Effective Treatment ofPhlyctenular Keratoconjunctivitiswith Oral Tetracycline

William W. Culbertson, MD, Andrew]. W. Huang, MD,Sid H. Mandelbaum, MD, Stephen C. Pflugfelder, MD,George T. Boozalis, MD, Darlene Miller, MS

Purpose: To determine the clinical characteristics, possible etiologic agents, andresponse to oral antibiotic therapy in patients with phlyctenular keratoconjunctivitis.. Methods: The authors reviewed the medical records of the 17 patients with phlyc­

tenular keratoconjunctivitis who were seen and treated at the Bascom Palmer EyeInstitute between 1981 and 1991.

Results: All 17 patients were younger than 18 years of age at the onset of theirdisease. Girls (n = 14) outnumbered boys (n = 3) 4:1. Significant incapacitating symptomsand ocular morbidity occurred frequently, including three perforated corneas. Five often patients who were tested for Chlamydia infection had positive test results and fivepatients possibly had early rosacea dermatitis. All patients experienced long-term re­mission of their ocular disease after a course of oral tetracycline or erythromycin. Twopatients demonstrated unique linear (fascicular) corneal phlyctenules.

Conclusion: Oral tetracycline or erythromycin treatment produces long-lasting re­mission of phlyctenular keratoconjunctivitis in affected children.Ophthalmology 1993;100: 1358-1366

Phlyctenular keratoconjunctivitis is a disorder character­ized by inflammatory conjunctival and corneal nodulesthat occurs primarily in girls. I The term phlyctenule isderived from the Greek word "phlyctena," meaning"blister," and early descriptions of the disease emphasizethe evolution of the corneal and conjunctival nodules toulceration (blister formation). 2 Before 1950, the diseaseoccurred predominantly in children with positive tuber­culin skin tests. Clinical and experimental evidencestrongly suggested that phlyctenular keratoconjunctivitis

Originally received: November 9, 1992.Revision accepted: February 8, 1993.

From the Bascom Palmer Eye Institute, University of Miami School ofMedicine, Department of Ophthalmology, Miami.

Presented at the American Academy of Ophthalmology Annual Meeting,Dallas, November 1992.

Supported in part by the Florida Lions Eye Bank, Miami, Florida.

Each author states that s/he has no proprietary interest in the developmentor marketing of this or a competing drug.

Reprint requests to William W. Culbertson, MD, Bascom Palmer EyeInstitute, PO Box 016880, Miami, FL 33101.

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represented a hypersensitivity reaction to tuberculin pro­tein. 3

-9 With the eradication ofendemic tuberculosis, the

disease has become less frequent, and almost all affectedpatients are found to have negative tuberculin skintests. 10, 11 However, nontuberculous phlyctenular kerato­conjunctivitis is still considered to be a delayed hypersen­sitivity reaction to foreign protein, usually to Staphylo­coccus.12,13

We report 17 young patients with phlyctenular kera­toconjunctivitis who experienced a prolonged or perma­nent inactivation of their disease after a course of oraltetracycline or erythromycin. In many cases, the patientshad been unsuccessfully treated for years with topical an­tibiotics and corticosteroids with only modest, temporaryrelief of symptoms.

Subjects and Methods

We reviewed the medical records of the 17 patients witha diagnosis of phlyctenular keratoconjunctivitis who weretreated at the Bascom Palmer Eye Institute during a 10-

Culbertson et al . Phlyctenular Keratoconjunctivitis

year period (1981-1991). The pertinent features of eachcase are summarized in Table 1. Over the IO-year periodof the study, eight different ophthalmologists treated thesepatients, and a variety of laboratory tests were obtained.Ten of the 17 patients had some form of assay for chla­mydial ocular infection, which included Giemsa cytologicevaluation, chlamydial cultures on McCoy cells, and/ormonoclonal immunofluorescent antibody stain of con­junctival smears for Chlamydia antigen (Syva, San Jose,CAl. Bacterial cultures of the lid and conjunctiva wereobtained in nine patients. Two patients were skin testedfor tuberculosis. The case histories of six patients whotypified the entire group are presented.

