Treatment Of Pyoderma Gangrenosum Research Articles

Successful treatment of pyoderma gangrenosum with guselkumab

AbstractGuselkumab, a monoclonal antibody known for its effective inhibition of T‐cell‐immunoactivity through specific binding to interleukin‐23 (IL‐23)‐cytokines, may be used for off‐label treatment of pyoderma gangrenosum (PG). Herein, we report two successful cases of off‐label treatment for PG, using guselkumab, after unsuccessful treatments with standard regimens of corticosteroids, immunomodulating therapy and other biological agents. Case 1 involves a 39‐year‐old female with treatment‐resistant peristomal PG post‐colectomy and ileostomy. Case 2 features a 35‐year‐oldfemale with treatment‐resistant PG, presenting with deep necrotic lower extremity ulcers. In both cases, we observed remarkable healing within months to a year. These two cases support the potential use of systemic IL‐23‐targetedtherapy for treatment‐resistant PG.

50982 Evaluating the Clinical Utility of Sulfasalazine in the Treatment of Pyoderma Gangrenosum: A Systematic Review

50982 Evaluating the Clinical Utility of Sulfasalazine in the Treatment of Pyoderma Gangrenosum: A Systematic Review

Management of pyoderma gangrenosum during pregnancy and breastfeeding: a systematic review.

Pregnancy is a conjectured risk factor for pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by painful ulcers. Even so, there are no available treatment guidelines for those with PG who are pregnant or breastfeeding. To describe existing treatment options, we systematically reviewed the literature on PG treatment in pregnant or breastfeeding patients. A search over four databases was completed in October 2022. Independent reviewers accomplished screening and data extraction. 18 articles met the inclusion criteria. 15 cases involved the treatment of PG during pregnancy, and three cases involved the treatment of PG while breastfeeding. Most patients did not have a history of PG prior to pregnancy (77.7%), and most did not have PG-associated comorbidity (61.1%). Of the cases involving treatment of PG during pregnancy, the majority (73%) found treatment success with a systemic corticosteroid (SCS). Only three cases reported an adverse outcome, including premature rupture of membranes and premature birth (16.7%); all these cases involved treatment with a SCS at >0.5 mg/kg/day during pregnancy. We present a treatment algorithm for pregnant or breastfeeding patients with PG. Our findings suggest prioritizing topicals and TNF inhibitors due to more favorable side effect profiles. However, there is a paucity of data on the safety of PG therapies in pregnancy and breastfeeding, and thus, controlled studies and pregnancy registries must be pursued.

Topical treatment of pyoderma gangrenosum: A systematic review.

Systemic immunosuppressants are the mainstay of treatment for pyoderma gangrenosum (PG), but they generally have significant side effects which may be avoided by limiting treatment to topical therapy. This review aimed to assess the efficacy and safety of topical treatments for PG. An extensive literature search identified nineteen suitable publications for analysis, including two open cohort studies, five case series and twelve single case reports. The quality of evidence in the publications was graded and data relating to topical PG treatment was extracted. The lack of randomised clinical trials investigating topical monotherapy for PG means that robust statistical analysis was not possible. The greatest weight of the current evidence for topical therapy favours either corticosteroids or calcineurin inhibitors. According to our review, both these options appear well tolerated with a few side effects and may have similar efficacy in speeding up the resolution of PG ulcers. Topical therapy could be considered for use in combination with systemic treatment. There may also be a role for isolated topical monotherapy in selected patients with PG, especially those with early or mild disease and those with idiopathic PG. However further research is needed to confirm this and establish optimal treatment approaches for this condition.

Current prescribing for pyoderma gangrenosum in the UK and access to biologic medications: results from a UK Dermatology Clinical Trials Network survey of dermatologists.

Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of patients. The use of biologic medications to treat PG is increasing, although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK National Health Service, limitations are placed on biologic prescribing for PG, leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first-line treatment for PG (90%, 34/38). Biologics have been used by 66% (25/38) of clinicians as second-line therapy, but 19% (7/38) have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.

