Summer 2021 • Vol 16 | No 1 Case report SA Ophthalmology Journal Idiopathic interstitial in a child 35

Idiopathic interstitial keratitis in a child

DA Erasmus MBBCh, MMed, Dip Ophth (SA); Registrar, Department of Neurosciences, Division of Ophthalmology, University of the Witwatersrand, Johannesburg, South Africa ORCID: https://orcid.org/0000-0002-8395-7080

R Höllhumer MBChB, MMed, FC Ophth(SA); Consultant ophthalmologist, Department of Neurosciences, Division of Ophthalmology, University of the Witwatersrand, Johannesburg, South Africa ORCID: https://orcid.org/0000-0002-4375-2224

Corresponding author: Dr DA Erasmus, 40 2nd Avenue, Parktown North, 2193; tel.: +27 76 462 3355; email: [email protected]

Abstract

Interstitial keratitis represents and new vessel investigations can help to establish the underlying cause of formation in the middle layers of the without tissue interstitial keratitis. loss. The most important infective aetiologies include herpes viruses, and . Keywords: interstitial, keratitis, inflammation, cornea, stroma Non-infectious causes such as Cogan’s syndrome should be considered in those cases with associated neurosensory Funding: No external funding was received. hearing loss. The pattern and laterality of inflammation together with the Conflict of interest: The authors have no conflicts of interest presence or absence of systemic features as well as relevant to declare. Severe Mild Moderate Moderate/Mild A * Dry Eye range like NEVER BEFORE

Introduction systemic features provides a clue to the a tuberculosis (TB) endemic area such as Interstitial keratitis is a non-ulcerative underlying cause of interstitial keratitis. South Africa. Parasitic infections causing inflammation and subsequent Interstitial keratitis can be broadly interstitial keratitis are very uncommonly vascularisation of the corneal stroma divided into infectious and non-infectious encountered in South Africa but imported which does not primarily involve the aetiologies. There is a paucity of cases may be due to entities such as epithelium or endothelium. The underlying information regarding interstitial keratitis , (river pathophysiology is believed to be a in Sub-Saharan Africa and in the paediatric blindness) and trypanosomiasis. cellular and humoral immune-mediated population more generally worldwide. The Non-infectious cases include Cogan’s type IV hypersensitivity response directed majority of cases that have an infectious syndrome, sarcoidosis, Hodgkin’s and

Contains towards corneal stromal antigens, aetiology in adults are viral (with herpes T-cell lymphoma, Kaposi’s sarcoma, gold HA** infective antigens or a combination of simplex virus comprising 35.1%) or and arsenic toxicity, and intraocular both.1,2 Clinically the infiltration may be treponemal (comprising approximately sclerosing inflammatory pseudotumour.1-3 diffuse, focal or multifocal and may be 18.6% of cases of both congenital and We present a case of idiopathic interstitial Taking care of all types of Dry Eyes located superficially or, more commonly, acquired infection); no identifiable cause keratitis in a South African child. deep within the stroma. It may be is found in 32% of cases. Other important unilateral or bilateral and be further viral infections in adults include Epstein- Case presentation *Pertains to the unique actuator of Artelac Splash Eye Drops and the unique formulation of Artelac Intense Rebalance Eye Drops. **Hyaluronic Acid. divided into active and inactive forms Barr virus (1%), human T-lymphocytic virus A seven-year-old black African female was Proprietary name: Artelac® Advanced Lipids Eye Drops. Contains 2 mg carbomer, medium chain triglycerides. Preservative: Cetrimide (10 g multi-dose only). Proprietary name: Artelac® Intense with the latter defined as a period of type I, mumps and varicella zoster virus bought in by her mother with a one-week Rebalance Eye Drops. Contains 0,15 % hyaluronic acid (as sodium hyaluronate), 0,5 % polyethylene glycol 8000, vitamin B12. Preservative: Oxyd® (a gentle preservative that converts to water, oxygen and salt at the surface of the eye in the 10 ml multi-dose unit only). Proprietary name: Artelac® Splash Eye Drops. Contains 0,24 % hyaluronic acid (as sodium hyaluronate) in the 10 ml multi-dose unit and no characteristic signs and symptoms (3.1%). Another important mycobacterial history of decreased vision (left eye worse 0,2 % hyaluronic acid (as sodium hyaluronate) in the single dose units. Both the 10 ml multi-dose and single dose units are preservative free. Proprietary name: Artelac® Moisture Eye Drops. Contains 0,32 % hypromellose. Preservative: Cetrimide (10 ml multi-dose only). in the preceding year. The topographical cause is tuberculosis (3.1%), although this than the right) with associated pain and For full prescribing information, refer to the instructions for use. Further information is available on request from Bausch + Lomb. © 2017 Bausch & Lomb Incorporated. ®/™ denote trademarks of distribution together with the presence of is expected to have greater relevance in redness. Furthermore, both of her wrists Bausch & Lomb Incorporated. Distributed by: Sofl ens (Pty) Ltd. Reg. No.: 1968/011787/07. 254 Hall Street, Centurion. Tel: +27 10 025 2100. www.bausch.co.za BL386/19 Case report Vol 16 | No 1 • Summer 2021 36 Idiopathic interstitial keratitis in a child SA Ophthalmology Journal

