Tropical Ulcer Research Articles

Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans.

Mycolactone is the exotoxin produced by Mycobacterium ulcerans and is the virulence factor behind the neglected tropical disease Buruli ulcer. The toxin has a broad spectrum of biological effects within the host organism, stemming from its interaction with at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. Although it has been shown that the toxin can passively permeate into host cells, it is clearly lipophilic. Association with lipid carriers would have substantial implications for the toxin’s distribution within a host organism, delivery to cellular targets, diagnostic susceptibility, and mechanisms of pathogenicity. Yet the toxin’s interactions with, and distribution in, lipids are unknown. Herein we have used coarse-grained molecular dynamics simulations, guided by all-atom simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties. The computed water-octanol partition coefficient indicates that mycolactone prefers to be in an organic phase rather than in an aqueous environment. Our results show that in a solvated membrane environment the exotoxin mainly localizes in the water-membrane interface, with a preference for the glycerol moiety of lipids, consistent with the reported studies that found it in lipid extracts of the cell. The calculated association constant to the model membrane is similar to the reported association constant for Wiskott-Aldrich syndrome protein. Mycolactone is shown to modify the physical properties of membranes, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and promotes inter-mixing of domains. This property has implications for the toxin’s cellular access, T-cell immunosuppression, and therapeutic potential.

Tropical ulcer plant treatments used by Papua New Guinea's Apsokok nomads

Ethnopharmacological relevanceThe tropical ulcer is a debilitating bacterial infection that is common in Papua New Guinea. Deploying healthcare infrastructure to remote and inaccessible rainforest locations is not practical, therefore local plants may be the best treatment option. Here we present an ethnobotanical survey of the tropical ulcer plant medicines used by the semi-nomadic Apsokok who roam the remote central mountains of Papua New Guinea's West New Britain Province. In vitro biological activity in assays relevant to tropical ulcer wound healing is also presented. Materials and methodsFocus groups and semi-structured interviews were used to acquire information on the uses of plants, vouchers of which were identified by comparison with authentic herbarium specimens. Antibacterial disc diffusion assays with Staphylococcus aureus and Fusobacterium ulcerans, MMP-9 enzyme inhibition and dermal fibroblast stimulation assays were carried out on plant saps and aqueous extracts of plant material. LC-MS was used to identify known plant metabolites. ResultsThe ethnobotanical survey identified sixteen species that were used to treat tropical ulcers, all of which were applied topically. A subset of twelve species were investigated further in vitro. Four species produced zones of inhibition with S. aureus, all 12 species provided low level inhibition of MMP-9 and 8 species stimulated dermal fibroblast proliferation, although cytotoxicity occurred at higher concentrations. The extract of Homalium foetidum Benth. inhibited S. aureus and MMP-9 while at lower sub-cytotoxic concentrations stimulated fibroblast proliferation. Trans-3-O-p-coumaroylquinic acid cis-3-O-p-coumaroylquinic acid were detected in the aqueous extract of H. foetidum. ConclusionsTopical application of plant saps to wounds results in very high localised concentrations of plant metabolites which is likely to result in inhibition of MMP proteases. H. foetidum is a candidate plant for tropical ulcer treatment in remote areas.

Draft Genome Sequence of Mycobacterium ulcerans S4018 Isolated from a Patient with an Active Buruli Ulcer in Benin, Africa

ABSTRACTCurrently, there are only two publicly available genomes of Mycobacterium ulcerans—the causative agent of the neglected, but devastating, tropical disease Buruli ulcer. Here, we report the draft genome sequence of isolate S4018, recovered from an active cutaneous lesion of a patient with Buruli ulcer in Benin, Africa.

Sticky swinging arm dynamics: studies of an acyl carrier protein domain from the mycolactone polyketide synthase.