Study Protocol: Autologous Platelet-Rich Plasma (PRP) Therapy in the Treatment of Pyoderma Gangrenosum: A Prospective, Open-Label, Randomized, Split-Ulcer Trial to Evaluate the Efficacy of Platelet-Rich Plasma Therapy in the Treatment of Chronic Pyoderma Gangrenosum

BACKGROUND Pyoderma gangrenosum (PG) presents as an ulceration of the lower extremities with deep, undermining, and violaceous borders. The disease is an orphan disease without any FDA-approved treatments. OBJECTIVE This study aims to evaluate the efficacy and safety of intralesional injectable and topical platelet-rich plasma (PRP) therapy in the treatment of chronic pyoderma gangrenosum ulcerations. METHODS Methodologically, this study will be conducted as a prospective, randomized, open-label split-ulcer study in patients with confirmed PG by PARACELSUS score. In each patient, up to three separate ulcerations will be randomized to receive either monthly intralesional PRP injections or a topical PRP solution at 0, 4, 8, and 12 weeks, while the third target lesion will receive standard wound care only. Patients will be followed up with at 16 weeks, one month after the completion of treatment. The primary endpoint for this study will be the composite proportion of the target ulcers achieving either complete resolution or a 50% reduction in the surface area at week 12. CONCLUSIONS This study intends to demonstrate the efficacy of an intralesional injectable or topical PRP therapy in the treatment of PG. If successful, PRP treatment may offer a new and effective option for patients with this debilitating disease.

A case report of Pyoderma gangrenosum (PG) associated with Antiphospholipid syndrome (APS) and systemic lupus erythematous (SLE)

Pyoderma gangrenosum (PG) is a noninfectious, inflammatory, ulcerative neutrophilic dermatosis that mainly involves the extensor surfaces of the legs. PG characteristically presents as a painful wound with suppurative as well as attenuated borders. PG-like wounds have been rarely reported in patients with APS and systemic lupus erythematous (SLE) patients. Rituximab can be effective in the treatment of PG. We report a woman with SLE and APS who developed extensive and progressive lesions consistent with PG that showed rituximab can be a potential treatment for it.

A Case Report of the First CEA Transplant in an HIV-Positive Burn Patient in South Africa Using a Novel Composite Culture Technique

AbstractResource-limited burn centers are usually devoid of cultured epithelial autografts (CEA) owing largely to prohibitive costs. A modified CEA technique at our burn center incorporated cost-effective, routinely-used dressings with favorable outcomes. One unknown concern was the immunosuppressive effect that extensive burns and potentially human immunodeficiency virus (HIV) infection may have on graft take. This case study reports on the graft take outcomes of the first CEA transplanted in an HIV-positive patient with extensive burns in South Africa, using this technique. Graft take was determined after 21 days at 80% and a long-term follow-up of 8 years indicated good pigmentation return and skin pliability. Delayed diagnosis of pyoderma gangrenosum caused partial graft loss; however, successful regrafting occurred after pyoderma gangrenosum treatment and eradication. The case was considered clinically successful. HIV may not directly affect graft take, but may result in immunosuppressive conditions that delay graft take success.

The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives.

Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.

Narrative Review: Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a skin lesion, characteristically a neutrophilic dermatosis, that can be complicated by rapid progression, necrosis, and ulceration. This is an important pathology to be discussed given that there are no established criteria for diagnosis or treatment. This review aims to elucidate characteristics and variations of PG that distinguish it from other ulcerative skin lesions. Variability in presentation can lead to missed or incorrect diagnosis, and some of the currently proposed criteria for categorizing and diagnosing PG have been included here. These criteria distinguish PG in terms of the nature of the lesion, the location, etiology, responsiveness to immunosuppressive therapy, and patient history. The etiology and pathogenesis of PG remain unknown, but we summarize prominent theories and explanations. Furthermore, recent research indicates that the incidence of PG has a strong correlation with autoimmune conditions, particularly inflammatory bowel disease. Major treatments for PG coincide with these findings, as the majority involve targeted anti-inflammatories, immunosuppressants, and surgical interventions. These treatments are addressed in this review, with added context for local versus systemic disease.

