Characterization of microbiota and histology of cultured sea cucumber Isostichopus badionotus juveniles during an outbreak of skin ulceration syndrome.

Due to the dramatic reduction of sea cucumber Isostichopus badionotus populations in the Yucatan Peninsula by overfishing and poaching, aquaculture has been encouraged as an alternative to commercial catching and restoring wild populations. However, the scarcity of broodstock, the emergence of a new disease in the auricularia larvae stage, and the development of skin ulceration syndrome (SUS) in the culture have limited aquaculture development. This study presents the changes in the intestine and skin microbiota observed in early and advanced stages of SUS disease in cultured juvenile I. badionotus obtained during an outbreak in experimental culture through 16S rRNA gene sequencing and histological evidence. Our results showed inflammation in the intestines of juveniles at both stages of SUS. However, more severe tissue damage and the presence of bacterial clusters were detected only in the advanced stages of SUS. Differences in the composition and structure of the intestinal and skin bacterial community from early and advanced stages of SUS were detected, with more evident changes in the intestinal microbial communities. These findings suggest that SUS was not induced by a single pathogenic bacterium. Nevertheless, a decrease in the abundance of Vibrio and an increase in Halarcobacter (syn. Arcobacter) was observed, suggesting that these two bacterial groups could be keystone genera involved in SUS disease.

Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

Accuracy of sentinel node mapping in Marjolin ulcer: Comparison of three different injection techniques.

BACKGROUND: Marjolin ulcer is a specific type of squamous cell cancer that can benefit from the use of lymphoscintigraphy.The purpose of this study was to evaluate 3 different injection techniques for sentinel node biopsy in patients with Marjolin ulcer. METHODS: Forty-eight patients with Marjolin ulcer (27 male and 21 female) ranging in age from 24 to 85 years were included in our study. Intratumoral (IT), peritumoral (PT) and periscar (PS) tissue injections of radiotracer were done in 9, 10, and 29 patients respectively. Injections were done 2-4 h before surgery. Lymphoscintigraphy was done for mapping the lymphatic drainage. During surgery, lymphatic mapping and sentinel node biopsy was performed using a handheld gamma probe. After harvesting sentinel nodes, regional lymph node dissection was done. RESULT: Sentinel node detection rate was higher in the PS group as compared to the IT and PT groups (89.6% vs. 50% and 22.2%) respectively. False negative rate was 0%. Pathologically involved sentinel nodes were detected in 16% of the included patients of our study which led to management change. None of the patients with pathologically non-involved sentinel nodes developed regional lymph node recurrence. CONCLUSION: Lymphatic mapping and sentinel node biopsy is feasible in Marjolin ulcer with high detection rate and low false negative cases which by detection of regional lymph node involvement can potentially change the management of patients. Injection site may be an important factor influencing the success of the procedure and injection of the mapping material in the peri-scar normal skin proximal to the lesion is the best technique.

Febrile Ulceronecrotic Mucha-Habermann Disease Associated With Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature.

ABSTRACT: Mucha-Habermann disease (MHD) is an inflammatory skin disease characterized by polymorphous eruptions of erythematous, necrotic macules that have been reported for similarities to cutaneous T-cell lymphoma. Febrile ulceronecrotic MHD (FUMHD) represents a severe variant of MHD, marked by ulcers, hemorrhagic bullae, and systemic symptoms. Herein, we report a case of a severely atypical lymphomatoid expression of FUMHD associated with hemophagocytic lymphohistiocytosis (HLH). A previously healthy 21-year-old woman was admitted to the hospital with a rapidly progressive necrotic papular rash. Physical examination revealed right orbital swelling, bilateral hemorrhagic auricular bullae, and multiple ulcerative purpuric papulonodules on the trunk, face, and extremities. Biopsy indicated a dermal and subcutaneous infiltrate of atypical CD8 + lymphocytes with loss of CD5 and reduction in CD7 expression, along with features of lymphomatoid vasculitis. A diagnosis of a severely atypical lymphomatoid expression of FUMHD was made. The patient also met 7 of 9 HLH-2004 criteria, leading to a diagnosis of HLH. Positron emission tomography/computed tomography, flow cytometry, and rheumatologic workup were unremarkable. Treatment with an eight-week course of etoposide and dexamethasone for HLH led to rapid clinical improvement. Over time, her skin lesions regressed and eventually scabbed over to leave hyperpigmented scars, confirming the diagnosis of MHD. She has remained stable, off therapy for 4 years. Although potentially fatal, FUMHD often exhibits favorable outcomes and may resolve without recurrence, as in our patient. FUMHD should be considered in the differential diagnosis for patients presenting with cutaneous CD8 + necrotizing angiocentric lymphoproliferative disease complicated by HLH.

