Local neutrophil and eosinophil extracellular traps formation in pyodermatitis pyostomatitis vegetans.

Pyodermatitis pyostomatitis vegetans is a rare inflammatory condition, affecting the skin and/or mucous membrane. Some cases include both skin and mucous involvement, whereas others develop either skin or mucous lesions only. The typically affected areas are the scalp, face, trunk and extremities, including the flexural areas and umbilicus. Clinical features show erosive granulomatous plaques, keratotic plaques with overlying crusts and pustular lesions. Among mucous lesions, oral mucosa is most frequently involved, and gingival erythema, shallow erosions, cobblestone-like papules on the buccal mucosa or upper hard palate of the oral cavity are also observed. Some of the lesions assume a 'snail track' appearance. Although there are several similarities between pyodermatitis pyostomatitis vegetans and other diseases, that is pyoderma gangrenosum, pemphigus vegetans and pemphigoid vegetans, the histopathological features of pyodermatitis pyostomatitis vegetans are unique in that epidermal hyperplasia, focal acantholysis and dense inflammatory infiltrates with intraepidermal and subepidermal eosinophilic microabscesses are observed. Direct immunofluorescence findings are principally negative. Activated neutrophils are supposed to play an important role in the pathogenesis of pyodermatitis pyostomatitis vegetans. The expression of IL-36 and neutrophil extracellular traps (NETs) was observed in the lesional skin, and additionally, eosinophil extracellular traps (EETs) was detected in pyodermatitis pyostomatitis vegetans. A possible pathogenic role of NETs and EETs in the innate immunity and autoinflammatory aspects of pyodermatitis pyostomatitis vegetans was discussed.

Blastomycosis-like pyoderma: A pitfall for the misdiagnosis of squamous cell carcinoma.

Blastomycosis-like pyoderma is a rare cutaneous disease presenting as solitary or multiple verrucous or ulcerated plaques and nodules in a susceptible patient. The diagnostic criteria include characteristic verrucous plaques with pustules and elevated borders, histopathologic findings of pseudoepitheliomatous hyperplasia with abscesses, growth of at least one bacterium in tissue culture, and exclusion of other infectious sources. This report describes a case of a 62-year-old man with poorly controlled type 2 diabetes mellitus who presented with plaques, nodules, and ulcers in both groins and the right ankle. The patient was initially misdiagnosed with multiple squamous cell carcinomas and underwent several operations. A review of the pathology slides revealed pseudoepitheliomatous hyperplasia with multiple dermal abscesses, while repeated wound and tissue cultures were positive for coagulase-negative Staphylococcus. Blastomycosis-like pyoderma was diagnosed. The patient was subsequently treated with culture-guided prolonged antibiotic therapy followed by intralesional steroid injection, which led to gradual resolution of the lesions.

Vegetative lesions associated with inhaled cocaine use.

We present two cases of vegetating exudative lesions involving the oral mucosa, in patients that are cocaine users, with findings in biopsy and in direct immunofluorescence consistent with the diagnosis of pyostomatitis vegetans-pyodermatitis vegetans.

Pyodermatitis-pyostomatitis vegetans: a case report and review of literature.

Pyodermatitis-pyostomatitis vegetans is a rare inflammatory dermatosis. There is a strong association between pyodermatitis-pyostomatitis vegetans and inflammatory bowel disease, particularly ulcerative colitis. Herein, we report a case of pyodermatitis-pyostomatitis vegetans with positive direct immunofluorescence staining findings and review the literature for the past 18 years to characterize the disease, its epidemiologic characteristics, its associations, and the pathology and direct and indirect immunofluorescence findings. The total number of cases was 38, including 22 men and 16 women, with an average age of forty. Direct immunofluorescence staining had been performed for 32 patients, of which 12 had positive findings. Of those with positive direct immunofluorescence, 6 patients showed IgA cell surface staining. A recent approach suggests that these immunological findings may not be accidental and indicates a possible overlap with autoimmune bullous diseases discussed in this review.

A perplexing case of superficial granulomatous pyoderma with sporotrichoid-like distribution.

