Recalcitrant Pyoderma Gangrenosum Research Articles

Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs.

Pyoderma gangrenosum (PG) is a rare, autoinflammatory disease leading to aseptic ulcers which carries a significant disease burden and is often difficult to treat, with many patients failing first-line treatment and requiring additional therapies. Such cases are typically referred to in the literature as "recalcitrant", "refractory", or "resistant", though little is known about the clinical characteristics of such cases. We performed a narrative literature review to characterize patient demographics and clinical course associated with difficult to treat pyoderma gangrenosum cases in order to identify trends to guide future clinical management and therapeutic innovation. We identified 148 cases with clinical manifestations and associated patient demographics stratified by ulcer and patient features. Consistent with previous work, a greater prevalence of PG was observed among female patients and those with a history of inflammatory bowel disease, however interestingly despite an aggressive course to their PG, few patients had comorbidities complicating their disease course. Additionally, despite the requirement of three or more treatments for most patients' disease to resolve, the majority healed within the typical window observed in previous clinical studies with low rates of recurrence. Biologics were the most common medication patients were on at time of remission. Collectively, our results suggest a potential benefit for a reduced threshold for biologic initiation in PG patients and a need for standardization of language in the field to facilitate treatment outcomes comparisons and interventions.

Conquering pyoderma gangrenosum: exploring non-steroidal treatment options

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis frequently related to chronic inflammatory bowel disease (IBD) and often associated with exacerbation of intestinal disease and/or loss of treatment efficacy. The mainstay of treatment is long-term immunosuppression, often with high doses of corticosteroids or low doses of ciclosporin. PG has been reported to respond to TNF alpha inhibitors. We report a patient of recalcitrant PG who responded very well to treatment with golimumab. A 61-year-old known case of PG since 4 years, who also had history of hypertension, pulmonary TB (treated), had been treated with dapsone, thalidomide, colchicine and corticosteroids in the past with partial response and frequent relapses. In February 2021, the patient while being on low-dose oral corticosteroids and colchicine, presented with large painful ulcer over back of his right thigh, which rapidly worsened. In agreement with the pulmonologist, the patient was started on Injection golimumab in addition to intravenous dexamethasone with slow tapering of steroid dosage following the improvement of the cutaneous lesion. Patient reported a near-total resolution of lesion after two doses. He is maintaining well with golimumab. PG can be poorly responsive despite adequate treatment with conventional modalities. High dose steroid therapy with all expected iatrogenic complications and treatment with cyclosporine in such an elderly patient with hypertension and history of tuberculosis seemed to be inappropriate. For all these reasons, a treatment with the TNF alpha inhibitor golimumab, appeared to be the most reasonable therapeutic choice for a patient.

An Integrated Systemic and Local Wound Management in Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis, whose management still represents a clinical challenge due to frequent unresponsive cases. The aim of our study was to evaluate the efficacy of a novel, combined approach including local wound management, based on the principle of PG-TIME and a systemic therapy with an anti interleukin (IL)-17A monoclonal antibody (mAb). We presented a case of a 37-year-old female patient, affected by multi-refractory PG. The patient was treated with a combined approach of both local and systemic therapy. Wound clinical improvement was assessed by Wound Bed Score (WBS), wound size was evaluated through 3D camera laser scanner, and pain was evaluated with visual analog scale (VAS). After 52 weeks of therapy, the association of local wound management with ixekizumab 80 mg [160 mg at time (T) 0; 80 mg every 2 weeks until week 12; 80 mg every 4 weeks] allowed us to perform skin grafting and obtain complete wound healing. Our clinical case demonstrated the efficacy of a novel combination therapy for the treatment of recalcitrant PG based on IL-17 mAbs and local wound management built on the main features of PG-TIME.

Recalcitrant pediatric pyoderma gangrenosum controlled with adalimumab

Introduction: Pyoderma gangrenosum (PG) refers to an autoinflammatory cutaneous disorder characterized by bizarre painful ulcerations. Clinical data of pediatric PG are rare in China. We herein present the first report of adalimumab in the treatment of pediatric PG in China. Case presentation: An 8-year-old boy presented with multiple painful ulcerations on both lower legs. He was diagnosed with PG according to his clinical manifestations and results of a histological examination. His condition showed resistance to corticosteroids, immunosuppressants, and even intravenous immunoglobulin. We then treated him with adalimumab, which induced remission of the disease. Discussion: PG poses both diagnostic and therapeutic challenges. Increased levels of inflammatory mediators, including interleukins 1β, 8, and 17 and tumor necrosis factor-α, induce development of the disease. Despite the availability of traditional treatments, new therapeutic regimens should be taken into consideration. Conclusion: No previous data regarding adalimumab for the treatment of pediatric PG have been reported in China. Our case demonstrates that adalimumab has a beneficial effect on pediatric patients with recalcitrant PG. However, further evaluation and long-term follow-up of this treatment are required. Because infliximab has been studied in a randomized, double blind, placebo-controlled trial, we anticipate forthcoming multicenter randomized trials and research of adalimumab.

