Six weeks of therapy with trifluridine and fluorometholone drops brought some improve- ment. Suddenly, 5 months after the original presenta- tion, severe pain ...
CASE REPORTS * ETUDES DE CAS
Acanthamoeba keratitis: problem
an emerging
clinical
Duff D. Horne,*t MD; Mary E. Frizell,t RT; Lorraine Ingham,t ART; Ronald G. Jans,4 MD, FRCPC; Stevan M. Gubash,*t MD, FRCPC; Chandar M. Anand,*t MD, FRCPC; Mohammed A. Athar,*§ PhD, MPH
Resume: La keratite a Acanthamoeba est reconnue de plus en plus fr6quemment, mais on la confond encore avec les keratites d'origine herpetique, fongique et bacterienne, ce qui entralne des erreurs de traitement. Trois cas illustrent les caracteristiques cliniques et pathologiques de la maladie. Une patiente portait des lentilles souples qu'elle a rincees avec de l'eau de puits non traitee. Le deuxieme sujet a subi une blessure 'a l'oeil et s'est lave les yeux avec de l'eau de puits. Le troisieme patient n'a signale aucun facteur predisposant. Dans les trois cas, la keratite a ete mal diagnostiquee au debut et mal traitee pendant assez longtemps avant qu'on diagnostique une keratite 'a Acanthamoeba. Un diagnostic plus rapide et un meilleur traitement de cette infection grave devraient ameliorer le pronostic.
Case reports
Case 1
The sensation of a foreign body developed in the right eye of a 35-year-old woman who used untreated well water to rinse her soft contact lenses. After therapy with gentamicin drops, prescribed by a general practitioner, an ophthalmologist diagnosed as herpetic keratitis a dendritiform corneal lesion, stromal infiltration and iritis. Six weeks of therapy with trifluridine and fluorometholone drops brought some improvement. Suddenly, 5 months after the original presentation, severe pain, stromal keratitis and a ring infiltrate with a corneal ulcer developed in the right eye. Cell cultures of corneal scrapings yielded a species of Acanthamoeba but not herpesvirus. Six months of therapy with topical miconazole, metronidazole, prednisolone and neomycin, as well as oral ketoconazole, resulted in T he infection Acanthamoeba keratitis is being a noninflamed, comfortable eye, although a residual recognized more frequently as a distinct, ring infiltrate persisted, and the patient required further vision-threatening ophthalmologic condition myopic correction. often associated with wearing soft contact lenses.'2 In Canada two cases were reported in 1990,341 but none Case 2 have since appeared in the literature. Because AcanA 42-year-old rancher, who did not wear contact thamoeba keratitis resembles herpetic, fungal or bacterial keratitis clinically, diagnosis and treatment may lenses, experienced sensations of burning and of a foreign body in his eyes while he worked in his haybarn. be erroneous.5 We report three cases of Acanthamoeba keratitis He washed his eyes with well water. After 5 weeks of that illustrate the need for awareness of the disease by treatment with sodium sulfacetamide, prescribed by an primary care physicians as well as ophthalmologists and emergency physician, the patient visited an ophthalmologist, who diagnosed as herpetic disciform keratitis, an laboratory physicians. From the departments of *Medical Microbiology and Infectious Diseases and of 4Ophthalmology, University of Calgary, Calgary, Alta.; tthe Provincial Laboratory of Public Health for Southern Alberta, Calgary, Alta.; and §the Calgary District Hospitals Group, Calgary, Alta.
