Case Report: Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne: A Single-Center Experience and Literature Review.

Objectives: This study aims to describe the characteristics of patients diagnosed with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome at a single center in China and provide an up-to-date literature review. Methods: The clinical data and genotype of three Chinese Han patients were carefully documented and studied. We also conducted a systematic literature review on PAPA syndrome. Results: A total of three patients were diagnosed with PAPA syndrome at our center from 2018 to 2020. Arthritis was observed in all three patients, while pyoderma gangrenosum (PG) was found in two patients and acne in one patient. Other manifestations included pathergy reaction, intermittent fever, oral ulcer, keratitis, proteinuria, and hematuria. The PSTPIP1 A230T mutation was identified in two patients, and a novel Y119C variation was revealed in a sporadic patient. A total of 76 patients with PAPA syndrome reported in 29 articles were included in our literature review. The classical triad of arthritis, PG, and acne was visible in only 16 (25.4%) patients, while 24 (38.1%) exhibited only one major symptom. Skin lesions were more commonly seen in patients with adult-onset disease than those with childhood-onset disease (100 vs. 83%), whereas arthritis was less common (50 vs. 98.1%). Steroid and/or biological agents were effective in most patients. Conclusions: The rarity and phenotypic heterogeneity associated with PAPA syndrome make the diagnosis a huge challenge to physicians, especially in adult patients. A significant portion of patients did not exhibit the full spectrum of the classical triad. Accordingly, gene testing is critically helpful for diagnosis.

Acute myeloid leukaemia presenting with ecthyma gangrenosum as the first manifestation: A case report.

RATIONALE: Ecthyma gangrenosum (EG) is an uncommon cutaneous infection usually associated with Pseudomonas aeruginosa bacteremia in immunocompromised patients, particularly those with underlying malignant diseases. Despite its rarity, especially in immunocompetent or nondiagnosed immunodeficiency patients, EG can present as the first manifestation of an underlying immunosuppression. PATIENT CONCERNS: A 42-year-old Japanese man was admitted to our hospital with a 3-day history of a painless red macule on his right forearm and fever. DIAGNOSES: Blood culture on admission revealed the presence of Pseudomonas aeruginosa, whereas pus culture of the skin lesion showed Pseudomonas aeruginosa and methicillin-susceptible Staphylococcus aureus positivity. INTERVENTIONS: Additional bone marrow aspirate examination and immunophenotyping were performed to confirm the diagnosis of acute promyelocytic leukaemia with PML-retinoic acid alpha receptor. OUTCOMES: The patient was successfully treated with a 14-day course of antibiotics, and no evidence of relapse was noted. The patient achieved complete remission after treatment for acute promyelocytic leukaemia. LESSONS: It should be kept in mind that EG is an important cutaneous infection that is typically associated with P aeruginosa bacteremia and the presence of underlying immunodeficiency, such as acute leukaemia.

Pyoderma gangrenosum associated with levamisole-adulterated cocaine in a c-ANCA positive patient.

Pyoderma gangrenosum (PG) is an inflammatory, ulcerative condition that is characterized by painful ulcers that commonly present on the lower extremities. Up to half of PG cases are associated with underlying systemic disease, including inflammatory bowel disease, various autoimmune conditions, and malignancy. Another well-known association is the manifestation of PG with recreational cocaine use, especially cocaine contaminated with the adulterant agent levamisole. Once utilized for its immunomodulatory capabilities, levamisole was withdrawn from the market in 2002. It has since been repurposed to potentiate the amphetamine-like effects and duration of cocaine and has reduced preparation cost. We present a 52-year-old woman with chronic maxillary sinusitis and cocaine use disorder presenting with a two-week history of painful ulcers on bilateral lower extremities, each with a purulent base and undermined, violaceous borders. Urine toxicology was positive for cocaine and serologic studies were positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and lupus anticoagulant. Underlying conditions, especially that of granulomatosis with polyangiitis, were considered and ultimately ruled out. The patient's lesions exhibited a marked response with a short course of oral corticosteroids, typical of PG associated with levamisole. This case highlights the crucial role that drug abstinence plays in the prevention of recurrence.

Pyoderma Gangrenosum Occurring in the Setting of Hypercortisolism Associated With Adrenocortical Adenoma: A Pathophysiological Paradox.

Pyoderma gangrenosum (PG) is a challenging, rare, ulcerating skin disease characterized by neutrophilic abundance and absence of infection, often associated with systemic diseases. We present a 25-year old previously healthy female with a 1.5-year history of treatment refractory PG. Features of Cushing’s syndrome such as facial plethora, striae, and lipodystrophy were noted on exam, which prompted several studies that ultimately revealed an adrenal adenoma. Following surgical excision of the adenoma, symptoms rapidly resolved and systemic immunosuppressants were discontinued. This rare case highlights the importance that adrenal adenoma and resultant Cushing’s syndrome may be a driver of PG despite the pathophysiologic paradox. J Drugs Dermatol. 2021;20(1):95-97. doi:10.36849/JDD.5566.

Novel Therapeutic Approaches and Targets for the Treatment of Neutrophilic Dermatoses, Management of Patients with Neutrophilic Dermatoses and Future Directions in the Era of Biologic Treatment.

Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders characterized by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. Universally accepted and validated guidelines for the management of neutrophilic dermatoses do not exist, also given the paucity of randomized controlled study and high-quality data. However, the literature on the effective use of biologic therapies is rapidly expanding. This article reviews the epidemiology, clinical characteristics, histopathologic features, and management of pyoderma gangrenosum as well as Sweet's syndrome, sub-corneal pustular dermatoses and bowel-associated dermatosis arthritis syndrome. The use of biologic agents, including tumor necrosis factor α-inhibitors, anti-IL1, anti-IL-17, and IL-23 are discussed in detail.

Surgical Treatment of Pyoderma Gangrenosum with Negative Pressure Wound Therapy and Skin Grafting, Including Xenografts: Personal Experience and Comprehensive Review on 161 Cases.

Significance: Pyoderma gangrenosum (PG) is a rare debilitating autoinflammatory ulcerative skin disease. No gold standard has been established for the treatment of PG. The role of surgical interventions and negative pressure wound therapy (NPWT) was discussed controversially until recently as these procedures might pose a trigger to further aggravate the condition. Recent Advances: Recent advances confirm the paradigm change that a surgical approach of PG with split thickness skin grafting (STSG) secured by NPWT is a safe and valuable treatment if performed under adequate immunosuppression. We elaborate this on the hand of a broad literature search retrieving 101 relevant articles describing 138 patients complemented with our personal experience on 23 patients, including 2 patients treated with a porcine xenodressing. Critical Issues: A wide range of surgical approaches have been reported, including xenografts. Treatment was finally successful in 86%, including the xenotransplant cases. Ten percent improved and failures were mainly reported without immunosuppression. Despite halting the inflammatory process, NPWT alone, without skin grafting, does not much accelerate healing time. The best surgical approach appears to be STSG fixed with NPWT as this leads to higher skin graft take. There remains the problem of the chronic nature of PG and the recurrence after tapering of immunosuppression or trauma; therefore, a sustained immunosuppressive treatment is suggested. Future Directions: While surgical treatment is supported by the published data, the exact immunosuppression is still evolving. Due to deeper insights into pathogenesis and growing clinical reports, a broader utilization of biologic treatments and a shift from tumor necrosis factor (TNF)-alpha to interleukin (IL)-12/23 or IL-23 antibodies alone are predictable, as IL-12/23 antibodies show good clinical responses with fewer side effects. The positive results with porcine xenodressings might be due to immunological effects of the xenomaterial; they appear promising, but are preliminary and should be confirmed in a larger patient collective.

IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation.

IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.

Pioderma gangrenoso y criptococosis cutánea primaria en un paciente con colitis ulcerosa / Pyoderma gangrenosum and primary cutaneous cryptococcosis in an ulcerative colitis patient

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Pyoderma gangrenosum and tumour necrosis factor alpha inhibitors: A semi-systematic review.

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that presents a therapeutic challenge. Tumour necrosis factor alpha (TNFα) inhibitors have been reported to successfully control PG. Our aim was to systematically evaluate and compare the clinical effectiveness of TNFα inhibitors in adults with PG. A literature search including databases such as PubMed, Embase, Scopus, and Web of Science was conducted, using search terms related to PG and TNFα inhibitors. Studies and case reports were included if patients were diagnosed with PG, over the age of 18 and administered TNFα inhibitor. A total of 3212 unique citations were identified resulting in 222 articles describing 356 patients being included in our study. The study we report found an 87% (95% CI: 83%-90%) response rate and a 67% (95% CI: 62%-72%) complete response rate to TNFα inhibitors. No statistically significant differences in the response rates (P = 0.6159) or complete response rates (P = 0.0773) to infliximab, adalimumab, and etanercept were found. In our study TNFα inhibitors demonstrated significant effectiveness with response and complete response rates supporting the use of TNFα inhibitors to treat PG in adults. Our study suggests that there is no significant difference in effectiveness among infliximab, adalimumab, and etanercept.

The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum.

BACKGROUND: The lack of objective diagnostic criteria renders pyoderma gangrenosum (PG) a diagnosis of exclusion. The diagnostic approaches proposed to date have not been systematically evaluated. Thus, PG remains a challenging and frequently misdiagnosed disorder. OBJECTIVES: To develop and assess a comprehensive, yet clinically practicable, sensitive diagnostic scoring system for PG. METHODS: Clinical history and images of a total of 60 participants with previously confirmed PG located on the lower extremity and a control cohort of 50 patients with venous leg ulcers were retrospectively evaluated by expert teams at two tertiary dermatological centres specializing in wound care using a newly developed diagnostic scoring system composed of 10 criteria. RESULTS: The three major diagnostic criteria are rapidly progressing disease, assessment of relevant differential diagnoses and a reddish-violaceous wound border (prevalent in 98% of patients with PG). Minor criteria (evident in 61-95% of patients with PG) include amelioration by immunosuppressant drugs, characteristically irregular shape of ulceration, extreme pain > 4/10 on a visual analogue scale and localization of lesion at the site of the trauma. Three additional criteria (observed in up to 60% of patients with PG) encompass suppurative inflammation in histopathology, undermined wound borders and systemic disease associated. A total score value of 10 points or higher indicates a high likelihood of PG and differentiates PG from venous leg ulcers. The initial letters of the above-listed criteria form the acronym PARACELSUS. CONCLUSIONS: The PARACELSUS score represents a novel, easily implementable, effective and sensitive diagnostic tool for PG.