Idiopathic Esophageal Ulcers Research Articles

Idiopathic esophageal ulceration in acquired immunodeficiency syndrome: successful treatment with misoprostol and viscous lidocaine

Objective: Esophageal ulceration is a common and important cause of morbidity in patients with acquired immunodeficiency syndrome (AIDS). After known causes are excluded, a subgroup remains with unexplained esophageal ulceration, known as idiopathic esophageal ulceration (IEU). The current therapy of IEU includes corticosteroids or, less frequently, thalidomide, although no placebo-controlled trials have been reported. The aim of this retrospective study was to determine the outcome of treating IEU with misoprostol and viscous lidocaine. Methods: A retrospective review of esophageal ulceration in AIDS identified seven subjects with IEU at our institution. IEU in these subjects was treated successfully with misoprostol, 200 μg, crushed and suspended in 2% viscous lidocaine, 15 ml, given orally a.c. and h.s. for 4 wk. Results: All patients reported symptomatic improvement within 2–3 days and complete resolution of their symptoms within 15 days. Healing of esophageal ulcerations was confirmed in five of seven subjects at a repeat endoscopy 8–12 wk later. Conclusions: Misoprostol, an antiulcer drug, has GI cytoprotective properties, and viscous lidocaine, a topical anesthetic, coats mucosal surfaces. We speculate that misoprostol when delivered topically is 3–6 times more effective than when delivered systemically. Considering the rapid resolution of symptoms, healing of ulcers, and lack of side effects, we believe that misoprostol crushed and suspended in viscous lidocaine should be considered for further evaluation in prospective, placebo-controlled trials of IEU.

Diagnosis and management of esophageal disease in the acquired immunodeficiency syndrome.

Esophageal disorders are common complications of human immunodeficiency virus (HIV)-infected patients. In a significant number of patients, the esophagus may be the site of the first acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness. We reviewed pertinent articles, obtained from a MEDLINE search, on the diagnosis and treatment of esophageal diseases in HIV disease. Infections are the most common cause of esophageal disease, and opportunistic disorders such as cytomegalovirus and idiopathic esophageal ulceration rarely present until the CD4 lymphocyte count falls below 100/mm3. Endoscopy is the most valuable tool for evaluating esophageal complaints in AIDS. Almost all esophageal infections in patients with AIDS are treatable; therefore, a thorough work-up is indicated. With the widespread use of more effective antiretroviral therapy including the protease inhibitors, there is a general consensus that the incidence of many opportunistic diseases appears to be decreasing.

A role for apoptosis in the pathogenesis of AIDS-related idiopathic esophageal ulcers.

Lack of understanding of the mechanism of tissue destruction associated with idiopathic esophageal ulcers (IEUs) poses a diagnostic and therapeutic dilemma for the clinician. The possible role of apoptosis in IEUs, as suggested by endoscopic and histologic observations, was investigated by examination of archival tissues for apoptosis-related DNA fragmentation using in situ nick end labeling (TUNEL). High levels of apoptosis were observed in mucosal cells immediately adjacent to IEUs. Apoptotic cells were virtually absent in normal control tissues, while the edges and bases of lesions and sloughed-off tissues in IEUs in human immunodeficiency virus (HIV)-infected patients showed elevated levels of apoptotic cell death. However, tissue samples from patients with esophageal ulcerations of known etiology showed no apoptosis of mucosal cells. These data support a role for apoptosis in the pathogenesis of IEUs and suggest a mechanism involving HIV-associated bystander killing of uninfected mucosal cells.

