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Current Protocols Nov 2023The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly... (Review)
Review
The purpose of this article is to provide an overview of existing pharmacological models of canine dermatitis. Canine models of dermatitis have contributed significantly to our current understanding of the pathology of dermatitis and to the development of corresponding pharmacological interventions. Specifically, canine atopic dermatitis (AD) is reviewed here, as it is one of the most common inflammatory skin diseases in dogs. Canine AD also shares clinicopathological features with human AD, making the dog a natural and optimal model for human disease. Thus, pharmacological models of canine AD may be uniquely applicable to human pharmacological research. In this article, particular attention is dedicated to relevant in vivo, in vitro, and ex vivo models of canine AD, skin barrier defect models, pruritus models, and skin immunology models. Additionally, models of superficial pyoderma and food allergy are also discussed. With understanding of findings from canine models, researchers can select the most salient features for future pharmacological drug development. © 2023 Wiley Periodicals LLC.
Topics: Animals; Dogs; Dermatitis, Atopic; Dog Diseases; Food Hypersensitivity; Pruritus; Skin
PubMed: 37996978
DOI: 10.1002/cpz1.935 -
Postgraduate Medical Journal Jun 2024Our objective in this study is to determine the atypical clinical presentations of cutaneous leishmaniasis (CL) patients diagnosed in Şanlıurfa province.
BACKGROUND
Our objective in this study is to determine the atypical clinical presentations of cutaneous leishmaniasis (CL) patients diagnosed in Şanlıurfa province.
METHODS
This retrospective study included 213 patients with atypical clinical presentations among 1751 patients diagnosed with CL between October 2019 and August 2022 in Şanlıurfa Oriental Boil Diagnosis and Treatment Center located in an endemic region for CL.
RESULTS
We found the prevalence of atypical CL to be 12.1%. The most common atypical lesions were lupoid 21 (9.8%), erysipeloid 16 (7.5%), impetiginous 16 (7.5%), recidivan 15 (7%), eczematous 15 (7%), ecthyma-like 13 (6.1%), pyoderma gangrenous-like 12 (5.6%), and sporotrichoid 12 (5.6%). Other lesions with atypical clinical presentations: chalazion-like, verrucous, dental sinus-like, psoriasiform, zosteriform, lymphoma-like, juvenile xanthogranuloma-like, volcano-like, paronychial, basal cell carcinoma-like, squamous cell carcinoma-like, herpes labialis-like, keratoacanthoma-like, chancriform, annular, lichenoid, mastocitoma-like, keloidal, epidermoid cyst-like, kaposi sarcoma-like, scar leishmaniasis, granulomatous cheilitis-like, mycetoma-like, molluscum contagiosum-like, discoid lupus erythematosus-like, and dermatofibroma-like.
CONCLUSIONS
In addition to the atypical clinical presentations previously reported, we also defined dermatofibroma-like, Kaposi sarcoma-like, dental sinus-like, juvenile xanthogranuloma-like, mastocytoma-like, and epidermoid cyst-like. It should be kept in mind that CL can clinically mimic many infectious, inflammatory, and neoplastic diseases, which should be considered in the differential diagnosis of long-term non-healing lesions, especially in endemic areas. Key message What is already known on this subject: CL is known as the great imitator disease in dermatology. What this study adds: In addition to the atypical clinical presentations previously reported, we also defined dermatofibroma-like, Kaposi sarcoma-like, dental sinus-like, juvenile xanthogranuloma-like, mastocytoma-like, and epidermoid cyst-like. How this study might affect research, practice, or policy: CL can clinically mimic many infectious, inflammatory and neoplastic diseases, which should be considered in the differential diagnosis of long-term non-healing lesions, especially in endemic areas.
PubMed: 38899808
DOI: 10.1093/postmj/qgae075 -
Pharmaceuticals (Basel, Switzerland) Nov 2023: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is...
