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Retinal Arteritis, Iridocyclitis, and Giardiasis
Retinal Arteritis, Iridocyclitis, and Giardiasis DAVID L. KNOX, MD, * JOHN KING, JR, MDt
Abstract: The intestinal parasite Giardia lamblia was found in the stools of three patients with retinal arteritis. Iridocyclitis was also present in two of these patients, who had not responded to treatment with systemic corticosteroids. Antiparasitic drug treatment was followed by improvement of ocular and systemic findings. [Key words: Giardia lamblia, giardiasis, iridocycl itis, retinal arteritis.] Ophthalmology 89: 1303-1308, 1982
Severe loss of vision from retinal arteritis occurred in three patients who were found to have gastrointestinal infection with the parasite Giardia lamblia. Ocular complications of Giardia infection were first reported in 1938 by Barraquer, 1 who described iridocyclitis, choroiditis, and hemorrhagic retinopathy. The present report is the first to describe retinal arteritis occurring in patients with giardiasis. The similarity of the arteritis in the three patients is striking.
CASE REPORTS Case 1. A 43-year-old white businessman and travelling salesman from North Carolina was in good health until late September 1969, when he began awakening at about 4:00 a.m. with a sense of restlessness. Early in October 1969, he had noted redness and slight discomfort on movement of the left eye. After several days he discovered that his vision was reduced. On October 24, 1969, he saw his ophthalmologist, who found a normal right eye with 6/6 (20/20) visual acuity. Vision in the left eye was 6/12 (20/40) with keratic precipitates and aqueous and vitreous flare and cells. Fundus examination found hazy media and diffuse whitening of the peripheral retina, with edema extending posteriorly to the equator. The optic disc was swollen, with venous congestion. The patient was hospitalized in North Carolina where all
From the Wilmer Ophthalmological Institute of The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland* and Thomasville, Georgia.t Presented as a poster at the Eighty-sixth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 1-6,1981. Reprint requests to David L. Knox, MD, Wilmer Institute, The Johns Hopkins Hospital, Baltimore, MD 21205. 0161-6420/82/1200/1303/$1.10
© American Academy of Ophthalmology
diagnostic studies were normal. Five stool specimens studied for ova and parasites were considered negative. He was treated with large doses of systemic steroids and intravenous adrenocorticotropic hormone (ACTH). The areas of retinal whitening coalesced; they extended from the periphery to the ends of the temporal retinal vessels, and then became fatty yellow in color. The retinal vessels in this area were surrounded by perivenous hemorrhages in the nerve fiber layer. At the time of discharge from the hospital in North Carolina, he had mild occult blood in his stool despite a bland diet. He was given antacids as an anti-ulcer regimen. Although receiving dexamethasone 3.75 mg by mouth every morning and also topical dexamethasone ointment and drops, his right eye developed 1 + aqueous flare and cells, but the vitreous remained clear. Visual acuity in the left eye deteriorated to 6/18 (20170), with 3 + flare and cells in the aqueous and vitreous. The fundus showed increased peripheral hemorrhages but less exudate. The retinal arteries had become irregularly thickened by a yellowish substance that prevented visualization of any flow of blood. The patient was seen at the Wilmer Institute in Baltimore on November 17, 1969, four weeks after the onset of visual symptoms. Vision in the right eye was 6/5 (20/15) and in the left eye was 6/18 (20170 +2). There was one cell visible in the right anterior chamber. The left eye had small keratic precipitates, 2 + aqueous flare and cells, a clear lens, and dense flare and cells in the vitreous. The fundus examination of the right eye was normal. The media of the left eye were hazy. Scattered "infiltrated" arteries, macular edema, and peripheral yellow subretinal deposits were present (Fig 1). Diagnostic studies in the Johns Hopkins Hospital revealed cysts but no trophozoites of G. LambLia and 1 + guaiac for occult blood in the stools. X-ray findings of the large and small bowel were interpreted as normal. A peroral capsule biopsy of the jejunum revealed intraluminal Giardia and slightly abnormal intestinal villi (Fig 2). On November 21, 1969, the patient was started on quinacrine (Atabrine®) 100 mg three times a day; oral corticosteroids were continued. One month later, vision in the left eye
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Fig 1. Top left, case 1, November 1969. Fundus of the left eye shows hazy vitreous and yellow-white deposits around thickened retinal arteries. Fig 2. Top right, case 1, November 1969. Jejunal biopsy specimen shows edematous epithelial cells and curvilinear Giardia lamblia, some of which are attached to epithelial cells (hematoxylin-eosin, XI500). Fig 3. Left, case 2, November 1970. Fundus of the right eye shows hazy vitreous and yellow-white shaggy thickening of the retinal arteries.
Figs 4A-C. Case 3, right eye, A, top left, April 21, 1980, before treatment, showing clear media, shaggy-white inferior retinal artery, "cotton wool" exudate, and inferior retinal ischemic edema. B, top right, May 5, 1980, after treatment, shows resolving retinopathy, lesser degree of white thickening of inferior artery, and less edema of inferior retina. C, left, May 19, 1980, showing further resolution after treat-
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KNOX AND KING • OCULAR CHANGES WITH GIARDIASIS
had decreased to 6/60 (201200). The inflammation in the anterior chamber and vitreous was still present. The perivascular lipid was still visible, and the retinal arteries were attenuated. In July 1970, vision in the left eye was light perception, and systemic corticosteroids were stopped. By September 1970, through hazy media, the retinal arteries seemed to be markedly attenuated, and there were large areas of excessive pigmentation. In April 1972, the left eye had vision of bare light perception, the anterior chamber was free of inflammation, and a mature cataract prevented visualization of the fundus. The right eye was normal. Comment. Gastrointestinal infection with G. Lamblia was the only abnormal systemic finding in this patient with retinal arteritis in the left eye and uveitis in both eyes. Absence of identifiable parasites in the stool specimens examined early in the course of his illness can be explained by either technician error or the fact that often when severe Giardia infection is present in the jejunum, no trophozoites or cysts can be demonstrated in stool specimens. Treatment with quinacrine (Atabrine®) was followed by complete resolution of anterior segment inflammation in the right eye and eventual improvement in the left eye. Unfortunately, prolonged inflammation and occlusion of the retinal vessels produced irreversible ocular damage. Case 2. A lO-year-old white boy from North Carolina was seen in November 1970 at the Wilmer Ophthalmological Institute for evaluation of a bilateral uveitis of one year's duration. His past medical history was normal until age 8, when he began to experience (one or two times per week) a postprandial, mucous bowel movement in which the stools were watery and "floated in the toilet." The stools were examined once for intestinal parasites, which were not seen. The patient had never been proctoscoped or had any x-ray contrast studies of stomach, small intestine or large bowel. He had been treated with parasympathetic blocking agents and an absorptive agent to control the diarrhea, which had been diagnosed as "colitis." At age 9, one year after onset of the" colitis," he awakened one morning with aching and throbbing of the left eye. The next day he complained of blurring vision of the left eye. He was seen by an ophthalmologist who started methylprednisolone (Medrol®) 4 mg by mouth, four times per day, and ACTH intramuscularly, and "eye drops" for a "uveitis." The pain decreased after systemic corticosteroids were started, but vision improved only slightly. While systemic corticosteroids were tapered to 2 mg of methylprednisolone per day, inflammation in the left eye returned. By January 1970, the patient developed inflammation in the right eye. Systemic corticosteroids were continued, which gave some relief to his abdominal pain, mucous colitis, and ocular inflammation. The patient was seen by a second ophthalmologist in January 1970, who found the posterior poles of both eyes appeared to be "perfectly normal," but heavy exudates between the equator and the ora serrata of both eyes. The anterior chamber reaction was slight in both eyes. Because the uveitis persisted and worsened despite use of oral and sub-Tenon' s injections of long-acting corticosteroids, he was hospitalized in May 1970. Vision was 6/12 (20/40) in the right eye, and hand movements in the left eye. Cyclophosphamide (Cytoxan®) was started, but stomach distress increased, and the cyclophosphamide therapy was stopped. In late October 1970, vision in the right eye worsened to perception of hand movements, and cyclophosphamide was restarted. After three days the nausea and
