Coin-shaped epithelial lesions following an acute attack of erythema multiforme minor with confocal microscopy findings

We report an interesting ocular finding of bilateral multiple coin-shaped epithelial lesions along with the confocal microscopy findings in a patient following an acute attack of erythema multiforme (EM) minor. A 30-year-old male presented with a history of watering and irritation in both eyes of three days duration. He was diagnosed to have EM minor and was on oral acyclovir. Slit-lamp examination revealed multiple coin-shaped epithelial lesions. Confocal microscopy showed a corresponding conglomerate of hyper-reflective epithelial lesions. The corneal lesions resolved over six weeks with oral steroids and acyclovir. An immunological mechanism is suspected.

Ocular manifestations following Steven-Johnson's syndrome (SJS) is common and have been well-described in literature. [1,2] However, ocular manifestations following an att ack of erythema multiforme (EM) minor is rare. [1] We report an interesting ocular fi nding of multiple coinshaped epithelial lesions along with the confocal microscopy fi ndings following an acute att ack of EM minor.

Case Report
A 30-year-old male presented to us with a history of watering and irritation in both eyes of three days duration. He was diagnosed to have EM minor following an att ack of viral fever with skin eruptions on the face, arms and legs along with shallow, aphthous ulcers, one week back. There was no history of any drug intake leading to the fever and occurrence of skin eruptions. The erythrocyte sedimentation rate (ESR) was 42 mm/h and the total white blood count was 12,000 cells/mm 3 with predominant neutrophils (72%). Routine urine examination was normal. Blood and urine cultures were negative for bacteria and fungi. Chest X-ray was normal. Antinuclear antibody and rheumatoid factor were negative. He was on oral acyclovir 800 mg fi ve times/ On examination, he had papular skin eruptions on the face, arms and legs with two shallow painful ulcers in the buccal mucosa [ Fig. 1]. His best-corrected visual acuity was 20/20 in both eyes. Slit-lamp examination in both eyes revealed multiple coin-shaped epithelial lesions, some showing central clearing [ Fig. 2 A, B]. There was no involvement of the stroma. Corneal sensation (tested with wisp of cott on) was normal. Rest of the anterior segment, intraocular pressures and fundus examination were normal. Confocal microscopy (HRT II, Rostock corneal module, Heidelberg, Germany) showed conglomerates of hyper-reflective epithelial cells corresponding to the coin-shaped epithelial lesions [ Fig. 3]. The subepithelial nerve plexus, the stroma and endothelium were normal. He was started on oral prednisone, 60 mg/day slowly tapered by 10 mg/day over six weeks along with ocular lubricants (1% carboxymethyl cellulose eye drops, four times a day). The skin and corneal lesions [ Fig. 4] resolved over six weeks. Repeat confocal microscopy showed normal epithelial cells, subepithelial nerve plexus, stroma with keratocytes and endothelium.

Discussion
Erythema multiforme is an acute mucocutaneous hypersensitivity reaction characterized by a skin eruption, with or without oral or other mucous membrane lesions. EM has been classifi ed into a number of diff erent variants based on the degree of mucosal involvement and the nature and distribution of the skin lesions. EM major (toxic epidermal necrolysis) is more severe, typically involving two or more mucous membranes with more variable skin involvement -which is used to distinguish it from SJS, where there is extensive skin involvement and signifi cant mortality and morbidity of 5-15%. [3] These features are considered to be sequelae of a cytotoxic immunologic att ack on keratinocytes expressing non-self antigens. These antigens are primarily microbial (viral or bacterial infection) or drugs. [3] Cytotoxic eff ector cells, CD8 + T lymphocytes in the epidermis, induce apoptosis of scatt ered keratinocytes and lead to satellite cell necrosis. On the other hand, EM minor typically aff ects no more than one mucosa, is the most common form and may be associated with symmetrical target lesions on the extremities. Herpes simplex virus-induced EM minor constitutes 15-60% of EM minor. The treatment is a combination of acyclovir and oral steroids. [3] Ocular involvement in EM minor is rare. Unlike SJS, ocular fi ndings in EM minor have not been very well-described in literature (Medline search). [1,2,4,5] We report an interesting ocular fi nding of coin-shaped lesions with some lesions showing central clearing confined to the epithelium of the cornea with no involvement of the underlying nerves or the stroma. Confocal microscopy fi ndings show conglomeration of hyper-refl ective lesions in the epithelium. The disappearance of these lesions following treatment is also documented on confocal microscopy. A probable immunological reaction targeted against the epithelial cells in the epithelium is speculated.

Conclusion
In this case report, an interesting ocular fi nding of coin-shaped epithelial lesions with central clearing along with the confocal microscopy fi ndings is reported in a patient following an acute att ack of EM minor.  Idiopathic, traumatic and congenital abnormalities are the most common causes of isolated fourth nerve palsy. Midbrain hemorrhage causing isolated fourth nerve palsy is extremely rare. [1] We report a patient with acute isolated fourth nerve palsy due to a midbrain bleed probably due to a cavernoma.

Case Report
An 18-year-old lady presented with four weeks of binocular vertical diplopia that was accentuated in the downward gaze. She also developed tinnitus episodically in the right ear. She gave no history of any systemic disease.
On examination, her uncorrected visual acuity was 20/20, N6 in both eyes. Her head position was normal. Her extraocular movements in the right eye were normal. Her left eye showed over-action of inferior oblique (+2) and under-action of superior oblique (-2). Cover test showed a small left hypertropia that increased on left head tilt (Beilschovosky's test positive). The left hypertropia was more in the right down gaze. Diplopia charting with red green goggles (red in front of the right eye and green in front of the left eye) showed vertical diplopia, with the red image higher than the green image, in the primary position, dextroversion, on down gaze and on right down gaze. The Department of Neuroophthalmology and Department of Neuropathology, Narayana Netaralaya, Bangalore, India Correspondence to: Dr. Raghavendra S, Narayana Nethralaya and Kanva Diagnostic Centre Bangalore, India. E-mail: raghavneuro@yahoo.com Manuscript received: 10.08.08; Revision accepted: 31.12.08 297_08 separation of images was maximal in the right down gaze. Pupils were equal, normally reacting to light. There was no relative aff erent pupillary defect. Near refl ex was present. Convergence was normal. The fundus examination with indirect ophthalmoscopy was within normal limits. Slit-lamp examination showed a normal anterior segment in both eyes. Corneal sensations were normal in both eyes. Facial nerves were normal. Hearing was clinically normal. Rinne's test was positive bilaterally and Weber's equal. Throat and neck movements were normal. There were no motor, cerebellar or sensory abnormalities in the limbs.
Magnetic resonance imaging (MRI) brain including contrast study showed a dorsal midbrain lesion in the area of right tectal plate that was hypointense on T2 weighted image and showed blooming on susceptibility and gradient T2 imaging without any fl ow voids surrounding the area located [ Fig. 1 A-D].
She was given prisms in the lower segment of the glasses to alleviate her diplopia in down gaze. In view of the strategic location and the minimal defi cit a decision for close follow-up and intervention if new symptoms develop was taken. At six months follow-up, she had no tinnitus or hearing disturbance and her defi cits remained same. A repeat MRI showed the lesion to be static.

Discussion
We here report a patient of isolated fourth nerve palsy