Optometry (2008) 79, 133-137 Phlyctenular keratoconjunctivitis in a patient with Staphylococcal blepharitis and ocular rosacea Maryke N. Neiberg, O.D., and Joseph Sowka, O.D. Nova Southeastern University College of Optometry, Fort Lauderdale, Florida. KEYWORDS Phlyctenular keratoconjunctivitis; Rosacea; Blepharitis; Tuberculosis Abstract BACKGROUND: Phlyctenular keratoconjunctivitis is a type IV hypersensitivity reaction to an inciting agent. The presentation is usually bilateral. The diagnosis can be difficult, especially if compounded by an underlying skin disorder such as rosacea. The 2 types of phlyctenules are differentiated based on the location on the eye, i.e., conjunctival or corneal. CASE REPORT: A 22-year-old man presented with painful, bilateral, elevated vascularized corneal lesions. Ultimately, the diagnosis was bilateral phlyctenular keratoconjunctivitis secondary to concurrent posterior blepharitis and recurrent ocular rosacea. The patient was treated with topical steroids and followed up with until his lids and corneas stabilized. He was then maintained with oral doxycycline and cyclosporine ophthalmic emulsion 0.5%. Lid hygiene and maintenance is a key factor in the course of the disease. CONCLUSION: Phlyctenular keratoconjunctivitis usually responds well to topical steroids, but any inciting agents should be identified and treated. Complications include corneal scarring, thinning, and perforation. Staphylococcus aureus is a common culprit, and tuberculosis as a possible cause should also be considered. Optometry 2008;79:133-137 Phlyctenular keratoconjunctivitis is an uncommon, multifaceted manifestation of a hypersensitivity reaction to an inciting agent. Phlyctenular keratoconjunctivitis is considered a nonspecific allergic response in the cornea or conjunctiva to a variety of distinct circumstances. 1-5 The differential diagnosis is complex, especially if compounded by an underlying skin disorder, such as ocular rosacea. 5 The management considerations are therefore dictated by a careful differential diagnosis. Conditions such as inflamed pterygium, infectious corneal ulcer, herpes simplex keratitis, and ocular cicatricial pemphigoid should be considered. Furthermore, the location of the lesion on the eye itself is a further differential refinement. Two distinct types of phlyctenules exist and are primarily differentiated by their location on the eye. Conjunctival phlyctenules are found typically at the limbal margin and bulbar conjunctiva. The chief complaint of patients with conjunctival phlyctenules is usually tearing and irritation. In contrast, corneal phlyctenules start at the limbal margin and migrate over the cornea, leaving a triangular leash of neovascular pannus in their wake. The corneal presentation often is symptomatically more severe than the conjunctival phlyctenules. 1,2 In severe cases of corneal phlyctenular keratitis, tuberculin protein hypersensitivity should be suspected. 1,6 Corresponding author: Maryke N. Neiberg, O.D., Nova Southeastern University College of Optometry, 200 South University Drive, Fort Lauderdale, Florida 33328. E-mail: Neiberg@nova.edu Case report A 22-year-old white man presented with complaints of severe pain in both eyes accompanied by light sensitivity, 1529-1839/08/$ -see front matter 2008 American Optometric Association. All rights reserved. doi:10.1016/j.optm.2007.09.015
134 Optometry, Vol 79, No 3, March 2008 Figure 1 Severe hyperemia and edema are present. Telangiectasia and lid debris can also be seen. A, B, Right eye. tearing, and blurry vision in both eyes. He also complained of red, irritated eyelids of approximately 3 weeks duration. This condition was recurrent and seemed worse in the spring. The patient recalled the first episode a few years before in the left eye (O.S.) and remembered that the episode started after a period of extreme emotional stress. He had previously been treated for acne vulgaris with isotretinoin (Accutane; Roche, Nutley, New Jersey) on 2 separate occasions and was currently not taking any ocular or oral medications. The patient tried to self medicate for the first week, twice daily, with steroid drops that he had gotten from his previous eye care professional during the last episode, which was more than a year before. The current episode was the first occurrence in his right eye (O.D.). External evaluation found a severely erythmatous face with redness most marked over the cheeks and