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1
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Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases. Pathogens 2023; 12:pathogens12030456. [PMID: 36986378 PMCID: PMC10058615 DOI: 10.3390/pathogens12030456] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/09/2023] [Accepted: 03/09/2023] [Indexed: 03/17/2023] Open
Abstract
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases.
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2
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Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review. Pathogens 2023; 12:pathogens12020272. [PMID: 36839544 PMCID: PMC9958715 DOI: 10.3390/pathogens12020272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/13/2023] [Accepted: 02/04/2023] [Indexed: 02/10/2023] Open
Abstract
Enhanced susceptibility to microbes, often resulting in severe, intractable and frequent infections due to usually innocuous organisms at uncommon sites, is the most striking feature in individuals with an inborn error of immunity. In this narrative review, based on the International Union of Immunological Societies' 2022 (IUIS 2022) Update on phenotypic classification of human inborn errors of immunity, the focus is on commonly encountered Combined Immunodeficiency Disorders (CIDs) with susceptibility to infections. Combined immune deficiency disorders are usually commensurate with survival beyond infancy unlike Severe Combined Immune Deficiency (SCID) and are often associated with clinical features of a syndromic nature. Defective humoral and cellular immune responses result in susceptibility to a broad range of microbial infections. Although disease onset is usually in early childhood, mild defects may present in late childhood or even in adulthood. A precise diagnosis is imperative not only for determining management strategies, but also for providing accurate genetic counseling, including prenatal diagnosis, and also in deciding empiric treatment of infections upfront before investigation reports are available.
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3
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Miller CQ, Saeed OAM, Collins K. Gastrointestinal histoplasmosis complicating pediatric Crohn disease: A case report and review of literature. World J Gastrointest Endosc 2022; 14:648-656. [PMID: 36303809 PMCID: PMC9593511 DOI: 10.4253/wjge.v14.i10.648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 09/05/2022] [Accepted: 09/21/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Infection with Histoplasma capsulatum (H. capsulatum) can lead to disseminated disease involving the gastrointestinal tract presenting as diffuse abdominal pain and diarrhea which may mimic inflammatory bowel disease (IBD).
CASE SUMMARY We report a case of 12-year-old boy with presumptive diagnosis of Crohn disease (CD) that presented with several months of abdominal pain, weight loss and bloody diarrhea. Colonoscopy showed patchy moderate inflammation characterized by erythema and numerous pseudopolyps involving the terminal ileum, cecum, and ascending colon. Histologic sections from the colon biopsy revealed diffuse cellular infiltrate within the lamina propria with scattered histiocytic aggregates, and occasional non-necrotizing granulomas. Grocott-Gomori’s Methenamine Silver staining confirmed the presence of numerous yeast forms suggestive of Histoplasma spp., further confirmed with positive urine Histoplasma antigen (6.58 ng/mL, range 0.2-20 ng/mL) and serum immunoglobulin G antibodies to Histoplasma (35.9 EU, range 10.0-80.0 EU). Intravenous amphotericin was administered then transitioned to oral itraconazole. Follow-up computed tomography imaging showed a left lower lung nodule and mesenteric lymphadenopathy consistent with disseminated histoplasmosis infection.
CONCLUSION Gastrointestinal involvement with H. capsulatum with no accompanying respiratory symptoms is exceedingly rare and recognition is often delayed due to the overlapping clinical manifestations of IBD. This case illustrates the importance of excluding infectious etiologies in patients with “biopsy-proven” CD prior to initiating immunosuppressive therapies. Communication between clinicians and pathologists is crucial as blood cultures and antigen testing are key studies that should be performed in all suspected cases of histoplasmosis to avoid misdiagnosis and inappropriate treatment.
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Affiliation(s)
- C Quinn Miller
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Omer A M Saeed
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
| | - Katrina Collins
- Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, United States
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4
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MacInnes R, Warris A. Paediatric Histoplasmosis 2000-2019: A Review of 83 Cases. J Fungi (Basel) 2021; 7:jof7060448. [PMID: 34199970 PMCID: PMC8229079 DOI: 10.3390/jof7060448] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 05/31/2021] [Accepted: 06/01/2021] [Indexed: 12/22/2022] Open
Abstract
Histoplasmosis is an endemic fungal infection that is confined to specific geographical regions. Histoplasma spp. are primary pathogens that cause disease in both immunocompetent and immunocompromised patients, ranging from a single-organ (mostly affecting the lungs) infection to life-threatening disseminated disease. Knowledge about the clinical epidemiology relies on data from adult populations; little is known about the patient and disease characteristics in the paediatric population. Therefore, a structured review of published cases of paediatric histoplasmosis between 2000 and 2019 was performed. A literature search of PubMed was conducted and the epidemiological and clinical data from 83 cases were analysed. The mean age at presentation was 9.5 ± 5.5 years, and 51% were girls. Two-thirds of the children were immunocompromised. The majority of children presented with disseminated disease. The most frequently observed clinical symptoms were respiratory symptoms, alongside non-specific systemic features, including fever, myalgia, fatigue and weight loss. The mortality rate was 11%. Histoplasmosis affects children of any age. Being immunocompromised is a risk factor for severe and disseminated disease. The lack of specific presenting features leads to underreporting and delay in diagnosis. To improve the recognition and outcome of histoplasmosis in childhood, increased awareness and surveillance systems are warranted.
