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Show Journal of Clinical Neuro- ophthalmology 11( 4); 246- 249. 1991. Bilateral Optic Neuritis following Bacille Calmette- Guerin ( BCG) Vaccination May- Yung Yen, M. D. and Jorn- Hon Liu, M. D. © 1991 Raven Press, ltd.. New York A 12- year- old PPD- negative girl developed bilateral optic neuritis with decreasing visual acuity 5 days after bacille Calmette- Guerin ( BCG) vaccination. Laboratory findings and computerized tomography scan of brain and orbit were negative. Cerebrospinal fluid study revealed 62 leukocytes ( 92% lymphocytes) per cubic millimeter and a protein level of 33 mg/ dl. The patient was treated with systemic steroids. The vision returned to normal in 4 weeks and the disc edema resolved in 6 weeks without residual deficit. The complications of BCG are discussed. Key Words: Optic neuritis-- BCG vaccination- Vaccine complications. Address correspondence and reprint requests to Dr. M.- Y. Yen at Department of Ophthalmology, Veterans General Hospital, Taipei, Taiwan, R. O. C. 11217. Presented at Eighth International Neuro- ophthalmology Symposium in Winchester, England, June 23- 29, 1990. From the Department of Ophthalmology. Veterans General Hn< Pit., 1 Y. ln~- Ming t\ l" di.: al Collegl', Taipei, Taiwan. Repub- Optic neuritis has been described as a rare complication with the use of several vaccines, including rabies ( 1), smallpox ( 2), swine flu (~ 5), trivalent measles, mumps and rubella vaccination ( 6), and diphtheria and tetanus toxoid ( 2). Optic neuritis occurs several days to 3 weeks after vaccination. It is associated with severe but temporary decrease in visual acuity, with a good prognosis leading to normal vision and minimal residual disc pallor, or it may cause a more severe complication leading to permanent visual loss ( 4). We recently found a young girl with bilateral optic neuritis following bacille Calmette- Guerin ( BCG) vaccination. We think it is the first case report dealing with BCG vaccination. CASE REPORT A previously healthy 12- year- old girl was admitted on October 17, 1988 with the chief complaint of bilateral marked loss of vision for 4 days. Prior to this episode, she had a completely negative medical and ocular history. Because of a negative PPO skin test, she received a BCG vaccination on October 6, 1988. Five days after the BCG vaccination ( October 11, 1988), she noticed blurred vision in both eyes. Visual acuity worsened subjectively during the ensuing 3 days and by October 13, 1988, she could hardly see objects. She was brought to our clinic and was admitted on October 17, 1988. Neurological examination was normal. Eye examination revealed a best corrected visual acuity of counting fingers at 20 em in each eye. Anterior segments and the extraocular movements were normal. Both optic discs were swollen and hyperemic, with splinter hemorrhages and engorged veins ( Fig. 1). Goldmann visual fields with V4e target revealed a large dense central scotoma in the right eye and temporal island in the left eye. Fluorescein angiography ( Fig. 246 BACILLE CALMETTE- GUERIN OPTIC NEURITIS 247 FIG. 1. Both discs were swollen and hyperemic, with splinter hemorrhages and engorged veins. 