Search Results (52)

This study investigates shared molecular mechanisms between pyoderma gangrenosum (PG) and inflammatory bowel disease (IBD) and systematically evaluates the therapeutic potential of JAK inhibitors targeting this pathway. Despite the clear clinical comorbidity, the core inflammatory pathways driving cross-tissue associations between the two diseases remain unclear. Furthermore, systematic mechanistic evidence is lacking regarding whether JAK inhibitors act by regulating shared pathological pathways in patients with comorbidities. To address this, this study integrated PG skin and IBD intestinal transcriptome data, single-cell transcriptomic data, and genome-wide association study (GWAS) meta-data from public databases. It employed a multi-level computational biology approach combining Mendelian randomization, weighted gene co-expression network analysis, protein interaction network construction, molecular docking simulations, and system dynamics modeling. The results revealed that genetic analysis confirmed IBD as a causal risk factor for PG, precisely identifying six shared genetic loci. Transcriptomic analysis identified a cross-tissue conserved inflammatory module centered on the JAK-STAT pathway, with JAK2 and STAT3 identified as network hubs. Molecular docking predicted high affinity of baricitinib for both JAK1 and JAK2, while system dynamics modeling demonstrated that its intervention effectively suppresses signaling in the shared inflammatory network. This study reveals the molecular basis of the “gut–skin axis” comorbidity between PG and IBD from a multi-omics integration perspective. It provides predictive computational evidence for the use of JAK inhibitors in targeted comorbidity therapy. Baricitinib is identified as a particularly promising candidate. These findings advance the transition from empirical drug use to mechanism-guided precision treatment strategies. Although this study provides multiscale computational simulation evidence, the lack of direct experimental validation of these predicted results necessitates further confirmation through in vitro and in vivo experiments. Full article

Carotid pseudoaneurysms are rare and potentially life-threatening, often necessitating urgent surgical intervention. Patients with myeloproliferative disorders (MPD) are predisposed to thrombotic and inflammatory complications. Pyoderma gangrenosum (PG), a rare neutrophilic dermatosis, is often misdiagnosed in postoperative settings. In the following article, we present a case of a 58-year-old woman with Philadelphia-negative MPD, neutrophilic leukocytosis, thrombocytosis, osteoporosis, and hypothyroidism, who presented with a giant left common carotid artery pseudoaneurysm. She underwent urgent surgical revascularization via bypass using an autologous reversed saphenous vein graft from the right thigh and external carotid artery ligation. Immediately postoperatively, the patient developed left hemiparesis. Initial CT scans showed bypass graft occlusion and right MCA stroke. Immediate thrombolysis resulted in complete motor recovery, although the bypass remained occluded. On postoperative day 10, necrotic wound lesions developed, initially treated as infectious. After worsening post-debridement, dermatologic evaluation raised suspicion for PG, confirmed by biopsy. She responded well to corticosteroid therapy. Four weeks later, the thigh wound became superinfected with Pseudomonas aeruginosa and Klebsiella pneumoniae, successfully treated with broad-spectrum antibiotics. The patient fully recovered within two months. This case illustrates the complex interplay between vascular, thrombotic, and inflammatory complications in patients with MPD and emphasizes the importance of multidisciplinary care and early recognition of PG. Full article

This article discusses the treatment course of an aggressive diabetic foot infection (DFI) complicated by the emergence of pyoderma gangrenosum (PG). A 67-year-old man with long-standing diabetes presented with a nonhealing DFI that prompted antibiotic treatment and surgical debridement. However, the coexistence of DFI and PG may create a conflict in the treatment approach, as treating one condition may exacerbate the other. The patient responded positively to systemic corticosteroids and infliximab, and, despite conflicting recommendations on debridement, surgical intervention proved necessary. This report advocates for early PG diagnosis using the Delphi model and stresses the need for ongoing research regarding surgical debridement in these complex scenarios. Full article

Background/Objectives: Pyoderma gangrenosum (PG) is a rapidly progressive, ulcerating condition that can cause large, painful lesions when uncontrolled. There is currently no standard of care treatment for severe PG ulcers refractory to systemic treatment. The present study aims to characterize the outcomes of placental allografts in treating severe PG lesions. Methods: A single institution retrospective chart review was conducted at the University of South Florida affiliated sites examining PG patients that received placental allograft treatment. Results: The review returned five patients with clinically diagnosed or biopsy-proven PG treated with placental allograft. In all five patients, application of placental allograft resulted in varying degrees of short-term (<1 month) improvement. Near-complete resolution was observed in one patient. Out of the 20 total allografts placed between the 5 patients, only one had an adverse event of infection within one week of placement. Grafts were otherwise very well tolerated by all patients. Conclusions: Placental allografts show promising adjunctive therapeutic potential for severe PG lesions with preliminary findings showing good viability and safety profiles. Future prospective controlled studies should be performed to further examine the viability of this adjunctive treatment in this disease. Full article