Type I modular polyketide synthases (PKSs) produce polyketide natural products by passing a growing acyl substrate chain between a series of enzyme domains housed within a gigantic multifunctional polypeptide assembly. Throughout each round of chain extension and modification reactions, the substrate stays covalently linked to an acyl carrier protein (ACP) domain. In the present study we report on the solution structure and dynamics of an ACP domain excised from MLSA2, module 9 of the PKS system that constructs the macrolactone ring of the toxin mycolactone, cause of the tropical disease Buruli ulcer. After modification of apo ACP with 4'-phosphopantetheine (Ppant) to create the holo form, (15)N nuclear spin relaxation and paramagnetic relaxation enhancement (PRE) experiments suggest that the prosthetic group swings freely. The minimal chemical shift perturbations displayed by Ppant-attached C3 and C4 acyl chains imply that these substrate-mimics remain exposed to solvent at the end of a flexible Ppant arm. By contrast, hexanoyl and octanoyl chains yield much larger chemical shift perturbations, indicating that they interact with the surface of the domain. The solution structure of octanoyl-ACP shows the Ppant arm bending to allow the acyl chain to nestle into a nonpolar pocket, whereas the prosthetic group itself remains largely solvent exposed. Although the highly reduced octanoyl group is not a natural substrate for the ACP from MLSA2, similar presentation modes would permit partner enzyme domains to recognize an acyl group while it is bound to the surface of its carrier protein, allowing simultaneous interactions with both the substrate and the ACP.

The diagnostic challenge of mapping elephantiasis in the Tigray region of northern Ethiopia.

In Ethiopia, lymphatic filariasis and podoconiosis are the two neglected tropical diseases planned to be mapped together within the recently launched Ethiopian neglected tropical diseases master plan (2013-2015). However, other disorders cause tropical lymphedema, and this report aims to identify clinical epidemiological aspects of limb swelling in northern Ethiopia and to provide an algorithm orienting the clinical diagnosis. Medical records of patients with lower limb elephantiasis attending the Italian Dermatological Centre of Mekele, Tigray capital city, over a 4-year period (2005-2009) were retrospectively analyzed. Nine variables were collected from the charts comprising demographic data, job, origin, literacy, clinical, histopathologic, microscopic, and cultural findings. Over a total of 511 patients, lymphedema resulted from trauma (40.7%), chronic venous insufficiency (12.5%), deep mycoses (10.8%), lymphatic filariasis (9.2%), elephantiasis nostras verrucosa (7.0%), tropical ulcer (6.3%), leprosy (4.9%), recurrent infections (3.1%), podoconiosis (1.8%), tuberculosis (1.0%), malignancy (1.3%), Kaposi's sarcoma (1.0%), leishmaniasis (0.2%), and neurofibromatosis (0.2%). Advanced-stage elephantiasis, chronic osteomyelitis, and podoconiosis not previously reported in Tigray were observed. Further epidemiological investigation and training programs addressed to healthcare providers at the peripheral level are needed to detect elephantiasis early, prevent disabilities, and improve patients' quality of life.

Medicinal plants of Papua New Guinea's Miu speaking population and a focus on their use of plant–slaked lime mixtures

Ethnopharmacological relevanceHere we present the results of an ethnobotanical survey of the medicinal plants used by the Miu, a virtually unresearched ethnolinguistic group who live in the mountainous interior of Papua New Guinea's West New Britain Province. We compare the findings for those previously reported for the neighbouring inland Kaulong speaking population. Three species, Trema orientalis, Spondias dulcis and Ficus botryocarpa are used in combination with locally prepared slaked lime to produce intensely coloured mixtures which are applied to dermatological infections. Their effects on dermal fibroblast viability with and without slaked lime are examined. The sap of F. botryocarpa which is used to treat tropical ulcers was examined further with assays relevant to wound healing. Materials and methodsFocus groups and semi-structured interviews were used to acquire information on the uses of plants, vouchers of which were collected and identified by comparison with authentic herbarium specimens. LC–MS and NMR were used to identify chemical components. Cell viability assays were used to examine the effects of added slaked lime on dermal fibroblasts. For the sap of F. botryocarpa, fibroblast stimulation assays and antibacterial growth inhibition with Bacillus subtilis were carried out. ResultsThe survey identified 33 plants and one fungal species, and clear differences with the inland Kaulong group despite their close proximity. Added slaked lime does not greatly increase the cytotoxicity of plant material towards dermal fibroblasts. The sap of F. botryocarpa contains the alkaloid ficuseptine as a single major component and displays antibacterial activity. ConclusionsThe results demonstrate the potential for variation in medicinal plant use amongst Papua New Guinea's numerous language groups. The addition of slaked lime to plant material does not appear to present a concern for wound healing in the amounts used. The sap of F. botryocarpa displays antibacterial activity at concentrations that would occur at the wound surface and could be used as a highly accessible alternative to conventional antiseptics for remote communities in Papua New Guinea.

Tropical leg ulcers in children: more than yaws.

