Primary immunodeficiency update: Part II. Syndromes associated with mucocutaneous candidiasis and noninfectious cutaneous manifestations - PubMed (original) (raw)
Review
Primary immunodeficiency update: Part II. Syndromes associated with mucocutaneous candidiasis and noninfectious cutaneous manifestations
Dominique C Pichard et al. J Am Acad Dermatol. 2015 Sep.
Abstract
Several primary immunodeficiencies (PIDs) have recently been described that confer an elevated risk of fungal infections and noninfectious cutaneous manifestations. In addition, immunologic advances have provided new insights into our understanding of the pathophysiology of fungal infections in established PIDs. We reviewed PIDs that present with an eczematous dermatitis in part I. In part II of this continuing medical education article we discuss updates on PIDs associated with fungal infections, their biologic basis in PIDs, and noninfectious cutaneous manifestations.
Published by Elsevier Inc.
Conflict of interest statement
Public disclosure statement: The authors have no conflict of interest to declare
Figures
Figure 1
Immune response to fungal infection. A. Pattern recognition receptors such as toll-like receptors (TLR) and C-type lectin receptors (e.g. Dectin-1) present on macrophages, dendritic cells, activate independent pathways. TLR2 and TLR4 use the adaptor protein MyD88 to activate nuclear factor kappa B (NF-κB). This transcription factor translocates into the nucleus and facilitates transcription of pro-inflammatory cytokines. Dectin-1 signals through the adaptor protein caspase recruitment domain family, member 9 (CARD-9), also activating NF-κB. Binding of interferon-γ (IFN) to its receptor on macrophages allows for homodimerization of signal transducer and activator of transcription 1 (STAT1). This transcription factor produces interferons and proinflammatory cytokines that inhibit Th17 cell development. B. Th17 cells, which produce cytokines critical for antifungal immunity, signal through STAT3. C. IL-17 receptors are expressed on numerous nonhematogenous cells. IL-17 binds its receptor allowing for activation of NF-κB through the adaptor protein ACT1, producing pro-inflammatory chemokines and cytokines that are important to the host defense against fungal organisms.
Figure 2
Multiple cutaneous fungal infections associated with STAT1 gain of function mutation. A. Trichophyton tonsurans dermatophyte infection on the thigh and extensive nail dystrophy (B) due to chronic fungal infection in an 18 year old female. Nail clippings identified septate hyphae.
Figure 3
Autoimmune polyendocrinopathy candidiasis, and ectodermal dysplasia. A. 38 year old male with alopecia universalis, vitiligo and nail dystrophy (B) secondary to recurrent candidal infection beginning at age 3.
Figure 4
Granuloma formation in PLAID syndrome. Widespread granulomatous disease in 21 year old with PLAID syndrome. Histopathology demonstrated sarcoid-like granulomas without central necrosis as well as diffuse, superficial dermal granulomatous inflammation.
Figure 5
Multiple dermatofibrosarcoma protuberans in ADA-SCID. A. Irregularly shaped red-brown plaque on the upper chest in 17 year old male with ADA-SCID. B. A depressed atrophic plaque with poorly-defined margins is seen on close examination. C. Histopathological analysis from 3 similar appearing lesions on this patient a revealed spindle-cell infiltrate, primarily in the reticular dermis (D). E. Immunohistochemistry demonstrates the spindle cell infiltrate strongly expresses CD34; RT-PCR testing from the specimen demonstrated the presence of COL1A1/PDGFB fusion transcripts. (C and D, Hematoxylin-eosin stain, original magnification: C, x40; D, x100; E, CD34 stain; original magnification x200.)
Figure 6
Cutaneous and systemic findings in GATA2 syndrome. Reprinted, with permission, from Spinner MA et al.
Figure 7
Cutaneous findings in GATA-2 deficiency. A. Extensive HPV infection with vulvar and anal intraepithelial neoplasia, cutaneous mycobacterial infection (B), and erythema nodosum-like panniculitis (C) in a 40 year old female with GATA2 deficiency.
Figure 8
WHIM syndrome. Confluent perianal condyloma and scattered verrucous papules on the buttock and perineum of a 4 year old with WHIM syndrome.
Similar articles
- Primary immunodeficiency update: Part I. Syndromes associated with eczematous dermatitis.
