Diagnosis of oesophageal mucormycosis managed with medical therapy alone.

Mucormycosis is an invasive mould that can cause aggressive infection, particularly in immunocompromised patients. Though oesophageal mucormycosis is relatively rare, it remains an elusive and devastating manifestation of this disease. The management is also challenging, due to surgical morbidity and contraindications such as thrombocytopenia in immunocompromised hosts. In this report, we present the case of a 60-year-old Lebanese man with newly diagnosed acute myeloid leukaemia who developed oesophageal mucormycosis after induction chemotherapy with idarubicin/cytarabine (7+3). The diagnosis was made when the patient developed febrile neutropenia and odynophagia. CT scan of the chest revealed a thickened oesophagus. Oesophagogastroduodenoscopy with biopsy, histopathology and PCR were performed, resulting in the diagnosis of Rhizopus microsporus The patient was successfully treated with liposomal amphotericin B and salvage posaconazole therapy without surgical intervention. We reviewed the clinical characteristics of the six published oesophageal mucormycosis reports from the literature.

Immunoglobulin G4-Related Disease Manifesting as Isolated, Typical, and Nontypical Gastroesophageal Lesion: A Research of Literature Review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory and fibrotic condition. The disease is characterized by tissue infiltration with dense lymphoplasmacytes and IgG4-positive plasma cells. SUMMARY: The aim of this study was to provide gastroenterologists with novel insights into evaluating the gastroesophageal involvement with IgG4-RD or mimickers of this condition and to give special attention to clinicopathological features. A literature review was performed using the PubMed database. A total of 39 studies presenting cases in the form of isolated, typical, and nontypical gastroesophageal involvement with IgG4-RD published between 2010 and 2018 were included. These studies were thoroughly reviewed for symptoms, lesion location, lesion type, lesion size, immune-histopathology, associated diseases, treatment, and follow-up. Of the 39 studies reviewed, 9 were esophageal IgG4-RD lesions, isolated esophageal IgG4-RD 66.66% (6/9), a typical form of esophageal IgG4-RD 11.11% (1/9), and nontypical form esophageal IgG4-RD 22.22% (2/9). The 30 gastric IgG4-RD that include isolated gastric IgG4-RD 46.66% (14/30), typical gastric IgG4-RD 40% (12/30), and nontypical gastric IgG4-RD 13.33% (4/30). The majority of lesions were inflammatory tumors, ulceration, nodular lesions, chronic gastritis, and malignant lesions. Key Messages: IgG4-RD may be manifested by isolated, typical and nontypical forms of gastroesophageal lesions and should be taken into consideration in the differential diagnosis. Corticosteroids may be the sole diagnostic treatment for this condition.

Structured Diagnostic Approach and Risk Assessment in Mucous Membrane Pemphigoid with Oesophageal Involvement.

Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital Würzburg. Twenty-one patients (70%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid.

Rare cause of odynophagia: Giant esophageal ulcer.

Gastrointestinal complications are a frequent cause of morbidity after transplantation and may affect up to 40% of kidney transplant recipients. Here we report a rare case of idiopathic giant esophageal ulcer in a kidney transplant recipient. A 37-year-old female presented with a one-week history of odynophagia and weight loss. Upon admission, the patient presented cold sores, and a quantitative cytomegalovirus polymerase chain reaction was positive (10(5) copies/mL). An upper endoscopy demonstrated the presence of a giant ulcer. Serological test and tissue biopsies were unable to demonstrate an infectious origin of the ulcer. Immunosuppression was reduced and everolimus was introduced. An empirical i.v. therapy with acyclovir was started, resulting in a dramatic improvement in symptoms and complete healing of the ulcer. Only two cases of idiopathic giant esophageal ulcer in kidney transplant recipients have been reported in the literature; in both cases, steroid therapy was successful without recurrence of symptoms or endoscopic findings. However, this report suggests that correction of immune imbalance is mandatory to treat such a rare complication.

[Esophageal aspergillosis in a patient with acute myelogenous leukemia and febrile neutropenia]. / Aspergilosis esofágica en una paciente con leucemia mieloide aguda y neutropenia febril.

Aspergillosis usually compromises the respiratory system, but can also affect others. We report a 46 yo female with acute myeloid leukemia, developed febrile neutropenia and dysphagia. Endoscopy revealed esophageal cytomegalovirus-like ulcers, but biopsies showed Aspergillus spp. It's important to consider aspergillosis in the differential diagnosis of esophageal lesions in high-risk patients.

[A case of esophageal actinomycosis in a patient with normal immunity].