Reprint requests to: Dr. Duff D. Horne, Provincial Laboratory of Public Health for Southern Alberta, PO Box 2490, MARCH 15, 1994
Calgary, AB T2P 2M7
CAN MED ASSOC J 1994; 150 (6)
923
epithelial defect and hypopyon in the right eye. Cell cul- and throat secretions, and animal stools.6 The life cycle tures of a corneal swab yielded Acanthamoeba sp. but of Acanthamoeba consists of a trophozoite and a cyst not herpesvirus. The therapy was changed to topical mi- stage. conazole, metronidazole and propamidine, plus oral keThe cases we have described illustrate the typical toconazole. After some improvement the corneal ulcer clinical features, risk factors and pathogenic features of and hypopyon recurred, necessitating further therapy. Acanthamoeba keratitis (Table 1). The infection is difThere was some improvement, but ultimately a corneal ficult to treat because cysts become embedded in graft was performed. corneal stroma. The recommended prolonged multipledrug regimen, begun early, includes topical propamiCase 3 dine, neomycin-polymyxin B, paromomycin, natamycin, miconazole and metronidazole., plus systemic A corneal ulcer developed in the right eye of a 48- ketoconazole.' 23 Recently, promising results have been year-old man who did not wear contact lenses and had obtained with 0.02% polyhexamethylene biguanide, no history of eye trauma. An ophthalmologist diagnosed which is used as a preservative in contact lens soluherpetic keratitis. After 3 weeks of therapy the ulcer be- tions. 4 came indolent, the eye became inflamed, and hypopyon Useful for laboratory diagnosis are corneal scrapdeveloped. Topical tobramycin and cefazolin were added ings and swabs, biopsy and surgical specimens, and conto the antiherpetic therapy with trifluridine and fluoro- tact lenses and their storage and rinsing solutions. Lowmetholone. Although cultures of an aspirate from the power microscopic examination of direct or stained right anterior eye chamber and scrapings of the cornea specimens, culture on non-nutrient agar seeded with bacwere negative for Acanthamoeba and herpesvirus, ther- teria, cell culture (which is also used in the diagnosis of apy for infection with the former was begun and antiher- herpetic keratitis) and histology are useful for confirmapetic therapy discontinued. However, owing to impend- tion.' '" ing perforation a corneal graft was performed. The severity, chronicity and difficulty in the treatHistopathological examination of the surgical specimen ment of Acanthamoeba keratitis, as well as the increased confirmed Acanthamoeba keratitis (Fig. 1). The patient use of contact lenses, make this infection serious. Physcontinued with the antimicrobial therapy, but the graft icians should be aware of the condition and its risk facshowed signs of rejection and reinfection with Acan- tors. Important in preventing infection and, possibly, thamoeba; the patient's vision worsened markedly. An- blindness are the education of patients in the safe and efother graft was anticipated. fective use of their contact lenses, the early recognition of the infection and the alerting of laboratories to test for Comments Acanthamoeba.
Members of the genus Acanthamoeba are ubiquitous and can be isolated from well, tap, bottled and swimming pool water, as well as sand, dust, human nasal
We thank Steve Rasmussen, MD, pathologist, Calgary District Hospitals Group, Calgary, for the histopathology photo and the histopathologic diagnosis of Acanthamoeba keratitis, and Bonnie Maclntyre for help in the preparation of the manuscript.
Typical features: severe ocular pain, photophobia, dendritiform corneal lesions, characteristic ring or stromal infiltrate (complete or partial), recurrent corneal epithelial and subepithelial breakdown and ulceration (refractory to treatment), edema, enlarged comeal nerves, in-
Fig. 1: Case 3: Section of cornea, stained by means of periodic acid-Schiff reaction, showing numerous doublewalled cysts of Acanthamoeba sp. (arrows), with characteristically wrinkled outer wall (exocyst) and smooth inner wall (endocyst), and degeneration of surrounding collagen stroma. Original magnification x 200, reduced by approximately 49%. 924
CAN MED ASSOC J 1994; 150 (6)
flammation, hypopyon, and diagnostic confusion with herpetic, fungal or bacterial keratitis. Risk factors: use of contact lenses, use of nonpreserved ophthalmologic products (e.g., homemade saline), exposure of eyes to nonsterile water sources (e.g., well, tap and surface water), contamination of contact-lens storage cases and of storage and rinsing solutions, trauma to the eye, compromised host defence mechanisms and corneal surgery. Pathogenic features: large inoculum of Acanthamoeba, bacterial colonization of cornea, contact lenses or accessories, and warm weather.