Treponema pallidum-induced prostaglandin E2 secretion in skin fibroblasts leads to neuronal hyperpolarization: A cause of painless ulcers.

BACKGROUND: Primary syphilis is characterized by painless ulcerative lesions in the genitalia, the aetiology of painless remains elusive. OBJECTIVES: To investigate the role of Treponema pallidum in painless ulcer of primary syphilis, and the mechanisms underlying painless ulcers caused by T. pallidum. METHODS: An experimental rabbit model of primary syphilis was established to investigate its effects on peripheral nerve tissues. Human skin fibroblasts were used to examine the role of T. pallidum in modulating neurotransmitters associated with pain and to explore the signalling pathways related to neurotransmitter secretion by T. pallidum in vitro. RESULTS: Treponema pallidum infection did not directly lead to neuronal damage or interfere with the neuronal resting potential. Instead, it facilitated the secretion of prostaglandin E2 (PGE2) through endoplasmic reticulum stress in both rabbit and human skin fibroblasts, and upregulation of PGE2 induced the hyperpolarization of neurones. Moreover, the IRE1α/COX-2 signalling pathway was identified as the underlying mechanism by which T. pallidum induced the production of PGE2 in human skin fibroblasts. CONCLUSION: Treponema pallidum promotes PGE2 secretion in skin fibroblasts, leading to the excitation of neuronal hyperpolarization and potentially contributing to the pathogenesis of painless ulcers in syphilis.

Kodamaea ohmeri Leg Skin Ulcer Infection in an Immunocompetent Patient: A Case Report.

INTRODUCTION: Kodamaea ohmeri is an emerging fungus recognised as an important pathogen in immunocompromised hosts, responsible for life-threatening infections. CASE PRESENTATION: We describe a case of a 69-year-old immunocompetent man with a long history of leg skin ulcers infected by K. ohmeri. This is the first case of leg wounds infected by K. ohmeri in an immunocompetent patient. The infection was successfully treated with voriconazole 200 mg daily. CONCLUSION: Though rare, K. ohmeri should be considered in patients with skin ulcers that are poorly responsive to medical treatment, even if not immunocompromised.

Macroscopic tumor dimension, sentinel lymph node outcome, and survival analysis among cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is characterized by a high risk of metastasis to distant organs and a substantial mortality rate. For planning treatment and assessing outcomes, the Breslow micrometric measurement is critical. The tumor macroscopic dimension is not considered a prognostic parameter in cutaneous melanoma, although there are studies showing that tumor size is an independent prognostic factor for melanoma-specific survival. Therefore, this study aimed to evaluate the macroscopic dimension of melanoma and other known prognostic factors (i.e., Breslow index, mitoses, regression, and ulceration) as predictors of sentinel lymph node outcome and survival outcome. METHODS: We performed a retrospective cross-sectional study of 227 melanoma lesions subjected to sentinel lymph node biopsy at two Brazilian referral centers. RESULTS: On univariate analysis, there was a statistically significant correlation between the largest macroscopic tumor dimension and the sentinel lymph node result (P = 0.001); however, on multivariate analysis considering all evaluated parameters, there was no significant difference between the sentinel lymph node result and the tumor macroscopic dimension (P = 0.2689). Regarding melanoma-specific survival, the macroscopic dimension showed no significant correlation (P = 0.4632) in contrast to Breslow's dimension (P < 0.0001). CONCLUSION: The Breslow thickness was the only significant factor related to both the sentinel lymph node outcome and melanoma specific survival among the evaluated variables.