vomiting returned, and the cyclophosphamide was stopped. Prednisone, 80 mg per day, was started. The patient was first seen in Baltimore on November 23, 1970. Vision was "count fingers" at 5 ft with the right eye, and at 8 ft in the left eye. The patient had a Cushingoid facies, carious teeth, and white eyes. Slit-lamp examination revealed no keratic precipitates, 1 + aqueous flare and cells in both eyes, and posterior synechia at 6:00 o'clock in the left eye. Posterior subcapsular lenticular opacities and diffuse vitreous pigmented and white cells were present. The intraocular pressure was 18 mm Hg in the right eye and 24 mm Hg in the left eye. Funduscopy of both eyes was difficult because of hazy media. The retinal arteries were very narrow and had yellowish-white exudate along them. Large patches of thick yellow material (6 to 10 disc diameters in size) were present within and beneath the retina inferiorly. In other areas, small patches of yellow material (1/4 disc diameter in size) were present (Fig 3). General physical examination revealed an irritable boy who had six carious, deciduous teeth. Laboratory studies found only a serum cholesterol level of 404 mg/dl (normal 150 to 300 mg/dl). The WBC count, eosinophil count, and erythrocyte sedimentation rate were normal. Because of his history of mucous colitis one to two years prior to the onset of his eye trouble and a favorable response to systemic corticosteroids, he was strongly suspected of having Crohn's disease. A stool specimen was studied for ova and parasites. The technician reported that trophozoites of Giardia were so numerous that they were "lined up like soldiers." Proctosigmoidoscopy revealed a friable rectal mucosa and thin brown mucus, similar to what had been seen in other patients with intestinal parasites. Results of x-ray contrast studies of the stomach, small bowel, and large bowel were interpreted as normal. Quinacrine (Atabrine®), 50 mg given orally three times a day, was started. There was a marked improvement in his attitude and behavior by the time he was discharged from the hospital, five days after admission. After treatment with quinacrine, the mucous colitis did not recur, but the uveitis (of one year's duration at the time of treatment) persisted. The boy eventually has required schooling as a blind person. Comment. In this patient, the presence of mucous colitis prior to the onset of ocular inflammation can be explained easily by giardiasis. That explanation was not proven, however, because G. Lamblia were not demonstrated as being present prior to his admission to the Johns Hopkins Hospital. It is possible, therefore, that the long-standing use of systemic corticosteroids and immunosuppressive therapy with cyclophosphamide altered his immune mechanisms, allowing Giardia infection to develop. However, treatment with quinacrine stopped the mucous colitis and improved the "irritability" that had been present prior to onset of the ocular inflammation. It is also possible that Giardia had caused the original colitis, but that the parasites (under the influence of steroids and immunosuppression) increased in numbers-so that when the patient was seen in Baltimore many trophozoites were found in a watery stool specimen. Case 3. A 39-year-old white female nursery school employee was first seen on April 21, 1980 in Thomasville, Georgia, complaining of a two-day loss of vision in her right eye. She stated that she had awakened with severe blurring of vision that rapidly progressed during several hours to a dense loss of vision in the central and superior field. There was no history of trauma, and the patient was apparently in
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good general health, with no symptoms of any recent illness. She had never been outside the area of southern Georgia and northern Florida. Ocular examination in Thomasville, Georgia found visual acuity of 6/120 (20/400) in the right eye, which was accomplished by her fixating slightly above the test letter. The left eye had a visual acuity of 6/6 (20/20) and no appreciable refractive error. Pupil reactions were normal in both eyes. Abnormal findings were confined to the right eye. The anterior chamber was clear, and no lenticular opacities were seen. A few vitreous inflammatory cells were present posteriorly. The optic disc was "flat" and slightly hyperemic, with a sharp outline. The inferior portion of the retina below the small cilioretinal artery was markedly ischemic. The inferior temporal artery near the disc was obscured by yellow, fuzzy perivascular material. The affected retina was light gray and somewhat mottled, but with retinal vessels clearly visible (Fig 4A). The macula showed loss of the reflex and was dark red. Fluorescein angiography was not performed. Stool examinations of the patient were initiated because one of the authors (JK) had attended a continuing education course at which the other author (DLK) had presented the clinical details of cases 1 and 2. The retinal arteritis of c'ase 3 was considered to be similar and thus worthy of study for the presence of Giardia. Laboratory studies found only a large number of G. Lamblia cysts in three different stool specimens. A presumptive diagnosis of retinal vasculitis caused by giardiasis was made, and the patient was started on quinacrine, 100 mg three times a day for ten days, and prednisone 60 mg per day, which was tapered gradually during ten days. The retinal ischemia rapidly cleared, and 14 days after start of therapy the retina returned to an almost normal color (Fig 4B). The macula showed pigment changes, and a dense central scotoma remained. Function of the inferior retina improved, and the patient was no longer aware of visual field loss except centrally. Visual acuity remained 6/120 (20/400) with slightly eccentric fixation (Fig 4C). Because of the possibility of water-born contamination, the local health department investigated the water supply of the community in which the patient lived. The water supply for 35 homes came from two large wells and from individual homesite wells. No water was treated. All the homes were served by individual septic tanks, 28% of which seeped, backed up, or had problems in bad weather. Giardia cysts were found in the stools from four children. Two of these children lived in homes served by individual wells. The present patient and the two other infected children, received water from one of the community wells. Comments. In this patient giardiasis was implicated because the retinal arteritis was morphologically similar to that seen previously in patient 1 and patient 2, and because therapy for giardiasis was followed by ocular improvement. In these three patients, appropriate laboratory tests ruled out the following diseases as the cause of the retinal arteritis: Beh«et's disease, drug allergy, cerebral granulomatous angiitis, herpes zoster, lupus erythematosus, pars planitis, polyarteritis nodosa, sarcoidosis, syphilis, and toxoplasmic retinitis.
