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1
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Campbell AP, Qiu L, Dillman JR, Trout AT, Szabo S, Lopez-Nunez OF, Pugmire BS, Schapiro AH. Endemic mycoses in children in North America: a review of radiologic findings. Pediatr Radiol 2023; 53:984-1004. [PMID: 36922418 PMCID: PMC10017348 DOI: 10.1007/s00247-023-05636-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 02/17/2023] [Accepted: 02/17/2023] [Indexed: 03/18/2023]
Abstract
Clinically significant endemic mycoses (fungal infections) in the United States (U.S.) include Blastomyces dermatitidis, Histoplasma capsulatum, and Coccidioides immitis/posadasii. While the majority of infections go clinically unnoticed, symptomatic disease can occur in immunocompromised or hospitalized patients, and occasionally in immune-competent individuals. Clinical manifestations vary widely and their diagnosis may require fungal culture, making the rapid diagnosis a challenge. Imaging can be helpful in making a clinical diagnosis prior to laboratory confirmation, as well as assist in characterizing disease extent and severity. In this review, we discuss the three major endemic fungal infections that occur in the U.S., including mycology, epidemiology, clinical presentations, and typical imaging features with an emphasis on the pediatric population.
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Affiliation(s)
- Abraham P Campbell
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
| | - Lisa Qiu
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
| | - Jonathan R Dillman
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Andrew T Trout
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Sara Szabo
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Oscar F Lopez-Nunez
- Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Brian S Pugmire
- Department of Radiology, Rady Children's Hospital San Diego, San Diego, CA, USA
| | - Andrew H Schapiro
- Department of Radiology, MLC 5031, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
- Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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2
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Ekeng BE, Itam-Eyo AE, Osaigbovo II, Warris A, Oladele RO, Bongomin F, Denning DW. Gastrointestinal Histoplasmosis: A Descriptive Review, 2001-2021. Life (Basel) 2023; 13:689. [PMID: 36983844 PMCID: PMC10051669 DOI: 10.3390/life13030689] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/15/2023] [Accepted: 02/27/2023] [Indexed: 03/08/2023] Open
Abstract
Gastrointestinal histoplasmosis (GIH) is infrequently described in people without underlying HIV infection. We aimed to compare the clinical presentation of GIH in people with and without HIV infection. We conducted a literature search of published cases of GIH from 2001-2021 and found 212 cases. Of these, 142 (67.0%) were male, and 124 (58.5%) had HIV infection. Most cases were from North America (n = 88, 41.5%) and South America (n = 79, 37.3%). Of the 212 cases, 123 (58.0%) were included in both clinical and pathological analyses. The remainder were excluded as details about clinical and pathological findings were not available. Of the 123 cases, 41 had HIV infection while 82 were without HIV infection. The diagnosis was predominantly by histopathology (n = 109, 88.6%). A significant proportion of people with HIV infection had abdominal pain as the most predominant symptom of GIH compared to those without HIV infection (65.9% versus 41.9%, p < 0.05). The colon was the most affected site with a slightly higher proportion in those with HIV infection compared with cases without HIV infection (46.3% versus 42.7%). The commonest pathologic findings were caecal and ileal ulcers. Caecal ulcers were significantly more frequent in cases with HIV infection compared to those without HIV (32.1% versus 7.1%, p < 0.05). Despite being more common in people with HIV infection, GIH also affects people without HIV infection with similar clinical presentations.
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Affiliation(s)
- Bassey E. Ekeng
- Medical Mycology Society of Nigeria, Lagos 101017, Nigeria
- Department of Medical Microbiology and Parasitology, University of Calabar Teaching Hospital, Calabar 540271, Nigeria
| | - Asa E. Itam-Eyo
- Department of Internal Medicine, University of Calabar Teaching Hospital, Calabar 540271, Nigeria
| | - Iriagbonse I. Osaigbovo
- Medical Mycology Society of Nigeria, Lagos 101017, Nigeria
- Department of Medical Microbiology, School of Medicine, College of Medical Sciences, University of Benin, Benin City 300213, Nigeria
| | - Adilia Warris
- Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter EX4 4QD, UK
| | - Rita O. Oladele
- Medical Mycology Society of Nigeria, Lagos 101017, Nigeria
- Department of Medical Microbiology and Parasitology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos 101017, Nigeria
| | - Felix Bongomin
- Department of Medical Microbiology & Immunology, Faculty of Medicine, Gulu University, Gulu P.O. Box 166, Uganda
| | - David W. Denning
- Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
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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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Histoplasmosis in Children; HIV/AIDS Not a Major Driver. J Fungi (Basel) 2021; 7:jof7070530. [PMID: 34209280 PMCID: PMC8305925 DOI: 10.3390/jof7070530] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Revised: 06/24/2021] [Accepted: 06/25/2021] [Indexed: 12/31/2022] Open
Abstract
The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, several cases of histoplasmosis were documented both in the pediatric and adult populations. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939-2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), Hyper immunoglobulin M and E syndromes (n = 15, 1.2%), pancytopenia (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.