Figure 1a. No abnormal facies, no saddle nose deformity or low- Figure 1b. Normal dentition set ears had begun to swell and become stiff General examination revealed no pallor, swollen, tender and warm to the touch approximately two weeks prior. Although jaundice, lymphadenopathy or pitting with clinical effusions as seen in Figure 1d. the patient denied this was painful, her oedema. Importantly there were no Both ankles were mildly tender without mother noted that it improved throughout stigmata of congenital syphilis infection any gross deformity. the day and was exacerbated by cold including Hutchinson’s teeth, mulberry Vision was recorded as 6/18 on the weather. There were no episodes of molars or sabre tibias (Figures 1a and right and counting fingers on the left with headaches, nausea, vomiting or tinnitus. b). The patient was able to walk unaided no improvement on pinhole. Both eyes Although the patient was HIV-exposed, without difficulty. Her left hand revealed had ciliary injection with multifocal areas her birth PCR was confirmed negative. a ‘Z’-shaped deformity with bilaterally of stromal inflammation and marginal The remaining maternal booking swollen and mildly tender proximal infiltrates that were more prominent on the bloods (including RPR) were negative. interphalangeal joints with associated Immunisation history was inconsistent, Boutonniere deformities as seen in with a period of six years elapsing without Figure 1c. Similarly, both wrists were coverage. Developmentally the patient’s mother reported that she had achieved normal milestones although she gave the history that her hearing was poor from a ‘young age’. Despite this she was coping well academically in Grade 2. At the age of 2 years the patient was diagnosed with juvenile idiopathic arthritis (JIA) following an episode of joint swelling. She was commenced on methotrexate, chloroquine and prednisone for the period 2012 to 2017 during which time she was reportedly well controlled. She was subsequently lost to follow-up and no further symptoms were reported until the most recent Figure 1c. Dorsal view of the hands presentation. She was otherwise well with showing ‘Z’-shaped deformity of the no other admissions. There are no known thumbs with swollen interphalangeal Figure 1d. Lateral view of the hands and contacts with TB. joints and wrists wrists showing wrist swelling Summer 2021 • Vol 16 | No 1 Case report SA Ophthalmology Journal Idiopathic interstitial keratitis in a child 37