nose. Apart from the patient s ruddy appearance, his complexion was clear. Both eyes were blepharospastic, and he was extremely photophobic. He did not wear glasses or contact lenses. Unaided visual acuities were 20/30 2 O.D. and 20/20 2 O.S. Pupils were equal, round, and responsive to light and accommodation and without a relative afferent pupil defect. Eye movements and confrontation fields were full. On gross observation, both eyelids were edematous and inflamed. Both lid margins were tyalotic. Multiple telangiectasias were noted on both the superior and inferior lids. The lashes were matted, and a serous discharge was present as shown in Figure 1. Biomicroscopic examination found significant conjunctival (grade 3 ) injection bilaterally, with marked injection temporally O.D., and inferiorly O.S. Episcleral injection and chemosis were present in both eyes. In the right eye, perilimbal injection was noted around the cornea. A raised, fleshy white lesion arising from the temporal cornea traversed well into the cornea to approximately the center of the pupil. The lesion was in a location inferior to the visual axis and was highly vascularized and stained with sodium fluorescein at the leading edge in a deep semicircular shape. Stromal infiltration surrounded the lesion well into the visual axis. The rest of the cornea stained diffusely in a punctate pattern as shown in Figure 2. The left cornea had a similar, though less severe, appearance. The heavily vascularized lesion originated from the inferior limbal margin and was surrounded by white infil- Figure 2 The phlyctenule can be seen in the right eye actively encroaching the cornea with a neovascular leash following in its wake. The left eye has a similar presentation. A, Right eye; B, left eye.
Neiberg and Sowka Clinical Care 135 Figure 3 The lids and corneas are quiescent with scarring and neovascularization remaining. A, Right eye; B, left eye. trate. The cornea stained diffusely. The lesion stained with sodium fluorescein at its leading edge. The anterior chambers were deep and quiet, and both irides were flat and intact. The eyelashes were significantly matted and crusted. The meibomian glands were inspissated and the tears frothy. The lens and vitreous were clear in both eyes. Intraocular pressure evaluation and dilated eye examination were deferred because of the significant corneal epithelial disruption and blepharospasm. Bilateral phlyctenular keratoconjunctivitis, presumed to be secondary to Staphylococcal toxin hypersensitivity and chronic blepharitis compounded by rosacea was diagnosed. Acne rosacea was suspected based on the malar rash and eyelid telangiectasias. The patient was started on a regimen of moxifloxacin HCL ophthalmic solution 0.5% (Vigamox; Alcon, Ft. Worth, Texas) drops 4 times daily in both eyes. The patient was instructed on gentle lid hygiene twice daily, and cold compresses were recommended. Artificial tears were recommended for use every 2 hours in both eyes. A drop of scopolamine 0.25% was instilled in both eyes in the office to improve comfort. Topical steroids were withheld at this visit because of the extensive corneal compromise and the need for bacterial prophylaxis. The patient was instructed to return in 24 hours for follow-up. He was referred for a dermatology consultation for ocular rosacea and tuberculosis screening from his primary health care provider. The dermatologist confirmed the diagnosis of rosacea and began an appropriate course of doxycycline therapy. Unfortunately, the patient never presented for tuberculosis testing. The patient was seen again as scheduled the next day and reported improvement in comfort, but his eyes were still inflamed and photophobic. Unaided visual acuities at this time were 20/30 2 O.D. and 20/30 2 O.S. Both pupils were now pharmacologically dilated. The lids were still edematous but showed some improvement. The conjunctival inflammation and chemosis was unchanged in both eyes. The punctate epithelial disruption of the corneal was significantly decreased in both eyes. The area of semicircular staining still persisted in the right eye at the leading edge of the lesion. The left eye stained less at the leading edge than the previous day. The condition was improving both subjectively and objectively. Prednisolone acetate 1% every 2 hours was added to his regimen. The moxifloxacin was continued as prescribed, 4 times daily in both eyes. Gentle lid hygiene and