Materiały źródłowe

• #1 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10889749/

  Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] The proposed pathophysiology of PG is associated with the interplay between innate and adaptive immunity and the state of autoinflammation with the crucial role of neutrophils. […] Pathogenesis of PG remains unclear. However, based on the existing research, it can be affirmed that it is a complex and multifactorial process. […] PG is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] Based on the existing reports, it can be inferred that genetic predisposition plays a significant role in the pathogenesis of PG.

• #2 Pyoderma gangrenosum: a review of pathogenesis and treatment – PubMed

  https://pubmed.ncbi.nlm.nih.gov/29406827/

  Pyoderma gangrenosum (PG) is a complex neutrophilic dermatosis that can occur as an idiopathic disease, in association with systemic conditions such as inflammatory bowel disease, as part of an inherited inflammatory syndrome. […] The main limitations to treatment have been an incomplete understanding of the pathogenesis. However, recent advances have been made in understanding the pathogenesis of this condition, and PG is now considered an autoinflammatory disease process. […] The presence of abnormal neutrophils and T-cells lead to immune dysregulation, leading to lesions of PG. Increased levels of inflammatory mediators including IL-1, IL-8, IL-17, and TNF- contribute to the development of the disease but there are still several unknown factors, including the trigger for immune dysregulation and additional contributory components of the immune system.

• #3 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] The proposed pathophysiology of PG is associated with the interplay between innate and adaptive immunity and the state of autoinflammation with the crucial role of neutrophils. […] Pathogenesis of PG remains unclear. However, based on the existing research, it can be affirmed that it is a complex and multifactorial process. […] Possible aberrant origins of inflammation encompass neutrophils, T cells, inflammasomes, keratinocyte apoptosis, and modifications in epigenetic patterns. […] Based on the existing reports, it can be inferred that genetic predisposition plays a significant role in the pathogenesis of PG.

• #4

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  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. […] Following antigenic priming in predisposed individuals, T helper (Th)17/Th1 skewing leads to the establishment of a neutrophil-dominant, self-maintaining, autoinflammatory milieu, with elevated levels of tumor necrosis factor-alpha (TNF-), interleukin (IL)-1, IL-1, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. […] Indeed, pathogenic variants of genes involved in inflammasome formation, including PSTPIP1, MEFV, NLRP3, NLRP12, and NOD2, leading to an exaggerated release of IL-1, have been documented in both syndromic (e.g., PAPA) and sporadic cases of PG.

• #5 Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management

  https://www.mdpi.com/2571-8800/4/3/28

  Pyoderma gangrenosum (PG) is a rare entity that is characterized by infiltration of neutrophils into the dermis, causing the formation of rapidly enlarging, painful and necrotic skin ulcers. The pathophysiology of PG is still poorly understood. However, genetic, autoimmune and autoinflammatory mechanisms have been proposed that could potentially explain the etiology of this ulcerating skin disorder. […] The most widely accepted theory is that PG is autoinflammatory in origin, driven by abnormalities of the innate immune system. There are several publications in support of this theory which will be discussed later in this review. […] Several hypotheses exist about the etiology of this ulcerating skin disease. Some studies suggest a complex interplay between genetics and autoimmunity as the underlying pathogenesis of pyoderma gangrenosum.

• #6 Pyoderma Gangrenosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/pyoderma-gangrenosum

  Etiology of pyoderma gangrenosum is unknown, but it can be associated with various systemic illnesses, including inflammatory bowel disease, rheumatoid arthritis, cancers, and hematologic disorders (eg, monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, polycythemia vera). It is thought to be mediated by an abnormal immune response. […] Pathophysiology of pyoderma gangrenosum is poorly understood but may involve problems with neutrophil chemotaxis. Interleukin-8 is overexpressed in lesions. […] Expansion of ulceration after surgical debridement strongly suggests pyoderma gangrenosum. […] Pyoderma gangrenosum is often associated with a systemic disorder and is probably immune-mediated.

• #7 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  Growing evidence suggests that individuals with a genetic predisposition and abnormal activation of the innate immune system create a conducive environment for the development of PG. […] Immune system dysregulation plays a crucial role in PG pathophysiology. […] PG may be induced or exacerbated by trauma (pathergy phenomenon). […] The occurrence of PG together with the autoinflammatory disorder—hidradenitis suppurativa, pyogenic arthritis, PG, acne, and hidradenitis suppurativa syndrome (PAPASH) and PG, acne, and hidradenitis suppurativa syndrome (PASH)—can be an indicator of autoinflammation in PG. […] Although IL-1α and IL-1β are acknowledged as one of the main inflammatory cytokines, only the first cytokine contributes to the development of PG. […] Cytokines suspected of contributing to PG are IL-36A and IL-36G, which are produced by epithelial cells when inflammation occurs.