Long-term remission achieved in a rare case of pyoderma gangrenosum and ulcerative colitis with surgery and postoperative infliximab.

Background Pyoderma gangrenosum (PG) is a rare extraintestinal manifestation of inflammatory bowel disease. In recent years, the use of biologics in PG has been on the rise and has shown promising results. The surgical treatment of PG remains a topic of debate, with limited reports on the use of postoperative biologic therapy. Case reprt: This case report describes a 52-year-old woman who presented with multiple skin ulcers, pus discharge, and bloody diarrhea. The patient was diagnosed with PG with ulcerative colitis based on medical history, ulcer appearance, histopathology, treatment response, and the presence of ulcerative colitis. Surgical intervention was performed to repair the ulcers and amputate the fourth finger and fourth toe of both feet. Additionally, infliximab induction therapy was initiated two weeks after the surgery. The patient's intestinal symptoms demonstrated improvement, and after 10 months of treatment, the lesions were completely healed with no recurrence of skin ulcers. Conclusions This case report highlights a rare instance of successful treatment for PG with ulcerative colitis through a combination of surgery and postoperative infliximab.

Multiple Pyoderma Gangrenosum Overlying AV Fistula Treated With Colchicine: A Case Report.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis which gives rise to painful ulcers. Pyoderma gangrenosum can be triggered by trauma, a phenomenon called pathergy. Here, we report the first case of PG arising from pathergy due to needle insertion overlying an arteriovenous fistula (AVF). This case report seeks to inform nephrologists about PG, this yet unreported presentation, and management in the context of hemodialysis. A 69-year-old woman presented to dermatology clinic for erythemato-violaceous plaques with central ulceration at the site of needle insertion overlying her AVF. The patient was known for chronic renal insufficiency secondary to C3 glomerulonephritis, for which she received hemodialysis. After an accidental burn which lead to appearance of a painful ulcer, following each needle insertion for hemodialysis, she would develop an erythematous papule that progressed to a painful ulcer with erythematous-violaceous borders. Pyoderma gangrenosum was clinically diagnosed and both clinical and paraclinical evaluation did not reveal any secondary cause of PG. Dialysis via AVF was suspended due to the risk of triggering more PG and was temporarily pursued by central venous catheter. The patient was initially treated with prednisone and topical corticosteroids. Furthermore, owing to the high recurrence rate of PG, colchicine was initiated in prevention to avoid resorting to immunosuppressive or long-term corticotherapy. The patient's lesions improved on prednisone, which was then tapered over 1 month. Following prednisone taper and continuing improvement of PG on colchicine and topical corticosteroids alone, the decision was taken to recommence dialysis via AVF after performing a negative pathergy test. Topical corticosteroids were ceased due to the risk of cutaneous atrophy and were replaced by pimecrolimus ointment. The patient has continued dialysis via AVF ever since, without recurrence. This is the first case reported of PG arising from pathergy due to needle insertion overlying an AVF. Colchicine may be a safe and effective therapy for long-term treatment of PG in the context of hemodialysis.

Treatment of pyoderma gangrenosum in pregnancy with certolizumab pegol

AbstractWe report a case of a 41‐year‐old woman who developed pregnancy‐associated pyoderma gangrenosum (PG) at 4 weeks gestation. She was initially treated with prednisone, however, due to lack of improvement and risk of systemic corticosteroids in pregnancy, underwent a prednisone taper and was initiated on certolizumab pegol (CZP). The patient experienced complete wound re‐epithelialization 1 month after CZP initiation. She had no pregnancy complications except for prednisone‐associated gestational diabetes and gave birth to a healthy baby. CZP is a tumour necrosis factor‐inhibitor with negligible placental transfer and no known adverse effects in pregnancy. Its efficacy and safety for autoinflammatory dermatoses in pregnancy are very promising. This is the first case to report CZP treatment for PG in a pregnant patient.

Minimum data set for treatment effectiveness in pyoderma gangrenosum (MIDSTEP): an international protocol of an e-Delphi study to develop a clinical physician-driven treatment effectiveness registry on behalf of the UPGRADE initiative.