Figure 2a. Left eye showing multifocal areas of inflammation and Figure 2b. Right eye showing multifocal areas of stromal deep vascularisation. Note the ‘salmon-patch’ lesion inferiorly inflammation and vascularisation left (Figures 2a and b). Three hundred-and- film was normal (Figure 3) and a tuberculin patient was started on dexamethasone sixty degrees of new vessels were noted skin test was negative (<5 mm) at 48 hours. 0.1% QID in both eyes, atropine 1% BD and deep within the stroma. There was a large, Auditory testing suggested moderately lanolin ointment at night. The patient was deep 3×3.2 mm ‘salmon-coloured’ nodule on severe conductive hearing loss in both the re-referred to paediatric rheumatology the inferior cornea on the left. Decreased right (Figure 4a) and left ear (Figure 4b). and restarted on methotrexate 12.5 mg corneal sensation and generalised punctate Thus, a working diagnosis of idiopathic once weekly, prednisone 20 mg daily epithelial erosions without larger areas interstitial keratitis was made and the and chloroquine 200 mg five times a of staining were present bilaterally. The Table I: Serological investigations week for serologically negative JIA. The anterior chambers were active with 2+ Blood Value patient showed significant improvement cells and 1+ flare although iris nodules or in symptoms and visual acuity – at her WCC 5.79 transillumination defects were absent. iCare two weeks follow-up her best corrected tonometry was 12 and 10 mmHg for the Hb 12.4 visual acuity had improved to 6/9 in both right and left eye respectively. The vitreous Platelets 387 eyes, and her corneal inflammation had was quiet in both eyes. Posterior segment ESR 31 decreased significantly – specifically the examinations were normal with vertical CRP 4 nodule in her left eye had decreased cup-to-disc ratios of 0.2 bilaterally and no RVD Negative evidence of retinal inflammation. Laboratory testing is shown in Table I TPHA Non-reactive (×2) which revealed an elevated erythrocyte ANA Negative sedimentation rate (ESR) and serum RF <10 angiotensin converting enzyme (ACE). Of CRP 4 note was that the mother’s T. pallidum S-ACE 83 antibodies were negative. The chest X-ray

Figure 4a. Right ear audiogram: moderate- to-severe conductive hearing loss

Figure 4b. Left ear audiogram: moderate-to- severe conductive hearing loss with mixed Figure 3. PA and lateral CXR frequency component @ 500 and 2000 kHz Case report Vol 16 | No 1 • Summer 2021 38 Idiopathic interstitial keratitis in a child SA Ophthalmology Journal

Figure 5a. Left eye at two-week follow-up. Note the decreased Figure 5b. Right eye at two-week follow-up showing improved inflammation and vascularisation. inflammation and vascularisation

