The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Angelo V Marzano - One of the best experts on this subject based on the ideXlab platform.
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PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment
American Journal of Clinical Dermatology, 2017Co-Authors: Massimo Cugno, Alessandro Borghi, Angelo V MarzanoAbstract:Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and Suppurative Hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and Suppurative Hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and ‘sterile’ neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.
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autoinflammation in pyoderma gangrenosum and its syndromic form pyoderma gangrenosum acne and Suppurative Hidradenitis
British Journal of Dermatology, 2017Co-Authors: Angelo V Marzano, Giovanni Damiani, Isabella Ceccherini, E Berti, Marco Gattorno, Massimo CugnoAbstract:SummaryBackground Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders. Objectives To determine a specific genetic background related to autoinflammation for PG. Methods We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Results In skin samples, the expression of interleukin (IL)-1β and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1. Conclusions Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.
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pyoderma gangrenosum and its syndromic forms evidence for a link with autoinflammation
British Journal of Dermatology, 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Abstract Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.
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Pyoderma gangrenosum and its syndromic forms: Evidence for a link with autoinflammation
'Wiley', 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndromes as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. In PAPA syndrome, different mutations involving the PSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease which cleaves inactive pro-interleukin (IL)-1 beta to its active isoform IL-1 beta. The overproduction of IL-1 beta triggers the release of a number of proinflammatory cytokines and chemokines which are responsible for the recruitment and activation of neutrophils, leading to a neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. PASH patients have recently been reported to present alterations of genes involved in well known autoinflammatory diseases, such as PSTPIP1, MEFV (mediterranean fever), NOD2 (nucleotide-binding oligomerization domain-containing protein 2) and NLRP3 (NOD-like receptor family, pyrin domain containing 3). Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation. This article is protected by copyright. All rights reserved
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association of pyoderma gangrenosum acne and Suppurative Hidradenitis pash shares genetic and cytokine profiles with other autoinflammatory diseases
Medicine, 2014Co-Authors: Angelo V Marzano, Francesco Caroli, Isabella Ceccherini, Marco Gattorno, Daniele Fanoni, Marta Rusmini, Alice Grossi, Clara De Simone, Orietta Borghi, Pier Luigi MeroniAbstract:The association of pyoderma gangrenosum, acne, and Suppurative Hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T- cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1b and its receptors I and II were significantly higher in PASH (P ¼0.028, 0.047, and 0.050, respectively) thanin controls.InPASHpatients, chemokinessuchas IL- 8( P ¼0.004), C-X-C motif ligand (CXCL) 1/2/3 (P ¼0.028), CXCL 16 (P ¼0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P ¼0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P ¼0.016 for Fas, P ¼0.006 for Fas ligand, P ¼0.005 for CD40, and P ¼0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1b, tumor necrosis factor- a, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical ofwell-knownAIDs,includinginflammatoryboweldiseases,andtheonly patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.
Massimo Cugno - One of the best experts on this subject based on the ideXlab platform.
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PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment
American Journal of Clinical Dermatology, 2017Co-Authors: Massimo Cugno, Alessandro Borghi, Angelo V MarzanoAbstract:Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and Suppurative Hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and Suppurative Hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and ‘sterile’ neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.
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autoinflammation in pyoderma gangrenosum and its syndromic form pyoderma gangrenosum acne and Suppurative Hidradenitis
British Journal of Dermatology, 2017Co-Authors: Angelo V Marzano, Giovanni Damiani, Isabella Ceccherini, E Berti, Marco Gattorno, Massimo CugnoAbstract:SummaryBackground Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders. Objectives To determine a specific genetic background related to autoinflammation for PG. Methods We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Results In skin samples, the expression of interleukin (IL)-1β and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1. Conclusions Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.
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pyoderma gangrenosum and its syndromic forms evidence for a link with autoinflammation
British Journal of Dermatology, 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Abstract Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.
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Pyoderma gangrenosum and its syndromic forms: Evidence for a link with autoinflammation
'Wiley', 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndromes as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. In PAPA syndrome, different mutations involving the PSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease which cleaves inactive pro-interleukin (IL)-1 beta to its active isoform IL-1 beta. The overproduction of IL-1 beta triggers the release of a number of proinflammatory cytokines and chemokines which are responsible for the recruitment and activation of neutrophils, leading to a neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. PASH patients have recently been reported to present alterations of genes involved in well known autoinflammatory diseases, such as PSTPIP1, MEFV (mediterranean fever), NOD2 (nucleotide-binding oligomerization domain-containing protein 2) and NLRP3 (NOD-like receptor family, pyrin domain containing 3). Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation. This article is protected by copyright. All rights reserved
Pier Luigi Meroni - One of the best experts on this subject based on the ideXlab platform.
