Ulcerative Pyoderma Gangrenosum Research Articles

Pyoderma Gangrenosum: A Retrospective Case Series of 44 Patients

Introduction: Pyoderma gangrenosum (PG) poses a significant dermatological challenge due to its rapidly evolving, painful, necrotic ulcerations. Understanding its multifaceted pathogenesis and diverse clinical presentation is crucial for effective management. Objectives: We aimed to analyze demographic characteristics, clinical manifestations, lesion distributions, systemic disease associations, therapeutic interventions, and patient outcomes in PG cases. Methods: Medical records from 2017 to 2023 of PG patients at IRCCS Sant’Orsola Malpighi Hospital, Bologna, Italy, were retrospectively analyzed. Inclusion criteria encompassed persistent ulcers with clinical and histological evidence of PG, excluding cases with alternative diagnoses or inadequate follow-up. Clinical evaluations, including pain assessment and lesion measurements, were conducted at diagnosis and follow-up visits. Results: A total of 44 patients were evaluated. Pain was a universal symptom, and tissue pathergy was documented in 28.6% of patients. Ulcerative PG was the most common subtype (88.1%). Associations with inflammatory bowel diseases (25%), rheumatoid arthritis (9.1%), and hematological diseases (17.2%) were noted. Lower limbs were frequently affected (63.6%). Treatment approaches included wound management, topical and systemic corticosteroids, and immunosuppressive therapy, with varying response rates. Conclusion: Advanced dressing and steroid therapy were pivotal in mild PG cases, while moderate to severe cases often associated with systemic diseases showed incomplete healing despite treatment, especially in patients with inflammatory bowel diseases and hematological disorders. This study contributes to understanding PG's complexities, highlighting the need for multidisciplinary management and further prospective research.

Analyzing Recurrence Rates in Pyoderma Gangrenosum

Pyoderma Gangrenosum (PG) is a rare skin disease characterized by rapid development of painful skin ulcers with violaceous borders that is often associated with inflammatory disorders.1,2 Treatment involves systemic immunosuppression alongside wound care management.2,3 Despite clinicians’ best efforts in implementing appropriate therapy, PG ulcers can recur, and there is minimal data regarding recurrence rates. We systematically reviewed Embase, MEDLINE, and Cochrane library for cases, case series, and clinical studies of confirmed PG to evaluate for recurrence rates. Recurrence was defined as the appearance of new ulcerations after complete initial healing. Our analysis found 269 studies with 351 patients. Among this cohort, 34 cases (10%) described one or more recurrence episodes. Within these 34 cases, ulcer locations were as follows: 20 (56%) on the lower extremities, 12 (33%) on the trunk, 1 (3%) on the upper extremities, 1 (3%) on the head, and 2 (5%) in unspecified areas. When analyzing the time of recurrence from initial healing, we found that 11 cases (29%) recurred in 3 months or less, 5 (14%) from 3 to 6 months, 1 (3%) from 6 to 12 months, and 7 (19%) after 12 months. 13 cases (35%) did not specify a timeline for recurrence, and 3 cases reported two recurrence episodes. In conclusion, our study investigates PG recurrence patterns and suggests that about 10% of patients with PG might experience recurrence after healing, which supports previously reported data.4 Future directions include the impact of treatment duration and treatment type (topical versus systemic) on recurrence rates.

Development of Postsurgical Pyoderma Gangrenosum with New Keloid after Keloid Resection.

Keloids are a dermal fibroproliferative disorder and can arise from trauma, acne, vaccination, and herpes zoster. Pyoderma gangrenosum (PG) is a painful ulcerative skin disorder that is associated with neutrophilic dysfunction. However, the pathophysiologies of keloids and PG are not fully understood. The authors encountered an unusual case of a 24-year-old woman who presented with an anterior chest keloid that bore an ulcer. The keloid was resected along with the ulcer, and histology revealed the ulcer to be a neutrophilic PG ulcer. A year after surgery, another ulcer developed in the scar. The ulcer met the PARACELSUS criteria of a postsurgical PG ulcer. After treatment with systemic prednisone and adalimumab for 250 days, the ulcer re-epithelialized. However, relapsed keloids were then observed at the PG site. Corticosteroid taping may be the safest therapy for patients with a history of PG. Conversely, if there is suspicion that a patient is prone to keloid development, diagnostic biopsies and surgical management of PG ulcers should be avoided or conducted with care.

