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Dermatology and Therapy Mar 2024Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical...
INTRODUCTION
Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25 June 2022.
METHODS
Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications.
RESULTS
Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY).
CONCLUSION
Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.
PubMed: 38451423
DOI: 10.1007/s13555-024-01122-2 -
Cureus Feb 2024Pyoderma gangrenosum (PG) is an autoinflammatory skin disease, and there is no definitive test or established criterion for its diagnosis yet. This report discusses a...
Pyoderma gangrenosum (PG) is an autoinflammatory skin disease, and there is no definitive test or established criterion for its diagnosis yet. This report discusses a case of a 34-year-old male patient who presented with an unassuming lesion that quickly worsened with physical manipulation. He was eventually diagnosed with PG. This report highlights the importance of a quick and accurate diagnosis of PG to prevent the worsening of a PG wound and its associated morbidity. It provides a detailed description of the condition accompanied by images to further spread awareness of this rare diagnosis.
PubMed: 38440039
DOI: 10.7759/cureus.53491 -
Clinical, Cosmetic and Investigational... 2024Pyoderma gangrenosum (PG) is a rare cause of skin ulcers in children, posing challenges in diagnosis and treatment. As the disease is often associated with conditions...
BACKGROUND
Pyoderma gangrenosum (PG) is a rare cause of skin ulcers in children, posing challenges in diagnosis and treatment. As the disease is often associated with conditions such as inflammatory bowel disease (IBD), rheumatoid arthritis, haematological disorders and other diseases, diagnosis and treatment often require cooperation with other medical departments. Accordingly, dissemination of information about the disease to doctors in departments other than dermatologists, especially paediatricians, can help in its early detection.
CASE PRESENTATION
The 11-year-old pediatric patient in the case initially diagnosed with acute febrile neutrophilic dermatosis was eventually confirmed as pustular PG through histopathological examinations of skin and other relevant examinations. The medical condition is lessened after treatment with a combination of glucocorticoids and adalimumab.
CONCLUSION
PG is relatively rare in clinical settings, particularly among pediatric patients exhibiting persistent high fever and signs of pustular pyoderma gangrenosum. This case underscores the importance of considering the potential diagnosis of pediatric pustular PG when confronted with a child presenting persistent high fever and pustules after trauma. Additionally, the proactive initiation of adalimumab emerges as a promising treatment option for pediatric IBD -associated pustular PG.
PubMed: 38435844
DOI: 10.2147/CCID.S449404 -
International Wound Journal Mar 2024We evaluated the primary application of crushed prednisolone combined with hydrocolloid powder for clinically diagnosed peristomal pyoderma gangrenosum (PPG). We present...
Clinical efficacy of crushed prednisolone and hydrocolloid powder in the primary treatment of peristomal pyoderma gangrenosum and correlation to in vitro drug release data.
We evaluated the primary application of crushed prednisolone combined with hydrocolloid powder for clinically diagnosed peristomal pyoderma gangrenosum (PPG). We present our data on this cohort and follow-up of our previous patients. Of the 23 patients who were commenced on this regime, 18 healed (78%). Twenty-two patients commenced on this regime as the primary treatment for their PPG, and for one, it was a rescue remedy after failed conventional therapy. Four patients with significant medical comorbidities failed to heal and one had their stomal reversal surgery before being fully healed. The proposed treatment regime for PPG is demonstrated to be effective, inexpensive and able to be managed in the patient's usual home environment. In vitro drug release analysis was undertaken, and data are presented to provide further insights into the efficacy of this regime.
Topics: Humans; Prednisolone; Pyoderma Gangrenosum; Powders; Drug Liberation; Treatment Outcome
PubMed: 38425135
DOI: 10.1111/iwj.14808 -
Journal of Burn Care & Research :... May 2024Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the...
Pyoderma gangrenosum is a rare dermatologic disorder that disrupts the skin barrier, requiring immunosuppressive therapy. We successfully used cefiderocol for the treatment of an extensively drug-resistant Pseudomonas aeruginosa bacteremia, and presumed osteomyelitis in a patient with severe pyoderma gangrenosum and associated immunosuppressive therapy while being medically optimized for skin grafting. We obtained bone and skin/subcutaneous tissue while the patient was on cefiderocol under an institutional review board-approved biologic waste recovery protocol. Cefiderocol concentrations in bone and skin/subcutaneous tissue were 13.9 and 35.9 mcg/g, respectively. The patient recovered from bacteremia and underwent autografting without further complications. Cefiderocol at approved dosing of 2 g IV (3-hour infusion) every 8 hours resulted in bone and skin/subcutaneous tissue concentrations adequate to treat extensively drug-resistant Gram-negative bacteria that remain susceptible to cefiderocol.
Topics: Humans; Anti-Bacterial Agents; Bacteremia; Bone and Bones; Cefiderocol; Cephalosporins; Drug Resistance, Multiple, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Pyoderma Gangrenosum; Skin; Skin Transplantation; Subcutaneous Tissue
PubMed: 38422368
DOI: 10.1093/jbcr/irae026 -
Joint Bone Spine Feb 2024
PubMed: 38417693
DOI: 10.1016/j.jbspin.2024.105712 -
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 -
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 -
Cureus Feb 2024Pyoderma gangrenosum of the breast following surgery is a rare aseptic inflammatory cutaneous condition that causes very rapid progressing and expanding painful...
Pyoderma gangrenosum of the breast following surgery is a rare aseptic inflammatory cutaneous condition that causes very rapid progressing and expanding painful ulceration of the surgical site and the adjacent skin. The greatest issue concerning pyoderma gangrenosum is its diagnosis. Almost invariably, it is misdiagnosed as a wound infection, which results in delayed identification, lengthy antibiotic regimens, and ineffective detrimental surgical debridements, causing significant patient disfigurement. We present a rare case report of pyoderma gangrenosum complicating the surgical site of the breast reduction procedure two months after simultaneous performance of operations including breast reduction, abdominoplasty, and lumbar liposuction. The diagnosis was established within four hours from the initial lesion and symptom presentation due to the accurate evaluation of photographs sent from the patient's mobile phone to the surgeon every half hour. Immediate appropriate treatment with oral corticosteroids within this time interval was initiated, resulting in favorable healing for the patient within four months.
PubMed: 38405660
DOI: 10.7759/cureus.54797 -
Clinical, Cosmetic and Investigational... 2024Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis clinically characterized by painful nodules, red papules or plaques that rapidly erode into...
Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis clinically characterized by painful nodules, red papules or plaques that rapidly erode into ulcers. We report a 53-year-old febrile male patient with acute peripheral arterial disease who underwent transtibial amputation after failed thrombolysis. Five days after amputation, an ulcer developed around the cannulation site of the right internal jugular vein that was indicative of pathergy. The patient's fever did not improve after surgery, and purpuric discoloration and punctate ulcers of the skin near the amputation site became apparent, leading to re-debridement. Finally, consultation with a dermatologist raised the possibility of postoperative PG, and additional laboratory tests revealed positive anticardiolipin autoantibodies consistent with antiphospholipid syndrome. The patient was treated with intravenous glucocorticosteroids and antibiotics, and the amputation wound and cannulation site ulcer were found to have healed at the 2-month follow-up. The current report raises the need for vascular surgeons to be aware of this uncommon etiology of arterial thrombosis, and the postoperative appearance of dermatosis and pathergy should alert for PG.
PubMed: 38404477
DOI: 10.2147/CCID.S451771