Ulcerative Skin Disease Research Articles

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.

Introduction of Mycobacterium ulcerans disease in the Bankim Health District of Cameroon follows damming of the Mapé River.

Buruli ulcer (BU) is an emerging ulcerative skin disease caused by infection with Mycobacterium ulcerans. Efforts to control its spread have been hampered by our limited understanding of M. ulcerans reservoirs and transmission, and the factors leading to the emergence of BU disease in a particular region. In this report we investigate an anecdotal link between damming the Mapé River in Cameroon and the emergence of BU in the Health Districts bordering Lake Bankim, the impoundment created by the Mapé dam. We used bacterial population genomics and molecular dating to find compelling support for a 2000 M. ulcerans introduction event that followed about 10 years after the filling of the newly created impoundment in 1988. We compared the genomic reconstructions with high-resolution satellite imagery to investigate what major environmental alterations might have driven the emergence of the new focus.

Putative paraneoplastic pemphigus in a dog: clinical and microscopic findings

In this case report, a dog with clinical and histopathological features of paraneoplastic pemphigus is described. A Lhasa apso with severe ulcerative oral and predominant facial skin disease had a thoracic mass histopathologically diagnosed as a thymoma. A concurrent disease-association was suspected. Cytologic examination of the oral lesions provided early clues to the dog’s ulcerative condition.

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.

Precipitous Declines in Northern Gulf of Mexico Invasive Lionfish Populations Following the Emergence of an Ulcerative Skin Disease

Invasive Indo-Pacific lionfish Pterois volitans/miles have become well-established in many western Atlantic marine habitats and regions. However, high densities and low genetic diversity could make their populations susceptible to disease. We examined changes in northern Gulf of Mexico (nGOM) lionfish populations following the emergence of an ulcerative skin disease in August 2017, when estimated disease prevalence was as high as 40%. Ulcerated female lionfish had 9% lower relative condition compared to non-ulcerated females. Changes in lionfish size composition indicated a potential recruitment failure in early summer 2018, when the proportion of new recruits declined by >80%. Remotely operated vehicle surveys during 2016–2018 indicated lionfish population density declined in 2018 by 75% on natural reefs. The strongest declines (77–79%) in lionfish density were on high-density (>25 lionfish per 100 m2) artificial reefs, which declined to similar levels as low-density (<15 lionfish per 100 m2) artificial reefs that had prior lionfish removals. Fisheries-dependent sampling indicated lionfish commercial spearfishing landings, commercial catch per unit effort (CPUE), and lionfish tournament CPUE also declined approximately 50% in 2018. Collectively, these results provide correlative evidence for density-dependent epizootic population control, have implications for managing lionfish and impacted native species, and improve our understanding of biological invasions.

Hemiarthroplasty in a patient with femoral neck fracture and pyoderma gangrenosum: a\xa0case report and review of the\xa0literature

BackgroundPyoderma gangrenosum is a rare ulcerating skin disease of unknown etiology, making its coincidence with orthopedic trauma a rare challenge. Patients are at risk of progression of the existing lesions and development of new lesions upon skin injury when surgical procedures are performed. To our knowledge, this is the first report in the literature of disease unrelated surgery during active pyoderma gangrenosum.Case presentationWe present a case of femoral neck fracture in a Caucasian patient with concurrent pyoderma gangrenosum localized in the axilla. Hemiarthroplasty was safely performed after disease activity was reduced with systemic corticosteroids. Tissue-protective wound closure was used together with perioperative corticosteroids and antibiotics. No signs of pyoderma gangrenosum developed at the surgical wound site, and the axillary lesions showed constant improvement until healing with scar tissue.ConclusionsIn our patient, the preoperative steroid treatment, perioperative antibiotics, and soft tissue protective surgical technique led to successful management of this rare coincidence.

Acute Lymphoblastic Leukemia in Childhood Following Pyoderma Gangrenosum

Pyoderma gangrenosum (PG) is a rare but serious ulcerating skin disease that occurs either idiopathically or associated with various systemic diseases and malignant tumors. Although the association of PG with myeloid malignant tumors is well known, their association with lymphoid malignant tumors, especially in children is extremely rare. We present here a case of PG in a 4-year and 4 months female child, diagnosed in the Pediatrics department, which had initially evolved well with oral corticosteroid therapy and a local dermocorticoid. The development was marked 7 months after stopping corticosteroid treatment by the occurrence of acute lymphoblastic leukemia. This case of PG is presented in the intention of increasing awareness of this uncommon condition with may occurring in association with haematological malignancy. PG may precede, develop concurrently with, or follow various conditions.

