Cutaneous manifestations of inflammatory bowel disease: basic characteristics, therapy, and potential pathophysiological associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease typically involving the gastrointestinal tract but not limited to it. IBD can be subdivided into Crohn's disease (CD) and ulcerative colitis (UC). Extraintestinal manifestations (EIMs) are observed in up to 47% of patients with IBD, with the most frequent reports of cutaneous manifestations. Among these, pyoderma gangrenosum (PG) and erythema nodosum (EN) are the two most common skin manifestations in IBD, and both are immune-related inflammatory skin diseases. The presence of cutaneous EIMs may either be concordant with intestinal disease activity or have an independent course. Despite some progress in research on EIMs, for instance, ectopic expression of gut-specific mucosal address cell adhesion molecule-1 (MAdCAM-1) and chemokine CCL25 on the vascular endothelium of the portal tract have been demonstrated in IBD-related primary sclerosing cholangitis (PSC), little is understood about the potential pathophysiological associations between IBD and cutaneous EIMs. Whether cutaneous EIMs are inflammatory events with a commonly shared genetic background or environmental risk factors with IBD but independent of IBD or are the result of an extraintestinal extension of intestinal inflammation, remains unclear. The review aims to provide an overview of the two most representative cutaneous manifestations of IBD, describe IBD's epidemiology, clinical characteristics, and histology, and discuss the immunopathophysiology and existing treatment strategies with biologic agents, with a focus on the potential pathophysiological associations between IBD and cutaneous EIMs.

Pyoderma gangrenosum after surgery for forefoot deformity in a patient with rheumatoid arthritis: A case report.

Pyoderma gangrenosum (PG) is a rare inflammatory skin disease characterised by skin ulcers that are associated with autoimmune diseases. Although the effectiveness of immunosuppression with glucocorticoids and tumour necrosis factor inhibitors in treating PG has been reported, the utility of negative-pressure wound therapy (NPWT) for severe ulcerative lesions in patients with PG remains controversial. Herein, we report the case of a 76-year-old woman with rheumatoid arthritis who developed PG after undergoing surgery for a forefoot deformity. The patient showed improvement in deep ulcer lesions through NPWT while receiving treatment with abatacept and systemic glucocorticoids. Subsequent topical glucocorticoid therapy led to the remission of the PG. This case suggests that NPWT, when used under immunosuppressive conditions, does not exacerbate the pathergy and may be beneficial for treating severe ulcerative PG.

[Differential diagnoses severe skin infections]. / Diagnostics différentiels des infections cutanées graves.

DIFFERENTIAL DIAGNOSES SEVERE SKIN INFECTIONS. The diagnosis of necrotizing soft tissue infection is a difficult clinical diagnosis, confirmed by surgical exploration and requiring urgent surgical treatment. The main differential diagnoses are non-necrotizing soft tissue infection, pyoderma gangrenosum, acute leg ischaemia, compartment syndrome and diabetic foot infection. It is important to know how to recognise these differential diagnoses because the management sometimes differs radically with, in the case of pyoderma gangrenosum, a risk of aggravation in the event of surgery.

DIAGNOSTICS DIFFÉRENTIELS DES INFECTIONS CUTANÉES GRAVES. Le diagnostic des dermohypo dermites bactériennes nécrosantes-fasciites nécrosantes (DHBN-FN) est un diagnostic clinique difficile, confirmé par l'exploration chirurgicale et qui nécessite un traitement chirurgical en urgence. Les principaux diagnostics différentiels sont les dermohypodermites bactériennes non nécrosantes (DHBNN), le pyoderma gangrenosum, l'ischémie aiguë de jambe, le syndrome des loges et l'infection du pied diabétique. Il est important de savoir reconnaître ces diagnostics différentiels car la prise en charge diffère parfois radicalement avec, dans le cas du pyoderma gangrenosum, un risque d'aggravation en cas de chirurgie.

Misdiagnosis of Pyoderma Gangrenosum Increases Medical Costs and Prolongs Hospital Stay: A Case Report.

