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Show {oumal of Clillical Nellro~ophthaill/ll/osy 7(1 );1-5, 1987. C1987 Raven Press; New York /.-.---. . . . . A.cll:fe.SyphiliticBlit1efhess In AIDS William Zambrano, M.D.,GerardoM. .perez, M.D.,' and J;Lawtoh Smith, .M:O. /", .,' - .'",.:..............' Wereteritly enc(j1.Ihteied. a. bisex1.Ialmariwith· AIDS who abruptly went. blind secoridaryt()syc philitic opticneuritis.,Toourknowledge;this is' the first'reporrof bilateral syphilitic optic neuritis in AIDS. .CASE REPORT A 23:year-oldblack bisexuaFmale was admitted Medical Serviceon September27, 1985with progressively increasirigdyspneaonexertionarid dry uriprbd uctive •cough. Chest x-rayshowedbi~ lateral lower lobeiriterstitial infiltrates. Bronchos-. '. .copy yielded positive touchpieparationsforPnelllIlocystis cilrinii,Serum assays for human TeelI leukeiniallymphotropic virus]II (HTLV~IIl) antibodies were positive. T~tellstudies showed inverted and decrea'sed helper to suppressor cell ratioof 0:1 (normal:-1.1-:3,S).thepatieritwas. freated with intravenous Bacfrimwith resolution of the respiratory complaints. Two days prior to termination of the Bactrim regirn.ert;he developed a fever of102°, •Enhanced computed tomography.' (CAT) scan ofthe .brainwasnormaLCerebro-. · spinal fluid (CSF) on OctoberS, 1985 revealed a .. dear fluid with-a protein of 0.48 gIL (normal: 0:16-0.24 g/L)a:nd 2 monocyfes'(Table 1).The CSF glucose was 4:3 mmollL(normal: 2.2-4.4mmoll · L).hidia ink, gram stain and acid fast srn.ears of theCSF wen~negative..Thefever resolved upon' cessation of •• frimethoprim/sulfatI1ethoxazole therapy. On. October8,J98S.thepatient was dis- . charged on one tablet of sulfadoXine/pytirn.eth-· arn.irie weekly for prophylaxis against PIll:'1111l0CI/Stis' carillii pneumonia. Six days. later; the patien(presented'tClBascom pa.lmer Eye Institute withal-'day history of de- · creased vision in the left eye. His ocularhistory was otherwise negative: He denied having diabetes mellitus, sickle'celldisease; hypertension, arthritis, or knownautoimmune·disease. To· ourknawledge,bilale~alsyphiliticap ticneuritis has . not been reported in conjunCtion with AIDS. We dommenta case ofabisexual man with AIDS whose vision deteriorated overnight from 20/20 in both eyes to total· . bilateral blindness as a result of syphilitic retrobulbar neuritis. The implications andmanagementbf leu tic disease in immunocompromised individuals are 'discussed. Key Words: AIDs-.Blindness-:-syphilis.. From the Basc6;TIPalmer Eye fnstitute,' University of Miami School of Medicine,Miami; Florida. ." Address correspondence and reprint requeststoWilliilm Zambrano',. M. D., Bascom Palmer Eye Institute, P.O. Box 016880,.Miami,··FL33101,U.S.A. FIG. L Slit-lamp examination showihgcells in vitreous. Normal values. CSF Protem, 0.16-0.24 giL; CSF Glucose, 2.2-44 mmol/L , ACid fast smear, India ink, gram stain. Bactenal, fungal, mycobacterial. 10/29/85 (after PCN) o Not done 3 2.8 mmol/L 0.72 giL Negative Negative Negative 10/15/86 (before PCN) 32 85% Monos; 15% Polys 87 3.3 mmol/L 1.58 giL Negative Negative Negative 10/5/85 4.3 mniol/L 048 Negative Negative Not done 2 100% Monos TABLE 1. CSF findings Findings White blood cells Differential Red blood Glucose Protem Stains' Cultures" VORL the left eye. Pupils were still dilated and fixed. The rotary nystagmus was decreased in amplitude and frequency. After 1 week of penicillin therapy, the patient's vision had improved so that he could perceive hand motions at 6 feet with the left eye, but he remained blind in the right eye. Repeat lumbar puncture. performed on. October 29, 1985 showed a clear fluid with no leukocytes, a protein of 0.72 giL, and glucose of 2.8 mmollLThe CSF VORL was nonreactive. Serum RPR titer dropped to 1:16. The penicillin was discontinued after 13 days, after the patient had received a total of 104,000,000 U. By November 5,1985, the patient's vision had improved to 20/40 in the left eye through a tubular field, but he remained blind in the right eye; The nystagmus had disappeared. Pupils were 6 mm in both eyes, unreactive to light in the right eye, and weakly reactive to light in the left. There Was now a brisk reaction to near stimuli in both eyes; Slit·lamp examination revealed cells in the vitreous (Fig. 1), and the fundus showed beginning pallor of both