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pyoderma gangrenosum and its syndromic forms evidence for a link with autoinflammation
British Journal of Dermatology, 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Abstract Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro-IL)-1β to its active isoform IL-1β. The overproduction of IL-1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well-known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.
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Pyoderma gangrenosum and its syndromic forms: Evidence for a link with autoinflammation
'Wiley', 2016Co-Authors: Angelo V Marzano, Alessandro Borghi, Pier Luigi Meroni, Massimo CugnoAbstract:Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndromes as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. In PAPA syndrome, different mutations involving the PSTPIP1 (proline-serine-threonine phosphatase-interacting protein 1) gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease which cleaves inactive pro-interleukin (IL)-1 beta to its active isoform IL-1 beta. The overproduction of IL-1 beta triggers the release of a number of proinflammatory cytokines and chemokines which are responsible for the recruitment and activation of neutrophils, leading to a neutrophil-mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. PASH patients have recently been reported to present alterations of genes involved in well known autoinflammatory diseases, such as PSTPIP1, MEFV (mediterranean fever), NOD2 (nucleotide-binding oligomerization domain-containing protein 2) and NLRP3 (NOD-like receptor family, pyrin domain containing 3). Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation. This article is protected by copyright. All rights reserved
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association of pyoderma gangrenosum acne and Suppurative Hidradenitis pash shares genetic and cytokine profiles with other autoinflammatory diseases
Medicine, 2014Co-Authors: Angelo V Marzano, Francesco Caroli, Isabella Ceccherini, Marco Gattorno, Daniele Fanoni, Marta Rusmini, Alice Grossi, Clara De Simone, Orietta Borghi, Pier Luigi MeroniAbstract:The association of pyoderma gangrenosum, acne, and Suppurative Hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T- cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1b and its receptors I and II were significantly higher in PASH (P ¼0.028, 0.047, and 0.050, respectively) thanin controls.InPASHpatients, chemokinessuchas IL- 8( P ¼0.004), C-X-C motif ligand (CXCL) 1/2/3 (P ¼0.028), CXCL 16 (P ¼0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P ¼0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P ¼0.016 for Fas, P ¼0.006 for Fas ligand, P ¼0.005 for CD40, and P ¼0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1b, tumor necrosis factor- a, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical ofwell-knownAIDs,includinginflammatoryboweldiseases,andtheonly patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.
Boursier, Mendeley G Data) - One of the best experts on this subject based on the ideXlab platform.
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Supplementary material Table S2. The 39 PSTPIP1 variants found in the study.
2020Co-Authors: Boursier, Mendeley G Data)Abstract:*Possible misdiagnosed PAMI Each variant was classified by the ISSAID expert consortium and is accessible in the Infevers database. When missing, the classification was assessed according to American College of Medical Genetics guidelines. Abbreviations: AIDs, autoinflammatory diseases; CD, Crohn disease; CRMO, chronic recurrent multifocal osteomyelitis; ISSAID, International Society of Systemic Auto-Inflammatory Diseases; FMF, familial Mediterranean fever; PAC, pyoderma gangrenosum with acne and ulcerative colitis; PAMI, PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne; PG, pyoderma gangrenosum; PAPASH; pyoderma gangrenosum, acne and Suppurative Hidradenitis with pyogenic arthritis; PASH, pyoderma gangrenosum, acne andsSuppurative Hidradenitis; VUS, variant of uncertain significance
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Supplementary material Figure S1. Schematic representation of the PSTPIP1 protein and its domains.
2019Co-Authors: Boursier, Mendeley G Data)Abstract:The functional domains are in green for F-BAR and orange for SH3. Critical codons are depicted as follows: Tryptophane 232 (Trp232) is required for interaction with the carboxyl‐terminal homology domain of PTP-PESTs. The association with PTP-PESTs inhibits tyrosine phosphorylation of wild-type PSTPIP1 on tyrosine 344 (Tyr344, but Tyr345 according to NM_003978.3) and Tyr367. Pathogenic and likely pathogenic known variants of PSTPIP1 are shown for each PSTPIP1-associated phenotype. Abbreviations: PAMI, PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne; PASH, pyoderma gangrenosum, acne and Suppurative Hidradenitis; PTP-PESTs, proline-, glutamic acid-, serine- and threonine-rich protein tyrosine phosphatases
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Supplementary material Table S1. Reported data for the 156 patients with PSTPIP1 variants.