Selected Case Reports

Case 1. A 7-year-old black girl had been followed for 2years with phlyctenular keratoconjunctivitis of the right eye. Shehad 20/30 visual acuity in the right eye, with follicles on boththe palpebral and bulbar conjunctiva. Phlyctenular nodules ex­tended 5 mm onto the inferior cornea. Topical corticosteroidsand oral antibiotics had been previously prescribed , but the pa­tient had never used them for more than a few days. She pre­sented with thinning and perforation of the right cornea, whichrequired temporary closure with cyanoacrylate glue (Fig IA).The patient was treated with tetracycline (250 mg orally 3 timesdaily for 3 months). The phlyctenular keratoconjunctivitis be­came inactive , and when the glue was removed the perforationwas sealed. The tetracycline was discontinued after 3 monthsbecause her teeth had become slightly yellow. The keratitis was

still inactive , without medication, 3 months later (Fig IB). Test­ing for Chlamydia infection was not performed, nor were lid OJ

conjunctival cultures done .Case 2. A 17-year-oldwhite girl (Fig 2A) had been followed

for 10 years with irritation and photophobia in both eyes asso­ciated with bilateral phlyctenular keratitis involving the inferiorcornea most marked in the left eye (Fig 2B). She had experiencedchalazia of both eyelids as a child and had been treated withtopical corticosteroid and antibiotic drops . Eyelid and conjunc­tival cultures for bacteria had been negative. Laboratory studiesfor Chlamydia were not performed. Her best-corrected visualacuity in the left eye had deteriorated from 20/20 to 20/60 be­cause of irregular corneal astigmatism induced by the phlycten­ular keratitis (Fig 2C). She had no facial dermatitis, althoughshe possibly had early rhinophyma (Fig 2a). A dermatologistcould not conclusively diagnose rosacea dermatitis. At 17 yearsof age, she was treated for the first time with oral tetracycline atan initial dose of 250 mg three times daily for 3 weeks followedby 250 mg once daily for 10 weeks. Within 4 weeks, there wasa dramatic decrease in symptoms and corneal inflammation (Fig2D). Improvement continued over the next 2 months witheventual complete resolution of active corneal and conjunctivalinflammation (Fig 2E). This quiescent state persisted withouttreatment during 3 years of follow-up.

Case 3 . A 12-year-old white girl had experienced recurrentirritation in the right eye for 5 years, which had responded toshort courses of topical corticosteroids. She presented with a 4­month history of a persistently red right eye that had not im­proved with the usual topical corticosteroid therapy . The best­corrected visual acuity was 20/60 in the right eye and 20/15 inthe left. She exhibited early rhino phyma and small pustules onthe nose and malar areas consistent with rosacea dermatitis (Fig3A). Modest lid scarring was present on the upper palpebral

Table 1. Summary of Cases

Age of Oral Antibiotic Treatment Follow-upPatient Onset Chlamydial Evidence of

No. (yrs) Sex Eye(s) Testing Rosacea Antibiotic Duration Duration Status

1 5 F aD NT 0 TCN 3 mos 6 mos Resolved2 7 F au NT TCN 3 mos 3 yrs Resolved3 7 F au G+;C- + TCN 5 mos 6 mos Resolved4 10 F as G-; IF- ; c- o TCN 6wks 3 mos Resolved5 15 M as G-; IF- 0 TCN 3 wks 3 wks Improved6 12 F as G+; IF+ 0 TCN 6wks 6 mos Resolved7 14 F as G- o TCN 3 wks 1 yr Resolved8 8 M as G+; C+ 0 DOXY; EMCN 2 mos 6 mos Resolved9 14 F as G+; IF+; c- o TCN 3 mos 6 mos Resolved

10 9 F au G-j IF- jc- o TCN 1 mo 9 mos Resolved11 3 M au NT TCN 9 mos 1 yr Resolved12 7 F au NT 0 EMCN 2wks 6 mos Resolved13 18 F au NT + TCN 1 mo 3 mos Resolved14 11 F au NT 0 TCN 3 mas 10 mas Resolved15 11 F au G-; IF+; C- EMCN 6wks 6 mos Resolved16 10 F au NT 0 TCN 6 wks 1 yr Resolved17 16 F au G-; IF-j c- o TCN 3 wks 10 mas Resolved

Ol) = right eye; as = left eye; au = both eyes; NT = not tested; G = Giemsa-stained conjunctival smear; IF = monoclon al immunofluore scentantibody stain for chlamydia; C = Chlamydia culture; + = positive test result ; - = negative test result ; TCN = oral tetracycline; EMCN = oralerythromycin.