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Affiliation(s)
- Rebecca MacInnes
- Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK;
| | - Adilia Warris
- Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK;
- MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter 4EX 4QD, UK
- Correspondence: ; Tel.: +44-1392-727593
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5
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Lee PP, Lao-Araya M, Yang J, Chan KW, Ma H, Pei LC, Kui L, Mao H, Yang W, Zhao X, Trakultivakorn M, Lau YL. Application of Flow Cytometry in the Diagnostics Pipeline of Primary Immunodeficiencies Underlying Disseminated Talaromyces marneffei Infection in HIV-Negative Children. Front Immunol 2019; 10:2189. [PMID: 31572394 PMCID: PMC6753679 DOI: 10.3389/fimmu.2019.02189] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 08/30/2019] [Indexed: 12/19/2022] Open
Abstract
Talaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations.
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Affiliation(s)
- Pamela P Lee
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,Department of Pediatrics, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Mongkol Lao-Araya
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Chiang Mai University, Chiang Mai, Thailand
| | - Jing Yang
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Koon-Wing Chan
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Haiyan Ma
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Lim-Cho Pei
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Lin Kui
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Huawei Mao
- Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Wanling Yang
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Xiaodong Zhao
- Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Muthita Trakultivakorn
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Chiang Mai University, Chiang Mai, Thailand
| | - Yu-Lung Lau
- Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.,Department of Pediatrics, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
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6
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Nehme F, Rowe K, El Hawari M, Assi M, Nassif I. Gastrointestinal histoplasmosis ileal stricture successfully treated with through-the-scope balloon dilation in a patient with hyperimmunoglobulin M syndrome. Clin J Gastroenterol 2018; 11:224-228. [DOI: 10.1007/s12328-018-0817-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2017] [Accepted: 01/08/2018] [Indexed: 11/29/2022]
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7
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Lee PP, Lau YL. Cellular and Molecular Defects Underlying Invasive Fungal Infections-Revelations from Endemic Mycoses. Front Immunol 2017; 8:735. [PMID: 28702025 PMCID: PMC5487386 DOI: 10.3389/fimmu.2017.00735] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 06/09/2017] [Indexed: 01/29/2023] Open
Abstract
The global burden of fungal diseases has been increasing, as a result of the expanding number of susceptible individuals including people living with human immunodeficiency virus (HIV), hematopoietic stem cell or organ transplant recipients, patients with malignancies or immunological conditions receiving immunosuppressive treatment, premature neonates, and the elderly. Opportunistic fungal pathogens such as Aspergillus, Candida, Cryptococcus, Rhizopus, and Pneumocystis jiroveci are distributed worldwide and constitute the majority of invasive fungal infections (IFIs). Dimorphic fungi such as Histoplasma capsulatum, Coccidioides spp., Paracoccidioides spp., Blastomyces dermatiditis, Sporothrix schenckii, Talaromyces (Penicillium) marneffei, and Emmonsia spp. are geographically restricted to their respective habitats and cause endemic mycoses. Disseminated histoplasmosis, coccidioidomycosis, and T. marneffei infection are recognized as acquired immunodeficiency syndrome (AIDS)-defining conditions, while the rest also cause high rate of morbidities and mortalities in patients with HIV infection and other immunocompromised conditions. In the past decade, a growing number of monogenic immunodeficiency disorders causing increased susceptibility to fungal infections have been discovered. In particular, defects of the IL-12/IFN-γ pathway and T-helper 17-mediated response are associated with increased susceptibility to endemic mycoses. In this review, we put together the various forms of endemic mycoses on the map and take a journey around the world to examine how cellular and molecular defects of the immune system predispose to invasive endemic fungal infections, including primary immunodeficiencies, individuals with autoantibodies against interferon-γ, and those receiving biologic response modifiers. Though rare, these conditions provide importance insights to host defense mechanisms against endemic fungi, which can only be appreciated in unique climatic and geographical regions.
