A Personal Critique on the State of Knowledge of Rosacea by Albert M. Kligman, M.D., Ph.D.

The article says, "...the National Institutes of Health, which with an annual budget of nearly 30 billion dollars, has not seen fit to fund a single grant for the investigation of rosacea. I have been turned down twice, based on the grounds, not directly stated of course, that rosacea is merely a “cosmetic” problem more appropriately funded by the skin care industry. As a result, we have voluminous literature, mainly focused on treatments sponsored by commercial interests; perhaps not the most credible source of unbiased research..."

"...What immediately stands out, which may shock the uninitiated, is the striking degree of controversy, conflict, confusion and contradictions, among the thicket of reports from all over the world. The parvenu to rosacea research will likely be puzzled by these quandaries, which may be off-setting to some, but an attraction to those who like to engage in fields where perplexities reign. There are profound disagreements among “experts” who write and talk about rosacea. I state forthrightly that the state of knowledge regarding the classification, pathogenesis, diagnosis and treatment of rosacea is embarrassing, if not scandalous, when compared to the impressive advances in all other fields of dermatologic research..."

Dr. Kligman notes that there are "Controversies Regarding the Nature, Classification and Diagnosis of Rosacea," and that one noted authority on rosacea, Francis Wilkin of the FDA, has proposed that rosacea isn't a disease but a condition. Wilkin "labels rosacea an ideotype, a cluster of signs and symptoms, apparently not a pathologic entity warranting a specific nosologic status."

Another controversy is that a noted rosacea researcher, Frank Powell, proposes that "episodes of flushing are not a prerequisite for making a diagnosis of rosacea, and that some patients can develop the full-blown disease without a prior history of frequent flushing." Another researcher "says that flushing is not a necessary stage in the sequence leading up to the full-blown 'red face'."

Dr.Kligman says, "I cite these disputes, not to disparage those who disagree with my views, but rather to emphasize the compelling need to expand support for rosacea research." He writes further on:

"I find it illuminating, even risible that of more than 90 papers which I have reviewed aimed at determining the efficacy of a variety of topical agents, not one concluded that the drug was ineffective. It seems that rosacea is a physician-friendly disorder in which everything works. This brings to mind the old clinical adage that when everything works, nothing works! Of course, we all understand how it happens that industry supported research is unlikely to yield negative results."

Another interesting point is "another paradox, namely that we can moderate this disease reasonably well, and greatly improve the quality of life for rosacea sufferers without a substantive understanding of its nature and pathogenesis."

Then he points out "that we cannot fully explain how some of our most effective drugs actually exert their therapeutic benefits. For example, the high efficacy of oral antibiotics, especially tetracyclines, is beyond doubt, a welcome mainstay of treatment. Yet, no pathogenic organism has been identified as causative. Rosacea is not an infectious disease and there is no evidence that antibiotics work by reducing the native microflora, which do not differ from normals. We have to contrive other explanations; the most popular one at present is that tetracyclines possess anti-inflammatory effects, along with other theoretical actions that might affect the course of this complex disease [3]. Tetracyclines have also been shown to have immuno-modulatory effects, to interfere with the production of pro-inflammatory cytokines and even to have unexpected therapeutic benefits in a surprising variety of unrelated dermatologic disorders [4]. We face the same dilemma in regard to the popular metronidazole topicals, which are undoubtedly helpful in maintaining improvement after the disorder has been brought under control. We have no idea how topical metronidazole works omay rival tetracyclines in efficacy [5, 6]."

Another new item Dr. Kligman points out is the "fact is we simply have no idea of the true prevalence since there never has been a credible epidemiological study of a random population."

He notes that "Rosacea has devastating effects on the quality of life for women. There is far too little appreciation of the high frequency of depression, anxiety and suicidal thoughts among women sufferers whose well being depends much more than men on an attractive appearance. This is all very interesting since all the clinical manifestations of rosacea are more severe in men in whom the unchecked disease ends up in rhinophyma, which never occurs in women. There is also a consensus that rosacea is more common in women; though we have no valid data on the actual female to male ratio this might be as high as 3 to 1 if not higher."

Dr. Kligman comments on the new NRS classification of rosacea into subtypes by saying, " In my view this is a vast oversimplification which will not solve the diagnostic dilemmas that confront us. I see no reason not to give equal nosologic status to granulomatous rosacea, rosacea conglobata, rosacea inversa (formerly called pyoderma faciale), rosacea fulminans, edematous rosacea (a devastating variety) or combinations with seborrheic dermatitis, lupus erythematosus, acne vulgaris, and still other variants. Reducing the classification to four sub-types does little to clarify and eliminate the inherent complexities of this mysterious disease. Nevertheless, the new classification is a good beginning since it awakens awareness of the necessity to develop robust diagnostic criteria. This is an area where clinicians and basic researchers can profitably come together to provide internationally approved
guidelines."

Dr. Kligman concludes with "I do not have the heart to take up other hotly contested issues which we will eventually have to deal with, namely the etiologic roles of Demodex and H. pylori. Controversies rage here also. Our lack of knowledge regarding many aspects regarding the pathogenesis of rosacea has greatly hampered our obligation to provide internationally agreed-upon guidelines for conducting studies which yield concordant results" and quotes Napolean by saying, "When asked what was needed to win a war, he is reputed to have said “Three things – money, money and money.”

It is a very cool article and everyone should read it in full at this url >

http://www.cunliffe-awards.org/pdfs/publikation_kligman.pdf