LE 15 MARS 1994
9. Moore MB, Ubelaker J, Silvary R et al: Scanning electron microscopy of Acanthamoeba castellanii: adherence to surfaces of new and used contact lenses and to human corneal button epithelium [abstr]. Ibid: S423
References 1. Krogstad DJ, Visvesvara GS, Walls KW et al: Blood and tissue protozoa. In Balows A, Hausler WJ Jr, Herman KL et al (eds): Manual of Clinical Microbiology, 5th ed, Am Soc for Microbiol, Washington, 1991: 744-750 2. Acanthamoeba keratitis associated with contact lenses - United States. MMWR 1986; 35: 405-408
10. Bottone EJ, Madayag RM, Qureshi MN: Acanthamoeba keratitis: synergy between amebic and bacterial cocontaminants in contact lens care systems as a prelude to infection. J Clin Microbiol 1992; 30: 2447-2450
3. Rabinovitch J, Chin Fook T, Hunter WS et al: Acanthamoeba keratitis in a soft-contact-lens wearer. Can J Ophthalmol 1990; 25: 25-28
11. Parrish CM, O'Day DM: Acanthamoeba keratitis following penetrating keratoplasty in a patient without other identifiable risk factors [abstr]. Rev Infect Dis 1991; 13 (suppl 5): S430
4. Beattie AM, Slomovic AR, Rootman DS et al: Acanthamoeba keratitis with two species of Acanthamoeba. Ibid: 260-262
12. Osato MS, Robinson NM, Wilhelmus KR et al: In vitro evaluation of antimicrobial compounds for cysticidal activity against Acanthamoeba. Ibid: S431-S435
5. Auran JD, Star MB, Jakobiec FA: Acanthamoeba keratitis: a review of the literature. Cornea 1987; 6: 2-26
13. Sharma S, Grinivasan M, George C: Diagnosis of Acanthamoeba keratitis - a report of four cases and review of literature. Ind J Ophthalmol 1990; 38: 50-56
6. De Jonckheere JF: Ecology of Acanthamoeba. Rev Infect Dis 1991; 13 (suppl 5): S385-S387 7. Donzis PB, Mondino BJ, Weissman BA: Microbial analysis of contact lens care system contaminated with Acanthamoeba. Am J Ophthalmol 1989; 108: 53-56
8. Seal DV, Dart J: Possible environmental sources of Acanthamoeba species that cause keratitis in contact lens wearers [abstr]. Rev Infect Dis 1991; 13 (suppl 5): S392
'CYT|hJTEC< (misoprostol) 10o0 8g ltHAPEUTIC CLASSIFICATION Mucosal Protective Agent DlCATONS CYTOTEC (misoprostol) is indicated for the prevention of NSAID-induced gastric ulcers. Patients at high risk ddeveloping NSAID-induced complications and who may require protection include: * Patients with a previous history of uerdisease or a significant gastrointestinal event. * Patients over 60 years of age. * Patients judged to be at risk because of peral poor health, severe concomitant medical disease, or patients who are poor surgical risks. * Patients disabled by joKsymptoms (e.g., HAQ Disability Index Score >1.5) or those with severe systemic manifestations of arthritis. * Patients Wing other drugs known to damage or exacerbate damage to the gastrointestinal tract such as corticosteroids or anticoagobnts. Patients taking a high dosage or multiple NSAIDs, including those available Over-The-Counter. The risk of NSAIDhinuced complications may be highest in the first three months of NSAID therapy. CYTOTEC is also indicated for the treatmentof NSAID-induced gastric ulcers (defined as > 0.3 cm in diameter) and for the treatment of duodenal ulcers. WITRAINDICATIONS Known sensitivity to prostaglandins, prostaglandin analogues, or excipients (microcrystalline and Iydroxypropyl methylcellulose, sodium starch glycolate and hydrogenated castor oil). Contraindicated in pregnancy. (See CLINICAL PHARMACOLOGY.) Women should be advised not to become pregnant while taking CYTOTEC (misoprostol). If pegnancy is suspected, use of the product should be