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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 -
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 -
Nature Reviews. Disease Primers Oct 2020Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral... (Review)
Review
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies.
Topics: Humans; Pyoderma Gangrenosum; Quality of Life
PubMed: 33033263
DOI: 10.1038/s41572-020-0213-x -
JAMA Dermatology Feb 2022
Topics: Humans; Pyoderma Gangrenosum
PubMed: 34910081
DOI: 10.1001/jamadermatol.2021.5001 -
Clinics in Podiatric Medicine and... Oct 2021Pyoderma gangrenosum (PG), which most frequently affects the lower extremity, is a complicated disease state that results from a combination of inflammation,... (Review)
Review
Pyoderma gangrenosum (PG), which most frequently affects the lower extremity, is a complicated disease state that results from a combination of inflammation, neutrophilic invasion, and genetic predisposition. There may also be certain comorbidities involved or it may be idiopathic. The many variations of PG mean that it often presents and responds differently to various treatments based on the specific case. Overall, there have been improvements in understanding the disease; however, further research should focus on finding better ways to predict and prevent this rapidly progressive, painful disease.
Topics: Comorbidity; Humans; Inflammation; Pyoderma Gangrenosum
PubMed: 34538436
DOI: 10.1016/j.cpm.2021.06.002 -
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 -
Dermatologic Clinics Apr 2024Pyoderma gangrenosum is a rare neutrophilic dermatosis that results in painful cutaneous ulcers and is frequently associated with underlying hematologic disorders,... (Review)
Review
Pyoderma gangrenosum is a rare neutrophilic dermatosis that results in painful cutaneous ulcers and is frequently associated with underlying hematologic disorders, inflammatory bowel disease, or other autoimmune disorders. Pathogenesis involves an imbalance between proinflammatory and anti-inflammatory mediators, leading to tissue damage from neutrophils. First-line treatment options with the greatest evidence include systemic corticosteroids, cyclosporine, and tumor necrosis factor alpha inhibitors. Other steroid-sparing therapies such as dapsone, mycophenolate mofetil, intravenous immunoglobulin, and targeted biologic or small molecule inhibitors also have evidence supporting their use. Wound care and management of underlying associated disorders are critical parts of the treatment regimen.
Topics: Humans; Pyoderma Gangrenosum; Immunosuppressive Agents; Cyclosporine; Adrenal Cortex Hormones; Skin Ulcer
PubMed: 38423680
DOI: 10.1016/j.det.2023.12.002 -
BMJ (Clinical Research Ed.) Sep 2023
Topics: Humans; Pyoderma Gangrenosum
PubMed: 37673429
DOI: 10.1136/bmj-2023-075863 -
Clinical and Experimental Dermatology Apr 2023Pyoderma gangrenosum can be associated with haematological malignancies but rarely a myeloproliferative neoplasm. A review of requests for molecular detection of... (Review)
Review
Pyoderma gangrenosum can be associated with haematological malignancies but rarely a myeloproliferative neoplasm. A review of requests for molecular detection of myeloproliferative neoplasm driver mutations in patients with pyoderma gangrenosum was performed and revealed that testing for these mutations is unwarranted in cases where there are no clinical, haematological or morphological features of a myeloproliferative neoplasm present.
Topics: Humans; Pyoderma Gangrenosum; Myeloproliferative Disorders; Hematologic Neoplasms
PubMed: 36702807
DOI: 10.1093/ced/llad037