Elephantiasis, Elastin, and Chronic Wound Healing

19 Lymphology 42 (2009) 19-25 ELEPHANTIASIS, ELASTIN, AND CHRONIC WOUND HEALING: 19TH CENTURY AND CONTEMPORARY VIEWPOINTS RELEVANT TO HYPOTHESES CONCERNING LYMPHEDEMA, LEPROSY, ERYSIPELAS, AND PSORIASIS – REVIEW AND REFLECTIONS T. J. Ryan Emeritus Professor of Dermatology, Oxford University and Oxford Brookes University, Oxford, United Kingdom ABSTRACT both wound healing and lymphedema, and a later third stage of organization includes Both wound healing and lymphedema fibrosis and precedes re-modeling. It is this have fibrosis of the skin in common. They organization phase that embraces a major also share destruction of elastin by elastases feature of repair which is overgrowth of from neutrophils as a significant feature. tissues. The skin is the most affected organ, These are not new observations, and the and it is skin care that is most often demanded writings of Unna and Kaposi are recalled. for wound healing and lymphedema. The contemporary observations on elastin by Destruction of elastin is a significant feature Gerli and his team are discussed in the light of lymphedema and has been noted in wound of these much earlier opinions. healing (2). It was in a review of the lymphatic Keywords: elephantiasis, wound healing, system in a skin physiology textbook (3) that elastin, elastases, fibroblast, leprosy, I first gave the necessary emphasis on elastin erysipelas, psoriasis as a feature of the healthy lymphatic that essentially contributes to its function (Fig. 1). Macdonald (1) has proposed that the Unna was quoted and in several Dermatology discipline of wound healing should embrace texts since that time (4-9), his views have lymphedema, and a World Health Organiza- received reemphasis. Like adipose tissue, tion (WHO) white paper on both should serve which I have also reviewed (10), I see elastin as a background to WHO taking them more as a neglected component of global signifi- seriously. Much needed for their management cance because of the part played in infectious is general knowledge about care of the skin. diseases such as leprosy Buruli ulcer and During the last few decades, manage- lymphatic filariasis. Gerli and his colleagues ment of wound healing and management of (11,12) have further developed and refined lymphedema have come to the fore as disci- this concept although earlier observations are plines that are both staged into early and late not featured in their publications. The concept phases of skin responses to injury affecting is that healthy lymphatics of the skin are the vascular systems of the skin with varying provided with a network of elastin fibers that degrees of transudation, exudation, and does three things: 1) Provides snap back and bleeding, followed by inflammation with its enhanced response to external movements. four cardinal signs. Swelling accompanies 2) Links the lymphatic to the epidermis (13). Permission granted for single print for individual use. Reproduction not permittion without permission of Journal LYMPHOLOGY 20 Fig 1: Orcein stain shows elastin fibers surrounding a lymphatic in the upper dermis and linking it by a tangential fiber to the overlying epidermis. Blood vessels in the normal upper dermis do not show a similar appearance and relationship to elastin. 3) Acts as a preferential pathway or guideline epidermis to the lymphatic is too rapid to from the epidermis to the lymphatic for happen without mechanical guidance and Langerhans cells and macromolecules that its failure to move readily in psoriasis entering or manufactured by the body’s first could be due to the release of elastases from line immune- surveillance system (14). the neutrophils that are a feature of that Our hypothesis is that destruction of condition (17). elastin contributes to lymphatic dysfunction, The historical texts that first described and it occurs most commonly due to but also confused the terminology of leprosy, activation of elastases mostly derived from lymphedema, erysipelas/cellulitis, and neutrophils. But this is not a new idea, and psoriasis are nevertheless informative about was well described in the 19th century. this topic and I have been consistent in If one focuses for a moment on elastases, quoting from such historical texts regarding then importance must be assigned to the each of these disorders over the past forty or neutrophil and macrophages, which are rich so years. in elastases and, worth noting, that the eosinophil is not. As I illustrated in a study 19 th Century Observations of leprosy (15), lymphatics lose their elastin adjacent to a granuloma. Parish (16) If one reads dermatology textbooks of emphasized that localization of infection was the 19th century and turns to the chapters on determined by inflammatory cells, and it is edema or elephantiasis, growth of