Pyoderma gangrenosum (PG) is a rare, immunological ulcerative, and necrotic inflammatory skin disease that can be easily misdiagnosed as cellulitis, abscess, diabetic foot ulcer, and other infectious diseases. Misdiagnosing PG leads to unnecessary surgical incision and debridement, which further exacerbates the lesion, ultimately leading to longer treatment periods and higher medical costs. Therefore, early and accurate diagnosis of PG is extremely important for its treatment. In particular, PG should be suspected in patients with inflammatory bowel disease.

Pyoderma Gangrenosum after Cardiac Surgery.

BACKGROUND: Pyoderma gangrenosum after cardiac surgery is a rare, noninfectious ulcerating skin disease mimicking sternal wound infection. METHODS: A systematic search of literature for pyoderma gangrenosum complicating cases of cardiac surgery was conducted between September 1985 and September 2020 on PubMed and Cochrane databases. A systematic review and detailed overview of clinical presentation, diagnostic, treatment, and outcome is provided. RESULTS: A total of 15 studies enclosing 15 patients suffering from pyoderma gangrenosum following cardiac surgery were identified. Onset of symptoms was observed after a median of 5 days. Patients were predominantly male (81.3%) with a median age of 64 years. Typical clinical presentation mimicked sternal site infection, mainly by means of mediastinitis. Specific signs were rapid progression, erythematous to violaceous color of the wound border, accompanied by unspecific symptoms including fever, malaise, and severe pain. Additionally, pathergy (development of ulcers at the sites of minor cutaneous trauma) was reported frequently. Biopsy is mandatory with a cutaneous neutrophilic inflammation confirming the diagnosis. Initial treatment mostly (75.0% of reported cases) was misled, addressing suspicion of surgical site infection. After correct diagnosis, the treatment was switched to an immunosuppressive therapy. Full sternal wound closure took between 5 weeks and 5 months. Reported case mortality was 12.5% in actually low-risk surgeries. CONCLUSION: Despite pyoderma gangrenosum has typical signs, it remains an exclusion diagnosis. The treatment is completely opposite to the main differential diagnosis-the typical surgical site infection. Knowledge about diagnosis and treatment is essential in the context of avoiding fatal mistreatment.

Diagnostic work-up and treatment in patients with pyoderma gangrenosum: retrospective analysis of US insurance claims-based data.

Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and "real-world" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population.

[Ulcerative colitis complicated by pyoderma gangrenosum and multiple aseptic abscesses].

A woman in her 30s was diagnosed with ulcerative colitis (UC) 4 years ago and treated with tacrolimus, azathioprine, and prednisolone 5mg (PSL). Skin ulcers appeared on the right lower leg during the course of treatment, diagnosed as pyoderma gangrenosum (PG). The patient initially improved with an increased PSL and infliximab dose, but then developed multiple skin ulcers and folliculitis throughout her body. She was transferred to our hospital for PG exacerbation treatment. She developed fever after transfer and contrast-enhanced computed tomography showed multiple abscesses in the lungs and kidneys. PSL was decreased and infliximab was discontinued. Antibiotic therapy and granulocyte/monocyte apheresis (GMA) were started. Fever persisted even after antibiotic treatment, and her general condition did not improve. A right renal abscess puncture was performed. Pus was sterile. A sterile abscess associated with PG was suspected. The PSL dose was increased to 1mg/kg and infliximab restarted. Thereafter, the patient's general condition improved, and both lung and renal abscesses contracted. Skin ulcer epithelialization was also observed. Abdominal symptoms were mild during the course of the disease, and colonoscopy showed only a localized ulcerative lesion in the rectum. The patient was later transferred to the department of dermatology at our hospital for PG treatment. Aseptic abscesses are caused by neutrophil infiltration without infection and have been reported to be associated with neutrophilic dermatosis and inflammatory bowel disease. UC-associated aseptic abscess is rare. This is only the sixth case in Japan. Aseptic abscesses can occur in various sites, including subcutaneous and deep organs, but this is the first kidney abscess case. In previous reports, PSL, infliximab, colchicine, and infliximab+GMA were used for aseptic abscesses associated with UC. They all showed abscess reduction. Aseptic abscesses associated with PG should be considered if abscess lesions occur during the course of UC, and a treatment strategy including enhanced immunosuppression should be considered.

