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Frontiers in Immunology 2018The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways...
The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease. A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS. A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin () and mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response. The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions.
Topics: Adaptor Proteins, Signal Transducing; Amyloid Precursor Protein Secretases; Cytokines; Cytoskeletal Proteins; Hidradenitis Suppurativa; Humans; Inflammation; Membrane Glycoproteins; Models, Immunological; Mutation; Signal Transduction; Skin
PubMed: 30619323
DOI: 10.3389/fimmu.2018.02965 -
The British Journal of Dermatology Jan 2019
Topics: Clinical Trials as Topic; Humans; Pyoderma Gangrenosum; Severity of Illness Index; Validation Studies as Topic
PubMed: 30171689
DOI: 10.1111/bjd.17122 -
Journal of Plastic, Reconstructive &... Jul 2018Post-surgical pyoderma gangrenosum (PSPG) is a rare inflammatory skin disorder of unknown aetiology. Given its similar presentation to wound infection and lack of...
BACKGROUND
Post-surgical pyoderma gangrenosum (PSPG) is a rare inflammatory skin disorder of unknown aetiology. Given its similar presentation to wound infection and lack of reliable diagnostic tests as well as pathognomonic clinical features, PSPG is difficult to diagnose. The aim of this review was to identify factors contributing to PSPG to aid with timely diagnosis and appropriate therapy.
METHODS
A systematic literature review was performed by following PRISMA guidelines, focusing on PSPG after reconstructive and aesthetic breast surgery. The online databases PubMed, Medline, EMBASE, Scopus, and Cochrane were used, and additionally, a Google search was performed.
RESULTS
A total of 68 articles describing 87 cases of PSPG following aesthetic and reconstructive breast surgery were found. The majority of PSPG (44%) occurred after breast reduction surgery and microsurgical breast reconstruction (16%). The most common associated conditions were malignancies in 37% and autoimmune deficiencies in 17%. Microbiological examinations were found to have a negative result in 90%. The median time from initial presentation with symptoms to correct diagnosis of PG was on average 12.5 days, with unsuccessful first-line therapy on average for 20.0 days. After the diagnosis of PG, medical therapy most commonly involved steroids in 84% and/or Cyclosporine A in 22% of the cases. On average, the duration of this therapy was 4.7 months.
CONCLUSION
The diagnosis of PSPG remains a challenging issue. However, according to the presented review, several distinct clinical signs in combination with lack of treatment response should prompt further investigation to promote timely diagnosis and correct treatment of this potentially debilitating disease.
Topics: Autoimmune Diseases; Breast Neoplasms; Cyclosporine; Dermatologic Agents; Diagnostic Errors; Female; Fever; Glucocorticoids; Humans; Immunosuppressive Agents; Leukocytosis; Mammaplasty; Mastectomy; Postoperative Complications; Pyoderma Gangrenosum; Skin Transplantation; Surgical Wound Infection; Time-to-Treatment
PubMed: 29748073
DOI: 10.1016/j.bjps.2018.03.013 -
American Journal of Clinical Dermatology Aug 2018There is little consensus regarding the prevalence and distribution of underlying systemic diseases among patients with pyoderma gangrenosum. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is little consensus regarding the prevalence and distribution of underlying systemic diseases among patients with pyoderma gangrenosum.
OBJECTIVE
The objective of this study was to synthesize existing data on the prevalence of associated systemic diseases in patients with pyoderma gangrenosum.
METHODS
We performed a systematic review and meta-analysis of observational studies in MEDLINE, EMBASE, and Scopus (1823-2017). The quality of evidence was assessed using a modified Newcastle-Ottawa Scale. A meta-analysis was performed using random-effects models to estimate pooled prevalence rates with 95% confidence intervals.
RESULTS
Twenty-one eligible studies comprising 2611 patients with pyoderma gangrenosum were included in the quantitative synthesis. The overall random-effects pooled prevalence of associated systemic diseases was 56.8% (95% confidence interval 45.5-67.4). The leading underlying disease was inflammatory bowel disease (17.6%; 95% confidence interval 13.0-22.7), followed by arthritis (12.8%; 95% confidence interval 9.2-16.9), hematological malignancies (8.9%; 95% confidence interval 6.5-11.6), and solid malignancies (7.4%; 95% confidence interval 5.8-9.1). In 16.3% (95% confidence interval 7.7-27.1) of cases, the onset of pyoderma gangrenosum was attributed to the pathergy phenomenon.
