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Zhang Z, Liang L, Jiang X, Shan J, Li S, Liu J, Dong Q, Wang X, Zhang H. Skin microbiome influences the progression of cutaneous squamous cell carcinoma through the immune system. World J Surg Oncol 2025; 23:129. [PMID: 40205611 PMCID: PMC11980248 DOI: 10.1186/s12957-025-03791-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 03/29/2025] [Indexed: 04/11/2025] Open
Abstract
Cutaneous squamous cell carcinoma (cSCC) is a type of skin tumor that develops in the epithelial cells. This disease has the second highest incidence of human skin cancers, with a high metastatic rate. While ultraviolet radiation significantly contributes to the genomic changes that support cSCC development, the dysbiosis of the skin microbiome and influence of the immune system also play important roles in this process. In this review, we discuss the effects of skin microbes and their metabolites on the immune system, including innate immune cells, T cells, and cytokines. We also discuss how Staphylococcus aureus and human papillomavirus can affect cSCC by impacting the immune system. Furthermore, we explore the antagonism of symbiotic microorganisms with cSCC-associated pathogens and their potential as novel therapeutic modalities.
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Affiliation(s)
- Zijian Zhang
- Shanxi University of Chinese Medicine, Taiyuan, China
| | - Lili Liang
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China.
- Department of Dermatology, Fenyang Hospital of Shanxi Province, Fenyang, China.
| | - Xiaoke Jiang
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China
| | - Jixuan Shan
- Shanxi University of Chinese Medicine, Taiyuan, China
| | - Siying Li
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China
| | - Jie Liu
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China
| | - Qinyi Dong
- Shanxi University of Chinese Medicine, Taiyuan, China
| | - Xinman Wang
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China
| | - Han Zhang
- Department of Dermatology, Shanxi Provincial People's Hospital (Fifth Hospital) of Shanxi Medical University, Taiyuan, China
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2
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Rau A, Silva GS, Margolis DJ, Chiesa Fuxench ZC. Adult and infantile seborrheic dermatitis: update on current state of evidence and potential research frontiers. Int J Dermatol 2024; 63:1495-1502. [PMID: 38876467 DOI: 10.1111/ijd.17324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 06/16/2024]
Abstract
Seborrheic dermatitis (SD) is a highly prevalent dermatological condition globally. The condition demonstrates bimodal presentation with what is commonly thought to be two subtypes: adult/adolescent seborrheic dermatitis (ASD) and infantile seborrheic dermatitis (ISD). Despite the common prevalence of ASD and ISD, there remains uncertainty around the underlying pathogenetic mechanisms, risk factors, and appropriate classification of the disease(s). This narrative review summarizes the current understanding of the epidemiology, presentation, and pathogenetic factors like epidermal barrier dysfunction, lipid abnormalities, and cutaneous microbiome for ASD and ISD. Elements such as immune responsiveness, neuroendocrine factors, and genetics in these disease states are also investigated. Throughout our review, we highlight shared features and discrepancies between ASD and ISD that are present in the literature and discuss potential avenues for future research that explore these disease states. We aim to contribute to the medical discourse on ASD and ISD and increase awareness of the need for additional research around these conditions, ultimately informing better targeting of therapeutics moving forward.
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Affiliation(s)
- Akash Rau
- Michigan State University College of Human Medicine, Grand Rapids, MI, USA
| | - Genevieve S Silva
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - David J Margolis
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Zelma C Chiesa Fuxench
- Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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3
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T S R, Waikhom S, K SK, Reddy ME. A Clinicoepidemiological Study of Cutaneous and Systemic Comorbidities of Seborrheic Dermatitis in Adolescent and Adult Females. Cureus 2023; 15:e40972. [PMID: 37503468 PMCID: PMC10370423 DOI: 10.7759/cureus.40972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2023] [Indexed: 07/29/2023] Open
Abstract
Background Seborrheic dermatitis is the most common, chronic inflammatory skin condition which is confined to the scalp, nasolabial folds, and regions rich in sebaceous glands for which no definitive cause has been found. Although the disease is more common, the comorbidities associated with it have not been studied in detail. This study aims to assess the prevalence of seborrheic dermatitis and its associated cutaneous and systemic comorbidities in adolescent and adult patients. Methodology This cross-sectional study was performed among 451 adolescent and adult female patients who visited the Department of Dermatology, Venereology, and Leprosy of R. Laxminarayanappa Jalappa Hospital and Research Centre, Kolar. Patients having symptoms such as scaly patches, inflamed skin, and stubborn dandruff were diagnosed with seborrheic dermatitis and included in the study. A detailed history was collected for assessing other cutaneous disorders. Results Out of the 451 female participants, 87% belonged to the age group of 21-30 years, with 60.9% having cutaneous and 28.3% having systemic comorbidities. Acne (13.3%) and diabetes mellitus (13.1%) were the most common cutaneous and systemic associated comorbidities, respectively. Conclusions Comorbidities of seborrheic dermatitis were more commonly seen in adult female patients, Some of the common cutaneous comorbidities were acne, alopecia areata, and folliculitis. Systemic comorbidities included diabetes, obesity, and hypertension. However, all of these comorbidities were not statistically significant.