: Immune-related cutaneous adverse events (ircAEs) are frequent and may reduce quality of life and consistent dosing. IL12/23 has been implicated in psoriasis, which is reminiscent of the psoriasiform/lichenoid ircAE phenotype. We report the use of ustekinumab as a therapeutic option. : Patients at Memorial Sloan Kettering Cancer Center, New York, who received immune checkpoint inhibitors and were treated with ustekinumab or had the keywords "ustekinumab" or "Stelara" in their clinical notes between 1 March 2017 and 1 December 2022 were retrospectively identified via a database query. Documentation from initial and follow-up visits was manually reviewed, and response to ustekinumab was categorized into complete cutaneous response (CcR, decrease to CTCAE grade 0), partial cutaneous response (PcR, any decrease in CTCAE grade exclusive of decrease to grade 0), and no cutaneous response (NcR, no change in CTCAE grade or worsening). Labs including complete blood count (CBC), cytokine panels, and IgE were obtained in a subset of patients as standard of care. Skin biopsies were reviewed by a dermatopathologist. : Fourteen patients with psoriasiform (85.7%), maculopapular (7.1%), and pyoderma gangrenosum (7.1%) ircAEs were identified. Ten (71.4%) receiving ustekinumab had a positive response to treatment. Among these 10 responders, 4 (40%) demonstrated partial cutaneous response and 6 (60%) demonstrated complete cutaneous resolution. Six patients (42.9%) experienced interruptions to their checkpoint inhibitor treatment as a result of intolerable ircAEs, and following ircAE management with ustekinumab, two (33.3%) were successfully rechallenged with their checkpoint inhibitors. On histopathology, patients primarily had findings of interface or psoriasiform dermatitis. No patients reported an adverse event related to ustekinumab. : Ustekinumab showed a benefit in a subset of patients with psoriasiform/lichenoid ircAEs. No safety signals were identified. However, further prospective randomized controlled trials are needed to confirm our findings.
PubMed: 38004414
DOI: 10.3390/ph16111548 -
Modern Rheumatology Case Reports Dec 2023Pyoderma gangrenosum (PG) is a rare inflammatory skin disease characterised by skin ulcers that are associated with autoimmune diseases. Although the effectiveness of...
Pyoderma gangrenosum (PG) is a rare inflammatory skin disease characterised by skin ulcers that are associated with autoimmune diseases. Although the effectiveness of immunosuppression with glucocorticoids and tumour necrosis factor inhibitors in treating PG has been reported, the utility of negative-pressure wound therapy (NPWT) for severe ulcerative lesions in patients with PG remains controversial. Herein, we report the case of a 76-year-old woman with rheumatoid arthritis who developed PG after undergoing surgery for a forefoot deformity. The patient showed improvement in deep ulcer lesions through NPWT while receiving treatment with abatacept and systemic glucocorticoids. Subsequent topical glucocorticoid therapy led to the remission of the PG. This case suggests that NPWT, when used under immunosuppressive conditions, does not exacerbate the pathergy and may be beneficial for treating severe ulcerative PG.
Topics: Female; Humans; Aged; Pyoderma Gangrenosum; Arthritis, Rheumatoid; Immunosuppressive Agents; Glucocorticoids
PubMed: 37638693
DOI: 10.1093/mrcr/rxad051 -
Rheumatology International Aug 2023Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role...
BACKGROUND
Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role in their pathogenesis.
OBJECTIVES
This study aimed to investigate the involvement of Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway in the pathogenesis of ISDs.
METHODS
The study analyzed a total of 117 skin biopsies, comprising 31 from pyoderma gangrenosum (PG), 25 from hidradenitis suppurativa (HS), 35 from psoriasis patients, and 26 from control subjects. To assess the expression levels of JAK/STAT pathway components, immunohistochemical staining was performed on both the dermal and epidermal layers of the skin. The Histo score (H score) was utilized as the immunoexpression score to evaluate the staining intensity.