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Affiliation(s)
- Pamela P Lee
- LKS Faculty of Medicine, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Yu-Lung Lau
- LKS Faculty of Medicine, Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.,Shenzhen Primary Immunodeficiencies Diagnostic and Therapeutic Laboratory, The University of Hong Kong-Shenzhen Hospital (HKU-SZH), Shenzhen, China
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8
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Hashemi H, Mohebbi M, Mehravaran S, Mazloumi M, Jahanbani-Ardakani H, Abtahi SH. Hyperimmunoglobulin E syndrome: Genetics, immunopathogenesis, clinical findings, and treatment modalities. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2017; 22:53. [PMID: 28567072 PMCID: PMC5426098 DOI: 10.4103/jrms.jrms_1050_16] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 01/23/2017] [Accepted: 01/30/2017] [Indexed: 11/16/2022]
Abstract
The hyperimmunoglobulin E syndromes (HIESs) are very rare immunodeficiency syndromes with multisystem involvement, including immune system, skeleton, connective tissue, and dentition. HIES are characterized by the classic triad of high serum levels of immunoglobulin E (IgE), recurrent staphylococcal cold skin abscess, and recurrent pneumonia with pneumatocele formation. Most cases of HIES are sporadic although can be inherited as autosomal dominant and autosomal recessive traits. A fundamental immunologic defect in HIES is not clearly elucidated but abnormal neutrophil chemotaxis due to decreased production or secretion of interferon γ has main role in the immunopathogenesis of syndrome, also distorted Th1/Th2 cytokine profile toward a Th2 bias contributes to the impaired cellular immunity and a specific pattern of infection susceptibility as well as atopic-allergic constitution of syndrome. The ophthalmic manifestations of this disorder include conjunctivitis, keratitis, spontaneous corneal perforation, recurrent giant chalazia, extensive xanthelasma, tumors of the eyelid, strabismus, and bilateral keratoconus. The diagnosis of HIES is inconclusive, dependent on the evolution of a constellation of complex multisystemic symptoms and signs which develop over the years. Until time, no treatment modality is curative for basic defect in HIES, in terms of cytokines/chemokines derangement. Of note, bone marrow transplant and a monoclonal anti-IgE (omalizumab) are hoped to be successful treatment in future.
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Affiliation(s)
- Hassan Hashemi
- Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.,Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Mohebbi
- Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.,Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Shiva Mehravaran
- Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran.,Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, USA
| | - Mehdi Mazloumi
- Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamidreza Jahanbani-Ardakani
- Isfahan Eye Research Center, Feiz Eye Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.,Isfahan Medical Students Research Center (IMSRC), Isfahan University of Medical Sciences, Isfahan, Iran
| | - Seyed-Hossein Abtahi
- Isfahan Eye Research Center, Feiz Eye Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.,Isfahan Medical Students Research Center (IMSRC), Isfahan University of Medical Sciences, Isfahan, Iran.,Department of Ophthalmology, Feiz Eye Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
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9
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Abstract
Elevated serum IgE has many etiologies including parasitic infection, allergy and asthma, malignancy, and immune dysregulation. The hyper-IgE syndromes caused by mutations in STAT3, DOCK8, and PGM3 are monogenic primary immunodeficiencies associated with high IgE, eczema, and recurrent infections. These primary immunodeficiencies are associated with recurrent pneumonias leading to bronchiectasis; however, each has unique features and genetic diagnosis is essential in guiding therapy, discussing family planning, and defining prognosis. This article discusses the clinical features of these primary immunodeficiencies with a particular focus on the pulmonary manifestations and discussion of the genetics, pathogenesis, and approaches to therapy.
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Affiliation(s)
- Alexandra F Freeman
- Laboratory of Clinical Infectious Diseases, NIAID, NHLBI, National Institutes of Health, Bethesda, MD, USA.
