Erythropoietic protoporphyria

Introduction

Erythropoietic protoporphyria (EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase, the terminal enzyme in the haem biosynthetic pathway, which catalyses the insertion of iron into protoporphyrin to form haem.1 Magnus et al[2] in 1961, were the first to characterize and name erythropoietic protoporphyria. They described a 35 year old man with a 27 years history of intense pruritus of exposed skin shortly after sun exposure. The first known case of EPP was described in 1926 as having ′hydroa aestivle without haematoporphyrinuria′.[2] Haeger-Aronson described the familial nature of EPP in 1963 by reporting three cases and two carriers in 3 generations of a family.[3]

Ferrochelatase occur in all nucleated cells, but mainly in the erythroid cells, since most of the haem is synthesized here for assembly into haemoglobin. Therefore bone marrow accounts for majority of protoporphyrin over production in EPP. Liver also contributes approximately 20% of excess protoporphyrin.[1] EPP manifests as variable degree of photosenitivity developing in childhood. We report a case of EPP presenting with severe photosensitivity and scarring.

Case Report

A 32-year-old man born out of nonconsanguinous marriage, presented with recurrent fluid filled lesions healing with scarring and pigmentation of 23 years duration. Hit complaint started at the age of 9 years as erythema and burning sensation over exposed areas with in one to four hours of sun exposure. He developed vesicles over exposed areas which ruptured within two to three days and healed with scarring and pigmentation in a reticulate pattern. Over next 2-3 years trunk was also involved. However the lesions reduced in severity and showed gradual improvement over years. There was no history of passing red coloured urine, any dental or skeltal abnormalities, mental retardation, epilepsy, photophobia, cataract, hearing defects, any systemic illness or similar complaints in the family.

Cutaneous examination revealed poikilodermatous skin changes consisting of hypo and hyperpigmentation and pitted scars scattered mainly over the photoexposed areas and upper trunk with few pustules [Figure - 1]. Sclerodermoid thickening of skin was evident over the dorsal aspect of the hands, forearms and the face. There was no telengiectasia or hypertrichosis over these areas. Palms and soles were spared. There was associated pallor.

Complete blood picture revealed low haemoglobin level of 6.5gm%. ESR was 150mm/hr. Peripheral smear showed normocytic normochromic anaemia. Urine examination, liver function tests, renal function tests, blood sugar levels, chest X-ray and ultrasound abdomen were normal. Serum immunoglobulin estimation showed elevated IgG and IgA levels with normal IgM level. Porphyrin estimation revealed very high protoporphyrin levels in RBC and stool with negative urinary porphyrins. Histopathology of skin taken from the dorsum of the hand showed hyperkeratosis, elongated rete ridges, mild pigment incontinence and perivascular lymphocytic infiltrate. Biopsy from the nail bed showed numerous hyphae and fungal spores on PAS staining.

Patient was treated with beta-carotene, haematinics and topical sunscreen with mild improvement.

Discussion

EPP is an autosomal dominant or autosomal recessive photodermatosis with variable penetrance.[1] Sporadic cases have also been reported. There is decreased activity of ferrochelatase enzyme up to 10-30% of the normal.[4] Protoporphyrin strongly absorbs light energy at 400-410nm (soret band). The absorbed light energy raises the ground state orbital electrons of proptoporphyrins to their excited singlet state. The excited molecule either emits fluoresce energy on biomolecules to bring about tissue damage directly or, tranfer the exciation energy to ground state molecular oxygen to produce reactive oxygen species which in turn produce tissue damage.[1]

EPP usually starts around 4 years of age, rarely between 8 and 21 years, characterized by immediate type of phototoxic reaction.[4] Symptoms occur within few minutes to one hour after sun exposure as oedematous urticarial erythematous plaques and eczematous lesions, with rarely vesicles, purura and crusted erosions. Repeated episodes result in mild to moderate scarring and sclerodermoid changes. Hypertrichosis is infrequent. Symptoms usually improve by 10-11 years. Less than 10% of patients develop servere liver failure. Cholelithiasis is often encountered with EPP and the gallstones are predominantly made of protoporphyrins.

Histopathology of EPP shows markedly thickened papillary dermal capillary walls and an amorphous, hyaline material deposited perivascularly and scattered throughout the dermis.4 Since protoporphyrin is a hydrophobic molecule, it is not soluble in water. Hence not present in the urine. Tratment modalities include avoidance of sun exposure, topical sunscreens and oral beta-carotene. Other modalities include PUVA and UVB therepy, oral cysteine, oral pyridoxine and antihistaminics. Oral cholestyramine resin, cholic acid, chenodeoxycholic acid are tried in cases with hepatic involvement. Liver transplantation is indicated as a last resort.[5] Shafi M et al,[6] in a series of three cases from Libya reported significant scarring in all the patients while deLeo et al7 reported scarring in only 19% of the cases.

In our case the high erythrocyte and stool protoporphyrin levels with negative urinary porphyrins associated with potosensitivity clinched the diagnosis of EPP. Our patient had delayed onset of disease with only persistent cutaneous involvement and anaemia without hepatic involvement.