2) demonstrated dye leakage at the optic discs and no vascular or macular pathology. The laboratory tests gave the following results: ESR 26 mm/ hr, WBC 12,300/ cumm, NIL = 75/ 23, IgG 1,970 mgldl ( normal range 1,186-- 1,800). Results of remaining tests, including VDRL, LE prep. rheumatoid factor, C- reactive protein, ANA, IgA, IgM, viral serology, and urinalysis, were normal. Chest roentgenograms and computerized tomography scan of brain were normal. A cerebrospinal fluid study revealed normal opening pressure, WBC 62/ cumm, NIL = 5/ 57, protein 33 mgldl, sugar 65 mgldl ( blood sugar 139 mg/ dl). Cultures including tuberculosis were negative for pathogens. A diagnosis of immunologic reaction due to BCG vaccination was suspected. Pulse therapy with Decadron ( 5 mg intravenous drip every 6 hours) was started on October 20, 1988, and discontinued on October 22, 1988, without tapering. Vision improved dramatically. Best corrected vision was OD 20/ 600, OS 20/ 200 on October 21; OD 20/ 200, OS 20/ 100 on October 23; OD 20/ 70, OS 20/ 50 on October 24. The patient was discharged without steroid therapy. Follow- up on November 16 revealed best corrected vision was 20/ 15 in each eye. She could read 15/ 15 for Ishihara color plates. Disc edema resolved and contrast sensitivity function was found to be normal on November 30, 1988. FIG. 2. Fluorescein angiography showed dye leakage at the optic discs and no vascular or macular pathology. , Clin Neuro- ophthalmol. Vol. 11. No. 4. 1991 248 M.- Y. YEN AND f.- H. LIU COMMENTS Bilateral optic neuritis is more commonly seen in children ( 7) and is frequently associated with systemic infections such as measles ( 7/ 8)/ mumps ( 9)/ and chickenpox ( 10/ 11). The pathogenesis by which a viral encephalitis could lead to the development of optic neuritis is not well established. However, a systemic autoimmune mechanism of demyelination somehow initiated by the virus itself seems likely ( 11). Farris and Pickard ( 12) reported six children with bilateral postinfectious optic neuritis. Five of the six patients had a history of upper respiratory or gastrointestinal illness presumably viral in nature. Five of the six patients also demonstrated marked neurologic deficits. All patients responded well to intravenous steroids therapy. Although our patient had abnormal spinal fluid that indicated an aseptic form of meningitis, she did not have prodromal illness or neurological symptoms and signs. The only history was that she received BCG vaccination 5 days prior to her visual impairment. Bacille Calmette- Guerin vaccine was originally isolated by Calmette and Guerin at the Pasteur Institute of Lille through the progressive attenuation of a virulent strain of Mycobacterium bovis. It has been used in the prevention of tuberculosis and as an immunological adjuvant in the treatment of various malignancies. The procedure has generally been regarded as safe. Complications have been reported to be uncommon. Osteomyelitis ( 13/ 14) due to BCG was reported during the 1970s with a frequency as high as 5/ 100/ 000. The mean incubation period was 18.5 months. The epiphyses of the long bone of the extremities were the most frequent sites of the infection. The frequency declined from 1978 to 1981 when a different BCG product was used. Local ulceration and regional suppurative lymphadenitis ( 13) were reported with a frequency of 0.1 to 5 per 1/ 000 infants and children under 1 year of age in many countries. Regional lymphadenitis is a delayed onset complication ( 15/ 16). The onset varied from 3 to 8 months after vaccination, averaging 6 months. Fourteen deaths ( 17) due to BCG vaccination have been reported. Granulomatous hepatitis ( 18)/ granulomatous lymphangitis ( 19)/ erythema multiforme ( 20)/ interstitial pneumonia ( 21)/ and absce. ss formation ( 22) have been reported as complications of BCG as an immunological adjuvant in the treatment of various malignancies. -. .1. ", r '~" mplication after BCG vac- I Clin Neuro- aphthalmol. Vol. 11. .',,,. _; cination is probably multifactorial and related to the dose and potency of the vaccine and depth of the injection. It has been suggested that highpotency vaccine was the cause of the problem, but inadequate mixing of the freeze- dried vaccine may also be a factor ( 23). This would lead to some