prednisone while lenalidomide was discontinued. At admission, translucent, dome-shaped papules, many of which had a hemorrhagic crateriform center, in different stages of healing were noted over his entire body (A). The results of initial laboratory testing and cross-sectional imaging were unremarkable. Subsequently, an upper endoscopy was performed and revealed a solitary, 2-mm, raised, erythematous ulcer with heaped-up borders in the mid-esophagus (B). A biopsy was done. A similar ulcer was found in the gastric body. Biopsy specimens from the ulcer edge stained strongly positive for varicella-zoster virus (C, varicella immunostain, orig. mag. 200). The same was true of a skin biopsy specimen obtained the following day.
1282 GASTROINTESTINAL ENDOSCOPY Volume 81, No. 5 : 2015
Despite empiric acyclovir treatment, the patient developed hepatitis, pancreatitis, and hypoxic respiratory failure. He died 2 days later from septic shock. DISCLOSURE All authors disclosed no financial relationships relevant to this publication. Chad Cornish, MD, Division of Gastroenterology and Hepatology, Elizabeth Urban, MD, PhD, Department of Internal Medicine, Christa Whitney-Miller, MD, Department of Pathology and Laboratory Medicine, Kira Mayo, MD, Department of Dermatology, George Philips, MD, Division of Digestive Diseases, Emory University Hospital, Atlanta, Georgia, USA http://dx.doi.org/10.1016/j.gie.2014.11.045
www.giejournal.org
At the Focal Point
Commentary Etymology of herpes is from the Greek: herpein, to creep, as it crept up in the case above. Varicella has a characteristic vesicular appearance caused by an enveloped linear, dsDNA varicella-zoster virus (VZV). Like other herpes viruses, it causes a primary infection (varicella or chickenpox) with seroconversion and subsequent lifelong latency (during which no antigens are expressed on the infected cell, to evade the immune system), primarily but not exclusively in sensory ganglias of cranial, dorsal root, and the autonomic nervous system. Reactivation causes localized neurologic disease with associated skin eruptions (herpes zoster or shingles; Greek: zoster, girdle or warrior’s belt; and shingles, translation in old French). In a severely immunosuppressed host, a disseminated VZV infection can occur. VZV is transmitted by droplets and by direct contact with the contents of the vesicles and is highly contagious. Virus shedding starts 2 days before onset of the rash. In immune-competent hosts, the lesions crust by 7 to 10 days and are no longer considered infectious. The development of new lesions more than a week after presentation suggests immunodeficiency. The incubation period is 11 to 20 days. Primary VZV infection occurring in adolescence and adult life (especially in hematopoietic stem cell transplant recipients, solid-organ transplant recipients, and patients receiving immunosuppression therapy) often is associated with more severe and life-threatening disease including visceral adverse events such as pneumonitis, encephalitis, hepatitis, and pancreatitis, with the most common cause of death from respiratory failure. In hematopoietic stem cell transplants, the recipient’s immune system can recover after successful engraftment. In solid-organ transplant, the recipient’s immune system never recovers its full potential because of lifelong immunosuppression therapy. In transplant patients, reactivation of VZV typically occurs later than in infection with cytomegalovirus or herpes simplex virus. VZV infection is the most common viral disease after hematopoietic stem cell transplantation (incidence 17%-50%), with a median interval of 3 to 6 months. In the majority of cases, cutaneous manifestations precede those of abdominal organ dissemination, making early diagnosis more likely and allowing prompt treatment to diminish mortality (9%-55%). In most cases, latent VZV is reactivated from the dorsal root ganglia, which share the afferent sympathetic fibers that supply the liver, pancreas, GI mucosa, and lungs. The evidence in the past decade suggests that the involvement of the GI system may be the rule rather than the exception and that the enteric nervous system can be a primary site of reactivation, with no cutaneous involvement. Because the clinical course is not uniform, it can be challenging to diagnose disseminated VZV. Severe abdominal pain is one of the most important symptoms and might be the only symptom of VZV infection in an immunosuppressed patient. An EGD with a biopsy of visible lesions can lead to prompt diagnosis. Real-time polymerase chain reaction assay and direct fluorescent antibody testing identify VZV from an array of clinical specimens. These methods are rapid and less expensive, compared with a culture. Enzyme-linked immunosorbent assay determines susceptibility to varicella and the need for immunization. Of interest, we came across a case report of VZV esophageal ulcer causing fistulization to bronchus in a patient with AIDS. Gastroenterologists and hepatologists can relate to and learn from this case because we are involved in caring for the inflammatory bowel disease (IBD) and liver transplant population. The Second European Evidence-Based Consensus on the Prevention of Opportunistic Infections in IBD 2014 recommended checking patient’s immunity with titers for measles, mumps, rubella, and varicella, regardless of their immunization or infection history. If patients are not immune, then live vaccine should be used at least 3 to 6 weeks before use of immunomodulators or biologics. Live vaccines must be avoided for at least 3 months after immunosuppressive therapy has been stopped (a month in case of steroids). Similar strong recommendations were made by the American Association for the Study of Liver Diseases at the 2014 annual meeting, for therapy before liver transplantation. Many immunosuppressed patients are unable to mount protective immune responses, especially in the setting of underlying diseases (eg, renal or hepatic insufficiency), allograft rejection, and immunosuppression therapy after transplantation. Therefore, an adequate vaccine response cannot be assumed. We thank the authors for sharing this case and for reminding us that prevention is better than cure or perhaps at least an attempt at prevention. Bhaumik Brahmbhatt, MD Fellow in Gastroenterology and Hepatology Mayo Clinic Florida Massimo Raimondo, MD Associate Editor for Focal Points
www.giejournal.org
Volume 81, No. 5 : 2015 GASTROINTESTINAL ENDOSCOPY 1283