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Figure 1. Case 1. A, a 7-year-old girl with cyanoacrylate glue, sealing theperforated corneal phlyctenule in the right eye before oral tetracyclinetreatment. B, inactive corneal scarring in the right eye 3 months afterdiscontinuing tetracycline and removal of the glue.

conjunctiva in both eyes (Fig 3B). There was superficial cornealvascularization and nodular infiltration in the inferior corneaand the bulbar conjunctiva in both eyes. In the right eye, theparacentral cornea was thinned to descemetocele level and asmall area oozed aqueous fluid as demonstrated by a positiveSeidel's test (Fig 3C). A Giemsa stain of an inferior palpebralconjunctival epithelial cell smear demonstrated basophilic in­tracytoplasmic inclusions consistent with Chlamydia species in­fection. However, conjunctival cultures for Chlamydia werenegative.

She was treated with oral tetracycline (250 mg 3 times dailyfor I month). Within 2 weeks, there was a marked decrease inthe corneal and conjunctival inflammation in both eyes withthickening of the thinned areas of the cornea in the right eyeand resolution of the aqueous leak (Fig 3D). The tetracyclinewas tapered to 250 mg once daily for an additional 4 monthsand discontinued. At this time, all active corneal inflammationhad resolved with regression and closure of the corneal vessels(Fig 3E). The corrected visual acuity in the right eye improvedto 20/25. There was no recurrence of active inflammation during6 months of follow-up.

Case 4. A IO-year-old white girl had experienced inter­mittent redness and irritation in the left eye for 4 months whichhad responded only temporarily to topical corticosteroids. Her

1360

best-corrected visual acuity was 20/20 in the right eye and 20/25 in the left. She had a palpable, nontender left preauricularlymph node. There was no evidence of rosacea dermatitis (Fig4A). The left eye demonstrated inferior corneal and diffusebulbarconjunctival nodules (Fig 4B) with an inferior superficial cornealpannus. Laboratory investigation for Chlamydia was negative.Lid and conjunctival cultures for bacteria demonstrated onlyPropionibacterium acnes. She was treated with tetracycline (250mg twice daily for 6 weeks)with dramatic resolution of the activekeratitis and conjunctivitis. During the fourth week of treatment,subepithelial infiltrates developed in the left cornea (Fig 4C)which resolved within 2 weeks while the patient was taking nospecific treatment other than tetracycline. She had no symptomsor active keratitis after 3 months of follow-up.

Case 5. A 22-year-old white man had been followed for 7years with a linear superficial vascularized corneal lesion in theleft eye (Fig 5A) which had slowly progressed inward in a radialfashion from the peripheral to paracentral cornea at the 3:30­and 7:30-0'clock positions (Fig 5B). This was associated withnodular conjunctival inflammation. He experienced recurrentepisodes of irritation which responded to topical corticosteroidtherapy. He presented with a 3-day history of increasing irritationand redness. His best-corrected visual acuity was 20/ I5 in theright eye and 20/40 in the left. There was no evidence of rosaceadermatitis. The right eye was normal but the left eye demon­strated an inferior palpebral conjunctival follicular response witha 3600 corneal pannus. The vascularized linear corneal lesionswere surrounded by anterior stromal cellular infiltration andhaze, and a focal inflammatory nodule was present at the centralend of the linear lesion (Fig 5B). Conjunctival cultures and im­munofluorescent staining of the conjunctival smears were neg­ative for Chlamydia. The patient was treated with oral tetra­cycline (250 mg 4 times daily for 6 weeks) with relief of symp­toms, return of 20/20 visual acuity, and resolution of activecorneal and conjunctival inflammation in the left eye.

Case 6. A healthy 17-year-old white girl had experiencedintermittent episodes of pain and redness in the left eye since12 years of age. She presented to us at 17 years of age with 20/20 visual acuity in both eyes. The right eye was normal. The lefteye showed two linear vascularized superficial corneal lesionswhich extended toward the central cornea from the 4:00- and8:00-0'clock positions from the periphery in a radial fashion,similar to the lesion seen in case 5 (Fig 6). A nodular focal areaof superficial corneal inflammation was present at the centralextent of the two lesions. There was no evidence of rosacea. Notreatment was recommended. The patient presented to anotherophthalmologist 7 months later with perforation of the corneaat the 4:00-0'clock position in the tract of the lesion. A lamellarcorneal patch graft was placed over the defect, and the patientwas treated with oral tetracycline (250 mg 3 times daily) with amarked reduction in corneal inflammation and regression ofthecorneal vessels. Giemsa and immunofluorescent staining ofconjunctival scrapings were positive for Chlamydia.

