Congenital erythropoietic porphyria: bringing evidence-based practice to a rare disease

ORIGINAL ARTICLES, p 888, 901

It is just over 100 years since Gunther’s landmark description of congenital erythropoietic porphyria (CEP). In the intervening century, studies of this rare disease have had major impacts on science. Gunther’s description prompted Friedrich Meyer-Betz to prove that porphyrins cause photosensitivity in man (in a painful and heroic exercise in self-experimentation). In the 1920s, a patient with CEP (Mathias Petry) provided Hans Fischer with thousands of biological samples (pre- and postmortem) from which he isolated the porphyrins and worked out their structures, for which he was awarded a Nobel prize. The genetic basis of the disease has been elucidated and much effort and ingenuity expended on in vitro gene therapy studies.

In contrast to these dazzling achievements, the clinical understanding and management of the disease has progressed little in the past 50 years, with the striking exception of bone marrow transplantation. The evidence base for treating this severe multiorgan disease is based on single case reports and small case series, and even the clinical features and natural history have never been systematically studied. Evidence is needed more than ever to decide which patients should be given a bone marrow transplant.

In this issue of the BJD, the detailed study by Katugampola et al. of 29 patients with CEP, including all known patients in the U.K., is a welcome advance.^1,2 For the first time a large number of patients has been studied in great detail to record the clinical features (skin, eyes and blood), the response to treatment and the genotype. The results are illuminating. They reveal the enormous spectrum from very mild skin disease alone, through to patients with severe photomutilation, chronic pain, loss of the use of the hands, blindness and fatal haematological complications.

There are two key findings. One is that disease onset before the age of 5 years and significant haematological involvement both turn out to be reliable predictors of poor prognosis. The other is the excellent long-term outcome in five of the six patients treated with a bone marrow transplant. These findings provide an evidence base to inform the decision as to when and whether to treat a child by bone marrow transplantation. In contrast to these clinical predictors, mutations predicted clinical features surprisingly poorly.

The authors’ practical approach is seen in the splitting of the results into two papers (both in this issue), one observational, the other focused on therapy.^1,2 The therapeutic data illustrate the difficulties that health services encounter in treating rare, severe, multisystem diseases. Patients received varying levels of medical care (or none at all) with an apparent lack of coordination between the different specialties involved. Even basic photoprotection with visible light sunscreens and window filter films had not been offered to some patients. The authors propose that optimal management needs a dedicated multidisciplinary clinical service. On the basis of their data the argument that such a service would improve patient outcomes seems overwhelming.

This study provides a model of the importance of moving the understanding of a very rare disease into the evidence-based era with comprehensive, clinical, management-oriented studies.