CONCLUSIONS
More than half of patients with pyoderma gangrenosum present with a relevant underlying disease. Inflammatory bowel disease and arthritis are the most frequently associated diseases. Relative to the reported literature, the pooled prevalence of arthritis and hematological malignancies is lower, while the pooled prevalence of solid malignancies is higher. Owing to the high level of heterogeneity among most of the comparisons, results should be interpreted with caution.
Topics: Arthritis; Humans; Inflammatory Bowel Diseases; Neoplasms; Pyoderma Gangrenosum
PubMed: 29721816
DOI: 10.1007/s40257-018-0356-7 -
The British Journal of Dermatology Aug 2018Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments.
BACKGROUND
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments.
OBJECTIVES
To review the effectiveness of systemic therapy for PG.
METHODS
We searched six databases for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time to healing and adverse effects.
RESULTS
We found 3326 citations and 375 articles underwent full-text review; 41 studies met the inclusion criteria. There were 704 participants in 26 retrospective cohort studies, three prospective cohort studies, seven case series, one case-control study, two open-label trials and two randomized controlled trials (RCTs). Systemic corticosteroids were the most studied (32 studies), followed by ciclosporin (21 studies), biologics (16 studies) and oral dapsone (11 studies). One RCT (STOP-GAP, n = 121) showed that prednisolone and ciclosporin were similar: 15-20% of patients showed complete healing at 6 weeks and 47% at 6 months. Another RCT (n = 30) found that infliximab was superior to placebo at 2 weeks (46% vs. 6% response), with a 21% complete healing rate at 6 weeks. Two uncontrolled trials showed 60% and 37% healing within 4 months for canakinumab and infliximab, respectively; other data suggest that patients with concurrent inflammatory bowel disease may benefit from biologics. The remaining studies were poor quality and had small sample sizes but supported the use of corticosteroids, ciclosporin and biologics.
CONCLUSIONS
Systemic corticosteroids, ciclosporin, infliximab and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.
Topics: Administration, Oral; Biological Products; Clinical Trials as Topic; Cyclosporine; Dapsone; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Injections, Intralesional; Injections, Intravenous; Observational Studies as Topic; Pyoderma Gangrenosum; Treatment Outcome
PubMed: 29478243
DOI: 10.1111/bjd.16485 -
Journal of the European Academy of... Jul 2018
Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Hematologic Diseases; Humans; Inflammatory Bowel Diseases; Lung Diseases; Pyoderma Gangrenosum
PubMed: 29377399
DOI: 10.1111/jdv.14828 -
Journal of the American Academy of... Jun 2018Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines...
BACKGROUND
Peristomal pyoderma gangrenosum (PPG) is an uncommon subtype of pyoderma gangrenosum. PPG is a challenging condition to diagnose and treat; no evidence-based guidelines exist.
OBJECTIVE
We sought to identify important clinical features of PPG and effective treatments available for its management.
METHODS
A systematic literature review of PPG was performed using PubMed, Medline, and Embase databases.
RESULTS
We describe 335 patients with PPG from 79 studies. Clinical features include a painful, rapidly progressing ulcer with undermined, violaceous borders with a history of ostomy leakage and local skin irritation or trauma. Systemic steroids are first-line therapy; infliximab and adalimumab provide concomitant control of active inflammatory bowel disease. Combination local and systemic therapy was commonly used. Wound dressings, vehicle selection, and appropriate ostomy devices to minimize leakage, irritation, and pressure-induced ischemia can improve healing. Distinct from classic ulcerative pyoderma gangrenosum, surgical approaches, such as stoma closure and resection of active inflammatory bowel disease, have an effective role in PPG management.
LIMITATIONS
PPG is a rare disease lacking randomized trials or diagnostic guidelines. Treatment duration and follow-up time among studies are variable.