Pyoderma Gangrenosum and inflammatory bowel disease: a combined medical and surgical approach - case report and literature review.

OBJECTIVE: Pyoderma Gangrenosum (PG) is an immune-mediated neutrophilic dermatosis, characterized by large painful ulcers occurring in various body segments. It can be associated to Inflammatory Bowel Disease (IBD) including both Ulcerative Colitis and Crohn Disease. Prompt and effective management is fundamental, due to its high morbidity and mortality rates. By presenting our clinical experience, we aimed at showing the efficacy of a combined therapeutic approach, in which the best of every specialty cooperates managing this hazardous disease. PATIENTS AND METHODS: We report on two patients attending our outpatient clinic with ulcerative skin lesions at the level of the back. Patient 1 suffered from Crohn disease and Patient 2 presented a positive history of abdominal pain, diarrhea with mucus and blood in the stool. Histological exam was performed with final diagnosis of PG associated with IBD. A Literature review was carried out in order to highlight the role of combined clinical-surgical management of PG in adult patients with IBD. RESULTS: Complete resolution of the lesions was achieved in 4 months and 3 months for each patient respectively without relapse. PubMed was searched from 2000 to 2020 with the following keywords: (Pyoderma) AND/OR (Pyoderma Gangrenosum) AND (Inflammatory Bowel Disease) AND/OR (Ulcerative Colitis) AND/OR (Crohn Disease) AND (Management). Seven papers were included (4 case reports, 2 case series, 1 comprehensive review) and reviewed using a descriptive checklist. CONCLUSIONS: PG should be treated by dedicated multidisciplinary teams, in which every specialist plays a crucial role from the diagnosis to the treatment and up to the long-term follow-up.

Understanding the zebras of wound care: an overview of atypical wounds.

Atypical wounds account for approximately 5% to 20% of chronic ulcerations. Typically, clinical suspicion of an uncommon etiology is warranted for wounds that do not show signs of healing with conventional care, that are associated with pain out of proportion to the clinical presentation, or that are atypical in appearance. This review provides a general overview of various atypical wound etiologies, clinical presentations and appearance, and current treatment protocols. The clinical presentation, pathophysiologic etiology, and current literature on each etiology are presented. The etiologies discussed are pyoderma gangrenosum, calciphylaxis, lichen planus, necrobiosis lipoidica, infectious ulcers, hidradenitis suppurativa, artefactual ulcers, hydroxyurea-induced ulcers, vasculopathies, and neoplastic ulcers. Patients with atypical wounds experience a poorer prognosis and slower healing rate compared with patients with typical wound etiologies (eg, vascular and diabetic wounds). Biopsy is often vital in wound care to identify and differentiate wound etiologies. It is important to note that multiple characteristics or histologic features can overlap in a biopsy with atypical wounds. Therefore, a biopsy will still require an understanding of the presentation of these different wounds and should only be used when appropriate. The proper diagnosis for an atypical wound can greatly hasten wound closure, decrease the cost for the patient and the health care system, and improve the patient's quality of life. Because of the limited availability of patient populations with atypical wound etiologies, literature concerning specific pathologies is limited. More research on each pathology is needed, as is a universally accepted treatment protocol for atypical wounds.

Neutrophilic Dermatoses in a Clinical Practice of Wound Care Professionals.

ABSTRACT: Diagnosing and treating neutrophilic dermatoses (NDs) in clinical practice can be challenging because of various presentations and stubborn treatment responses. Establishing a diagnosis is necessary, though, because many NDs are associated with underlying conditions, including malignancy. In this article, the authors provide information about Sweet syndrome, pyoderma gangrenosum, and other NDs and describe their clinical presentation, pathophysiology, diagnostic criteria, and associated conditions. The authors also present a case report describing the coexistence of two NDs and hidradenitis suppurativa in one patient and review the treatment modalities for those conditions.

