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Journal of Ayub Medical College,... 2023The first description of Pyoderma gangrenosum (PG) was made about a century ago. It is difficult to understand the aetiology, pathophysiology, and therapy of PG. This... (Review)
Review
The first description of Pyoderma gangrenosum (PG) was made about a century ago. It is difficult to understand the aetiology, pathophysiology, and therapy of PG. This disease is believed to be caused by a systemic inflammatory response to neutrophil chemotaxis and faulty innate immune system control. Nearly fifty percent of the cases have underlying systemic symptoms. Significant improvements in PG management have been made over the years. The main goals of treatment are to reduce inflammation and speed up the healing of the PG wound. Even though the most recent medicines show promise, they are found on isolated case reports. The majority of patients are typically managed with topical treatment and local wound care, while resistant cases necessitate immunosuppressive medications. More progress can be made with improvements in technology in deciphering this complex disease and getting a greater understanding of the condition. The present standard therapies for refractory PG are not well supported by studies. In refractory PG, corticosteroids and cyclosporine have historically been administered. Tumour necrosis factor inhibitors are becoming a viable option; nonetheless, this requires careful research and upkeep. This review intended to describe the current trends in managing the PG. Several next-generation treatment options including the conventional therapies introduced to treat PG. We encompass the advantages and disadvantages of new treatments for PG.
Topics: Humans; Pyoderma Gangrenosum; Inflammation; Administration, Topical
PubMed: 38406909
DOI: 10.55519/JAMC-S4-12085 -
Annals of the Rheumatic Diseases May 2024To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by...
OBJECTIVES
To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in .
METHODS
Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation. Cytokine levels in the skin were evaluated by immunohistochemistry. Responsiveness to Janus kinase (JAK) inhibitors was evaluated ex vivo with peripheral blood mononuclear cells and in vivo in five treatment-refractory PAPA patients.
RESULTS
The knock-in mouse model of PAPA did not recapitulate the human disease. In a human myeloid cell line model, PAPA-associated mutations activated the pyrin inflammasome, but not the NLRP3, NLRC4 or AIM2 inflammasomes. Pyrin inflammasome activation was independent of the canonical pathway of pyrin serine dephosphorylation and was blocked by the p.W232A mutation, which disrupts pyrin-PSTPIP1 interaction. IFN-γ priming of monocytes from PAPA patients led to IL-18 release in a pyrin-dependent manner. IFN-γ was abundant in the inflamed dermis of PAPA patients, but not patients with idiopathic pyoderma gangrenosum. Ex vivo JAK inhibitor treatment attenuated IFN-γ-mediated pyrin induction and IL-18 release. In 5/5 PAPA patients, the addition of JAK inhibitor therapy to IL-1 inhibition was associated with clinical improvement.
CONCLUSION
PAPA-associated mutations trigger a pyrin-IL-18-IFN-γ positive feedback loop that drives PAPA disease activity and is a target for JAK inhibition.
Topics: Pyoderma Gangrenosum; Arthritis, Infectious; Humans; Animals; Mice; Acne Vulgaris; Inflammasomes; Disease Models, Animal; Interferon-gamma; Janus Kinase Inhibitors; Mice, Knockout; Cytoskeletal Proteins; Feedback, Physiological; Adaptor Proteins, Signal Transducing; Pyrin; Mutation; Phosphoproteins; Gene Knock-In Techniques; Interleukin-18; THP-1 Cells
PubMed: 38408849
DOI: 10.1136/ard-2023-225085 -
Clinics in Dermatology 2023Hidradenitis suppurativa (HS) is a clinically heterogeneous disease with a broad spectrum of clinical features. Attempts to classify HS into distinct clinical phenotypes...
Hidradenitis suppurativa (HS) is a clinically heterogeneous disease with a broad spectrum of clinical features. Attempts to classify HS into distinct clinical phenotypes could lead to a better understanding of the condition and the development of individualized treatment protocols. We summarize some of the existing phenotype classifications and present our experience with 250 patients and their many clinical presentations. We have emphasized the pathophysiologic and clinical overlap between HS and pyoderma gangrenosum. The more severe presentations can include erosive and ulcerative lesions, sometimes associated with vegetative changes leading to diagnostic quandaries. We propose a new phenotype of pyoderma gangrenosum-like HS in which painful ulcerative or vegetative lesions appear in sites affected by HS, their activity coincides with the flareups of classic inflammatory manifestations of HS, and they heal with cribriform or atrophic scars.
Topics: Humans; Hidradenitis Suppurativa; Pyoderma Gangrenosum; Pain
PubMed: 37652191
DOI: 10.1016/j.clindermatol.2023.08.025 -
Frontiers in Immunology 2023This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by...
INTRODUCTION
This scoping review explores the effectiveness of IL-1 pathway inhibitors in managing PSTPIP1-associated inflammatory diseases (PAID). These diseases are marked by abnormal IL-1 pathway activation due to genetic mutations.
