Marzano AV, Cugno M, Trevisan V et al.Role of inflammatory cells, cytokines and matrix metalloproteinases in neutrophil-mediated skin diseases. Clin Exp Immunol 162:100-7

Unità Operativa di Dermatologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Università degli Studi di Milano, Milano, Italy.
Clinical & Experimental Immunology (Impact Factor: 3.04). 10/2010; 162(1):100-7. DOI: 10.1111/j.1365-2249.2010.04201.x
Source: PubMed


Pyoderma gangrenosum (PG) is a rare, immune-mediated inflammatory skin disease presenting with painful ulcers having undermined edges. Less commonly, bullous and vegetative variants exist. Histology consists of a neutrophil-rich dermal infiltrate. We characterized immunohistochemically the infiltrate in different variants of PG and in another neutrophilic dermatosis as Sweet's syndrome. We studied 21 patients with PG, eight with Sweet's syndrome and 20 controls, evaluating skin immunoreactivity for inflammatory cell markers (CD3, CD163 and myeloperoxidase), cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-8 and IL-17], metalloproteinases (MMP-2 and MMP-9) and vascular endothelial growth factor (VEGF). Immunoreactivities of CD3, CD163, myeloperoxidase, TNF-α, IL-8, IL-17, MMP-2, MMP-9 and VEGF were significantly higher in both PG and Sweet's syndrome than in controls (P=0·0001). Myeloperoxidase (neutrophil marker), IL-8 (cytokine chemotactic for neutrophils) and MMP-9 (proteinase-mediating tissue damage) were expressed more significantly in both ulcerative and bullous PG than in vegetative PG as well as in Sweet's syndrome (P=0·008-P=0·0001). In ulcerative PG, the expression of CD3 (panT cell marker) and CD163 (macrophage marker) were significantly higher in wound edge than wound bed (P=0·0001). In contrast, the neutrophil marker myeloperoxidase was expressed more significantly in wound bed than wound edge (P=0·0001). Our study identifies PG as a paradigm of neutrophil-mediated inflammation, with proinflammatory cytokines/chemokines and MMPs acting as important effectors for the tissue damage, particularly in ulcerative and bullous PG where damage is stronger. In ulcerative PG, the wound bed is the site of neutrophil-recruitment, whereas in the wound edge activated T lymphocytes and macrophages pave the way to ulcer formation.

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Available from: Daniele Fanoni, May 14, 2015
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    Immunological investigations 01/2015; 44(3):1-16. DOI:10.3109/08820139.2014.988720 · 1.99 Impact Factor
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    • "Pyoderma gangrenosum (PG) is a so far poorly characterized, challenging destructive neutrophil-mediated autoinflammatory disease with an incidence of 0.3-1.0/100.000 [1-5]. Langan et al. showed in 2012 an adjusted incidence rate standardized to European standard populations of 0.63 (95% confidence interval (CI) 0.57-0.71) "
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    ABSTRACT: Pyoderma gangrenosum (PG) is a rarely diagnosed ulcerative neutrophilic dermatosis with unknown origin that has been poorly characterized in clinical studies so far. Consequently there have been significant discussions about its associated factors and comorbidities. The aim of our multicenter study was to analyze current data from patients in dermatologic wound care centers in Germany in order to describe associated factors and comorbidities in patients with PG. Retrospective clinical investigation of patients with PG from dermatologic wound care centers in Germany. We received data from 259 patients with PG from 20 different dermatologic wound care centers in Germany. Of these 142 (54.8%) patients were female, 117 (45.2%) were male; with an age range of 21 to 95 years, and a mean of 58 years. In our patient population we found 45.6% with anemia, 44.8% with endocrine diseases, 12.4% with internal malignancies, 9.3% with chronic inflammatory bowel diseases and 4.3% with elevated creatinine levels. Moreover 25.5% of all patients had a diabetes mellitus with some aspects of potential association with the metabolic syndrome. Our study describes one of the world's largest populations with PG. Beside the well-known association with chronic bowel diseases and neoplasms, a potentially relevant new aspect is an association with endocrine diseases, in particular the metabolic syndrome, thyroid dysfunctions and renal disorders. Our findings represent clinically relevant new aspects. This may help to describe the patients' characteristics and help to understand the underlying pathophysiology in these often misdiagnosed patients.
    Orphanet Journal of Rare Diseases 09/2013; 8(1):136. DOI:10.1186/1750-1172-8-136 · 3.36 Impact Factor
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    • "The name suggests an infectious agent but autoimmune mechanisms, neutrophil dysfunction, and disturbance of cellular immunity seem to be implicated. The accumulation of neutrophils in the skin lesions, similar with Sweet syndrome (acute febrile neutrophilic dermatosis) supporting the inclusion of PG within the spectrum of neutrophilic dermatoses [3]. The frequency of pathergy (development of new lesions or aggravation of existing ones following local injuries) suggests altered inflammatory responses to nonspecific stimuli. "
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    ABSTRACT: Introduction Pyoderma gangrenosum (PG) is a rare sterile neutrophilic dermatosis characterized by painful recurrent ulcerations. It is frequently associated with inflammatory bowel disease, rheumatoid arthritis, or malignancies. PG is a diagnosis of exclusion, and it is based on clinical presentation, histology, history of an underlying disease, and exclusion of other causes of ulceration. Case Report The authors report a 62-year-old male who developed a nonhealing ulcer at the site of incision following nephrectomy for renal cell carcinoma. Past medical history included chronic lymphocytic leukemia treated with rituximab. Histology of the skin lesion showed a phlegmonous nonspecific inflammation without being able to differentiate between a necrotizing wound infection and PG. The patient’s condition was initially diagnosed as an infectious process and treated accordingly. After unsuccessful results with systemic antibiotics, high-dose corticosteroids induced prompt healing of the wound. On these bases, the diagnosis of postoperative PG within chronic lymphocytic leukemia and renal cell carcinoma was made. Conclusion Faced with postoperative necrotizing ulceration resistant to correctly administered antibiotics, PG must be considered. In such condition, the diagnosis must not be guided primarily by histology and early advice of a dermatologist is recommended.
    06/2013; 2(1). DOI:10.1007/s40121-013-0008-4
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