DISCUSSION Giardia LambLia is a flagellated, binucleate protozoan, 12 to 14 microns long, which in man prefers to 1306
inhabit the jejunum. Giardia occur as motile trophozoites or as immobile cystS. 2 ,3 Giardia was first 'Observed in 1681 by Von Leeuwenhoek, with his microscope, while looking at a suspension made from his own stools. The usual mode of infection is by ingestion of water contaminated by human sewage, although there is evidence that animal reservoirs such as deer, rabbits, beavers, or sheep may discharge viable cysts into pristine, crystal clear mountain streams. Areas of endemic infection include Russia, Iran, and Uruguay.4 Epidemics of giardiasis have occurred when sewage lines crossed water supplies, which was the explanation for an outbreak in Aspen, Colorado. 5 A more recent epidemic occurred when a woman, after changing the diapers of her unrealizedly infected grandson, contaminated her own home-canned salmon, which she was preparing for fellow workers. 6 Giardia live and multiply in the jejunum, where their sucker plates attach the organisms to swollen microvilli of intestinal epithelial cells 7 (Fig 2). Giardia have been demonstrated within the substantia propria of human jejunal villa8 and in rabbit Peyer's patches of lymphoid cells. 9 As of this writing, G. Lamblia has never been demonstrated by histopathology or electron microscopy to occur in any extraintestinal tissue. The gastrointestinal symptoms of giardiasis include burning epigastric distress, excessive burping and belching in the evening and night, abdominal cramps, flatulence, diarrhea or constipation, malodorous stools, anorexia, and weight 10ss.lO In contrast, heavily-infected persons may be entirely asymptomatic. Diagnosis is often difficult. Multiple stool examinations may reveal no organisms, a few cysts, or many motile trophozoites. Freshly passed or purged stools can increase the yield. Aspiration, capsule biopsy, or an "enterotest" of jejunal tissues and juices are sometimes the only way to demonstrate the organisms. 11 In some instances, even when no organisms are found, the patient's symptoms may be so characteristic and the responses to treatment so prompt that a presumptive diagnosis can be made. Treatment is with quinaquine hydrochloride (Atabrine®) at a dosage of 100 mg three times per day for 10 days, and/or metronidazole (Flagyl®) 250 mg three times per day for seven to ten days. Rechecking the stools in several weeks is advisable, both because of possible inadequacy of treatment or possible reinfection. Retreatment may be required. Study of family members may be indicated, and, if necessary, a search for the source of infection. Extraintestinal manifestations are varied. The largest series is that of Webster 10 in 1958. He reported an analysis of 32 patients. Welch 12 in 1944 described the findings of 29 patients. "Nervousness" was present in 23 of Webster's 32 patients. Emotional instability of nervousness was described in 9 of Welch's 29 patients. Headaches, seizures, pulmonary infiltrates, lymphadenopathy, and an eosinophilia of 9% were reported in a 6-year-old
KNOX AND KING • OCULAR CHANGES WITH GIARDIASIS
child who had a positive skin test for tuberculosis and had Giardia organisms in his stools. Urticaria was noted in six of Webster's 32 patients and has been featured in other reports. 14 In our search of the literatun~, we found no report of biopsy of an urticarial wheal in a case of giardiasis. Dizziness in nine patients and palpitation and fever in seven patients were reported by Webster. All extraintestinal symptoms rapidly resolve after therapy with quinacrine or metronidazole. Most of the reports on the ocular complications of giardiasis are written in French. This may reflect a high frequency of giardiasis in France, or an interest in correlations of ocular disease with various intestinal parasites. In the English language, there was only one report 3 of eye disease associated with giardiasis. If the association has been made in Russia, such a report has not been indexed in the English literature. . In 1938 Barraquer1 first reported eye disease in patients with giardiasis. Fundus lesions such as diffuse chorioretinal edema, subretinal hemorrhage; hyperplasia or loss of pigment epithelium, and vitreous hemorrhage are the most common findings. Barraquer reported his observations of choroiditis, hemorrhagic retinopathy, or iridocyclitis in patients who had diarrhea and stools positive for Giardia. Treatment with oxyaminophenylarsinic acid (Treparsol) was followed by improvement in diarrhea and the ocular condition. Barraquer did not state how many patients he had seen, or how many patients had each of the various ocular abnormalities. N. R. Dechiens, in discussing Barraquer's paper,! confirmed Barraquer's observations. It is of interest that Barraquer also described Entamoeba intestinalis (forme minuta) and Entamoeba coli as being often found with Giardia in patients with ocular fundus disease. Combined treatment with oxyaminophenylarsinic acid and emetine cleared the stools of parasites and stopped the diarrhea. Clinical improvement after any of several medications prevents a "therapeutic response" argument as to which parasite was responsible for the ocular inflammation. Also, quinacrine is effective against both G. lamblia and Entamoeba histolytica. Other reports have described the presence of E. histolytica, which is the same as Barraquer's E. intestinalis (forme minuta), as being associated with central serous choroidosis 15 or amebic choroidosis. 16 E. coli and Endolimax nana, different parasites, have (in the experience of one of the present authors, DLK) also been associated with subretinal hemorrhagic exudative choroidopathy of a type similar to that seen with amebiasis. In 1961 Carroll, Anast, and Birch 3 reported (from Chicago) the details of a 9-year-old girl who had a subretinal hemorrhagic and exudative chorioretinopathy. Systemic evaluation included tests for ova and parasites in the stools. G. lamblia was found. Treatment with quinacrine was followed by improvement in one eye, with reduction of subretinal fluid and hemorrhage in two weeks. Vision improved from 20/400 to 20/100 in the poorer eye. The stools were cleared of Giardia.