patients receiving a higher dose than others. Decreased host resistance has been reported as a cause of BCG dissemination following vaccination with BCG ( 24). Our patient developed bilateral optic neuritis following BCG vaccination. The time course of 5 days between injection and onset of complication is appropriate for allergic reaction to injected foreign protein. Steroid therapy was effective in this patient, as evidenced by a rapid improvement in vision and in the appearance of the optic disc. Awareness of this relationship will alert us to the diagnostic possibility and its future documentation. REFERENCES 1. Cormack HS. Anderson LAP. Bilateral papillitis following antirabic- inoculation: recovery. Br J Ophthalmol 1934; 18: 167- 9. 2. McReynolds WU, Havener WH, Petrohelos MA. Bilateral optic neuritis following small- pox vaccination and diphtheria tetanus toxoid. Am J Dis Child 1953; 86: 601- 4. 3. Perry D, Mallen FJ, Grodin RW, Cossari AJ. Reversible blindness in optic neuritis associated with influenza vaccination. Ann OphthalmoI1979; 11: 545- 50. 4. Cangemi FE, Bergen RL. Optic atrophy following swine flu vaccination. Ann OphthalmoI1980; 12: 857-- 63. 5. Bienfang DC, Kantrowitz FG, Nobel JL, Raynor AM. Ocular abnormalities after influenza immunization. Arch OphthalmoI1977; 95: 1649. 6. Kazarain EL, Gager WE. Optic neuritis complicating measles, mumps, and rubella vaccination. Am J Ophthalmol 1978; 86: 544- 7. 7. Kennedy C. Carroll FD. Optic neuritis in children. Arch OphthalmoI1960; 63: 747- 55. 8. Strom T. Acute blindness as post- measles complication. Acta Paediatr 1953; 42: 60-- 5. 9. Riffenburgh RS. Ocular manifestations of mumps. Arch OphthalmoI1961; 66: 739- 43. 10. Miller DH, Kay R. Schon F. Optic neuritis following chickenpox in adults. JNeuroI1986; 233: 182- 4. 11. Selbst RG, Selhorst JB, Harison JW, Myer Ee. Parainfectious optic neuritis: report and review following varicella. Arch NeuroI1983; 40: 347- SO. 12. Farris BK, Pickard DJ. Bilateral postinfectious optic neuritis and Intravenous steroid therapy in children. Ophthalmology 1990; 97: 339- 45. 13. Eickhoff Te. Bacille Calmette- Guerin ( BCG) vaccine. In Plotkin SA and Mortimor EA Jr. ( ed). Vaccines. WB Saunders, Philadelphia, 1988: 372~ 6. 14. Bottiger M, Romanus V, de Verdier C/ Boman G. Osteitis and other complications caused by generalized BCG- itis. Acta Paediatr Scand 1982; 71: 471~. 15. Tam PK, Stroebel AB, Saing H, Lau JT, Ong GB. Caseating reglonallymphadenitis complicating BCG vaccination: a report of 6 cases. Arch Dis Child 1982; 57: 952- 4. 16. Ea~ ton PA, Hershfield ES. Lymphadenitis as a late complication of BCG vaccination. Tubercle 1984; 65: 20~. BACILLE CALMETTE- GUERIN OPTIC NEURITIS 249 17. Mande R. Cases of fatal generalized BCG disease. In Mande R ( ed). BCG vaccination. Dawsons, London, 1968. 18. Flippin T, Mukherji B, Dayal Y. Granulomatous hepatitis as a late complication of BCG immunotherapy. Cancer 1980; 46: 1759~ 2. 19. Kirkwood JM, Ariyan S, Nordlund 11, Forget BM. Granulomatous lymphangitis. Cancer 1982; 50: 1299- 303. 20. Tschen EH, Jessen RT, Robertson G, Becker LE. Erythema multifonne as a complication of BCG scarification technique. Arch DermatoI1979; 1l5: 614-- 5. 21. Israel- Biel D, Venet A, Sandron D, Ziza JM, Chretien J. Pulmonary complications of intravesical bacille CalmetteGuerin immunotherapy. Am Rev Respir Dis 1987; 135: 763. 22. Felix EL, Jessup JM, Cohen MH. Severe complications of intralesional BCG therapy in an unsensitized patient. Arch Surg 1978; 113: 89~. 23. Close GC, Gmar M. Caseating regional lymphadenitis complicating BCG vaccination. Arch Dis Child 1983; 58: 939- 40. 24. Blattner RJ. Generalized BCG infection. J Pediatr 1964; 65: 311- 4. 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