The acute attack of porphyria

It has long been recognized that patients with certain types of porphyria are subject to bizarre neurologic episodes or “acute attacks.” This syndrome has captured the imagination of both clinicians and edical historians, the latter debating earnestly and regularly whether porphyria was the cause of George III of Britain's “madness” or Mary, Queen of Scots' abdominal pain and how this may have affected the course of history.¹ For individuals affected by either acute intermittent porphyria (AIP), variegate porphyria (VP) or hereditary coproporphyria (HC), the episode is, however, of far greater practical than of philosophical import as it represents perhaps the major determinant of their morbidity and mortality. It was therefore thought pertinent to include a chapter on this syndrome in the text, although it is aimed at those medical practitioners whose interest in the porphyrias is primarily dermatologie.     

Drug therapy in the acute porphyrias

The thrust of this chapter will be on drug therapy in the acute porphyrias. Specifically, avoidance of those drugs that might precipitate an acute neurologic episode or “acute attack” will be discussed. In the realm of the dermatologist, this will apply to patients with one of two disorders: variegate porphyria (South African genetic porphyria, VP) and hereditary coproporphyria (HC). The third of the acute porphyrias, acute intermittent porphyria (AIP), is not associated with skin lesions and such patients are accordingly unlikely to consult a dermatologist. In this chapter, we shall neither deal with the important topic of drug therapy during an acute attack nor precipitation or treatment by drugs of the purely cutaneous porphyrias; these subjects will be addressed elsewhere in this volume.     

Epidermodysplasia verruciformis

Epidermodysplasia verrucif ormis (EV) is a rare, lifelong disease induced by a diversity of specific human papillomaviruses (HPVs) including, in some instances, the HPVs which induce plane warts in the general population.^1–4 EV provides a model of cutaneous viral oncogenesis, in which virus and host factors are important determinants.

The disease starts usually in early childhood. The lesions, as a rule, do not appear at birth, even in familial cases, in spite of the heavy viral infection of the mother. The reason for this latency period is not known.     

Hematologic and hepatic manifestations of the cutaneous porphyrias

This chapter has dealt with five photocutaneous forms of human porphyria. The forms are a diverse group of disorders with many different hematologic, hepatologic, and neurologic manifestations. In essence, most photocutaneous porphyrias occurring in childhood will relate to congenital erythropoietic porphyria or protoporphyria. The nature of the skin lesions and a study of the heme precursor profile in red cells, plasma, urine, and feces should easily distinguish these two conditions. CEP is a disease wherein photomutilation is a dominant concern and aggressive new approaches of therapy also have been discussed. In protoporphyria, the dermatologic problem is less severe and the dermatologist should be aware that a subset of patients could develop active liver disease that may lead to fatal cirrhosis. Novel approaches of therapy have been briefly alluded to. With regard to postpubertal photocutaneous porphyria, the classic porphyria cutanea tarda syndrome is associated with liver disease, usually alcoholic with siderosis, and the treatment by phlebotomy to reduce hepatic iron is highly effective. The potential danger of liver carcinoma has been discussed. In subsets of porphyria cutanea tarda, this can be an endemic disease relating to environmental factors, ie, ingestion of polyhalogenated hydrocarbons. The biochemical diagnosis can be attained by fairly straight-forward solvent extraction analyses of urine and feces, showing the dominance of uroporphyrin excretion in the urine and coproporphyrin in the feces. Chromatographic techniques in plasma, bile, and feces reveal a PCT-specific porphyrin: isocoproporphyrin. Rare subtypes with hematologic manifestations, ie, hepatoerythropoietic porphyria and CEP, indicate the wide spectra of disorders that might be associated with a spontaneous deficiency of uroporphyrinogen decarboxylase activity. These latter syndromes are, however, rare. Two hereditary hepatic porphyrias, ie, autosomal dominantly inherited VP and HCP, have been briefly discussed. The hepatic lesion is metabolic, not morphologic, and its expression by the liver relates to its adaptive response to induction of microsomal hemoproteins by a variety of exogeneous and endogeneous compounds, eg, drugs and hormones. Photocutaneous lesions of HCP and VP are identical to PCT, the latter having no neurologic sequelae. In the former two, however, exposure of persons to drugs, such as the hydantoins and barbiturates, can lead to potentially fatal acute porphyric attacks.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cervical condyloma planum

Condylomata were defined and described as wart-like lesions with papillary projections often observed on the skin and mucosa of the anogenital area. Cytologic, histologic, and colposcopic studies have demonstrated that the condylomatous lesion on the cervix presents itself more frequently as a flat lesion than a classical exophytic papillary one.

Condyloma planum represents a new lesion on the human cervix, not described until 1977.^1,2 The viral etiology of this new type of condyloma has been confirmed in three ways: by the electron microscopic observation of human papillomavirus (HPV) particles, ^1,3–8 by the identification of viral antigen using the peroxidaseantiperoxidase technique,^9–13 and by demonstrating the presence of the HPV DNA sequences using molecular cloning and hybridization techniques.^5,14     

The history of genodermatoses

A complete history of the genodermatoses would include as background a full history of both dermatology and genetics. This is obviously beyond the scope of this chapter. Since McKusick's book catalogs 1364 genetic diseases,¹ of which several hundred are manifested in the skin, this work concentrates on the history of the growth in understanding of one group of genodermatoses: the ichthyoses.