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Affiliation(s)
- Rajashekar T S
- Dermatology, Venereology and Leprosy, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, IND
| | - Savana Waikhom
- Dermatology, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, IND
| | - Suresh Kumar K
- Dermatology, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, IND
| | - Meghana E Reddy
- Dermatology, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, IND
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4
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Mustarichie R, Rostinawati T, Pitaloka DAE, Saptarini NM, Iskandar Y. Herbal Therapy for the Treatment of Seborrhea Dermatitis. Clin Cosmet Investig Dermatol 2022; 15:2391-2405. [PMID: 36387964 PMCID: PMC9651010 DOI: 10.2147/ccid.s376700] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 09/08/2022] [Indexed: 09/12/2023]
Abstract
Seborrhea dermatitis is a skin disorder that usually appears on parts of the body that have high density of sebaceous glands, such as the face, chest, and scalp. Clinical manifestations that generally appear as scaly skin and erythema. Seborrhea dermatitis is also known as one of the causes of alopecia. Treatments that can be used for seborrhea dermatitis are antifungal, anti-inflammatory, keratolytic, and coal tar. There are concerns about poor adherence, resistance, and some side effects of drugs that have been used in the treatment of seborrhea dermatitis. Concerns regarding these issues increase the urgency for the development of new therapeutic agents in the treatment of seborrhea dermatitis. Research on medicinal plants has enormous potential to produce compounds with new structures and bioactivity. This review discusses clinical and in vitro studies related to the activity of several medicinal plants that have potential as a treatment for seborrhea dermatitis, as well as the compounds that play a role in these activities. Literature searches were carried out on the PubMed, Taylor & Francis, and SpringerLink databases using Boolean Operators to get 25 articles that match the keywords used. Of the 25 articles, six were clinical trials, while 19 were in vitro studies of Malassezia. Several plants have potential as promising therapeutic agents for the treatment of seborrhea dermatitis by inhibiting the growth of Malassezia, decreasing sebum secretion, and decreasing symptoms associated with seborrhea dermatitis such as itching, pain or burning sensation, and redness.
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Affiliation(s)
- Resmi Mustarichie
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Tina Rostinawati
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Dian Ayu Eka Pitaloka
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Nyi Mekar Saptarini
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
| | - Yoppi Iskandar
- Biological Pharmacy Department, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia
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5
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Hobi S, Cafarchia C, Romano V, Barrs VR. Malassezia: Zoonotic Implications, Parallels and Differences in Colonization and Disease in Humans and Animals. J Fungi (Basel) 2022; 8:jof8070708. [PMID: 35887463 PMCID: PMC9324274 DOI: 10.3390/jof8070708] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 12/13/2022] Open
Abstract
Malassezia spp. are commensals of the skin, oral/sinonasal cavity, lower respiratory and gastrointestinal tract. Eighteen species have been recovered from humans, other mammals and birds. They can also be isolated from diverse environments, suggesting an evolutionary trajectory of adaption from an ecological niche in plants and soil to the mucocutaneous ecosystem of warm-blooded vertebrates. In humans, dogs and cats, Malassezia-associated dermatological conditions share some commonalities. Otomycosis is common in companion animals but is rare in humans. Systemic infections, which are increasingly reported in humans, have yet to be recognized in animals. Malassezia species have also been identified as pathogenetic contributors to some chronic human diseases. While Malassezia species are host-adapted, some species are zoophilic and can cause fungemia, with outbreaks in neonatal intensive care wards associated with temporary colonization of healthcare worker’s hands from contact with their pets. Although standardization is lacking, susceptibility testing is usually performed using a modified broth microdilution method. Antifungal susceptibility can vary depending on Malassezia species, body location, infection type, disease duration, presence of co-morbidities and immunosuppression. Antifungal resistance mechanisms include biofilm formation, mutations or overexpression of ERG11, overexpression of efflux pumps and gene rearrangements or overexpression in chromosome 4.
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Affiliation(s)
- Stefan Hobi
- Department of Veterinary Clinical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University, Tat Chee Avenue, Kowloon, Hong Kong, China
- Correspondence: (S.H.); (V.R.B.)
| | - Claudia Cafarchia
- Department of Veterinary Medicine, University of Bari, Str. prov. per Casamassima Km 3, Valenzano, (Bari), 70010, Italy; (C.C.); (V.R.)
| | - Valentina Romano
- Department of Veterinary Medicine, University of Bari, Str. prov. per Casamassima Km 3, Valenzano, (Bari), 70010, Italy; (C.C.); (V.R.)
| | - Vanessa R. Barrs
- Department of Veterinary Clinical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University, Tat Chee Avenue, Kowloon, Hong Kong, China
- Centre for Animal Health and Welfare, City University of Hong Kong, Kowloon Tong, Hong Kong, China
- Correspondence: (S.H.); (V.R.B.)