Pichard DC, Freeman AF, Cowen EW. Pichard DC, et al. J Am Acad Dermatol. 2015 Sep;73(3):355-64; quiz 365-6. doi: 10.1016/j.jaad.2015.01.054. J Am Acad Dermatol. 2015. PMID: 26282794 Free PMC article. Review. - Cutaneous markers of primary immunodeficiency diseases in children.
Berron-Ruiz A, Berron-Perez R, Ruiz-Maldonado R. Berron-Ruiz A, et al. Pediatr Dermatol. 2000 Mar-Apr;17(2):91-6. doi: 10.1046/j.1525-1470.2000.01721.x. Pediatr Dermatol. 2000. PMID: 10792794 - Cutaneous manifestations of primary immunodeficiency diseases in children.
Moin A, Farhoudi A, Moin M, Pourpak Z, Bazargan N. Moin A, et al. Iran J Allergy Asthma Immunol. 2006 Sep;5(3):121-6. Iran J Allergy Asthma Immunol. 2006. PMID: 17237563 - Cutaneous manifestations of primary immunodeficiency.
Sillevis Smitt JH, Kuijpers TW. Sillevis Smitt JH, et al. Curr Opin Pediatr. 2013 Aug;25(4):492-7. doi: 10.1097/MOP.0b013e3283623b9f. Curr Opin Pediatr. 2013. PMID: 23744097 Review. - [Cutaneous manifestations in primary immunodeficiency diseases].
Bojtor AE, Sárdy M, Maródi L. Bojtor AE, et al. Orv Hetil. 2018 Jun;159(23):937-947. doi: 10.1556/650.2018.30994. Orv Hetil. 2018. PMID: 29860885 Review. Hungarian.
Cited by
- A horse or a zebra? Unusual manifestations of common cutaneous infections in primary immunodeficiency pediatric patients.
Ollech A, Simon AJ, Lev A, Stauber T, Sherman G, Solomon M, Barzilai A, Somech R, Greenberger S. Ollech A, et al. Front Pediatr. 2023 Mar 6;11:1103726. doi: 10.3389/fped.2023.1103726. eCollection 2023. Front Pediatr. 2023. PMID: 36950172 Free PMC article. - Synergistic Effect of the Combination of Deferoxamine and Fluconazole In Vitro and In Vivo against Fluconazole-Resistant Candida Spp.
An L, Tan J, Wang Y, Liu S, Li Y, Yang L. An L, et al. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0072522. doi: 10.1128/aac.00725-22. Epub 2022 Oct 26. Antimicrob Agents Chemother. 2022. PMID: 36286552 Free PMC article. - Druggable monogenic immune defects hidden in diverse medical specialties: Focus on overlap syndromes.
Boz V, Zanchi C, Levantino L, Riccio G, Tommasini A. Boz V, et al. World J Clin Pediatr. 2022 Mar 9;11(2):136-150. doi: 10.5409/wjcp.v11.i2.136. eCollection 2022 Mar 9. World J Clin Pediatr. 2022. PMID: 35433297 Free PMC article. Review. - [In vivo study on the effects of intercellular adhesion operon of Staphylococcus epidermidis on the inflammation associated with bacteria-fungal mixed biofilm].
Zhang G, Wan Z, Wang X, Huang Y, Zhou Y, Chen Y, Lei Y, Qiao L. Zhang G, et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2021 Oct 15;35(10):1328-1335. doi: 10.7507/1002-1892.202104061. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2021. PMID: 34651489 Free PMC article. Chinese. - Importance of Candida Antigenic Factors: Structure-Driven Immunomodulation Properties of Synthetically Prepared Mannooligosaccharides in RAW264.7 Macrophages.
Paulovičová E, Paulovičová L, Farkaš P, Karelin AA, Tsvetkov YE, Krylov VB, Nifantiev NE. Paulovičová E, et al. Front Cell Infect Microbiol. 2019 Nov 8;9:378. doi: 10.3389/fcimb.2019.00378. eCollection 2019. Front Cell Infect Microbiol. 2019. PMID: 31788453 Free PMC article.
References
- Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature immunology. 2005;6:1123–1132. - PubMed
- van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med. 2011;365:54–61. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical