Mucopolysaccharides (MPS; an older term), comprise a heterogeneous group of extracellular molecules, each consisting of a core protein(a proteoglycan) with covalently joined linear carbohydrates(a glycosaminoglycan). These molecules are important biomarkers and probes for exploring disease mechanisms.
At the VIII Dermatology International Congress in Copenhagen of 1930, Heinrich Adolf Gottron reported increased metachromatic staining in Dermatomyositis (DM) skin lesions. Gradually, the clinical literature has come to use Gottron’s papules (GP), red to violet plaques over the metacarpalphalangeal distal, and proximal interphalangeal joints as characteristic findings in DM. Although there are recent discussions of the sensitivity and specificity of GP and DM, the term GP has stood the test of time. Medical students are in awe when they learn that this finding can be a sign of inflammatory muscular disease and underlying internal malignancy. Now, these papules can also be a clue to the mechanisms of DM and its intriguing pathophysiology.
The general concept that “structural” molecules can interact with and modify the interactions of growth factors and other molecules is now well accepted. Those interactions can involve receptors on the cell surface and bridging molecules that may be covalently or non-covalently bound to the structural molecule. Such interactions may modulate inflammatory responses.
With this in mind, I refer you to Kim et al’s JID article reporting detailed studies of the MPS in GP. The glycosaminoglycan in GP is a chondroitin-4- sulfate (C4S). It interacts with both CD44 variant7 and osteopontin. Both of those latter molecules have roles in modulating immune responses, as discussed by Kim et al.
A novel feature of this investigation addressed the question that has intrigued investigators for almost a century: the reason for GP’s localization to the extensor surface over hand joints. The reasons for skin disease location are often discussed but rarely approached experimentally.
The role of the constant mechanical stretching of the extensor skin during ordinary circumstances was approached experimentally. Normal human fibroblasts were cultured on a tissue culture matrix, with a glass bead under their tissue culture matrix and another glass bead underneath the cell and its supporting membrane; pressure was applied above the culture. For me, this experiment recalls the fairytale princess who slept on a pea. The matrix around stretched fibroblasts was compared with non-stretched fibroblasts. The stretched cells produced increased levels of the CD 44 variant7 protein and its mRNA, which could have a role with osteopontin in contributing to inflammation and the increases in C4S.
Cells interact both biochemically and physically with their environment, and the mechanical and physical interactions reported by Kim et al can be considered within the realm of “mechanobiology”. The laboratory techniques and the analyses involved may differ from those used in classical immunology and biochemistry, and no doubt they will be used in more studies of the skin. Given its potential insights, mechanobiology should be a rapidly growing science for skin biology, akin to “plastics” — as recommended to the character Benjamin in “”http://www.imdb.com/title/tt0061722/“>The Graduate”. I discussed the increasing importance of engineering analysis in biology in the 75th anniversary issue of JID.
Your blogger has been afflicted by disease eponyms for several decades, as he has downed obscure names, drowning his neurons with eponyms for clinical syndromes since he was a resident. More recently, I have been concerned that eponyms may divide specialties and establish individual knowledge clubs. The issues related to eponyms are discussed in two articles in the British Medical Journal (Whitworth, 2007; Woywodt and Matteson, 2007).
Some eponyms have been removed or de-emphasized on the basis of an individual’s notariety. Reiter and Wegener are the two most prominent examples; due to their activities related to National Socialism in Germany, The primary names of their eponymous designated diseases have been replaced with “reactive arthritis” and “idiopathic necrotizing vasculitis”, respectively (Strous and Edelman, 2007).
“Gottron papules” can be a useful shorthand; instead of GP, I could have described the lesions as “symmetrical, disposed, shiny, well-delimited atrophic purplish papules on the extensor aspects of the digits, usually over joints, etc.” Even when their exact basis is known, there may not be a simple molecular name or shorthand for the overall clinical lesion. Therefore, this eponym enhances communication. But what about the man for whom they are named?
Heinrich Adolf Gottron (1890-1974) was Professor and Chair of Dermatology in Breslau Germany during National Socialism and was “exonerated by the denazification committee in 1945”. He was appointed as professor and chairman in Tübingen in 1946, after Breslau was ceded to Poland after World War II. After the war he “was a notable representative of post-war dermatology”. From a brief review there seems no strong evidence that this eponym is being used inappropriately. Important academic and historical details of Gottron’s career can be found in the History of German Language Dermatology.
In the over 80 years since Gottron’s report, investigative studies of the skin and immune system are increasing in DM, and further studies may lead us to understand its frequent association with muscle disease and internal malignancies.
- History of German Language Dermatology edited by A. Scholz, K. Holubar, G. Burg, W. Burgdorf, H Gollnick. Wiley-VCH Verlag, 2009.
- Strous,RD and Edelman,MC. Eponyms and the Nazi era: time to remember and time for change. IMAJ 9:207-214, 2007
- Whitworth,JA Should eponyms be abandoned? No. BMJ 335:425, 2007.
- Woywodt,A and Matteson, E. Should eponyms be abandoned? Yes BMJ 335:424,2007.
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This image (from Stories from Hans Andersen, with illustrations by Edmund Dulac, London, Hodder & Stoughton, Ltd., 1911) is in the public domain and can be found on Wikipedia.com.