Superficial granulomatous pyoderma (SGP) is a rare pyoderma gangrenosum (PG) variant that differs from classic PG in that the ulcers tend to be more superficial, lack a rapidly advancing border, and are not typically associated with an underlying systemic disease. The ulcers are most commonly painless and located on the trunk, with a clean granulating base. They generally do not show undermining but may have a vegetative border. Lesions usually respond well to either topical or intralesional corticosteroids with complete healing. The classic histopathologic finding is a "three-layer granuloma" in the superficial dermis consisting of central neutrophilic inflammation and necrosis, a surrounding layer of histiocytes and multinucleated giant cells, and an outer most layer of plasma cells and eosinophils. Herein, we present a unique case of SGP with sporotrichoid-like distribution on the lower extremity.

A synthetic M protein peptide synergizes with a CXC chemokine protease to induce vaccine-mediated protection against virulent streptococcal pyoderma and bacteremia.

Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain's ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100-1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.

Establishing a canine superficial pyoderma model.

AIMS: Pyoderma, predominantly associated with Staphylococcus pseudintermedius, is a common skin infection of dogs that typically requires long-lasting treatments, complicated by increasing antimicrobial resistance. To investigate new treatment strategies, we aimed at establishing a dog model of pyoderma that closely mimics the natural disease. METHODS AND RESULTS: We inoculated six laboratory beagles with a methicillin-susceptible strain of S. pseudintermedius. One millilitre of approximately 107 , 108 , 109 CFU per ml was topically applied onto clipped and tape stripped area of dog skin, which was then treated with a dermaroller (microneedle size: 500 µm) immediately after administration. Dogs were monitored daily, suspect pustules were cultured for S. pseudintermedius and evaluated by cytological and histopathological methods. After 24 h, all dogs developed papules and pustules at all three bacterial inoculation sites, which worsened over the next 48 h. Cytological samples of all skin lesions revealed neutrophils with intracellular cocci. Histopathology confirmed subcorneal neutrophilic pustular dermatitis with intralesional cocci and acantholytic keratinocytes, consistent with superficial pyoderma. Staphylococcus pseudintermedius was isolated from pustules of all dogs and confirmed to be the inoculating strain. The results were replicated in all dogs after a wash out period of 6 weeks. CONCLUSIONS: These data demonstrate the feasibility of establishing a dog model of pyoderma. SIGNIFICANCE AND IMPACT OF THE STUDY: The new model can be used to evaluate novel prevention and treatment options for canine pyoderma.

Heterogeneity of blastomycosis-like pyoderma: A selection of cases from the last 35 years.

Blastomycosis-like pyoderma is a form of pyoderma with variable clinical findings and histopathological features. We present a case series of 39 patients collected over a 35-year period to demonstrate its clinical features and histological findings. The most common clinical presentations found were solitary plaques, solitary nodules, sinuses, crypts, verrucous plaques and discharge, usually on sun-exposed skin. The most common histopathological findings were chronic granulomatous inflammation, suppurative inflammation, sinus and abscess formation, pseudoepitheliomatous hyperplasia, transepidermal elimination and scarring. We discuss its treatment and the recent literature that has focused on its response to acitretin.

Clinical, microscopic and microbial characterization of exfoliative superficial pyoderma-associated epidermal collarettes in dogs.

BACKGROUND: The microscopic and microbial features of the spreading epidermal collarettes of canine exfoliative superficial pyodermas are poorly characterized. OBJECTIVES: To characterize the clinical, cytological, microbial and histopathological features of epidermal collarettes in five dogs. RESULTS: Cytology from the margins of collarettes identified neutrophils, extracellular and intracellular cocci within neutrophils but no acantholytic keratinocytes. Phenotypic and genotypic analyses identified all bacterial isolates from the centre and margin of five epidermal collarettes as Staphylococcus pseudintermedius. PCRs of collarette-associated Staphylococcus strains did not amplify genes encoding for the known exfoliative toxins expA and expB, whereas the predicted siet and speta amplification products were detected in all isolates. Microscopically, epidermal collarettes consisted of interfollicular, epidermal spongiotic pustules. Advancing edges of lesions consisted of peripheral intracorneal clefts in the deep stratum disjunctum above an intact stratum compactum; they contained lytic neutrophil debris, bacterial cocci and fluid, but no acantholytic keratinocytes. This intracorneal location of bacteria was confirmed using Gram stains and fluorescent in situ hybridization with eubacterial- and Staphylococcus-specific probes. The indirect immunofluorescence staining patterns of desmoglein-1, desmocollin-1, claudin-1, E-cadherin and corneodesmosin were discontinuous and patchy in areas of spongiotic pustules, whereas only that of corneodesmosin was weaker and patchy in advancing collarette edges. CONCLUSION: Epidermal collarettes represent unique clinical and histological lesions of exfoliative superficial pyodermas that are distinct from those of impetigo and superficial bacterial folliculitis. The characterization of possible causative staphylococcal exfoliatin proteases and the role of corneodesmosin in collarette pathogenesis deserve further investigation.

Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV): A clinicopathologic study of 7 cases at a tertiary referral center.

BACKGROUND: Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV) is a rare inflammatory mucocutaneous disease associated with inflammatory bowel disease. OBJECTIVE: We sought to evaluate the clinicopathologic findings of PSV-PDV in a series of 7 patients. METHODS: We conducted a retrospective review of all cases of PSV-PDV at the Mayo Clinic from 1995 to 2014. RESULTS: Seven patients with PSV-PDV were included, and all had inflammatory bowel disease. Three had Crohn's disease and 4 had ulcerative colitis. Three patients had peripheral blood eosinophilia. Two had concomitant pyoderma gangrenosum in which pyoderma gangrenosum lesions were recalcitrant to therapy. Primary sclerosing cholangitis was seen in 3 patients. Two patients had direct and 3 had indirect immunofluorescence findings. Tissue eosinophilia was seen in the majority of mucosal and cutaneous lesions. LIMITATIONS: Limited sample size and retrospective study design are limitations. CONCLUSIONS: PSV-PDV is associated with inflammatory bowel disease and primary sclerosing cholangitis and may precede gastrointestinal symptoms. Immunofluorescence findings in select PSV-PDV cases may indicate possible overlap with autoimmune bullous disease. Tissue eosinophilia may be helpful in distinguishing PSV-PDV from pyoderma gangrenosum. Strict control of bowel disease and close monitoring of patients with subclinical disease is warranted.

Pyoderma Vegetans Misdiagnosed as Verrucous Carcinoma.

Pyoderma vegetans, a rare disorder of the skin, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis. It is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. Here, the authors report the case of a 33-year-old man who was misdiagnosed as having verrucous carcinoma for 4 years.

Pyodermatitis vegetans of the vulva.

Pyodermatitis vegetans (PV) is a rare inflammatory dermatosis of unknown etiology and difficult diagnosis characterized by vesiculopustular, exudative, and vegetating plaques usually localized in the axillary, genital, and oral region. It bears similarities to pemphigus vegetans but clinical history, histology, and immunofluorescence help confirm the diagnosis. Pyodermatitis vegetans is often associated with an underlying gastrointestinal disorder, especially ulcerative colitis. No standardized treatment plan is available for PV. Its evolution tends to follow the progression of the underlying disorder. We report a patient with vulvar PV with good response to systemic antibiotics and corticosteroids.

Deep pyoderma caused by Burkholderia cepacia complex associated with ciclosporin administration in dogs: a case series.

BACKGROUND: Bacteria of the Burkholderia cepacia complex (Bcc) are ubiquitous Gram-negative bacilli associated with fatal nosocomial infections in humans; multi-antibiotic resistance makes this organism a serious threat in hospital settings. OBJECTIVE: To describe the historical, clinicopathological and treatment characteristics of Bcc-associated deep skin infections in dogs. ANIMALS: Six dogs with skin infections in which skin bacterial cultures resulted in pure growth of Bcc. METHODS: Retrospective study with review of medical records and skin biopsies. RESULTS: All dogs were receiving oral ciclosporin at the time of skin infection development. All dogs were castrated males and four of six were West Highland white terriers. Cutaneous lesions consistent with deep pyoderma were confined mainly to the trunk. In all dogs skin cytology revealed a strong inflammatory response, with moderate to abundant numbers of intracellular (neutrophils and macrophages) and extracellular bacilli. In three dogs histopathology showed a multifocal, nodular to coalescing pyogranulomatous dermatitis associated with multifocal folliculitis and furunculosis. Tissue Giemsa and Gram stains identified numerous Gram-negative rods within macrophages. Antimicrobial susceptibility testing revealed multidrug-resistant Bcc strains with sensitivity to trimethoprim/sulfonamides in all dogs and to marbofloxacin, piperacillin and ceftazidime in three dogs. Successful treatment was achieved in all dogs using trimethoprim/sulfonamides or quinolones (marbofloxacin, ciprofloxacin) or doxycycline in conjunction with ciclosporin withdrawal. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinicians should be aware of the rare potential for Bcc-associated deep skin infections in dogs receiving oral ciclosporin. Owners should be made conscious of the potential transmission risk to humans or other animals.