| | - Kenneth N Olivier
- Laboratory of Clinical Infectious Diseases, NIAID, NHLBI, National Institutes of Health, Bethesda, MD, USA
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10
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11
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Odio CD, Milligan KL, McGowan K, Rudman Spergel AK, Bishop R, Boris L, Urban A, Welch P, Heller T, Kleiner D, Jackson MA, Holland SM, Freeman AF. Endemic mycoses in patients with STAT3-mutated hyper-IgE (Job) syndrome. J Allergy Clin Immunol 2015; 136:1411-3.e1-2. [PMID: 26292779 PMCID: PMC4641001 DOI: 10.1016/j.jaci.2015.07.003] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 06/17/2015] [Accepted: 07/03/2015] [Indexed: 01/17/2023]
Affiliation(s)
- Camila D Odio
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md
| | - Ki Lee Milligan
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md
| | - Katherine McGowan
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md
| | - Amanda K Rudman Spergel
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md
| | | | - Lisa Boris
- Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick, Md
| | - Amanda Urban
- Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick, Md
| | - Pamela Welch
- Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick, Md
| | - Theo Heller
- National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Md
| | | | | | - Steven M Holland
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md
| | - Alexandra F Freeman
- National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, Md.
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12
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Romano RC, Soape MM, Thirumala S, Ghandour E. Disseminated histoplasmosis mimicking metastatic disease of the colon and omentum: Report of a case and literature review. Arab J Gastroenterol 2015. [DOI: 10.1016/j.ajg.2015.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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13
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14
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Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K. The hyperimmunoglobulin E syndrome--clinical manifestation diversity in primary immune deficiency. Orphanet J Rare Dis 2011; 6:76. [PMID: 22085750 PMCID: PMC3226432 DOI: 10.1186/1750-1172-6-76] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2011] [Accepted: 11/15/2011] [Indexed: 11/10/2022] Open
Abstract
The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities - the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impaired Th17 cells differentiation and to a downregulation of an antimicrobial response. A mutation in the dedicator of the cytokinesis 8 gene has been identified as the cause of many cases with autosomal recessive hyper-IgE syndrome and, in one patient, a mutation in tyrosine kinase 2 gene has been demonstrated. In this paper, the authors provide a review of the clinical manifestations in the hyper-IgE syndromes with particular emphasis on the diversity of their phenotypic expression and present current diagnostic guidelines for these diseases.
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Affiliation(s)
- Aleksandra Szczawinska-Poplonyk
- Department of Pediatric Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, 27/33 Szpitalna Street, Poznan, Poland.
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15
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Vinh DC. Insights into human antifungal immunity from primary immunodeficiencies. THE LANCET. INFECTIOUS DISEASES 2011; 11:780-92. [PMID: 21958581 DOI: 10.1016/s1473-3099(11)70217-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Some mendelian (monogenic) disorders directly conferring increased susceptibility are associated with diverse infectious organisms, whereas others are restricted in scope to specific genera or even to one species. So far, most investigations of primary immunodeficiency disorders have focused on those conferring susceptibility to viral, bacterial, or mycobacterial infections, providing powerful insight into human determinants of host resistance to these microbes. Monogenic disorders that increase susceptibility to fungal infections are increasingly being recognised. Although infections associated with these disorders are probably less common than are iatrogenic associated mycoses, they provide valuable insight into human immunity to fungal infections. Investigation of these immunological pathways will ultimately lead to improvements in management of such infections in secondarily immunocompromised patients.
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Affiliation(s)
- Donald C Vinh
- Infectious Disease Susceptibility Program, Division of Infectious Diseases and Division of Immunology, Department of Medicine, McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada.
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16
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Abstract
Autosomal dominant hyperimmunoglobulin E syndrome (HIES, or Job syndrome) is a rare primary immunodeficiency characterized by elevated immunoglobulin E (IgE), eosinophilia, recurrent skin and pulmonary infections, dermatitis, and connective tissue and skeletal abnormalities. A 26-year-old male with known HIES presented with abdominal pain and diarrhea. Imaging showed sigmoid diverticulitis without abscess or perforation. Conservative management with antibiotics failed, and he developed a peridiverticular abscess, which was percutaneously drained with plans for elective resection. He returned four days later with progression of his diverticulitis, requiring partial colectomy with primary anastomosis. To our knowledge, this is the first case of diverticulitis in HIES. Diverticulitis is rare in younger individuals, raising the possibility that the connective tissue abnormalities of HIES patients may predispose them to colonic diverticula. Although the majority of complications are sinopulmonary and skin infections, diverticulitis should be considered in the differential of intra-abdominal processes in HIES.
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17
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Abstract
Intestinal biopsies constitute an ever-increasing portion of the pathologist's workload, accounting for nearly two-thirds of specimens accessioned yearly by the pathology department at The Children's Hospital of Philadelphia. The widespread use of endoscopy and gastrointestinal biopsies in current clinical practice presents the pathologist with a diversity of intestinal mucosal appearances corresponding to disease states of variable clinical severity, requiring close collaboration between clinician and pathologist for optimal interpretation. Many of the entities resulting in severe diarrhea of infancy have been recognized only in the last several decades, and although rare, the study of these disorders, especially when combined with the powerful methods of present-day genetics and molecular biology, has afforded important insights into enterocyte development and function, and intestinal immunity and tolerance. Other conditions once considered infrequent, such as celiac disease, have now been recognized to be much more common and can present with a wide range of pathologic features.
