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JAMA Dermatology Nov 2023
Topics: Humans; Pyoderma Gangrenosum; Pain; Patient Reported Outcome Measures
PubMed: 37728937
DOI: 10.1001/jamadermatol.2023.3115 -
American Journal of Clinical Dermatology Jul 2024Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been...
BACKGROUND AND OBJECTIVE
Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that can be associated with primary immunodeficiency. The pathogenesis of PG has not yet been elucidated, although contributions from dysregulation of the immune system in patients with apparent genetic predispositions have been postulated. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review with the objective of identifying inborn errors of immunity in the presence of PG as well as their clinical characteristics of severity including number of PG lesions and anatomic areas affected, and treatment outcomes.
METHODS
A literature search was performed using PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science through August 24, 2023, for studies published in English using the search terms: "pyoderma gangrenosum," "inborn error of immunity," "immune defect*," and a list of genetic mutations potentially associated with PG.
RESULTS
Seventy-four cases of PG associated with inborn errors of immunity were identified. The results demonstrate an association of PG with a variety of inborn errors of immunity, including genetic mutations not classically associated with the condition. Genetic mutations such as BTK, IL1RN, ITGB2, LPIN2, MEFV, NFkB1, NLRP3, NLRP12, NOD2, PSMB8, PLCG2, PSTPIP1, RAG1, TTC37, and WDR1, as well as complement component 2/complement component 4 (C2/C4) and complement component 7 (C7) deficiencies were identified in the presence of either idiopathic or syndromic PG. Of note, mutations in genes such as PSMB8, NLRP3, and IL1RN were found to be associated with a more severe and atypical course of PG, whereas mutations in RAG1 as well as those causing a C2/C4 deficiency were associated with the mildest clinical presentations of PG. Mutations in NFkB1, ITGB2, and PSTPIP1 were associated with the most heterogeneous clinical presentations.
CONCLUSIONS
Human inborn errors of immunity may be implicated in the genetic predisposition to PG and may influence the clinical presentation. Due to the rarity of these diseases, further work must be done to describe the association between inborn errors of immunity and PG. Identifying inborn errors of immunity that may contribute to the development of PG may assist in further elucidating the mechanism of PG, guiding targeted treatment, and improving clinical outcomes for these patients.
PubMed: 38951460
DOI: 10.1007/s40257-024-00875-y -
Preventive Veterinary Medicine May 2024Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and...
Antimicrobial resistance within Staphylococcus pseudintermedius poses a significant risk for the treatment of canine pyoderma and as a reservoir for resistance and potential zoonoses, but few studies examine long-term temporal trends of resistance. This study assesses the antimicrobial resistance prevalence and minimum inhibitory concentration (MIC) trends in S. pseudintermedius (n=1804) isolated from canine skin samples at the Cornell University Animal Health Diagnostic Center (AHDC) between 2007 and 2020. Not susceptible (NS) prevalence, Cochran-Armitage tests, logrank tests, MIC and MIC quantiles, and survival analysis models were used to evaluate resistance prevalence and temporal trends to 23 antimicrobials. We use splines as predictors in accelerated failure time (AFT) models to model non-linear temporal trends in MICs. Multidrug resistance was common among isolates (47%), and isolates had moderate to high NS prevalence to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, the macrolides/lincosamides, the tetracyclines, and trimethoprim-sulfamethoxazole. However, low levels of NS to amikacin, rifampin, and vancomycin were observed. Around one third of isolates (38%) were found to be methicillin resistant S. pseudintermedius (MRSP), and these isolates had a higher prevalence of NS to all tested antimicrobials than methicillin susceptible isolates. Amongst the MRSP isolates, one phenotypically vancomycin resistant isolate (MIC >16 µg/mL) was identified, but genomic sequence data was unavailable. AFT models showed increasing MICs across time to the beta-lactams, chloramphenicol, the fluoroquinolones, gentamicin, and the macrolides/lincosamides, and decreasing temporal resistance (decreasing MICs) to doxycycline was observed amongst isolates. Notably, ATF modeling showed changes in MIC distributions that were not identified using Cochran-Armitage tests on prevalence, MIC quantiles, and logrank tests. Increasing resistance amongst these S. pseudintermedius isolates highlights the need for rational, empirical prescribing practices and increased antimicrobial resistance (AMR) surveillance to maintain the efficacy of current therapeutic agents. AFT models with non-linear predictors may be a useful, breakpoint-independent, surveillance tool alongside other modeling methods and antibiograms.
