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Primary Vaccinia of the Eyelids*
AMERICAN JOURNAL OF VOLUME 34
OPHTHALMOLOGY
MARCH, 1951
NUMBER 3
PRIMARY VACCINIA O F T H E EYELIDS* TREATMENT BY AUREOMYCIN J. HARRY KING, JR., M.D.,
AND WILLIAM A. ROBIE,
M.D.
Honolulu, Hazvaii
Accidental vaccination of the eye is very uncommon considering the great number of vaccinations which are performed daily. Ap proximately 200 cases have been reported in the past 50 years. 1 There are, no doubt, many cases which have been unreported or unrecognized. Ocular involvement may concern the eye lids, the conjunctiva, or the cornea. This is usually caused by contamination from a pri mary vaccinia in the same patient or another person. The skin of the lids and the conjunc tiva are the most common sites for these le sions and the cornea becomes involved in about one third of those affected.1 The result ing scarring of the lids and conjunctiva may necessitate plastic repair. Corneal involve ment frequently results in visual damage and may mean total loss of the globe. Some authors 2 feel that the lid scarring is much less severe than that which follows the usual vaccination of the arm or leg. This may be due to the fact that there is less virus present on the lids and mat the lesion is kept moist by the tears which may have same anti viral effect. In cases of contamination from the same patient some immunity may also be present from the original vaccination. It is extremely important to prevent cor neal involvement when the lids or conjunc tiva became infected. Treatment in the past has been mostly symptomatic. Atkinson and Scullard,3 however, investigated various * From Tripler General Hospital.
therapeutic measures aimed specifically against the vaccinia virus. They suggested methods of treatment which appeared to be of value experimentally in preventing corneal involvement. They had no opportunity to apply these measures to the human being. They advised: (1) The avoidance of trauma which might possibly cause corneal inoculation, especially exercising great care in opening the swollen lids. (2) The use of cuffs for young children to keep them from touching the lids with the fingers. (3) The application of potassium permanganate ( 1 : 100,000), tincture of iodine, metaphen, or mercury bichloride (1:10,000) directly to the lesion as soon as the condition is diag nosed. (4) The administration of ascorbic acid, both locally and systemically, because of its oxidizing properties. (5) Immune serum against the virus vaccinia, given by injection to increase general immunity, and applied lo cally to inactivate the virus. They found that sulfanilamide and sulfapyridine did not inhibit the action of the virus. Some encouragement in the treatment of certain virus infections has recently been given by use of aureomycin. Marked viricidal effect has been noted experimentally and clin ically against the psittacosis-lymphogranuloma venereum group of organisms.* The virus of primary atypical pneumonia,"' 6 den dritic conjunctivitis due to herpes simplex virus,7 and inclusion conjunctivitis7 all have responded to aureomycin therapy. This potent antiviral action suggests a 339
340
J. HARRY KING, JR., AND WILLIAM A. ROBIE
similar effectiveness agajnst the vaccinia virus, whose elementary bodies resemble those of lymphogranuloma venereum. In a recent case of massive multiple pri mary vaccinia of the eyelids, the use of aureomycin, together with the measures al ready mentioned, was followed by dramatic subsidence of the lesions. REPORT OF THE CASE
Vaccinia of the lids in this patient was considered a primary inoculation, either transferred from the original site which did not "take" or from the brother who had a primary reaction. History. A boy, aged two years, was seen in the eye clinic on August 25, 1949, with a history of having had a red "pimple" on the outer portion of the lower lid five days be fore. The mother stated that this became a yellow "blister" in several days, and was followed by multiple similar lid lesions the day prior to coming to the eye clinic. Two weeks before the appearance of the first lid lesion the child had been vaccinated on the left upper arm with no reaction. A brother was vaccinated at the same time and received a primary vaccinia reaction. Examination showed marked inflammation and edema of the lids of the right eye, with numerous vesicles and early pustules of both lid margins. The lesions were discrete, mostly pustular and umbilicated, varying in diam eter from three to six mm. They covered both lid margins from the inner to the outer canthus (fig. 1). Marked induration of the lids and con junctiva was present but no lesions involved the conjunctiva or cornea. The eye could not be opened voluntarily and it was difficult to open it manually. There was tenderness and swelling of the preauricular and submaxillary glands on the same side. No other skin lesions were noted on the body and there were no constitutional symptoms. A smear and culture of mucoid material from the conjunctiva revealed no specific or