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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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6
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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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7
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Arora M, Bagi P, Strongin A, Heimall J, Zhao X, Lawrence MG, Trivedi A, Henderson C, Hsu A, Quezado M, Kleiner DE, Venkatesan AM, Holland SM, Freeman AF, Heller T. Gastrointestinal Manifestations of STAT3-Deficient Hyper-IgE Syndrome. J Clin Immunol 2017; 37:695-700. [PMID: 28803389 DOI: 10.1007/s10875-017-0429-z] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 08/01/2017] [Indexed: 12/13/2022]
Abstract
OBJECTIVE STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations. We sought to describe the gastrointestinal (GI) manifestations of this disease. METHODS Seventy subjects aged five to 60 years with a molecular diagnosis of AD-HIES were evaluated at the National Institutes of Health (NIH). Data collection involved a GI symptom questionnaire and retrospective chart review. RESULTS In our cohort of 70 subjects, we found that 60% had GI symptoms (42/70). The most common manifestations were gastroesophageal reflux disease (GERD) observed in 41%, dysphagia in 31%, and abdominal pain in 24%. The most serious complications were food impaction in 13% and colonic perforation in 6%. Diffuse esophageal wall thickening in 74%, solid stool in the right colon in 50% (12/24), and hiatal hernia in 26% were the most prevalent radiologic findings. Esophagogastroduodenoscopy (EGD) demonstrated esophageal tortuosity in 35% (8/23), esophageal ulceration in 17% (4/23), esophageal strictures requiring dilation in 9% (2/23), and gastric ulceration in 17% (4/23). Esophageal eosinophilic infiltration was an unexpected histologic finding seen in 65% (11/17). CONCLUSION The majority of AD-HIES subjects develop GI manifestations as part of their disease. Most notable are the symptoms and radiologic findings of GI dysmotility, as well as significant eosinophilic infiltration, concerning for a secondary eosinophilic esophagitis. These findings suggest that the STAT3 pathway may be implicated in a new mechanism for the pathogenesis of several GI disorders.
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Affiliation(s)
- Manish Arora
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Preet Bagi
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Anna Strongin
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Jennifer Heimall
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA
| | - Xiongce Zhao
- Office of Director, NIDDK, NIH, Bethesda, MD, USA
| | - Monica G Lawrence
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA
| | - Apurva Trivedi
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD, USA
| | - Carolyn Henderson
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA
| | - Amy Hsu
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA
| | | | | | | | - Steven M Holland
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA
| | - Alexandra F Freeman
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA.
| | - Theo Heller
- Liver Diseases Branch, NIDDK, NIH, 10 Center Drive, Bldg 10, Bethesda, MD, 20892, USA.
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8
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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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9
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Schulze AB, Heptner B, Kessler T, Baumgarten B, Stoica V, Mohr M, Wiewrodt R, Warneke VS, Hartmann W, Wüllenweber J, Schülke C, Schäfers M, Wilmes D, Becker K, Schmidt LH, Groll AH, Berdel WE. Progressive histoplasmosis with hemophagocytic lymphohistiocytosis and epithelioid cell granulomatosis: A case report and review of the literature. Eur J Haematol 2017; 99:91-100. [DOI: 10.1111/ejh.12886] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2017] [Indexed: 01/08/2023]
Affiliation(s)
| | - Britta Heptner
- Department of Medicine A; University Hospital Muenster; Muenster Germany
| | - Torsten Kessler
- Department of Medicine A; University Hospital Muenster; Muenster Germany
| | - Birgit Baumgarten
- Department of Medicine A; University Hospital Muenster; Muenster Germany
| | - Viorelia Stoica
- Department of Medicine B; University Hospital Muenster; Muenster Germany
| | - Michael Mohr
- Department of Medicine A; University Hospital Muenster; Muenster Germany
| | - Rainer Wiewrodt
- Department of Medicine A; University Hospital Muenster; Muenster Germany
| | | | - Wolfgang Hartmann
- Gerhard Domagk Institute of Pathology; University Hospital Muenster; Muenster Germany
| | - Jörg Wüllenweber
- Institute of Medical Microbiology; University Hospital Muenster; Muenster Germany
| | - Christoph Schülke
- Department of Clinical Radiology; University Hospital Muenster; Muenster Germany
| | - Michael Schäfers
- Department of Nuclear Medicine; University Hospital Muenster; Muenster Germany
| | - Dunja Wilmes
- National Reference Center for Cryptococcosis, Scedosporiosis, and Endemic Mycoses; Robert Koch Institute; Berlin Germany
| | - Karsten Becker
- Institute of Medical Microbiology; University Hospital Muenster; Muenster Germany
| | | | - Andreas H. Groll
- Infectious Disease Research Program; Department of Pediatric Hematology/Oncology; Center for Bone Marrow Transplantation; University Hospital Muenster; Muenster Germany
| | - Wolfgang E. Berdel
- Department of Medicine A; University Hospital Muenster; Muenster Germany
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10
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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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11