Background: Autoinflammatory bone disorders are rare, non-infectious inflammatory conditions that primarily involve the skeleton, most commonly presenting as chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO). Less frequently, they occur in the context of Mendelian syndromes such as Majeed syndrome, deficiency of the interleukin-1 receptor antagonist (DIRA), and pyogenic arthritis; pyoderma gangrenosum; and acne (PAPA) syndrome. Given the role of IL-1-driven innate immune dysregulation across these bone disorders, and the growing, though heterogeneous, clinical experience with IL-1 blockade, this review maps and critically appraises the available evidence on canakinumab in autoinflammatory bone disorders. Methods: We systematically searched PubMed and the Cochrane Library (English, inception–July 2025) and screened ClinicalTrials.gov. Eligible reports included any case reports/series describing canakinumab use in autoinflammatory bone disorders (CNO/CRMO, Majeed, DIRA, PAPA). Results: Six publications met the inclusion criteria (one case series, five case reports; 10 patients). Complete responses were reported in all three patients with Majeed syndrome and in two patients with sporadic CRMO associated with systemic features. Partial responses occurred in two additional sporadic CRMO cases, while no meaningful response was documented in DIRA. No interventional trials of canakinumab were identified on ClinicalTrials.gov for CNO/CRMO, Majeed, DIRA, or PAPA. Conclusions: Although the role of IL-1 in the pathogenesis of autoinflammatory bone disease provides a rationale for IL-1 blockade, evidence for canakinumab remains limited and heterogeneous, precluding definitive conclusions. Indicators of benefits appear most consistently in Majeed syndrome and in selected CRMO phenotypes. Full article

Background: Primary cutaneous B-cell lymphomas (CBCLs) are a rare and heterogeneous group of lymphomas, among which the anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) represents an exceptionally rare entity. Although they typically present as painless and non-ulcerated skin lesions, rare variants may exhibit atypical clinical features. Pyoderma gangrenosum (PG) is a rare inflammatory ulcerative disease that may overlap clinically with other ulcerative dermatoses and pose diagnostic challenges due to the absence of standardized differential algorithms. Methods: An 85-year-old male presented with multiple rapidly progressive, painful, ulcerative lesions, initially misdiagnosed as PG and treated with oral cyclosporine with no clinical response. Skin biopsy specimens underwent detailed histopathological and immunohistochemical evaluation. Results: The analyses revealed dense infiltration of atypical large lymphoid cells, with CD20, CD45, and CD30 positivity, and a Ki-67 proliferation index of approximately 90%, consistent with primary cutaneous A-DLBCL. Owing to the delayed correct diagnosis, the patient’s condition deteriorated rapidly, leading to his death before appropriate therapy could be initiated. Conclusions: The case documents an exceptionally rare cutaneous presentation of A-DLBCL, expanding the extremely limited literature on this enigmatic entity. Furthermore, it underscores the fundamental role of early skin biopsy in the differential diagnosis of non-specific ulcerative lesions, which is critical for ensuring appropriate treatment administration within the therapeutic window in cases of malignancy. Full article

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by chronic, painful ulcerations. Despite increasing evidence suggesting immunological dysregulation, the role of IL-36 cytokines in PG remains poorly defined. To evaluate serum levels of IL-36α, IL-36β, IL-36γ, IL-36Ra, IL-37, and IL-38 in PG patients compared to healthy controls, and to assess their correlation with selected clinical parameters and cytokine ratios. 44 PG patients and 40 healthy controls were included in this case–control study. Serum cytokine levels were measured using ELISA. Correlations between cytokine levels and clinical features were analyzed using nonparametric tests. PG patients showed significantly lower serum levels of IL-36α and IL-36γ (p = 0.0003 and p = 0.02, respectively), with no difference in IL-36β. Conversely, levels of IL-36Ra, IL-37, and IL-38 were significantly higher in PG patients (p < 0.0001 for all). In the PG group, significant positive correlations were observed between IL-36α and IL-36β, and between IL-36β and IL-36γ, while IL-37 correlated negatively with IL-38. IL-36α was inversely associated with serum IgA levels and total ulcer surface area, and IL-36γ correlated negatively with white blood cell count. Our findings reveal a dysregulated IL-36 cytokine profile in pyoderma gangrenosum, marked by reduced serum levels of IL-36α and IL-36γ and elevated levels of IL-36Ra, IL-37, and IL-38. This may reflect a compensatory response to chronic inflammation. The inverse correlation between IL-36α and ulcer size suggests its potential involvement in wound healing. Despite lower serum levels of agonists, local biological activity of IL-36 cytokines may remain elevated due to tissue-level activation and consumption. These results highlight the therapeutic relevance of targeting the IL-36 pathway—particularly in treatment-resistant cases—and support further research into cytokine activity beyond serum concentration to guide novel therapeutic strategies. Full article