METHODS
Our methodology adhered to a pre-published protocol and involved a thorough search of MEDLINE and EMBASE databases up to February 2022, following the Joanna Briggs Institute Reviewer's Manual and the PRISMA Extension for Scoping Reviews. The review included studies reporting on IL-1 pathway inhibitor use in PAID patients.
RESULTS
From an initial pool of 5,225 articles, 36 studies involving 43 patients were selected. The studies predominantly used observational designs and exhibited diversity in patient demographics, treatment approaches, and outcomes. Anakinra and canakinumab demonstrated promise in treating sterile pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) and PSTPIP1-associated myeloid-related-proteinemia inflammatory (PAMI) syndromes, with scant data on other syndromes. Notably, there was a paucity of information on the adverse effects of these treatments, necessitating cautious interpretation of their safety profile.
CONCLUSION
Current evidence on IL-1 pathway inhibitors for PAID is primarily from observational studies and remains limited. Rigorous research with larger patient cohorts is imperative for more definitive conclusions. Collaborative efforts among specialized research centers and international health initiatives are key to advancing this field.
Topics: Humans; Acne Vulgaris; Adaptor Proteins, Signal Transducing; Antibodies, Monoclonal, Humanized; Arthritis, Infectious; Cytoskeletal Proteins; Interleukin 1 Receptor Antagonist Protein; Interleukin-1
PubMed: 38259483
DOI: 10.3389/fimmu.2023.1339337 -
Anais Brasileiros de Dermatologia 2024Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application... (Review)
Review
BACKGROUND
Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application practices, both cutaneous and systemic complications can arise. Adverse reactions can be grouped into five classes: inflammatory, infectious, neoplastic, aesthetic, and miscellaneous. On histopathology, inflammatory reactions can exhibit a lichenoid pattern or present as spongiotic dermatitis, granulomatous reactions, pseudolymphoma, pseudoepitheliomatous hyperplasia, or scleroderma/morphea-like changes. This article reviews tattoo complications, including their clinical and histopathological characteristics.
METHODS
An open search was conducted on PubMed using the terms "tattoo", "complications", and "skin". No limits were set for period, language, or publication type of the articles.
RESULTS
Reactions to tattoos are reported in up to 67% of people who get tattooed, with papulonodular and granulomatous reactions being the most common. Some neoplastic complications have been described, but their causality is still debated. Any pigment can cause adverse reactions, although red ink is more frequently associated with them. Patients with pre-existing dermatoses may experience exacerbation or complications of their diseases when getting tattoos; therefore, this procedure is not recommended for this patient group.
CONCLUSIONS
Dermatological consultation is recommended before getting a tattoo, as well as a histopathological examination in case of complications. In patients who develop cutaneous inflammatory reactions following tattooing, additional studies are recommended to investigate systemic diseases such as sarcoidosis, pyoderma gangrenosum, atopic dermatitis, and neoplasms. It is important for physicians to be trained in providing appropriate care in case of complications.
Topics: Tattooing; Humans; Skin Diseases; Coloring Agents; Risk Factors; Skin
PubMed: 38521707
DOI: 10.1016/j.abd.2023.07.004 -
Cureus Apr 2024Pyoderma gangrenosum is a rare ulcerative skin disease of uncertain etiology, which in some cases can be misdiagnosed as an infectious process. In even more unique...
Pyoderma gangrenosum is a rare ulcerative skin disease of uncertain etiology, which in some cases can be misdiagnosed as an infectious process. In even more unique cases, this can occur in the postoperative period. Termed postsurgical pyoderma gangrenosum, this type of inflammatory skin condition requires a high index of suspicion to be able to appropriately treat and reduce complications. We present a 55-year-old female who presented with multiple wounds following mastopexy and abdominoplasty. With a prompt diagnosis and a multidisciplinary approach, we could accurately care for the patient and minimize poor aesthetic sequela.
PubMed: 38738036
DOI: 10.7759/cureus.58060 -
Joint Bone Spine Feb 2024
PubMed: 38417693
DOI: 10.1016/j.jbspin.2024.105712 -
Dermatology Practical & Conceptual Apr 2024
Disparities in Financial Burden, Outcomes, and Comorbidities Among Pediatric Patients With Pyoderma Gangrenosum With and Without Mental Health Disorders in a Multivariate Analysis of the 2016 Kids' Inpatient Database.
PubMed: 38810044
DOI: 10.5826/dpc.1402a57 -
Frontiers in Immunology 2023Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have...
Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have underlying IBD, suggesting shared but unknown mechanisms of pathogenesis. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concomitant intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) as well as pro-inflammatory cellular and soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating low density IL-1β primed neutrophils that undergo enhanced NETosis at inflamed tissue sites supported by an increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD.
Topics: Humans; Animals; Mice; Pyoderma Gangrenosum; Neutrophils; Disease Models, Animal; Inflammatory Bowel Diseases; Inflammation
PubMed: 37475852
DOI: 10.3389/fimmu.2023.1148893 -
Journal of Translational Medicine May 2024
Topics: Humans; Bibliometrics; Pyoderma Gangrenosum; History, 20th Century; History, 21st Century; Biomedical Research
PubMed: 38802936
DOI: 10.1186/s12967-024-05306-4