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Affiliation(s)
- Pierre Russo
- Department of Pathology and Laboratory Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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18
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Abstract
We describe a 14-year-old girl with hyperimmunoglobulin E (Job) syndrome who presented with fatigue, abdominal pain, fever, and weight loss. Endoscopic examination of the terminal ileum revealed ulceration, edema, and erythema. Histopathologic findings of the terminal ileum demonstrated intracellular yeast forms compatible with Histoplasma capsulatum. The patient was treated with oral itraconazole and had a rapid and complete response.
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19
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Magno P, DE Jesus-Aponte R, Vazquez GJ, Garrastegui D, Torres EA. Abdominal pain and weight loss in an HIV-infected patient. J Dig Dis 2008; 9:48-51. [PMID: 18251794 DOI: 10.1111/j.1443-9573.2007.00317.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Priscilla Magno
- Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland, USA.
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20
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Antachopoulos C, Walsh TJ, Roilides E. Fungal infections in primary immunodeficiencies. Eur J Pediatr 2007; 166:1099-117. [PMID: 17551753 DOI: 10.1007/s00431-007-0527-7] [Citation(s) in RCA: 140] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2007] [Revised: 05/11/2007] [Accepted: 05/19/2007] [Indexed: 12/17/2022]
Abstract
Patients with phagocytic, cellular, combined and other primary immunodeficiencies exhibit immune deficits that confer increased susceptibility to fungal infections. A number of yeasts and moulds, most commonly Candida and Aspergillus but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon, Penicillium and other, rarely isolated, fungal organisms, have been variably implicated in causing disease in patients with chronic granulomatous disease, severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency. Differences in the spectrum of fungal pathogens as well as in the incidence and clinical presentation of the infections may be observed among patients, depending upon different immune disorders. Fungal infections in these individuals may occasionally be the presenting clinical manifestation of a primary immunodeficiency and can cause significant morbidity and potentially fatal outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and establishment of diagnosis should actively be pursued using appropriate imaging, mycological and histological studies. A number of antifungal agents introduced over the last fifteen years, such as the lipid formulations of amphotericin B, the second-generation triazoles, and the echinocandins, increase the options for medical management of these infections. Surgery may also be needed in some cases, while the role of adjunctive immunotherapy has not been systematically evaluated. The low incidence of primary immunodeficiencies in the general population complicates single-center prospective or retrospective clinical studies aiming to address diagnostic or therapeutic issues pertaining to fungal infections in these patients.
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Affiliation(s)
- Charalampos Antachopoulos
- Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA
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DeWitt CA, Bishop AB, Buescher LS, Stone SP. Hyperimmunoglobulin E syndrome: Two cases and a review of the literature. J Am Acad Dermatol 2006; 54:855-65. [PMID: 16635666 DOI: 10.1016/j.jaad.2005.10.022] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2005] [Revised: 10/10/2005] [Accepted: 10/18/2005] [Indexed: 11/18/2022]
Abstract
Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month-old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.
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Affiliation(s)
- Christine A DeWitt
- Division of Dermatology, Southern Illinois University School of Medicine, Springfield, Illinois, USA
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22
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Oh YS, Lisker-Melman M, Korenblat KM, Zuckerman GR, Crippin JS. Disseminated histoplasmosis in a liver transplant recipient. Liver Transpl 2006; 12:677-81. [PMID: 16555316 DOI: 10.1002/lt.20742] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
A 61-yr-old liver transplant recipient presented with abdominal cramping and nonbloody diarrhea resulting in orthostasis. Multiple ulcerations throughout the colon were seen during endoscopy, and biopsies from the ulcer edges revealed histoplasmosis. Treatment with a course of itraconazole improved the diarrhea. The patient later presented with pericarditis and symptomatic pleural effusions, the latter of which was confirmed to be a result of disseminated histoplasmosis. Treatment with amphotericin B led to resolution. Histoplasmosis should be considered in liver transplant patients with diarrhea and large ulcers in the colon. The presence of disseminated histoplasmosis should be ruled out once colonic histoplasmosis has been diagnosed.
