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American Journal of Clinical Dermatology Sep 2022Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving... (Review)
Review
Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.
Topics: Dermatitis; Humans; Inflammation; Neutrophils; Pyoderma Gangrenosum
PubMed: 35606650
DOI: 10.1007/s40257-022-00699-8 -
Giornale Italiano Di Dermatologia E... Oct 2020Pyogenic arthritis, pyoderma gangrenosum (PG) and acne (PAPA) syndrome is an autosomal dominant autoinflammatory syndrome due to mutations in proline-serine-threonine... (Review)
Review
Pyogenic arthritis, pyoderma gangrenosum (PG) and acne (PAPA) syndrome is an autosomal dominant autoinflammatory syndrome due to mutations in proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) gene and presenting with cutaneous and articular manifestations. Other autoinflammatory syndromes caused by mutations in PSTPIP1 gene or characterized by clinical findings overlapping with those found in PAPA syndrome have been recently included in the group of PAPA spectrum disorders. These disorders are PASH (PG, acne and hidradenitis suppurativa [HS]), PAPASH (PASH associated with pyogenic sterile arthritis), PsAPASH (PASH combined with psoriatic arthritis [PsA], PASS (PG, acne, ankylosing spondylitis, with or without HS), PAC (PG, acne and ulcerative colitis [UC]) and PAMI syndrome (PSTPIP1-associated myeloid-related-proteinemia inflammatory syndrome). Except for PAPA and PAMI, no specific pathogenetic mutations have been identified in these syndromes. Dermatologists should be aware that PG, acne and HS may represent cutaneous signs hiding the presence of these rare entities. Systemic corticosteroids, a number of immunosuppressants and biologics, such as interleukin (IL)-1 antagonists and tumour necrosis factor (TNF) α inhibitors, are nowadays therapy for these diseases. A pathogenesis-driven treatment is the near future in the management of these conditions.
Topics: Acne Vulgaris; Arthritis, Infectious; Humans; Pyoderma Gangrenosum
PubMed: 32618443
DOI: 10.23736/S0392-0488.20.06629-8 -
Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts.JAMA Dermatology Apr 2018Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition not compatible with...
IMPORTANCE
Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition not compatible with clinical decision making or inclusion for clinical trials.
OBJECTIVE
To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum.
EVIDENCE REVIEW
Diagnostic criteria were created following a Delphi consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were validated against peer-reviewed established cases of pyoderma gangrenosum and mimickers using k-fold cross-validation with methods of multiple imputation.
FINDINGS
Delphi exercise yielded 1 major criterion-biopsy of ulcer edge demonstrating neutrophilic infiltrate-and 8 minor criteria: (1) exclusion of infection; (2) pathergy; (3) history of inflammatory bowel disease or inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating within 4 days of appearing; (5) peripheral erythema, undermining border, and tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an anterior lower leg; (7) cribriform or "wrinkled paper" scar(s) at healed ulcer sites; and (8) decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Receiver operating characteristic analysis revealed that 4 of 8 minor criteria maximized discrimination, yielding sensitivity and specificity of 86% and 90%, respectively.
CONCLUSIONS AND RELEVANCE
This Delphi exercise produced 1 major criterion and 8 minor criteria for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a guideline for clinicians, allowing for fewer misdiagnoses and improved patient selection for clinical trials.
Topics: Area Under Curve; Biopsy; Consensus; Delphi Technique; Humans; Neutrophils; Pyoderma Gangrenosum; ROC Curve; Skin; Skin Ulcer
PubMed: 29450466
DOI: 10.1001/jamadermatol.2017.5980 -
Drugs Sep 2023Pyoderma gangrenosum is a rare neutrophilic dermatosis that leads to exceedingly painful ulcerations of the skin. Although the exact pathogenesis is not yet fully... (Review)
Review
Pyoderma gangrenosum is a rare neutrophilic dermatosis that leads to exceedingly painful ulcerations of the skin. Although the exact pathogenesis is not yet fully understood, various auto-inflammatory phenomena with increased neutrophil granulocyte activity have been demonstrated. Despite the limited understanding of the pathogenesis, it is no longer a diagnosis of exclusion, as it can now be made on the basis of validated scoring systems. However, therapy remains a major multidisciplinary challenge. Various immunosuppressive and immunomodulatory therapies are available for the treatment of affected patients. In addition, concomitant topical pharmacologic therapy, wound management and pain control should always be addressed. Corticosteroids and/or cyclosporine remain the systemic therapeutics of choice for most patients. However, in recent years, there has been an increasing number of studies on the positive effects of biologic therapies such as inhibitors of tumour necrosis factor-α; interleukin-1, interleukin-17, interleukin-23 or complement factor C5a. Biologics have now become the drug of choice in certain scenarios, particularly in patients with underlying inflammatory comorbidities, and are increasingly used at an early stage in the disease rather than in therapy refractory patients.
Topics: Humans; Pyoderma Gangrenosum; Skin; Pain Management; Biological Products; Cyclosporine
PubMed: 37610614
DOI: 10.1007/s40265-023-01931-3 -
Journal of the American Academy of... May 2022Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk. (Review)
Review
BACKGROUND
Hidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk.