• #8 Pathophysiology of pyoderma gangrenosum (PG): An updated review – EM consulte

  https://www.em-consulte.com/article/1001184/pathophysiology-of-pyoderma-gangrenosum-pg-an-upda

  Pyoderma gangrenosum is a challenging skin condition to identify and treat because of its multifactorial pathogenesis. […] Abnormalities in the function of inflammatory cytokines, the immune system, and neutrophils combined with specific genetic mutations predispose patients to develop this complex disease process. […] Early recognition of patients at risk for pyoderma gangrenosum, the necessity to improve its early diagnosis, and the future outlook of targeted and personalized therapies relies on the improved comprehension of the complex pathogenesis of pyoderma gangrenosum.

• #9 Pyoderma Gangrenosum – Creative Biolabs

  https://www.creative-biolabs.com/complement-therapeutics/pyoderma-gangrenosum.htm

  The etiology of pyoderma gangrenosum is incompletely understood, but dysregulation of the immune system (abnormal chemotaxis, neutrophil migration, phagocytosis, bactericidal ability, and abnormal neutrophil trafficking) is believed to be involved. […] Furthermore, genetic alternation also contributes to the pathophysiology of PG. […] Compared with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), seronegative arthritis, autoimmune hepatitis, etc., PG is considered one of the rare neutrophilic dermatoses, characterized by aseptic neutrophilic infiltration and systemic inflammation. So neutrophils dysfunction plays an assignable role in the etiology of PG. […] Elevated levels of inflammatory mediators have been found in lesions of PG, suggesting a pathological relationship between abnormal immune reactions and PG. T cells, macrophages, proinflammatory cytokine (IL1 and its receptor, IL-8, IL-23, TNF-, Fas, FasL, CD40, CD40L, CXCL 1/2/3, CXCL 16, etc.) are reported to be significantly increased in PG lesions.

• #10 Pyoderma gangrenosum – a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-19

  PG was initially thought to be caused by bacterial infection in the immunocompromised host. Fulbright et al. hypothesized that PG results from an aberrant immune response to yet unidentified factors. Depositions of proteins in skin vessels in PG lesions have suggested an Arthus-like reaction. Since inflammatory bowel disease is the most common underlying disorder, cross-reacting antigens in the bowel and the skin could be responsible for secondary cutaneous manifestation. […] Cellular analysis in PG demonstrated aberrant integrin oscillations on neutrophils and aberrant neutrophil tracking of patients with PG. Pathways to protect the epidermis from neutrophil infiltration seem to be insufficient in PG resulting in tissue necrosis.

• #11 Pyoderma gangrenosum: a review with special emphasis on Latin America literature | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pyoderma-gangrenosum-review-with-special-articulo-S0365059619300686

  Pyoderma gangrenosum is a neutrophilic dermatosis characterized by chronic ulcers due to an abnormal immune response. […] Pathogenesis is not well understood, but studies have suggested an abnormal immune response in patients with genetic predisposition, hence PG is classified within the spectrum of neutrophilic and auto-inflammatory syndromes. […] Neutrophilic dysfunction has been implicated in the pathogenesis of PG. […] Neutrophilic dysfunction shares the same pro-inflammatory effectors found in auto-inflammatory syndromes. Both are characterized by an over-activated innate immune system leading to the increased assembly of inflammasomes. […] Inflammasomes are responsible for the activation of the caspase 1, a protease that cleaves the pro-interleukin IL-1 into functionally active IL-1. The overproduction of IL-1 triggers the release of several pro-inflammatory cytokines and chemokines, inducing the recruitment and activation of neutrophils and subsequent neutrophil-mediated inflammation.

• #12

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  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. […] Following antigenic priming in predisposed individuals, T helper (Th)17/Th1 skewing leads to the establishment of a neutrophil-dominant, self-maintaining, autoinflammatory milieu, with elevated levels of tumor necrosis factor-alpha (TNF-), interleukin (IL)-1, IL-1, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. […] Indeed, pathogenic variants of genes involved in inflammasome formation, including PSTPIP1, MEFV, NLRP3, NLRP12, and NOD2, leading to an exaggerated release of IL-1, have been documented in both syndromic (e.g., PAPA) and sporadic cases of PG.

• #13

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  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. […] Following antigenic priming in predisposed individuals, T helper (Th)17/Th1 skewing leads to the establishment of a neutrophil-dominant, self-maintaining, autoinflammatory milieu, with elevated levels of tumor necrosis factor-alpha (TNF-), interleukin (IL)-1, IL-1, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. […] Indeed, pathogenic variants of genes involved in inflammasome formation, including PSTPIP1, MEFV, NLRP3, NLRP12, and NOD2, leading to an exaggerated release of IL-1, have been documented in both syndromic (e.g., PAPA) and sporadic cases of PG.

• #14 Pyoderma gangrenosum – Wikipedia

  https://en.wikipedia.org/wiki/Pyoderma_gangrenosum

  Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. […] Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as interleukin (IL)-8, IL-1, IL-6, interferon (IFN)-, granulocyte colony-stimulating factor, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-9, MMP10, and elafin have all been reported to be elevated in patients with pyoderma gangrenosum. […] One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma, including surgical wounds.

