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Darier-White disease, also known as keratosis follicularis, is a relatively common genodermatosis (frequency between 1 in 36 000 and 1 in 100 000) with autosomal dominant inheritance and late age of onset.1 Clinical features consist of disseminated warty papules and plaques with an affinity to the seborrhoeic areas of the body. The disease may be exacerbated by sun exposure or sweating and never remits.
Ocular involvement in keratosis follicularis is relatively uncommon. Most of the affected patients have dry eye syndrome with and without Sjögren’s syndrome. Possible corneal manifestations are peripheral arcus lipoides-like opacifications, asymptomatic nebular dot-like opacities of the peripheral corneal epithelium, and central epithelial surface irregularities.2–4
We describe the first case of recurrent severe bilateral corneal ulcerations with perforation in a female patient with keratosis follicularis.
A 74 year old woman was referred to the university eye hospital with complaints of redness and reduced visual acuity in the left eye. She had no significant ocular history. She and her two daughters have been suffering from keratosis follicularis (Darier-White disease) for many years.
On first examination (February 2001) best corrected visual acuity was 0.8 in the right eye and 0.3 in the left eye. Both eyes showed pathological Schirmer’s tear test.
Slit lamp examination showed blepharitis marginalis on both eyes, thickened, knobbly lid margins, and a rarefication of the eyelashes. In the left eye there was a descemetocele without corneal perforation or intraocular inflammation (Fig 1A).
Microbiological examination of the conjunctiva indicated Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans.
The left eye was treated with ofloxacin and cyclosporin A eye drops. Additionally, both eyes were treated with artificial tears, and the clinical picture slowly improved over the next 9 days.
Four weeks later (March 2001) visual acuity was 0.7 in the left eye. Examination of the left eye revealed corneal staining and thinning at the 6 o’clock position. There were no signs of inflammation. Antibiotic therapy was discontinued.
Seven weeks later (April/May 2001) the patient reported foreign body sensation in the right eye. Slit lamp examination demonstrated 3+ conjunctival injection, 3+ anterior chamber cells, ulceration of the cornea at the peripheral 6 o’clock position, a descemetocele, anterior and posterior synechiae (Fig 1B). The aspect of the left eye was similar to the previous examination 7 weeks earlier.
The patient was again hospitalised and placed on topical ofloxacin and mydriatics. Microbiological examination indicated again Staphylococcus aureus, and additionally Candida albicans and Blastomyces. Therefore, topical antimycotic eyedrops were added.
During follow up the corneal infiltration and intraocular inflammation in the right eye slowly reduced.
Nine weeks after discharge (August 2001) the patient returned to the hospital. She reported burning of the right eye for 5 days. The therapy with ofloxacin had been discontinued 3 weeks previously, only the therapy with artificial tears had been continued.
Visual acuity was 0.02 in the right eye and 0.7 in the left eye. The right eye showed 3+ conjunctival injection, 3+ anterior chamber cells, and ulceration of the cornea. A corneal perforation at the peripheral 6 o’clock position was closed by an incarceration of the iris. The anterior chamber was flattened.
After intensive topical and intravenous antibiotic therapy and insertion of punctum plugs infection and inflammation slowly reduced. Visual acuity did not improve. The patient was discharged and was again controlled by her ophthalmologist.
We report a 74 year old woman patient with recurrent bilateral corneal ulceration and uniocular perforation probably associated with keratosis follicularis.
Keratosis follicularis (Darier-White disease) is caused by mutations in the ATP2A2 gene, which encodes the Ca2+ ATPase 2 isoform. This defect results in disturbed cell to cell adhesion and differentiation of the epidermis.6
Histopathological hallmarks of the disease are focal suprabasal clefting due to acantholysis, and subsequent dyskeratotic round epidermal cells (“corps ronds”) with overlying columns of parakeratosis.1
In our patient the recurrent corneal ulcerations with subsequent perforation could be explained by the participation of the ectodermal ocular tissues in keratosis follicularis: the lacrimal gland, the eyelids, and the corneal epithelium. A combination with Sjögren’s syndrome, dry eyes, oral mucosal lesions, and involvement of the salivary gland is known from the literature.7 A histological examination of the eyelids in one patient showed a characteristic epidermal involvement, but no participation of the specific adnexal glands of the lid margin. It was presumed that the knobbly, scaling lid margin could provoke symptoms and sequelae similar to seborrhoeic blepharitis.4 Recurrent localised or widespread cutaneous viral infections and secondary bacterial overgrowth is also common. Bacteria and fungi can colonise the keratotic debris.7
In our patient keratosis follicularis probably resulted in dry eye syndrome with reduced corneal protection and microbiological colonisation of the skin and ocular surface. Impaired functionality of desmosomes of the corneal epithelium caused the recurrent corneal ulcerations with perforation. Therefore it can be concluded that the increased risk of ocular complications in keratosis follicularis may include severe corneal infection. Beside the long term dermatological medical care an intensive ocular therapy with lubricants and antibiotics may help to avoid this ocular complication.