optic discs (Figs. 2 and 3). The cotton-wool spots persisted (Fig. 4). Examination on October 14, 1985 revealed a best corrected visual acuity of 20/20, both eyes. Visual fields were normal. The pupils were 4mmin both eyes and were weakly reactive to light. No relative afferent pupillary defect was noted. External ex· amination revealed numerous healing herpetiform vesicular lesions on the first and second trigeminal division dermatomes not involving the lid margin or nose. Ouctions and versions were intact. No nystagmus was present. Slit-lamp examination re· vealed a moderate number of red cells in the anterior vitreous of the left eye. Applanation tensions were normal. Indirectophfhalmoscopyshowed numerous scattered cotton-wool spots in the right eye without evidence of phlebitis or hemorrhages. The macula and disc were within normal limits. The left eye revealed a normal disc, macula, and vessels with. scatteredcotton·woolspots throughout and a vitreous hemorrhage layered in~ feriorly, No retinal tears were detected. The patient was instructed to remain in bed with his head elevated and to return for follow·up examination in one week. However, he awoke. the. next. morning essentially. blind in both eyes; Examination then re~ vealed that he had nO light perception in the right eye and could perceive hand motion at 2':"'3 inches with the left eye.• Pupils were 6 mm in the right eye and 7 mm in the left and were unreactive to light or near stimuli. Motilitywasintact.There was marked rotary nystagmus in all fields ofgaze. Results of slit~lampand fundus examinations were unchanged. Tensions by applanation /were normal. The patient was readmitted to the hose pital. Neurological examina ti6nand CATscan of brain with enhancement were normal.CSF examination on October 15,1985 revealed a protein of 1.58 giL, 32 white blood cells (WBC) (poly 150/c, mono 85%), and glucose of 3,3 mrrlol/L. gram stain, acid fast smear of CSF were negative. CSFVORLwasnonreactive (Table 1). The following day the patient was totally blind in both eyes. Pupils continued dilated and fixed but con· stricted to pilocarpine F1c,drops.The clinical im· pression. at this time Was that patient had meningitis and bilateral retrobulbar optic neuritis. However, a combination of optic neuritis and cortical blindness could not be excluded. Intravenous aqueous penicillin G (2,000,000 U/4 h) was advised until results of serologic tests for syphilis could be reported. Two days later, serum ra pidplasma reagin (RPR) was reported reactive at a titer of 1:512 an'-l FL\-ABS4+. Within 3 days of penicillin :' 1"1 f)v,thep,li< ""gained light perception in I I SYPHILITIC BLINDNESS IN AIDS 3 FIG. 2. Optic nerve pallor, right eye. On November 12, 1985 the patient's vision was 20/60 in the left eye but he was still blind in the right eye. Pupils were unchanged. The rotary nystagmus had reappeared. The results of the fundus examination of the posterior pole were unchanged but revealed peripheral confluent white patches in both eyes consistent with cytomegalovirus (CMV) retinitis. CMV serum and cerebrospinal fluid titers were low positive. On January 1, 1986, the patient was totally blind in both eyes. The funduscopic findings were consistent with end-stage CMV retinitis. Subsequent determination of the serum RPR on January 28, FIG. 3. Fundus, left eye, showing optic atrophy and retinal hemorrhages. FIG. 4. Cotton wool spots, right eye. 1986 showed a titer of 1:8 (Table 2). One month later, an anterior chamber paracentesis was performed. The examination of the aqueous humor done by Dr. Pierre Collart at the Institut Alfred Fournier in France revealed a 4+ TPHA. DISCUSSION AIDS is a disease caused by the human T-cell leukemia/lymphotropic virus III (HTLV-III). It affects bisexual and homosexual men (73% of the total), intravenous drug users (17%), Haitian immigrants (3%), recipients of blood products containing the virus (1 %), heterosexual contacts of individuals with AIDS or at risk for AIDS (1 %), and a few who fall into none of the known risk groups (1). The ophthalmic findings in AIDS have been recently emphasized (2-7). The reported cases of syphilis in 1985 included 27,143 of primary and secondary, 21,689 of early latent, and 18,414 of late latent and late (Centers for Disease Control). There were 129 reported cases of AIDS in 1981. By