Basal Cell Carcinoma in Erythropoietic Protoporphyria: All About Ultraviolet Light?

To the Editor:

We read with interest the publication by Reitmeier et al ¹ in the November issue of the Journal of Cutaneous Medicine and Surgery. The investigators report on the manifestation of basal cell carcinoma (BCC) in a patient with erythropoietic protoporphyria (EPP).

EPP is a hereditary metabolic disorder caused by a marked catalytic deficiency of ferrochelatase, the last enzyme in heme biosynthesis. ² Because of its often nonspecific clinical manifestation with onset in early childhood, the disease can be overlooked for years, often leading to a substantial delay between disease onset and diagnosis, ³ as in the patient described by Reitmeier et al. ¹ Clinically, EPP is characterized by cutaneous photosensitivity, including pain, burning, itching, and stinging of the skin within minutes of exposure to ultraviolet (UV) light, followed by erythema and swelling. Although some patients will tolerate UV exposure better than others, we agree with the investigators that over time, most affected individuals usually acquire an individual strategy of sunlight avoidance. ³ Therefore, the manifestation of BCC in such an individual indeed must be considered rather uncommon, although we are aware of at least 3 patients with EPP within our porphyria center who also concomitantly developed BCC (D. Mihailovic, personal communication).

BCC is the most frequent cutaneous malignancy worldwide, with a manifestation peak in the sixth to seventh decade of life. Although we agree with Reitmeier et al ¹ that high cumulative exposure to UV irradiation is probably the most important etiopathogenetic factor for BCC in general, the investigators did not list other known and likewise important risk factors for the development of this tumor. These factors include Fitzpatrick skin types I and II, radiotherapy, immunosuppression, higher socioeconomic status, 1 or more previous episodes of BCC in the medical history, a positive family history, and distinct genetic defects. ⁴ To us, the latter aspect seems of particular importance in the patient described by Reitmeier et al, ¹ considering the uncommon early manifestation at the age of 24 years. Thus, we would like to emphasize that not only basal cell nevus syndrome should be ruled out as a possible genetic tumor predisposition syndrome conferring susceptibility to BCC development but also Bazex-Dupré-Christol syndrome, Rombo syndrome, Oley syndrome and xeroderma pigmentosum. ⁴

Reitmeier et al ¹ mention that their patient has not yet been treated with afamelanotide, a synthetic analogue of α-melanocyte-stimulating hormone. Afamelanotide has been convincingly shown to diminish symptoms of acute photosensitivity in patients with EPP. ⁵ However, at this time there is no evidence that it can protect against the development of epithelial skin cancer. Thus, patients with EPP, in particular those with medical histories of cutaneous malignancy, should still exert effective sun protection measures, even when being treated with afamelanotide.

Taken together, we think that in the patient described by Reitmeier et al, ¹ a genetically determined susceptibility to the development of BCCs might be pathogenetically more important than UV light, in particular given that the patient avoided the sun. Furthermore, regular dermatologic tumor screening examinations, genetic counseling, and possibly molecular genetic diagnostics would be recommended.