TREATMENT OF PERSISTENT ESOPHAGEAL ULCER IN A PEDIATRICS PATIENT WITH AIDS♦ 54

A 2 year old girl, perinataly infected with HIV Presented to University Hospital of Brooklyn with dysphagia and odynophagia to both liquids and solids. Her weight and height were at 10th percentile and she had lost 6 pounds over 7 weeks. Hepatosplenomegaly as well as swollen cervical, axillary and inguinal nodes were noted. Upper GI endoscopy revealed 6 esophageal ulcers from 0.5 cm to 6 cm in diameter with sharp smooth, raised borders and erythematous base at 8 cm above lower esophageal sphincter. Pending results of pathology/microbiology she was treated with IV acyclovir which she failed to respond. Diagnosis of Idiopathic esophageal ulcers was made and treatment with prednisone was started. Repeat endoscopy after 10 days revealed marked healing, but symptoms and endoscopic findings recurred within a month while prednisone was being tapered. She responded quickly to increased dose, but different attempts to wean her from steroids failed, and eventually she did not respond at all. She was then started on Thalidomide 100mg Q.D. ×2 weeks, on compassionate basis. Based on endoscopic findings which showed improvement, Thalidomide was continued with 100 mg TIW for 8 weeks. By the end of this period she started taking soft foods by mouth and was switched to 100 mg Thalidomide twice/week. She is currently on regular diet for the age without complaint. Her clinical/neurological findings as well as laboratory values including CD4 count did not change.

Thalidomide treatment for idiopathic esophageal ulcers in patients with HIV

Esophageal ulcers may cause troubling symptoms in patients infected with human immunodeficiency virus (HIV). The ulcers are hyperalgic, interfere with nutrition, and cause general debilitation.1 The ulcers can occur as a result of infection from Candida, herpes simplex virus, or more commonly from cytomegalovirus. The ulcers may also form as a result of malignant diseases such as Kaposi\'s sarcoma or lymphoma. When investigation fails to reveal a cause for the ulcers, many patients are treated empirically with oral corticosteroids.

Symptom-specific use of upper gastrointestinal endoscopy in human immunodeficiency virus-infected patients yields high dividends.

The yield of upper gastrointestinal endoscopy (esophago-gastroduodenoscopy; EGD) in human immunodeficiency virus (HIV)-infected patients based on presenting symptoms has not been well studied. We studied consecutive patients with documented HIV infection undergoing EGD at a large innercity hospital between August 1, 1990 and December 31, 1993; all had presenting symptoms and indications for EGD prospectively recorded at the time of EGD. All endoscopic abnormalities were routinely subjected to biopsy, and extensive histopathological evaluation was performed. EGD was considered helpful when the findings stimulated specific therapeutic intervention other than antifungal or antacid medications. The specific indications for EGD in 156 patients were as follows: esophageal symptoms, 102 patients (65%); abdominal pain, 18 (12%); upper gastrointestinal bleeding, 25 (16%); refractory nausea and vomiting, 11 (7%). Overall, pathologic findings were identified in 116 patients (74%): in refractory esophageal symptoms, 82%; upper gastrointestinal bleeding, 92%; abdominal pain, 39%; nausea and vomiting, 27%. EGD with biopsy identified a specifically treatable opportunistic disorder other than Candida in 80 patients (51%), including idiopathic esophageal ulcer (22%) or viral esophagitis and/or duodenitis (29%). EGD was not helpful in 22.3% of cases, those involving Candida (12.3%) and peptic ulcer disease (PUD)-related causes (10%). The mean CD4 count of patients with opportunistic pathologic findings (24/mm3, n = 79) was significantly lower than that of patients with PUD/gastroesophageal reflux disease (GERD) (167/mm3, n = 9) or negative EGDs (165/mm3, n = 35). Overall, the results of EGD influenced patient management in 78% of cases. We conclude that selective symptom-specific use of EGD, particularly in patients with esophageal symptoms refractory to antifungal therapy or gastrointestinal bleeding, usually identifies specifically treatable abnormalities, whereas EGD is less useful for the evaluation of abdominal pain or nausea and vomiting.

Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer

Background: Establishing a diagnosis of viral esophagitis in patients with human immunodeficiency virus (HIV) infection has important clinical relevance. However, the number of biopsies required to diagnose viral esophagitis is currently unknown. Methods: Over a 34-month period, all HIV-infected patients with esophageal ulcer underwent 10 biopsies of the largest and/or most accessible lesion, primarily from the ulcer base. The first 3 specimens were placed in one formalin container, the second 3 in another, and 4 additional specimens in the third. Standard histopathologic methods were employed, as well as in situ hybridization or immunohistochemical studies in most patients, and viral cytopathic effect was defined using previously proposed criteria. Patients were then treated on the basis of the results of the initial biopsy specimens with both clinical and endoscopic follow-up. Results: One hundred HIV-infected patients with esophageal ulcer were studied. Cytomegalovirus (CMV) was considered etiologic in 50 patients. Of these 50 patients, the first three biopsy specimens were sufficient to diagnosisCMV in 40 (80%). In 5 patients (10%), the first two sets were negative with only the third set of biopsies positive. Similarly, of the 4 patients with simultaneous CMV and herpes simplex virus (HSV) esophagitis, three sets of biopsy specimens were required for diagnosis of both agents in 3 patients. HSV esophagitis alone was found in 2 patients; diagnostic viral inclusions were present in the first 3 biopsies in each patient. Thirty-five patients had HIV-associated idiopathic esophageal ulcer; only one of these patients was misdiagnosed. Conclusions: At least 10 biopsies may be required to exclude viral esophagitis in HIV-infected patients. If biopsy specimens are adequate and no evidence of viral cytopathic effect has been found, the patient may be treated on the basis of the results of the initial clinical, endoscopic, and pathologic findings with close clinical follow-up rather than repeat endoscopy. (Gastrointest Endosc 1996;44:587-93.)

Esophageal Ulcers in AIDS

Letters15 May 1996Esophageal Ulcers in AIDSPere Domingo, MD, Josep Ris, MD, and Joaquin Lopez-Contreras, MDPere Domingo, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this author, Josep Ris, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this author, and Joaquin Lopez-Contreras, MDUniversitat Autonoma de Barcelona; Barcelona, SpainSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read with interest the recent report by Wilcox and associates [1] and noted two outstanding findings: 1) the high prevalence of idiopathic esophageal ulcers and the excellent initial response to prednisone therapy and 2) the high percentage of patients with ulcer recurrence. In 13 of 35 patients with esophageal ulcers (37.1%), ulcerations recurred despite an initial clinical and endoscopic response [1].We have recently cared for seven HIV-infected patients who had idiopathic esophageal ulcers. All had advanced disease. Three patients were initially treated with a 2-week regimen of prednisone, 0.5 mg/kg of body weight per day, ...

Esophageal Ulcers in AIDS

Letters15 May 1996Esophageal Ulcers in AIDSLouis-Jean Couderc, MD, Evelyne Balloul, MD, and Isabelle Caubarrere, MDLouis-Jean Couderc, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this author, Evelyne Balloul, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this author, and Isabelle Caubarrere, MDHopital Foch; 92150 Suresnes, FranceSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Wilcox and colleagues [1] documented the high prevalence of idiopathic esophageal ulcers in patients with human immunodeficiency virus (HIV) infection and suggested that steroids be used in these patients. We previously reported that thalidomide was beneficial for esophageal ulceration and the HIV wasting syndrome [2, 3]. With treatment, the symptoms of aphthous ulceration, myalgia, and fever abated within 2 weeks. The patients required prolonged maintenance therapy because of recurrence when the daily thalidomide dose was tapered from 100 mg to 50 mg. No neurologic adverse effects occurred, although patients were treated simultaneously with azidothimidine. We suggest that ...

Esophageal ulceration in human immunodeficiency virus infection. Causes, response to therapy, and long-term outcome.

