Bol Med Hosp Infant Mex 2004; Vol 61 (1):. 29-34 ORIGINAL ARTICLE Herpetic esophagitis in the immunosuppressed child Dr. Gerardo Blanco Rodríguez Service of Thoracic Surgery and Endoscopy, Hospital Infantil de Mexico, Mexico D. F. , Mexico. Dra. Yolanda Peña Alonso Rocio Pathology Department, Hospital Infantil de Mexico, Mexico D. F.
, Mexico. Dr. Jaime Penchyna Grub Dr. Adrian Ponce Trujillo Dr. Espinosa Placido Rosas Dr. Jorge Rivas Madriñán Service of Thoracic Surgery and Endoscopy, Hospital Infantil de Mexico, Mexico D. F. , Mexico. Request for reprints: Dr.
Gerardo Blanco Rodriguez, Service Thoracic Surgery and Endoscopy, Hospital Infantil de Mexico Federico Gomez, Dr. Marquez # 162, Col. Doctores, Deleg. Cuauhtémoc, CP 06720, Mexico, DF, Mexico. Date Received: 17/07/2003 Approval date: 30-10-2003. SUMMARY Introduction. Herpes esophagitis is a disease that occurs mainly in immunosuppressed patients; until 1985 most cases were diagnosed during autopsies, what has changed with the advent of endoscopy. Material and methods. records of immunosuppressed patients who were asked endoscopy and biopsies January 1992 to June 2002 were reviewed, analyzed: age, sex, symptoms, oral lesions, endoscopic and histological findings and underlying disease. Results. 137 cases were analyzed, of which 12 had esophagitis herpes virus group, 6 were female and 6 male; age ranged from 14 months to 15 years.
Five patients had leukemia, 5 had any solid tumor, Kawasaki disease 1 and 1 Kidney transplant. The main symptoms were dysphagia and drooling. Ten patients had lesions in the oral mucosa and endoscopy showed ulcers and white patches. Histological studies in these cases showed characteristic changes of herpes virus infection. Conclusion. Twelve immunosuppressed patients with esophageal symptoms had esophagitis herpes virus. The most constant symptoms were dysphagia and drooling. Endoscopy locates lesions and by taking biopsies reach the etiologic diagnosis and indicate the management to follow. KEYWORDS. Herpetic esophagitis; endoscopy; biopsy. ABSTRACT Introduction. Herpetic esophagitis is mainly in immunocompromised Patients Observed; Were before 1985 most cases diagnosed at autopsy but has changed esta With the introduction of endoscopy.
Material and methods. Clinical charts of immunocompromised Patients (n = 137) in Which an endoscopic procedure was practiced, from January 1992 to June 2002 Were reviewed period; age, gender, symptoms, oral lesions, main disease, endoscopic histopathological findings, Were reviewed. Results. Herpetic esophagitis was found in 12 of 137 cases, 6 Were females; age varied from 14 months to 15 years; main disease was leukemia in 5 cases, a solid in 5 tumor, Kawasaki’s disease in 1, and renal transplant in 1. Main symptoms Were Observed dysphagia and syalorrhea; In 10 cases oral lesions Were present. Esophageal ulceration and white plaques Were Observed in the endoscopic study and the characteristic of Herpes virus infection Changes Were Observed in the histopathological study. Conclusion. We present 12 cases of herpetic esophagitis in immunocompromised children in Whom syalorrhea and dysphagia Were the main symptoms. KEY WORDS. Herpetic esophagitis; immunocompromised children. Introduction There are different microorganisms capable of damaging the esophageal mucosa in the immunosuppressed patient, these Candida ranks first, followed by herpes virus. fifteen
Herpetic esophagitis is a disease that occurs primarily in immunocompromised 1,2,6-8 but has also been reported in patients immunocompetent children. 4,6,9,10 In most reports prior to 1985 diagnosis of this entity was made by autopsy, causing 5. 7 to 25% of esophageal ulcers. Endoscopy has established the diagnosis in early stages, allowing timely treat the sick and avoid complications that endanger life. Although there are approximately 70 types of herpes virus in nature, only Herpes simplex types I and II, Herpes zoster, Epstein Barr virus, Cytomegalovirus Herpes VIII and cause infection in humans. 2. 7 From the above, Herpes simplex I, Herpes zoster and may cause ulcerative esophagitis. 3. 5 Because the injuries caused by these viruses are morphologically indistinguishable, it is necessary to consider other clinical features such as the presence of skin lesions. 7 It has reported an increase in the frequency of herpes virus esophagitis 1. 2 in immunocompromised patients with cancer or who have been transplanted; found as predisposing factors in these cases the use of chemotherapy and radiotherapy 1-3. 5 steroids.