in size and vascularity (Figures 5a and between the ages of five and 20 years with a be associated with sectoral sclerokeratitis.1 b). Stromal vessels were still present peak at nine to 11 years.1,2,4 Associated ocular TB was excluded in our patient due to lack although systemic symptoms had almost findings include generalised iris atrophy, of contacts, a negative chest X-ray and a completely settled. Over subsequent visits posterior synechiae and a salt-and-pepper negative tuberculin skin test at 48 hours. the clinical picture continued to improve, fundus. In some instances a ‘salmon-patch’ The bilateral pattern and deep nature of and topical steroids were slowly tapered is seen which represents a particularly the vessels were also not supportive of TB to once daily maintenance doses. intense area of neovascularisation with infection. or without subsequent extravasation of Cogan’s syndrome is a rare disorder that Discussion blood cells.2 Systemic manifestations may classically affects young white adults and We present a paediatric case of idiopathic include the classical Hutchinson’s triad of presents with non-syphilitic interstitial interstitial keratitis in a patient known with sensorineural deafness, anomalous and keratitis and sensorineural hearing loss JIA. The patient responded to topical steroid widely spaced ‘peg-like’ teeth and interstitial that is similar in nature to Meniere’s disease therapy with full recovery of vision. The keratitis. Other findings may include (sudden onset of tinnitus and vertigo differential diagnosis for this presentation cognitive impairment, a ‘saddle-shaped’ in the setting of chronic hearing loss). includes herpes simplex virus (HSV) or nose, frontal bossing, overgrowth of the The most serious systemic associations immune stromal interstitial keratitis, maxilla, mulberry molars and ‘sabre tibias’.1,2 include aortitis, aortic dilatation, valvular syphilitic interstitial keratitis, TB interstitial Although our patient has a salmon regurgitation, brain infarction and lower keratitis as well as Cogan’s syndrome. patch in the left eye, syphilis was actively limb ischaemia. Less serious manifestations HSV interstitial keratitis typically presents excluded by negative serology results in are protean – including fever, fatigue, with a unilateral diffuse or sectoral both the child and her mother as well weight loss, hepatosplenomegaly, pattern of inflammation. Importantly as a lack of characteristic stigmata of arthralgia and urticaria among others.10 The the vascularisation is deep and is often congenital syphilis infection. pathogenesis remains unclear although associated with an iritis, diminished corneal Despite a very high incidence and co-infection with C. pneumoniae has been sensation, iris atrophy and a history of prevalence of systemic disease, ocular TB postulated.11,12 Hayes et al. proposed a relapsing disease. Although elevated ESR remains rare. This is further compounded classification system in 1980 that divided and serum-ACE results are consistent with by the challenge in making a diagnosis due Cogan’s syndrome into typical and atypical diffuse inflammation from viral aetiologies, to extremely low yield of M. tuberculosis forms. The former retains Cogan’s initial HSV was considered unlikely as they tend (even with PCR techniques) and difficulty definition of non-syphilitic interstitial to present unilaterally and be associated in obtaining ocular tissues for biopsy.5-7 The keratitis and typical audio-vestibular with iris atrophy or increased pressures. A most common manifestations of ocular disease appearing not more than two favourable response to therapy that did not TB include granulomatous uveitis and years after the onset of ocular symptoms. include an antiviral agent is also supportive choroiditis; corneal involvement is typically The case definition for atypical Cogan’s of a non-viral aetiology. rare (accounting for only 6.8% of all ocular syndrome was later significantly broadened Congenital syphilis forms the majority TB cases). A high index of suspicion is thus to include any ocular inflammation (with of syphilitic interstitial keratitis (87%) and necessary to make a diagnosis.8,9 Corneal or without interstitial keratitis), audio- is associated with unilateral inflammation TB may take the form of phlyctenulosis, vestibular symptoms (with or without a that becomes bilateral in 80% of cases. peripheral ulcerative keratitis and interstitial Meniere’s-type picture) and a delay of more A diffuse pattern with deep and extensive keratitis, and appears to be a result of an than two years between the onset of ocular vascularisation with a predilection for the exuberant host-immune response rather and auditory symptoms.10,12-14 The pattern superior cornea is classically described. than the direct effect of the organism itself. of interstitial keratitis is typically bilateral, Vertical transmission from the mother may The pattern of interstitial keratitis is usually occurs rapidly and resolves gradually with occur during primary, secondary or latent unilateral and sectoral with a more anterior topical steroids, with frequent episodes phases of infection and classically presents or mid-stromal vascularisation which may of recurrence.1 Our patient was thoroughly Summer 2021 • Vol 16 | No 1 Case report SA Ophthalmology Journal Idiopathic interstitial keratitis in a child 39