Actinomycosis is a chronic suppurative disease and caused by Actinomycosis species, principally Actinomyces israelii, which are part of the normal inhabitant on the mucous membrane of the oropharynx, gastrointestinal tract, and urogenital tract. It usually affects cervicofacial, thoracic and abdominal tissue. Cervicofacial type has the highest percentage of occurrence with 50%. Actinomycosis frequently occurs following dental extraction, jaw surgery, chronic infection or poor oral hygiene. It may also be considered as an opportunistic infection in immunocompromised patients such as malignancy, human immunodeficiency virus infection, diabetes mellitus, steroid usage or alcoholism. But, actinomycosis rarely occurs in adults with normal immunity and rare in the esophagus. We report an unusual case of esophageal actinomycosis which was developed in a patient with normal immunity and improved by therapy with intravenous penicillin G followed oral amoxicillin, and we also reviewed the associated literature.

Toll-like receptor 9 is a novel biomarker for esophageal squamous cell dysplasia and squamous cell carcinoma progression.

BACKGROUND: Stimulation of Toll-like receptor 9 (TLR9) has been linked to invasion in various cancer cells in vitro. We investigated TLR9 expression in normal, dysplastic and malignant esophageal squamous epithelium. METHODS: TLR9 expression was analyzed by immunohistochemistry in 46 cases of esophageal squamous cell carcinoma, including 12 cases with adjacent squamous dysplasia and 24 cases with normal esophageal epithelium. TLR9 expression was compared with tumor grade, stage, proliferation, apoptosis and vascular density. RESULTS: In normal esophageal squamous epithelium, TLR9 staining intensity decreased linearly from the basal layers to the superficial layers (p < 0.001). Strong TLR9 expression was detected across full thickness of high-grade dysplasia, the intensity clearly differing from the normal squamous epithelium and squamous cell carcinoma (p < 0.001). All squamous cell carcinomas exhibited TLR9 expression that was positively associated with a high grade (p < 0.05), the presence of lymph node metastases (p < 0.05) and previously undetected distant metastases (p < 0.05). CONCLUSIONS: Expression of TLR9 in the basal parts of normal esophageal epithelium suggests a role related to cell proliferation and differentation. TLR9 upregulation detected in dysplastic epithelium and in disseminated carcinomas indicates that this protein may serve as a novel marker for esophageal squamous dysplasia and carcinoma with metastatic potential.

Immunohistochemical characterization of lymphocyte and myeloid cell infiltrates in spirocercosis-induced oesophageal nodules.

Spirocerca lupi is a nematode that infects the dog's oesophagus and promotes the formation of an inflammatory fibroblastic nodule that progresses to sarcoma in approximately 25% of cases. Spirocercosis-associated oesophageal sarcoma is an excellent and under-utilized spontaneous model of parasite-associated malignancy. The inflammatory infiltrate of paraffin-embedded, non-neoplastic oesophageal nodules (n = 46), neoplastic nodules (n = 25) and normal oesophagus (n = 14) was examined by immunohistochemistry using MAC387 (myeloid cells), CD3 (T cells), Pax5 (B cells) and FoxP3 (T regulatory cells) antibodies. Myeloid cells predominated in 70% of nodules, in pockets around the worms' migratory tracts and in necro-ulcerative areas in neoplastic cases. T cells predominated in 23% of cases with a focal or diffuse distribution, in the nodule periphery. No significant differences were observed between neoplastic and non-neoplastic stages. FoxP3+ cells were observed in low numbers, not significantly different from the controls. The inflammation in spirocercosis is characterized by pockets of pus surrounded by organized lymphoid foci. There was no evidence of a local accumulation of FoxP3+ cells, unlike many previous studies that have reported an increase in FoxP3+ T cells in both malignancies and parasite infections. The triggering factor(s) driving the malignant transformation of the spirocercosis-associated chronic inflammatory nodule warrants further investigation.

Lichenoid paraneoplastic pemphigus in the absence of detectable antibodies.

Paraneoplastic pemphigus (PNP) has been described as an antibody-mediated mucocutaneous disease occurring almost exclusively in patients with lymphocytic neoplasms. We describe 4 patients with the clinical features of the lichenoid variant of PNP in the absence of detectable autoantibodies. On the basis of these findings, we conclude that the spectrum of PNP likely includes patients with disease predominantly or exclusively mediated by cytotoxic T cells rather than autoantibodies. The pathophysiology and range of PNP disease are likely more complex than was initially believed.

Evaluation of cytokines (MIG, IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-10) during the different evolutive phases of chagasic esophagopathy.