January of 1986 the total had reached 16,458 (1). It is of interest that although 50% of all men with primary, secondary or early latent syphilis interviewed in the United States in 1980 were homosexual or bisexual (8), there have been limited reports of concurrent ocular syphilis and AIDS (9,10). One would expect that the population at risk for AIDS is at an increased risk for any sexually transmitted disease. This case demonstrates acute bilateral syphilitic retrobulbar neuritis in just such a J (Ii" Neuro-oplttlwlmol. Vol. 7. No. ]. ]987 4 W. ZAMBRANO ET AL. TABLE 2. Serology Quantitative Date Sample VORL FTA-ABS TPI 10/17/85 (before PCN) Serum 1:512 4+ Not done 10/30/85 (after PCN) Serum 1:16 4+ Not done 1/29186 Serum 1:8 Not done Not done 2128/86 Aqueous Not done 4+ 3+ 5/14/86 Serum 1:16 PCN. penicillin: TPI, Treponema pallidum immobilization. patient. Although the existence of syphilitic retrobulbar neuritis as a disease entity has been questioned (11), acute syphilitic optic neuritis has been well described (12). Factors leading to the diagnosis of syphilitic retrobulbar optic neuritis in our patient are: (a) 4+ reactive serum FTA-ABS; (b) elevated pre-treatment serum RPR (1:512) with dramatic improvement post-treatment (1:8); (c) 4 + FTA-ABS and 4 + TPHA in the aqueous humor; (d) elimination of CSF monocytosis with substan-tial decrease in CSF protein concent!. :on following penicillin therapy; (e) clinical return of vision from amaurosis to 20/40 in the left eye; (f) return of pupillary function; (g) bilateral total visual loss without adequate fundus explanation; and (h) a normal CAT scan. Although it could be argued that cytomegalovirus has been reported to cause retrobulbar neuritis in the AIDS population (7) we believe that it is very unlikely to have been the etiologic agent in our patient. Retrobulbar neuritis secondary to CMV is unlikely to improve. Likewise, acute retinal necrosis would not have improved with penicillin therapy alone. Further, the temporal relationship of penicillin therapy and clinical improvement strongly suggests a cause-effect relationship. The fact that the CSF VORL was nonreactive is not discouraging, given the many reports of documented neurosyphilis with negative serology (12-15). Anatomic studies demonstrate that the begin- Newly Diagnosed AIDS/ARC \/ FTA-ABS (+) VORL (-) \I FTA-ABS (-) VORL (-) \/ FTA-ABS (+) VORL (+1 Follow Quant. VORL Every 3 .onths /\ \/ CSF**==>(-)==>NEURO,===>(-) Eye Exam \/ YES=========== \/ Adequate* Treatment? (+) (+) : : : : : : : : : : IV PCN X 10 days /\ /\ CSF==>(-)===> Neuro, (1f not /\ done) Eye .. Exam \/ NO====> \/ YES \/ Neuro, =======c=c> Eye Exam \/ Follow Quant. VORL/FTA-ABS Every 3 lIonths /\ /\ \/ Adequate* Treatment? \/ NO \/ (+ ) \/ (+) IV PCN X 10 Days \/ \/ Follow Quant. Treat As VDRL Every 3 .onths==<==Latent Syphilis .. \I : :===<===c=Normal (-) Treat As Latent Syphilis \I Follow Quant. VORL Every 3 aonths *AS DESCRIBED BY THE CDC **CSF EXAMINATION: CELLS, PROTEIN, VORL, ELECTROPHORESIS, COLLODIAL GEL FIG. 5. Treatment recommendation. SYPHILITIC BLINDNESS IN AIDS 5 ning of syphilitic optic atrophy takes place in the intracranial portion of the optic nerves or in the chiasm, or both (13). It is in this portion where the most extensive inflammatory-demyelinating process is located. In a few instances, atrophic changes may start in the intracanalicular portion or even in the retrobulbar part of the optic nerves, but such instances are the exception. Immediately behind the bulb there is atrophy of the nerve fibers without inflammation. As one approaches the middle portion of the orbital region, round cell infiltrations, consisting of plasma cells and lymphocytes, make their appearance both in the pia and in the interior of the optic nerves, increasing in number in the direction of the intracanalicular part, and becoming most numerous in the intracranial portion of the optic nerves and in the chiasm. Therefore, there can be considerable degeneration of the optic nerves in the presence of normal-appearing discs. In exceptional cases of syphilitic optic atrophy, the inflammatory changes may reach up to the discs producing the ophthalmoscopic appearance of a former optic neuritis. The natural history of syphilis in the AIDS population needs to be carefully examined. Does syphilis follow a more fulminant