592 Bn'tishlJournal ofOphthalmology 1992; 76: 592-593

Photodamage of the conjunctiva in patients with Br J Ophthalmol: first published as 10.1136/bjo.76.10.592 on 1 October 1992. Downloaded from porphyria cutanea tarda

Helga Hammer, Irma Korom

Abstract Table I Clinicalfindings on external ocular structures in Ninety two patients with porphyria cutanea patients with porphyria cutanea tarda (PCT) and in a tarda (PCT) were examined ophthal- matched control group micaily in a paired case control study. The Patients with Control group incidence ofpinguecula and ofpterygium was 8 Symptoms PCT(n=92) (n= 184) and2 times higherrespectively, inPCT patients Hypertrichosis in the periorbital to area 76 4 p<0-001 than in the control group. The photodamage Solar elastosis in the temporal the conjunctiva is considered to be a result region 81 47 p<0-001 in the Favre-Racouchet disease 7 1 p<0-01 of the photoactivity of uroporphyrin Erosive lesions on lids 9 0 p<0-001 tissues. Pinguecula 63 16 p<0-001 (BrJ' Ophthalmol 1992; 76: 592-593) Pterygium 8 7 p>0-10

Porphyria cutanea tarda (PCT) is a chronic OPHTHALMIC EXAMINATIONS polyaetiological disorder in porphyrin bio- Slit-lamp examination, ophthalmoscopy, visual synthesis, caused by a deficiency of field examination, tonometry, Schirmer test, uroporphyrinogen III decarboxylase in the liver corneal staining, and colour vision test were cells, with typical skin and liver findings, as well carried out in all patients and controls. as pronounced uroporphyrin excretion in the urine.' The skin manifestations are bullous erosive lesions triggered on the face and the PORPHYRIN DETERMINATION backs of the hands by minor mechanical trauma, Urinary and faecal porphyrins were analysed by milia formation, melanosis, hypertrichosis in the thin-layer chromatography.4 eyebrows and the zygomatic area, chronic actinic skin changes, and pseudoscleroderma. The evidence suggests that the photoactivity ofexcess HISTOLOGY porphyrin in the plasma and/or tissues is involved The biopsy specimens were obtained from the in the cutaneous manifestations. involved conjunctiva of six patients with PCT.

In the past few years, 92 patients with PCT The tissues were fixed in formaldehyde solution http://bjo.bmj.com/ have been examined ophthalmically. In this (10% neutral formalin), embedded in paraffin, study the results of examinations of external and sectioned in 5 um thicknesses. The sections ocular structures (lids, conjunctiva, corneas, and were stained with haematoxylin and eosin and scleras) are reported. resorcin and fuchsin.

Patients and methods Results on September 24, 2021 by guest. Protected copyright. A paired case control study was performed.2 For The incidence of clinical symptoms on the every patient with PCT, two controls were external ocular structures is given in Table 1. matched according to age (plus or minus 3 years In 68 male and eight female patients with PCT was allowed) sex, and skin type on the basis of hypertrichosis was seen in the periorbital area. the tendency to burn and to tan3; furthermore, Frequently, diffuse solar elastosis in the temporal the members ofthe two groups worked in similar region and sometimes also solar elastosis with circumstances (indoor or outdoor). The fre- quencies of the pathological findings were compared by the X2 test.

PATIENTS The study involved 92 patients with PCT (81 Department of Ophthalmology, Albert men and 11 women; mean age 47-3 (SD 4 8) Szent-Gyorgyi Medical years). The diagnosis was based on the por- University, Szeged, phyrin profiles (uroporphyrinuria and Hungary 7-carboxylporphyrinuria) and on the clinical H Hammer manifestations. Department of Dermatology I Korom CONTROL GROUP Correspondence to: Dr Helga Hammer, PO Box The members ofthe control group suffered from 407, H-6701 Szeged, chronic venous insufficiency Hungary. psoriasis vulgaris, Figure I A nodule (yellow-brown in colour) on the temporal Accepted for publication of the legs, eczema, urticaria, or allergic contact side ofthe cornea in the intrapalpebral portion of the bulbar 14 May 1992 dermatitis. conjunctiva. Photodamage ofthe conjunctiva inpatients withporphyria cutanea tarda 593