ganisms. Smears and cultures from a large lid pustule likewise were negative for bac teria. The material from the pustule produced a classical vaccinia when it was inoculated upon a rabbit's thigh on two occasions. A small reddish papule followed inoculation on the rabbit on the third day which then progressed to an umbilicated vesicle and a yellowish pus tule. This was finally followed by crusting. Material from several lesions was frozen for preservation and later was implanted upon fertile egg yolk as a culture medium. These cultures died in the first 24 hours, however, and it was therefore impossible to demonstrate typical vaccinia growth and Guarnieri bodies upon microscopic examina tion. Treatment was begun immediately to pre vent spread to the cornea, and consisted of: 1. Mild restraint of hands. The patient was an exceptionally cooperative two-yearold child who required restraining only dur-' ing his sleeping hours. 2. Aureomycin per mouth (50 mg./Kg./ 24 hr.) for 96 hours (250 mg. every eight hours). 3. Aureomycin borate eye drops (5.0 mg./ cc.) by flushing the conjunctival sac and lid lesions four times daily for seven days. 4. Penicillin (aqueous) 100,000 units in tramuscularly, twice daily, for five days. 5. Potassium permanganate (1:100,000) solution made fresh daily, wet compresses for one-half hour, four times daily. 6. Ascorbic acid (50 mg., twice daily) by mouth. Course. Striking improvement was noted in 24 hours. The edema began to subside and the lid lesions, although moist, were station ary in character. The lids could be manually opened with less force, and the conjunctiva and cornea were uninfected. In 72 hours, there was almost complete subsidence of the condition. Edema was very slight, and the pustules were desiccated in appearance. Four days after treatment was
PRIMARY VACCINIA OF THE EYELIDS
begun, the ulcers had completely healed and depressed scars remained on both lids (fig. 2). There was loss of lashes in the middle third of the upper lid where the largest lesion had been and on two small areas of the lower lid. No permanent sequelae other than mild scarring was noted after two weeks. COMMENT
Certain observations might lead one to sus pect the correctness of the diagnosis in this case. The rapid abatement of the lid lesions was most unusual. The lack of a primary take on the arm and the late appearance of the lid lesions two weeks after the vaccina tion were not characteristic. A small primary take on the lid may have been present prior to this time, however, as the mother was not too certain about the date of its origin. At the time the patient was first seen her*e the lesions resembled those of a third to fourth day vaccinia. It is probable that the child became infected from contami nation by the brother's vaccinia. The appearance of the discrete, elevated, pustular lesions which later became umbilicated, was identical with that seen in vac cinia.8 The inoculation of this material upon a rabbit's thigh, causing the production of typical vaccinia, was confirmatory of the causative agent. Complement fixation and agglutination tests were not done due to the unavailability of the necessary antivaccinial serum.
341
SUMMARY AND CONCLUSIONS
A case of multiple vaccinia of the eyelids in a two-year-old boy, without a primary take elsewhere, is reported. In addition to methods of treatment previously advocated by others,3 aureomycin locally and parenterally was em ployed. The lesions abated in 72 hours and there was complete disappearance of the con dition in four days. This is a dramatic re covery compared to the usual 28- to 31-day course of untreated vaccinia.8 It is impossible to state definitely that aureomycin was the cause of the rapid sub sidence of this condition in view of the fact that other methods of treatment were used. Penicillin is not generally considered to possess potent antiviral action. It was used in this case as a precaution against secondary bacterial infection. The known value of aureomycin as a viricidal agent, however, lends credence to the assumption that it was effective against vaccinia. The use of aureomycin parenterally and locally appears to be a promising therapeutic measure in ocular vaccinia as a means of pre venting damaging sequelae which may even cause loss of vision. It is hoped that this re port will stimulate further investigation in order to determine the therapeutic effect of this antibiotic in ocular and other vaccinial complications. APO 438, c/o Postmaster, San Francisco.
REFERENCES
1. Atkinson, W. S., and Scullard, G. Vaccinia with ocular involvement. Arch. Ophth., 23:584-585, 1940. 2. : Arch. Ophth., 23:587, 1940. 3. : Arch. Ophth., 23 :590, 1940. 4. Morgan, H. J.: Medicine of the Year. Philadelphia, Lippincott, 1949, p. 5. 5. Schoenbach, E. B., and Bryer, M. S.: J.A.M.A., 139 :275, 1949. 6. Kneeland, Y., Rose, H. M., and Gibson, C. D.: Am. J. Med., 6:41, 1949. 7. Braley, A. E., and Sanders, M.: Aureomycin in ocular infections. A preliminary report J.A.M.A., 138:426-427,1948. 8. Stimson, P. M.: Common Contagious Diseases. Philadelphia, Lea, 1940, p. 287.
OPHTHALMOLOGY
MARCH, 1951
NUMBER 3
PRIMARY VACCINIA O F T H E EYELIDS* TREATMENT BY AUREOMYCIN J. HARRY KING, JR., M.D.,
AND WILLIAM A. ROBIE,
M.D.
