Pyoderma gangrenosum is a challenging skin condition to identify and treat because of its multifactorial pathogenesis. It is a rare cutaneous manifestation diagnosed clinically by exclusion of ...infection, neoplasia, thrombophilia, and other inflammatory conditions. Pathogenetic and treatment studies are scarce. Abnormalities in the function of inflammatory cytokines, the immune system, and neutrophils combined with specific genetic mutations predispose patients to develop this complex disease process. Early recognition of patients at risk for pyoderma gangrenosum, the necessity to improve its early diagnosis, and the future outlook of targeted and personalized therapies relies on the improved comprehension of the complex pathogenesis of pyoderma gangrenosum.
Sweet's syndrome, also known as Acute Febrile Neutrophilic Dermatosis, is a rare inflammatory condition. It is considered to be the prototype disease of neutrophilic dermatoses, and presents with ...acute onset dermal neutrophilic lesions, leukocytosis, and pyrexia. Several variants have been described both clinically and histopathologically. Classifications include
. The cellular and molecular mechanisms involved in Sweet's syndrome have been difficult to elucidate due to the large variety of conditions leading to a common clinical presentation. The exact pathogenesis of Sweet's syndrome is unclear; however, new discoveries have shed light on the role of inflammatory signaling, disease induction, and relationship with malignancy. These findings include an improved understanding of inflammasome activation, malignant transformation into dermal infiltrating neutrophils, and genetic contributions. Continued investigations into effective treatments and targeted therapy will benefit patients and improve our molecular understanding of inflammatory diseases, including Sweet's syndrome.
Background
Pyoderma gangrenosum (PG) is a rare inflammatory skin condition characterized by painful, irregularly shaped skin ulcers mainly affecting the lower extremities. PG rarely affects the head ...and neck, making the diagnosis of this condition even more challenging. A high index of suspicion is paramount in the diagnosis of PG, especially after surgical procedures.
Methods
We describe a clinical case of a patient with initially undiagnosed PG of the scalp who underwent surgical excision and full thickness skin graft with subsequent graft necrosis as initial clue for the diagnosis.
Results
Twenty months after initial presentation, this patient healed with a multimodal medical approach of immunosuppressive therapy and wound care.
Conclusion
Prompt recognition of PG by physicians assessing any surgical wounds is vital in reducing misdiagnosis and improving patient outcomes.
Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic dermatosis that is occasionally associated with primary immunodeficiency. Though contributions from dysregulation of the innate immune ...system, neutrophil dysfunction and genetic predisposition have been postulated, the precise pathogenesis of PG has not yet been elucidated. This article reviews reported cases of coexisting PG and primary immunodeficiency in order to gain insight into the complex pathophysiology of PG. Our findings suggest that variations in genes such as RAG1, ITGB2, IRF2BP2 and NFκB1 might play a role in genetically predisposing patients to develop PG. These studies support the feasibility of the role of somatic gene variation in the pathogenesis of PG which warrants further exploration to guide targeted therapeutics.
Neutrophil-mediated skin diseases, originally named neutrophilic dermatoses (NDs), are a group of conditions due to an altered neutrophil recruitment and activation, characterized by polymorphic ...cutaneous manifestations with possible internal organ involvement. Although a number of diseases are included in this setting, the two prototypic forms are pyoderma gangrenosum (PG) and Sweet's syndrome (SS) which usually present with skin ulcers and plaque-type lesions, respectively. They have central features significantly overlapping with autoinflammatory conditions which manifest as repeated episodes of tissue inflammation. However, in contrast to appropriate inflammatory responses to insults or to autoimmune disease, there is an absence of identifiable pathogens, autoantibodies, or autoreactive lymphocytes. The recognition of monogenic autoinflammatory diseases which can present with NDs has led to study several genes involved in autoinflammation in NDs. Based on discovering of a number of mutations involving different autoinflammatory genes, neutrophil-mediated skin diseases are nowadays regarded as a spectrum of polygenic autoinflammatory conditions. Although disease mechanisms have not yet been completely elucidated, NDs are recognized as diseases involving dysfunctional cellular signaling mediated by pathways mainly related to inflammasome and IL-1 with the contributory role of IL-17 and other effector molecules. The precise elucidation of the above-mentioned pathologic mechanisms may pave the way to tailored treatments for patients with different neutrophil-mediated skin diseases.
Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with ...undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.
Pyoderma gangrenosum (PG) is an inflammatory condition characterized by chronic cutaneous ulcerations. There are three proposed PG diagnostic frameworks (Su, PARACELSUS, Delphi); however, they lack ...consensus, and their performance has not yet been validated in a well-defined cohort of patients with PG. In this cross-sectional retrospective cohort study, we sought to evaluate and compare the concordance of these diagnostic frameworks within a single-institution cohort of patients with PG. There were 47 patients from an initial 76 identified by International Classification of Diseases-9 and/or International Classification of Diseases-10 codes, where two PG experts agreed in their diagnosis of PG on the basis of clinical descriptions, photographs, and pathology. This group was the PG cohort by which we evaluated the performance and concordance of the diagnostic frameworks. The PARACELSUS score identified the highest proportion of patients with PG (89% 42 of 47 patients), followed by Delphi and Su criteria, each at 74% (35 of 47 patients). Assessment of multirater agreement found that the three criteria agreed in their diagnoses for 72% of the patients (95% confidence interval = 60–85%); chance-adjusted agreement was determined to be 0.44 (95% confidence = 0.16–0.68, Fleiss’ kappa). Future research should seek to refine these diagnostic frameworks and identify targeted methods of testing to reduce rates of PG misdiagnosis and patient misclassification in clinical trials.
The objective of this study was to develop a pilot physician driven patient pyoderma gangrenosum (PG) registry to summarise patient baseline demographics, PG‐related medical history, treatments, and ...outcomes for patients with pyoderma gangrenosum. Standardised patient information was collected prospectively during clinical encounters between December 2019 and July 2021 at a single academic institution. Eligibility criteria for the study was a diagnosis of pyoderma gangrenosum determined by a PARACELSUS score of at least 10 for ulcerative patients. Main outcome measures included demographic data, PG related history and comorbidities, past and current treatments, healing outcomes, hospitalisations and recurrences of PG. The Pyoderma Gangrenosum Study (PYGAS) Registry currently includes 52 patients with 56 target lesions of four distinct PG subtypes (41 ulcerative, 12 peristomal, 2 vegetative and 1 bullous). For the 38 patients with 41 total ulcerative PG lesions, referrals to our institution most commonly came from dermatologists (42.1%). The median follow‐up time in our initial registry was 5.5 months (95% CI = 4.1–11.5 months), with average time between follow‐up visits at 1.1 months. These ulcers were most commonly treated with first‐line systemic immunosuppressants (70.6%), such as corticosteroids or cyclosporine. Additional use of systemic immunomodulators at baseline visit was statistically significantly associated with healing (P = 0.048). This pilot study suggests that use of systemic immunomodulators has an impact on healing of PG patients. Wound care regimens are variable, and assessing their impact on treatment outcomes could be challenging. Standardisation of both wound care regimens and data collection in prospective clinical studies is necessary to assess their impact in PG treatment outcomes.
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