ARTICLE
Erythropoietic protoporphyria was first described in detail by Magnus
[1] and Langhof [2] in 1961. An early diagnosis remains difficult to establish
since the beginning is often insidious, with only subjective signs before
skin lesions appear.
We report a new case, that illustrates very well the discrepancy between
the functional discomfort due to photosensitivity and the lack of cutaneous
lesions.
Case report
A healthy 4-year-old girl, with no particular medical history, had suffered
from solar intolerance for two years. She described it as a burning discomfort,
sometimes associated with itching of the back of the hands, that occurred
soon after prolonged sun exposure. These symptoms persisted for a few
days and usually prevented sleep. She often tried to diminish the pain
by cooling her hands with cold water. Her mother reported that she cried
and was restless during these crises. Initially, there were no visible
skin changes. After one year of recurrent painful episodes, a mild erythema
and oedema of the face appeared, with peeling of the nose skin and a brownish
aspect to the hands developed. The parents denied any familial history
of photosensitivity.
Phototesting was performed with:
a 1,000 Watts Xenon Lamp solar simulator (wavelength 240 to 1,100
nm), the Dermolum UM-W (Muller Electronik Optik, RFA), using a short wavelength
cut-off filter (WG 305, 1 mm thickness) and an infrared cut-off water-filter;
the Jetsun 55, with a 2,000 Watts UV quartz-high pressure lamp
with a filter allowing irradiation from 320 to
460 nm.
The MED (minimal erythema dose) was normal (1,093 mJ/cm2;
normal > 878 mJ/cm2) for the phototype. UVB phototesting
(10 DEM fractionized over three days, that is to say 3,633 mJ/cm2
three times) provoked itching on the hand. UVA phototesting (30 J) on
the other hand produced no effect.
Blood tests showed neither anaemia nor hepatic dysfunction, and immunological
tests for lupus erythematosus were negative. An abnormally high level
of protoprophyrin was detected in red cells (9,737 mmol/l; normal <
1,900 mmol/l), whereas urinary porphyrins and fecal coproporphyrins were
within normal limits.
The diagnosis of erythropoietic protoporphyria was established. Sun
avoidance and photoprotection were recommended, and treatment associating
ß-carotene with canthaxanthin was initiated, with satisfactory results
(Phenoro®, 2 capsules a day).
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Erythropoietic protoporphyria is a rare disorder of heme synthesis,
although it is the most frequent type of porphyria in childhood. It is
characterized by a congenital defect in the intramitochondrial enzyme
ferrochelatase [3]. The defect results in accumulation of free protoporphyrin
IX in erythrocytes, liver (hepatocytes) and skin fibroblasts. Inheritance
follows an autosomal dominant pattern with variable penetrance. The gene
is localized on the short arm of chromosome 18. Nevertheless, a reduction
of enzyme activity to 10-30% (less than 50%) of normal suggests a more
complex genetic mechanism. An autosomal recessive inheritance or a gene
mutation affecting the activity of ferrochelatase have been suggested.
Clinically, the disease consists of, in decreasing order of frequency,
in burning (97%), swelling (94%), itching (88%), redness of exposed skin
(69%), scarring (19%), pain (16%), vesicules (3%) and purpuric lesions
(3%) [4]. Some children have subjective symptoms of burning and pain without
obvious signs: they may be suspected of being hypochondriacs or psychoneurotics
[5]. Repeated light exposure can secondarily cause lichenified skin lesions.
Erythropoietic protoporphyria is a relatively
benign disease among the photosensitivity disorders. The most serious
complication is the development of hepatic disease, that occurs in 5 to
10% of the cases. Free protoporphyrin aggregates form solid deposits within
hepatocytes and small biliary radicles, with subsequent obstruction of
bile flow, portal inflammation, fibrosis, and cirrhosis. About 1% of patients
develop fatal hepatic disease [3].
It is important to be aware of erythropoietic protoporphyria, in cases
where sun exposure is repeatedly responsible for various symptoms, including
psychiatric manifestations. The lack of family history of photosensitivity
does not exclude the diagnosis. Family investigation must be always proposed.
The most important diagnostic criterion for erythropoietic protoporphyria
is an elevated level of free protoporphyrin in erythrocytes. Plasma protoporphyrin
and fecal porphyrins are also often elevated. Urinary porphyrins are normal.
A blood smear microscopic examination shows a red fluorescence in 5 to
30% of erythrocytes. Cutaneous biopsy in sun-exposed skin reveals accumulation
of a
perivascular, amorphous, hyaline-like substance, with positive periodic
acid Schiff staining in the papillary dermis, associated with complement
and immunoglobulin deposition [6]. Phototesting is unnecessary for diagnosis
and is often negative. In our case, itching could have been either psychological
or related to the visible light produced by the Dermolum.
Treatment of photosensitivity involves the complete
avoidance of sunlight, which is often not possible. Photoprotection with
conventional sunscreens, which absorb UVB radiation and the lower end
of the UVA region, is usually ineffective [3]. The most effective treatment
of erythropoietic protoporphyria seems to be oral ß-carotene and/or
canthaxanthin. Doses must be progressively increased to maintain blood
carotene levels between 600 and 800 µg/dl. A complete clinical effect
is achieved after about 1 to 3 months of therapy. If after this time,
there has been no significant increase in tolerance to sunlight, ß-carotene
should be discontinued [3].
The consequences of this treatment are a salmon-pink skin colour and
retinal crystal deposition that can be irreversible (for patients treated
over long periods). Therapeutic trials with phototherapy, terfenadine,
pyridoxine and cysteine, are encouraging. Some patients have improved
clinically with UVB phototherapy [3]. This wavelength is not absorbed
by porphyrins, and therefore does not cause photosensitivity. The increased
melanization and the hyperplasia of the epidermis may contribute to the
photoprotection provoked by UVB phototherapy. PUVA treatment from March
to June (optimal period) would enable the patients to remain in the sun
three times longer, but the protective effect diminishes by the end of
the summer. Cholestyramine may be useful for treating patients who develop
liver disease. For acute hepatic failure, blood transfusion may be of
benefit, until liver transplantation is possible.
REFERENCES
1. Magnus IA, Jarrett A, Prankerd TAJ, Rimington C. Erythropoietic protoporphyria:
a new porphyria syndrome with solar urticaria due to protoporphyrinaemia.
Lancet 1961; II: 448-51.
2. Langhof H. Mueller H., Rietschel L. Untersuchungen zur familiären
protoporphyrinamischen Lichturticaria. Arch Klin Exp Dermatol 1961;
212: 506-18.
3. Todd DJ. Erythropoietic protoporphyria. Br J Dermatol 1994;
131: 751-66.
4. Harber LC, Poh-Fitzpatrick FB, Walther RR, Grossman ME. Cutaneous
aspect of the porphyrias. Acta Derm Venereol (Stockholm) 1988;
195: 555-64.
5. De Selys R, Decroix J, Frankart M, Hassoun A, Willocx D, Pirard C,
Bourlond A. Protoporphyrie érythropoïétique. Ann
Dermatol Venereol 1988, 115: 555-60.
6. Marcoux C, Bourlond A. Protoporphyrie érythropoïétique.
Ultrastructure du complexe basal péricapillaire dans le derme superficiel.
Ann Dermatol Venereol 1988; 115: 561-4.
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