RESULTS
The results indicated that all components of the JAK/STAT signaling pathway, except JAK2 and STAT6 in PG, JAK1, STAT4, and STAT6 in HS, and JAK1 in psoriasis, were overexpressed in the dermal skin compared to the control group (p < 0.05). Psoriatic skin had higher expression of STAT6 than both PG and HS and higher expression of JAK2 than PG (p < 0.05). Additionally, HS biopsies had higher expression of JAK2 and STAT6 compared to PG (p < 0.05). JAK1 expression was higher in PG than in HS, psoriasis, and the control group (mean H score was 265.8, 184.8, 191.4, and 113.1, p < 0.05, respectively).
CONCLUSIONS
This study provides new insights into the potential contribution of the JAK/STAT pathway to the pathogenesis of ISDs. The findings suggest that targeting this pathway could be a promising therapeutic strategy for treating these disorders.
PubMed: 37558928
DOI: 10.1007/s00296-023-05418-y -
Plastic and Reconstructive Surgery.... Jan 2024Pyoderma gangrenosum is a neutrophilic dermatosis characterized by immune dysfunction and pathergy. Thus, it is frequently seen in patients with underlying systemic... (Review)
Review
Pyoderma gangrenosum is a neutrophilic dermatosis characterized by immune dysfunction and pathergy. Thus, it is frequently seen in patients with underlying systemic illnesses or postoperatively. For the performance of the debridement or closure of the resultant defect, plastic surgeons are often involved in the care of pyoderma patients. However, both procedures may exacerbate the injury. Therefore, plastic surgeons must be familiar with the presentation of postsurgical pyoderma to avoid further damage and safely repair related soft tissue defects. A systematic search of the PubMed/Medline database was performed using the following keywords: "pyoderma gangrenosum" and "surgery." This online database search has identified 656 studies published between 1958 and 2022. Only reconstructed cases of postsurgical pyoderma gangrenosum were selected. Twenty-eight patients who developed pyoderma after dermatologic, plastic, orthopedic, cardiovascular, general, or obstetric surgery were included in this study. The average time to the PG presentation and diagnosis was 5.5 and 17 days, respectively. Diagnostic scoring tools were not used, and the diagnosis was primarily based on histopathology after repeated treatment failures. The patients received split- or full-thickness skin grafts, local, pedicled, and free flaps. An estimated 82.1% underwent skin grafting, whereas 42.9% underwent flap reconstruction. In addition, 21.4% got both the graft and flap. Accurate diagnosis of PSPG, prevention of further surgical injury, and timely medical management are vital for improving patient outcomes. Reconstruction can be performed, if required. However, despite the availability of different reconstructive techniques, there is no standard approach to the management of the PSPG.
PubMed: 38250211
DOI: 10.1097/GOX.0000000000005505 -
Veterinary World Nov 2023Methicillin-resistant Staphylococci (MRS) seriously threatens animal and human health. Repeated antibiotic use allows the bacteria to develop resistance to several...
BACKGROUND AND AIMS
Methicillin-resistant Staphylococci (MRS) seriously threatens animal and human health. Repeated antibiotic use allows the bacteria to develop resistance to several antibiotic classes and become multidrug-resistant (MDR). Canine pyoderma, a common skin condition in dogs, is mainly caused by Staphylococci, including MRS. Detecting this infection in all canine populations is crucial to develop a proper preventive plan. This study estimated the prevalence, antibiogram, and risk factors of MRS in canine patients at a referral animal hospital in Khon Kaen, Thailand.
MATERIALS AND METHODS
Skin swabs and relevant information were collected from 56 client-owned dogs that visited the hospital from September 2019 to September 2020. Staphylococci colonies were subjected to molecular identification and antibiotic susceptibility tests using an automated system (VITEK 2). These colonies were also genetically identified using multiplex-polymerase chain reaction (PCR) and sequencing. The A gene, encoding methicillin resistance, was detected using simplex-PCR. The risk factors of MRS infection and their association with MRS infection were analyzed using logistic regression and the Chi-square test, respectively.
RESULTS
The prevalence of MRS was found to be 35.7% (20/56 dogs). By species, methicillin-resistant was found in 24 of 104 isolates (23.1%), and all samples were MDR. Receiving systemic antibiotics in the past 6 months was a major risk factor associated with MRS infection (p < 0.05; odds ratio (OR) > 1). In addition to the MRS isolates, the A gene was also detected in methicillin-susceptible Staphylococci isolates. This might be because of the high expression of I, and mutations in c-di-AMP cyclase DacA, RelA, and Fem proteins.