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.

El Ni\xf1o drives a widespread ulcerative skin disease outbreak in Galapagos marine fishes

Climate change increases local climatic variation and unpredictability, which can alter ecological interactions and trigger wildlife disease outbreaks. Here we describe an unprecedented multi-species outbreak of wild fish disease driven by a climate perturbation. The 2015–16 El Niño generated a +2.5 °C sea surface temperature anomaly in the Galapagos Islands lasting six months. This coincided with a novel ulcerative skin disease affecting 18 teleost species from 13 different families. Disease signs included scale loss and hemorrhagic ulcerated patches of skin, fin deterioration, lethargy, and erratic behavior. A bacterial culture isolated from skin lesions of two of the affected fish species was identified by sequencing of the 16S rRNA gene as a Rahnella spp. Disease prevalence rates were linearly correlated with density in three fish species. In January 2016, disease prevalence reached 51.1% in the ring-tailed damselfish Stegastes beebei (n = 570) and 18.7% in the king angelfish Holacanthus passer (n = 318), corresponding to 78% and 86% decreases in their populations relative to a 4.5-year baseline, respectively. We hypothesize that this outbreak was precipitated by the persistent warm temperatures and lack of planktonic productivity that characterize extreme El Niño events, which are predicted to increase in frequency with global warming.

The Vasculopathy of Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare autoimmune disease mainly characterized by muscle and skin involvement. Vasculopathy is considered central to the pathogenesis of the disease. The exact nature of vasculopathy is not yet understood but it is a complex process with both an inflammatory and a non-inflammatory, occlusive component. Impaired function of JDM vasculature includes immune complex deposition, altered expression of cell adhesion molecules predominantly inducing Th17 cell infiltration, and endothelial cell dysfunction. Development of vasculopathy is associated with the severe extra-muscular manifestations of JDM, such as gastrointestinal and cardiac manifestations, interstitial lung disease, ulcerative skin disease or development of calcinosis, and portends a poor prognosis. Correlation of histopathological findings, autoantibodies, and extensive diagnostic workup represent key elements to the early detection of vasculopathic features and early aggressive treatment. Monitoring of vasculopathy remains challenging due to the lack of non-invasive biomarkers. Current treatment approaches provide variable benefit, but better understanding of the essential pathogenic mechanisms should help lead to improved outcomes. Whilst acknowledging that evidence is limited, this review aims to describe the vasculopathy of JDM in the context of pathophysiology, clinical features, and treatment of disease.

First Report of an Emerging Ulcerative Skin Disease in Invasive Lionfish

An emerging ulcerative skin disease in invasive lionfish in Florida and Caribbean Sea is being tracked. Diseased lionfish were first reported in summer 2017 from the northern Gulf of Mexico with additional reports in 2018. Florida Fish and Wildlife Conservation Commission, University of Florida, and other fish health scientists are investigating this disease, but initial evaluations have not yet identified a cause. More advanced diagnostics are underway to better understand the factors causing this disease/syndrome and its potential to spread to other species. Researchers are also examining the lethal and chronic effects of this disease on individual fish, as well as its effect on lionfish populations, the lionfish fishery, and reef fish communities. Researchers and Extension Personnel (IFAS/SeaGrant) are asking stakeholders to report and document any ulcerated or otherwise diseased lionfish in FL and the Caribbean.

Pyoderma Gangrenosum: A Review for the Gastroenterologist.

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease of unknown etiology often associated with systemic inflammatory conditions, most commonly inflammatory bowel disease (IBD). The most common presentation of PG is spontaneous rapid formation of an extremely painful ulcer on the extremities, associated with significant morbidity and mortality. Rarely, PG can also occur as a chronic peristomal complication or as an acute postoperative complication of a surgical wound. The clinical course is unpredictable; it may not correlate with IBD activity and may even precede a diagnosis of IBD. Pyoderma gangrenosum is a diagnosis of exclusion. Treatment is challenging, often involving a variety of immunosuppressive therapies. This review aims to provide an update for the gastroenterologist on the pathogenesis, presentation, diagnosis, and management of PG, a rare complication of IBD.

Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies.

Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Small sample size was the main limitation. We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.