Topics: Humans; Animals; Dogs; Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents; Chloramphenicol; Lincosamides; Fluoroquinolones; beta-Lactams; Gentamicins; Macrolides; Microbial Sensitivity Tests; Dog Diseases; Staphylococcal Infections; Staphylococcus
PubMed: 38493570
DOI: 10.1016/j.prevetmed.2024.106170 -
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 -
Tierarztliche Praxis. Ausgabe K,... Oct 2023A 4-year-old, spayed female mixed breed dog was presented with large crater-like, well-demarcated, erosive and ulcerative necrotic lesions of the skin, elevated body...
A 4-year-old, spayed female mixed breed dog was presented with large crater-like, well-demarcated, erosive and ulcerative necrotic lesions of the skin, elevated body temperature and lethargy, that began 14 days after vaccination and treatment with fluralaner and milbemycin/praziquantel. Cytology revealed severe pyogranulomatous inflammation with moderate numbers of extracellular microorganisms. Histopathologic examination showed severe multifocal pyogranulomatous dermatitis and panniculitis with severe dermal edema and severe neutrophilic exocytosis with band-like infiltration of the lower portion of the epidermis consistent with pyoderma gangrenosum. Despite intensive immunosuppressive and antimicrobial therapy and intensive inpatient care, the dog was euthanized 16 days after admission due to complications with clinical signs of sepsis, acute dyspnea and thoracic effusion.
Topics: Dogs; Female; Animals; Pyoderma Gangrenosum; Immunosuppressive Agents; Anti-Infective Agents; Skin; Dog Diseases
PubMed: 37956667
DOI: 10.1055/a-2174-6948 -
Pharmaceuticals (Basel, Switzerland) Jun 2024is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for... (Review)
Review
is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.
PubMed: 38931415
DOI: 10.3390/ph17060748 -
Dermatologic Clinics Apr 2024Acute febrile neutrophilic dermatosis, or Sweet syndrome, has been described in 1964 and is now considered as a prototypical condition of the group of the neutrophilic... (Review)
Review
Acute febrile neutrophilic dermatosis, or Sweet syndrome, has been described in 1964 and is now considered as a prototypical condition of the group of the neutrophilic dermatoses. Since this time, many clinical conditions have been included in this group and a clinical-pathological classification in 3 subgroups has been proposed. Neutrophilic infiltrates can localize in all internal organs. This defines the neutrophilic disease, which induces difficult diagnostic and therapeutic problems. Autoinflammation is the main pathophysiological mechanism of the neutrophilic dermatoses. There is a special link between myeloid malignancies (leukemia and myelodysplasia) and the neutrophilic dermatoses.
Topics: Humans; Pyoderma Gangrenosum; Skin; Inflammation; Sweet Syndrome; Dermatitis; Neutrophils
PubMed: 38423676
DOI: 10.1016/j.det.2023.08.001 -
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 -
Orthopedics 2023A 78-year-old man with a history of multiple cancers presented with severe shoulder pain, elevated inflammatory markers, an ulcerating skin lesion along the anterior...
