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Ocular involvement in congenital erythropoietic porphyria (Günther's disease): cytopathological evaluation of conjunctival and corneal changes
  1. J HILLENKAMP,
  2. T REINHARD
  1. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Dermatology
  3. Department of Ophthalmology
  4. Institute of Cytopathology
  5. Department of Ophthalmology
  1. C FRITSCH
  1. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Dermatology
  3. Department of Ophthalmology
  4. Institute of Cytopathology
  5. Department of Ophthalmology
  1. A KERSTEN
  1. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Dermatology
  3. Department of Ophthalmology
  4. Institute of Cytopathology
  5. Department of Ophthalmology
  1. A BÖCKING
  1. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Dermatology
  3. Department of Ophthalmology
  4. Institute of Cytopathology
  5. Department of Ophthalmology
  1. R SUNDMACHER
  1. Department of Ophthalmology, Heinrich-Heine-University, Düsseldorf, Germany
  2. Department of Dermatology
  3. Department of Ophthalmology
  4. Institute of Cytopathology
  5. Department of Ophthalmology
  1. Dr J Hillenkamp, The Rayne Institute, St Thomas's Hospital, London SE1 7EH, UK hillenka{at}hotmail.com

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Editor,—The porphyrias are a group of rare inherited disorders caused by specific enzymatic defects of the haem biosynthetic pathway. Congenital erythropoietic porphyria (CEP) is an extremely rare autosomal recessively inherited disorder of the haem synthesis pathway first described by Günther in 1911.1Clinical symptoms are caused by a homozygous defect of the enzyme uroporphyrinogen III synthase2 which leads to severe anaemia and the accumulation of the biologically inactive type I porphyrins, particularly uroporphyrin I and coproporphyrin I, mainly in bones, erythrocytes, skin, and teeth. Excessive amounts of uroporphyrin and other porphyrin metabolites deposited in skin induce phototoxic, oxygen dependent damage characterised by subepidermal blistering with severe inflammation and subsequent ulceration and scarring of all light exposed skin areas. The phototoxic damage can lead to severe mutilations of hands, fingers, and face, particularly nose, ears, lips, and eyelids. Since 1874 approximately 130 cases of CEP have been reported worldwide. To date there is no known treatment. The only preventive measure is absolute avoidance of sunlight.3

To our knowledge, there are currently onlyfour patients living in Germany. There are no family relations among our patients.

CASE REPORTS

Patient 1 was a 38 year old man. Visual acuity was right eye: 0.3, left eye: 0.2. There was scarring of the entire face, bilaterally severely scarred retracted eye lids with incomplete lid closure (Fig 1), loss of eye lashes, scarred conjunctiva with symblepharon, corneal vascularisation and hyperkeratotic plaques in both eyes (Fig 2), with chronic recurrent corneal erosions.

Figure 1

Patient 1. Scarring of light exposed facial skin areas. Incomplete lid closure. Nasal prosthesis.

Figure 2

Patient 1. Bright eye: scarred retracted eye lids, lagophthalmos, corneal vascularisation and hyperkeratotic plaque.

There was corneal surface stabilisation with subsequent improvement of visual function to right eye: 0.5, left eye: 0.2 with topical supportive measures.

Patient 2 was a 55 year old woman. Visual acuity was right eye: 0.8, left eye: 0.4. there was scarring of the entire face, bilateral lid closure was almost complete, loss of eye lashes, scarred conjunctiva with hyperkeratotic plaques, scleral tissue substance defect and a clear cornea. Stabilisation of the ocular surface and visual function with topical supportive measures was carried out.

Patient 3 was a 42 year old man. Visual acuity was right eye: 1.25, left eye: 1.0. there were scarred eye lids with incomplete lid closure in the left eye, scarred conjunctival and scleral alterations with conjunctival hyperkeratotic plaques in the left eye, bilaterally scarred eye lids with symblepharon in both eyes, and a clear cornea. Stabilisation of the ocular surface and visual function with topical supportive measures was carried out. The patient had mutilated hands and fingers.

Patient 4 was a 34 year old man. Visual acuity was right eye: 0.2 (amblyopia), left eye: 1.0. There was intact lid closure, comparatively mild conjunctival scarring, and clear cornea. Stabilisation of the ocular surface and visual function with topical supportive measures was carried out.

Because of the clinical similarity to xeroderma pigmentosum which is known to be associated with a predisposition to malignant changes of light exposed cells4 and because the cell alterations of the ocular surface in CEP have not yet been characterised, we aimed to rule out malignant conjunctival or corneal cell changes by cytopathological evaluation of brush smears obtained from the ocular surface, a well established method.56 It revealed hyperkeratotic squamous cells, few granulocytes and lymphocytes with inflammative activation and degenerative unclear changes. Malignant or dysplastic cell changes of the ocular surface were excluded in all four patients.

Topical lubrication has led to improvement or at least stabilisation of visual function in all our patients. All patients reported subjective improvement of distressing foreign body sensation with topical treatment.

COMMENT

Alterations of lids, conjunctiva, and sclera, as well as the changes of other light exposed parts of the skin, are directly related to the described toxic effect of sunlight.

The corneal changes, on the other hand, have two causes. Firstly, conjunctival scarring causes a disturbance of the mucin layer of the tear film which in turn leads to a dry eye syndrome. Secondly, the dry eye syndrome is further aggravated by severely scarred eyelids with incomplete lid closure leading to lagophthalmos.

Inadequate closure of the lids not only results in corneal drying but also leads to increased exposure of the cornea, the conjunctiva and the sclera to sunlight. Overall, in CEP, lagophthalmos seems to be the main cause of severe aggravation of ocular surface symptoms.

Our clinical findings are in accordance with reports of CEP patients in the literature.7-9 In light and electron microscopy, Uedaet al found a reduced number of keratocytes, leucocytes, a thickened basement membrane of corneal and conjunctival blood vessels, and microfibrillar material in the extracellular space of the conjunctival stroma.7 There are no reports of malignant cell changes in the literature. The cytopathological evaluation of brush smears obtained from the ocular surface of our patients are compatible with these findings.

Attempts to correct lagophthalmos surgically cannot stop the ongoing scarring of the eyelids. We therefore recommend avoiding surgical treatment of scarred eyelids in CEP.

Hamard et al reported only temporary benefit from surgical correction of the eye lids because of impaired postoperative wound healing.10 We believe that supportive topical measures are the only recommendable treatment.

In summary, phototoxic alterations of the eyelids, the conjunctiva and the sclera represent the underlying pathological mechanism leading to ocular complications in CEP. Scarring of the eyelids may result in lagophthalmos with severe keratopathy and further aggravation of light induced damage to conjunctiva and sclera. The risk of development of neoplastic conjunctival or corneal cell changes appears to be low.

Acknowledgments

Presented at the annual meeting of the German Ophthalmologic Society (DOG), Berlin, 1999.

References

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