Hypoxia enhances secretion of matrix metalloproteinases in bovine dermal fibroblasts: an in vitro approach to bovine digital dermatitis

ABSTRACTDermal fibroblasts are of great importance in skin homeostasis. They are responsible for the synthesis and remodelling of extracellular proteins by the way of synthesis of some specific kind of Matrix Metalloproteinases (MMPs). Imbalance between MMPs and their tissue inhibitors (TIMPs) are known to involve ulcerative wounds in many tissues, including skin. In veterinary medicine, bovine digital dermatitis (BDD) is an ulcerative skin disorder of dairy cattle. To date, Koch’s postulate has not yet been fulfilled for the pathogenesis. In present study, we tested in vitro role of hypoxia if it evokes a response in MMP-1, MMP-2 and MMP-13 enzymes and their inhibitors in bovine dermal fibroblasts. Dermal fibroblasts were exposed to hypoxia in various time periods (6, 12 and 24 h). Immunoblotting revealed 6-, 12- and 24-h hypoxia, which resulted in 43.5%, 75% and 65% increase in MMP-1, 76%, 61% and 55% increase in MMP-2 and 80%, 78% and 55% increase in MMP-13 enzymes levels, respectively. We observed slight increases in TIMP-1 and TIMP-2 enzymes, but differences between treatment and control groups did not show any statistical significance. Our findings indicate that hypoxia induces MMP-1, MMP-2 and MMP-13 enzymes and may contribute to pathogenesis of BDD through in the development of in vivo lesions.

Oral Pyoderma Gangrenosum: Diagnosis, Treatment and Challenges: A Systematic Review.

Pyoderma gangrenosum (PG) is a distinctive ulcerative skin disorder of unknown etiology, associated with an underlying systemic disease in up to 70% of cases. The condition is characterized by the appearance of one or more necrotic ulcers with a ragged undermined violaceous border and surrounding erythema. Lesions are often initiated by minor trauma. The condition can affect any anatomical site, however the head and neck are rarely involved. Although the oral cavity is subject to recurrent minor trauma through everyday activities such as mastication and oral hygiene, as well as during dental treatment, oral lesions appear to be extremely rare. In an effort to provide a detailed explanation of the oral manifestations of PG, a systematic search was conducted using medical databases. A total of 20 cases of PG with oral involvement were reported in the English and French literature. The objectives of this article are to present the pertinent diagnostic criteria and to discuss the differential diagnosis and therapeutic modalities.

Effectiveness of rifampicin-streptomycin for treatment of Buruli ulcer: a systematic review.

Buruli ulcer (BU) disease is a chronic ulcerative skin disease caused by Mycobacterium ulcerans, which can lead to extensive destruction of the skin, soft tissues and occasionally of bones. Although several antibiotics have demonstrated bactericidal activity against M. ulcerans in vitro, no consensus on their clinical efficacy against M. ulcerans in humans has been reached. The objective of the systematic review was to examine the clinical effectiveness of various antibiotic regimens for the treatment of BUs. The current review considered trials that included patients of all ages with BUs. The current review considered trials that evaluated antibiotic regimens compared to no antibiotics or surgery in patients with BUs. The current review considered randomized and non-randomized controlled trials (RCTs). In the absence of RCTs, other research designs such as before and after trials and clinical trials with only an intervention arm were considered for inclusion in a narrative summary. The primary outcome of interest were the treatment success rates among the various antibiotics used. Secondary outcomes included changes in lesion size, recurrence of ulcers and incidence of adverse events. The search strategy aimed to find both published and unpublished trials. A three-step search strategy was utilized in this review and included English language trials published after 1990. A search across the major databases was conducted up to December 2014. Using the Joanna Briggs Institute (JBI) standardized appraisal tool, two reviewers independently assessed the methodological quality of the trials. A third independent reviewer was available to appraise trials if the two original reviewers disagreed in their assessments. There were no disagreements in findings between the two independent reviewers. Data were extracted using the standardized JBI data extraction instruments. Statistical pooling was not possible due to heterogeneity, hence results have been presented in the narrative form. Seven studies involving a total of 712 patients were included in the final review. Higher treatment success rates ranging from 96% to 100% at the six months follow-up were reported among patients treated with rifampicin-streptomycin for eight weeks (RS8) in two studies. Treatment success with rifampicin-streptomycin for 12 weeks, with surgery at the 12 weeks follow-up, was 91%. In the two studies that investigated the effect of rifampicin-streptomycin for two weeks followed by rifampicin-clarithromycin for six weeks and rifampicin-streptomycin for four weeks followed by rifampicin-clarithromycin for four weeks, treatment success was reported to be 93% and 91%, respectively, at the 12 months follow-up. A significant decrease in the median lesion size at the eight weeks follow-up was reported in patients who were treated with RS8, and a 10-30% decrease in lesion size was reported in those treated with RS12 at the four weeks follow-up. Treatment success and reduction in lesion size were higher in patients treated with RS8 in the only RCT that compared rifampicin-streptomycin for four weeks followed by rifampicin-clarithromycin for six weeks to RS8, and there was no difference in outcomes, which indicates that local preferences could dictate the treatment option. Evidence obtained from this systematic review indicates that surgery will remain necessary for some ulcers; however, detection of early lesions and treatment with antibiotics would have a greater impact on the control of M. ulcerans disease. Further large multicenter RCTs investigating the type and optimal duration of oral antibiotic treatment for patients with M. ulcerans disease are urgently needed.