• #15

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  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. […] Following antigenic priming in predisposed individuals, T helper (Th)17/Th1 skewing leads to the establishment of a neutrophil-dominant, self-maintaining, autoinflammatory milieu, with elevated levels of tumor necrosis factor-alpha (TNF-), interleukin (IL)-1, IL-1, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. […] Indeed, pathogenic variants of genes involved in inflammasome formation, including PSTPIP1, MEFV, NLRP3, NLRP12, and NOD2, leading to an exaggerated release of IL-1, have been documented in both syndromic (e.g., PAPA) and sporadic cases of PG.

• #16 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  Growing evidence suggests that individuals with a genetic predisposition and abnormal activation of the innate immune system create a conducive environment for the development of PG. […] Immune system dysregulation plays a crucial role in PG pathophysiology. […] PG may be induced or exacerbated by trauma (pathergy phenomenon). […] The occurrence of PG together with the autoinflammatory disorder—hidradenitis suppurativa, pyogenic arthritis, PG, acne, and hidradenitis suppurativa syndrome (PAPASH) and PG, acne, and hidradenitis suppurativa syndrome (PASH)—can be an indicator of autoinflammation in PG. […] Although IL-1α and IL-1β are acknowledged as one of the main inflammatory cytokines, only the first cytokine contributes to the development of PG. […] Cytokines suspected of contributing to PG are IL-36A and IL-36G, which are produced by epithelial cells when inflammation occurs.

• #17 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  It has been reported that another cytokine associated with neutrophils and the development of PG may be IL-25, also known as IL-17E. […] The importance of IL-6, IL-8, IL-17, and IL-23 in PG pathomechanisms was suggested by Rubas et al. […] Therapy with the use of tumor necrosis factor (TNF) succeeded in treating PG and therefore underlined the possible importance of this cytokine in the pathophysiology of PG. […] The association between PG and adaptive immunity has not been fully established. However, some data that support this theory exist. […] Data suggest that PG has a characteristic of an autoimmune disease course of relapses and remissions.

• #18 Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments

  https://digitalcommons.kansascity.edu/studentpub/73/

  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-, interleukin (IL)-1, IL-1, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. […] For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

• #19 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  It has been reported that another cytokine associated with neutrophils and the development of PG may be IL-25, also known as IL-17E. […] The importance of IL-6, IL-8, IL-17, and IL-23 in PG pathomechanisms was suggested by Rubas et al. […] Therapy with the use of tumor necrosis factor (TNF) succeeded in treating PG and therefore underlined the possible importance of this cytokine in the pathophysiology of PG. […] The association between PG and adaptive immunity has not been fully established. However, some data that support this theory exist. […] Data suggest that PG has a characteristic of an autoimmune disease course of relapses and remissions.

• #20 Pyoderma Gangrenosum in a Patient with Bruton’s X-linked Agammaglobulinemia: Shared Pathogenesis of Altered Tumor Necrosis Factor Alpha? | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/pyoderma-gangrenosum-in-a-patient-with-brutons-x-linked-agammaglobulinemia-shared-pathogenesis-of-altered-tumor-necrosis-factor-alpha/

  Individuals with Brutons X-linked agammaglobulinemia (XLA) inherit a defect in the Btk gene, critical for B-cell differentiation. […] The coexistence of pyoderma gangrenosum (PG) in a patient with Brutons XLA has been rarely reported. PG is an uncommon, ulcerating, neutrophilic dermatosis. […] Anti-TNF agents have been effective in treating some patients with PG, suggesting TNF-alpha may play a role in the pathogenesis of PG. […] The coexistence of pyoderma gangrenosum (PG) with Brutons XLA has been rarely reported, with only four reports in the literature. […] Although the etiology is unknown, an immune-mediated process is implicated. […] The success of TNF agents suggests that this proinflammatory cytokine may play a role in PG pathogenesis. […] Here we show immunohistochemically the presence of TNF-alpha within a PG lesion.

• #21 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10889749/

  Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] The proposed pathophysiology of PG is associated with the interplay between innate and adaptive immunity and the state of autoinflammation with the crucial role of neutrophils. […] Pathogenesis of PG remains unclear. However, based on the existing research, it can be affirmed that it is a complex and multifactorial process. […] PG is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] Based on the existing reports, it can be inferred that genetic predisposition plays a significant role in the pathogenesis of PG.