tissues is possible that the cutting of the connection well described. of elastin to the lymphatic is part of the Contemporary writers on the history of process of localization. But, it is also a factor massage for lymphedema usually begin by in the changing resilience of the tissue after referring to Winiwarter (18) Die Elephantiasis wounding. and to Vodder (19), who laid much emphasis I have also suggested (14) that the on the techniques employed for shifting of Langerhans cell’s brisk movement from the lymph. However, the term elephantiasis as Permission granted for single print for individual use. Reproduction not permittion without permission of Journal LYMPHOLOGY 21 earlier writers emphasized is applied to a tissue depending on structure, this is essential condition in which an excess of lymph is reading. This 19th century text is thoughtful often less noteworthy than the hypertrophy and discursive especially about the of the many tissue components. Furthermore, collaboration between the lymphatic and prior to the mid-19th century, the term venous system in a wide ranging description elephantiasis was used to describe several of skin diseases. The following are some disorders including leprosy. Two references illustrative quotes. are particularly helpful when searching for P23 – “Every oedema of the lymph spaces the early descriptions of elephantiasis. separates the elastic fibres.” On this page he Hebra and Kaposi (20) describe in great also makes the point that when edema is due detail the early Greek, Roman, Arabic, and to external injury of epithelium, abundant later European writings on swelling of limbs mitoses swarming in the basal prickle layer is and genitalia and include the conditions “an unfailing symptom” and which today we which most contemporary practitioners would recognize as a repair response for would recognize as lymphedema. But they which skin care is well justified. state “we use the term Elephantiasis Arabum P26 – Following whealing with stinging to indicate a hypertrophy of the fibrous tissue nettles: “The rapid forcible dilation of these of the cutis and of the sub-cutaneous pre-existing lymph channels is evidenced in connective tissue.” This is an emphasis on the irregular course of the overstretched, overgrowth and “we convince ourselves, at frequently torn elastic fibres, here and there the same time, that the oedema is, at any rate, crowded together into bundles.” This theme of slight in proportion to the thickening of the the destruction of the elastic tissue is returned leg, and in the sense of resistance is much to frequently (viz p39). more considerable than in ordinary dropsy, P32 – “Physiology teaches that during anasarca, and resembles that of sclerema.” rest, no lymph flows from the incised larger Later focus on lymph has refined approaches lymph channels of the extremities, although to its removal but somewhat ignored the issue every superficial bloodless incision into the of how one manages hypertrophy. In this text papillary body shows that on the surface of by Kaposi the dilated lymphatics, the recur- the cutis no inconsiderable quantities of rent inflammatory episodes, and the effect of lymph are continuously produced.” elevation and bandaging are well described. P32 – “no hindrances in the way of the The second main historical review is by lymph channels from the skin to the lymph Erasmus Wilson (21), which better than most glands and from here to the subclavia, not describes the disease leprosy Elephantiasis even the complete obliteration of the thoracic Graecorum (noted by the Greeks) and duct would be sufficient to explain one single conveys how confusing was this early misuse edema of the skin. We are, therefore, of the term. Equally confusing at this time in compelled to abandon all these theories of the mid-19th century was the use of the term edema, which seek the cause of edema in lepra for psoriasis. lymph vessels themselves...” Unna’s book (22) is of great interest Unna makes the point (p33) that edema because of its insight into both lymphedema is most often due to leakage from the venous and tissue hypertrophy in response to edema. system. “The lymph vessels form, physio- He describes very well the different responses logically, only a relief track for the lymph of the tissues affected by edemas of differing during the numerous alterations in calibre of etiology. His descriptions of the damage done the veins of the skin, brought about by every to elastic tissue and the hypertrophy of movement.” This is a point perhaps collagen have not been surpassed. For anyone insufficiently made in the 21st century. interested in the likely effect of massage on a Unna makes the point that in the edema Permission granted for single print for individual use. Reproduction

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