Post-surgical pyoderma gangrenosum is a rare neutrophilic dermatosis that may occur after surgical procedures, mimicking a wound infection. Early recognition is crucial to prevent unnecessary debridement and worsening of lesions due to pathergy. We report the case of a 67-year-old woman who underwent nipple-sparing mastectomy for invasive breast carcinoma with immediate reconstruction using a tissue expander. In the early postoperative period, she developed an extensive sterile necrotic–ulcerative inflammation of the left breast, unresponsive to broad-spectrum antibiotics and repeated surgical revisions. Histopathology revealed an aseptic neutrophilic infiltrate, confirming the diagnosis of post-surgical pyoderma gangrenosum. The patient responded favorably to high-dose corticosteroid therapy, achieving complete wound healing and definitive reconstruction with a TRAM flap. This case highlights the importance of considering post-surgical pyoderma gangrenosum in the differential diagnosis of inflammatory postoperative complications in breast oncology surgery. Prompt diagnosis and early initiation of immunosuppressive therapy within a multidisciplinary approach are key to preserving tissues and ensuring optimal functional and aesthetic outcomes. Full article

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L., has emerged as a promising multifunctional agent in dermatology and cosmetic science. The review provides an updated synthesis of CBD’s topical therapeutic potential, challenges, and evolving regulatory frameworks. CBD exhibits diverse biological effects, including anti-inflammatory, antioxidant, antibacterial, analgesic, lipostatic, antiproliferative, moisturising, and anti-ageing properties through interactions with the skin’s endocannabinoid system (ECS), modulating CB1, CB2, TRPV channels, and PPARs. Preclinical and clinical evidence support its efficacy in managing acne, psoriasis (including scalp psoriasis), atopic and seborrheic dermatitis, and allergic contact dermatitis. CBD also relieves pruritus through neuroimmune modulation and promotes wound healing in conditions such as pyoderma gangrenosum and epidermolysis bullosa. In hair disorders such as androgenetic alopecia, it aids follicular regeneration. CBD shows promise in managing skin cancers (melanoma, squamous cell carcinoma, Kaposi sarcoma) and pigmentation disorders such as melasma and vitiligo. It enhances skin rejuvenation by reducing oxidative stress and boosting collagen and hydration. However, there are challenges regarding CBD’s physicochemical stability, skin penetration, and regulatory standardisation. As consumer demand for natural, multifunctional skincare grows, further research is essential to validate its long-term safety, efficacy, and optimal formulation strategies. Full article

Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article

Introduction. The pathophysiology of Pyoderma Gangrenosum (PG) involves altered innate and adaptive immunity, mutagenic and epigenetic changes, the autoinflammatory state, and the overexpression of cytokines. This study investigated the potential contribution of inflammation, redox signaling, and the immune system in the pathogenesis of PG. Materials and Methods. This case–control study included 36 patients with PG and 30 controls. We have determined the serum concentrations of acute phase proteins (C-reactive protein—CRP, alpha1 glycoprotein acid—AGPA, Albumin), interleukin-17A -IL-17A, β2 microglobulin-β2MG, reduced glutathione-GSH, oxidized glutathione- GSSG, the GSH/GSSG ratio, and hematological parameters (white blood cells-WBC, neutrophil-lymphocyte ratio-NLR, erythrocyte sedimentation rate-ESR) in patients with PG compared with controls. Furthermore, we have evaluated the variations in these markers before and after treatment in PG patients. Results. The serum concentrations of acute phase proteins (CRP, AGPA, and Albumin) and the IL-17A, β2MG, GSH, GSSG, and GSH/GSSG ratio were significantly different between the PG group and controls. Hematological parameters (WBC, NLR, and ESR), acute phase proteins (CRP, AGPA, and albumin), and IL-17A showed an exaggerated and persistent inflammatory response in patients with PG. In patients with PG associated with systemic diseases, the dysregulation of the biochemical events was more severe. Conclusions. The acute phase proteins, β2MG-MHC class I complex, and the GSH-GSSG system are unbalanced in PG. Our results could improve the diagnosis and our understanding of the pathogenic basis of PG. Full article