• #22 Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management

  https://www.mdpi.com/2571-8800/4/3/28

  Despite the fact that PG is classified as a neutrophilic dermatosis, one theory proposes that the pathophysiology of the disease is actually driven by autoreactive T cells which destroy pilosebaceous units. […] Currently, the most accepted theory regarding the pathophysiology of PG proposes that it is an autoinflammatory disease versus being autoimmune in origin. […] Pyoderma gangrenosum is seen as part of the hereditary autoinflammatory syndromes PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis), SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) and PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis), which supports the theory that it is a disease rooted in an autoinflammatory origin. […] The findings above indicate, overall, that PG and its associated syndromes can be classified as a spectrum of autoinflammatory diseases, all with the common pathophysiologic factor of genetic mutations which lead to increased inflammasome assembly and the upregulation of PRR’s, causing an overactivation of the innate immune system.

• #23 Pyoderma gangrenosum: challenges and solutions | CCID

  https://www.dovepress.com/pyoderma-gangrenosum-challenges-and-solutions-peer-reviewed-fulltext-article-CCID

  PG is currently considered an inflammatory disease within the spectrum of neutrophilic disorders, which includes many diseases exhibiting an extraordinary clinical heterogeneity. Nevertheless, these disorders are linked by the presence of perivascular and diffuse neutrophilic infiltrates with no identifiable infectious agents. Additionally, neutrophilic diseases commonly occur in association with an underlying systemic condition such as malignancy, neutropenia, rheumatologic diseases, infections, auto-inflammatory syndromes, and immunodeficiency. Moreover, neutrophilic diseases are frequently triggered by medications and pathergy, the latter being a typical sign of PG that is certainly involved in post-surgical and peristomal PG. […] The similarities between PG and neutrophilic diseases suggest that underlying common inflammatory pathways probably converge to their pathophysiology, leading to abnormalities in polymorphonuclear neutrophils (PMN) recruitment or homeostasis. In PG and other neutrophilic diseases, elevated skin and/or circulating levels of the pro-inflammatory cytokines (IL1, IL6, TNF-, IFN-, G-CSF) and, particularly, of the potent PMN attracting chemokines, namely IL8/CXCL8 and CXCL1,2,3, along with skin infiltration by T cells, particularly at the edge of the PG ulcer, suggests an active recruitment of PMN to the skin.

• #24 Pyoderma Gangrenosum – Creative Biolabs

  https://www.creative-biolabs.com/complement-therapeutics/pyoderma-gangrenosum.htm

  Pyoderma gangrenosum has been reported in association with congenital complement deficiencies, especially the deficiencies of C2, C4, and C7. Deficiencies of C7 is associated with decreased neutrophil chemotaxis, phagocytosis, and opsonization, similar to the immunologic abnormalities described in patients with PG.

• #25 Pyoderma gangrenosum: challenges and solutions | CCID

  https://www.dovepress.com/pyoderma-gangrenosum-challenges-and-solutions-peer-reviewed-fulltext-article-CCID

  PG is currently considered an inflammatory disease within the spectrum of neutrophilic disorders, which includes many diseases exhibiting an extraordinary clinical heterogeneity. Nevertheless, these disorders are linked by the presence of perivascular and diffuse neutrophilic infiltrates with no identifiable infectious agents. Additionally, neutrophilic diseases commonly occur in association with an underlying systemic condition such as malignancy, neutropenia, rheumatologic diseases, infections, auto-inflammatory syndromes, and immunodeficiency. Moreover, neutrophilic diseases are frequently triggered by medications and pathergy, the latter being a typical sign of PG that is certainly involved in post-surgical and peristomal PG. […] The similarities between PG and neutrophilic diseases suggest that underlying common inflammatory pathways probably converge to their pathophysiology, leading to abnormalities in polymorphonuclear neutrophils (PMN) recruitment or homeostasis. In PG and other neutrophilic diseases, elevated skin and/or circulating levels of the pro-inflammatory cytokines (IL1, IL6, TNF-, IFN-, G-CSF) and, particularly, of the potent PMN attracting chemokines, namely IL8/CXCL8 and CXCL1,2,3, along with skin infiltration by T cells, particularly at the edge of the PG ulcer, suggests an active recruitment of PMN to the skin.

• #26 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  It has been reported that another cytokine associated with neutrophils and the development of PG may be IL-25, also known as IL-17E. […] The importance of IL-6, IL-8, IL-17, and IL-23 in PG pathomechanisms was suggested by Rubas et al. […] Therapy with the use of tumor necrosis factor (TNF) succeeded in treating PG and therefore underlined the possible importance of this cytokine in the pathophysiology of PG. […] The association between PG and adaptive immunity has not been fully established. However, some data that support this theory exist. […] Data suggest that PG has a characteristic of an autoimmune disease course of relapses and remissions.