Squamous cell carcinoma of verrucous type in the setting of prior pyoderma gangrenosum: a case report.

INTRODUCTION: Pyoderma gangrenosum and cutaneous squamous cell carcinoma are two conditions well reported in the literature and may exist concurrently in the same patient. In fact, there have been reports of misdiagnosis of one for the other. The two conditions occurring in the same location, however, has not yet been reported. CASE DESCRIPTION: We report the case of a 57-year-old Caucasian male with history of pyoderma gangrenosum of the right lateral tibial area who developed squamous cell carcinoma of verrucous type at the same site. Excisional surgery was considered to treat this patient, but he was ultimately managed with radiation therapy to the affected area due to the size of the lesion and the risk of triggering proliferation of the pyoderma gangrenosum. CONCLUSIONS: We hope that this case report will add to the literature of both conditions, show a unique presentation of both conditions, and emphasize the inclusion of both pyoderma gangrenosum and squamous cell carcinoma when developing a differential diagnosis of a chronic, nonhealing wound.

Onset of Pyoderma Gangrenosum in Patients on Biologic Therapies: A Systematic Review.

OBJECTIVE: To summarize clinical outcomes of paradoxical pyoderma gangrenosum (PG) onset in patients on biologic therapy. METHODS: The authors conducted MEDLINE and EMBASE searches using PRISMA guidelines to include 57 patients (23 reports). RESULTS: Of the included patients, 71.9% (n = 41/57) noted PG onset after initiating rituximab, 21.1% (n = 12/57) noted tumor necrosis factor α (TNF-α) inhibitors, 5.3% (n = 3/57) reported interleukin 17A inhibitors, and 1.8% (n = 1/57) reported cytotoxic T-lymphocyte-associated protein 4 antibodies. The majority of patients (94.3%) discontinued biologic use. The most common medications used to resolve rituximab-associated PG were intravenous immunoglobulins, oral corticosteroids, and antibiotics, with an average resolution time of 3.3 months. Complete resolution of PG in TNF-α-associated cases occurred within an average of 2.2 months after switching to another TNF-α inhibitor (n = 1), an interleukin 12/23 inhibitor (n = 2), or treatment with systemic corticosteroids and cyclosporine (n = 3), systemic corticosteroids alone (n = 1), or cyclosporine alone (n = 1). CONCLUSIONS: Further investigations are warranted to determine whether PG onset is associated with underlying comorbidities, the use of biologic agents, or a synergistic effect. Nevertheless, PG may develop in patients on rituximab or TNF-α inhibitors, suggesting the need to monitor and treat such adverse effects.

Efficacy of cytapheresis for induction therapy and extra-intestinal skin manifestations of ulcerative colitis.

INTRODUCTION: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. METHODS: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. RESULTS: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. CONCLUSION: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

Acupuncture-exacerbated pyoderma gangrenosum associated with IgG multiple myeloma.

INTRODUCTION: PG is an uncommon, noninfectious neutrophilic dermatosis. Very few cases of bullous PG as the first manifestation of IgG myeloma have been reported. HE4, a novel marker for human cancers, may be a promising marker of bone destruction and disease progression in patients with hematologic malignancies and PG lesions. CASE REPORT: The authors report a case of a 49-year-old female who presented with painful patches located on the lower extremities for the past 5 months, and then had lesions that rapidly progressed to necrotic ulcers after unregulated acupuncture therapy. During the treatment procedure, underlying IgG κ-type myeloma was diagnosed. After the diagnosis was confirmed, the patient underwent chemotherapy, and the lesions started to heal and gradually showed scarring. The current report also discusses the potential value of HE4 as applied to malignancies that present with PG and bone destruction. CONCLUSIONS: Once the diagnosis of the underlying systemic disease is confirmed, patients with PG should simultaneously receive aggressive treatment for the primary disease. More emphasis should be put on HE4 regarding the progression of monoclonal gammopathy-related PG with bone destruction to provide new ideas to understand the pathogenesis of this disease.

Granulocyte and monocyte adsorptive apheresis for pyoderma gangrenosum.