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6
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Kentley J, Allawh R, Rao S, Doyle A, Ahmad A, Nadhan K, Proby C, Harwood CA, Chung CL. The burden of cutaneous disease in solid organ transplant recipients of color. Am J Transplant 2021; 21:1215-1226. [PMID: 32659869 DOI: 10.1111/ajt.16210] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Revised: 06/11/2020] [Accepted: 07/02/2020] [Indexed: 01/25/2023]
Abstract
Organ transplant recipients (OTRs) are at increased risk of cutaneous malignancy. Skin disorders in OTRs of color (OTRoC) have rarely been systematically assessed. We aimed to ascertain the burden of skin disease encountered in OTRoC by prospectively collecting data from OTRs attending 2 posttransplant skin surveillance clinics: 1 in London, UK and 1 in Philadelphia, USA. Retrospective review of all dermatological diagnoses was performed. Data from 1766 OTRs were analyzed: 1024 (58%) white, 376 (21%) black, 261 (15%) Asian, 57 (3%) Middle Eastern/Mediterranean (ME/M), and 48 (2.7%) Hispanic; and 1128 (64%) male. Viral infections affected 45.1% of OTRs, and were more common in white and ME/M patients (P < .001). Fungal infections affected 28.1% and were more common in ME/M patients (P < .001). Inflammatory skin disease affected 24.5%, and was most common in black patients (P < .001). In addition, 26.4% of patients developed skin cancer. There was an increased risk of skin cancer in white vs nonwhite OTRs (HR 4.4, 95% CI 3.5-5.7, P < .001): keratinocyte cancers were more common in white OTRs (P < .001) and Kaposi sarcoma was more common in black OTRs (P < .001). These data support the need for programs that promote targeted dermatology surveillance for all OTRs, regardless of race/ethnicity or country of origin.
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Affiliation(s)
- Jonathan Kentley
- Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK.,Department of Dermatology, Chelsea and Westminster Hospital, London, UK
| | - Rina Allawh
- Montgomery Dermatology, Lankenau Institute for Medical Research, King of Prussia, Wynnewood, Pennsylvania, USA
| | - Swati Rao
- Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Alden Doyle
- Department of Medicine, University of Virginia, Charlottesville, Virginia, USA
| | - Amar Ahmad
- Department of Cancer Intelligence, Cancer Research UK, London, UK
| | - Kumar Nadhan
- Department of Dermatology, John H Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Charlotte Proby
- Jacqui Wood Cancer Centre, School of Medicine, University of Dundee, Dundee, UK
| | - Catherine A Harwood
- Department of Dermatology, Royal London Hospital, Barts Health NHS Trust, London, UK.,Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK
| | - Christina L Chung
- Montgomery Dermatology, Lankenau Institute for Medical Research, King of Prussia, Wynnewood, Pennsylvania, USA
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Lin HS, Lin PT, Tsai YS, Wang SH, Chi CC. Interventions for bacterial folliculitis and boils (furuncles and carbuncles). Cochrane Database Syst Rev 2021; 2:CD013099. [PMID: 33634465 PMCID: PMC8130991 DOI: 10.1002/14651858.cd013099.pub2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Bacterial folliculitis and boils are globally prevalent bacterial infections involving inflammation of the hair follicle and the perifollicular tissue. Some folliculitis may resolve spontaneously, but others may progress to boils without treatment. Boils, also known as furuncles, involve adjacent tissue and may progress to cellulitis or lymphadenitis. A systematic review of the best evidence on the available treatments was needed. OBJECTIVES To assess the effects of interventions (such as topical antibiotics, topical antiseptic agents, systemic antibiotics, phototherapy, and incision and drainage) for people with bacterial folliculitis and boils. SEARCH METHODS We searched the following databases up to June 2020: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five trials registers up to June 2020. We checked the reference lists of included studies and relevant reviews for further relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed systemic antibiotics; topical antibiotics; topical antiseptics, such as topical benzoyl peroxide; phototherapy; and surgical interventions in participants with bacterial folliculitis or boils. Eligible comparators were active intervention, placebo, or no treatment. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'clinical cure' and 'severe adverse events leading to withdrawal of treatment'; secondary outcomes were 'quality of life', 'recurrence of folliculitis or boil following completion of treatment', and 'minor adverse events not leading to withdrawal of treatment'. We used GRADE to assess the certainty of the evidence. MAIN RESULTS We included 18 RCTs (1300 participants). The studies included more males (332) than females (221), although not all studies reported these data. Seventeen trials were conducted in hospitals, and one was conducted in clinics. The participants included both children and adults (0 to 99 years). The studies did not describe severity in detail; of the 232 participants with folliculitis, 36% were chronic. At least 61% of participants had furuncles or boils, of which at least 47% were incised. Duration of oral and topical treatments ranged from 3 days to 6 weeks, with duration of follow-up ranging from 3 days to 6 months. The study sites included Asia, Europe, and America. Only three trials reported funding, with two funded by industry. Ten studies were at high risk of 'performance bias', five at high risk of 'reporting bias', and three at high risk of 'detection bias'. We did not identify any RCTs comparing topical antibiotics against topical antiseptics, topical antibiotics against systemic antibiotics, or phototherapy against sham light. Eleven trials compared different oral antibiotics. We are uncertain as to whether cefadroxil compared to flucloxacillin (17/21 versus 18/20, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.70 