The management of yaws has changed in recent years. Mass treatment with oral azithromycin has replaced intramuscular benzathine benzylpenicillin. Treponemal and non-treponemal serology (equivalent to TPHA and RPR) point-of-care blood testing is now available. In addition, recent studies in yaws endemic regions have shown that a significant number of leg ulcers in children which are clinically suggestive of yaws are caused by Haemophilus ducreyi. It is noteworthy that the World Health Organization has also set the ambitious goal to eliminate yaws by 2020.

Contribución al estudio de la blastomicosis

El estudio de la Blastomícosís ha adquirido importancia, en razón de que en estos últimos tiempos se ha señalado la gran discusión de la dolencia, pues, ubicada su localización geográfica en el corazón de la América tropical, ofrece en Bolivia, Brasil y Perú el mayor número de ejemplares clínicos, y es tanto más importante su conocimiento para nosotros, en razón de su caracterización que ha dado fundamento para separar del grupo de úlceras tropicales, conocidas con el nombre vulgar de Espundia, un conjunto de casos clínicos en los que no es hallaba la leishmania productora, y en los cuales el Dr. E. ESCOMEL encontró en 1914, por primera vez en el Perú, un hongo del género Blastomiceto.

Tropical Ulcer on a Human Tibia from 5000 Years Ago in Northern Italy

AbstractThe term tropical ulcer, as applied to bone pathology, describes the specific pathologic phenomenon of the presence of a well‐defined osteomatous shelf formation on the anteromedial aspect of the tibia. Despite the appellation ‘tropical,’ this pathology is not geographically limited to tropical regions, although it has not previously been reported from continental Europe. Observations of a 4583 BP burial from the Tanaro River area of Northern Italy represent the first such case. Dating of the site to the time of climate change at the end of the first Glacial suggests that hot–warm, humid conditions may have allowed the occurrence of this bone pathology, the first observed in continental Europe. A second explanation is the possible migration of an individual to Italy from an area that is more conventionally considered tropical. Copyright © 2013 John Wiley & Sons, Ltd.

The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward.

The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward.

A traumatized human papillomavirus lesion mimics a chronic tropical ulcer

International Journal of DermatologyVolume 53, Issue 2 p. e90-e92 Correspondence A traumatized human papillomavirus lesion mimics a chronic tropical ulcer Delwar Hossain DD, Delwar Hossain DD Department of Dermatology and Venereology, University of Science and Technology Chittagong, Chittagong, Bangladesh E-mail: [email protected]Search for more papers by this author Delwar Hossain DD, Delwar Hossain DD Department of Dermatology and Venereology, University of Science and Technology Chittagong, Chittagong, Bangladesh E-mail: [email protected]Search for more papers by this author First published: 14 March 2013 https://doi.org/10.1111/j.1365-4632.2012.05614.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume53, Issue2February 2014Pages e90-e92 RelatedInformation

A Review on Biology, Epidemiology and Public Health Significance of Leishmaniasis

Leishmaniasis is a major vector-borne disease caused by obligate intramacrophage protozoa of the genus Leishmania, and transmitted by the bite of phlebotomine female sand flies of the genera Phlebotomus and Lutzomyia, in the old and new worlds, respectively. Among 20 well-recognized Leishmania species known to infect humans, 18 have zoonotic nature, which include agents of visceral, cutaneous, and mucocutaneous forms of the disease, in both the old and new worlds. Currently, leishmaniasis show a wider geographic distribution and increased global incidence. Environmental, demographic and human behaviors contribute to the changing landscape for zoonotic cutaneous and visceral leishmaniasis. The primary reservoir hosts of Leishmania are sylvatic mammals such as forest rodents, hyraxes and wild canids, and dogs are the most important species among domesticated animals in the epidemiology of this disease. These parasites have two basic life cycle stages: one extracellular stage within the invertebrate host (phlebotomine sand fly), and one intracellular stage within a vertebrate host. Co-infection with HIV intensifies the burden of visceral and cutaneous leishmaniasis by causing severe forms and more difficult to manage. The disease is endemic to Ethiopia, and the clinical signs are not pathognomic. The visceral form (Kala-azar) may be confused with other similar conditions such as malaria, tropical splenomegaly, schistosomiasis, milliary tuberculosis, and brucellosis. Similarly, cutaneous leishmaniasis should be differentiated from disease like tropical ulcers, impetigo and leprosy. There are several methods of laboratory diagnosis of leishmaniasis, including parasitological, immunological and molecular. Different forms of treatments are available including oral, parenteral, and topical medications such as pentavalent antimonials, liposomal amphotericin B, miltefosine and paromomycin. Methods of control are largely limited to destruction of animal reservoirs, treatment of infected humans, and management of sand fly populations. Development of an effective vaccine against leishmaniasis has been largely unsuccessful and hinders its prevention.