3. 5 the frequency of this complication occurs in patients of this hospital, what are the most common symptoms and endoscopic findings it is unknown. So the aim of this study was to establish the frequency of herpetic esophagitis and clinical characteristics of immunosuppressed patients merited endoscopy and biopsy at a pediatric tertiary hospital care. Material and methods Records of immunocompromised patients who underwent endoscopy and biopsy January 1992 to June 2002 and were selected who underwent histopathological diagnosis of herpetic esophagitis were reviewed. We analyzed: sex, age, symptoms, presence of lesions in the oral cavity or skin, endoscopic findings, histopathological changes, underlying disease and the relationship of the lesion with the last cycle of chemotherapy or steroids. For the endoscopic procedure, all patients were placed peripheral venous access, were monitored with electrocardiograph and pulse oximeter, carrying out examination of the oral cavity, balanced general anesthesia with endotracheal intubation was administered, it was performed panendoscopy with endoscope Olympus brand 7. 8 mm in children under one year or under 10 kg weight and 9. 8 mm Pentax videopanendoscopio older; esophagus, stomach and duodenum was revised, taking biopsies of lesions, which were placed in formalin eosin and sent to the Pathology Department, where they were set eight to ten hours, embedded in paraffin, making cuts 4 μ of thick hematoxylin and eosin staining. Histopathological diagnosis of herpetic esophagitis was established when there was ulceration or erosion of the esophageal epithelium and epithelial disruption adjacent characterized by globose degeneration of epithelial cells, with small intranuclear type Cowdry A eosinophilic inclusions or inclusions covering the entire core, Cowdry type B besides multinucleated cells. 4 results A total of 137 records of immunosuppressed, studied 82 patients were male (59.
8%) and 55 female (40. 2%). Of these, only 12 (8. 8%) was documented herpes virus in histopathology, of which six were male and six female; by age group were found, two infants, three preschool, four school and three teenagers. The underlying disease was leukemia in five cases, three osteosarcoma, one with Wilm’s tumor, one with Hodgkin’s disease, one with Kawasaki disease and a kidney transplant for chronic renal failure. Ten patients had received prior chemotherapy; patients with Kawasaki and the transplanted were taking steroids. Clinical symptoms were dysphagia in eight, six drooling, vomiting in two, gastrointestinal bleeding in two, one had asthenia, weakness, cough, fever, shortness of breath and headache, abdominal pain in another. The findings in the oropharynx mucosa were: ulcers in four cases, three white plaques, ulcers with two white plaques, congestion and edema of the gums in one, without the presence of injury two. None of the patients had skin lesions. As for the medical management, six cases received no prior treatment, two antibiotic, antiviral and antifungal, one antibiotic and antiviral, other gamma globulin, antibiotic and antiviral, antifungal and two only. Endoscopic findings were: Seven patients with ulcers in lower third (one confluent), three with white plaques, which were small, medium or large, two ulcers and plates (Fig. 1), two further mucosa hyperemic and friable in one mucosal bleeding and mucosal purplish one aspect. Histological sections of all biopsies showed mucosal ulceration in most cases.
In the bed of the ulcer had mixed inflammatory infiltrate; epithelial cells adjacent to the ulcer showed abundant cytoplasm, sometimes hyaline aspect, vesicular nuclei and eosinophilic inclusions small, Cowdry type A, and intranuclear inclusions displacement homogeneous chromatin towards the nuclear membrane (Cowdry type B); in seven cases they were identified multinucleated cells with nuclei “bag of marbles” which sometimes were in the shed from the mucosa (Figs. 2 to 4) epithelium. Three cases also showed bacterial colonization and two fungi. One of the patients had lesions in the oral mucosa was made a scraping showed multinucleated cells with homogeneous intranuclear inclusions. Discussion , Although rare, esophageal herpes virus infection is seen most frequently in the immunocompromised patient. Most series have been reported in adults and as necropsy findings, and few cases of children with this disease. For the diagnosis of herpes esophagitis caused by endoscopy plays a key role, not only because it allows the visualization of lesions but also perform brushing or biopsy. In this series there was no gender predominance. He appeared in all age groups from infants. All patients had a disease or predisposing medical treatment; in 83. 3% it was due to a neoplastic disease; 83. 3% had a history of having received prior chemotherapy; while two (16.
7%) steroid use was documented. Of neoplastic diseases, leukemia had half and half solid tumors. What differs with McBane and Gross, 1 reported that a third of his cases had a hematologic disease (7 of 23 patients), followed by solid tumors in chemotherapy or radiotherapy (4 of 23), immunosuppression for rheumatoid diseases (6 23), and in 2 of 23 kidney transplant; only one a predisposing factor was found. While Agha et al. 2 reported immunosuppression in the 12 patients in their series, three with histiocytosis, two with leukemia, three diabetes, steroid use two, one with burns, two kidney transplants, one with carcinomatosis and one HIV +. Nash and Ross 4 reported in their study of 14 autopsies of adults, as a predisposing factor, malignant neoplasms in four (leukemia, lymphoma, breast cancer, lung cancer), renal transplantation in three, major surgery of aorta in two, burns two, aplastic anemia, brain abscess, and viral myocarditis in one of each. Levine et al. 8 reported a predisposing factor in six patients (malignancy or immunosuppressive therapy). In studies it is reported that symptoms vary from asymptomatic patients, even dysphagia, sore throat, chest pain and gastrointestinal bleeding. In this study 1,2,4,7,8,11 symptoms were present in all cases. It predominating dysphagia (66. 7%), followed by salivation (50%), vomiting (16. 7%), bleeding (16.
7%), general (8. 3%) symptoms, unlike what was reported by McBane and Gross 1 no pain found chest as a symptom, reported in his study dysphagia in 52%, nausea or vomiting in 39%, fever in 35% and bleeding in 34%. Agha et al. 2 reported prevalence odynophagia (10 of 12) and bleeding (3 of 12). Lightdale et al. 5 dysphagia and chest pain observed in 100% of patients. Levine et al. 8 reported in four of six patients and two sore throat gastrointestinal bleeding. oropharyngeal lesions were found in 83. 3% of patients: isolated in 33. 3%, ulcers with whitish plaques in 16. 7%, 25% white plaques, ulcers Gingivostomatitis 8. 3%; without injuries oropharynx 16.
7%. While Lightdale et al. 5 and Levine et al. 8 they found only in 50% of cases and Gross McBane and only 1 in 20%. Endoscopic findings reported include: inflammation 1 vesicles, ulcers 1-3,5,7-9 1 to 3. 8 resizable and typically shaped volcano, 2 more common in lower third, 5,7,9 and pseudomembranes , 1,2,8,9 of which the only typical herpes lesion vesicles are. 3 In this study found no blisters, ulcers finding 75%, of which 90% were in the lower third and 10% in the middle third; of these, 16. 7% were accompanied by white plaques. Being in only 25% white plaques. In addition ulcer patients was found in two hyperemic and friable esophageal mucosa, the purple one and another esophageal mucosa, esophageal bleeding. The findings regarding the ulcer are similar to those of McBane and Gross, one who was found in 17 of 23 patients (73. 91%), pseudomembranes in 5 of 23 patients (21. 74%); while Levine and col.