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Affiliation(s)
- Young S Oh
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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23
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Zerbe CS, Holland SM. Disseminated histoplasmosis in persons with interferon-gamma receptor 1 deficiency. Clin Infect Dis 2005; 41:e38-41. [PMID: 16028145 DOI: 10.1086/432120] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2005] [Accepted: 04/12/2005] [Indexed: 11/03/2022] Open
Abstract
Mutations in the interferon (IFN)-gamma receptor predispose to infection with bacille Calmette-Guérin, nontuberculous mycobacteria, and Salmonella organisms. We identified a patient with recurrent disseminated Histoplasma capsulatum osteomyelitis who had an autosomal dominant form of IFN-gamma receptor 1 deficiency (i.e., a 4-bp deletion at or near base 818). IFN-gamma-mediated immunity is important in the control of histoplasmosis.
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Affiliation(s)
- Christa S Zerbe
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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Jani JC, Brown R, Kajdacsy-Balla A, Guzman G. Pathologic Quiz Case: A Woman With Human Immunodeficiency Virus With Right Lower Quadrant Pain and Ascending Colon Mass. Arch Pathol Lab Med 2005; 129:259-61. [DOI: 10.5858/2005-129-259-pqcaww] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Jigna C. Jani
- From the Departments of Pathology (Drs Jani, Kajdacsy-Balla, and Guzman) and Gastroenterology (Dr Brown), University of Illinois at Chicago
| | - Russell Brown
- From the Departments of Pathology (Drs Jani, Kajdacsy-Balla, and Guzman) and Gastroenterology (Dr Brown), University of Illinois at Chicago
| | - Andre Kajdacsy-Balla
- From the Departments of Pathology (Drs Jani, Kajdacsy-Balla, and Guzman) and Gastroenterology (Dr Brown), University of Illinois at Chicago
| | - Grace Guzman
- From the Departments of Pathology (Drs Jani, Kajdacsy-Balla, and Guzman) and Gastroenterology (Dr Brown), University of Illinois at Chicago
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Abstract
The hyper-immunoglobulin E (IgE) syndromes (HIES) are primary immunodeficiencies characterized by the clinical triad of recurrent staphylococcal abscesses, recurrent cyst-forming pneumonia, and an elevated serum IgE level of >2000 IU/ml. Most cases are sporadic; however, multiplex families displaying autosomal dominant (AD) and autosomal recessive (AR) inheritance have been described. In most sporadic and AD cases, the HIES clinical triad is part of a multisystem disorder including abnormalities of the soft tissue, skeletal, and dental systems. In contrast, those with AR-HIES have severe molluscum contagiosum and other viral infections and may develop severe neurological complications. Unlike patients with sporadic HIES and AD-HIES, those with AR-HIES lack skeletal or dental involvement and do not develop lung cysts. Additional variants of HIES are discussed in this review. The etiology of HIES is still unresolved. Recent research points toward a skewed T helper 1 (Th1) cell/Th2 cell ratio and the involvement of chemokines. Therapy for HIES is directed at prevention and management of infections by using sustained systemic antibiotics and antifungals along with topical therapy for eczema and drainage of abscesses. Anti-staphylococcal antibiotic prophylaxis is useful. Interferons, immunoglobulin supplementation, or low-dose cyclosporine A have been reported to benefit selected patients, but they are not generally indicated.
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Affiliation(s)
- Bodo Grimbacher
- Department Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Freiburg, Germany.
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26
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Abstract
Gastrointestinal histoplasmosis (GIH) is an uncommon disease with protean manifestations. It may occur as a result of mediastinal histoplasmosis or in the setting of progressive dissemination. GIH may be misdiagnosed as inflammatory bowel disease, malignancy, or other intestinal diseases leading to inappropriate therapies and unnecessary surgical interventions. Patients with bowel obstruction, perforation, or bleeding, and systemic findings suggestive of histoplasmosis should be evaluated for GIH. This is especially true for immunosuppressed patients, especially those with AIDS. Diagnosis first requires consideration of histoplasmosis in the differential in patients with the above types of gastrointestinal abnormalities, and second, familiarity with a battery of mycologic and serologic tests. Progressive disseminated histoplasmosis (PDH) is lethal if left untreated, and treatment is highly effective. This review will focus on the clinical and histopathologic features of GIH, the approach to diagnosis, and recommendations for treatment.