PCR Typing of Mycobacterium ulcerans Lineages Based on Large Sequence Polymorphisms

Genetic fine typing of Mycobacterium ulcerans, the causative agent of the neglected tropical disease Buruli ulcer, has long been hampered by the remarkable genetic homogeneity of patient isolates. However, large sequence polymorphisms (LSPs), mainly originating from insertional-deletional genomic events, allow the differentiation between major lineages of M. ulcerans and other mycolactone producing mycobacteria (MPMs). Here, we describe an LSP-based rapid PCR typing scheme for these mycobacteria. Application of this approach to a selection of mycobacterial strains isolated from Buruli ulcer patients in Japan shows that they belong to the M. ulcerans Asian haplotype.

Medicinal plants potential and use by pastoral and agro-pastoral communities in Erer Valley of Babile Wereda, Eastern Ethiopia

BackgroundEthiopian plants have shown remarkably effective medicinal values for many human and livestock ailments. Some research results are found on medicinal plants of the south, south west, central, north and north western parts of Ethiopia. However, there is lack of data that quantitatively assesses the resource potential and the indigenous knowledge on use and management of medicinal plants in eastern Ethiopia. The main thrust of the present ethnobotanical study centres around the potential and use of traditional medicinal plants by pastoral and agro-pastoral communities in Babile Wereda (district) of eastern Ethiopia. The results can be used for setting up of conservation priorities, preservation of local biocultural knowledge with sustainable use and development of the resource.Materials and methodsFifty systematically selected informants including fifteen traditional herbalists (as key informants) participated in the study. Semi-structured interviews, discussions and guided field walk constituted the main data collection methods. Techniques of preference ranking, factor of informant consensus and Spearman rank correlation test were employed in data analysis. Medicinal plant specimens were collected, identified and kept at the National Herbarium (ETH) of Addis Ababa University and Haramaya University Herbarium.ResultsFifty-one traditional medicinal plant species in 39 genera and 28 families were recorded, constituting 37% shrubs, 29% trees, 26% herbs, 6% climbers and 2% root parasites. Leaves contributed to 35.3% of the preparations, roots (18.8%) and lower proportions for other parts. Formulations recorded added to 133 remedies for 54 human ailments, in addition to some used in vector control. The majority of remedies were the juice of single species, mixtures being generally infrequent. Aloe pirottae, Azadirachta indica and Hydnora johannis were the most cited and preferred species. Aloe pirottae, a species endemic to Ethiopia, is valued as a remedy for malaria, tropical ulcer, gastro-intestinal parasites, gallstone, eye diseases and snake bite. The jel extracted from dried and ground plant material, called SIBRI (Oromo language), was acclaimed as a cleaner of the human colon. Concoction made from leaf, seed and flower of Azadirachta indica was given for treatment of malaria, fungal infections and intestinal worms. Root preparations from Hydnora johannis were prescribed as remedy for diarrhoea, haemorrhage, wound and painful body swelling, locally called GOFLA (Oromo language).ConclusionsThe study documented many well known and effective medicinal species of relevance for human healthcare, including for the treatment of malaria which is rampant in the area as it is in many parts of Ethiopia. This underscores the importance of the traditional medicinal plants for the people living in the area and the potential of the resource for development. Consequently, the study area deserves urgent conservation priority coupled with mechanisms for the protection of the associated indigenous medical lore as well as development and effective use of the medicinal plant resource.