Case 7. A 14-year-old asymptomatic white girl was seenbecause of a prominent follicular response in the inferior con­junctival fornix which had been noted by her parents. Her visualacuity was 20/20 in both eyes. She had bilateral nontenderpreauricular lymphadenopathy and prominent upper and lowerpalpebral and bulbar conjunctival follicles. Peripheral nodularanterior stromal and epithelial infiltrates were observed in bothcorneas. There was no evidence of rosacea dermatitis. A biopsyof the bulbar conjunctiva showed follicle-like nodules consistingof a central area of B lymphocytes and histiocytes surroundedby a mantle oflymphocytes (Fig 7). Giemsa stains of conjunctivalsmears showed lymphocytes and polymorphonuclear cells but

Culbertson et al . Phlyctenular Keratoconjunctivitis

Figure 2. Case 2. A, a 17-year-old girl with bilateral phlyctenular keratoconjunctivitis in both eyes demonstrates possible early rhinophyma. Noticethe absence of facial pustules. B, active corneal phlyctenule in the left eye at 12 years of age. C, progression of phlyctenular keratitis in the left eyeat 17 years of age before tetracycline treatment. D, marked improvement in phlyctenular keratitis in the left eye 4 weeks after institution of oraltetracycline therapy. E, inactive corneal scar in the left eye 11 months after completing the 3-month course of oral tetracycline.

no intraepithelial inclusions. The patient was treated with oraltetracycline (250 mg 4 times daily for 3 weeks) with resolutionof the follicles and keratitis. She returned I year later with arecurrence of similar findings. Treatment with oral tetracycline(250 mg 3 times daily for 6 weeks) again resulted in resolutionof her clinical findings. Follow-up I year later showed no reac­tivation of her keratoconjunctivitis.

Results

The results ofour review of these 17 cases of phlyctenularkeratoconjunctivitis are summarized in Table 1. All casesoccurred in children or teen-agers who ranged in age from3 to 18 years at the onset of their symptoms. Girls pre-

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Figure 3. Case 3. A, rosacea dermatitis with pustules and rhinophyma in a 12-year-old girl. B, conjunctival scarring on the palpebral surface of theright upper eyelid. C, extensive area of phlyctenular keratitis in the right eye with corneal perforation (arrow) before oral tetracycline treatment. D,marked decrease in corneal inflammation and healing of leaking descemetocele after 2 weeks of tetracycline treatment. E, resolution of all activecorneal and conjunctival inflammation in the right eye with return of 20/25 visual acuity 5 months after treatment.

dominated (82%)over boys (18%).Both eyeswere affectedin II patients (65%), whereas in 6 patients (35%) the dis­ease was detectable in only one eye. Of the ten patientsin whom laboratory evaluation for conjunctival Chla­mydia infection was performed, five (50%) had at leastone positive test for Chlamydia. Random conjunctival

1362

and eyelid cultures for bacteria performed in nine patientswere negative for pathogens, including Staphylococcusaureus. The two patients undergoing tuberculin skin test­ing had negative test results (cases 9 and 14). Clinicalsuspicion of early rosacea dermatitis was present in fivepatients, although a definite clinical diagnosis could be

Culbertson et al . Phlyctenular Keratoconjunctivitis

Figure 4. Case 4. A, a lO-year-old girl with phlyctenular keratoconjunctivitis in the left eye exhibits only freckles, with no evidence of rosacea. B,typical bulbar conjunctival nodules in the left eye seen best with the slit-lamp beam shined tangentially across the surface of the globe. C, subepithelialcorneal infiltrates in the left eye developing during the fourth week of tetracycline treatment.

made in only two of these (cases 3 and 13). All patientswere otherwise healthy.

The majority of patients (n = 14) were treated withoral tetracycline alone for 3 weeks to 9 months. One pa­tient was treated with both erythromycin and doxycycline(case 8) and one was switched to erythromycin when gas­trointestinal distress developed after 2 days of treatmentwith tetracycline. One young patient (case 2) receivederythromycin as her only treatment. In all patients whowere followed for 3 months or more (n = 16), a long­lasting, if not indefinite, resolution of symptoms and clin­ical findings occurred. No patients returned for retreat­ment except case 7, who had received only 3 weeks oftetracycline initially, When retreated for 6 weeks, her ker­atoconjunctivitis resolved indefinitely.