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.

The role of split-thickness skin grafting in the treatment of vasculitic and pyoderma gangrenosum ulcers in a multidisciplinary wound centre.

Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains unclear. This study aimed to investigate the need for surgical intervention as well as the outcome and safety of skin grafting in the treatment of 46 patients with vasculitic ulcers and 34 with pyoderma gangrenosum ulcers using data recorded in the validated Wound Registry. Of the 80 patients with atypical ulcers, 14% (n = 11) were treated surgically; these patients were older (p = 0.039), had lower mobility status (p = 0.002), and more often pulmonary diseases, rheumatoid arthritis, and previous arterial procedures (p = 0.007; p = 0.031; p = 0.031, respectively) than those treated conservatively. Of 181 ulcers, 15% (n = 27) were surgically treated, 78% once and 22% multiple times. During follow-up, 92.3% of both surgically and conservatively treated ulcers with available data healed. Of the surgically treated ulcers, median healing time after first surgical procedure was 96 days, and post-surgical complications were considered mild or unrelated to surgery. Our results suggest that if surgery is indicated, skin grafting is a safe and efficient treatment method provided that multidisciplinary approach is applied.

Combination Therapy of Topical Antioxidant Gel and Platelet-Rich Plasma (PRP) in Pyoderma Gangrenosum Ulcer: A Case Report

Combination Therapy of Topical Antioxidant Gel and Platelet-Rich Plasma (PRP) in Pyoderma Gangrenosum Ulcer: A Case Report

Unresolved Malady of Pyoderma Gangrenosum: A Study of its Profile and Outcome in a Tertiary Care Center

Introduction: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of uncertain etiology characterized by rapidly progressive, painful skin ulcers, and is often difficult to diagnose. The common underlying disease associations include rheumatoid arthritis (RA), inflammatory bowel disease (IBD), autoimmune inflammatory conditions, and malignancies, both hematological and solid organ tumors. Aims and Objectives of the Study: Assess the demographics, clinical presentation and associated systemic diseases, and response to treatment of patients with pyoderma gangrenosum. Materials and Methods: In this retrospective study, all cases diagnosed as PG were evaluated along with disease associations and outcomes over a 5-year period. Results: A total of 42 patients’ charts were studied of which, ulcerative PG was seen in 86.4%, pustular in 16.8%, bullous in 14.4%, and vegetative in 2.4% patients, respectively. Thirty-six percentage of them had RA, 12% had non-RA connective tissue disease, 9.6% had IBD, 9.6% had chronic liver disease, and 4.8% had malignancy. Positive pathergy was seen in 57% of our study patients. Multiple morphological types with recurrences were more common in patients with positive pathergy. Mortality was seen in 9.6% of patients. Statistics: Descriptive statistics were reported as mean with standard deviation, number, and percentages. Association between the clinical characteristics of the variables was done using Chi-square test. Conclusion: PG with multiple morphological types with multifocality is frequently associated with exacerbation of the underlying disease. RA was the most common association found. Recurrent disease was more common in older patients (>40 years).

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

The presence of neutrophil extracellular traps in different forms of pyoderma gangrenosum

AbstractWe demonstrated that there were abundant neutrophil extracellular traps (NETs) in the skin biopsies from various types of pyoderma gangrenosum (PG), based on the observation of extended and compact areas of immunolabeling of MPO and Cit H3 proteins. We suggest that neutrophils could undergo an aberrant NET formation in the lesions of PG patients, in the vast majority of idiopathic PG. We did not detect NETs in the skin ulcers of an antiphospholipid syndrome patient with a similar appearance to classical ulcerative PG, while rich NETs were found in the various types of PG. These findings suggest that the presence of NETs in skin tissues could serve as a marker for making differential diagnoses of various types of PG from other similar conditions.