Expression and Correlation of HER2/P53/VEGF in Marjolin's Ulcer.

Marjolin's ulcer is described as malignant lesions developed in the injured skin, which can cause several kinds of malignancies. Our results showed that no HER2 but p53 was detected in Majorlin's ulcer samples. Meanwhile, by statistical analysis, we found that the positive rate of p53 in Majorlin's ulcer samples was associated with the pathological type of ulcer canceration and degree of tumor differentiation. The positive expression rate of vascular endothelial growth factor (VEGF) was 62.5% in poorly differentiated squamous cell carcinoma (SCC), 39.4% in moderately differentiated SCC, and 66.7% in well-differentiated SCC, respectively. Furthermore, some cases of Majorlin's ulcer with positive P53 were negative for VEGF, while some cases with positive VEGF were negative for P53. Image superposition showed that VEGF expression was absent or minimal in p53-positive cases. However, P53 was not expressed or rarely expressed in VEGF-positive cases. Our results of this study will suggest that P53 can be used as the mark of Marjolin's ulcer differentiation, and there may be some interaction between P53 and VEGF in Marjolin's ulcer. The regulation of microenvironment in the oncogenesis, progression, and differentiation of Marjolin's ulcer is complex and needs further study.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

[Marjolin's ulcer associated with verrucous carcinoma in an immunocompromised patient]. / Úlcera de Marjolin asociada a carcinoma verrugoso en paciente inmunocomprometido.

Background: Marjolin's ulcer is the malignant degeneration of any chronic wound, with a latency period from tissue injury to variable malignant transformation that may occur up to 30 years later. Among the associated neoplasms, squamous cell carcinoma (SCC) is the predominant lineage in up to 71% of cases. The verrucous carcinoma variant has been estimated to have a low presentation, being described in the literature as 2% of all SCC and reported anecdotally in immunosuppressed patients, which justifies the objective of this publication. Clinical case: 65-year-old female patient with a history of being a carrier of human immunodeficiency virus (HIV) infection, who presented a verrucous carcinoma associated to a Marjolin ulcer secondary to herpes zoster and infection of soft tissues in the right leg, with a latency period of 10 years from the initial infectious process to histopathological confirmation. Conclusions: The finding of a verrucous carcinoma on a Marjolin ulcer has been little described in literature, with a lower incidence in the context of a patient with a history of being a carrier of HIV infection, finding 7 case reports, the oldest from 1998. For this reason, it is important to have diagnostic suspicion, to carry out an adequate study protocol and always making clinical-pathological correlation, in order to establish timely and individualized treatment.

Introducción: la úlcera de Marjolin es la degeneración maligna de cualquier herida crónica, con un periodo de latencia desde la lesión tisular a la transformación maligna variable que puede presentarse hasta 30 años después. De las neoplasias asociadas, el carcinoma espinocelular es la estirpe predominante hasta en 71% de los casos. La variante de carcinoma verrugoso se ha estimado con una presentación baja, pues ha sido descrito en la literatura como el 2% de todos los carcinomas espinocelulares y reportado de manera anecdótica en pacientes inmunosuprimidos, lo que justifica el objetivo de esta publicación. Caso clínico: mujer de 65 años con el antecedente de ser portadora de infección por virus de inmunodeficiencia humana (VIH), que presentó un carcinoma verrugoso asociado a una úlcera de Marjolin secundaria a herpes zóster e infección de tejidos blandos en pierna derecha, con un periodo de latencia de 10 años desde el proceso infeccioso inicial hasta la confirmación histopatológica. Conclusiones: el hallazgo de un carcinoma verrugoso asentado sobre una úlcera de Marjolin ha sido poco descrito en la literatura, con una menor incidencia en el contexto de un paciente con antecedente de ser portador de infección por VIH, ante lo cual encontramos 7 reportes de caso, el más antiguo de 1998. Por este motivo es importante contar con la sospecha diagnóstica, para poder hacer un protocolo de estudio adecuado y siempre haciendo correlación clínico-patológica, con la finalidad de instaurar un tratamiento oportuno e individualizado.