To determine the causes of esophageal ulceration, the response rate to currently available therapies, and the long-term outcome in patients with human immunodeficiency virus (HIV) infection. Prospective cohort study. An urban county hospital. Consecutive patients with HIV infection and endoscopically detected esophageal ulceration during a 4-year period. Causes of ulcers were determined from clinical, endoscopic, and pathologic findings. Standard medical therapies for the identified causes were instituted, and ulcer healing was endoscopically confirmed when possible. Symptomatic and endoscopic response to therapy and long-term outcome, including survival. 100 patients with esophageal ulcer were identified. Ulcers caused by cytomegalovirus alone were the most common (n = 45); idiopathic ulcers were almost as frequent (n = 40). Herpes simplex virus esophagitis alone was identified as a cause in only 5 patients. Several potential causes of ulcer were found in 5 patients, including Candida esophagitis in 27 patients. Ten patients developed more than one cause of ulceration during long-term follow-up. Eighty-five patients had specific medical therapy for their identified disorders and had an overall response rate of 98%. Median survival from time of diagnosis was 8.9 months (range, 2 days to > 42 months). A difference in median survival was found between patients with cytomegalovirus esophagitis and those with idiopathic esophageal ulcer (7.6 months compared with 13.1 months; P = 0.03). Given 1) the broad spectrum of causes of esophageal ulceration, 2) that each of these causes requires specific therapy, and 3) the apparent high response rate, it is important to do endoscopic evaluation with mucosal biopsy in patients with HIV infection so that a diagnosis can be established and appropriate therapy instituted. Despite effective therapy, long-term survival is poor; however, long-term remission and survival may occur in some patients.

ESOPHAGEAL INFECTIONS

Infections of the esophagus are unusual in the general population and strongly imply immunodeficiency, although immunocompetent individuals are not exempt. HIV infection is predominant among risk factors for infectious esophagitis. For all immunocompromised patients, the most frequently identified esophageal pathogens are Candida, CMV, and HSV. Peculiar to HIV-infected patients are idiopathic esophageal ulcers as well as unusual bacteria and parasites. Patterns of presentation differ with each infecting organism, and clinical features should be used as a guide in achieving a correct diagnosis. For example, a patient with AIDS presenting with esophageal symptoms and thrush, along with abdominal pain, nausea, vomiting, and fever, is unlikely to resolve all symptoms with empiric antifungal therapy alone. Parsimony of diagnosis does not hold among immunodeficient patients in whom concurrent infections are common. Accurate and timely diagnoses are essential as effective treatments are available for particular etiologies. Finally, among immunocompromised patients, all esophageal symptoms are not necessarily due to an infection, and possible diagnoses of pill esophagitis, acid-peptic injury, or structural and functional abnormalities should not be overlooked.

Esophageal Disease in Human Immunodeficiency Virus Infection

Up to 40% of patients with the acquired immunodeficiency syndrome may develop symptoms of esophageal disease. Candida esophagitis is responsible for the majority of the cases of esophageal disease; cytomegalovirus, herpes simplex, idiopathic esophageal ulcers, and Kaposi's sarcoma account for most of the remaining cases. Although endoscopy with esophageal biopsy and brushing is the gold standard for the diagnosis of esophageal disease in the acquired immunodeficiency syndrome, we generally recommend initial empiric therapy with an antifungal agent in patients with esophageal symptoms. Since effective treatment is available for most cases of esophageal disease in the acquired immunodeficiency syndrome, we recommend endoscopic evaluation in patients who do not respond to empiric therapy within 1 to 2 weeks.

Idiopathic esophageal ulceration in the acquired immunodeficiency syndrome: radiologic reappraisal in 10 patients.

Idiopathic esophageal ulceration in patients with AIDS has previously been described. Establishing this diagnosis is important because of the excellent response of these ulcers to corticosteroid therapy. We studied 10 such patients with esophagography and endoscopy. HIV was isolated from the ulcer base in six of the 10 patients utilizing various techniques including in situ hybridization. No other organisms were found. All of the ulcers were in the distal half of the esophagus and were solitary in eight of the 10 patients. The solitary ulcers were large (2.5 x 2.0 cm to 12 x 9 cm) and deep (> 0.5 cm) with undermined margins. In three patients, fistulae arose from the distal esophagus and crossed the gastroesophageal junction. In one patient, a huge idiopathic ulcer perforated into the mediastinum. These latter findings are not seen in the more common ulcerating AIDS esophagitides due to herpes simplex and cytomegalovirus.