In 1961 Djabri and Diallinas 17 reported three patients from Franceschetti's Clinic in Geneva, Switzerland. All were adults. Two had inflammatory cells in the anterior chamber. The fundi of these patients had irregular macular edema, with reduced acuity. Treatment with antiparasitic medication was followed by improvement in acuity and resolution of the retinal edema. One of the patients had an 8% eosinophilia. In all three patients, Giardia was not demonstrated by stool examination but only by duodenal aspiration. Riccil 8 in 1961 described three patients with "Leber's pseudoalbuminuric retinitis" (composed of edema of the optit disc and macula, and retinal hemorrhage). One patient had three intestinal parasites: Ankylostoma, E. nana, and G. lamblia. After treatment with antiparasitic drugs and systemic corticosteroids, complete resolution of the papilledema occurred. Collier and Adias 19 reported a patient with vitreous hemorrhage and giardiasis. Vitreous hemorrhage has also been reported 20 in patients with intestinal infection by Ascaris. Macular lesions, iridocyclitis, a retinitis identical to that in toxoplasmosis, and a uveomeningitis were described in a report 21 that described the presence of Oxyuris and Tricephalus in the stool and Trichomonas vagina lis . One of us (DLK) has found Giardia infection in 18 patients with the following ocular findings: iridocyclitis, four patients; a toxoplasmic type of retinitis, three; retinal arteritis, two; pars planitis, two; and keratitis, episcleritis, iritis, exudative retinal detachment, amebic choroidosis, chorioretinal atrophy, and nutritional amblyopia, one case of each. The three patients in our present report all had funduscopic evidence of inflammation of retinal arteries. Shaggy, patchy, opaque yellow thickenings of the walls of the arteries were seen in all three. Anterior chamber and vitreous inflammation (iridocyclitis) occurred bilaterally in two of the patients. Irritable behavior occurred in the same two patients who had iridocyclitis. The persistent irritability stopped promptly with treatment in case 2. All three patients were found to have G. lamblia in their stools at the time of active ocular inflammation. Two of the patients had had negative stool examinations earlier in the course of their disease. In case 1, after treatment, there was immediate improvement in iridocyclitis of the right eye. In the left eye the iridocyclitis slowly quieted, but vision and the retina did not return to normal. Patient 2 had no improvement in vision in either eye. The inflammatory process had been active for 12 months in patient 2, and for one month in patient L With combined antiparasitic and anti-inflammatory therapy, patient 3 had rapid improvement in her affected eye. Patients 1 and 2 had not improved with only systemic steroids. After prolonged disease, ocular tissues develop changes that specific antimicrobial or combined antimicrobial and antiinflammatory therapy cannot reverse. Patient 3 had the best response to combined early therapy with metronazolamide (Flagyl®) and systemic 1307
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steroids. Even so, visual acuity was reduced permanently. A further expianation for failure of treatment to improve vision in these patients is the nature of the arteritis-induced vascular occlusive process that impairs blood supply causing irreversible necrosis of ocular tissue. Prolonged inflammation can also alter affected blood vessels so that they cannot reopen. Retinal arteritis from infection with G. lamblia could be explained by direct invasion of the eye and its arteries by the organism. There is no histopathologic evidence for or against this concept, since there are no reports of microscopic study of ocular tissue in patients with giardiasis. Urticaria, which ocCurs in a few patients with giardiasis, is the extraintestinal manifestation most similar to the retinal arteritis and ocular inflammation reported here. These urticarial lesions on histopathologic examination have inflamed arteries with diffuse infiltrates composed of polymorphonuclear, lymphoid, arid eosinophilic inflammatory cells. The patchy, scattered urticarial lesions are similar to the patchy nature of these patients' retinal arteritis. It must be assumed at this time that the extraintestinal manifestations of giardiasis are allergic in nature. Treatment with quinacrine or metronazolamide is followed by resolution of extraintestinal manifestations and the gastrointestinal symptoms such as diarrhea. These responses argue either for an extraintestinal tissue infection by G. lamblia or an allergic mechanism, since both dfugs are absorbed through the gut and then diffuse into other tissues-such as the vaginal mucosa, where the drug metrohazolamide combats Trichomonas vaginalis; or in blood or liver, where quinacrine acts on malarial parasites. In the gut, therapeutic eradication of organisms, which are providing a source of antigen, could also explain resolution of urticaria and other allergic manifestations. Study of these three patients, an understanding of the pathophysiology of giardiasis, and an absence of other disease in these cases leads us to the coqclusion that the retinal arteritis was probably caused by giardiasis, either acting as a direct extraintestinal infection or through an allergic mechanism. We, therefore, also emphasize the need to search for intestinal parasites in all patients with ocular inflammation, and especialiy in patients with retinal arteritis.
ACKNOWLEDGMENTS The authors thank Connie S. Lawson, Carol King, and J. David Andrews for assistance during preparation of the manuscript.
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REFERENCES 1. Barraquer I. Sur la coincidence de la lambliase et de certaines lesions du fond de l'oeil. Bull Soc Pathol Exot (Paris) 1938; 31:55-8. 2. Faust EC, Russell PF. Craig and Faust's Clinical Parasitology, 6th ed. Philadelphia: Lea and Febiger, 1957. 3. Carroll ME, Anast BP, Birch CL. Giardiasis and uveitis. Arch Ophthalmol 1961; 65:775-8. 4. Wolfe MS. Giardiasis. JAMA 1975; 233:1362-5. 5. Moore GT, Cross WM, McGuire 0, et al. Epidemic giardiasis at a ski resort. N Eng I J Med 1969; 281 :402 - 7. 6. Osterholm MT, For/ang JC, Ristinen TL, et al. An outbreak of food borne giardiasis. N Engl J Med 1981; 304:24-8. 7. Takano J, Yardley JH. Jejunal lesions in patients with giardiasis and malabsorption: an electron microscopic study. Bull Johns Hopkins Hosp 1965; 116:413-29. 8. Brandborg LL, Tankersley CB, Gottlieb S, et al. Histological demonstration of mucosal invasion by Giardia lamblia in man. Gastroenterology 1967; 52:143-50. 9. Owen RL, Nemanic PC, Stevens DP. Ultrastructural observations on giardiasis in a murine model. I. Intestinal distribution, attachment, and relationship to the immune system of Giardia muris. Gastroenterology 1979; 76:757 -69. 10. Webster BH. Human infection with Giardia lamblia. An analysis of 32 cases. Am J Digest Dis (New Series) 1958; 3:64-71. 11. Thomas GE, Goldsmid JM, Wicks AC. Use of the Entero-Test duodenal capsule in the diagnosis of giardiasis. A preliminary study. S Afr Med J 1974; 48:2219-20. (Entero Test capsules are available from the Health Development Corporation, 2551 Casey Ave., Bldg. 2, Mountain View, CA 94043). 12. Welch PB. Giardiasis with unusual clinical findings. Preliminary report. Am J Digest Dis 1943; 10:52-5. 13. Graux, Milbled. Infiltrat labile encephalo-pneumo-ganglionnaire avec eosinophilie sanguine et lambliase. Rev Neurol 1956; 95:405-6. 14. Harris RH, Mitchell JH. Chronic urticaria due to Giardia lamblia. Arch Dermatol Syph 1949; 59:587-9 15. Braley AE, Hami Iton HE. Central serous choroidosis associated with amebiasis. A record of nine cases. Arch Ophthalmol 1957; 58:1-14. 16. King RE, Praeger DL, Hallett Jw. Amebic choroidosis. Arch Ophthalmol 1964; 72: 16- 22. 17. Djabri SE, Diallinas N. L'importance de la lambliase comme facteur etiologique dans la chorioretinite centrale sereuse. Ophthalmologica 1964; 147:264-72. 18. Ricci A. La retinite pseudo-albuminurique de Leber (retinitis stellata) Ann Oculist 1961; 194:1038-47. 19. Collier M, Adias L. L'lambliase et hemorragie du vitre. Bull Soc Med Pau 1961; 43:133-9. 20. Drouet, Thomas, Cordier, Algan. Origine parasitaire de certaines hemorragies recidivantes du vitre. Bull Mem Soc Fr Ophtalmol 1949; 62:250-3. 21. Druault-Toufesco N. Les lesions maculaires en rapport avec les parasites intestinaux. Bull Mem Soc Fr Ophtalmol 1960; 73:144-51.