CONCLUSION
A high prevalence of MRS and MDR was observed in the studied population, which might be potentially due to improper antibiotic use by the owners and horizontal transfer of drug-resistance genes.
PubMed: 38152262
DOI: 10.14202/vetworld.2023.2340-2348 -
Journal of the European Academy of... May 2024The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily,... (Review)
Review
The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily, IL-36 plays a pivotal role in both innate and adaptive immune responses. Of the four IL-36 isoforms, three have agonist activity (IL-36α, IL-36β, IL-36γ) and the fourth has antagonist activity (IL-36 receptor antagonist [IL-36Ra]). All IL-36 isoforms bind to the IL-36 receptor (IL-36R). Binding of IL-36α/β/γ to the IL-36R recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates downstream signalling pathways mediated by nuclear transcription factor kappa B and mitogen-activated protein kinase signalling pathways. Antagonist binding of IL-36Ra to IL-36R inhibits recruitment of IL-1RAcP, blocking downstream signalling pathways. Changes in the balance within the IL-36 cytokine family can lead to uncontrolled inflammatory responses throughout the body. As such, IL-36 has been implicated in numerous inflammatory diseases, notably a type of pustular psoriasis called generalized pustular psoriasis (GPP), a chronic, rare, potentially life-threatening, multisystemic skin disease characterised by recurrent fever and extensive sterile pustules. In GPP, IL-36 is central to disease pathogenesis, and the prevention of IL-36-mediated signalling can improve clinical outcomes. In this review, we summarize the literature describing the biological functions of the IL-36 pathway. We also consider the evidence for uncontrolled activation of the IL-36 pathway in a wide range of skin (e.g., plaque psoriasis, pustular psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis and pyoderma gangrenosum), lung (e.g., idiopathic pulmonary fibrosis), gut (e.g., intestinal fibrosis, inflammatory bowel disease and Hirschsprung's disease), kidney (e.g., renal tubulointerstitial lesions) and infectious diseases caused by a variety of pathogens (e.g., COVID-19; Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pneumoniae infections), as well as in cancer. We also consider how targeting the IL-36 signalling pathway could be used in treating inflammatory disease states.
PubMed: 38779986
DOI: 10.1111/jdv.19935 -
JAAD Case Reports Jul 2023
PubMed: 37342401
DOI: 10.1016/j.jdcr.2023.05.016 -
Inflammatory Bowel Diseases Feb 2024Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammatory bowel disease (IBD) is a multisystem disease impacting various body systems including musculoskeletal, ocular, skin, hepatobiliary, pulmonary, cardiac, and haematological systems. The extraintestinal manifestations of IBD are frequent, common in both ulcerative colitis (UC) and Crohn's disease (CD), and impact the morbidity and mortality of patients.
METHODS
The Embase, Embase classic, and PubMed databases were searched between January 1979 and December 2021. A random effects model was performed to find the pooled prevalence of joint, ocular, and skin extraintestinal manifestations of UC and CD.
RESULTS
Fifty-two studies were included that reported on 352 454 patients. The prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in all IBD, UC, and CD was 24%, 27%, and 35% respectively. The prevalence between UC and CD were similar for pyoderma gangrenosum and axial joint manifestations. Ocular manifestations were found to be more common in CD than in UC. Peripheral joint manifestations and erythema nodosum were found to be more common in CD than UC.
DISCUSSION
To our knowledge, this is the first meta-analysis that reports on the prevalence of at least 1 joint, ocular, or skin extraintestinal manifestation in IBD. Our results are largely consistent with figures and statements quoted in the literature. However, our findings are based on significantly larger cohort sizes. Thus, our results have the potential to better power studies and more accurately counsel patients.
Topics: Humans; Prevalence; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Pyoderma Gangrenosum
PubMed: 37042969
DOI: 10.1093/ibd/izad061