• #27 Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management

  https://www.mdpi.com/2571-8800/4/3/28

  Despite the fact that PG is classified as a neutrophilic dermatosis, one theory proposes that the pathophysiology of the disease is actually driven by autoreactive T cells which destroy pilosebaceous units. […] Currently, the most accepted theory regarding the pathophysiology of PG proposes that it is an autoinflammatory disease versus being autoimmune in origin. […] Pyoderma gangrenosum is seen as part of the hereditary autoinflammatory syndromes PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis), SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) and PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis), which supports the theory that it is a disease rooted in an autoinflammatory origin. […] The findings above indicate, overall, that PG and its associated syndromes can be classified as a spectrum of autoinflammatory diseases, all with the common pathophysiologic factor of genetic mutations which lead to increased inflammasome assembly and the upregulation of PRR’s, causing an overactivation of the innate immune system.

• #28 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10889749/

  Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] The proposed pathophysiology of PG is associated with the interplay between innate and adaptive immunity and the state of autoinflammation with the crucial role of neutrophils. […] Pathogenesis of PG remains unclear. However, based on the existing research, it can be affirmed that it is a complex and multifactorial process. […] PG is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] Based on the existing reports, it can be inferred that genetic predisposition plays a significant role in the pathogenesis of PG.

• #29 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. […] The proposed pathophysiology of PG is associated with the interplay between innate and adaptive immunity and the state of autoinflammation with the crucial role of neutrophils. […] Pathogenesis of PG remains unclear. However, based on the existing research, it can be affirmed that it is a complex and multifactorial process. […] Possible aberrant origins of inflammation encompass neutrophils, T cells, inflammasomes, keratinocyte apoptosis, and modifications in epigenetic patterns. […] Based on the existing reports, it can be inferred that genetic predisposition plays a significant role in the pathogenesis of PG.

• #30 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://www.mdpi.com/1422-0067/25/4/2440

  Growing evidence suggests that individuals with a genetic predisposition and abnormal activation of the innate immune system create a conducive environment for the development of PG. […] Immune system dysregulation plays a crucial role in PG pathophysiology. […] PG may be induced or exacerbated by trauma (pathergy phenomenon). […] The occurrence of PG together with the autoinflammatory disorder—hidradenitis suppurativa, pyogenic arthritis, PG, acne, and hidradenitis suppurativa syndrome (PAPASH) and PG, acne, and hidradenitis suppurativa syndrome (PASH)—can be an indicator of autoinflammation in PG. […] Although IL-1α and IL-1β are acknowledged as one of the main inflammatory cytokines, only the first cytokine contributes to the development of PG. […] Cytokines suspected of contributing to PG are IL-36A and IL-36G, which are produced by epithelial cells when inflammation occurs.

• #31 Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease | Scientific Reports

  https://www.nature.com/articles/s41598-023-31914-z

  Pyoderma gangrenosum (PG) is a rare inflammatory skin disease classified within the spectrum of neutrophilic dermatoses. […] The pathophysiology of PG is yet incompletely understood but a prominent role of genetics facilitating immune dysregulation has been proposed. […] Genetically altered pathways involved in immune system biology and wound repair appear to be nodal pathogenic drivers in PG pathogenesis. […] The role of genetics in PG pathogenesis is perhaps best illustrated in PG-associated genetic syndromes. […] Through Variant Enrichment Analysis (VEA), a bioinformatic pipeline applicable for Whole Exome Sequencing (WES) data, this study aimed at disclosing the potential role of altered molecular pathways in determining the clinical severity of unrelated PG cases. […] Both in the multilesional and unilesional groups, VEA workflow applied to WES data showed immune and wound repair processes in PG susceptibility and severity modulation.

• #32 Pyoderma gangrenosum: challenges and solutions | CCID

  https://www.dovepress.com/pyoderma-gangrenosum-challenges-and-solutions-peer-reviewed-fulltext-article-CCID

  Genetic abnormalities have been found in patients with PG in the context of PAPA, PAPASH (initially described as PASS pyogenic arthritis, PG, acne, and hidradenitis suppurativa), and PASH (PG, acne, and hidradenitis suppurativa) syndromes in genes that code for an aberrant production of IL1, namely PSTPIP1 gene, or in its promoters. In cases of PG associated with IBD, genetic abnormalities have occasionally been found concerning loci for IL8RA, and TIMP3 and TRAF31P2 genes, which code respectively for an MMP inhibitor and a protein that interacts with TNF receptor-associated factors, involved in the IL17 immune pathway. […] Rarely, PG appears during the treatment with infliximab, etanercept, or G-CSF. Nevertheless, most reports confirm the benefit of therapy with the different TNF inhibitors, which further support an underlying immunologic mechanism in PG pathogenesis.

• #33 Pyoderma Gangrenosum: A Review of Updates in Diagnosis, Pathophysiology and Management

  https://www.mdpi.com/2571-8800/4/3/28

  Despite the fact that PG is classified as a neutrophilic dermatosis, one theory proposes that the pathophysiology of the disease is actually driven by autoreactive T cells which destroy pilosebaceous units. […] Currently, the most accepted theory regarding the pathophysiology of PG proposes that it is an autoinflammatory disease versus being autoimmune in origin. […] Pyoderma gangrenosum is seen as part of the hereditary autoinflammatory syndromes PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis), SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) and PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis), which supports the theory that it is a disease rooted in an autoinflammatory origin. […] The findings above indicate, overall, that PG and its associated syndromes can be classified as a spectrum of autoinflammatory diseases, all with the common pathophysiologic factor of genetic mutations which lead to increased inflammasome assembly and the upregulation of PRR’s, causing an overactivation of the innate immune system.