Abstract: The intestinal parasite Giardia lamblia was found in the stools of three patients with retinal arteritis. Iridocyclitis was also present in two of these patients, who had not responded to treatment with systemic corticosteroids. Antiparasitic drug treatment was followed by improvement of ocular and systemic findings. [Key words: Giardia lamblia, giardiasis, iridocycl itis, retinal arteritis.] Ophthalmology 89: 1303-1308, 1982
Severe loss of vision from retinal arteritis occurred in three patients who were found to have gastrointestinal infection with the parasite Giardia lamblia. Ocular complications of Giardia infection were first reported in 1938 by Barraquer, 1 who described iridocyclitis, choroiditis, and hemorrhagic retinopathy. The present report is the first to describe retinal arteritis occurring in patients with giardiasis. The similarity of the arteritis in the three patients is striking.
CASE REPORTS Case 1. A 43-year-old white businessman and travelling salesman from North Carolina was in good health until late September 1969, when he began awakening at about 4:00 a.m. with a sense of restlessness. Early in October 1969, he had noted redness and slight discomfort on movement of the left eye. After several days he discovered that his vision was reduced. On October 24, 1969, he saw his ophthalmologist, who found a normal right eye with 6/6 (20/20) visual acuity. Vision in the left eye was 6/12 (20/40) with keratic precipitates and aqueous and vitreous flare and cells. Fundus examination found hazy media and diffuse whitening of the peripheral retina, with edema extending posteriorly to the equator. The optic disc was swollen, with venous congestion. The patient was hospitalized in North Carolina where all
From the Wilmer Ophthalmological Institute of The Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland* and Thomasville, Georgia.t Presented as a poster at the Eighty-sixth Annual Meeting of the American Academy of Ophthalmology, Atlanta, Georgia, November 1-6,1981. Reprint requests to David L. Knox, MD, Wilmer Institute, The Johns Hopkins Hospital, Baltimore, MD 21205. 0161-6420/82/1200/1303/$1.10
© American Academy of Ophthalmology
diagnostic studies were normal. Five stool specimens studied for ova and parasites were considered negative. He was treated with large doses of systemic steroids and intravenous adrenocorticotropic hormone (ACTH). The areas of retinal whitening coalesced; they extended from the periphery to the ends of the temporal retinal vessels, and then became fatty yellow in color. The retinal vessels in this area were surrounded by perivenous hemorrhages in the nerve fiber layer. At the time of discharge from the hospital in North Carolina, he had mild occult blood in his stool despite a bland diet. He was given antacids as an anti-ulcer regimen. Although receiving dexamethasone 3.75 mg by mouth every morning and also topical dexamethasone ointment and drops, his right eye developed 1 + aqueous flare and cells, but the vitreous remained clear. Visual acuity in the left eye deteriorated to 6/18 (20170), with 3 + flare and cells in the aqueous and vitreous. The fundus showed increased peripheral hemorrhages but less exudate. The retinal arteries had become irregularly thickened by a yellowish substance that prevented visualization of any flow of blood. The patient was seen at the Wilmer Institute in Baltimore on November 17, 1969, four weeks after the onset of visual symptoms. Vision in the right eye was 6/5 (20/15) and in the left eye was 6/18 (20170 +2). There was one cell visible in the right anterior chamber. The left eye had small keratic precipitates, 2 + aqueous flare and cells, a clear lens, and dense flare and cells in the vitreous. The fundus examination of the right eye was normal. The media of the left eye were hazy. Scattered "infiltrated" arteries, macular edema, and peripheral yellow subretinal deposits were present (Fig 1). Diagnostic studies in the Johns Hopkins Hospital revealed cysts but no trophozoites of G. LambLia and 1 + guaiac for occult blood in the stools. X-ray findings of the large and small bowel were interpreted as normal. A peroral capsule biopsy of the jejunum revealed intraluminal Giardia and slightly abnormal intestinal villi (Fig 2). On November 21, 1969, the patient was started on quinacrine (Atabrine®) 100 mg three times a day; oral corticosteroids were continued. One month later, vision in the left eye
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Fig 1. Top left, case 1, November 1969. Fundus of the left eye shows hazy vitreous and yellow-white deposits around thickened retinal arteries. Fig 2. Top right, case 1, November 1969. Jejunal biopsy specimen shows edematous epithelial cells and curvilinear Giardia lamblia, some of which are attached to epithelial cells (hematoxylin-eosin, XI500). Fig 3. Left, case 2, November 1970. Fundus of the right eye shows hazy vitreous and yellow-white shaggy thickening of the retinal arteries.
Figs 4A-C. Case 3, right eye, A, top left, April 21, 1980, before treatment, showing clear media, shaggy-white inferior retinal artery, "cotton wool" exudate, and inferior retinal ischemic edema. B, top right, May 5, 1980, after treatment, shows resolving retinopathy, lesser degree of white thickening of inferior artery, and less edema of inferior retina. C, left, May 19, 1980, showing further resolution after treat-
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KNOX AND KING • OCULAR CHANGES WITH GIARDIASIS
had decreased to 6/60 (201200). The inflammation in the anterior chamber and vitreous was still present. The perivascular lipid was still visible, and the retinal arteries were attenuated. In July 1970, vision in the left eye was light perception, and systemic corticosteroids were stopped. By September 1970, through hazy media, the retinal arteries seemed to be markedly attenuated, and there were large areas of excessive pigmentation. In April 1972, the left eye had vision of bare light perception, the anterior chamber was free of inflammation, and a mature cataract prevented visualization of the fundus. The right eye was normal. Comment. Gastrointestinal infection with G. Lamblia was the only abnormal systemic finding in this patient with retinal arteritis in the left eye and uveitis in both eyes. Absence of identifiable parasites in the stool specimens examined early in the course of his illness can be explained by either technician error or the fact that often when severe Giardia infection is present in the jejunum, no trophozoites or cysts can be demonstrated in stool specimens. Treatment with quinacrine (Atabrine®) was followed by complete resolution of anterior segment inflammation in the right eye and eventual improvement in the left eye. Unfortunately, prolonged inflammation and occlusion of the retinal vessels produced irreversible ocular damage. Case 2. A lO-year-old white boy from North Carolina was seen in November 1970 at the Wilmer Ophthalmological Institute for evaluation of a bilateral uveitis of one year's duration. His past medical history was normal until age 8, when he began to experience (one or two times per week) a postprandial, mucous bowel movement in which the stools were watery and "floated in the toilet." The stools were examined once for intestinal parasites, which were not seen. The patient had never been proctoscoped or had any x-ray contrast studies of stomach, small intestine or large bowel. He had been treated with parasympathetic blocking agents and an absorptive agent to control the diarrhea, which had been diagnosed as "colitis." At age 9, one year after onset of the" colitis," he awakened one morning with aching and throbbing of the left eye. The next day he complained of blurring vision of the left eye. He was seen by an ophthalmologist who started methylprednisolone (Medrol®) 4 mg by mouth, four times per day, and ACTH intramuscularly, and "eye drops" for a "uveitis." The pain decreased after systemic corticosteroids were started, but vision improved only slightly. While systemic corticosteroids were tapered to 2 mg of methylprednisolone per day, inflammation in the left eye returned. By January 1970, the patient developed inflammation in the right eye. Systemic corticosteroids were continued, which gave some relief to his abdominal pain, mucous colitis, and ocular inflammation. The patient was seen by a second ophthalmologist in January 1970, who found the posterior poles of both eyes appeared to be "perfectly normal," but heavy exudates between the equator and the ora serrata of both eyes. The anterior chamber reaction was slight in both eyes. Because the uveitis persisted and worsened despite use of oral and sub-Tenon' s injections of long-acting corticosteroids, he was hospitalized in May 1970. Vision was 6/12 (20/40) in the right eye, and hand movements in the left eye. Cyclophosphamide (Cytoxan®) was started, but stomach distress increased, and the cyclophosphamide therapy was stopped. In late October 1970, vision in the right eye worsened to perception of hand movements, and cyclophosphamide was restarted. After three days the nausea and