Pyoderma gangrenosum (PG) is a rare inflammatory condition with an immense disease burden that remains understudied. With limited approved treatments and low-quality clinical evidence, PG continues to have poor patient outcomes. Unfortunately, improvement in PG treatments and patient care is based on additional research endeavors that can only be developed from existing high-quality data. The following protocol outlines the development of the Minimum Data Set for Treatment Effectiveness in Pyoderma gangrenosum (MIDSTEP), a core set of domains and domain items for the Pyoderma Gangrenosum Treatment Effectiveness (PyGaTE) international registry. The outcomes and benefits are focused on providing real-world data for physicians to improve their clinical decisions on PG treatment and inform clinical trial design, promoting clinical research among the international scientific community. MIDSTEP is a multi-phase project. The first phase will produce a domain item list from a literature review to take into the second phase which would finalize the core data set by an e-Delphi exercise. There will be a single stakeholder group participating together in the e-Delphi consisting of PG experts (healthcare providers, researchers, methodologists, industry representatives, and regulators), ulcerative PG patients, and PG patient advocates. The methodology outlined in the protocol is a systematic method based on several guidelines through COMET and established dermatologic registries and outcome sets with systematic methodologies of their own. The third phase will identify the instruments for the items, the 'when to measure' the items, and the platform for the registry. The last phase is the implementation and continued maintenance of the international registry PyGaTE. By solidifying a consensus on standardized outcomes and collecting information on PG treatment effectiveness in a centralized database, existing treatments can be compared more systematically and analyzed with increased evidence. MIDSTEP and the PyGaTE international registry will have the ambitious goal to generate and disseminate real-world data that can be used by all stakeholders to improve health outcomes for PG patients. Future potential for the outcome of this project includes the development of a gold-standard PG treatment.

The Clinical Characteristics of Patients With Pyoderma Gangrenosum in a Tertiary Referral Hospital: A Retrospective Cohort Study.

Since pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis, epidemiological and clinical data on the disease are scarce. In this single-center retrospective study, we aim to evaluate the clinical characteristics, underlying systemic associations and treatment modalities in patients with PG in a university hospital between 2014 and 2022. It is known that PG most commonly affects the lower extremities, but extracutaneous involvement should also be kept in mind. PG is usually associated with various comorbidities that share a similar inflammatory pathogenesis with the disease. The prevalence of PG-related comorbidities varies in different studies, arthritis and solid organ malignancies were observed most frequently in the current study. Non-PG-related comorbidities including diabetes mellitus, hypertension and peripheral vascular disease can adversely affect wound healing and limit treatment options; therefore, a holistic approach to patients with PG is crucial. Consistent with literature, the mainstay of treatment for PG is systemic corticosteroids and cyclosporine. However, the implementation of biologic agents in treatment-resistant patients is an increasingly important issue in the literature. Antitumor necrosis factors (anti-TNFs) are the most commonly preferred biological therapies, and these agents seem to have paved the way for a paradigm shift in the treatment of PG. In the present study, a relatively high per cent of (23.3%) patients treated with anti-TNFs, most commonly infliximab (87.5%). Recurrence was observed in 46.7% of our patients in the follow-up period and the relapse rate was found to be higher in patients using multiple systemic agents compared to those using single agents (64.7% vs 23.1%, P < .05). In conclusion, we emphasize that early diagnosis and treatment by considering the patient's comorbidities are important in preventing complications, and biologic treatments seem particularly promising in treatment-resistant patients.

The Role of Ultra-High-Frequency Ultrasound in Pyoderma Gangrenosum: New Insights in Pathophysiology and Diagnosis.