• #34 Pyoderma Gangrenosum – Dermatology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.856.5.

  Pyoderma gangrenosum (PG) is caused by genetic alterations of the immune system (both innate and adaptive), leading to inflammasome activation, cytokine production, and neutrophilic infiltration. […] Genetic mutations, neutrophil dysfunction, and abnormal inflammation contribute to the pathogenesis and clinical manifestations of PG. […] These PG-associated genetic syndromes share proinflammatory pathways and/or molecules (eg, interleukin 1 [IL-1]) underlying the pathogenesis of PG and associated conditions, such as IBD and psoriasis.

• #35 The Pathophysiology and Treatment of Pyoderma Gangrenosum—Current Options and New Perspectives

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10889749/

  Immune system dysregulation plays a crucial role in PG pathophysiology. […] PG may be induced or exacerbated by trauma (pathergy phenomenon). […] The occurrence of PG together with the autoinflammatory disorder hidradenitis suppurativa, pyogenic arthritis, PG, acne, and hidradenitis suppurativa syndrome (PAPASH) and PG, acne, and hidradenitis suppurativa syndrome (PASH) can be an indicator of autoinflammation in PG. […] Although IL-1 and IL-1 are acknowledged as one of the main inflammatory cytokines, only the first cytokine contributes to the development of PG. […] The association between PG and adaptive immunity has not been fully established. However, some data that support this theory exist. […] Data suggest that PG has a characteristic of an autoimmune disease course of relapses and remissions.

• #36 Pyoderma Gangrenosum: Symptoms, Causes, and Treatment — DermNet

  https://dermnetnz.org/topics/pyoderma-gangrenosum

  Pyoderma gangrenosum is an autoinflammatory disease (excessive response to an internal antigen) due to some form of neutrophil dysfunction. T lymphocytes and cytokines are involved. There may be a genetic predisposition. […] Injury to the skin is a common trigger (the pathergic response), and a surgical trigger is well known, and often misinterpreted as a wound infection.

• #37 Pyoderma Gangrenosum: Symptoms, Causes, and Treatment — DermNet

  https://dermnetnz.org/topics/pyoderma-gangrenosum

  Pyoderma gangrenosum is an autoinflammatory disease (excessive response to an internal antigen) due to some form of neutrophil dysfunction. T lymphocytes and cytokines are involved. There may be a genetic predisposition. […] Injury to the skin is a common trigger (the pathergic response), and a surgical trigger is well known, and often misinterpreted as a wound infection.

• #38

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  Unsurprisingly, trauma (i.e., pathergy) is among the best documented trigger factors of PG, as it entails the release of PG-driving cytokines such as IL-36 and IL-8 from keratinocytes, an event that may be sufficient in the setting of concurrent genetic predisposition. […] Complement system, and particularly neutrophil-attractant anaphylatoxin C5a, NETosis, regulatory T-cell unbalance, B cells as well as fibroblasts and monocytes/macrophages all add to the multi-layered pathophysiology of PG. […] Although PG pathogenesis remains incompletely elucidated, our understanding of its molecular underpinnings will pave the way for targeted treatments.

• #39 Pyoderma Gangrenosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/pyoderma-gangrenosum

  Etiology of pyoderma gangrenosum is unknown, but it can be associated with various systemic illnesses, including inflammatory bowel disease, rheumatoid arthritis, cancers, and hematologic disorders (eg, monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, polycythemia vera). It is thought to be mediated by an abnormal immune response. […] Pathophysiology of pyoderma gangrenosum is poorly understood but may involve problems with neutrophil chemotaxis. Interleukin-8 is overexpressed in lesions. […] Expansion of ulceration after surgical debridement strongly suggests pyoderma gangrenosum. […] Pyoderma gangrenosum is often associated with a systemic disorder and is probably immune-mediated.

• #40 Pyoderma Gangrenosum – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/pyoderma-gangrenosum

  Etiology of pyoderma gangrenosum is unknown, but it can be associated with various systemic illnesses, including inflammatory bowel disease, rheumatoid arthritis, cancers, and hematologic disorders (eg, monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, polycythemia vera). It is thought to be mediated by an abnormal immune response. […] Pathophysiology of pyoderma gangrenosum is poorly understood but may involve problems with neutrophil chemotaxis. Interleukin-8 is overexpressed in lesions. […] Expansion of ulceration after surgical debridement strongly suggests pyoderma gangrenosum. […] Pyoderma gangrenosum is often associated with a systemic disorder and is probably immune-mediated.