vomiting returned, and the cyclophosphamide was stopped. Prednisone, 80 mg per day, was started. The patient was first seen in Baltimore on November 23, 1970. Vision was "count fingers" at 5 ft with the right eye, and at 8 ft in the left eye. The patient had a Cushingoid facies, carious teeth, and white eyes. Slit-lamp examination revealed no keratic precipitates, 1 + aqueous flare and cells in both eyes, and posterior synechia at 6:00 o'clock in the left eye. Posterior subcapsular lenticular opacities and diffuse vitreous pigmented and white cells were present. The intraocular pressure was 18 mm Hg in the right eye and 24 mm Hg in the left eye. Funduscopy of both eyes was difficult because of hazy media. The retinal arteries were very narrow and had yellowish-white exudate along them. Large patches of thick yellow material (6 to 10 disc diameters in size) were present within and beneath the retina inferiorly. In other areas, small patches of yellow material (1/4 disc diameter in size) were present (Fig 3). General physical examination revealed an irritable boy who had six carious, deciduous teeth. Laboratory studies found only a serum cholesterol level of 404 mg/dl (normal 150 to 300 mg/dl). The WBC count, eosinophil count, and erythrocyte sedimentation rate were normal. Because of his history of mucous colitis one to two years prior to the onset of his eye trouble and a favorable response to systemic corticosteroids, he was strongly suspected of having Crohn's disease. A stool specimen was studied for ova and parasites. The technician reported that trophozoites of Giardia were so numerous that they were "lined up like soldiers." Proctosigmoidoscopy revealed a friable rectal mucosa and thin brown mucus, similar to what had been seen in other patients with intestinal parasites. Results of x-ray contrast studies of the stomach, small bowel, and large bowel were interpreted as normal. Quinacrine (Atabrine®), 50 mg given orally three times a day, was started. There was a marked improvement in his attitude and behavior by the time he was discharged from the hospital, five days after admission. After treatment with quinacrine, the mucous colitis did not recur, but the uveitis (of one year's duration at the time of treatment) persisted. The boy eventually has required schooling as a blind person. Comment. In this patient, the presence of mucous colitis prior to the onset of ocular inflammation can be explained easily by giardiasis. That explanation was not proven, however, because G. Lamblia were not demonstrated as being present prior to his admission to the Johns Hopkins Hospital. It is possible, therefore, that the long-standing use of systemic corticosteroids and immunosuppressive therapy with cyclophosphamide altered his immune mechanisms, allowing Giardia infection to develop. However, treatment with quinacrine stopped the mucous colitis and improved the "irritability" that had been present prior to onset of the ocular inflammation. It is also possible that Giardia had caused the original colitis, but that the parasites (under the influence of steroids and immunosuppression) increased in numbers-so that when the patient was seen in Baltimore many trophozoites were found in a watery stool specimen. Case 3. A 39-year-old white female nursery school employee was first seen on April 21, 1980 in Thomasville, Georgia, complaining of a two-day loss of vision in her right eye. She stated that she had awakened with severe blurring of vision that rapidly progressed during several hours to a dense loss of vision in the central and superior field. There was no history of trauma, and the patient was apparently in
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good general health, with no symptoms of any recent illness. She had never been outside the area of southern Georgia and northern Florida. Ocular examination in Thomasville, Georgia found visual acuity of 6/120 (20/400) in the right eye, which was accomplished by her fixating slightly above the test letter. The left eye had a visual acuity of 6/6 (20/20) and no appreciable refractive error. Pupil reactions were normal in both eyes. Abnormal findings were confined to the right eye. The anterior chamber was clear, and no lenticular opacities were seen. A few vitreous inflammatory cells were present posteriorly. The optic disc was "flat" and slightly hyperemic, with a sharp outline. The inferior portion of the retina below the small cilioretinal artery was markedly ischemic. The inferior temporal artery near the disc was obscured by yellow, fuzzy perivascular material. The affected retina was light gray and somewhat mottled, but with retinal vessels clearly visible (Fig 4A). The macula showed loss of the reflex and was dark red. Fluorescein angiography was not performed. Stool examinations of the patient were initiated because one of the authors (JK) had attended a continuing education course at which the other author (DLK) had presented the clinical details of cases 1 and 2. The retinal arteritis of c'ase 3 was considered to be similar and thus worthy of study for the presence of Giardia. Laboratory studies found only a large number of G. Lamblia cysts in three different stool specimens. A presumptive diagnosis of retinal vasculitis caused by giardiasis was made, and the patient was started on quinacrine, 100 mg three times a day for ten days, and prednisone 60 mg per day, which was tapered gradually during ten days. The retinal ischemia rapidly cleared, and 14 days after start of therapy the retina returned to an almost normal color (Fig 4B). The macula showed pigment changes, and a dense central scotoma remained. Function of the inferior retina improved, and the patient was no longer aware of visual field loss except centrally. Visual acuity remained 6/120 (20/400) with slightly eccentric fixation (Fig 4C). Because of the possibility of water-born contamination, the local health department investigated the water supply of the community in which the patient lived. The water supply for 35 homes came from two large wells and from individual homesite wells. No water was treated. All the homes were served by individual septic tanks, 28% of which seeped, backed up, or had problems in bad weather. Giardia cysts were found in the stools from four children. Two of these children lived in homes served by individual wells. The present patient and the two other infected children, received water from one of the community wells. Comments. In this patient giardiasis was implicated because the retinal arteritis was morphologically similar to that seen previously in patient 1 and patient 2, and because therapy for giardiasis was followed by ocular improvement. In these three patients, appropriate laboratory tests ruled out the following diseases as the cause of the retinal arteritis: Beh«et's disease, drug allergy, cerebral granulomatous angiitis, herpes zoster, lupus erythematosus, pars planitis, polyarteritis nodosa, sarcoidosis, syphilis, and toxoplasmic retinitis.