discontinued. WARNINGS Women of childbearing potential should employ adequate contraception (i.e., oral contraceptives or intrauterdevices) while receiving CYTOTEC (misoprostol). (See CONTRAINDICATIONS.) Nursing Mothers: It is unlikely th CYTOTEC is excreted in human milk since it is rapidly metabolized throughout the body. However, it is not kno th abe metabolite (misoprostol acid) is excreted in human milk. Therefore, CYTOTEC should not be administer ri mohers because the potential excretion of misoprostol acid could cause significant diarrhea in nursing lk: Safety and effectiveness in patients below the age of 18 have not been established. foll ECAUTIONS Selection of Patients: Caution should be used when using symptomatology as the s mpain ow-up procedure, since CYTOTEC (misoprostol) has not been shown to have an effect e. hould btBefore treatment is undertaken, a positive diagnosis of duodenal ulcer or NSAI Iced ga to 0s by most b Tl general health of the patient should be considered. Misoprostol is rapidly tion.1 g1exal or hep meabolites. Nevertheless, caution should be exercised when patients have deh a-leading t CLINICAL PHARMACOLOGY: Pharmacokinetics.) Diarrhea: Rare instances ehy or those i irr , ion have been reported. Patients with an underlying condition s erl .1&prescribed. f ion, were it to occur, would be dangerous, should be mu ageorthos s renallyX Impaired: Considerations forbe Dosa but tm Renly ISTRAy sign See DOSAGE l ipaired the pharmacokinetics may affected, Dosage ots with renal ents TIN). No routine dosage adjustment is reco ge (1 00 a ihr mayneed to be reduced if the usual dose is n -astartingobs p of misoof tol aci d rum protein gOID) is recommended. Drug Interactions: taz a, aar,, not proprame, was affected digoxin, by: indomethacin, 1Wol) cylic acid (300 chlorot rofen, chlorpr e, an nolol, tiamterene, cimetidi i minophe the since co to i 84% 0 ignificant not lowered the rom clinicalt52° sopr pro Wml) hort. In labora studies, misoprostol has n imination half-life _ bnding of misopro tion oxidase system, and therefore should - linked hepatic ml n the c shown no signifi nzodiazepines or oth normally metabolized by this system. No of theophylline, noteafect the m 1 een observed to dot e CLINICAL PHARMACOLOGY.) Some drug nacti ibutable to misopros acity to produce hypension through peripheral vasodilation. The posta tins _ rostaglandin analogues hav not produced hypotension at dosages effective in promoting the resut s lIs to date indicate that CYTO ith caution in the presence of disease states where hypotension healing o lc vertheless, CYTOTEC should h r disease or coronary artery disease. Epileptic seizures have might precipitere complications, e.g., cerebra staglandins and prostaglandin a ues administered by routes other than oral. Therefore, misoteen reported used in known ,leptics only when their epilepsy is adequately controlled and then only when prstol tablets exected benefits __mptomatic responses to CYTOTEC do not preclude the presence of gastric maignancy. In subjects receiving CYTOTEC (misoprostol) 400 or 800 p, daily in clinical ADVERSE REACTIONS s tidls, the most frequent gastrointestinal adverse events were diarrhea, abdominal pain and flatulence. The average incidences of these events were 11.4%, 6.8% and 2.9%, respectively. In clinical trials using a dosage regimen of 400 pg bid, the incidence of diarrhea was 12.6%. The events were usually transient and mild to moderate in severity. Diarrhea, when it MARCH 15, 1994
14. Larkin DFP, Kilvington S, Dark JKG: Treatment of Acanthamoeba keratitis with polyhexamethylene biguanide. Ophthal-