cysts and comedones (Favre-Racouchot) were absorption spectrum of the porphyrins), and the observed. These findings were significantly rarer more penetrating light of the subsidiary peaks Br J Ophthalmol: first published as 10.1136/bjo.76.10.592 on 1 October 1992. Downloaded from in the control group. between 500 and 600 nm, raises the porphyrin to In 63 patients, yellow-brown nodules were its singlet or triplet excited state. Excited seen on either side ofthe cornea in the area ofthe porphyrins can react directly with tissues and lid fissure, which never extended onto the molecules within the cell, or they allow transfer limbus (Fig 1). During slit-lamp examination we of the excitation energy to molecular oxygen, observed foamy-like degenerative changes on the thereby producing oxygen radicals and surface of these nodules, which macroscopically peroxides.'0 The exposure of porphyrins to 400- resembled the structure of a pinguecula. Histo- 410 nm radiation results in complement logically, the epithelium was slightly thickened activation" and the release of mediators from and hyperpigmentation was seen in the basal mast cells.'2 The biological effects of oxygen layer. The immediate subepithelial stroma radicals, mast cell-derived mediators, and contained amorphous, faintly basophilic staining anaphylotoxin, generated as a consequence of material, and the stromal fibres were fragmented complement activation, may account for the and partially coiled. The histological findings damage ofthe sunlight-exposed tissues.1' Though corresponded to the microscopic structure of the photoactivity of the porphyrins explains pinguecula. In the control group typical many aspects of the pathophysiology of tissue pinguecula was observed in only 16 persons. damage in porphyria, there are still many Pterygium was seen in eight patients with PCT unanswered questions. For example, what and in seven controls. accounts for hypertrichosis in the periorbital Ectropion, blepharochalasis, symblepharon, areas of patients with PCT? comeal and scleral abnormalities were not Pterygium and pinguecula are consequences found in either the porphyric or the control ofthe actinic damage ofthe conjunctiva. 14 This is group. indicated by the facts that they appear in every case in the interpalpebral fissure, their frequency increases in proportion to age, the time spent in Discussion sunlight and the intensity of the solar radiation, The porphyrias are a group of diseases in which and their tissue structures are highly reminiscent there are deficiencies of the metabolic pathway of that of solar elastosis of the skin. We consider leading to the synthesis of haem. The error is that their high incidence in PCT is a consequence recognised as lying either in the imperfect of the phototoxic effect of the uroporphyrin synthesis ofenzymeshavingan aberrant structure accumulated in the tissues. We did not observe or in the slowed synthesis ofa perfect compound. the previously reported serious effects of photo- The most important feature of the current damage in porphyria - that is, ectropion, classification of porphyrias is that the metabolic symblepheron, blepharochalasis, and sclero- disorder can in all cases be localised to one malacia. The explanation of this may be that a

specific enzyme within the haem biosynthetic longer time is required for their emergence, but http://bjo.bmj.com/ pathway. in our cases the treatment (phlebotomy and PCT is the most common form of porphyria. chloroquine) led to normalisation of the The basic biochemical defect is a reduced activity porphyrin excretion in 3-6 months. of uroporphyrinogen decarboxylase in the liver, which in the overproduction and 1 Moore RM, McColl ELK, Rimington C, Goldberg A. Disorders results ofporphyrin metabolism. New York: Plenum, 1987: 179-200. increased excretion of uroporphyrin and poly- 2 Mantel N, Haenszel W. Statistical aspects of the analysis of

The cause of the data from retrospective studies ofdisease. J Natl Cancer Inst on September 24, 2021 by guest. Protected copyright. carboxylated porphyrins. 1959; 22:719-28. reduced enzyme activity is unclear, but appears 3 Melski JW. Tannenbaum L, Parrish JA, Fitzpatrick TB, to be a result of complex interactions of both Bleich HL. Oral methoxsalen photochemotherapy for the treatment of psoriasis: a co-operative clinical trial. J Invest genetic and acquired factors.' Derm 1977; 68: 328-35. In the present study, actinic damage of the 4 Doss M. Analytical and preparative thin-layer chromatography of porphyrin methyl esters. Z klin Chem klin Biochem 1970; periorbital skin was observed in 88 ofthe 92 PCT 8:197-207. patients, with erosive lesions on the lids in nine. 5 Seval D, Burger D. Ocular involvement on cutaneous porphyria: a clinical and histological report. Arch Ophthal- Pinguecula and pterygium were eight and two mol 1971; 85: 580-5. times, respectively, more frequent in the PCT 6 Toppel L. Veranderungen des Augenhintergrundes bei Porphyria cutanea tarda. Munch Med Wochenschr 1965; 107: group than in the matched controls (Table 1). 933-7. Though other authors have described lid scars 7 Barnes HD, Boshoff PH. Ocular lesions in patients with porphyria. Arch Ophihalmol 1952; 48: 567-80. and ectropion,56 we did not observe these in any 8 Gisod P. Les signes ophthalmologiques de la porphyrie of the patients, nor did we see those severe congenitale. Ann Oculist (Paris) 1969; 202: 937-51. 9 Douglas WH. Congenital porphyria. General and ocular changes ofthe externed ocular structures (scleral manifestations. Trans Ophthalmol Soc UK 1972; 92: 541-53. ulceration and and symblepharon) 10 Spikes JD. Photodynamic reactions in photomedicine. In: perforation, Regan JD. Parrish JA, eds. The science ofphotomedicine. New observed in congenital porphyria.7-9 York: Plenum, 1982: 113. skin lesions are clinically 11 Lim HW, Gigli I. Role of complement in porphyrin-induced Sunlight-induced photosensitivity. J Invest Dermatol 1981; 76: 4-9. characteristic of PCT. The evidence suggests 12 Lim HW, Wasserman Si, Gigli I. Differential effects of that the phototoxic effect of porphyrins is protoporphyrin and uroporphyrin on murine mast cells. J Invest Derm 1987; 88: 281-6. involved in the cutaneous manifestations. The 13 Lim HW. Pathophysiology of cutaneous lesion in porphyrias. of light with a wavelength of around Sem Hematol 1989; 26: 114-9. absorption 14 Spencer WH. Ophthalmic pathology. Philadelphia: Saunders, 400 nm (which corresponds to the peak in the 1985: 174-6.