compresses were to be continued. His condition improved over a period of several weeks, during which the topical antibiotics were discontinued and the topical steroids tapered appropriately. Once the condition cleared, the patient was instructed to maintain lid hygiene indefinitely. Topical cyclosporine (Restasis; Allergan, Irvine, California) was prescribed twice daily for any meibomian gland dysfunction related dry eye. Resolution is shown in Figure 3. Discussion Two distinct types of phlyctenular keratoconjunctivitis exist and are differentiated by the location of the phlyctenules on either the conjunctiva or the cornea. Conjunctival phlyctenules are usually found at the junction of the limbal margin and bulbar conjunctiva. The chief complaint typically is mild tearing and irritation. Conjunctival phlyctenules present as small, white nodules that are surrounded by hyperemia. The most common site for phlyctenules is the inferior cornea, usually between 8 and 4 o clock. 1,2 In the other, more severe form of corneal phlyctenular keratoconjunctivitis, a white wedge-shaped lesion with vascularization and leading ulceration of the lesion is present. 1,2,6,7,10 These usually are bilateral, and patients often present with matted lashes, tylosis ciliaris, and madarosis indicating chronic blepharitis. Corneal phlyctenules start at the limbal margin and migrate over the cornea, leaving a triangular leash of vascularized pannus in their wake. The presentation often is symptomatically more severe. 1,2,6 The corneal phlyctenular nodule may soften, ulcerate, and form a triangular scar or may be accompanied by a superficial punctate epithelial disruption. 6
136 Optometry, Vol 79, No 3, March 2008 Both the conjunctiva and the phlyctenular scrapings of the affected eye contain mononuclear phagocytes, dendritic Langerhans cells, polymorphonuclear leukocytes, and T- lymphocytes at the basal epithelial layers. Most of the cells in both scrapings are HLA-DR positive. Underlying stromal infiltrate consists of mononuclear (mostly monocytes) and polymorphonuclear leukocytes. The association of the T- lymphocytes and monocytes provides evidence that the phlyctenules are associated with a delayed immune response such as tuberculosis or Staphylococcal toxin hypersensitivity in which monocytes and monocyte derived cells play a central role. 8,9 These findings support the hypothesis that cell-mediated immunity is responsible for the pathogenesis of phlyctenular eye disease. A large percentage of cases of phlyctenular keratoconjunctivitis are caused by a type IV hypersensitivity reaction to Staphylococcus and tuberculosis; however, there are numerous other causes such as mycobacterium, Chlamydia, fungal, or parasitic pathogens. 1,2-4,6,10,11 The ubiquitous Staphylococcus aureus is frequently involved in chronic blepharitis and suppurative keratitis and is a common cause of phlyctenular keratoconjunctivitis. 1,2,4,11 Multiple staphylococcal conjunctival phlyctenules may occur at the same time, and the presentation is usually bilateral. 1 Interestingly, staphylococcal conjunctival phlyctenules are often more resistant to steroid treatment than tuberculin corneal phlyctenules associated with severe presentation. 1,6 Of note is a possible association between phlyctenular keratoconjunctivitis and ocular rosacea, but it is not clear if ocular rosacea has a causative role in phlyctenulosis. 5,12 In ocular rosacea, corneal thinning and neovascularization with infiltrates may be present. The lids appear red, and telangiectatic blood vessels are present, often in conjunction with redness and pustules found on the cheeks, nose, chin, and forehead. The symptoms of rosacea keratitis present variably. Rosacea often is accompanied by episcleritis and frequent chalazia, a result of the overgrowth of the staphylococcal flora on the patient s eyelids. Chalazion and hordeolum as a result of meibomian gland dysfunction are common signs of rosacea-related disease. 13-15 Rosacea is considered to be an inflammatory disorder, possibly of the same type IV hypersensitivity allergic (delayed, cell mediated) mechanism as phlyctenulosis. 13-15 Management of phlyctenular keratoconjunctivitis is aimed at eradication of precipitating conditions and topical antiinflammatory therapy. When accompanied by rosacea, the treatment strategy may include lifestyle changes to avoid triggers, such as sun or cold exposure, stress, and a change in diet. Topical corticosteroid drops should be prescribed to quiet inflammation and prevent anterior stromal scarring. 