moll992;99:185-191 15. Johns KJ, Head SW, Robinson RD et al: Examination of the contact lens with light microscopy: an aid in diagnosis of Acanthamnoeba keratitis [abstr]. Rev Infect Dis 1991; 13 (suppl 5): S425
occurred, usually developed early in the course of therapy, was self limiting and required discontinuation of CYTOTEC in less than 2% of the patients. The incidence of diarrhea can be minimized by adjusting the dose of CYTOTEC, by administering after food, and by avoiding co-administration of CYTOTEC with magnesium-containing antacids. Gynecological: Women .disorders: spotting (0.7%), cramps who received CYTOTEC during clinical trials reported the followiog gynecolo ,derly: There were no significant (0.6%), hypermenorrhea (0.5%), menstrual disorder (0.3%) and dysmeoo w r; 0 years of age or older, comdifferences in the safety profile of CYTOTEC in approximately 500 ulc pared with younger patients. Confusion has been reported in a small nu if patients i, #ost marketing surveillance ported by more than 1% reactions of CYTOTEC. Incidence greater than 10%: In clinical trials, t llowing che (2.4%), dyspepsia sea (3.2%),g the dru of the subjects receiving CYTOTEC and may be causally rel erences between the were n ,ally signific (2.0%), vomiting (1.3%) and constipation (1.1%). However. $i.i ,i incidences of these events for CYTOTEC and p mended adult oral d Il r Th n f DOSAGE AND ADMINISTRATION Tret 800 pg a day stric ulc eatmentf AIDmnd ntetion dosage of CYTOTEC (misoprostol) for t appropriate, physi scribed e sche ording ta in divided doses. NSAIDs sho r: The recomken afte TEC shou simu sly. e CYTOTEC and NSAIDs ar weeks in two or four o denal ul 00 pg p TEC (mi i 1 mended adult oral d ime with food. Antacids be tei dose 0 g qid or 40 equally divided do ued for a total of 4 weeks unless e nt sh pain. d as needed for (aluminum based her of who may not have In the enami end been documented patients less ti by healinQs' e conti f fu er 4 weeks Use in Elderly and Renally eks, therapy with CYTOTEC afte ful rD kineti i p atients with varying degrees of renal impairtmnt Ph Ai oximate douhlin of Tl~, C m pared to normals. There was no clear correlation owed a f age the pharmacokinetics may be affected. In both irment and AU. In suojects ov een degree cokinetic changes are not clinica nificant. No routine dosage adjustment is recommended in ent groups ts with renal ment. Dosage may need to be reduced if the usual dose is not tolerated. In h patie w range (100 pg DID) is recommended. toil _ j _ f B _-upg tablets are white to off-white, scored, hexagonal with SEARLE 1461 _ CYTOTE of 120 and 500 tablets. CYTOTEC 100 pg tablets are white to off-white, round n one side availahle i en tal e_ EARLE e ned on one side and CYTOTEC on the other available in bottles of 100 tablets. ° Store 400 Iroquois Shore Road Patient Insert. Pharma _ _ _ Oakville,L6HOntario 1M5
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rences: 1. Elliott DP. Annals of Pharmacotherapy 1990;24:954-957. 2. Agrawal NW, et al. Annals of Internal Medicine 3. Cryer B, Feldman M. Arch Intern Med June 1992;152:1145-1153. 4. Fries JF. J of Musculoskeletal Medicine 1991,2:21-28. 5. Gabriel SE, et al. Annals of Internal Medicine 1991;115(10):787-796 6. CYTOTEC8 Product Monograph, Searle Canada Inc. 7. Graham DY, Agrawal NM, Roth SH. The Lancet 1988;2:1277-1280.
1991;115(3):195-200.
PA
Product Monograph available upon request.
Proven Protection
zCYTOTEC® AJLDo (misoprostol) 200 gg
WITH FOOD
CAN MED ASSOC J 1994: 150 (6)
925