to 1.16; 41 participants; 1 study; 10 days of treatment) or azithromycin compared to cefaclor (8/15 versus 10/16, RR 1.01, 95% CI 0.72 to 1.40; 31 participants; 2 studies; 7 days of treatment) differed in clinical cure (both very low-certainty evidence). There may be little to no difference in clinical cure rate between cefdinir and cefalexin after 17 to 24 days (25/32 versus 32/42, RR 1.00, 95% CI 0.73 to 1.38; 74 participants; 1 study; low-certainty evidence), and there probably is little to no difference in clinical cure rate between cefditoren pivoxil and cefaclor after 7 days (24/46 versus 21/47, RR 1.17, 95% CI 0.77 to 1.78; 93 participants; 1 study; moderate-certainty evidence). For risk of severe adverse events leading to treatment withdrawal, there may be little to no difference between cefdinir versus cefalexin after 17 to 24 days (1/191 versus 1/200, RR 1.05, 95% CI 0.07 to 16.62; 391 participants; 1 study; low-certainty evidence). There may be an increased risk with cefadroxil compared with flucloxacillin after 10 days (6/327 versus 2/324, RR 2.97, 95% CI 0.60 to 14.62; 651 participants; 1 study; low-certainty evidence) and cefditoren pivoxil compared with cefaclor after 7 days (2/77 versus 0/73, RR 4.74, 95% CI 0.23 to 97.17; 150 participants; 1 study; low-certainty evidence). However, for these three comparisons the 95% CI is very wide and includes the possibility of both increased and reduced risk of events. We are uncertain whether azithromycin affects the risk of severe adverse events leading to withdrawal of treatment compared to cefaclor (274 participants; 2 studies; very low-certainty evidence) as no events occurred in either group after seven days. For risk of minor adverse events, there is probably little to no difference between the following comparisons: cefadroxil versus flucloxacillin after 10 days (91/327 versus 116/324, RR 0.78, 95% CI 0.62 to 0.98; 651 participants; 1 study; moderate-certainty evidence) or cefditoren pivoxil versus cefaclor after 7 days (8/77 versus 5/73, RR 1.52, 95% CI 0.52 to 4.42; 150 participants; 1 study; moderate-certainty evidence). We are uncertain of the effect of azithromycin versus cefaclor after seven days due to very low-certainty evidence (7/148 versus 4/126, RR 1.26, 95% CI 0.38 to 4.17; 274 participants; 2 studies). The study comparing cefdinir versus cefalexin did not report data for total minor adverse events, but both groups experienced diarrhoea, nausea, and vaginal mycosis during 17 to 24 days of treatment. Additional adverse events reported in the other included studies were vomiting, rashes, and gastrointestinal symptoms such as stomach ache, with some events leading to study withdrawal. Three included studies assessed recurrence following completion of treatment, none of which evaluated our key comparisons, and no studies assessed quality of life. AUTHORS' CONCLUSIONS We found no RCTs regarding the efficacy and safety of topical antibiotics versus antiseptics, topical versus systemic antibiotics, or phototherapy versus sham light for treating bacterial folliculitis or boils. Comparative trials have not identified important differences in efficacy or safety outcomes between different oral antibiotics for treating bacterial folliculitis or boils. Most of the included studies assessed participants with skin and soft tissue infection which included many disease types, whilst others focused specifically on folliculitis or boils. Antibiotic sensitivity data for causative organisms were often not reported. Future trials should incorporate culture and sensitivity information and consider comparing topical antibiotic with antiseptic, and topical versus systemic antibiotics or phototherapy.
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Affiliation(s)
- Huang-Shen Lin
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Chiayi, Taiwan
| | - Pei-Tzu Lin
- Department of Pharmacy, Chang Gung Memorial Hospital, Yulin, Yulin, Taiwan
| | - Yu-Shiun Tsai
- Medical Library, Chang Gung Memorial Hospital, Chiayi, Puzih, Taiwan
| | - Shu-Hui Wang
- Department of Dermatology, Far Eastern Memorial Hospital, New Taipei, Taiwan
| | - Ching-Chi Chi
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
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De Rosa N, Paddon V, Glanville A, Parsi K. Dermatological Disease in Australian Heart and Lung Transplant Recipients. Dermatology 2020; 237:629-634. [PMID: 32942278 DOI: 10.1159/000510055] [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: 03/15/2020] [Accepted: 07/09/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Research examining skin disease in heart and lung transplant recipients in Australia is limited. This study aims to determine the spectrum of skin diseases encountered in Australian heart and lung transplant recipients, their effect on quality of life, and potential risk factors for skin cancer. METHODS Ninety-four participants were recruited from an Australian heart and lung transplant centre between March and December 2016. The participants were asked to fill out a questionnaire which included the Dermatology Life Quality Index and were examined for malignant and non-malignant skin disease. The association of study variables with the presence of skin cancer and Dermatology Life Quality Index score were examined using logistic regression analysis. RESULTS A dermatological diagnosis was made in 82 patients (87%). Actinic keratosis was the most common diagnosis, affecting 50 participants (53%), followed by skin cancer (41; 44%) and warts (14; 15%). Other non-malignant skin diseases were less common. Risk factors associated with skin cancer on multivariate modelling included age at transplantation and a history of ≥5 post-transplant skin cancers. Skin disease had a negative effect on the quality of life of a minority of patients. CONCLUSION Actinic keratosis and skin cancer are very frequent in Australian heart and lung transplant recipients and more common than non-malignant skin diseases. Routine dermatological surveillance at regular intervals is advised.