8 found in his series of six to three patients with ulcers: two plates and one with ulcers and plaques; and Lightdale et al. 5 refer ulcers and erosions in two of four patients two. Agha et al. 2 endoscopy performed eight of his 12 patients, finding in all esophagitis predominantly in distal third, and in six ulcers, and exudates in the eight; the location is similar to that found in this study with presence of ulcers distal eight of nine patients. It can be concluded that although the ulcer is an injury that should suggest herpes esophagitis is not pathognomonic of this disease, so the biopsy and / or brushing is necessary to reach the correct diagnosis. In contrast esophagram 2,7,8 ulcers can be observed and plates; 2, 8 in this study patients was performed by endoscopy accessibility, this being more specific for lesions of the esophageal mucosa and for biopsy or brushing. The diagnosis is established by histopathologic or brushing study by culture or biopsy. 1 to 4. 8 In all patients in this study the diagnosis was established by biopsy. Morphological changes of herpetic esophagitis are characteristic and it is interesting that in this study, the inflammatory infiltrate was mixed bed of ulcer, unlike what has been observed in other studies. 4,12 is sometimes difficult to establish the diagnosis because the biopsy does not always include the adjacent epithelium in these cases may be useful to some of the more specific techniques such as immunoperoxidase staining or in situ hybridization, using an oligonucleotide probe specific for herpes simplex type I, which is employed in tissue sections included in parafina. 13 Whenever possible, it is recommended to send a fraction of the culture sample, since the sensitivity of the crop is higher than the cytological or histological study. 1
The loss of integrity of the epithelial barrier may be the gateway to other microorganisms, so herpetic esophagitis may be associated with bacteria or fungi, as observed in five cases: three showed colonization by bacteria and two fungi. Gross McBane and one report associated in 23 patients, ten bacterial infection, fungal nine, cytomegalovirus, Pneumocystis carinii in three and two. They have been reported complications caused by herpes simplex, such as bleeding, esophageal perforation, fistula and visceral dissemination, 2 finding only bleeding in one case and spread to the stomach and duodenum in two cases. Nash and Ross 4 reported herpes infection in other organs in six of his 14 autopsies; no such complications were found in cases of this study. REFERENCES 1. McBane RD, JB Gross. Herpes esophagitis: clinical syndrome, endoscopic appearance, and in 23 Patients diagnosis. Gastroint Endosc 1991; 37: 600-3. [Links] 2. Agha CF, Lee HH, Nostrant TT. Herpetic esophagitis: a diagnostic challenge in immunocompromissed Patients.
Am J Gastroenterol 1986; 81: 246-53. [Links] 3. Kadakia SC. Viral esophagitis: the endoscopic appearance. Gastroint Endosc 1992; 38: 633-4. [Links] 4. Nash G, Ross JS. Herpetic esophagitis: a common cause of esophageal ulceration. Hum Pathol 1974; 5: 339-45. [Links] 5.
Lightdale CJ, Wolf DJ, Marcucci RA, Salyer WR. Herpetic esophagitis in patient with Cancer: ante mortem diagnosis by cytology brush. Cancer 1977; 39: 223-6. [Links] 6. Rolston KV. Upper gastrointestinal disease in human immunodeficiency virus-infected Individuals. Arch Intern Med 1992; 152: 881-2. [Links] 7. Weiden PL, MD Schuffler. Herpes esophagitis complicating Hodgkin’s disease. Cancer 1974; 33: 1100-2.
[Links] 8. Levine MS, Laufer I, Kressel HY, HM Friedman. Herpes esophagitis. Am J Roentgenol 1981; 136: 863-6. [Links] 9. Ashenburg C, Rothstein FC, Dahams BB. Herpes esophagitis in the immunocompetent child. J Pediatr 1986; 108: 584-7. [Links] 10. Bastian JF, Kaufman IA.
Herpes simplex esophagitis in a healthy 10 year old boy. J Pediatr 1982; 100: 426-7. [Links] 11. Corey L, Spear PG. With viruses herpes simplex infections. N Engl J Med 1986; 314: 749-57. [Links] 12. Greenson JK, Beschorner WE, Boinott JK, JH Yardley. Prominent mononuclear cell infiltrate is characteristic of herpes esophagitis. Human Pathol 1991; 22: 541-9. [Links]
13. Bruner JM. Oligonuclotide probe for Herpes virus: use in paraffin sections. Mod Pathol 1990; 3: 635-8. [Links]