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Revista Espanola de Enfermedades... Aug 2023Peristomal ulcer is a frequent complication that, in most cases, is mild and responds to topical treatment. In much less frequent cases, it is associated with other...
Peristomal ulcer is a frequent complication that, in most cases, is mild and responds to topical treatment. In much less frequent cases, it is associated with other pathologies, such as Crohn's disease, requiring in these cases systemic treatment, including surgery. The differential diagnosis between Cutaneous Inflammatory Bowel Disease and Pyoderma Gangrenosum is interesting, although both are managed in a similar way.
Topics: Humans; Crohn Disease; Inflammatory Bowel Diseases; Pyoderma Gangrenosum; Administration, Topical; Wound Healing
PubMed: 35791785
DOI: 10.17235/reed.2022.8909/2022 -
Archives of Dermatological Research Jun 2024Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome is a rare condition characterized by clinical features of all three dermatologic conditions. The...
BACKGROUND
Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) syndrome is a rare condition characterized by clinical features of all three dermatologic conditions. The management of PASH syndrome is difficult, with no consensus on treatment guidelines. Since PASH syndrome can increase morbidity and adversely impact quality of life, better characterization of effective therapies is needed.
METHODS
A retrospective cohort study was conducted to identify all patients with pyoderma gangrenosum (PG) treated at The Ohio State University Wexner Medical Center between 2015 and 2021. PG diagnosis was confirmed via PARACELSUS score. Subsequent chart review identified eight patients with concomitant hidradenitis suppurativa (HS) and acne who were clinically diagnosed with PASH syndrome.
RESULTS
Eight patients were clinically diagnosed with PASH syndrome based on their clinical presentation at our institution. Seven patients had failed some type of medical therapy prior to presentation, including topical corticosteroids, oral corticosteroids, oral antibiotics, and biologics. One patient had also tried surgical drainage at an outside institution. Six patients were effectively treated with biologics, usually in combination with other therapies. One patient experienced improvement of her skin lesions after diagnosis and treatment of her underlying hematologic malignancy.
CONCLUSIONS
Medical management with biologics in combination with corticosteroids and/or antibiotics was effective in the management of most patients. Diagnosis and treatment of an underlying condition should be prioritized in refractory cases. If workup is negative, surgical management may be considered. Further investigation with a greater number of patients is required to develop management guidelines for PASH syndrome.
Topics: Humans; Pyoderma Gangrenosum; Female; Retrospective Studies; Acne Vulgaris; Hidradenitis Suppurativa; Adult; Male; Anti-Bacterial Agents; Young Adult; Middle Aged; Biological Products; Treatment Outcome; Quality of Life; Syndrome; Adolescent; Adrenal Cortex Hormones
PubMed: 38878169
DOI: 10.1007/s00403-024-03125-7 -
JAAD Case Reports Jul 2023
PubMed: 37342401
DOI: 10.1016/j.jdcr.2023.05.016 -
Joint Bone Spine Feb 2024
PubMed: 38417693
DOI: 10.1016/j.jbspin.2024.105712 -
Frontiers in Immunology 2023Inflammatory bowel disease (IBD) is a chronic inflammatory disease typically involving the gastrointestinal tract but not limited to it. IBD can be subdivided into... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disease typically involving the gastrointestinal tract but not limited to it. IBD can be subdivided into Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) are observed in up to 47% of patients with IBD, with the most frequent reports of cutaneous manifestations. Among these, pyoderma gangrenosum (PG) and erythema nodosum (EN) are the two most common skin manifestations in IBD, and both are immune-related inflammatory skin diseases. The presence of cutaneous EIMs may either be concordant with intestinal disease activity or have an independent course. Despite some progress in research on EIMs, for instance, ectopic expression of gut-specific mucosal address cell adhesion molecule-1 (MAdCAM-1) and chemokine CCL25 on the vascular endothelium of the portal tract have been demonstrated in IBD-related primary sclerosing cholangitis (PSC), little is understood about the potential pathophysiological associations between IBD and cutaneous EIMs. Whether cutaneous EIMs are inflammatory events with a commonly shared genetic background or environmental risk factors with IBD but independent of IBD or are the result of an extraintestinal extension of intestinal inflammation, remains unclear. The review aims to provide an overview of the two most representative cutaneous manifestations of IBD, describe IBD's epidemiology, clinical characteristics, and histology, and discuss the immunopathophysiology and existing treatment strategies with biologic agents, with a focus on the potential pathophysiological associations between IBD and cutaneous EIMs.
Topics: Humans; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative; Pyoderma Gangrenosum; Erythema Nodosum
PubMed: 37954590
DOI: 10.3389/fimmu.2023.1234535 -
Pediatric Rheumatology Online Journal Nov 2023Rheumatic patients have a higher frequency of tuberculosis(TB) than the general population. This study aimed to describe children and adolescents with TB and rheumatic...
BACKGROUND
Rheumatic patients have a higher frequency of tuberculosis(TB) than the general population. This study aimed to describe children and adolescents with TB and rheumatic diseases(RD) who were being treated in a reference center.
METHODS
A series of TB cases were investigated in a reference center for childhood TB in Rio de Janeiro, Brazil, from 1995 to 2022.
RESULTS
Fifteen patients with underlying RD and TB were included with 8(53%) being female. The mean age at RD diagnosis was 7.10years (SD ± 0,57 years), and the mean age at TB diagnosis was 9.81 years(SD ± 0.88 years). A total of 9 cases of pulmonary TB(PTB) and 6 cases of extrapulmonary TB-pleural(2), joint/osteoarticular(1), cutaneous(1), ocular(1), and peritoneal(1)- were described. The RD observed in the 15 patients included juvenile idiopathic arthritis(9), juvenile systemic lupus erythematosus(3), juvenile dermatomyositis(1), polyarteritis nodosa(1), and pyoderma gangrenosum(1). Among the immunosuppressants/immunobiologics, methotrexate(8) was the most commonly used, followed by corticosteroids(6), etanercept(2), mycophenolate mofetil(1), cyclosporine A(1), adalimumab(1), and tocilizumab(1). The most common symptoms were fever and weight loss, and a predominance of PTB cases was noted. GeneXpert MTB/RIF® was performed in six patients and was detectable in two without rifampicin resistance; Xpert Ultra® was performed in five patients, and traces with indeterminate rifampicin resistance were detected in three. One female patient discontinued treatment, and another passed away.
CONCLUSIONS
The case series demonstrated the importance of suspecting and investigating TB in RD affected patients who are using immunosuppressants/ immunobiologics, particularly in countries with high rates of TB such as Brazil.
Topics: Humans; Child; Female; Adolescent; Male; Rifampin; Mycobacterium tuberculosis; Sensitivity and Specificity; Brazil; Tuberculosis; Rheumatic Diseases; Immunosuppressive Agents
PubMed: 37950309
DOI: 10.1186/s12969-023-00918-4 -
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 -
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 -
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 -
Journal of the American Academy of... Jun 2024
Review
PubMed: 38906261
DOI: 10.1016/j.jaad.2024.05.086