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Affiliation(s)
- Nicholas De Rosa
- Department of Dermatology, Royal Darwin Hospital, Tiwi, Northwest Territories, Australia,
| | - Vanessa Paddon
- Department of Dermatology, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia
| | - Allan Glanville
- The University of New South Wales, Sydney, New South Wales, Australia.,Department of Thoracic Medicine, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia
| | - Kurosh Parsi
- Department of Dermatology, St. Vincent's Hospital Sydney, Sydney, New South Wales, Australia.,The University of New South Wales, Sydney, New South Wales, Australia
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Adalsteinsson JA, Kaushik S, Muzumdar S, Guttman-Yassky E, Ungar J. An update on the microbiology, immunology and genetics of seborrheic dermatitis. Exp Dermatol 2020; 29:481-489. [PMID: 32125725 DOI: 10.1111/exd.14091] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 02/07/2020] [Accepted: 02/27/2020] [Indexed: 12/11/2022]
Abstract
The underlying mechanism of seborrheic dermatitis (SD) is poorly understood but major scientific progress has been made in recent years related to microbiology, immunology and genetics. In light of this, the major goal of this article was to summarize the most recent articles on SD, specifically related to underlying pathophysiology. SD results from Malassezia hydrolysation of free fatty acids with activation of the immune system by the way of pattern recognition receptors, inflammasome, IL-1β and NF-kB. M. restricta and M. globosa are likely the most virulent subspecies, producing large quantities of irritating oleic acids, leading to IL-8 and IL-17 activation. IL-17 and IL-4 might play a big role in pathogenesis, but this needs to be further studied using novel biologics. No clear genetic predisposition has been established; however, recent studies implicated certain increased-risk human leucocyte antigen (HLA) alleles, such as A*32, DQB1*05 and DRB1*01 as well as possible associations with psoriasis and atopic dermatitis (AD) through the LCE3 gene cluster while SD, and SD-like syndromes, shares genetic mutations that appear to impair the ability of the immune system to restrict Malassezia growth, partially due to complement system dysfunction. A paucity of studies exists looking at the relationship between SD and systemic disease. In HIV, SD is thought to be secondary to a combination of immune dysregulation and disruption in skin microbiota with unhindered Malassezia proliferation. In Parkinson's disease, SD is most likely secondary to parasympathetic hyperactivity with increased sebum production as well as facial immobility which leads to sebum accumulation.
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Affiliation(s)
| | - Shivani Kaushik
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Sonal Muzumdar
- Department of Dermatology, University of Connecticut, Farmington, Connecticut
| | - Emma Guttman-Yassky
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jonathan Ungar
- Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York
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10
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Larsen HK, Thomsen LT, Haedersdal M, Dehlendorff C, Schwartz Sørensen S, Kjaer SK. Risk of genital warts in renal transplant recipients-A registry-based, prospective cohort study. Am J Transplant 2019; 19:156-165. [PMID: 30080315 DOI: 10.1111/ajt.15056] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 07/08/2018] [Accepted: 07/25/2018] [Indexed: 01/25/2023]
Abstract
Genital warts (GWs) are a risk factor for subsequent human papillomavirus (HPV)-related anogenital cancers. In this register-based, prospective cohort study, we estimated the risk of GWs in renal transplant recipients (RTRs) compared with a nontransplanted cohort. In a nationwide database, we identified first-time RTRs in Denmark during 1996 to 2015. For each RTR, 50 age- and sex-matched nontransplanted individuals were selected from the population registry. Information on GWs, sociodemographic characteristics, HPV vaccination, and other causes of immunosuppression was retrieved from registries. We estimated the cumulative incidence of GWs and used Cox regression to estimate hazard ratios (HR) of GWs in RTRs vs non-RTRs. We included 3268 RTRs and 162 910 non-RTRs without GWs 1 year before baseline. RTRs had higher hazard of GWs than non-RTRs (HR = 3.30; 95% confidence interval, 2.76-3.93, adjusted for sex, age, education, and income). The increased hazard of GWs compared with non-RTRs was more pronounced in female than in male RTRs. Although not statistically significant, the hazard tended to be higher in RTRs with functioning grafts compared with RTRs on dialysis after graft failure. The hazard of GWs was increased <1 year after transplantation and remained increased during ≥10 years. In conclusion, RTRs had substantially higher risk of GWs than non-RTRs.