Endoscopic Characterization of Idiopathic Esophageal Ulceration Associated with Human Immunodeficiency Virus Infection

Idiopathic esophageal ulcerations (IEUs) associated with human immunodeficiency virus (HIV) infection are now recognized as an important cause of esophageal disease in this population. Limited radiographic and endoscopic reports have almost uniformly described these lesions as solitary and giant. Over a 28-month period, we identified 68 IEUs endoscopically in 23 patients. Most patients had long-standing HIV infection and a low CD4(+) lymphocyte count. Multiple ulcers were identified in 57% of endoscopies. Giant ulcers were seen in one-third, with 37% < or = 1 cm in greatest dimension. Most of the lesions were in the mild- to distal esophagus. The ulcers were characterized as either shallow or intermediate in depth in 53%, with a deep ulcer in 7%. A "heaped-up" appearance of the ulcer was identified in 40%. An esophageal mucosal bridge(s) was seen in two patients. In contrast to previous reports, IEUs are variable endoscopically in number, size, and appearance. Given this lack of uniformity in appearance, which may mimic other causes of esophageal ulceration, all HIV-infected patients with an esophageal ulceration should undergo endoscopy with biopsy to obtain a definitive diagnosis.

Chronic idiopathic esophageal ulceration in the acquired immunodeficiency syndrome. Characterization and treatment with corticosteroids.

Study objectives were to characterize the clinical syndrome of chronic idiopathic esophageal ulceration in patients with acquired immunodeficiency syndrome (AIDS), to determine the extent of local human immunodeficiency virus (HIV) infection, and to evaluate the effect of corticosteroid therapy upon symptoms and healing. Twelve AIDS patients with chronic esophageal ulcers whose etiology remained unknown after clinical evaluation were the subjects. All patients complained of severe odynophagia, chest pain, and weight loss. Barium radiography and endoscopy demonstrated large, undermined ulcers with severe acute inflammation. No evidence of herpes simplex viruses I or II, cytomegalovirus, fungi, or tumors were found histologically. Evidence of HIV was found in all ulcers using a combination of RNA in situ hybridization, immunohistochemistry, and quantitative antigen capture enzyme-linked immunosorbent assay of tissue homogenates. Steroid therapy by the oral or intravenous routes or by direct intralesional injection resulted in pain relief, weight gain in 10 patients, and ulcer healing in five patients. A characteristic clinical syndrome of chronic idiopathic esophageal ulceration may occur in patients with AIDS, related to local HIV infection in the esophagus. Corticosteroids relieve symptoms and may promote healing of the ulcer.

HIV-1 gp41 Antigen Demonstration in Esophageal Ulcers with Acquired Immunodeficiency Syndrome

Esophageal ulcers associated with acquired immunodeficiency syndrome (AIDS) may be chronic, debilitating, and resistant to antifungal or antiviral therapy. The therapeutic management of these lesions remains controversial due to the difficulty in identifying pathogenic agent(s). We review previously published cases and describe three AIDS patients with esophageal ulcers that stained by immunoperoxidase techniques for human immunodeficiency virus (HIV)-1 surface glyloprotein (gp41). All three showed symptomatic resolution and healing of their ulcers with corticosteroid therapy. We believe this documentation of HIV-1 gp41 antigen within mononuclear cells of esophageal ulcers in AIDS supports a role of the HIV-1 virus in the pathophysiology of idiopathic esophageal ulcers in patients with AIDS. These cases further support a role for corticosteroid therapy in the treatment of esophageal ulcers resistant to antifungal and antiviral therapy in patients with AIDS.