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Affiliation(s)
- Charles J Kahi
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University Medical Center, UH 4100, 550 N. University Boulevard, Indianapolis, IN 46202, USA
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27
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Lee JT, Dixon MR, Murrell Z, Konyalian V, Agbunag R, Rostami S, French S, Kumar RR. Colonic Histoplasmosis Presenting as Colon Cancer in the Nonimmunocotnpromised Patient: Report of a Case and Review of the Literature. Am Surg 2004. [DOI: 10.1177/000313480407001105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Histoplasma capsulatum is an important pathogen that is the most commonly diagnosed endemic mycosis in the gastrointestinal tract of immunocompromised hosts. Failure to recognize and treat disseminated histoplasmosis in AIDS patients invariably leads to death. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, and depending on the layer of bowel wall involved present as bleeding, obstruction, perforation, or peritonitis. Because they can be variable in appearance, they may be mistaken for Crohn's disease or malignant tumors. Four distinct pathologic patterns of GI histoplasmosis have been described that all have differing clinical presentations. We report a case of a non-AIDS patient who presented with a near-obstructing colonic mass suspicious for advanced malignancy but was found to have histoplasmosis on final pathology. The patient underwent successful operative resection, systemic antifungal therapy, and extensive workup for immunosuppressive disorders, which were negative. The patient was from an area in Mexico known to be endemic for histoplasmosis. This is the first report of a colonic mass lesion occurring in a non-AIDS patient, and review of the worldwide literature regarding GI histoplasmosis reveals excellent long-term survival with aggressive therapy. We discuss the surgical and medical management of colonic histoplasmosis in this report.
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Affiliation(s)
- Jason T. Lee
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Matthew R. Dixon
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Zuri Murrell
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Viken Konyalian
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Rodolfo Agbunag
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Sassan Rostami
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, California
| | - Samuel French
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, California
| | - Ravin R. Kumar
- Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
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Hertan H, Nair S, Arguello P. Progressive gastrointestinal histoplasmosis leading to colonic obstruction two years after initial presentation. Am J Gastroenterol 2001; 96:221-2. [PMID: 11197256 DOI: 10.1111/j.1572-0241.2001.03479.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A 37-yr-old man from Ecuador presented with abdominal pain, diarrhea, and weight loss. Endoscopy revealed duodenal histoplasmosis. The patient improved with antifungal therapy but was readmitted 2 yr later with diarrhea and fever. Colonoscopy revealed histoplasmosis lesions, including a constricting transverse colon lesion. The patient refused surgery and died of colonic perforation. We discuss the diagnosis and management of gastrointestinal histoplasmosis in this report.
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Affiliation(s)
- H Hertan
- Division of Gastroenterology, Our Lady of Mercy Medical Center, New York Medical College, Bronx 10466, USA
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Kane S, Brasitus T. Histoplasmosis capsulatum as a cause of lower gastrointestinal bleeding in common variable immunodeficiency. Dig Dis Sci 2000; 45:2133-5. [PMID: 11215727 DOI: 10.1023/a:1026680317424] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Infection with Histoplasma capsulatum is the most common systemic fungal infection in the United States, but symptomatic gastrointestinal disease is rare. Gastrointestinal involvement is seen in patients with an established immunosuppressed state that predates any infection. We report a patient presenting with gastrointestinal bleeding ultimately diagnosed with disseminated histoplasmosis. Work-up led to the diagnosis of common variable immunodeficiency, a diagnosis not previously described as associated with gastrointestinal histoplasmosis. Resolution of the colonic ulcer was documented after appropriate antifungal therapy, underscoring the importance of including this infectious process in the differential of a patient without other risk factors for colonic ulceration.
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Affiliation(s)
- S Kane
- The University of Chicago Hospitals, Illinois, USA
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30
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Abstract
Colon perforation from hyperimmunoglobulin E syndrome is very rare, and only one case has been reported in the English-language literature. Herein, the authors report another case of colon perforation experienced in hyperimmunoglobulin E syndrome. The patient was an 8-year-old girl with frequent infection, eczematoid dermatitis, and an increased serum level of immunoglobulin E. During admission, panperitonitis developed caused by colon perforation. Treatment was resection of the perforated segment of the colon and a double-barrel colostomy. The patient has been doing well 18 months after treatment.