The production of cytokines (MIG, IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-10) was studied in 39 individuals, including 28 with chagasic esophagopathy and 11 nonchagasic patients with gastroesophageal reflux disease. A sandwich enzyme immunoassay employing monoclonal antibody pairs specific for each cytokine was used. IFN-gamma and MIG production was significantly higher in patients with megaesophagus compared to control. Furthermore, in the absence of stimulation TNF-alpha levels were lower in the chagasic group than in the control group. In addition, significantly lower TNF-alpha levels were observed for the advanced form of the disease compared to the nonadvanced form. These results support the hypothesis that, although patients with advanced phase of megaesophagus present low number of CD4+ T lymphocytes, PBMC from this patients are able to respond up specific antigen stimulation.

Candidiasis esofágica en pacientes inmunocompetentes: estudio clínico e inmunológico / Clinical and immunological study of 10 immunocompetent patients with esophageal candidiasis

Background: Esophageal candidiasis is associated with conditions that cause an immune depression. It is a defining disease for AIDS, is observed in poorly controlled diabetics, in patients with renal or hepatic failure, in patients with cancer and in subjects using medications causing immunosuppression or broad spectrum antimicrobials. Aim: To report the features of 10 immunocompetent patients with esophageal candidiasis. Patients and methods: Six males and four females aged between 48 and 82 years, without conditions associated with immunosuppression, in whom an esophageal candidiasis was found on an upper gastrointestinal endoscopy. Delayed skin hypersensitivity to eight antigens, Iymphocyte subpopulations, yeast phagocytosis and neutrophil chemotaxis were measured. Results: Six patients had a low CD4 Iymphocyte count and seven had a low CD8 count. Seven patients were anergic on skin hypersensitivity challenge. Yeast phagocytosis was abnormal in one patient and neutrophil chemotaxis was abnormal in two. Humoral immunity was normal in all subjects. All patients were treated with oral fluconazole in doses of 150 mg/day for 14 days, with complete resolution of candidiasis in all. Conclusions: Patients with esophageal candidiasis, have frequent alterations of cellular immunity, that must be diagnosed and treated.

[Clinical and immunological study of 10 immunocompetent patients with esophageal candidiasis]. / Candidiasis esofágica en pacientes inmunocompetentes: estudio clínico e inmunológico.

BACKGROUND: Esophageal candidiasis is associated with conditions that cause an immune depression. It is a defining disease for AIDS, is observed in poorly controlled diabetics, in patients with renal or hepatic failure, in patients with cancer and in subjects using medications causing immunosuppression or broad spectrum antimicrobials. AIM: To report the features of 10 immunocompetent patients with esophageal candidiasis. PATIENTS AND METHODS: Six males and four females aged between 48 and 82 years, without conditions associated with immunosuppression, in whom an esophageal candidiasis was found on an upper gastrointestinal endoscopy. Delayed skin hypersensitivity to eight antigens, lymphocyte subpopulations, yeast phagocytosis and neutrophil chemotaxis were measured. RESULTS: Six patients had a low CD4 lymphocyte count and seven had a low CD8 count. Seven patients were anergic on skin hypersensitivity challenge. Yeast phagocytosis was abnormal in one patient and neutrophil chemotaxis was abnormal in two. Humoral immunity was normal in all subjects. All patients were treated with oral fluconazole in doses of 150 mg/day for 14 days, with complete resolution of candidiasis in all. CONCLUSIONS: Patients with esophageal candidiasis, have frequent alterations of cellular immunity, that must be diagnosed and treated.

Aberrant esophageal HLA-DR expression in a high percentage of patients with Crohn's disease.

Esophageal histology is not well studied in patients with Crohn's disease (CD). We, therefore, analyzed the histologic and immunohistologic appearance of esophageal mucosa in CD. Biopsy specimens taken from the esophagus of 57 consecutive patients with known CD of the large and/or small bowel, of 200 Crohn's-free controls, of 15 cases with ulcerative colitis, and of 5 cases with viral esophagitis were evaluated. In controls, most patients had either HLA-DR negative esophageal epithelium or showed focal or diffuse basal staining. HLA-DR expression of all epithelial layers (transepithelial staining) was observed in only four (2%) control subjects, in one case with herpes esophagitis, but not in patients with ulcerative colitis. In contrast, transepithelial HLA-DR expression was found in 19 (33%) patients with CD (p < 0.0001). In CD patients, it was associated with a significantly increased epithelial content in T-cells (CD3+, TIA-1+, granzyme B+), B-cells (CD79a+), natural killer cells (CD57+), and macrophages (CD68+). There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication. Transepithelial esophageal HLA-DR expression is common in CD. Immunohistochemistry may prove useful in supporting the histologic diagnosis of CD in staging procedures, for initial diagnosis as well as in doubtful cases.

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

BACKGROUND: 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. METHODS: We reviewed pertinent articles, obtained from a MEDLINE search, on the diagnosis and treatment of esophageal diseases in HIV disease. RESULTS: 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. CONCLUSIONS: 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.