A 78-year-old man with a history of multiple cancers presented with severe shoulder pain, elevated inflammatory markers, an ulcerating skin lesion along the anterior shoulder, symptoms concerning for septic arthritis, and a lytic lesion of the humeral head. A negative work-up for malignancy prompted infectious work-up and biopsies, revealing positive methicillin-sensitive cultures, yet a curious finding of perivascular lymphocytic infiltrates and fibrinoid necrosis from both the dermal vessel wall from a skin biopsy and humeral head bone biopsy, suggestive of pyoderma gangrenosum. This was a previously undocumented presentation of pyoderma gangrenosum invasion into a large joint with concomitant bacterial septic arthritis. [. 2023;46(5):e321-e325.].
PubMed: 36067061
DOI: 10.3928/01477447-20220831-07 -
Frontiers in Veterinary Science 2023Dogs with allergic dermatitis often suffer concurrent skin and ear infections. The objective of this study was to retrospectively quantify the number of systemic and...
INTRODUCTION
Dogs with allergic dermatitis often suffer concurrent skin and ear infections. The objective of this study was to retrospectively quantify the number of systemic and topical antimicrobial transactions in dogs with allergic dermatitis, following administration of oclacitinib or a glucocorticoid, compared to dogs that did not receive a pruritus therapy when there is an initial diagnosis of pyoderma. A secondary objective was to demonstrate that dogs on oclacitinib use fewer antimicrobials and concomitant therapies over time and have improved quality of life.
MATERIALS AND METHODS
This was a retrospective case-control study using a large, centralized database to identify canine patients receiving pruritus therapy along with a concurrent diagnosis of pyoderma. For the second objective, 58 client-owned dogs diagnosed with allergic dermatitis were enrolled in a prospective owner and dog quality of life and treatment satisfaction (QoL&TS) study that also evaluated concomitant therapy use over time. In Part A, data consisted of anonymous transaction records from 1,134 hospitals across the United States, representing pyoderma visits between December 2018 and December 2019. Odds ratios comparing the relative odds of having additional antimicrobial agent transactions were calculated, given initial pruritus therapy compared to dogs that did not receive pruritus therapy. Parametric bootstrapping was used to calculate goodness-of-fit statistics. In part B, dogs entered the study on Day 0 and returned for examination on Days 14, 21, 30, and 60. Owner determination of QoL&TS was performed on Days 0, 1, 3, 14, 21, 30, and 60. On Days 0, 14, 21, and 60, a veterinarian assessed concomitant therapies and dermatitis severity scoring. Least Squares Means and Standard Errors for QoL&TS, and Dermatitis Vet VAS (Visual Analog Scale) Scores were calculated using a Linear Mixed Model Approach for Repeated Measures (α = 0.05). The percent reduction in therapies was also calculated.
RESULTS
Dogs that received oclacitinib (n = 5,132) or a glucocorticoid ( = 7,024) had reduced odds (OR: 0.8091; = 0.0002 and OR: 0.7095; < 0.0001, respectively) of having a follow up antimicrobial drug transaction after initial antimicrobial therapy compared to dogs with no pruritus therapy at the initial visit ( = 12,997). In part B, oclacitinib demonstrated a statistically significant improvement in QoL&TS scores over time QoL ( < 0.05). Veterinarian assessment showed a 70% reduction in dermatitis severity over time ( < 0.05), supporting oclacitinib's anti-inflammatory effects. Oclacitinib therapy was also associated with an 83% reduction in concomitant treatments, including a 100% reduction in systemic antimicrobial therapy over eight weeks.
DISCUSSION
Dogs receiving oclacitinib showed no increase in antimicrobial therapy transactions compared to glucocorticoid recipients at the initial pyoderma diagnosis. Having a pruritus therapy at the index pyoderma visit reduced the odds of subsequent antimicrobial transactions. In addition to reducing concomitant therapy usage, oclacitinib improved owner and pet QoL, suggesting a paradigm shift in treatment success that could reshape allergic pruritus therapy recommendations. The study provides empirical evidence of oclacitinib's reduction in antibacterial therapy, supporting its therapeutic value and antimicrobial stewardship.
PubMed: 37745208
DOI: 10.3389/fvets.2023.1207582