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.

Rapid response to spesolimab in a patient with severe refractory pyoderma gangrenosum.

We report on a patient with severe ulcerative pyoderma gangrenosum that was recalcitrant to systemic corticosteroid, tumour necrosis factor antagonist and ciclosporin treatment and finally controlled when spesolimab was added to the treatment regimen.

41989 Comparison of the performance of published diagnostic criteria for ulcerative pyoderma gangrenosum

41989 Comparison of the performance of published diagnostic criteria for ulcerative pyoderma gangrenosum

Neutrophil extracellular traps formation in the lesional skin of various types of pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a chronic neutrophilic disorder characterized by recurrent painful ulcers. Aseptic inflammation by neutrophils plays an essential role, and neutrophil extracellular traps (NETs) formation can contribute to the pathogenesis of PG. Seventy-five patients were diagnosed as having PG in our department, among which 58 ulcerative, 4 bullous, 3 pustular and 10 vegetative type. We examined the 20 skin biopsy specimens (11 ulcerative, 3 bullous, 2 pustular and 4 vegetative type), and local NETs formation in various types of PG was compared among each type. The biopsied specimens were double labelled for myeloperoxidase, citrullinated histone H3. Immunofluorescent images indicated that the histopathologic location and depth of NETs formation in PG varied by the clinical subtypes. In ulcerative PG, NETs formation was observed in the upper to deep dermis. In bullous PG, NETs formation was mainly observed in the epidermis. Pustular type showed NETs formation in the epidermis near the pustules, and in vegetative type, showed NETs formation mainly in the upper dermis. These results indicate that NETting neutrophils play an important role in the pathogenesis of various forms of PG, although the location and depth of NETs formation in the skin lesion of PG differ depending on each type. Further studies are necessary to examine what factors identify different clinical features of PG.

From Daily to Rarity - A Case Report of Ulcerative Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is classified as a non-infectious neutrophilic dermatosis with poorly understood etiology. Pathergy, which is major trauma caused by a minor incident, has been associated as a preceding event for PG. The epidemiology of the disease reveals patients who present with PG have associated underlying conditions with the most common comorbidities reported as inflammatory bowel disease, rheumatoid arthritis, hematological and solid organ malignancies. Pyoderma gangrenosum is considered a diagnosis of exclusion. It is commonly a missed diagnosis leading to delays in treatment. A diagnostic guide which clinicians can use is the PARACELSUS score. The following case report will focus on a relatively healthy 50-year-old female with a past medical history of hypertension who is in complete remission from breast cancer. This case highlights the importance of keeping PG in the differential diagnosis in patients without a history of autoimmune disease.

Unusual Case of Ulcerative Pyoderma Gangrenosum with Perianal Involvement and Severe Cellulitis in Diabetes

Unusual Case of Ulcerative Pyoderma Gangrenosum with Perianal Involvement and Severe Cellulitis in Diabetes

A Rare Case of Recurrent Pyoderma Gangrenosum

Introduction: Pyoderma gangrenosum (PG) is a rare non-infectious disorder, and presents as solitary or multiple, fragile papules that progresses to ulcer and necrotic tissue. Autoimmune is the favored pathophysiology associated with this chronic inflammatory skin disease. Systemic disease such as inflammatory bowel disease, rheumatoid arthritis, and haematological disorders often accompany PG. We report a case of recurred PG in 60 year old male with no evidence of associated systemic condition. Case Presentation: A 60 year-old male complained of 1 month-long painful ulceration on his left chest. The lesion started as a pustule which gradually increased in size and broke into painful ulcer. The patient had similar skin lesion, five and three years prior to this admission on the lower abdomen and lower limbs respectively. Both episodes healed more than a year. The diagnosis of ulcerative PG was established based on the physical and histopathological examination. The patient was treated with prednisone and moist wound care. The ulceration responded rapidly. Discussion: Pyoderma gangrenosum is associated with underlying disease in up to two-thirds of case. It occurs typically in adults between 40 and 60 years of age. Although PG predilection is typically lower extremities, any body site can be affected, especially following a trauma. Our patient presented with recurred PG but showed no other systemic condition. Autoinflammatory disease are clinically characterized by recurrent episode and the treatment is quite challenging for its tendency to become chronic, relapsing, or reversible ulcer. Conclusion. We report a rare case of recurred ulcerative PG with no symptom of associated systemic disease who responded rapidly with oral steroid treatment and moist wound care. Keywords: Pyoderma gangrenosum, ulcerative, autoimmune, case report, steroid.