2019Co-Authors: Boursier, Mendeley G Data)Abstract:For simplification, we have used in tables a short protein denomination such as A230T for p.(Ala230Thr). *This "asymptomatic" patient experienced chronic fatigue, arthralgia and myalgia. **This patient is homozygous for the variant described. Abbreviations: ACMG, American College of Medical Genetics; AIDs, autoinflammatory diseases; CD, Crohn disease; CRMO, chronic recurrent multifocal osteomyelitis; CRP, C-reactive protein; FRA, familial recurrent arthritis; HGVS, Human Genome Variation Society; FMF, familial Mediterranean fever; PAC, pyoderma gangrenosum with acne and ulcerative colitis; PAMI, PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne; PG, pyoderma gangrenosum; PAPASH; pyoderma gangrenosum, acne and Suppurative Hidradenitis with pyogenic arthritis; PASH, pyoderma gangrenosum, acne and Suppurative Hidradenitis; VUS, variant of uncertain significance
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Supplementary material Table S2. The 39 PSTPIP1 variants found in the study.
2019Co-Authors: Boursier, Mendeley G Data)Abstract:For simplification, we have used in tables a short protein denomination such as A230T for p.(Ala230Thr). Each variant was classified by the ISSAID expert consortium and is accessible in the Infevers database (Shinar, Ceccherini, Rowczenio, et al. ISSAID/EMQN Best Practice Guidelines for the Genetic Diagnosis of Monogenic Autoinflammatory Diseases in the Next Generation Sequencing Era. submitted). When missing, the classification was assessed according to American College of Medical Genetics guidelines. Abbreviations: AIDs, autoinflammatory diseases; CD, Crohn disease; CRMO, chronic recurrent multifocal osteomyelitis; ISSAID, International Society of Systemic Auto-Inflammatory Diseases; FMF, familial Mediterranean fever; PAC, pyoderma gangrenosum with acne and ulcerative colitis; PAMI, PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome; PAPA, pyogenic sterile arthritis, pyoderma gangrenosum, and acne; PG, pyoderma gangrenosum; PAPASH; pyoderma gangrenosum, acne and Suppurative Hidradenitis with pyogenic arthritis; PASH, pyoderma gangrenosum, acne andsSuppurative Hidradenitis; VUS, variant of uncertain significance
Marco Gattorno - One of the best experts on this subject based on the ideXlab platform.
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autoinflammation in pyoderma gangrenosum and its syndromic form pyoderma gangrenosum acne and Suppurative Hidradenitis
British Journal of Dermatology, 2017Co-Authors: Angelo V Marzano, Giovanni Damiani, Isabella Ceccherini, E Berti, Marco Gattorno, Massimo CugnoAbstract:SummaryBackground Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders. Objectives To determine a specific genetic background related to autoinflammation for PG. Methods We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and Suppurative Hidradenitis). Results In skin samples, the expression of interleukin (IL)-1β and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1. Conclusions Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.
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association of pyoderma gangrenosum acne and Suppurative Hidradenitis pash shares genetic and cytokine profiles with other autoinflammatory diseases
Medicine, 2014Co-Authors: Angelo V Marzano, Francesco Caroli, Isabella Ceccherini, Marco Gattorno, Daniele Fanoni, Marta Rusmini, Alice Grossi, Clara De Simone, Orietta Borghi, Pier Luigi MeroniAbstract:The association of pyoderma gangrenosum, acne, and Suppurative Hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T- cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1b and its receptors I and II were significantly higher in PASH (P ¼0.028, 0.047, and 0.050, respectively) thanin controls.InPASHpatients, chemokinessuchas IL- 8( P ¼0.004), C-X-C motif ligand (CXCL) 1/2/3 (P ¼0.028), CXCL 16 (P ¼0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P ¼0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P ¼0.016 for Fas, P ¼0.006 for Fas ligand, P ¼0.005 for CD40, and P ¼0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1b, tumor necrosis factor- a, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical ofwell-knownAIDs,includinginflammatoryboweldiseases,andtheonly patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.