Negative-pressure wound therapy as an adjunct to treating pyoderma gangrenosum

Negative-pressure wound therapy has been shown to be effective in re-epithelialisation in recalcitrant pyoderma gangrenosum. This case documents a patient whose co-morbidities limited the standard treatment options and required an alternative management plan. The STOP GAP randomised control trial found that both oral prednisolone and ciclosporin were equally effective in the treatment of pyoderma gangrenosum. However, in this case, the patient had type 2 diabetes and prednisolone resulted in persistently elevated blood glucose levels. Lower doses were ineffective and it was subsequently stopped once other treatments showed a clinical improvement. A recent diagnosis of breast cancer prevented the use of ciclosporin and other immunosuppressive treatments. After multidisciplinary discussion, involving breast surgeons, oncology, dermatology and tissue viability, doxycycline was commenced alongside a portable negative-pressure device with twice weekly tissue viability input. The introduction of this device resulted in a rapid reduction in the wound size and facilitated healing with an excellent outcome.

Dehydrated Human Amnion/Chorion Membrane Allograft for Treatment of Recalcitrant Pyoderma Gangrenosum in PASH Syndrome and Systemic Lupus Erythematosus

Abstract We describe the case of a 73-year-old male patient with personal history of pulmonary malignancy, who in a follow up scan, presented multiple areas of nodular wall thickening of small bowel loops. Ultrasound revealed hypoechoic areas of mural thickening with well-defined borders and loss of the layered echostructure of the intestinal wall. The pathology study confirmed the diagnosis of metastasis. Intestinal metastases are a rare entity that should be taken into consideration to avoid under-diagnosis.

Polyneuropathy developing after infliximab therapy in a patient with recalcitrant pyoderma gangrenosum

Polyneuropathy developing after infliximab therapy in a patient with recalcitrant pyoderma gangrenosum

Treatment of Recalcitrant Pyoderma Gangrenosum with Ulcerative Colitis by Adalimumab Injection.

Treatment of Recalcitrant Pyoderma Gangrenosum with Ulcerative Colitis by Adalimumab Injection.

Recalcitrant pyoderma gangrenosum treated with cyclosporine in an infant

Recalcitrant pyoderma gangrenosum treated with cyclosporine in an infant

Refractory pyoderma gangrenosum treated with infliximab in an infant

We report the case of an 11-month-old boy with severe recalcitrant pyoderma gangrenosum refractory to prednisone, dapsone and ciclosporin. Treatment with infliximab was well tolerated, and resulted in an excellent clinical response that has been sustained for 15 months. The characteristics of this condition in children and the use of infliximab in infants are both reviewed.

Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab

Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab

Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab

Severely recalcitrant pyoderma gangrenosum successfully treated with ustekinumab

Interleukin 23 Expression in Pyoderma Gangrenosum and Targeted Therapy With Ustekinumab

Interleukin (IL)-23 is involved in the pathogenesis of the chronic inflammatory Crohn disease. Pyoderma gangrenosum (PG) is often associated with and can even be the first manifestation of this disease and has abundant neutrophilic infiltration. Because IL-23 plays a critical role in driving inflammation associated with IL-17 production and especially neutrophil recruitment, we suspect that PG might be driven by a pathogenetic mechanism similar to that of inflammatory bowel diseases or psoriasis. Tissue sample analysis showed highly elevated expression of IL-23 on both transcriptional and protein level in a recalcitrant PG lesion. On the basis on these data, a treatment targeting the p40 subunit of the heterodimeric IL-23 with the monoclonal antibody ustekinumab was started. Therapy with ustekinumab resulted in a significant decrease of IL-23 expression in PG and healing after 14 weeks of treatment. No relapse occurred in a 6-month follow-up period. Our data provide evidence of an IL-23-dominated inflammatory infiltrate in PG. This might specify a new concept for PG pathophysiology and suggests a possibility for using ustekinumab as a therapeutic agent in this disease.