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Affiliation(s)
- Helle Kiellberg Larsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Dermato-Venereology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Louise T Thomsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Merete Haedersdal
- Department of Dermato-Venereology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Christian Dehlendorff
- Unit of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Søren Schwartz Sørensen
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Susanne K Kjaer
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Obstetrics and Gynecology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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11
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Lin HS, Lin PT, Tsai YS, Wang SH, Chi CC. Interventions for bacterial folliculitis and boils (furuncles and carbuncles). Cochrane Database Syst Rev 2018. [DOI: 10.1002/14651858.cd013099] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Huang-Shen Lin
- Chang Gung Memorial Hospital, Chiayi; Division of Infectious Diseases, Department of Internal Medicine; 6, Sec West, Chia-Pu Road Puzih Chiayi Taiwan 61363
| | - Pei-Tzu Lin
- Chang Gung Memorial Hospital, Chiayi; Department of Pharmacy; 6, Sec West, Chia-Pu Rd Puzih Chiayi Taiwan 61363
- Chang Gung University of Science and Technology; Department of Nursing; 2, Sec West, Chia-Pu Rd Puzih Chiayi Taiwan 61363
| | - Yu-Shiun Tsai
- Chang Gung Memorial Hospital, Chiayi; Medical Library; 6, Sec West, Chia-Pu Rd Puzih Chiayi Taiwan 61363
| | - Shu-Hui Wang
- Far Eastern Memorial Hospital; Department of Dermatology; 21, Sec 2, Nanya S Rd Banciao District New Taipei Taiwan 22060
- Fu Jen Catholic University; Graduate Institute of Applied Science and Engineering, College of Science and Engineering; 510, Zhongzheng Rd Xinzhuang Dist New Taipei Taiwan 24205
| | - Ching-Chi Chi
- Chang Gung University; College of Medicine; Taoyuan Taiwan
- Chang Gung Memorial Hospital, Linkou; Department of Dermatology; 5, Fuxing St Guishan Dist Taoyuan Taiwan 33305
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12
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Ciccarese G, Trave I, Herzum A, Gariazzo L, Cozzani E, Rebora A, Parodi A, Drago F. Dermatological infections in organ transplant recipients: a retrospective study on 222 patients. J Eur Acad Dermatol Venereol 2018; 33:e36-e38. [PMID: 29953681 DOI: 10.1111/jdv.15153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- G Ciccarese
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - I Trave
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - A Herzum
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - L Gariazzo
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - E Cozzani
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - A Rebora
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - A Parodi
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
| | - F Drago
- DISSAL Section of Dermatology, University of Genoa, Genoa, Italy
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13
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Garrido PMC, Borges-Costa J. Skin disorders in renal transplant recipients: a retrospective study. An Bras Dermatol 2018; 92:638-641. [PMID: 29166499 PMCID: PMC5674695 DOI: 10.1590/abd1806-4841.20176040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Accepted: 07/07/2016] [Indexed: 11/21/2022] Open
Abstract
Background Immunosuppressive therapy, which is necessary to avoid graft rejection in
renal transplant recipients, presents an increased risk of several
pathologies, namely infectious and neoplastic. Objectives To identify the most frequent skin diseases and their clinical and
demographical risk factors within a population of renal transplant
recipients. Methods A retrospective study of renal transplant recipients referred to dermatology
visit and observed for the first time from January 2008 to December
2014. Results The study included 197 patients, 120 men (60,9%). Mean age was 50,7 years
(±13,4). 12 patients (6,1%) had previous skin cancer. Infections were
the most frequent reason of referral (93/197; 44%). From the total referred,
18,3% (36/197) presented pre-cancerous lesions. Malignancy was diagnosed in
36 patients (18,3%), with 29 non-melanoma skin cancers (14,7%) and 7 Kaposi
sarcomas (3,6%). Ratio of basal cell carcinoma to squamous cell carcinoma
was 1,1:1. Non-melanoma skin cancer was significantly associated with older
age (p = 0,002), male gender (p = 0,028), history of previous skin cancer (p
= 0,002) and higher duration of immunosuppressive therapy (p<0,001). Study limitations Retrospective study, with data from the first visit in dermatology. We didn't
made classification on skin-types. Conclusions The great incidence of cutaneous infections and skin cancer is responsible
for a significant morbidity. It is important to assure the regular
dermatological follow-up of renal transplant recipients, which will promote
the prevention, an early diagnosis and an efficient treatment.
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Affiliation(s)
| | - João Borges-Costa
- Unidade de Investigacao em Dermatologia, Faculdade de Medicina da Universidade de Lisboa (FMUL) - Lisbon, Portugal.,Clinica Dermatologica da Universidade de Lisboa, Centro Hospitalar Lisboa Norte, EPE (CHLN) - Lisbon, Portugal
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14
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Naldi L, Venturuzzo A, Invernizzi P. Dermatological Complications After Solid Organ Transplantation. Clin Rev Allergy Immunol 2018; 54:185-212. [PMID: 29177692 DOI: 10.1007/s12016-017-8657-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Organ transplant recipients (OTRs) are a population at high risk for cutaneous adverse events. Their early recognition and appropriate treatment is an important component of the clinical management of OTRs and should be optimally dealt with by dermatologists working in the context of a transplant dermatology clinic. Skin examination should be a standard procedure before performing organ transplantation to assess conditions which may be difficult to manage after the transplant procedure has been performed or which may represent a contraindication to transplantation, e.g., malignant melanoma. It also offers an opportunity to educate patients on skin care after organ transplantation. Skin infections can occur at any time after organ transplantation and include viral, bacterial, and fungal opportunistic infections. The risk of reactivation of latent viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), is high. Bacterial infections are frequent and may be caused by unusual agents such Actinomyces, Mycobacteria, Legionella, or Nocardia. A large spectrum of fungal infections may occur, ranging from superficial (e.g., dermatophytes) to deeper and more severe ones (Alternaria, Aspergillus, Cryptococcus, Histoplasma). Drug-related idiosyncratic reactions usually occur early after the introduction of the causative drug, e.g., hypersensitivity reaction to azathioprine. On the long-term run, cutaneous effects due to cumulative drug toxicity, e.g., sebaceous hyperplasia from cyclosporine, may appear. Rare immunologically driven inflammatory reactions may occur in OTRs such as GVH or autoimmune disease. Tumors are particularly frequent. Kaposi's sarcoma, associated with persistent human herpes virus 8 (HHV8) infection, and cutaneous anaplastic large-cell lymphoma (ALCL) occur early after transplantation. Other cancers, such as nonmelanoma skin cancer (NMSCs), associated with persistent human papillomavirus (HPV) infections, malignant melanoma, Merkel cell carcinoma, or adnexal tumors, manifest later with an incidence which is much higher than observed in the general population. The incidence increases further after a first NMSC occurs.
