Histopathologic Improvement with Lymphedema Management, Léogâne, Haiti

Wilson, Susan F.; Guarner, Jeannette; Valme, Alix L.; Louis‐Charles, Jacky; Jones, Tara L.; Addiss, David G.

doi:10.3201/eid1011.040548

Cited by 31 publications

(29 citation statements)

References 25 publications

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“…Nevertheless, our data reveal that aberrant expression of a single gene is sufficient to affect both lymphatic and blood vessels and predispose to the development of secondary lymphedema, thus suggesting a crucial, possibly even “gatekeeping”, role for AM in this disorder, at least upon wounding. In addition, our study uncovers a previously unrecognized spectrum of potential AM targets in human skin by demonstrating that CLR is expressed in both lymphatic and blood vessel endothelium, as well as in the epidermis, which are all affected in lymphedematous organs (Wilson et al , 2004; Tabibiazar et al , 2006; Rockson, 2008a; Nakamura et al , 2009). …”

Section: Discussionmentioning

confidence: 66%

“…The structural and functional abnormalities in lymphedematous skin reflect a multicellular response to impaired extracellular fluid mobilization and can be distinguished from other mechanisms that lead to interstitial edema (Rockson, 2008a). The presence of epidermal thickening is pathognomonic of lymphedema (Wilson et al , 2004; Tabibiazar et al , 2006; Rockson, 2008a). Lymphedema predisposes to collagen and lipid deposition, cutaneous hypercellularity, progressive fibrosis, and susceptibility to infections (Rockson, 2001; Rutkowski et al , 2010; Wu et al , 2011).…”

Section: Introductionmentioning

confidence: 99%

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Adrenomedullin Haploinsufficiency Predisposes to Secondary Lymphedema

Nikitenko

Shimosawa

Henderson

et al. 2013

Journal of Investigative Dermatology

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Secondary lymphedema is a debilitating condition, and genetic factors predisposing to its development remain largely unknown. Adrenomedullin (AM) is peptide encoded, together with proadrenomedullin N-terminal peptide (PAMP), by the Adm gene (adrenomedullin gene). AM and its putative receptor calcitonin receptor–like receptor (CLR) are implicated in angiogenesis and lymphangiogenesis during embryogenesis and wound healing, suggesting their possible involvement in secondary lymphedema. To investigate whether AM deficiency predisposes to secondary lymphedema, we used heterozygous adult mice with Adm gene-knockin stop mutation, which selectively abrogated AM, but preserved PAMP, expression (AdmAM+/Δ animals). After hind limb skin incision, Adm messenger RNA expression was upregulated in wounded tissue of both AdmAM+/+ and AdmAM+/Δ mice. However, only AdmAM+/Δ animals developed limb swelling and histopathological lymphedematous changes, including epidermal thickening, elevated collagen fiber density, and increased microvessel diameter. Secondary lymphedema was prevented when circulating AM levels in AdmAM+/Δ mice were restored by systemic peptide delivery. In human skin, CLR was expressed in tissue components affected by lymphedema, including epidermis, lymphatics, and blood vessels. Our study identified a previously unrecognized role for endogenous AM as a key factor in secondary lymphedema pathogenesis and provided experimental in vivo evidence of an underlying germ-line genetic predisposition to developing this disorder.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Adrenomedullin Haploinsufficiency Predisposes to Secondary Lymphedema

Nikitenko

Shimosawa

Henderson

et al. 2013

Journal of Investigative Dermatology

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“…In the subcutaneous fat, thickening and fibrosis of the septa with lipophagic changes and adipocyte necrosis in fat lobules can be observed (Miteva et al 2010). In contrast, in LE, the epidermis and dermis thicken because of hyperkeratosis and fibrolamellar hyperplagia, respectively (Wilson et al 2004). In subcutaneous tissue, fat accumulates with fibrosis of mainly the interlobular septa (Fumiere et al 2007).…”

Section: Discussionmentioning

confidence: 96%

Skin and Subcutaneous Tissue Strain in Legs with Lymphedema and Lipodermatosclerosis

Suehiro

Morikage

Murakami

et al. 2015

Ultrasound in Medicine & Biology

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“…Unlike in lymphatic filariasis (LF)[5], podoconiosis lymphoedema appears to affect men and women equally[6]. A cross-sectional survey of an endemic region in Southern Ethiopia estimated a prevalence of 5.46% in this area, which, projected to the population now living on irritant soil in Ethiopia, suggests that one million Ethiopians may be affected[6].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of a Simple Lymphoedema Treatment Regimen in Podoconiosis Management in Southern Ethiopia: One Year Follow-Up

Sikorski

Ashine²,

Zeleke³

et al. 2010

PLoS Negl Trop Dis

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BackgroundPodoconiosis is a non-filarial elephantiasis caused by long-term barefoot exposure to volcanic soils in endemic areas. Irritant silicate particles penetrate the skin, causing a progressive, debilitating lymphoedema of the lower leg, often starting in the second decade of life. A simple patient-led treatment approach appropriate for resource poor settings has been developed, comprising (1) education on aetiology and prevention of podoconiosis, (2) foot hygiene (daily washing with soap, water and an antiseptic), (3) the regular use of emollient, (4) elevation of the limb at night, and (5) emphasis on the consistent use of shoes and socks.Methodology/Principal FindingsWe did a 12-month, non-comparative, longitudinal evaluation of 33 patients newly presenting to one clinic site of a non-government organization (the Mossy Foot Treatment & Prevention Association, MFTPA) in southern Ethiopia. Outcome measures used for the monitoring of disease progress were (1) the clinical staging system for podoconiosis, and (2) the Amharic Dermatology Life Quality Index (DLQI), both of which have been recently validated for use in this setting. Digital photographs were also taken at each visit. Twenty-seven patients completed follow up. Characteristics of patients completing follow-up were not significantly different to those not. Mean clinical stage and lower leg circumference decreased significantly (mean difference -0.67 (95% CI −0.38 to −0.96) and −2.00 (95% CI −1.26 to −2.74), respectively, p<0.001 for both changes). Mean DLQI diminished from 21 (out of a maximum of 30) to 6 (p<0.001). There was a non-significant change in proportion of patients with mossy lesions (p = 0.375).Conclusions/SignificanceThis simple, resource-appropriate regimen has a considerable impact both on clinical progression and self-reported quality of life of affected individuals. The regimen appears ideal for scaling up to other endemic regions in Ethiopia and internationally. We recommend that further research in the area include analysis of cost-effectiveness of the regimen.

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Histopathologic Improvement with Lymphedema Management, Léogâne, Haiti

Abstract: Basic management improves the histologic profile of limbs in patients with filarial lymphedema.

Cited by 31 publications

References 25 publications

Adrenomedullin Haploinsufficiency Predisposes to Secondary Lymphedema

Adrenomedullin Haploinsufficiency Predisposes to Secondary Lymphedema

Skin and Subcutaneous Tissue Strain in Legs with Lymphedema and Lipodermatosclerosis

Effectiveness of a Simple Lymphoedema Treatment Regimen in Podoconiosis Management in Southern Ethiopia: One Year Follow-Up

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