DISCUSSION Giardia LambLia is a flagellated, binucleate protozoan, 12 to 14 microns long, which in man prefers to 1306
inhabit the jejunum. Giardia occur as motile trophozoites or as immobile cystS. 2 ,3 Giardia was first 'Observed in 1681 by Von Leeuwenhoek, with his microscope, while looking at a suspension made from his own stools. The usual mode of infection is by ingestion of water contaminated by human sewage, although there is evidence that animal reservoirs such as deer, rabbits, beavers, or sheep may discharge viable cysts into pristine, crystal clear mountain streams. Areas of endemic infection include Russia, Iran, and Uruguay.4 Epidemics of giardiasis have occurred when sewage lines crossed water supplies, which was the explanation for an outbreak in Aspen, Colorado. 5 A more recent epidemic occurred when a woman, after changing the diapers of her unrealizedly infected grandson, contaminated her own home-canned salmon, which she was preparing for fellow workers. 6 Giardia live and multiply in the jejunum, where their sucker plates attach the organisms to swollen microvilli of intestinal epithelial cells 7 (Fig 2). Giardia have been demonstrated within the substantia propria of human jejunal villa8 and in rabbit Peyer's patches of lymphoid cells. 9 As of this writing, G. Lamblia has never been demonstrated by histopathology or electron microscopy to occur in any extraintestinal tissue. The gastrointestinal symptoms of giardiasis include burning epigastric distress, excessive burping and belching in the evening and night, abdominal cramps, flatulence, diarrhea or constipation, malodorous stools, anorexia, and weight 10ss.lO In contrast, heavily-infected persons may be entirely asymptomatic. Diagnosis is often difficult. Multiple stool examinations may reveal no organisms, a few cysts, or many motile trophozoites. Freshly passed or purged stools can increase the yield. Aspiration, capsule biopsy, or an "enterotest" of jejunal tissues and juices are sometimes the only way to demonstrate the organisms. 11 In some instances, even when no organisms are found, the patient's symptoms may be so characteristic and the responses to treatment so prompt that a presumptive diagnosis can be made. Treatment is with quinaquine hydrochloride (Atabrine®) at a dosage of 100 mg three times per day for 10 days, and/or metronidazole (Flagyl®) 250 mg three times per day for seven to ten days. Rechecking the stools in several weeks is advisable, both because of possible inadequacy of treatment or possible reinfection. Retreatment may be required. Study of family members may be indicated, and, if necessary, a search for the source of infection. Extraintestinal manifestations are varied. The largest series is that of Webster 10 in 1958. He reported an analysis of 32 patients. Welch 12 in 1944 described the findings of 29 patients. "Nervousness" was present in 23 of Webster's 32 patients. Emotional instability of nervousness was described in 9 of Welch's 29 patients. Headaches, seizures, pulmonary infiltrates, lymphadenopathy, and an eosinophilia of 9% were reported in a 6-year-old
KNOX AND KING • OCULAR CHANGES WITH GIARDIASIS
child who had a positive skin test for tuberculosis and had Giardia organisms in his stools. Urticaria was noted in six of Webster's 32 patients and has been featured in other reports. 14 In our search of the literatun~, we found no report of biopsy of an urticarial wheal in a case of giardiasis. Dizziness in nine patients and palpitation and fever in seven patients were reported by Webster. All extraintestinal symptoms rapidly resolve after therapy with quinacrine or metronidazole. Most of the reports on the ocular complications of giardiasis are written in French. This may reflect a high frequency of giardiasis in France, or an interest in correlations of ocular disease with various intestinal parasites. In the English language, there was only one report 3 of eye disease associated with giardiasis. If the association has been made in Russia, such a report has not been indexed in the English literature. . In 1938 Barraquer1 first reported eye disease in patients with giardiasis. Fundus lesions such as diffuse chorioretinal edema, subretinal hemorrhage; hyperplasia or loss of pigment epithelium, and vitreous hemorrhage are the most common findings. Barraquer reported his observations of choroiditis, hemorrhagic retinopathy, or iridocyclitis in patients who had diarrhea and stools positive for Giardia. Treatment with oxyaminophenylarsinic acid (Treparsol) was followed by improvement in diarrhea and the ocular condition. Barraquer did not state how many patients he had seen, or how many patients had each of the various ocular abnormalities. N. R. Dechiens, in discussing Barraquer's paper,! confirmed Barraquer's observations. It is of interest that Barraquer also described Entamoeba intestinalis (forme minuta) and Entamoeba coli as being often found with Giardia in patients with ocular fundus disease. Combined treatment with oxyaminophenylarsinic acid and emetine cleared the stools of parasites and stopped the diarrhea. Clinical improvement after any of several medications prevents a "therapeutic response" argument as to which parasite was responsible for the ocular inflammation. Also, quinacrine is effective against both G. lamblia and Entamoeba histolytica. Other reports have described the presence of E. histolytica, which is the same as Barraquer's E. intestinalis (forme minuta), as being associated with central serous choroidosis 15 or amebic choroidosis. 16 E. coli and Endolimax nana, different parasites, have (in the experience of one of the present authors, DLK) also been associated with subretinal hemorrhagic exudative choroidopathy of a type similar to that seen with amebiasis. In 1961 Carroll, Anast, and Birch 3 reported (from Chicago) the details of a 9-year-old girl who had a subretinal hemorrhagic and exudative chorioretinopathy. Systemic evaluation included tests for ova and parasites in the stools. G. lamblia was found. Treatment with quinacrine was followed by improvement in one eye, with reduction of subretinal fluid and hemorrhage in two weeks. Vision improved from 20/400 to 20/100 in the poorer eye. The stools were cleared of Giardia.
