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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 -
Journal of the American Academy of... Sep 2022
Topics: Humans; Pyoderma Gangrenosum; Rituximab; Treatment Outcome
PubMed: 34942295
DOI: 10.1016/j.jaad.2021.12.028 -
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 Jul 2024Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been...
BACKGROUND AND OBJECTIVE
Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been elucidated, although contributions from dysregulation of the immune system in patients with apparent genetic predispositions have been postulated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review with the objective of identifying inborn errors of immunity in the presence of PG as well as their clinical characteristics of severity including number of PG lesions and anatomic areas affected, and treatment outcomes.
METHODS
A literature search was performed using PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science through August 24, 2023, for studies published in English using the search terms: "pyoderma gangrenosum," "inborn error of immunity," "immune defect*," and a list of genetic mutations potentially associated with PG.
RESULTS
Seventy-four cases of PG associated with inborn errors of immunity were identified. The results demonstrate an association of PG with a variety of inborn errors of immunity, including genetic mutations not classically associated with the condition. Genetic mutations such as BTK, IL1RN, ITGB2, LPIN2, MEFV, NFkB1, NLRP3, NLRP12, NOD2, PSMB8, PLCG2, PSTPIP1, RAG1, TTC37, and WDR1, as well as complement component 2/complement component 4 (C2/C4) and complement component 7 (C7) deficiencies were identified in the presence of either idiopathic or syndromic PG. Of note, mutations in genes such as PSMB8, NLRP3, and IL1RN were found to be associated with a more severe and atypical course of PG, whereas mutations in RAG1 as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in NFkB1, ITGB2, and PSTPIP1 were associated with the most heterogeneous clinical presentations.
CONCLUSIONS
Human inborn errors of immunity may be implicated in the genetic predisposition to PG and may influence the clinical presentation. Due to the rarity of these diseases, further work must be done to describe the association between inborn errors of immunity and PG. Identifying inborn errors of immunity that may contribute to the development of PG may assist in further elucidating the mechanism of PG, guiding targeted treatment, and improving clinical outcomes for these patients.
PubMed: 38951460
DOI: 10.1007/s40257-024-00875-y -
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 -
Frontiers in Immunology 2022Hidradenitis suppurativa were associated with comorbidities in various organ systems. Inflammatory dermatological diseases such as pyoderma gangrenosum were reported to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hidradenitis suppurativa were associated with comorbidities in various organ systems. Inflammatory dermatological diseases such as pyoderma gangrenosum were reported to be associated with hidradenitis suppurativa. Nevertheless, as for the association between hidradenitis suppurativa and psoriasis, evidences were insufficient. In many studies, the association between psoriasis and hidradenitis suppurativa has been reported. However, some evidence seems to be controversial. The purpose of the systematic review and meta-analysis was to assess whether there was significant association between HS and psoriasis.
METHODS
On June 01, 2022, we appraised 2,795 articles from databases including PubMed, Web of Science and Embase. Search syntaxes were based on 'hidradenitis suppurativa' or 'acne inversa' with "psoriasis", "comorbidities" or 'epidemiology'. Synonyms were determined based on MeSH terms and Emtree. Observational results that evaluated the odds ratio for people with hidradenitis suppurativa who had psoriasis were extracted for qualitative synthesis.
RESULTS
After the selection process of the initial 2,795 studies, ten observational studies, including 3 cohort studies, 1 case-control study, and 6 cross-sectional studies, were extracted for critical appraisal. Based on the integration of 7 studies (with more than 560,000 participants included), people with hidradenitis suppurativa had a higher risk of having psoriasis, with a 2.67-fold risk (95% CI, 1.84, 3.87). The association remained in the sensitivity analyses utilizing strict adjustment models. In the analysis that only included studies with a similar study design and adjustments in obesity-related factors, the risk of people with hidradenitis suppurativa having psoriasis was 3.24 (95% CI, 2.27, 4.62). In male patients with HS, the risk of having psoriasis was 4.30-fold higher than male patients without HS (95% CI, 2.37, 7.78). Likewise, in an analysis including 3 cross-sectional studies, the risk of female HS patients having psoriasis was 3.94-fold higher than female HS-free patients (95% CI, 2.34, 6.63).
CONCLUSIONS
The co-occurrence of hidradenitis suppurativa and psoriasis can greatly increase the burden of the disease. Psoriasis could be one of the critical comorbidities of hidradenitis suppurativa and should be recommended for future screening and follow up. The association between the two diseases should be kept in mind in managing hidradenitis suppurativa patients. More prospective studies are needed to establish the true magnitude of the association between psoriasis and hidradenitis suppurativa.