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Affiliation(s)
- Luigi Naldi
- Department of Dermatology, AULSS 8 - Ospedale San Bortolo, viale Rodolfi 37, 36100, Vicenza, Italy.
- Study Center Italian Group for Epidemiologic Research in Dermatology (GISED), Bergamo, Italy.
| | - Anna Venturuzzo
- Study Center Italian Group for Epidemiologic Research in Dermatology (GISED), Bergamo, Italy
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
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15
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Ash MM, Jolly PS. A Case Report of the Resolution of Multiple Recalcitrant Verrucae in a Renal Transplant Recipient After a Mycophenolate Mofetil Dose Reduction. Transplant Proc 2017; 49:213-215. [PMID: 28104140 DOI: 10.1016/j.transproceed.2016.11.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Accepted: 11/22/2016] [Indexed: 10/20/2022]
Abstract
Renal transplant recipients are at an increased risk of developing verrucae due to chronic immunosuppression, and certain therapies may confer a greater risk. Herein, we describe a 51-year-old woman with a 10-year-old unrelated kidney transplant who developed numerous therapy-resistant verrucae while on mycophenolate mofetil and tacrolimus maintenance immunosuppression. Over several years of immunosuppressant therapy, she declined the approach of reducing her mycophenolate mofetil dose to potentially improve her verrucae. Unfortunately, she later developed graft rejection requiring reversion to peritoneal dialysis. Within months of reducing her mycophenolate mofetil dose (her tacrolimus dose remained unchanged), she experienced dramatic resolution of many of her verrucae. In the current case, the observed clinical improvement may have resulted from either the total reduction of immunosuppression or the specific reduction of mycophenolate mofetil. Consequently, mycophenolate mofetil may contribute to the refractory nature of verrucae within renal transplant recipients, and further research should determine the relationship between verrucae development and both specific immunosuppressant therapies and the degree of immunosuppression.
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Affiliation(s)
- Mark M. Ash
- Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA
| | - Puneet S. Jolly
- Department of Dermatology, University of North Carolina, Chapel Hill, North Carolina, USA.
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16
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Superficial Fungal Infections. Infect Dis (Lond) 2017. [DOI: 10.1016/b978-0-7020-6285-8.00014-9] [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: 11/23/2022] Open
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17
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Developments in L2-based human papillomavirus (HPV) vaccines. Virus Res 2016; 231:166-175. [PMID: 27889616 DOI: 10.1016/j.virusres.2016.11.020] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 11/17/2016] [Accepted: 11/18/2016] [Indexed: 11/21/2022]
Abstract
Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP vaccines limits the number of included VLP types and thus the vaccines' spectrum of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition, current vaccines do not protect against cutaneous HPV types causing benign skin warts, or against beta-papillomavirus (betaPV) types implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes that induce low-titer yet broadly cross-neutralizing antibodies to heterologous PV types and provide cross-protection in animal challenge models. Efforts to increase the low immunogenicity of L2 (poly)-peptides and thereby to develop broader-spectrum HPV vaccines are the focus of this review.
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18
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Inflammatory Cutaneous Diseases in Renal Transplant Recipients. Int J Mol Sci 2016; 17:ijms17081362. [PMID: 27548160 PMCID: PMC5000757 DOI: 10.3390/ijms17081362] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Revised: 08/09/2016] [Accepted: 08/09/2016] [Indexed: 11/17/2022] Open
Abstract
Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients-in agreement with the general action of immunosuppressant therapies in reducing inflammation-we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.
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19
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Imko-Walczuk B, Okuniewska A, Prędota-Głowacka A, Jaśkiewicz J, Placek W, Włodarczyk Z, Dębska-Ślizień A, Rutkowski B. Benign Cutaneous Disease Among Polish Renal Transplant Recipients. Transplant Proc 2016; 48:1660-6. [DOI: 10.1016/j.transproceed.2016.02.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Revised: 02/15/2016] [Accepted: 02/24/2016] [Indexed: 12/18/2022]
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20
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Savoia P, Cavaliere G, Fava P. Risk of infectious diseases and cutaneous tumours in solid organ recipients: A meta-analysis of literature. World J Meta-Anal 2015; 3:11-19. [DOI: 10.13105/wjma.v3.i1.11] [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: 07/22/2014] [Revised: 09/08/2014] [Accepted: 11/19/2014] [Indexed: 02/05/2023] Open
Abstract
AIM: To compare the risk of cutaneous infections and tumours in kidney transplant recipients with data recently published about this topic.
METHODS: In the present work, we evaluated the incidence of bacterial, fungal and viral cutaneous infectious diseases and the development of skin cancers in a cohort of 436 patients who underwent a renal transplantation. The median age at transplantation of our patients was 50 years and the median duration of the immunosuppression was of 7.2 years. Data obtained from our cohort were compared with those obtained by a systematic review of the literature of the last 20 years about the same topic.