In 1961 Djabri and Diallinas 17 reported three patients from Franceschetti's Clinic in Geneva, Switzerland. All were adults. Two had inflammatory cells in the anterior chamber. The fundi of these patients had irregular macular edema, with reduced acuity. Treatment with antiparasitic medication was followed by improvement in acuity and resolution of the retinal edema. One of the patients had an 8% eosinophilia. In all three patients, Giardia was not demonstrated by stool examination but only by duodenal aspiration. Riccil 8 in 1961 described three patients with "Leber's pseudoalbuminuric retinitis" (composed of edema of the optit disc and macula, and retinal hemorrhage). One patient had three intestinal parasites: Ankylostoma, E. nana, and G. lamblia. After treatment with antiparasitic drugs and systemic corticosteroids, complete resolution of the papilledema occurred. Collier and Adias 19 reported a patient with vitreous hemorrhage and giardiasis. Vitreous hemorrhage has also been reported 20 in patients with intestinal infection by Ascaris. Macular lesions, iridocyclitis, a retinitis identical to that in toxoplasmosis, and a uveomeningitis were described in a report 21 that described the presence of Oxyuris and Tricephalus in the stool and Trichomonas vagina lis . One of us (DLK) has found Giardia infection in 18 patients with the following ocular findings: iridocyclitis, four patients; a toxoplasmic type of retinitis, three; retinal arteritis, two; pars planitis, two; and keratitis, episcleritis, iritis, exudative retinal detachment, amebic choroidosis, chorioretinal atrophy, and nutritional amblyopia, one case of each. The three patients in our present report all had funduscopic evidence of inflammation of retinal arteries. Shaggy, patchy, opaque yellow thickenings of the walls of the arteries were seen in all three. Anterior chamber and vitreous inflammation (iridocyclitis) occurred bilaterally in two of the patients. Irritable behavior occurred in the same two patients who had iridocyclitis. The persistent irritability stopped promptly with treatment in case 2. All three patients were found to have G. lamblia in their stools at the time of active ocular inflammation. Two of the patients had had negative stool examinations earlier in the course of their disease. In case 1, after treatment, there was immediate improvement in iridocyclitis of the right eye. In the left eye the iridocyclitis slowly quieted, but vision and the retina did not return to normal. Patient 2 had no improvement in vision in either eye. The inflammatory process had been active for 12 months in patient 2, and for one month in patient L With combined antiparasitic and anti-inflammatory therapy, patient 3 had rapid improvement in her affected eye. Patients 1 and 2 had not improved with only systemic steroids. After prolonged disease, ocular tissues develop changes that specific antimicrobial or combined antimicrobial and antiinflammatory therapy cannot reverse. Patient 3 had the best response to combined early therapy with metronazolamide (Flagyl®) and systemic 1307
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steroids. Even so, visual acuity was reduced permanently. A further expianation for failure of treatment to improve vision in these patients is the nature of the arteritis-induced vascular occlusive process that impairs blood supply causing irreversible necrosis of ocular tissue. Prolonged inflammation can also alter affected blood vessels so that they cannot reopen. Retinal arteritis from infection with G. lamblia could be explained by direct invasion of the eye and its arteries by the organism. There is no histopathologic evidence for or against this concept, since there are no reports of microscopic study of ocular tissue in patients with giardiasis. Urticaria, which ocCurs in a few patients with giardiasis, is the extraintestinal manifestation most similar to the retinal arteritis and ocular inflammation reported here. These urticarial lesions on histopathologic examination have inflamed arteries with diffuse infiltrates composed of polymorphonuclear, lymphoid, arid eosinophilic inflammatory cells. The patchy, scattered urticarial lesions are similar to the patchy nature of these patients' retinal arteritis. It must be assumed at this time that the extraintestinal manifestations of giardiasis are allergic in nature. Treatment with quinacrine or metronazolamide is followed by resolution of extraintestinal manifestations and the gastrointestinal symptoms such as diarrhea. These responses argue either for an extraintestinal tissue infection by G. lamblia or an allergic mechanism, since both dfugs are absorbed through the gut and then diffuse into other tissues-such as the vaginal mucosa, where the drug metrohazolamide combats Trichomonas vaginalis; or in blood or liver, where quinacrine acts on malarial parasites. In the gut, therapeutic eradication of organisms, which are providing a source of antigen, could also explain resolution of urticaria and other allergic manifestations. Study of these three patients, an understanding of the pathophysiology of giardiasis, and an absence of other disease in these cases leads us to the coqclusion that the retinal arteritis was probably caused by giardiasis, either acting as a direct extraintestinal infection or through an allergic mechanism. We, therefore, also emphasize the need to search for intestinal parasites in all patients with ocular inflammation, and especialiy in patients with retinal arteritis.
ACKNOWLEDGMENTS The authors thank Connie S. Lawson, Carol King, and J. David Andrews for assistance during preparation of the manuscript.
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REFERENCES 1. Barraquer I. Sur la coincidence de la lambliase et de certaines lesions du fond de l'oeil. Bull Soc Pathol Exot (Paris) 1938; 31:55-8. 2. Faust EC, Russell PF. Craig and Faust's Clinical Parasitology, 6th ed. Philadelphia: Lea and Febiger, 1957. 3. Carroll ME, Anast BP, Birch CL. Giardiasis and uveitis. Arch Ophthalmol 1961; 65:775-8. 4. Wolfe MS. Giardiasis. JAMA 1975; 233:1362-5. 5. Moore GT, Cross WM, McGuire 0, et al. Epidemic giardiasis at a ski resort. N Eng I J Med 1969; 281 :402 - 7. 6. Osterholm MT, For/ang JC, Ristinen TL, et al. An outbreak of food borne giardiasis. N Engl J Med 1981; 304:24-8. 7. Takano J, Yardley JH. Jejunal lesions in patients with giardiasis and malabsorption: an electron microscopic study. Bull Johns Hopkins Hosp 1965; 116:413-29. 8. Brandborg LL, Tankersley CB, Gottlieb S, et al. Histological demonstration of mucosal invasion by Giardia lamblia in man. Gastroenterology 1967; 52:143-50. 9. Owen RL, Nemanic PC, Stevens DP. Ultrastructural observations on giardiasis in a murine model. I. Intestinal distribution, attachment, and relationship to the immune system of Giardia muris. Gastroenterology 1979; 76:757 -69. 10. Webster BH. Human infection with Giardia lamblia. An analysis of 32 cases. Am J Digest Dis (New Series) 1958; 3:64-71. 11. Thomas GE, Goldsmid JM, Wicks AC. Use of the Entero-Test duodenal capsule in the diagnosis of giardiasis. A preliminary study. S Afr Med J 1974; 48:2219-20. (Entero Test capsules are available from the Health Development Corporation, 2551 Casey Ave., Bldg. 2, Mountain View, CA 94043). 12. Welch PB. Giardiasis with unusual clinical findings. Preliminary report. Am J Digest Dis 1943; 10:52-5. 13. Graux, Milbled. Infiltrat labile encephalo-pneumo-ganglionnaire avec eosinophilie sanguine et lambliase. Rev Neurol 1956; 95:405-6. 14. Harris RH, Mitchell JH. Chronic urticaria due to Giardia lamblia. Arch Dermatol Syph 1949; 59:587-9 15. Braley AE, Hami Iton HE. Central serous choroidosis associated with amebiasis. A record of nine cases. Arch Ophthalmol 1957; 58:1-14. 16. King RE, Praeger DL, Hallett Jw. Amebic choroidosis. Arch Ophthalmol 1964; 72: 16- 22. 17. Djabri SE, Diallinas N. L'importance de la lambliase comme facteur etiologique dans la chorioretinite centrale sereuse. Ophthalmologica 1964; 147:264-72. 18. Ricci A. La retinite pseudo-albuminurique de Leber (retinitis stellata) Ann Oculist 1961; 194:1038-47. 19. Collier M, Adias L. L'lambliase et hemorragie du vitre. Bull Soc Med Pau 1961; 43:133-9. 20. Drouet, Thomas, Cordier, Algan. Origine parasitaire de certaines hemorragies recidivantes du vitre. Bull Mem Soc Fr Ophtalmol 1949; 62:250-3. 21. Druault-Toufesco N. Les lesions maculaires en rapport avec les parasites intestinaux. Bull Mem Soc Fr Ophtalmol 1960; 73:144-51.