On the origin of Mycobacterium ulcerans, the causative agent of Buruli ulcer

BackgroundMycobacterium ulcerans is an unusual bacterial pathogen with elusive origins. While closely related to the aquatic dwelling M. marinum, M. ulcerans has evolved the ability to produce the immunosuppressive polyketide toxin mycolactone and cause the neglected tropical disease Buruli ulcer. Other mycolactone-producing mycobacteria (MPM) have been identified in fish and frogs and given distinct species designations (M. pseudoshottsii, M. shinshuense, M. liflandii and M. marinum), however the evolution of M. ulcerans and its relationship to other MPM has not been defined. Here we report the comparative analysis of whole genome sequences from 30 MPM and five M. marinum.ResultsA high-resolution phylogeny based on genome-wide single nucleotide polymorphisms (SNPs) showed that M. ulcerans and all other MPM represent a single clonal group that evolved from a common M. marinum progenitor. The emergence of the MPM was driven by the acquisition of the pMUM plasmid encoding genes for the biosynthesis of mycolactones. This change was accompanied by the loss of at least 185 genes, with a significant overrepresentation of genes associated with cell wall functions. Cell wall associated genes also showed evidence of substantial adaptive selection, suggesting cell wall remodeling has been critical for the survival of MPM. Fine-grain analysis of the MPM complex revealed at least three distinct lineages, one of which comprised a highly clonal group, responsible for Buruli ulcer in Africa and Australia. This indicates relatively recent transfer of M. ulcerans between these continents, which represent the vast majority of the global Buruli ulcer burden. Our data provide SNPs and gene sequences that can differentiate M. ulcerans lineages, suitable for use in the diagnosis and surveillance of Buruli ulcer.ConclusionsM. ulcerans and all mycolactone-producing mycobacteria are specialized variants of a common Mycobacterium marinum progenitor that have adapted to live in restricted environments. Examination of genes lost or retained and now under selective pressure suggests these environments might be aerobic, and extracellular, where slow growth, production of an immune suppressor, cell wall remodeling, loss or modification of cell wall antigens, and biofilm-forming ability provide a survival advantage. These insights will guide our efforts to find the elusive reservoir(s) of M. ulcerans and to understand transmission of Buruli ulcer.

Comparative ethnobotany and in-the-field antibacterial testing of medicinal plants used by the Bulu and inland Kaulong of Papua New Guinea

Ethnopharmacological relevanceThe island of New Britain in Papua New Guinea is an area of great floristic and cultural diversity that has received little attention from ethnobotanists. Here we present the results of a comparative medicinal ethnobotanical survey of the Bulu and inland Kaulong; two distinct people groups inhabiting lowland rainforest on different sides of the island. A high proportion of species are used in the treatment of bacterial infections and plants with antibacterial activity were identified in the field using a specially developed antibacterial assay kit. Follow up testing with human pathogens was used to evaluate active plant material in more detail. Materials and methodsRapid appraisal techniques were used to survey both people groups with all data corroborated by three or more separate sources. Plants from both groups were tested in-the-field with a portable antibacterial test kit based on the agar diffusion assay, using a pressure cooker to sterilise glassware and media. Follow up laboratory based tests were carried out using standardised agar dilution protocols for drug resistant and drug sensitive strains of Staphylococcus aureus and Streptococcus pneumoniae. ResultsWe find surprisingly little overlap in the plant species used by the two people groups with only 1 out of 70 species used for the same purpose. There is also a difference in emphasis in the conditions treated with 53% of Kaulong medicinal plants dedicated to treating tropical ulcers compared with only 8% of in the Bulu group. In-the-field testing identified Garcinia dulcis bark (a Kaulong tropical ulcer treatment) to have antibacterial activity and follow up tests against a drug resistant strain of Staphylococcus aureus (a pathogen implicated in tropical ulcer pathogenesis) revealed the crude bark extract to be potently active with an MIC of just 1mg/ml. ConclusionsThe results demonstrate extreme differences in medicinal plant use between two people groups living a mere 100 km apart and suggests the two medicinal plant systems have developed in isolation from one another. In-the-field antibacterial testing of plant extracts was found to be a valuable technique that enabled early identification of active plant material.

Secondary Buruli Ulcer Skin Lesions Emerging Several Months after Completion of Chemotherapy: Paradoxical Reaction or Evidence for Immune Protection?

BackgroundThe neglected tropical disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is an infection of the subcutaneous tissue leading to chronic ulcerative skin lesions. Histopathological features are progressive tissue necrosis, extracellular clusters of acid fast bacilli (AFB) and poor inflammatory responses at the site of infection. After the recommended eight weeks standard treatment with rifampicin and streptomycin, a reversal of the local immunosuppression caused by the macrolide toxin mycolactone of M. ulcerans is observed.Methodology/Principal FindingsWe have conducted a detailed histopathological and immunohistochemical analysis of tissue specimens from two patients developing multiple new skin lesions 12 to 409 days after completion of antibiotic treatment. Lesions exhibited characteristic histopathological hallmarks of Buruli ulcer and AFB with degenerated appearance were found in several of them. However, other than in active disease, lesions contained massive leukocyte infiltrates including large B-cell clusters, as typically found in cured lesions.Conclusion/SignificanceOur histopathological findings demonstrate that the skin lesions emerging several months after completion of antibiotic treatment were associated with M. ulcerans infection. During antibiotic therapy of Buruli ulcer development of new skin lesions may be caused by immune response-mediated paradoxical reactions. These seem to be triggered by mycobacterial antigens and immunostimulators released from clinically unrecognized bacterial foci. However, in particular the lesions that appeared more than one year after completion of antibiotic treatment may have been associated with new infection foci resolved by immune responses primed by the successful treatment of the initial lesion.