Pyoderma gangrenosum (PG), a chronic aseptic inflammatory skin disease characterized by skin ulcers with elevated and undermined borders, is resistant to conventional therapies. PG is elicited by activated neutrophils and macrophages and is often associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis, aortitis syndrome, and hematopoietic disorders. This single-center study assessed the efficacy and safety of selectively depleting myeloid-lineage leukocytes in patients with PG. Patients with PG, aged 20 or over, received 5 or 10 treatment sessions of granulocyte and monocyte adsorption apheresis (GMA), once or twice a week. Treatment efficacy was assessed based on the rate of skin ulcer reduction, the visual analog scale of pain, and the physician's global assessment of the skin lesions. A complete response (CR) was obtained in eight patients, a nearly complete response (nCR) in three patients, and a partial response (PR) in two patients. In four of the other six, the disease remained stable (SD) and in two we observed disease progression (PD). No severe adverse events were recorded. Our results suggest that GMA is a useful and safe treatment modality for PG.

Pyoderma Gangrenosum: A Literature Review.

Pyoderma gangrenosum (PG), which most frequently affects the lower extremity, is a complicated disease state that results from a combination of inflammation, neutrophilic invasion, and genetic predisposition. There may also be certain comorbidities involved or it may be idiopathic. The many variations of PG mean that it often presents and responds differently to various treatments based on the specific case. Overall, there have been improvements in understanding the disease; however, further research should focus on finding better ways to predict and prevent this rapidly progressive, painful disease.

How to Save a Limb: Identification of Pyoderma Gangrenosum.

We report the case of a 67-year-old woman with a painful expanding ulcer on the left leg of 2 months' duration that initially was diagnosed as a skin and soft tissue infection (SSTI) with plans for surgical debridement. Upon dermatologic consultation, surgery was canceled due to the possible diagnosis of pyoderma gangrenosum (PG) and risk of pathergy. Notable features of this patient included a history of inflammatory bowel disease (IBD), poor response to antibiotics, chronicity, lack of signs of sepsis, potential complications of surgical intervention, and ultimately a response to immunosuppressive agents.

Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids.

An 18-year-old woman was admitted to our hospital with fever, diarrhea and painful skin ulcers in both pretibial areas starting 19 days earlier. The skin lesions appeared deep necrotic ulcers with violaceous undermined borders. She had been diagnosed as ulcerative colitis and primary sclerosing cholangitis (PSC) 6 and 5 years before, respectively, and had stopped having regular check-up and refused medication for years. Her clinical history and skin lesions led us to suspect of pyoderma gangrenosum (PG). The skin biopsy showed aseptic abscess formation with neutrophils infiltration in the dermis without bacteria. Thus, she was diagnosed with PG. 1 mg/kg/day of prednisolone was administered and ten sessions of granulocyte and monocyte adsorption apheresis (GMA) were started. Magnetic resonance cholangiography showed multifocal bile duct strictures due to PSC. Total colonoscopy revealed ulcerative pancolitis with spared normal mucosa in the rectum. After the treatments, her symptoms and the skin lesion improved dramatically. She was discharged on the 45th day with 25 mg/day of prednisolone. In conclusion, this is the first reported case of PG with PSC-associated colitis that showed dramatic response to the concomitant GMA therapy with corticosteroids. Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

Case to highlight a rare differential diagnosis of necrotising fasciitis in the presence of a stoma: peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum (PPG) is a rare clinical entity, which can masquerade as the more common and lethal necrotising fasciitis. The authors present a case of PPG in a 65-year-old woman who underwent robotic abdominoperineal resection for low rectal carcinoma and returned 8 days postoperation for peristomal skin ulcerations and pain, accompanied by leucocytosis; thus, she was treated as per necrotising fasciitis and underwent surgical debridement. Thereafter, her wound continued to worsen despite conventional wound care with vacuum-assisted closure and demonstrated signs of pathergy. The case was referred to dermatology where a diagnosis of PPG was made. This case report presents a cautionary tale for fellow clinicians, highlights the diagnostic challenge, and presents an updated literature review on diagnosis and management of this unique condition.