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The name “porphyria,” from the outset, aimed at describing not the disease but the porphyrin compounds themselves-lustrous purple crystals which emitted a characteristic red fluorescence in solution when exposed to near ultraviolet light. This name is derived from the Greek ~&~poa, meaning purple.

In ancient times, this was the color of royalty and such an association was not lost where investigators in the past have apocryphally related the “madnesses” of the royal houses of Stuart and Hanover to pre-existent acute porphyria. Many of the described features are suggestive of this condition-dark urine, abdominal pain, and neuropsychiatric behavior. Definitive proof of the association, however, is lacking.

In a dermatologic sense, the presence of porphyria is less easy to miss. Indeed, suggestions that werewolves were in fact patients with congenital porphyria are attractive. Some of the attendant dermatologic features, such as hypertrichosis, skin mutilation, and a natural avoidance of sunlight make this hypothesis more easily sustained; but, again, proof is lacking.

This CLINIC brings together a number of essays on the various dermatologic features of porphyria, together with inevitable discussion on the coexistent acute features of certain forms of these diseases, and the biochemical features and changes characteristic of these various forms. The most significant, recent advances in the understanding of the biochemical features of these diseases have revolved around observations on the changes in protoporphy- rinogen oxidase in the biosynthetic pathway in variegate porphyria. This means that the general processes of control and function of the pathway, provided early in the proceedings, facilitate the complete understanding of the other biosynthetic changes in each of these diseases.

These alterations in the biosynthetic pathway are fundamentally enzymic and allow a precise enzymic definition of each of these conditions which makes it easier to support the current clinical characterization of the various conditions into acute and nonacute or derma- tologic forms of these diseases. From these biochemical features, it is therefore simple to appreciate the likely chemicopathologic presentation of these conditions. The primary devel- opment in this field, other than that of the enzymic changes, is in the role of high performance liquid chromatography in showing the specific patterns of porphyrin production and excre- tion in these conditions.

The reasons for the dermatologic features of the diseases are well covered by Maureen B. Poh-Fitzpatrick, who presents each of the probable explanations for the photoactivity of porphyrins, and the extrapolation of this into the exceedingly interesting use of porphyrins in the photochemical treatment of cancer.

Means of moderating such photoactivity in treatment of dermatologic features of at least one of these conditions, erythropoietic protoporphyria, with beta-carotene are also discussed. In addition to the dermatologic changes induced by porphyrins, it is not always appreciated that such compounds in excess are toxic in other soft tissues. The specific features of such toxicity are developed by Neville Pimstone who has, in his chapter, emphasized the hepato- toxic component of the nonacute porphyrias.

In addition to the dermatologic features, the acute porphyrias present with a number of factors attributable to neurologic change. Such neurologic manifestations are limited to the three acute conditions and are probably due to either excess production of 5-aminolevulinic acid or diminution of heme- and hemoprotein synthesis, or indeed a combination of these. The reasons for induction of such acute attacks are few, and primary among these is the use of drugs that alter biosynthetic pathway function. From human and animal studies, it has been

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possible to derive lists of drugs which are “safe” and “unsafe” for use in the porphyrias, and these are given in the chapter on drug induction of the porphyrias.

In addition to inducing porphyria, certain drugs may be used to provide animal models of these conditions. Such experimental porphyrias are discussed by George D. Sweeney. Of particular interest in this sphere are the changes made by halogenated hydrocarbons and a range of other compounds. It is from such studies that evidence has developed for the primary modes of biosynthetic control of the processes of heme synthesis.

A book of this type would be incomplete without some description of the types of genetic porphyria that might be found in animals. Claude Rimington provides an overview of these conditions, primarily bovine and porcine congenital porphyria.

Finally, the aim of this book is as a “festschrift” to pay tribute to Lennox Eales, a preemi- nent worker in this area of research. This is done handsomely by Sir Abraham Goldberg, in his historic overview, and by Ralph Kirsch, and Solly Benatar, all of whom knew him, both personally and professionally. In South Africa, he was presented with a unique opportunity to investigate these diseases, and this he did productively, over a quarter of a century, with much enthusiasm, providing considerable insight into the natural history, treatment, and provenance of porphyria.

Peter B. Disler, PhD, MBBCh, FCP (SA) Michael R. Moore, PhD

Guest Editors