1 Care should be exercised because corneal thinning may be exacerbated with the overuse of corticosteroid drops. Topical cyclosporin A recently has been found to be a viable management option in cases of phlyctenular keratoconjunctivitis. 17 Oral tetracyclines are beneficial in the management of phlyctenular keratoconjunctivitis and can be especially helpful in cases in which ocular rosacea exists concurrently. 5,12,14,15 The outcome of limbal phlyctenular keratoconjunctivitis typically is quite good because these lesions usually heal without scarring, although they may become secondarily infected and scar. In cases of corneal phlyctenules, the prognosis is more guarded because corneal scarring and vascularization are more common. 1,6 In rare instances, corneal perforation is possible. 16 Patients may need prolonged systemic treatment of underlying diseases such as tuberculosis or parasitic infection, if present. Conclusion This case details the somewhat uncommon concurrent findings of corneal phlyctenules, blepharitis, and ocular rosacea. Phlyctenular keratoconjunctivitis responds well to topical treatment, but any inciting agents should be established and treated. In the case of rosacea, concomitant dermatologic care and lifestyle changes may be necessary to control the disease. A course of oral doxycycline often is prescribed to treat rosacea and phlyctenular keratoconjunctivitis concomitantly. Topical ocular steroids are essential to treat phlyctenules and prevent stromal scarring, but care should be taken to protect the patient from corneal thinning that could lead to perforation. Lid hygiene and maintenance are key predictive factors in the course of the disease. A multifaceted treatment plan aimed at eradicating each condition is necessary to effect a positive outcome. References 1. Rohatgi J, Dhaliwal U. Phlyctenular eye disease: a reappraisal. Jpn J Ophthalmol 2000;44(2):146-50. 2. Beauchamp GR, Gillette TE, Friendly DS. Phlyctenular keratoconjunctivitis. J Pediatr Ophthalmol Strabismus 1981;18(3):22-8. 3. Hussein AA, Nasr ME. The role of parasitic infection in the aetiology of phlyctenular eye disease. J Egypt Soc Parasitol 1991;21(3):865-8. 4. Bialasiewicz AA, Holbach L. Phlyctenular keratoconjunctivitis in bacterial epibulbar infections. Klin Monatsbl Augenheilkd 1987;191(4):260-3. 5. Blaustein BH, Gurwood AS. Recurrent phlyctenular keratoconjunctivitis: a forme fruste manifestation of rosacea. Optometry 2001;72(3): 179-84. 6. Singal A, Aggarwal P, Pandhi D, et al. Cutaneous tuberculosis and phlyctenular keratoconjunctivitis: a forgotten association. Indian J Dermatol Venereol Leprol 2006;72(4):290-2. 7. Durquety MC, Le Rebeller MJ, Jouneaux P. Marginal phlyctenular keratoconjunctivitis of tuberculous origin (bovine tuberculosis). Bull Soc Ophthalmol Fr 1986;86(8-9):1049-50, 1052. 8. abu el Asrar AM, Geboes K, Maudgal PC, et al. Immunocytological study of phlyctenular eye disease. Int Ophthalmol 1987;10(1):33-9. 9. abu el-asrar AM, Van den Oord JJ, Geboes K, et al. Phenotypic characterization of inflammatory cells in phlyctenular eye disease. Doc Ophthalmol 1988;70(4):353-62. 10. Koppert HC, van Rij G. The phlycten, a come-back? Doc Ophthalmol 1982;52(3-4):339-45.
Neiberg and Sowka Clinical Care 137 11. Ostler HB, Lanier JD. Phlyctenular keratoconjunctivitis with special reference to the staphylococcal type. Trans Pac Coast Otoophthalmol Soc Annu Meet 1974;55:237-52. 12. Culbertson WW, Huang AJ, Mandelbaum SH, et al. Effective treatment of phlyctenular keratoconjunctivitis with oral tetracycline. Ophthalmology 1993;100(9):1358-66. 13. Wilkin J, Dahl M, Detmar M, et al. National Rosacea Society Expert Committee. Standard grading system for rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol 2004;50(6):907-12. 14. Stone DU, Chodosh J. Ocular rosacea: an update on pathogenesis and therapy. Curr Opin Ophthalmol 2004;15(6):499-502. 15. Stone DU, Chodosh J. Oral tetracyclines for ocular rosacea: an evidence-based review of the literature. Cornea 2004;23(1):106-9. 16. Ostler HB. Corneal perforation in nontuberculous (staphylococcal) phlyctenular keratoconjunctivitis. Am J Ophthalmol 1975;79(3): 446-8. 17. Doan S, Gabison E, Gatinel D, et al. Topical cyclosporine A in severe steroid-dependent childhood phlyctenular keratoconjunctivitis. Am J Ophthalmol 2006;141(1):62-6.