OBJECTIVE
To provide evidence-based screening recommendations for comorbidities linked to HS.
METHODS
Systematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria.
RESULTS
Screening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity.
LIMITATIONS
Screening recommendations represent one component of a comprehensive care strategy.
CONCLUSIONS
Dermatologists should support screening efforts to identify comorbid conditions in HS.
Topics: Canada; Comorbidity; Female; Hidradenitis Suppurativa; Humans; Metabolic Syndrome; Pyoderma Gangrenosum
PubMed: 33493574
DOI: 10.1016/j.jaad.2021.01.059 -
International Journal of Molecular... Mar 2020Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform... (Review)
Review
Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.
Topics: Cytokines; Dermatomyositis; Erythema; Humans; Neoplasms; Paraneoplastic Syndromes; Pemphigus; Pyoderma Gangrenosum; Skin; Skin Diseases; Sweet Syndrome
PubMed: 32245283
DOI: 10.3390/ijms21062178 -
Wounds : a Compendium of Clinical... Jan 2016Pyoderma gangrenosum is an unusual cause of skin ulcerations that wound specialists must be prepared to recognize. There is no diagnostic test since it is a diagnosis of... (Review)
Review
Pyoderma gangrenosum is an unusual cause of skin ulcerations that wound specialists must be prepared to recognize. There is no diagnostic test since it is a diagnosis of exclusion, and if the disease is not recognized it can quickly become much worse. Pathergy, whereby a lesion begins or worsens due to trauma, such as a scrape, bite, debridement, surgery, or biopsy, is seen with pyoderma and requires special consideration. This case series and review will summarize the salient features of pyoderma and its treatment with an emphasis on the controversial role of surgery with pyoderma.
Topics: Anti-Infective Agents; Contraindications; Debridement; Diagnosis, Differential; Disease Progression; Early Diagnosis; Glucocorticoids; Humans; Methylprednisolone; Practice Guidelines as Topic; Prednisone; Pyoderma Gangrenosum; Wound Healing
PubMed: 26779805
DOI: No ID Found -
Clinical Medicine (London, England) May 2019Pyoderma gangrenosum (PG) is a reactive non-infectious inflammatory dermatosis falling under the spectrum of the neutrophilic dermatoses. There are several subtypes,...
Pyoderma gangrenosum (PG) is a reactive non-infectious inflammatory dermatosis falling under the spectrum of the neutrophilic dermatoses. There are several subtypes, with 'classical PG' as the most common form in approximately 85% cases. This presents as an extremely painful erythematous lesion which rapidly progresses to a blistered or necrotic ulcer. There is often a ragged undermined edge with a violaceous/erythematous border. The lower legs are most frequently affected although PG can present at any body site. Other subtypes include bullous, vegetative, pustular, peristomal and superficial granulomatous variants. The differential diagnosis includes all other causes of cutaneous ulceration as there are no definitive laboratory or histopathological criteria for PG. Underlying systemic conditions are found in up to 50% of cases and thus clinicians should investigate thoroughly for such conditions once a diagnosis of PG has been made. Treatment of PG remains largely anecdotal, with no national or international guidelines, and is selected according to severity and rate of progression. Despite being a well-recognised condition, there is often a failure to make an early diagnosis of PG. This diagnosis should be actively considered when assessing ulcers, as prompt treatment may avoid the complications of prolonged systemic therapy, delayed wound healing and scarring.
Topics: Diagnosis, Differential; Early Diagnosis; Humans; Pyoderma Gangrenosum
PubMed: 31092515
DOI: 10.7861/clinmedicine.19-3-224 -
Ugeskrift For Laeger Jun 2021Pyoderma gangrenosum is a diagnostic and therapeutic challenge. A misdiagnosis or delayed diagnosis can lead to increased morbidity and death. A fast workup and... (Review)
Review
Pyoderma gangrenosum is a diagnostic and therapeutic challenge. A misdiagnosis or delayed diagnosis can lead to increased morbidity and death. A fast workup and initiation of treatment is essential. In this review, we present new diagnostic criteria, which can ease the diagnosis, and we summarise the evidence of different treatment modalities. The evidence points towards local immunosuppressive treatment in mild disease, supplemented by systemic glucorticosteroids, ciclosporin or tumour necrosis factor-alpha inhibitors in severe cases. Other biologics are emerging.
Topics: Diagnostic Errors; Humans; Immunosuppressive Agents; Pyoderma Gangrenosum
PubMed: 34120685
DOI: No ID Found -
Journal of Vascular Surgery. Venous and... Mar 2017Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other... (Review)
Review
OBJECTIVE
Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions.
METHODS
An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported.
RESULTS
Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed.
CONCLUSIONS
Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients.
Topics: Anemia, Sickle Cell; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antiphospholipid Syndrome; Antirheumatic Agents; Antisickling Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Calciphylaxis; Cardiovascular Agents; Chronic Disease; Cryoglobulinemia; Diagnosis, Differential; Embolism, Cholesterol; Erythema Nodosum; Humans; Hydroxyurea; Leg Ulcer; Panniculitis; Pyoderma Gangrenosum; Steroids; Thromboangiitis Obliterans; Vasculitis; Wound Healing
PubMed: 28214498
DOI: 10.1016/j.jvsv.2016.09.006