"Hurricane-like" Presentation of a Recurrent Marjolin's Ulcer in a Young Female.

Marjolin's ulcer (MU) with rapid progression and multiple distant metastases is rare. We report a case of an MU of the thigh developing in a postburn scar, which after successful R0 resection developed multiple bony and visceral metastasis to femur, vertebra, skull, lung, and liver within 3 months of excision. We highlight the "hurricane-like" recurrence in an MU, which is unusual for the metachronous disease. We stress that MUs, unlike conventional wisdom, need a thorough metastatic workup at presentation, and prognostication of a possible rapidly progressive course after surgery which may lead to grave prognosis and mortality.

Diagnosis and management of systemic sclerosis-related calcinosis.

INTRODUCTION: Calcinosis is common in patients with systemic sclerosis (SSc) and refers to the sub-epidermal deposition of calcium salts in the skin. SSc-related calcinosis is associated with significant morbidity, including through cutaneous ulceration and predisposition to become infected. AREAS COVERED: After briefly addressing aetiopathogenesis, we describe the clinical burden of SSc-associated calcinosis and provide a structured and practical clinical approach to diagnosis and assessment, including discussion of the role of different imaging modalities. The multi-faceted treatment of SSc-associated calcinosis is presented under three broad headings of 'general measures,' and 'medical treatment' and 'surgical treatment.' We adopted a narrative approach to identify relevant manuscripts to inform our review. EXPERT OPINION: SSc-related calcinosis is an area of major unmet clinical need and for too long has been a neglected area of research. Safe and effective treatments are badly needed to improve patient quality of life and outcomes. To facilitate future clinical trials, we require increased understanding of pathogenesis (to inform selection of potential targeted therapies) and reliable outcome measures, including those which will measure the impact and severity of calcinosis from the patient perspective. International collaborative research is ongoing to develop outcome measures and treatments for this potentially devastating complication of SSc.

The Effects of Skin Temperature Changes on the Integrity of Skin Tissue: A Systematic Review.

OBJECTIVE: To determine whether changes in skin temperature can affect the integrity of skin. METHODOLOGY: The authors conducted a systematic literature search as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. They searched the CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, MEDLINE Complete, Academic Search Ultimate, and HyDi databases for articles examining the effects of skin temperature on skin integrity published through April 2020. Two independent reviewers scored the methodologic quality of the 13 included studies. RESULTS: Only 11 studies were included in the qualitative analysis, as the other two articles had a critical risk of bias. There is strong evidence to indicate that an increase in skin temperature leads to changes in skin structure and function. However, ulcer formation was more affected by intrinsic and extrinsic factors, rather than by temperature alone. CONCLUSION: Further high-quality randomized controlled trials are required to investigate the direct effect of skin temperature on ulceration.

Neuropathic ulcers in leprosy: clinical features, diagnosis and treatment.

Leprosy is a neglected disease caused by Mycobacterium leprae and Mycobacterium lepromatosis, and is related to significant disabilities resulting from the neural damage generated by this mycobacteria. Neuropathic ulcers-lesions that can appear at the plantar and extra-plantar levels-are one such disability, and diagnosis requires an adequate dermatological, neurological and microbiological evaluation. The treatment of these lesions is based on a multidisciplinary approach that includes debridement of the necrotic tissue, controlling infections, reducing pressure areas, optimising blood flow, and nerve decompression. This review aims to describe the clinical features, diagnostic methods and treatment of neuropathic ulcers in leprosy. The diagnostic methods and medical management used in leprosy ulcers are based on those used for diabetic foot. This requires radical change as these diseases are immunologically and physiologically very different.