Severe recalcitrant pyoderma gangrenosum treated with infliximab

Conflicts of interest: none declared. Sir, We previously reported a case of a 17‐year‐old gentleman with severe recalcitrant pyoderma gangrenosum (PG), who was successfully treated with a combination of mycophenolate mofetil (MMF) and ciclosporin.1 This is an update on this patient's progress, 6 years later. Following complete healing of the PG ulcers affecting the right posterior thigh, immunosuppression was weaned down over 15 months, with only one relapse. He was off treatment for 16 months before he developed a recurrence of the ulceration on the right thigh and a new area of ulceration on the right posterior calf (Fig. 1). Despite recommencing immunosuppressants including prednisolone 25 mg daily, MMF 2 g daily and ciclosporin 6 mg kg−1 day−1, he developed progressive ulceration and we decided to treat him with infliximab. Repeat screening investigations including comprehensive gastrointestinal investigations failed to reveal any underlying cause for the recurrent PG. A dramatic response was seen following three infusions of infliximab given one month apart, at a dose of 3 mg kg−1 (Fig. 2). This resulted in the complete remission of the PG over a 4‐month period. Following the initial infusion a 50% reduction in the size of the ulcers was achieved within 7 days. Treatment was well tolerated with no adverse reactions noted. Ciclosporin and prednisolone were gradually withdrawn with no signs of recurrence of PG at 6 months follow‐up. He remains on MMF 1·5 g daily. Regular wound examination and swabs revealed no evidence of any secondary infection.

Pyoderma gangrenosum complicated by herpes simplex virus infection

High-dose immunosuppression used in the treatment of pyoderma gangrenosum predisposes patients to opportunistic infections. A 66-year-old man presented with recalcitrant pyoderma gangrenosum in which the ulcer itself became infected with herpes simplex virus type 1. This patient was immunosuppressed with multiple agents including topical and oral corticosteroids, cyclosporin, mycophenolate mofetil, intravenous immunoglobulin and infliximab. However, the patient's ulcer continued to extend despite this. It was not until the presence of this virus was detected using polymerase chain reaction on a viral swab of the lesion and oral aciclovir was commenced that the ulcer began to heal. In addition, a fungal granuloma developed on this patient's left forearm as a complication of the potent immunosuppression, which was resolved following treatment with oral voriconazole.

Successful treatment of recalcitrant pyoderma gangrenosum with infliximab complicated by tuberculosis despite negative screening tests

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Recalcitrant giant pyoderma gangrenosum occurring after minor surgery: A successful outcome with mycophenolate mofetil treatment

Recalcitrant giant pyoderma gangrenosum occurring after minor surgery: A successful outcome with mycophenolate mofetil treatment

When is Recalcitrant Pyoderma Gangrenosum Truly Recalcitrant?

Background: The literature supports many different therapies used in recalcitrant pyoderma gangrenosum, which suggests that the pathophysiology is not yet understood. Our hypothesis is that certain patient demographic factors, including age or size of ulcer at presentation, may predict a poor clinical outcome. Objective: The goal of our study was to stimulate an analysis of pyoderma gangrenosum treatment failures to identify predisposing conditions that would increase the likelihood of failure. Conclusion: Patients older than 50 years of age or with an ulcer greater than 25 cm in diameter may have a poor outcome, but a systematic review of pyoderma gangrenosum treatment failures should be undertaken to support this hypothesis.

A Study of Musculoskeletal Manifestations in 12 Patients with SAPHO Syndrome

Synovium and synovial fluid findings in SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome have not been well characterized, and only a few patients have been described in the Americas. We describe clinical, pathologic, and synovial fluid findings in 12 patients with the SAPHO syndrome: hidradenitis suppurativa (7), acne fulminans or conglobata (3), acneiform folliculitis (1) and palmoplantar pustulosis (1). Routine synovial fluid studies were performed in 6 patients, and light and transmission electron microscopic studies were performed in synovium in 2 patients and in bone in 1. The most common musculoskeletal manifestations included erosive or non-erosive oligoarthritis involving metacarpal phalangeal (MCP) and metatarsal phalangeal (MTP) joints as seen in 9 patients, sclerosis of the sacroiliac joints as seen in 5 patients, and osteitis pubis as seen in 1. Three patients had signs of skeletal hyperostosis. The patients with acne fulminans and acneiform folliculitis had chronic aseptic multifocal osteomyelitis. Synovial fluid was sterile in 7, mildly inflammatory in 5, and highly inflammatory in 2. Electron microscopic studies of synovium in 2 patients and of bone in 1 were not useful to detect microorganisms. Three African-American patients with hidradenitis suppurativa presented with pyoderma gangrenosum, and 2 of them had leukocytoclastic vasculitis, and a life threatening course unresponsive to antibiotics, corticosteroids and immunosuppressive therapy. SAPHO in the Americas is most severe in African-Americans with hidradenitis suppurativa, and it presents with heterogeneous musculoskeletal and cutaneous manifestations including erosive polyarthritis or oligoarthritis with nonspecific mild inflammatory fluid. Leukocytoclastic vasculitis and recalcitrant pyoderma gangrenosum were seen in 2 of our patients with the most severe hidradenitis suppurativa. SAPHO syndrome may present with clinical manifestations similar to those seen with seronegative spondyloarthropathies, but it has distinctive cutaneous, radiographic articular, and bone manifestations. Sites of chronic infection need aggressive antibiotic therapy and may need surgical resection.