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.

Mixed connective tissue disease-enigma variations?

In 1972, Sharp et al. described a new autoimmune rheumatic disease that they called MCTD, characterized by overlapping features of SSc, SLE, PM/DM, high levels of anti-U1snRNP and low steroid requirements with good prognosis. MCTD was proposed as a distinct disease. However, soon after the original description, questions about the existence of such a syndrome as well as disputes over the features initially described began to surface. The conundrum of whether MCTD is a distinct disease entity remains controversial. We undertook a literature review, focusing on the articles reporting new data about MCTD published in the last decade, to determine whether any new observations help to answer the conundrum of MCTD. After reviewing recent data, we question whether the term MCTD is appropriately retained, preferring to use the term undifferentiated autoimmune rheumatic disease.

Risk factors for AIDS-defining illnesses among a population of poorly adherent people living with HIV/AIDS in Atlanta, Georgia.

In order to achieve the programmatic goals established in the National HIV/AIDS Strategy, virologic suppression remains the most important outcome within the HIV care continuum for individuals receiving antiretroviral therapy (ART). Therefore, clinicians have dedicated substantial resources to improve adherence and clinic retention for individuals on ART; however, these efforts should be focused first on those most at risk of morbidity and mortality related to AIDS. Our study aimed to characterize the factors that are associated with AIDS-defining illnesses (ADIs) amongst people living with HIV (PLHIV) who are poorly adherent or retained in care in order to identify those at highest risk of poor clinical outcomes. We recruited 99 adult PLHIV with a history of poor adherence to ART, poor clinic attendance, or unsuppressed viral load (VL) from the Infectious Disease Program (IDP) of the Grady Health System in Atlanta, Georgia between January and May 2011 to participate in a survey investigating the acceptability of a financial incentive for improving adherence. Clinical outcomes including the number of ADI episodes in the last five years, VLs, and CD4 counts were abstracted from medical records. Associations between survey items and number of ADIs were performed using chi-square analysis. In our study, 36.4% of participants had ≥1 ADI in the last five years. The most common ADIs were Pneumocystis jirovecii pneumonia, recurrent bacterial pneumonia, and esophageal candidiasis. Age <42.5 years (OR 2.52, 95% CI = 1.08-5.86), male gender (OR 3.51, 95% CI = 1.08-11.34), CD4 nadir <200 cells/µL (OR 11.92, 95% CI = 1.51-94.15), unemployment (OR 3.54, 95% CI = 1.20-10.40), and travel time to clinic <30 minutes (OR 2.80, 95% CI = 1.20-6.52) were all significantly associated with a history of ≥1 ADI in the last five years. Awareness of factors associated with ADIs may help clinicians identify which poorly adherent PLHIV are at highest risk of HIV-related morbidity.

[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.

Occupational egg allergy in an embryological research facility.

BACKGROUND: Hen and quail eggs are commonly used in embryological research. While immunoglobin E (IgE)-associated allergy to hens' egg proteins is recognized in employees in the food industry, there are no previous reports from workers in embryological research. Two newly identified cases prompted us to examine the extent of this problem in a university laboratory. AIMS: To determine the prevalence and determinants of sensitization to egg among a group of workers in an embryological research laboratory. METHODS: Following the identification of egg sensitization in two research workers, we surveyed 116 employees from a single embryology research laboratory in 2005. Sensitization to egg was assessed by skin prick tests and/or specific IgE measurement and examined in relation to a number of potential determinants, including the extent of appropriate control measures. RESULTS: Four employees were sensitized to egg, each with digestive symptoms of egg allergy. All had worked directly with eggs, giving a prevalence of specific sensitization in that group of 6.1% (95% confidence interval (CI) [1.7%, 14.8%]). There was a statistically significant trend for those sensitized to report a shorter duration of exposure to eggs and less frequent use of hygiene control measures to reduce exposure. CONCLUSIONS: Sensitization to eggs among those occupationally exposed to egg protein in research work occurs more commonly than in the general population. The presence of digestive symptoms after eating eggs may be indicative of sensitization to egg and should be incorporated into health evaluation of exposed workers.