Corneal perforation occurred in three patients beforeoral antibiotic therapy (cases 1,3, and 6). The conditionsof all three patients stabilized after tetracycline therapy.

Discussion

Phlyctenular keratoconjunctivitis is a disorder occur­ring primarily in children characterized by inflamma-

tory superficial conjunctival or corneal nodules. 1 Ac­cording to Duke-Elder.? it has been described in classicalGreek and Arabic literature with later definitive de­scriptions by de Saint-Yves!" (1722) and Wardrop"(1808). Associations with reactive tuberculin skin tests,staphylococcal blepharitis, and facial skin lesions haveall been documented in early publications.3- 6, 10- 13, 16 Asa result of these clinical observations and studies withanimal models, phlyctenular keratoconjunctivitis hasbeen traditionally thought to develop as a delayed typehypersensitivity response to foreign microbial pro­tein. 17

-22 Clinical strategies directed toward either

eliminating the microbe (for instance, Staphylococcus)or desensitizing the patient have only produced modestand inconsistent clinical improvement.6,13,23,24 How­ever, almost all patients respond to topical corticoste­roid therapy, but unfortunately, when this treatment isdiscontinued, the disease usually recurs."

With the elimination of endemic tuberculosis in theUnited States after 1950,phlyctenular keratoconjunctivitiswas encountered much less often, usually in patients whohad negative tuberculin skin test results. 10,1 I This "non­tuberculous" phlyctenulosis has been associated with other

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Figure 5. Case 5. A, early "fascicular't-type phlyctenules (arrows) in theleft cornea seen in a lfi-year-old boy. B, the same patient at 22 years ofage with progression of fascicular phlyctenules (arrows).

Figure 6. Case 6. Fascicular phlyctenules (arrows) originating at the4:00- and 8:00-0'clock positions in the left eye in a 17-vear-old girl, similarto case 5. Perforation of the cornea occurred 7 months later at the 4:00­o'clock position.

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Figure 7. Case 7. Histopathologic section of bulbar conjunctival biopsyof a l-l-year-old girl with conjunctival and corneal phlyctenulosis. Noduleconsists of a germinal center with an outer mantle of lymphocytes sur­rounding a central area of B lymphocytes and histiocytes.

bacteria (particularly S. aureus), fungi, parasites, Chla­mydia, and rosacea dermatitis. 10-12,26-28

Our cases were consistent with previous descriptionsof phlyctenular keratoconjunctivitis reported in the lit­erature in both the pre-endemic and post-endemic tuber­culosis eras. As in these reports, the disorder affected pri­marily young girls who exhibited typical inflammatoryconjunctival and corneal nodules. Many patients had beenmanaged with topical corticosteroids with only temporaryimprovement. Symptomatic morbidity occurred very of­ten with frequent absences from school, visits to theophthalmologist, inability to keep the eyes open, and psy­chologic disturbances. Mild to moderate visual loss wastypical, and three patients experienced corneal perfora­tions.

The remarkable finding in our study was the promptand long-lasting response ofall the patients to orally ad­ministered antibiotics, most frequently tetracycline.Unexpectedly, indefinite remissions of previouslychronic disease activity were universally observed afterdiscontinuation of the oral antibiotic treatment. Side ef­fects of this antibiotic treatment consisted of temporarygastrointestinal discomfort in one patient and mild yel­lowing of the teeth in another. The disease remissionappeared to be equally complete whether tetracycline orerythromycin was used. Since these two antibiotics havedifferent chemical structures and mechanisms of actionon bacteria, it is unlikely that a nonspecific anti-inflam­matory effect of both drugs could account for the long­lasting disease remission observed. Any anti-inflamma­tory effects would be expected to be transient, and thephlyctenular disease activity would recur once the drugwas discontinued, as is observed after cessation oftopicalsteroids. It would seem more reasonable that their an­tibiotic effect suppressed a causative microbe such as P.aenes or Chlamydia trachomatis. This beneficial effectof tetracycline is like that reported by Zaidman andBrowrr" in a series of six children with clinical featuressimilar to ours.