CONCLUSIONS
Key clinical characteristics of PPG are highlighted. Several treatments, including a more prominent role for surgical intervention, may be effective for PPG treatment.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Biological Products; Colitis, Ulcerative; Crohn Disease; Disease Management; Drug Therapy, Combination; Enterostomy; Female; Humans; Male; Postoperative Complications; Prognosis; Pyoderma Gangrenosum; Reoperation; Severity of Illness Index; Skin Care; Surgical Stomas
PubMed: 29288099
DOI: 10.1016/j.jaad.2017.12.049 -
Clinical Reviews in Allergy & Immunology Dec 2017Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often... (Review)
Review
Autoimmune liver diseases, which include mainly autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and the variant syndromes, are often associated with extrahepatic autoimmune diseases. However, the association with cutaneous diseases is less well described. In the present article, we provide a systematic literature review on skin manifestations linked to each of these four autoimmune liver diseases, excluding skin manifestations of systemic diseases. The association of autoimmune hepatitis with vitiligo is well known, with a particular striking association with type 2 autoimmune hepatitis, a condition occurring almost entirely in children and adolescents, much rarer and more aggressive than type 1 autoimmune hepatitis; probable associations are also identified with alopecia areata, psoriasis, and pyoderma gangrenosum. Primary biliary cholangitis is not linked to lichen planus as previously assumed, but to vitiligo, psoriasis and the very rare amicrobial pustulosis of the folds. The proposed diagnostic criteria for this latter condition include the presence of anti-mitochondrial autoantibodies, the serological hallmark of primary biliary cholangitis. The very strong association of primary sclerosing cholangitis with inflammatory bowel diseases hampers the search for an association with skin diseases, since inflammatory bowel diseases have a strong association with various dermatological condition, including neutrophilic dermatoses and erythema nodosum. Nevertheless, a probable association of primary sclerosing cholangitis with psoriasis is identified in this review. Variant syndromes, also called overlap syndromes, are likely associated with vitiligo as well, which is not surprising, since autoimmune hepatitis is a feature of these conditions and they may share regions of the MHC.
Topics: Autoimmune Diseases; Autoimmunity; Cholangitis; Hepatitis; Humans; Liver; Liver Diseases; Psoriasis; Skin; Vitiligo
PubMed: 28993983
DOI: 10.1007/s12016-017-8649-9 -
The Australasian Journal of Dermatology Aug 2018Bacterial skin infections in Indigenous children in Australia frequently lead them to access primary health care. This systematic review aims to identify and analyse...
BACKGROUND/OBJECTIVES
Bacterial skin infections in Indigenous children in Australia frequently lead them to access primary health care. This systematic review aims to identify and analyse available studies describing the treatment and prevention of bacterial skin infections in Indigenous children.
METHODS
Electronic databases including Scopus, MEDLINE, CINAHL, ProQuest, Informit and Google Scholar were searched. Studies in English published between August 1994 and September 2016, with the subject of bacterial skin infections involving Indigenous children and conducted in Australia, New Zealand, the USA or Canada were selected.
RESULTS
Initially 1474 articles were identified. After the application of inclusion and exclusion criteria, 10 articles remained. Strategies for the treatment and prevention of bacterial skin infections included the management of active infections and lesions, improving environmental and personal hygiene, the installation of swimming pools and screening and treatment.
CONCLUSION
There is a need for more, rigorous, large-scale studies to develop evidence for appropriate, culturally acceptable methods to prevent and manage bacterial skin infections in Indigenous children in Australia. The problem is complex with multiple determinants. Until underlying socioeconomic conditions are addressed skin infections will continue to be a burden to communities.
Topics: Adolescent; Anti-Bacterial Agents; Australia; Child; Child, Preschool; Housing; Humans; Hygiene; Infant; Infant, Newborn; Native Hawaiian or Other Pacific Islander; Skin Diseases, Bacterial; Swimming Pools; Toilet Facilities; Young Adult
PubMed: 28752615
DOI: 10.1111/ajd.12680 -
The British Journal of Dermatology Feb 2018Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Treatment regimens for refractory cases are nonstandardized. Intravenous immunoglobulin (IVIG) is an... (Meta-Analysis)
Meta-Analysis
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis. Treatment regimens for refractory cases are nonstandardized. Intravenous immunoglobulin (IVIG) is an emerging treatment with reported success, but the efficacy of IVIG for PG is unknown. In this systematic review of cases and case series, we assessed the efficacy of IVIG for the treatment of PG, as observed at our institution and reported in the literature. A retrospective chart review at two tertiary care hospitals between 2000 and 2015, and literature searches in PubMed/MEDLINE, EMBASE and Web of Science from all years were conducted. In total, there were 49 patients, including 43 patients from 26 articles and six institutional cases. There was complete or partial response in 43 (88%) patients and complete response in 26 (53%) patients. The mean time to initial response to treatment and treatment length were 3·5 (SD 3·3) weeks and 5·9 (SD 7·8) months, respectively. On average, 2·6 treatments had been trialled before IVIG initiation. IVIG was administered with systemic steroids in 43 (88%) cases. Mild adverse events, especially nausea and headache, were reported in 12 (24·5%) patients. Our systematic review suggests a potential role for IVIG as adjuvant therapy for refractory PG. Prospective clinical trials testing the efficacy of IVIG for refractory PG are needed to validate these findings.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Pyoderma Gangrenosum; Treatment Outcome; Young Adult
PubMed: 28742926
DOI: 10.1111/bjd.15850