Hidradenitis Suppurativa-Related Autoinflammatory Syndromes: An Updated Review on the Clinics, Genetics, and Treatment of Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PASH), Pyogenic Arthritis, Pyoderma gangrenosum, Acne and Suppurative Hidradenitis (PAPASH), Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO), and Rarer Forms.

Hidradenitis suppurativa (HS) is an autoinflammatory skin disorder of the terminal hair follicle, which can present in sporadic, familial, or syndromic form. A classification has been proposed for the latter, distinguishing cases associated with a known genetic condition, with follicular keratinization disorders or with autoinflammatory diseases. This review focuses on the clinical and genetic features of those entities (ie, pyoderma gangrenosum [PG], acne and HS; PG, acne, pyogenic arthritis and HS; psoriatic arthritis, PG, acne and HS; synovitis, acne, pustulosis, hyperostosis, osteitis; and so forth) for which the collective term HS-related autoinflammatory syndromes is proposed.

Quality of Life with Neutrophilic Dermatoses.

Neutrophilic dermatoses (NDs) encompass a wide range of cutaneous and extracutaneous manifestations, many of which impair quality of life (QoL) and are difficult to treat. Although NDs are transient and mild, others are chronic, severely debilitating conditions with profound impacts on QoL, including pain, mental health, occupational limitations, and sexual health implications. Current literature lacks attention to these unique care challenges to the ND patient population. The authors aim to summarize what is currently known about QoL in NDs and identify which diseases would benefit from additional research and disease-specific QoL assessment.

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.

The "Understanding Pyoderma Gangrenosum, Review and Assessment of Disease Effects (UPGRADE)" Project: a protocol for the development of the core outcome domain set for trials in pyoderma gangrenosum.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects approximately 0.3-6 out of every 100,000 people worldwide. Clinical trials are scarce but there is growing interest in using newer and more targeted therapeutics to achieve disease remission. However, there are no standardized instruments to measure outcomes in PG and, therefore, future clinical trials are hampered by the absence of established and accurate means of assessment and comparison. Therefore, we aim to produce an internationally accepted core outcome set (COS) that will overcome this obstacle. This protocol outlines our intended approach to achieve the first part of this process, establishing a core outcome domain set. METHODS: An international team of PG stakeholders, consisting of physicians, wound care nurses, patients, scientists and industry representatives, has been assembled for the purpose of building a comprehensive and universally established set of core outcome domains. During the first step, we will generate items of relevance using a nominal process from all stakeholders. Items will be distilled and collapsed into potential domains and subdomains. A systematic review of current methods for reporting PG has already been published and domains identified in this work will be considered in the generation of the core domains set. During the second step, after the potential domains and subdomains are identified, stakeholders will participate in an e-Delphi exercise to rate the importance of (sub)domains. A final consensus meeting will be organized with the goal of establishing a core domain set. CONCLUSION: Pyoderma gangrenosum lacks an established COS and previously published clinical trials have used inconsistent measures established from similarly inconsistent domains. As a first step this study seeks to create a core domain set within the COS, to build the foundation for future core outcome work for PG.

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.

Atypical Pyoderma Gangrenosum in the Setting of Venous and Arterial Insufficiency.

Ulcers of mixed etiology are diagnostically elusive and challenging to treat, especially when rare conditions are superimposed. Pyoderma gangrenosum (PG) is an autoinflammatory, ulcerative skin disease that is difficult to diagnose. Diagnostic criteria exist but there are no specific clinical tests to identify it. We discuss a case of PG initially diagnosed as venous ulcer in the setting of peripheral artery disease, complicated by superinfection, refractory to standard wound care, multiple surgical debridements, revascularization, negative pressure therapy, and parenteral antibiotics. Findings differentiating PG from other wound etiologies are explored, with the aim of improving clinical recognition of this condition.

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

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

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.

Characterization of Legal Claims Involving Patients with Pyoderma Gangrenosum.

OBJECTIVE: To review the litigation literature related to patients with pyoderma gangrenosum (PG) to characterize the legal issues they face. DATA SOURCES: Data sources include law databases Casetext and Lexis Nexis. STUDY SELECTION: All disability and medical liability claims directly involving patients with PG were included. DATA EXTRACTION: Data extraction came directly from Casetext and Lexis Nexis. All cases extracted came from September 1965 to December 2020. This resulted in 32 cases, 18 of which were excluded because they did not mention the plaintiff having a diagnosis of PG (n = 14). DATA SYNTHESIS: The review found a total of six medical liability cases in which adverse health outcomes were reported, including prolonged suffering (2/6 cases), unnecessary treatments or procedures (2/6), exacerbation of disease (1/6 cases), and permanent scarring (1/6 cases). Despite this, two plaintiffs won their case and only one of them received any monetary award. Similarly, of the eight disability claims in the review, four were ruled in the favor of the plaintiffs and only two resulted in immediate awarding of benefits. Half of medical liability cases occurred in correctional facilities after the denial of appropriate care. CONCLUSIONS: The findings demonstrate a need for access to specialty care in incarcerated populations. Cases that occurred in a hospital setting also stress the importance of initiatives such as telemedicine to efficiently increase access to care in a cost-effective manner. Further, PG has been recognized as a severe impairment in disability claims despite patients being denied because they were deemed able to perform other work.