• #41 Pyoderma gangrenosum: a review of pathogenesis and treatment – PubMed

  https://pubmed.ncbi.nlm.nih.gov/29406827/

  Pyoderma gangrenosum (PG) is a complex neutrophilic dermatosis that can occur as an idiopathic disease, in association with systemic conditions such as inflammatory bowel disease, as part of an inherited inflammatory syndrome. […] The main limitations to treatment have been an incomplete understanding of the pathogenesis. However, recent advances have been made in understanding the pathogenesis of this condition, and PG is now considered an autoinflammatory disease process. […] The presence of abnormal neutrophils and T-cells lead to immune dysregulation, leading to lesions of PG. Increased levels of inflammatory mediators including IL-1, IL-8, IL-17, and TNF- contribute to the development of the disease but there are still several unknown factors, including the trigger for immune dysregulation and additional contributory components of the immune system.

• #42 Pyoderma Gangrenosum Associated With Inflammatory Bowel Disease. Report of Two Cases With Good Response to Infliximab | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-pyoderma-gangrenosum-associated-with-inflammatory-articulo-S2173574312000068

  Among the extraintestinal manifestations of inflammatory bowel disease (IBD), pyoderma gangrenosum (PG) often poses a therapeutic challenge. We describe two cases of PG associated with inflammatory bowel disease, who responded to treatment with Infliximab. […] The pathogenesis of PG is not fully elucidated but appears to be an immune-mediated injury similar to IBD. Therefore, various therapies that act to control the inflammatory response, such as infliximab, have been used in its treatment. It has also been speculated that the effect of infliximab in PG is a consequence of the healing of intestinal lesions underlying IBD, or is a direct drug effect on skin injuries. […] In the cases reported, treatment with infliximab proved to be able to achieve remission of PG associated with Crohn’s disease after failure of immunosuppressive therapy.

• #43 Pyoderma Gangrenosum Associated With Inflammatory Bowel Disease. Report of Two Cases With Good Response to Infliximab | Reumatología Clínica

  https://www.reumatologiaclinica.org/en-pyoderma-gangrenosum-associated-with-inflammatory-articulo-S2173574312000068

  Among the extraintestinal manifestations of inflammatory bowel disease (IBD), pyoderma gangrenosum (PG) often poses a therapeutic challenge. We describe two cases of PG associated with inflammatory bowel disease, who responded to treatment with Infliximab. […] The pathogenesis of PG is not fully elucidated but appears to be an immune-mediated injury similar to IBD. Therefore, various therapies that act to control the inflammatory response, such as infliximab, have been used in its treatment. It has also been speculated that the effect of infliximab in PG is a consequence of the healing of intestinal lesions underlying IBD, or is a direct drug effect on skin injuries. […] In the cases reported, treatment with infliximab proved to be able to achieve remission of PG associated with Crohn’s disease after failure of immunosuppressive therapy.

• #44 Pyoderma gangrenosum – Wikipedia

  https://en.wikipedia.org/wiki/Pyoderma_gangrenosum

  Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. […] Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as interleukin (IL)-8, IL-1, IL-6, interferon (IFN)-, granulocyte colony-stimulating factor, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-9, MMP10, and elafin have all been reported to be elevated in patients with pyoderma gangrenosum. […] One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma, including surgical wounds.

• #45 Pyoderma gangrenosum: a review with special emphasis on Latin America literature | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pyoderma-gangrenosum-review-with-special-articulo-S0365059619300686

  IL-17 appears to be crucial in the recruitment of neutrophils in auto-inflammation and acts synergistically with tumor necrosis factor (TNF). […] Finally, IL-1, IL-17, and TNF- activate and increase the production of matrix metalloproteinases (MMPs), which are overexpressed in the inflammatory infiltrate of PG, causing an inflammatory insult and the consequent destruction of the involved tissue. […] In conclusion, PG is the result of innate immune system over-activation via inflammasomes, coupled with the activation of the adaptive immune system, triggered by an external insult (e.g., pathergy) and/or a possible internal trigger in a genetically predisposed individual.

• #46 Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease | Scientific Reports

  https://www.nature.com/articles/s41598-023-31914-z

  Our results fall in line with this premise and, indeed, JAK inhibition is shaping up as a compelling treatment option for PG, although its long-term safety is still under investigation. […] Dysregulated or absent autophagy results in a wide range of conditions, including inflammatory and immune-mediated skin diseases. […] In conclusion, we described altered biological pathways in PG patients, particularly involved in immune system, in neutrophils-related inflammation and in wound repair, confirming that these processes are nodal pathogenic drivers in PG pathogenesis.

• #47 Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease | Scientific Reports

  https://www.nature.com/articles/s41598-023-31914-z

  Our results fall in line with this premise and, indeed, JAK inhibition is shaping up as a compelling treatment option for PG, although its long-term safety is still under investigation. […] Dysregulated or absent autophagy results in a wide range of conditions, including inflammatory and immune-mediated skin diseases. […] In conclusion, we described altered biological pathways in PG patients, particularly involved in immune system, in neutrophils-related inflammation and in wound repair, confirming that these processes are nodal pathogenic drivers in PG pathogenesis.