RESULTS: Infectious diseases were the most frequent dermatological disorders that were diagnosed after transplantation, affecting about the 16.5% of patients. Herpes virus reactivation occurs in about the 35% of patients and is more common within 6 mo from transplantation, whereas when the immunosuppression is reduced, skin infections are mainly represented by Human Papilloma Virus infections and localized mycosis, such as pityriasis versicolor and superficial candidiasis. Bacterial infections were relatively rare and occur mainly in the first months after transplantation. The cumulative risk to develop skin cancer enhance significantly over the time, as consequence of long-term immunosuppressive regiments. Endogenous and exogenous risk factors, as well as the schedule of immunosuppression can play a role and justify the different incidence of skin cancer in the various series.
CONCLUSION: Skin infections and cancer, commonly diagnosed in transplanted patients, impact on survival and life-quality, justifying the realization of follow-up programs for the early diagnosis and treatment.
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21
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Schellenbacher C, Kwak K, Fink D, Shafti-Keramat S, Huber B, Jindra C, Faust H, Dillner J, Roden RBS, Kirnbauer R. Efficacy of RG1-VLP vaccination against infections with genital and cutaneous human papillomaviruses. J Invest Dermatol 2013; 133:2706-2713. [PMID: 23752042 PMCID: PMC3826974 DOI: 10.1038/jid.2013.253] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2013] [Accepted: 05/15/2013] [Indexed: 12/20/2022]
Abstract
Licensed human papillomavirus (HPV) vaccines, based on virus-like particles (VLPs) self-assembled from major capsid protein L1, afford type-restricted protection against HPV types 16/18/6/11 (or 16/18 for the bivalent vaccine), which cause 70% of cervical cancers (CxCas) and 90% of genital warts. However, they do not protect against less prevalent high-risk (HR) types causing 30% of CxCa, or cutaneous HPV. In contrast, vaccination with the minor capsid protein L2 induces low-level immunity to type-common epitopes. Chimeric RG1-VLP presenting HPV16 L2 amino acids 17–36 (RG1 epitope) within the DE-surface loop of HPV16 L1 induced cross-neutralizing antisera. We hypothesized that RG1-VLP vaccination protects against a large spectrum of mucosal and cutaneous HPV infections in vivo. Immunization with RG1-VLP adjuvanted with human-applicable alum-MPL (aluminum hydroxide plus 3-O-desacyl-4′-monophosphoryl lipid A) induced robust L2 antibodies (ELISA titers 2,500–12,500), which (cross-)neutralized mucosal HR HPV16/18/45/37/33/52/58/35/39/51/59/68/73/26/69/34/70, low-risk HPV6/11/32/40, and cutaneous HPV2/27/3/76 (titers 25–1,000) using native virion- or pseudovirion (PsV)-based assays, and a vigorous cytotoxic T lymphocyte response by enzyme-linked immunospot. In vivo, mice were efficiently protected against experimental vaginal challenge with mucosal HR PsV types HPV16/18/45/31/33/52/58/35/39/51/59/68/56/73/26/53/66/34 and low-risk HPV6/43/44. Enduring protection was demonstrated 1 year after vaccination. RG1-VLP is a promising next-generation vaccine with broad efficacy against all relevant mucosal and also cutaneous HPV types.
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Affiliation(s)
- Christina Schellenbacher
- Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria
| | - Kihyuck Kwak
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Dieter Fink
- Institute of Laboratory Animal Science, Veterinary University Vienna, Vienna, Austria
| | - Saeed Shafti-Keramat
- Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria
| | - Bettina Huber
- Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria
| | - Christoph Jindra
- Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria
| | - Helena Faust
- Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden
| | - Joakim Dillner
- Department of Laboratory Medicine, Medical Epidemiology and Biostatistics, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Richard B S Roden
- Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Reinhard Kirnbauer
- Laboratory of Viral Oncology (LVO), Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Medical University Vienna (MUW), Vienna, Austria.
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23
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Abstract
Nonneoplastic mucocutaneous lesions are frequent in organ transplant recipients. Many of them are caused by a direct toxicity of immunosuppressive drugs, in particular glucocorticoids and cyclosporine. The effects of these agents are dose- and time-dependent. Glucocorticoids can cause acne, Cushingoid appearance, irregular purpuric areas, friable skin, and wide and violaceous stripes. Cyclosporine can cause hypertrichosis, pilosebaceous lesions, and gum hypertrophy. Patients with esthetic changes may show poor adherence to treatment with these immunosuppressive agents that may lead to progressive graft dysfunction. Apart from this direct toxicity, vigorous immunosuppression may render the transplant recipients more susceptible to mucocutaneous infections. Fungal infection, viral warts, and bacterial folliculitis are the most frequent types of mucocutaneous infection. Some fungal infections, such as oral candidiasis and pityriasis versicolor, are relatively trivial, but other mycotic infections can cause severe or disfigurating lesions. Among viral infections, warts and condylomata caused by human papilloma virus are frequent and may favor the development of nonmelanoma skin cancer. Bacterial infections are usually trivial in the early period after transplantation, being represented almost exclusively by folliculitis. However, subcutaneous infections may cause a necrotizing fasciculitis which is a life-threatening disorder, usually sustained by polymicrobial pathogens.
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Affiliation(s)
- Claudio Ponticelli
- Division of Nephrology, Istituto Scientifico Humanitas, Rozzano, Milan, Italy.
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