Scleral necrosis in congenital erythropoietic porphyria: A case report and review of the literature.

A 28-year-old presented with complaints of severe pain and redness in the left eye since 2 weeks. He had similar complaints in the right eye 2 years back for which he had undergone a scleral patch graft. Best corrected visual acuity was 20/20 in both eyes. The right had a well vascularized scleral graft and rest of the anterior segment was normal. The left eye had inferior conjunctival congestion with an area of the scleral melt with uveal show just temporal to the limbus in the interpalbebral area. The cornea was clear and anterior chamber was quiet in the left eye. Applanation tonometry and fundus evaluation were normal in both eyes. Physical examination revealed hyperpigmented skin lesion, hypertrichosis and absorption of distal phalanges. Laboratory, ocular and physical findings confirmed the diagnosis of congenital erythropoietic porphyria. He was on oral steroids 40 mg/day since 2 weeks and topical antibiotics and lubricants. He was advised to continue the same and was taken up for scleral patch graft with fibrin glue in the left eye. Postoperatively he was continued on topical and oral steroids and lubricants.3 weeks later the left eye had stabilized however patient came with a melt in the right eye. Since it was an early melt, we went ahead with cyanoacrylate glue and bandage contact lens in the right eye and started him on topical steroids for the right eye also. Three months later both the eyes were stable, and the patient was gradually tapered off the steroids.

Introduction

Porphyrias are a group of metabolic disorders involving heme synthesis. Acquired or inherited deficiency of one of the eight enzymes known to be involved in porphyrin metaobolism can lead to porphyrias. Patients with porphyria might have neurovisceral symptoms, photosensitivity or both. Neurological porphyrias have increased levels of porphyrin precursors, which are not photosensitive so cutaneous symptoms are not found,[1] whereas the photosensitive porphyrias have increased levels of porphyin. Ocular complications are rarely reported in porphyria. Among those that are reported scleral necrosis, corneal and conjunctival scarring, ectropion, and hypertrichosis are the commonest.[234]

We herein report a case of congenital erythropoietic porphyria (CEP) presenting as acute necrotizing scleritis with extensive scleral thinning requiring a scleral patch graft who developed a scleral melt in the other eye during the course of treatment of the primarily affected eye along with the literature review of ophthalmic manifestations.

Case Report

A 28-year-old male presented with a 2 weeks history of severe pain and redness in the left eye. There had been similar complaints in the right eye 2 years back and as per his previous records a scleral patch graft had been performed elsewhere for the scleral melt. His best-corrected visual acuity (BCVA) was 20/20 in both the eyes. Slit lamp evaluation of both eyes revealed a normal cornea. A raised triangular white plaque was noted in the conjunctiva adjacent to the limbus in the interpalpebral area at the 3’o and 9’o clock meridian. The conjunctiva overlying the raised area was scarred. The right eye revealed site of vascularized and conjunctivalized prior scleral patch graft 4 mm × 4 mm temporal to the limbus [Figure 1]. The left eye had conjunctival congestion. A 4.5 mm × 4.5 mm area of the scleral melt with minimal uveal pigments was seen at the temporal limbus [Figure 2]. This was associated with tenderness. Anterior chamber was quiet. Clinically there was no evidence of any infection. Intraocular pressure by applanation tonometry and dilated fundus evaluation were normal in both eyes.

Figure 1

At presentation postscleral patch graft done elsewhere 2 years back showing no current evidence of inflammation

Figure 2

At presentation 4.5 mm × 5 mm area of scleral necrosis and thinning along the temporal limbus with exposed uveal pigments with surrounding inflammation

Physical evaluation revealed hyperpigmentation of the skin with varying degrees of scarring and blisters, hypertrichosis, flat nasal bridge and resorption of distal phalanges [Figures 3 and 4]. Blood counts were normal and rheumatological work up was negative. He gave a history of photosensitivity since childhood and his younger brother having expired a year back from complications related to CEP. Based on his medical and family history and clinical features he was being treated elsewhere for a presumptive diagnosis of CEP. Laboratory evaluation at our tertiary eye care center revealed pink colored urine, altered liver enzymes. Urine examination for coproporphyrin and uroporphyrin was positive. The patient was referred to a dermatologist who also confirmed the diagnosis. A diagnosis of necrotizing scleritis in the left eye secondary to CEP was made based on the above findings.

Figure 3

Systemic features suggestive of hyperpigmentation of skin, hypertrichosis, resorption of ears

Figure 4

Systemic features suggestive of resorption of distal phalanges noted in both upper extremity

The patient had already been initiated on systemic steroids (40 mg/day) and topical lubricants for 2 weeks at the time of presentation. In view of significant scleral thinning with early uveal show, a scleral patch graft was planned for in the left eye. Intraoperatively the necrotic area was debrided, and donor sclera was fashioned using a 5.5 mm trephine. The graft was anchored to the host bed using fibrin glue (Tissel kit, Baxter AG, Vienna, Austria) and reinforced with 6 interrupted 9–0 nylon sutures (M/S GN corporation Ltd., Yamanashi, Japan). The surrounding conjunctiva was then advanced to cover the graft and stuck using fibrin glue. Postoperatively the patient was started on tapering dose of topical steroids and lubricants. The dose of systemic steroids was increased to 60 mg/day (1 mg/kg) with weekly tapering. Continued need for ultraviolet (UV) protective glasses was emphasized. When examined 3 weeks later, the left eye was noted to be healing well with subsidence of symptoms [Figure 5], however early melt was noted over the area of previous scleral patch graft in the right eye associated with pain [Figure 6]. There was moderate tenderness with the adjacent area being inflamed. Cyanoacrylate glue was applied for tectonic stability, and a bandage contact lens was placed and tapering doses of topical steroids was initiated. On further enquiry, the patient admitted to not using UV protective glasses regularly, and strict need for the same was reemphasized.