• #48 Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease | Scientific Reports

  https://www.nature.com/articles/s41598-023-31914-z

  Our results fall in line with this premise and, indeed, JAK inhibition is shaping up as a compelling treatment option for PG, although its long-term safety is still under investigation. […] Dysregulated or absent autophagy results in a wide range of conditions, including inflammatory and immune-mediated skin diseases. […] In conclusion, we described altered biological pathways in PG patients, particularly involved in immune system, in neutrophils-related inflammation and in wound repair, confirming that these processes are nodal pathogenic drivers in PG pathogenesis.

• #49 Pyoderma gangrenosum: a review with special emphasis on Latin America literature | Anais Brasileiros de Dermatologia

  https://www.anaisdedermatologia.org.br/en-pyoderma-gangrenosum-review-with-special-articulo-S0365059619300686

  IL-17 appears to be crucial in the recruitment of neutrophils in auto-inflammation and acts synergistically with tumor necrosis factor (TNF). […] Finally, IL-1, IL-17, and TNF- activate and increase the production of matrix metalloproteinases (MMPs), which are overexpressed in the inflammatory infiltrate of PG, causing an inflammatory insult and the consequent destruction of the involved tissue. […] In conclusion, PG is the result of innate immune system over-activation via inflammasomes, coupled with the activation of the adaptive immune system, triggered by an external insult (e.g., pathergy) and/or a possible internal trigger in a genetically predisposed individual.

• #50 Pyoderma gangrenosum: challenges and solutions | CCID

  https://www.dovepress.com/pyoderma-gangrenosum-challenges-and-solutions-peer-reviewed-fulltext-article-CCID

  The mechanisms responsible for the clinical heterogeneity of skin lesions in neutrophilic disorders ulcers in PG, skin plaques in SS and folliculitis and aphthous ulcers in Behets disease, as well as their associated manifestations remain unknown. Nevertheless, differences in the balance of Treg/Th17, the relative intensity of the expression of cytokines and MMPs, and a different genetic background may in part justify the different patterns of skin aggression in these diseases. […] PG also shares many features with auto-inflammatory disorders, including the chronic remitting course, the dysregulation of the innate immune system with neutrophil recruitment and activation, and a role for excessive cytokine production. Additionally, PG lesions are almost always observed in patients with PAPA syndrome, a rare inherited auto-inflammatory syndrome with excessive IL1 production.

• #51

  https://link.springer.com/article/10.1007/s40265-023-01931-3

  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. […] It seems that abnormal activation of the innate immune system in patients with genetic predisposition provide an ideal state for PG to develop. However, neutrophil-T cell crosstalk causing the activation of Th17 downstream cytokines is now supported by gene expression studies. […] Although the underlying pathomechanisms are not clearly known, it must be assumed that a dysregulated inflammatory reaction with disturbed migration and activation of neutrophil granulocytes also occurs as a result of the drugs in genetically predisposed individuals. Keratinocyte apoptosis and alteration of epigenetic mechanisms might play a role as well.

• #52 Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Rare Case Involving Mandibular, Elbow, and Pubic Ulcers | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/90522-pyoderma-gangrenosum-in-inflammatory-bowel-disease-a-rare-case-involving-mandibular-elbow-and-pubic-ulcers

  Pyoderma gangrenosum (PG) is a rare, inflammatory skin condition primarily characterized by painful ulcers with undermined borders, commonly occurring on the lower extremities. […] Though the pathogenesis of PG remains unclear, it is described as an inflammatory disease within the spectrum of neutrophilic dermatoses. […] In this condition, it is proposed that neutrophil dysfunction and an overly active innate immune system trigger the release of pro-inflammatory cytokines and chemokines. […] These MMPs, found in high concentrations in PGs inflammatory infiltration, along with the clonal expansion of T-cells, may play a role in tissue damage and impaired wound healing. […] The relationship between IBD and PG is not fully understood, but it is plausible that a connection exists based on shared underlying immune system dysfunction.

• #53

  https://link.springer.com/article/10.1007/s40257-022-00699-8

  Unsurprisingly, trauma (i.e., pathergy) is among the best documented trigger factors of PG, as it entails the release of PG-driving cytokines such as IL-36 and IL-8 from keratinocytes, an event that may be sufficient in the setting of concurrent genetic predisposition. […] Complement system, and particularly neutrophil-attractant anaphylatoxin C5a, NETosis, regulatory T-cell unbalance, B cells as well as fibroblasts and monocytes/macrophages all add to the multi-layered pathophysiology of PG. […] Although PG pathogenesis remains incompletely elucidated, our understanding of its molecular underpinnings will pave the way for targeted treatments.

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