worked up for Cogan’s syndrome although References interstitial keratitis and granulomatous uveitis this is unlikely without classic symptoms of 1. Perez V. Interstitial keratitis. Ocul Immunol of tubercular origin. Eye Contact Lens. 2014 vertigo and tinnitus. Furthermore, audiology Uveitis Found. 2001 Nov;VI. Mar;40(2):13-15. testing was consistent with a conductive 2. Weisenthal R, Daly MK, de Freitas D, Feder 9. Rafiezadeh P, Schmack I, Shajari M, Kohnen rather than a sensorineural fallout RS, Orlin SE, Tu EY, et al. External disease and T. Autoimmune keratitis in mycobacterium which likely reflects repeated middle ear cornea. San Francisco, California: American tuberculosis. J Curr Ophthalmol. 2018 May infections in adolescence. Academy of Ophthalmology; 2019. pp 357-59. 18;30(4):381-83. (American Academy of Ophthalmology Basic 10. Azami A, Maleki N, Kalantar Hormozi M, Tavosi Conclusion and Clinical Science Course 2019-2020). Z. Interstitial keratitis, vertigo, and vasculitis: Interstitial keratitis represents an 3. Schwartz GS, Harrison AR, Holland EJ. Etiology typical Cogan’s syndrome. Case Rep Med. 2014 exuberant hypersensitivity reaction and of immune stromal (interstitial) keratitis. Mar 4;2014:1-4. vascularisation within the corneal stroma Cornea. 1998 May;17(3):278-81. 11. Norton EWD, Cogan DG. Syndrome of that is often associated with an underlying 4. Dahl AA. Interstitial keratitis: Overview, nonsyphilitic interstitial keratitis and systemic disease. There is very little pathophysiology, epidemiology. 2020 vestibuloauditory symptoms: a long-term information regarding the epidemiology May 8 [cited 2020 Aug 18]; Available follow-up. AMA Arch Ophthalmol. 1959 May of interstitial keratitis in the paediatric from: https://emedicine.medscape.com/ 1;61(5):695-97. population of Sub-Saharan Africa. The article/1194376-overview 12. Vollertsen RS, McDonald TJ, Younge BR, Banks pattern and laterality of interstitial keratitis 5. Bayraktutar BN, Uçakhan-Gündüz Ö. Ocular PM, Stanson AW, Ilstrup DM. Cogan’s syndrome: together with relevant systemic findings tuberculosis with progressive unilateral 18 cases and a review of the literature. Mayo and laboratory investigations can give the corneal melting. Case Rep Ophthalmol. 2015 Clin Proc. 1986 May 1;61(5):344-61. clinician a clue about the underlying cause. Sep 3;6(3):293-97. 13. Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci Important diagnoses to consider include 6. Sarah B, Batoul MS, Ibtissam H, Ouafa H, Said AS. Cogan syndrome: studies in thirteen HSV, congenital and acquired syphilis, A, Abdeljalil M. Corneal manifestations of patients, long-term follow-up, and a review TB and Cogan’s syndrome. In a large tuberculosis: about 2 cases. Am J Med Case of the literature. Medicine (Baltimore). proportion of cases the underlying cause is Rep. 2016;4(5):160-64. 1980;59(6):426-41. never identified. The non-ulcerative nature 7. Alvarez GG, Roth VR, Hodge W. Ocular 14. Martínez-Osorio H, Fuentes-Páez G, Calonge of interstitial keratitis means that the visual tuberculosis: diagnostic and treatment M. Severe keratopathy in paediatric Cogan’s prognosis is generally favourable when the challenges. Int J Infect Dis. 2009 Jul;13(4):432-35. syndrome. Rheumatology. 2006 Aug  underlying cause is treated. 8. Kamal S, Kumar R, Kumar S, Goel R. Bilateral 18;45(12):1576-77.

More potent1* More bioavailability2** More e ect2**

**Prolong corneal contact time with DexaGel 1,2 For greater anti-inflammatory effect vs dexamethasone solution 1,2 Equivalent efficacy and safety compared to prednisolone 1

*Compared to prednisolone. **Compared to dexamethasone solution. References: 1. Struck HG, et al. Comparison of 0.1% dexamethasone phosphate eye gel (Dexagel) and 1% prednisolone acetate eye suspension in the treatment of post-operative infl ammation after cataract surgery. Graefes Arch Clin Exp Ophthalmol. 2001 Oct;239(10):737-42. 2. Data on fi le. Study No. 008 PHA 94; Dr Morgenstern et al.; 1995.

Scheduling status: S4 Proprietary name and dosage form: Dexagel (Eye Gel). Composition: Each 1 g contains: 0,985 mg Dexamethasone sodium phosphate. Preservative: Benzododecinium chloride 0,01 % m/m. Pharmacological classifi cation: A 15.2 Ophthalmic preparations with corticosteroids. Registration number: 37/15.2/0275. © 2003 Bausch & Lomb Incorporated. ®/™ donate trademarks of Bausch & Lomb Incorporated. Applicant: Sofl ens (Pty) Ltd. Reg. No.: 1968/011787/07. 254 Hall Street, Centurion, 0157. Tel: +27 10 025 2100. www.bausch.co.za For full prescribing information, refer to the professional information as approved by the South African Health Products Regulatory Authority (SAHPRA). BL343/18