Reproducibility of a quantitative cutaneous cytological technique.

BACKGROUND: Cutaneous cytology is a valuable tool for diagnosis of canine superficial pyoderma. Current published reproducible techniques are semiquantitative. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the reproducibility of a quantitative method for skin surface cytology in dogs with superficial pyoderma. ANIMALS: Impression smears were collected from five normal dogs and 20 dogs with clinical and cytological evidence of superficial pyoderma. METHODS: Four investigators evaluated 10 oil immersion fields (OIF) on 25 slides, selecting fields with inflammatory cells, nuclear streaming and or keratinocytes under ×10 magnification. Investigators repeated blinded evaluations of all slides at least twice. For each OIF, polymorphonuclear leukocytes (PMNs), intracellular (IC) cocci, extracellular (EC) cocci, IC rods, EC rods and yeast were quantified. Nuclear streaming was scored as present or absent. For each parameter, within-reader and between-reader agreements were expressed by the intraclass correlation (ICC) value (≤0.20 poor, 0.21-0.40 fair, 0.41-0.60 moderate, 0.61-0.80 good and 0.81-1.00 excellent) or kappa statistic (κ). RESULTS: Reproducible parameters included: PMNs (ICC = 0.58), nuclear streaming (ICC = 0.68), EC cocci (ICC = 0.64) and IC cocci (ICC = 0.32). When qualified as present or absent, within-reader κ for IC cocci was 0.71. The method demonstrated 93% sensitivity in identifying dogs with superficial pyoderma and 51% specificity in identifying normal dogs according to established criteria. However, if criteria for normal dogs were limited to the absence of PMNs and IC bacteria, sensitivity of 64% and specificity of 98% were demonstrated. CONCLUSIONS AND CLINICAL IMPORTANCE: For several parameters, including PMNs, nuclear streaming, EC cocci and IC cocci, a reproducible, quantitative cytological technique was identified.

Pyodermatitis-pyostomatitis vegetans: a case report and systematic review focusing on oral involvement.

BACKGROUND: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare mucocutaneous disease characterized by multiple pustules and it is considered a marker for inflammatory bowel disease (IBD). The oral manifestations of this condition are referred to as pyostomatitis vegetans (PSV). PURPOSE: To investigate which features could help in establishing the diagnosis of PSV, with or without cutaneous lesions, based on information retrieved from all cases of PSV described in the literature. A case of PV from the authors was also included in the analysis. METHODS: An electronic search was undertaken, last updated in August 2022. Inclusion criteria included publications reporting cases of PSV, with the diagnosis confirmed by the pathological examination of oral or skin lesions, and presence of IBD. RESULTS/CONCLUSIONS: Sixty-two publications with 77 cases of PSV and an associated IBD were included. Features that are helpful in establishing the diagnosis of PSV are snail track appearance of oral lesions, an associated IBD (which is not always symptomatic), evidence of intraepithelial clefting on microscopic examination of oral lesions, and peripheral blood eosinophilia. A gold standard for the management of PSV does not exist and high-level evidence is limited. There is no established therapeutic protocol for PSV and management primarily consists of topical and/or systemic corticosteroids, antirheumatic drugs (sulfasalazine, mesalazine), monoclonal antibody (infliximab, adalimumab) immunosuppressives (azathioprine, methotrexate), antibiotics (dapsone), or a combination of these. The risk of recurrence of oral lesions is considerable when the medication dose is decreased or fully interrupted.