Pyoderma gangrenosum (PG) is a neutrophilic dermatological disease, whose pathogenesis is still poorly clarified. Because of the lack of validated criteria for diagnosis and response, PG treatment is still challenging and should be differentiated in the inflammatory and non-inflammatory phases. Our study aimed to provide a new semi-quantitative approach for PG diagnosis and monitoring, identifying ultra-high-frequency ultrasound (UHFUS) early biomarkers associated with the transition between the two phases. We enrolled 13 patients affected by painful PG lesions evaluated during the inflammatory phase (T0) and during the non-inflammatory phase (T1): pain was measured by the Visual Analogue Scale (VAS); clinical features were recorded through digital photography; epidermis and dermis ultrasound (US) characteristics were evaluated by UHFUS examination with a 70 MHz probe (Vevo MD® FUJIFILM VisualSonics). In T1 UHFUS examination, the presence of hyperechoic oval structures was lower compared to T0 (p value < 0.05). An hyperechogenic structure within the oval structure, suggestive of a hair tract, was evident in T0 and absent in T1 (p value < 0.05). In T0, blood vessels appear as U-shaped and V-shaped anechoic structures with a predominance of U-shaped vessels (p value < 0.05) compared to the more regular distribution found in T1. Finding early biomarkers of the transition from the inflammatory to the non-inflammatory phase could provide new insight in terms of therapeutic decision making and response monitoring. The differences found by this study suggest a potential use of UHFUS for the development of an objective standardized staging method. Further investigations will be necessary to confirm our preliminary results, thus providing a turning point in PG early detection, differential diagnosis and treatment monitoring.

A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1β-primed neutrophils.

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.

Clinical guidance of pyoderma gangrenosum 2022.

Pyoderma gangrenosum (PG) is a rare, neutrophilic skin disease. For the purpose of accurate diagnosis and proper treatment of PG, the Japanese clinical practice guidance for PG developed by the Japanese Dermatological Association was published in 2022. In this guidance, clinical aspects, pathogenesis, current therapies, and clinical questions on PG are described from the viewpoints of current knowledge and evidence-based medicine. Here, the English version of the Japanese clinical practice guidelines for PG is presented and is intended to be widely referred to in the clinical examination and treatment of PG.

Ustekinumab in the treatment of acute disseminated pyoderma gangrenosum in a patient with Crohn's disease.

Pyoderma gangrenosum (PG) is an auto-inflammatory dermatosis characterized by lesions that often cause ulcers. We present a case of successful ustekinumab treatment for acute general PG in a 31-year-old woman with coexisting Crohn's disease (CD). For a month, the patient suffered from skin ulcers, two of them deep and necrotic; a histopathological examination revealed PG. Treatment included: methylprednisolone, azathioprine, betamethasone, gentamicin and zincic ointments, antiseptic compresses, and adalimumab therapy. Due to resistance to the implemented treatment, the patient was enrolled in a clinical trial that included the administration of an anti-cytokines drug, ustekinumab. Subsequently, a significant reduction was observed in the severity of symptoms of PG with no relapse. The use of ustekinumab in patients with PG who have an inadequate response to current treatment or cannot receive first-line treatment can be considered. This applies especially to patients with accompanying autoimmune diseases such as CD.

Successful long‐term treatment of pyoderma gangrenosum with secukinumab

AbstractPyoderma gangrenosum (PG) belongs to the group of classical neutrophilic dermatoses and is characterised by painful ulcerations. While the clinical features have been well described, the underlying pathological mechanisms are incompletely understood and adequate treatment remains challenging. A 63‐year‐old male patient had suffered from recalcitrant ulcerations on the back, groins and legs for over 20 years. Due to suspicion of PG, a skin biopsy of the flank was obtained, which was confirming the suspected diagnosis. Following several frustrating attempts to treat, another skin biopsy was carried out and a cytokine profile by quantitative reverse transcription polymerase chain reaction was performed. Compared to healthy skin, a notable upregulation of interleukin (IL)‐17A and IL‐8 was detected. Subsequently, treatment with the anti‐IL17 antibody secukinumab was started. After 3 months of treatment, the PG area was 0 cm2. Due to the discontinuation of the drug by the patient typical PG lesions reappeared, all of which disappeared again within a few weeks of restarting secukinumab therapy. At month 23, the PG area was again 0 cm2 and this complete response was maintained under secukinumab therapy to this day (76 months after the onset of secukinumab therapy). This case of a patient with therapy‐resistant PG and subsequent long‐term responsiveness to anti‐IL‐17 therapy supports the potential importance of the Th17 axis in PG. Collectively, treatment of PG using IL‐17 antagonists seems to be very promising.