Culbertson et al . Phlyctenular Keratoconjunctivitis

On the basis of our study, we recommend treatmentwith oral tetracycline (250 mg 3 times daily for 3 weeksfollowed by 250 mg once daily for 2 months). Physiciansand patients should be aware of the risks of using oraltetracycline, including yellowing of the teeth and de­creased bone growth in children younger than 8 years ofage and photodermatitis and gastrointestinal irritation inall patients. In children younger than 8 years of age,erythromycin (25 mg/kg in 4 divided doses) may be usedalternatively. Our experience with the extended use oforal erythromycin is limited, and the advice of the patient'spediatrician should be obtained.

The cause of phlyctenular disease in our patients isuncertain. Concurrent chlamydial infection was a possi­bility in five of ten of our patients who were tested forChlamydia. Similarly, Bialasiewicz and Holbach'" de­scribed two patients with classic phlyctenular keratocon­junctivitis with evidence of conjunctival chlamydial in­fection. Thygeson,'? likewise, described a patient withphlyctenulosis associated with evidence of lymphogran­uloma venereum chlamydial infection. Our patients whowere positive for Chlamydia infection did not demonstrateother typical findings of inclusion conjunctivitis, nor werethey in the typical age groups for Chlamydia infection(all were between 7 and 14 years of age). We could notestablish a route that these patients may have acquiredtheir chlamydial infection. However, the permanent ben­eficial effects of tetracycline or erythromycin could be ex­plained by the known ability of these drugs to successfullyeradicate chlamydial infections. It is possible that thenumber of patients who truly had chlamydial infectionwas incorrect, given the inherent inaccuracies of the var­ious tests for Chlamydia that we used (sensitivitiesrangingfrom 40%-70%, depending on the test).

Another possible predisposing factor could be rosaceadermatitis. Ocular rosacea shares many features withphlyctenular keratoconjunctivitis but usually has its onsetin adults between the ages of 30 and 50 years.30

-34 It is

difficult to diagnose in children because the typical featuresof facial pustules, bimalar telangiectatic vessels, and rhi­nophyma have not yet developed. Four of the 5 patientsdescribed by Zaidman and Brown" and 5 of 17 of ourpatients had some clinical manifestations consistent withrosacea dermatitis. Possibly, additional patients willeventually express features of rosacea once they becomeadults. The initial effectiveness of tetracycline would beexplained if the patients had rosacea because tetracyclinehas been demonstrated to be beneficial in controlling boththe ocular and dermatologic manifestations of rosacea.35,36

Approximately 50% of patients with ocular rosacea whoinitially respond to oral tetracycline eventually experiencerecurrence of ocular disease.I'<" In contrast, none of ourpatients demonstrated reactivation of their phlyctenulardisease after tetracycline treatment during the period offollow-up.

Two patients (cases 5 and 6) presented with an unusualsubtype of phlyctenular keratitis which is similar to the"fascicular" keratitis described by Thygeson" and Duke­Elder.2 The precise linear progression along a radius to­ward the center of the cornea was initially diagnosed as

an occult injury in both cases. The significance of thismanifestation of phlyctenular keratoconjunctivitis is em­phasized by the eventual perforation ofthe cornea in onepatient who initially was not treated. Both patients re­sponded to oral tetracycline therapy.

Many patients demonstrated bulbar and palpebralconjunctival nodules such as in case 4 (Fig 4B). Histo­pathologically, these consisted of a central area ofB lym­phocytes and histiocytes surrounded by a mantle of lym­phocytes as seen in the bulbar conjunctival biopsy in case7 (Fig 7). This finding is similar to the mononuclear cellnodules found by Hoang-Xuan and co-authors" in con­junctival biopsies from patients with ocular rosacea. Intheir cases, these nodules were demonstrated to consistpredominantly of CD4 helper/inducer cells, and the au­thors postulated that the conjunctival inflammation intheir patients with rosacea was evidence for a type IVhypersensitivity reaction. Likewise, the corneal and con­junctival nodules seen in our patients and other patientswith phlyctenular keratoconjunctivitis are the morpho­logic expression of delayed hypersensitivity to diverseperiocular antigens, including bacteria such as Chlamydia.

Summary

Although phlyctenular keratoconjunctivitis is infrequentlyencountered today, affected children often suffer signifi­cant ocular morbidity including pain, visual loss, and cor­neal perforation. The etiology of this clinical syndromein an individual patient may include chlamydial infectionand/or rosacea in addition to other previously describedetiologic agents. Treatment with oral tetracycline orerythromycin provides long-lasting or even permanentremission of the disease in the majority of patients.

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