Background: Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that frequently occurs in association with systemic diseases such as inflammatory bowel disease (IBD). This case report describes a 23-year-old female with Crohn’s disease (CD) who developed PG and was successfully treated with adalimumab. The objective of this study is to present the clinical course, treatment approach, and outcomes while reviewing the existing literature on the efficacy of adalimumab in PG management. Methods: A case report is presented, detailing clinical presentation, diagnostic evaluation, and treatment strategy. Additionally, a systematic review was conducted using PubMed to assess studies on adalimumab in PG, focusing on treatment response, remission rates, and adverse effects. Results: The patient presented with ulcerative lesions on her lower extremities and sacroiliitis. After corticosteroid therapy, adalimumab was initiated, leading to significant ulcer healing, reduced back pain, and CD remission. The systematic review identified seven studies on adalimumab in PG. Findings suggest that adalimumab is effective in steroid-refractory cases, with remission achieved in a significant proportion of patients. The most common adverse effects were infections, but overall, adalimumab showed a favorable safety profile. Conclusions: This case highlights the importance of early diagnosis and multidisciplinary management of PG in CD patients. Adalimumab appears to be a promising therapeutic option, particularly for steroid-resistant PG, though further research is needed to establish standardized treatment protocols. Full article

Background/Objectives: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly developing, painful ulcerative lesions. It exhibits pathergy, a phenomenon in which minor trauma or injury to the skin triggers an exaggerated inflammatory response. This leads to the development of new skin lesions or the worsening of existing ones. Treatment typically involves a combination of corticosteroids and immunosuppressive agents. However, even with effective therapy, the overall management of pyoderma gangrenosum remains challenging, and wound healing can be prolonged. The development of pyoderma gangrenosum after breast cancer surgery is rare, and its presence complicates the treatment of patients requiring additional oncologic therapy. In particular, the effect of radiation on these lesions is not well documented. Given the known skin toxicity of radiotherapy and its negative impact on wound healing, the use of adjuvant breast radiation raises significant concerns in this context. Methods: We present the case of a 66-year-old female with Stage IIB invasive ductal carcinoma of the left breast who developed postoperative pyoderma gangrenosum after breast-conserving surgery. The patient was treated with systemic corticosteroids and cyclosporine, and then subsequently underwent standard-of-care adjuvant chemotherapy and radiation. Results: During therapy, she demonstrated rapid resolution of her pyoderma gangrenosum without experiencing excess skin toxicity. Conclusions: While the literature on the direct application of radiation in pyoderma gangrenosum is limited, our case provides evidence supporting the safety of radiation therapy in oncologic cases complicated by this disease. In addition to receiving the benefit of adjuvant therapy for her breast cancer, our patient demonstrated an improvement in her postoperative PG with no adverse skin effects. Full article

Paraneoplastic dermatoses (PDs) belong to a group of rare and polymorphous dermatoses, and they can often be the first sign of underlying malignancies. Therefore, dermatologists should be able to identify skin features to identify earlier underlying neoplasms. Indeed, lack of familiarity with cutaneous clues of internal malignancies can lead to a delay in the diagnosis and an impairment of the prognosis of the patients. In this review, we described several PDs, including more common and rarer PD. Indeed, while malignant acanthosis nigricans, characterized by velvety, verrucous, hyperpigmented plaques that usually affect intertriginous areas, is a well-known PD, necrolytic migratory erythema is usually misdiagnosed because its clinical features can be similar to seborrheic dermatitis. Furthermore, we focused on two paradigmatic PDs, namely paraneoplastic autoimmune multiorgan syndrome (PAMS) and paraneoplastic dermatomyositis. Indeed, PAMS represents a paradigmatic form of obligate PD, which is always associated with an underlying neoplasm, while paraneoplastic dermatomyositis belongs to the facultative PD, which can be associated with neoplasia in a variable percentage of cases. Full article

Neutrophil-mediated inflammation is a key feature of immune-mediated chronic skin disorders, but the mechanistic understanding of neutrophil involvement in these conditions remains incomplete. Dapsone, colchicine, and tetracyclines are established drugs within the dermatologist’s therapeutic armamentarium that are credited with potent anti-neutrophilic effects. Anti-neutrophilic drugs have established themselves as versatile agents in the treatment of a wide range of dermatological conditions. Some of these agents are approved for the management of specific dermatologic conditions, but most of their current uses are off-label and only supported by isolated reports or case series. Their anti-inflammatory and immunomodulatory properties make them particularly valuable in managing auto-immune bullous diseases, neutrophilic dermatoses, eosinophilic dermatoses, interface dermatitis, and granulomatous diseases that are the focus of this review. By inhibiting inflammatory pathways, reducing cytokine production, and modulating immune responses, they contribute significantly to the treatment and management of these complex skin conditions. Their use continues to evolve as our understanding of these diseases deepens, and they remain a cornerstone of dermatological therapy. Full article