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Affiliation(s)
- E H Hwang
- Department of Pediatric Surgery and Pathology, Yonsei University College of Medicine, Seoul, Korea
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31
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Misago N, Tanaka T, Takeuchi M, Oka S. Necrotizing fasciitis in association with hyperimmunoglobulin E syndrome. J Dermatol 1995; 22:673-6. [PMID: 8537554 DOI: 10.1111/j.1346-8138.1995.tb03896.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A case of necrotizing fasciitis in association with hyperimmunoglobulin E (HIE) syndrome is reported. The patient was a 17-year-old Japanese boy with a clinical history of recurrent skin and pulmonary infections and eczematoid dermatitis, markedly elevated serum levels of IgE, and coarse facies. He had a gangrenous swelling on the lower abdominal wall, and his general condition was poor with high fever. The involved site was accompanied by subcutaneous gas; the culture of the pus of the lesion grew anaerobes without mixed growth of Staphylococcus aureus. Exhaustive debridement of necrotic fascia, which extended much farther than the gangrenous area, and administration of antibiotics had a curative effect on the gangrenous soft tissue infection. To the best of the authors' knowledge, this is the first published case of necrotizing fasciitis in association with HIE syndrome.
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Affiliation(s)
- N Misago
- Department of Dermatology, Sasebo Kyosai Hospital, Japan
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32
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Marshall JB, Singh R, Demmy TL, Bickel JT, Everett ED. Mediastinal histoplasmosis presenting with esophageal involvement and dysphagia: case study. Dysphagia 1995; 10:53-8. [PMID: 7859535 DOI: 10.1007/bf00261282] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Esophageal involvement with histoplasmosis is uncommon, but has been recognized in two clinical settings. Most commonly, the esophagus becomes involved as a result of contiguous mediastinal lymphadenopathy. Such patients usually present with dysphagia secondary to midesophageal compression or stricture. The esophagus can also be involved in cases of disseminated histoplasmosis. Esophageal ulcers or nodular lesions are the usual clinical manifestations in this setting. We report a case of mediastinal histoplasmosis with esophageal narrowing and mucosal ulceration that presented with dysphagia. The diagnosis was established at thoracotomy by the histologic finding of necrotizing granulomas and a positive fungal stain. The case was successfully treated with amphotericin B. The literature on esophageal and gastrointestinal histoplasmosis is reviewed.
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Affiliation(s)
- J B Marshall
- Department of Medicine, University of Missouri School of Medicine, Columbia 65212
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PACINI DAVIDL, FRIEDMAN ROGERA, BRADY MICHAELT, SHANNON BARRYT, QUALMAN STEPHENJ, ANDERSON DONALDC. Pneumocystis cariniiPneumonia in an Infant with the Hyperimmunoglobulinemia E Syndrome*. ACTA ACUST UNITED AC 1989. [DOI: 10.1089/pai.1989.3.21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Abstract
Three cases are reported of gastrointestinal histoplasmosis in patients who came from the Caribbean or South America and had lymphoma, acquired immunodeficiency syndrome, and prior local radiation therapy. The patients had small-bowel obstruction with ileal involvement, mucosal erythema, and friability on colonoscopy with colonic involvement and an exophytic rectal mass with rectal involvement. Review of the 77 reported cases of gastrointestinal histoplasmosis shows that this is a clinical subset of disseminated histoplasmosis. With gastrointestinal involvement, pulmonary symptoms are uncommon and gastrointestinal symptoms predominate. Fever is less common than in other forms of dissemination. The most common lesions are a mass or ulcers, which often mimic inflammatory bowel disease or carcinoma. Terminal ileal involvement predominates in one third. The complement fixation test was positive in about three quarters of cases tested, but the skin test is not diagnostically useful. In one quarter of patients there is other evidence of immunosuppression. In the immunosuppressed, gastrointestinal histoplasmosis must be considered, even in a patient from a nonendemic area, who presents with lesions appearing like carcinoma or inflammatory bowel disease. When feasible, endoscopic examination and biopsy with stains and culture for histoplasmosis is recommended for diagnosis. Medical management is recommended, with surgery reserved for acute emergencies or when mandatory for diagnosis.
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Affiliation(s)
- M S Cappell
- Department of Medicine, Albert Einstein College of Medicine, New York, New York 10461
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35
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Hutto JO, Bryan CS, Greene FL, White CJ, Gallin JI. Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Gastroenterology 1988; 94:808-12. [PMID: 3338649 DOI: 10.1016/0016-5085(88)90257-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
A 29-yr-old woman presenting with granulomatous colitis and a chronic perirectal abscess was found to have localized cryptococcosis associated with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome. Similarity to previous cases of esophageal cryptococcosis and ileocecal histoplasmosis suggests an association between the hyperimmunoglobulinemia E-recurrent infection syndrome and localized fungal infections of the alimentary tract. To our knowledge, this is the first well-documented case of cryptococcosis confined to the colon and perirectal tissues.
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Affiliation(s)
- J O Hutto
- University of South Carolina School of Medicine, Columbia
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