Klinisch relevante Differenzialdiagnosen

Approximately one quarter of all patients with leg ulcers do not have a "vascular" ulcer, i.e. an ulcer of venous, mixed venous-arterial, or arterial origin. The differential diagnosis encompasses approximately 70 entities, amongst a selection of particular clinical relevance. Martorell hypertensive-ischemic leg ulcer and its two "imitators" pyoderma gangrenosum and necrotizing vasculitides of the skin, necrotic skin infections (e.g., ecthyma, tropical ulcer, and others), chronic wounds caused by physical trauma (contusion (deep dissecting hematoma), radiotherapy or cryotherapy of skin cancers at the leg), leg ulcers in the context of congenital diseases (e. g., Klinefelter syndrome or sickle cell anemia), skin ulcers caused by medical toxicity (hydroxyurea, anagrelide, methotrexate), and last not least ulcerating skin cancer at the legs, primary or secondary in an area of chronic inflammation. Clinical presentations and a pragmatical algorhythm to diagnosis and treatment of these entities are discussed.

Skeletal Manifestations of Skin Ulcer in the Lower Leg

ABSTRACTSkin ulcers of the lower leg are known to cause both destructive and, more commonly, bone‐forming lesions. Typically, bone‐forming lesions in this disorder have clearly defined margins although there may be extensive reactive bone formation involving much or all of the adjacent diaphysis. These lesions are best described in patients from tropical areas, and in these environmental contexts, these are known as tropical ulcers, but leg ulcers can be caused by a variety of diseases and conditions, of which vascular insufficiency plays an important role among the elderly. The lesions are important clinically because of the disability associated with the ulcer and because of complications that can develop including osteomyelitis and cancer. In most cases, the bone lesions caused by ulcer are easily diagnosed in archaeological human skeletal remains and provide some insight into the prevalence of this disorder in antiquity.In this paper, we review the gross and radiological manifestations of bone lesions resulting from overlying skin ulcer in tibiae of 13 cases including archaeological and modern medically documented skeletons. In two of the cases, there is medical documentation regarding the presence of a chronic ulcer on the lower leg. The objectives of this paper were to explore the diversity of bone lesions associated with ulcers of the tibia and to provide an improved basis for the diagnosis of this disorder in human skeletal remains. Copyright © 2011 John Wiley & Sons, Ltd.

Imaging of a Marjolin's Ulcer: A Case Report

“Marjolin’s ulcer”refers to malignancies that developed in chronic venous ulcers, scars, or sinuses (1, 2). These malignancies also arise from various scars, including chronic ulcerations, inflammation, and fistulas after a long period of latency. Malignant transformation takes approximately 35 years. The incidence of malignant skin tumors that developed from scar tissue is 0.1-2.5%. Burn scars are the most common lesion causing this malignancy (3). The most common malignancy that arises from a Marjolin’s ulcer is squamous cell carcinoma, whereas basal cell carcinomas are rare. The malignancy is frequently multiple in the floor of an ulcer (3). The pathogenesis of a Marjolin’s ulcer is controversial (1, 3). Ulcer osteomas develop as a result of the heaping up of periosteum and associated subperiosteal sclerosis, and were seen as a knob-like mass protruding from the bone surface (1). These masses are rare in patients with chronic ulcers (1); however, they are frequently seen in patients with tropical ulcers, occurring in form of cutaneous leishmaniasis, which is a skin infection caused by a single-celled parasite that is transmitted by sandfly bites (4). A previous report described gadopentetate dimeglumine-enhanced magnetic resonance imaging (MRI) as a useful tool for evaluating a Marjolin’s ulcer (2). A multidisciplinary approach using three-dimensional computed tomography (CT) and positron emission tomography J Korean Soc Radiol 2011;64:593-598