course in these patients? Is current therapy for syphilis adequate in the immunocompromised individual? A case of failure of recommended treatment for secondary syphilis in a patient without known immune compromise has recently been reported (16). The persistence of treponemal forms following adequate therapy has been described (17). Is the AIDS patient subject to reexacerbations of disease without reinfection because of these persistent treponemal forms? If so, is prophylactic or continuous penicillin therapy to be advocated for AIDS patients? Our patient responded well serologically after a total dose of over 100,000,000 U of intravenous aqueous penicillin G. A repeat VDRL titer 4 months after therapy has shown further decrease of titer from 1:16 to 1:8. A repeat VDRL titer at 7 months post-therapy was 1:16. We will continue to monitor the patient's serum VDRL serology on a regular basis. Because of the implications of systemic syphilis, it should be suspected in AIDS patients and appropriate laboratory tests should be given routinely to them. We recommend a baseline quantitative VDRL and FTA-ABS test for all patients upon initial diagnosis of AIDS or AIDS-related complex (ARC). If these are reactive, and no history of prior treatment is given, we recommend a spinal fluid examination. If the CSF is abnormal, then intravenous penicillin therapy would be advised. If initial VDRL and FTA-ABS are negative, or if prior history of adequate treatment is given, we would follow the serum VDRL quantitative titer routinely and retreat according to CDC guidelines if evidence of reinfection and/or reexacerbation arises. Our present treatment recommendations are summarized in flow chart fashion in Figure 5 (18). Finally, the dramatic return of good (20/40) vision in this originally blind patient points out the necessity of considering syphilis in the differential diagnosis of acute visual loss in all patient populations. REFERENCES 1. Updates: Acquired Immunodeficiency Syndrome- United States. MMWR 1986;35:17-21. 2. Sprio TJ. The acquired immunodeficiency syndrome. 01'11thallllic F01'1l111 1985;3:109-12. 3. Khadem M, Kalish SB, Goldsmith L Fetkenhour C, O'Grady RB, Phair JP, Chrobak M. Ophthalmologic findings in acquired immune deficiency syndrome (AIDS). Arch OphthalllloI1984;102:201-6. 4. Freeman WR, Lerner CV, Mines JA, Lash RS, Nadel AI. Starr, MB, Tapper ML. A prospective study of the opthalmologic findings in the acquired immune deficiency syndrome. Alii I Opl1thalllloI1984;97:133-42. 5. Palestine AG, Rodrigues MM, Macher AM, et. al. Ophthalmic involvement in acquired immunodeficiency syndrome. Ophtlwl11l010gl/ 1984;91:1092-9. 6. Gal A, Pollack A, Oliver M. Ocular findings in the acquired immunodeficiency syndrome. Br I OphtlwlnIOI1984;68:23841. 7. Friedman AH. The retinal lesions of the acquired immune deficiency syndrome. Trans Alii Ophtha/lllol Soc 1984; 82:447 -88. 8. Holmes KK. Svphilis. In: Petersdorf RG, Adams RD, Braunwald E, Isselbacher KI. Martin JB, Wilson JD, eds. Harrtsoll's prillci"les of 111 te 1'1111 I Illedicille. New York: McGraw-Hill Book Company, 1983:1035. 9. Zaidman GW. Neurosyphilis and retrobulbar neuritis in a patient with AIDS. AIIII Opilt/wllllo/1986;18:260-1 10. Zaidman GW, Weinberg RS, Humphrey WT. Acquired syphilitiC uveitis in homosexuals. Ophthal11lolog1/ 1983;90 (August suppl):106 11. Arruga I. Valentines I. Mauri F, Roca G, Salom R, Rufi G. Neuroretinitis in acquired syphilis. Opl1t1wllll%glf 1985; 92:262-70. 12. Stokes JH, Beerman H, Ingraham NR. Modem dillical sll/,l1it% SY, diaSllosl5, lI'catnle'lt, case stlidl/. Philadelphia:' WB Saunders Co, 1945:993-4. 13. Bruetsch WL. Sypl1llltic optiC atropl1y. Springfield, IL: Thomas, 1953;65-89; 96, 97. 14. Weinstein JM, Lexow SS, Ho P, Spickards A. Acute syphilitic optic neuritis. Arcl1 Opl1tl1alllloI1981;99:1392-5. 15. Spoor TC, Wynn P, Hartel Wc' Bryan CS. Ocular syphilis acute and chronic. I Clill Nelll'0-ophtitalllloI1983;3:197-203, 16. Markovitz, et al. Failure of recommended treatment for secondary syphilis, lAMA 1986;225:1767-8. 17. Duke-Elder S. Neliro-opl1thalnlOloSl/ (Systelll of o/,ht/wlll/ofoSl/, Vol. XII). London: Henry Kimpton, 1971:173-91. 18. Hart G. Syphilis tests in diagnostic and therapeutic decision making. AIIII III tent Mcd 1986;104:368-76. I Clm NCllro-ol'hlhaimoi. Vol. 7, No. 1. 1987 |