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Leon JA, Fry LC, Mönkemüller K. Perianal Fistula, Weight Loss, and Skin Rash: Good Job Making the Diagnosis. Gastroenterology 2015; 149:1697-9. [PMID: 26480885 DOI: 10.1053/j.gastro.2015.09.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 09/22/2015] [Indexed: 12/02/2022]
Affiliation(s)
- José A Leon
- Department of Medicine, Baptist South Hospital, Montgomery, Alabama
| | - Lucía C Fry
- Department of Medicine, Baptist South Hospital, Montgomery, Alabama; Division of Gastroenterology, Otto-von-Guericke University, Magdeburg, Germany
| | - Klaus Mönkemüller
- Department of Medicine, Baptist South Hospital, Montgomery, Alabama; Division of Gastroenterology, Otto-von-Guericke University, Magdeburg, Germany; Basil I. Hirschowitz Endoscopic Center of Excellence, Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Alabama
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12
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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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Abstract
: Hyper-IgE syndrome is a primary immunodeficiency marked by abnormalities in the coordination of cell-cell signaling with the potential to affect TH17 cell, B cell, and neutrophil responses. Clinical manifestations include recurrent skin and lung infections, serum IgE elevation, connective tissue repair and development alterations, and the propensity for vascular abnormalities and tumor development. Signal transducer and activator of transcription 3 (STAT3) signaling, dedicator of cytokinesis 8 (DOCK8) signaling, and tyrosine kinase 2 (TYK2) signaling alterations have been implicated in 3 forms of hyper-IgE syndrome.
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15
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Risk of infection and prevention in pediatric patients with IBD: ESPGHAN IBD Porto Group commentary. J Pediatr Gastroenterol Nutr 2012; 54:830-7. [PMID: 22584748 DOI: 10.1097/mpg.0b013e31824d1438] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Combined immunosuppression by immunomodulators and biological therapy has become standard in the medical management of moderate-to-severe inflammatory bowel disease (IBD) because of clearly demonstrated efficacy. Clinical studies, registries, and case reports warn of the increased risk of infections, particularly opportunistic infections; however, already in the steroid monotherapy era, patients are at risk because it is accepted that a patient should be considered immunosuppressed when receiving a daily dose of 20 mg of prednisone for 2 weeks. Prescriptions increasingly involve azathioprine, methotrexate, and various biological agents. The TREAT registry evaluated safety in >6000 adult patients, half of them treated with infliximab (IFX) for about 1.9 years. IFX-treated patients had an increased risk of infections and this was associated with disease severity and concomitant prednisone use. The REACH study, evaluating the efficacy of IFX in children with moderate-to-severe Crohn disease, refractory to immunomodulatory treatment, reports serious infections as the major adverse events and their frequency is higher with shorter treatment intervals. The combination of immunosuppressive medications is a risk factor for opportunistic infections. Exhaustive guidelines on prophylaxis, diagnosis, and management of opportunistic infections in adult patients with IBD have been published by a European Crohn's and Colitis Organization working group, including clear evidence-based statements. We have reviewed the literature on infections in pediatric IBD as well as the European Crohn's and Colitis Organization guidelines to present a commentary on infection prophylaxis for the pediatric age group.
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Abstract
Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a primary immunodeficiency with a wide array of clinical features caused by dominant negative mutations in STAT3. In recent years, not only the clinical phenotype of the disease has been expanded with recognition of features such as arterial aneurysms, but also our understanding of the pathogenesis of the disease has greatly improved.
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Affiliation(s)
- Kathryn J Sowerwine
- Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA
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Case report of a young child with disseminated histoplasmosis and review of hyper immunoglobulin e syndrome (HIES). Clin Mol Allergy 2011; 9:14. [PMID: 22126402 PMCID: PMC3248830 DOI: 10.1186/1476-7961-9-14] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Accepted: 11/29/2011] [Indexed: 01/24/2023] Open
Abstract
Type 1 hyper IgE syndrome (HIES), also known as Job's Syndrome, is an autosomal dominant disorder due to defects in STAT3 signaling and Th17 differentiation. Symptoms may present during infancy but diagnosis is often made in childhood or later. HIES is characterized by immunologic and non-immunologic findings such as recurrent sinopulmonary infections, recurrent skin infections, multiple fractures, atopic dermatitis and characteristic facies. These manifestations are accompanied by elevated IgE levels and reduced IL-17 producing CD3+CD4+ T cells. Diagnosis in young children can be challenging as symptoms accumulate over time along with confounding clinical dilemmas. A NIH clinical HIES scoring system was developed in 1999, and a more recent scoring system with fewer but more pathogonomonic clinical findings was reported in 2010. These scoring systems can be used as tools to help in grading the likelihood of HIES diagnosis. We report a young child ultimately presenting with disseminated histoplasmosis and a novel STAT3 variant in the SH2 domain.
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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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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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