Topics: Humans; Male; Female; Cross-Sectional Studies; Case-Control Studies; Hidradenitis Suppurativa; Psoriasis; Comorbidity
PubMed: 36532043
DOI: 10.3389/fimmu.2022.1033844 -
Journal of the American Academy of... Jun 2020Pyoderma gangrenosum (PG) is a devastating neutrophilic dermatosis that may be associated with trauma or systemic diseases. The associations, characteristics, and...
BACKGROUND
Pyoderma gangrenosum (PG) is a devastating neutrophilic dermatosis that may be associated with trauma or systemic diseases. The associations, characteristics, and temporal relationship of PG with hematologic malignancies are not well understood.
OBJECTIVE
We performed a systematic review of PG associated with hematologic malignancies using data from case reports, case series, and retrospective studies.
METHODS
We searched MEDLINE, EMBASE, Scopus, and Web of Science from each database's inception to December 12, 2018. Two reviewers independently selected studies and extracted data.
RESULTS
Two hundred seventy-nine publications met the inclusion criteria (340 cases). Myelodysplastic syndrome (MDS) was the most commonly reported hematologic malignancy associated with PG, followed by monoclonal gammopathy of undetermined significance and acute myeloid leukemia. The mean age of patients was 56.5 years, with males being more common. There was a predominance of the ulcerative PG subtype and multifocal distributions across all hematologic malignancies. The majority of MDS cases preceded PG, which was reversed for MGUS.
LIMITATIONS
The data were limited by reporting bias because PG subtypes rely on the rendered diagnosis reported. In addition, the classification for hematologic malignancies has evolved since 1978.
CONCLUSION
Patients with PG should be evaluated for hematologic malignancies, with MDS being the most common.
Topics: Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Monoclonal Gammopathy of Undetermined Significance; Myelodysplastic Syndromes; Pyoderma Gangrenosum
PubMed: 31560977
DOI: 10.1016/j.jaad.2019.09.032 -
Journal of Plastic, Reconstructive &... Jan 2024Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that can develop at a surgical site. Diagnosis can be challenging at its presentation causing... (Review)
Review
BACKGROUND
Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis that can develop at a surgical site. Diagnosis can be challenging at its presentation causing delays in appropriate treatment. The aim of this study is to review the current literature as well as to describe the clinical presentation, diagnostic pathway, and treatment of PG after reduction mammaplasty in order to define a standardized multidisciplinary diagnostic and therapeutic approach. In the future, this may ease early identification and prompt treatment, and eventually minimize severe morbidity and long-term sequelae.
METHODS
The entire PubMed/Medline database was screened following the PRISMA guidelines to identify studies describing PG that have occurred after reduction mammoplasty.
RESULTS
Twenty-eight articles including 31 patients reported a PG after breast reduction surgery between January 1988 and March 2022. Twenty-one (68%) patients presented with skin ulcerations, 14 (45%) with erythema, and 5 (16%) with vesicles. Out of the 30 cases that underwent bilateral surgery, 18 (60%) developed PG bilaterally. In 12 out of 31 patients, nipple-areolar complex (NAC) involvement was evaluated, though in 10 patients (83%) the NAC was spared. Of the 20 patients (65%) who underwent skin biopsies for histopathological examination, 18 (90%) showed neutrophilic infiltration of the dermal layers. All 31 patients (100%) showed rapid clinical improvement after the introduction of immunosuppressive therapy.
CONCLUSIONS
PG can result in devastating skin alterations also after reduction mammoplasty, if misdiagnosed. However, it presents with constant yet unspecific local and general signs and symptoms that can be recognized to early initiate an appropriate pharmacological treatment.
Topics: Female; Humans; Pyoderma Gangrenosum; Mammaplasty; Skin; Mastectomy; Immunosuppression Therapy
PubMed: 38118291
DOI: 10.1016/j.bjps.2023.11.041 -
Anais Brasileiros de Dermatologia 2019Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. Despite the existence of diagnostic criteria, there...
Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. Despite the existence of diagnostic criteria, there is no gold standard for diagnosis or treatment. In Latin America, recognizing and treating pyoderma gangrenosum is even more challenging since skin and soft tissue bacterial and non-bacterial infections are common mimickers. Therefore, this review aims to characterize reported cases of pyoderma gangrenosum in this region in order to assist in the assessment and management of this condition. Brazil, Mexico, Argentina, and Chile are the countries in Latin America that have reported the largest cohort of patients with this disease. The most frequent clinical presentation is the ulcerative form and the most frequently associated conditions are inflammatory bowel diseases, inflammatory arthropaties, and hematologic malignancies. The most common treatment modalities include systemic corticosteroids and cyclosporine. Other reported treatments are methotrexate, dapsone, and cyclophosphamide. Finally, the use of biological therapy is still limited in this region.
Topics: Diagnosis, Differential; Humans; Latin America; Prevalence; Pyoderma Gangrenosum
PubMed: 31789268
DOI: 10.1016/j.abd.2019.06.001 -
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