Pathology of finfish and mud crabs Scylla serrata during a mortality event associated with a harbour development project in Port Curtis, Australia.

The objective of this study was to assess the extent and describe the nature of a multi-species marine finfish and crustacean disease event that occurred in Gladstone Harbour, Australia, 2011-2012. Finfish were examined for this study in January to April 2012 from sites where diseased animals were previously observed by the public. Gross abnormalities, including excessive skin and gill mucus, erythema, heavy ecto-parasitism, cutaneous ulceration, corneal opacity, and exophthalmos, were higher (25.5%) in finfish from Gladstone Harbour (n = 435) than in those from an undeveloped reference site, 250 km to the north (5.5%, n = 146, p < 0.0001). Microscopic abnormalities, especially non-infectious erosive to ulcerative dermatitis and internal parasitism, were more prevalent in fish from Gladstone Harbour (n = 34 of 36, prevalence = 94.4%) than in fish from the reference site (3 of 23, prevalence = 13.0% p < 0.0001). The prevalence of shell lesions was higher in mud crabs Scylla serrata sampled from Gladstone Harbour (270 of 718, prevalence = 37.5%) than from the reference site (21 of 153, prevalence = 13.7%; p < 0.0001). The significantly higher prevalence of ulcerative skin disease and parasitism in a range of species suggests affected animals were subjected to influences in Gladstone Harbour that were not present in the control sites. The disease epidemic coincided temporally and spatially with water quality changes caused by a harbour development project. The unique hydrology, geology, and industrial history of the harbour, the scope of the development of the project, and the failure of a bund wall built to retain dredge spoil sediment were important factors contributing to this epidemic.

Tricenter analysis of cofactors and comorbidity in patients with pyoderma gangrenosum

Pyoderma gangrenosum (PG) is a rare neutrophilic, ulcerative skin disease of largely unknown pathophysiology. In this study, potentially relevant cofactors and comorbidities in patients with PG from three dermatological wound care centers in Germany were evaluated. Of the 121 patients assessed, women (66.9%) were more frequently affected than men. Patient age ranged from 18 to 96 years (mean 59.8). Wound size varied from 1-600cm² (mean 65.6cm²), and the pain intensity was predominantly very high (VAS 1-10, mean 7). The lower legs were most commonly (71.9%) affected. Overall, 12 (9.9%) patients had inflammatory bowel disease (ulcerative colitis, 5.8%; Crohn's disease, 4.1%), 14.1% exhibited rheumatic comorbidities. Neoplasms were found in 20.6% of patients, with 6.6% classified as hematological and 14.0% as solid neoplasms. With respect to criteria for the metabolic syndrome, obesity was found in 69.4%, arterial hypertension in 57.9%, and diabetes mellitus in 33.9% of patients. The present data analysis confirms the association of PG with metabolic syndrome and neoplasms. In the future, these aspects should be included in the targeted diagnostic workup of patients with PG and subsequently treated in a timely fashion.

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes

Background/Aims: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. Methods: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). Results: The greatest levels of β-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (μg/μl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. Conclusion: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent.

Pyoderma gangrenosum in an abdominal surgical site: a case report

Pyoderma gangrenosum (PG) is an uncommon, ulcerative skin disease that is often associated with systemic diseases. Herein, we report a development of PG in a surgical site after cholecystectomy that was difficult to discriminate from surgical site infection. The patient was a 74-year-old man who had previously been diagnosed with myelodysplastic syndrome (MDS). Laparoscopic cholecystectomy was planned under diagnosis of cholecystolithiasis, but we converted to open cholecystectomy. The surgical wound was partially erythematous 4 days after surgery. In spite of opening the wound, cleansing it with sterile saline, and administration of antibiotics, inflammation spread with erosion. The clinical manifestations and histopathologic features of biopsy specimen indicated that diagnosis of PG associated with MDS was most likely. Administration of glucocorticoids made a rapid response of skin inflammation. The differential diagnosis of postoperative wound healing complications that were unresponsive to conventional wound local care and antibiotic therapy should include PG, especially in patients with systemic diseases such as MDS.