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.

[Linear IgA disease of the oral mucosa with pharyngeal and esophageal involvement]. / Lineare IgA-Erkrankung der Mundschleimhaut mit pharyngealer und ösophagealer Beteiligung.

A 69-year-old man presented with multiple recurrent oral ulcerations for about 20 years. After he began having difficulty in breathing and swallowing, esophagogastroscopy was performed and showed ulcerations, erosions and scars on the mucous membrane of the pharynx as well of the esophagus. Linear IgA disease (LAD) was diagnosed based on histopathological and immunofluorescence examinations. In this patient with LAD, the buccal, pharyngeal and esophageal mucosa was affected without involvement of the skin.

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.

A URA3 null mutant of Candida albicans (CAI-4) causes oro-oesophageal and gastric candidiasis and is lethal for gnotobiotic, transgenic mice (Tgepsilon26) that are deficient in both natural killer and T cells.

Current data suggest that functional URA3 genes are necessary for the full pathogenesis of Candida albicans. Herein it is shown that a putatively avirulent URA3/URA3 null mutant of C. albicans (CAI-4) can colonize the murine alimentary tract, invade oro-oesophageal and gastric tissues with yeasts and hyphae, evoke a granulocyte-dominated inflammatory response, and kill transgenic mice that are deficient for both natural killer cells and T cells. Because C. albicans-colonized (gnotobiotic) mice lack a viable prokaryotic microbiota, this study also demonstrates that the gut microbiome is not required to supply the mutant's nutritional needs. The gnotobiotic murine model described herein can be used to assess the capacity of C. albicans mutants to colonize and infect cutaneous, mucosal and systemic tissues and kill the susceptible host via a clinically common, natural route of infection; namely the alimentary tract.

Oesophageal pemphigoid: a rare cause of dysphagia.

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease which affects the skin and mucous membranes. Oesophageal involvement is rare and has previously been limited to case reports and case series. A recent large case series of 477 PV patients showed that 26/477 (5.4%) had symptomatic oesophageal involvement. We present the case of a 54-year-old Somalian lady with a 10-year history of cutaneous PV, currently in remission, who developed dysphagia and odynophagia and was subsequently found to have oesophageal PV involvement with multiple flaccid bullae which were positive for anti-DSG3 antibodies on in-direct immunofluorescence. She had her treatment switched from azathioprine to mycophenolate and prednisolone, leading to resolution of her symptoms.

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.

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.

The CREST syndrome: a distinct serologic entity with anticentromere antibodies.

The CREST syndrome is a variant of systemic sclerosis characterized by the presence of calcinosis. Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly and telangiectasia. The serums of 27 patients with the CREST syndrome have been examined for the presence of antinuclear antibodies. Twenty-six of 27 (98 percent) serums contained high titers (> one:80) of an antibody that produces a discrete speckled pattern of immunofluorescence on a human laryngeal carcinoma cell line (HEp-2). The antibody has been shown to react with the centromeric region of metaphase chromosomes. This antibody was also found in three of 14 patients with Raynaud's disease, in one of 60 patients with systemic lupus erythematosus, in three of 26 patients with systemic sclerosis with diffuse scleroderma and in one of 15 patients with mixed connective tissue disease. The antibody was not detected in the serums of patients with rheumatoid arthritis. Sjögren's sicca complex or linear scleroderma. Patients with osteoarthritis who were age- and sex-matched to the group with the CREST syndrome did not have anticentromere antibodies. Autoantibodies found in other connective tissue diseases (anti-DNA, anti-RNP, Sjögren's syndrome antigen B (anti-SS-B) were not found in serums from patients with the CREST syndrome. A case report illustrating the appearance of the anticentromere antibody at a time when Raynaud's phenomenon antedated the clinical diagnosis of CREST syndrome is presented.