Assessing the Discriminatory Ability of Diagnostic Criteria for Ulcerative Pyoderma Gangrenosum and Its Mimickers

This comparative effectiveness research study assesses the discriminatory ability of diagnostic criteria for pyoderma gangrenosum.

Features that define clinical severity of ulcerative pyoderma gangrenosum: a Delphi consensus study of experts and patients on behalf of the US Medical Dermatology Society.

Features that define clinical severity of ulcerative pyoderma gangrenosum: a Delphi consensus study of experts and patients on behalf of the US Medical Dermatology Society.

Clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of pyoderma gangrenosum.

This study was aimed to evaluate the clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of ulcer wound of patients with pyoderma gangrenosum (PG). From August 2014 to February 2022, 30 patients with pyoderma gangrenosum ulcer wounds were selected as the research objects and randomly divided into the observation group (n=12) and the control group (n=18) in this retrospective study. The patients in observation group were treated with VSD combined with flap transplantation and immunosuppressive agent treatment, while the control group was treated with normal dressing change combined with hormone and cyclosporine. The ulcer wound healing time and dressing change times were compared between the two groups. All the 30 cases of two groups healed after corresponding treatment. The wound healing time of ulcer in the observation group was 35-40 days, with an average healing time of (35.83 ± 1.95) days, and the wound healing time of the control group was 60-200 days, with an average healing time of (44.14 ± 9.67) days. The healing time of observation groups was significantly shorter than that in the control group (t=4.652, P < .05). The frequency of dressing change in the observation group was seven-eight times, with an average of (7.17 ± 0.39) times, and the frequency of dressing change in the control group was 75-86 times, with an average of (79.22 ± 3.62) times. The difference between the two groups was significant (t=6.214, P < .05). The treatment of VSD combined with flap transplantation and immunosuppressive agent treatment promote ulcer wound healing of pyoderma gangrenosum.

Pyoderma gangrenosum and dehydrated human amnion/chorion membrane: a potential tool for an orphan disease.

Pyoderma gangrenosum (PG) is an often-misdiagnosed, painful, inflammatory and ulcerative skin disorder. It is an orphan disease, where standard wound treatments such as sharp surgical debridement are contraindicated. This retrospective case series sought to evaluate the application of dehydrated human amnion/chorion membrane (DHACM) as a skin substitute in cases that were refractory to a range of standard-of-care techniques. This retrospective case series involved wounds which failed to close with standard escalating treatments, including anti-inflammatory and immunosuppressive therapies. Subjects were transitioned to DHACM and wound sizes were monitored until closure. Wounds (n=5) for all three subjects had stalled with standard therapies for at least 2.5 months but responded quickly to routinely applied DHACM treatments, and closure was achieved in each case. This retrospective pilot case series examined the use of DHACM as an alternative wound treatment for PG patients failing standard therapies. DHACM treatments re-initiated the trajectory towards wound closure for each stalled PG ulcer. The results suggest a treatment algorithm starting with early recognition, wound closure via treatment escalation, and lastly a gradual reduction in treatment for durable closure. DHACM treatment should be formally evaluated as an adjunct to PG ulcers that have remained refractory to more commonly used immunomodulating therapies.