Figure 5

Three weeks postscleral patch graft left eye showing a well vascularized graft with a quiet eye

Figure 6

Three weeks postscleral patch graft the right eye presenting with an area of melt over the previous scleral graft with surrounding inflammation clinically showing no evidence of infection

When examined 3 months later both the eyes were quiet [Figure 7a and b]. The scleral graft had integrated well in the left eye. Cyanoacrylate glue was in situ in the right eye and the sclera showed early vascularization. The patient was asymptomatic and was advised to gradually taper off steroids.

Figure 7

(a) Three months later a quiet left eye showing a well-integrated and vascularized scleral patch graft (b) Three months later a quiet cyanoacrylate glue and bandage contact lens in situ with subsidence of inflammation in the right eye

Discussion

Congenital erythropoietic porphyria or Gunther's disease is an extremely rare autosomal recessive disorder with deficiency of Uroporphyrinogen III cosynthase. Based on the time of onset of symptoms, clinical features, and increased levels of uroporphyrin 1 and coproporphyin 1 in urine and absence of neurological symptoms our patient was diagnosed with CEP.[5]

We performed a thorough literature review of ophthalmic manifestations of CEP in the Pubmed search engine using the terms “ocular features of porphyria/ocular involvement in CEP” was done. Chumbley et al. were the first to report ocular manifestation in a patient with porphyria cutanea tarda.[2] Table 1 summarizes the cases of CEP with ocular manifestations published so far in the literature. The age of the patients ranged from 9 to 55 years of which there were 17 males and 5 females. Patients presented with varied ocular features ranging from blepharitis to conjunctival and corneal scarring to scleral necrosis. Most of them were started on topical and systemic steroids to control inflammation and advised photoprotection. The parts exposed to UV rays of sun like the skin, lids, conjunctiva, cornea and sclera are the most vulnerable to being affected though the exact mechanism is still poorly understood. The dermatological changes are believed to be due to increased accumulation of porphyrin metabolites in the skin inducing phototoxic, oxygen dependent damage causing blistering with inflammation and subsequent scarring on exposure to sunlight. A similar mechanism can be the cause for conjunctival scarring in the interpalpberal area as was noted in our patient.

Table 1

Literature review of patients presenting with ocular manifestations in patients with CEP

Cytopathological evaluation of the conjunctival surface in these patients by Hillenkamp et al.[4] revealed hyperkeratotic squamous cells with low-grade inflammatory cells thus supporting the use of steroids in these patients. Takamura et al.[18] reported increased levels of tear porphyrins in these patients and also found that the levels correlated with the severity levels. In severe cases, retention of tear porphyrins can cause scleral melting necessitating a scleral patch graft for tectonic support. However, the basic pathophysiology continues, and there can be recurrent scleral melts over a period as was noted in our case.

Most of the cases reported so far in the literature have had scleral necrosis with clear corneas. The corneal involvement reported by Hillenkamp et al. appears more exposure related due to scarred lids. Scleral involvement occurs most commonly in the interpalpebral area. This is because porphyrin and its metabolites accumulate in the blood vessels supplying the sclera and cause phototoxicity, the same mechanism responsible for dermatological changes. Increased tear porphyrin levels alone may not be the causative factor for scleral necrosis as the cornea remains relatively unaffected in these eyes. A combination of accumulated toxic metabolites in scleral end vessels with increased tear porphyrin levels probably predisposes sclera to necrosis and melt, sparing the cornea. Thus protection from UV rays forms the main stay of treatment in these patients. Use of steroids is to primarily control inflammation and prevent further necrosis. Our patient developed recurrent scleral melt in the other eye over the area of previous graft despite being on oral steroids, highlighting that steroids therefore do not have a protective role in these cases.

Earlier reports have described the use of amniotic membrane transplantation (AMT). However in extensive areas of the scleral melt an AMT alone might not suffice, and a scleral graft would be required for tectonic support. The use of fibrin glue to secure the graft[19] facilitates better and faster securing of the graft enhanced with minimal reinforcing sutures. For systemic management, oral administration of charcoal or beta-carotene, hypertransfusion, splenectomy and recently bone marrow transplantation have been discussed, but photoprotection still forms the mainstay of treatment.[20]

To conclude CEP is an extremely rare form of porphyria and patients can present with ocular manifestations. Prompt diagnosis and appropriate management can prevent progression to globe threatening conditions. However, further studies to understand the actual pathophysiology of the disease are required. Porphyrin metabolites accumulate in the blood vessels supplying the sclera inducing phototoxic damage in the palpebral area, whereas cornea receives its blood supply from the limbal arcade, which is not exposed to sunlight and therefore incidence of scleral involvement is much more than cornea. This reemphasizes the importance of photoprotection in the prevention of ocular manifestations of CEP.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.