Honolulu, Hazvaii
Accidental vaccination of the eye is very uncommon considering the great number of vaccinations which are performed daily. Ap proximately 200 cases have been reported in the past 50 years. 1 There are, no doubt, many cases which have been unreported or unrecognized. Ocular involvement may concern the eye lids, the conjunctiva, or the cornea. This is usually caused by contamination from a pri mary vaccinia in the same patient or another person. The skin of the lids and the conjunc tiva are the most common sites for these le sions and the cornea becomes involved in about one third of those affected.1 The result ing scarring of the lids and conjunctiva may necessitate plastic repair. Corneal involve ment frequently results in visual damage and may mean total loss of the globe. Some authors 2 feel that the lid scarring is much less severe than that which follows the usual vaccination of the arm or leg. This may be due to the fact that there is less virus present on the lids and mat the lesion is kept moist by the tears which may have same anti viral effect. In cases of contamination from the same patient some immunity may also be present from the original vaccination. It is extremely important to prevent cor neal involvement when the lids or conjunc tiva became infected. Treatment in the past has been mostly symptomatic. Atkinson and Scullard,3 however, investigated various * From Tripler General Hospital.
therapeutic measures aimed specifically against the vaccinia virus. They suggested methods of treatment which appeared to be of value experimentally in preventing corneal involvement. They had no opportunity to apply these measures to the human being. They advised: (1) The avoidance of trauma which might possibly cause corneal inoculation, especially exercising great care in opening the swollen lids. (2) The use of cuffs for young children to keep them from touching the lids with the fingers. (3) The application of potassium permanganate ( 1 : 100,000), tincture of iodine, metaphen, or mercury bichloride (1:10,000) directly to the lesion as soon as the condition is diag nosed. (4) The administration of ascorbic acid, both locally and systemically, because of its oxidizing properties. (5) Immune serum against the virus vaccinia, given by injection to increase general immunity, and applied lo cally to inactivate the virus. They found that sulfanilamide and sulfapyridine did not inhibit the action of the virus. Some encouragement in the treatment of certain virus infections has recently been given by use of aureomycin. Marked viricidal effect has been noted experimentally and clin ically against the psittacosis-lymphogranuloma venereum group of organisms.* The virus of primary atypical pneumonia,"' 6 den dritic conjunctivitis due to herpes simplex virus,7 and inclusion conjunctivitis7 all have responded to aureomycin therapy. This potent antiviral action suggests a 339
340
J. HARRY KING, JR., AND WILLIAM A. ROBIE
similar effectiveness agajnst the vaccinia virus, whose elementary bodies resemble those of lymphogranuloma venereum. In a recent case of massive multiple pri mary vaccinia of the eyelids, the use of aureomycin, together with the measures al ready mentioned, was followed by dramatic subsidence of the lesions. REPORT OF THE CASE
Vaccinia of the lids in this patient was considered a primary inoculation, either transferred from the original site which did not "take" or from the brother who had a primary reaction. History. A boy, aged two years, was seen in the eye clinic on August 25, 1949, with a history of having had a red "pimple" on the outer portion of the lower lid five days be fore. The mother stated that this became a yellow "blister" in several days, and was followed by multiple similar lid lesions the day prior to coming to the eye clinic. Two weeks before the appearance of the first lid lesion the child had been vaccinated on the left upper arm with no reaction. A brother was vaccinated at the same time and received a primary vaccinia reaction. Examination showed marked inflammation and edema of the lids of the right eye, with numerous vesicles and early pustules of both lid margins. The lesions were discrete, mostly pustular and umbilicated, varying in diam eter from three to six mm. They covered both lid margins from the inner to the outer canthus (fig. 1). Marked induration of the lids and con junctiva was present but no lesions involved the conjunctiva or cornea. The eye could not be opened voluntarily and it was difficult to open it manually. There was tenderness and swelling of the preauricular and submaxillary glands on the same side. No other skin lesions were noted on the body and there were no constitutional symptoms. A smear and culture of mucoid material from the conjunctiva revealed no specific or
ganisms. Smears and cultures from a large lid pustule likewise were negative for bac teria. The material from the pustule produced a classical vaccinia when it was inoculated upon a rabbit's thigh on two occasions. A small reddish papule followed inoculation on the rabbit on the third day which then progressed to an umbilicated vesicle and a yellowish pus tule. This was finally followed by crusting. Material from several lesions was frozen for preservation and later was implanted upon fertile egg yolk as a culture medium. These cultures died in the first 24 hours, however, and it was therefore impossible to demonstrate typical vaccinia growth and Guarnieri bodies upon microscopic examina tion. Treatment was begun immediately to pre vent spread to the cornea, and consisted of: 1. Mild restraint of hands. The patient was an exceptionally cooperative two-yearold child who required restraining only dur-' ing his sleeping hours. 2. Aureomycin per mouth (50 mg./Kg./ 24 hr.) for 96 hours (250 mg. every eight hours). 3. Aureomycin borate eye drops (5.0 mg./ cc.) by flushing the conjunctival sac and lid lesions four times daily for seven days. 4. Penicillin (aqueous) 100,000 units in tramuscularly, twice daily, for five days. 5. Potassium permanganate (1:100,000) solution made fresh daily, wet compresses for one-half hour, four times daily. 6. Ascorbic acid (50 mg., twice daily) by mouth. Course. Striking improvement was noted in 24 hours. The edema began to subside and the lid lesions, although moist, were station ary in character. The lids could be manually opened with less force, and the conjunctiva and cornea were uninfected. In 72 hours, there was almost complete subsidence of the condition. Edema was very slight, and the pustules were desiccated in appearance. Four days after treatment was
PRIMARY VACCINIA OF THE EYELIDS
begun, the ulcers had completely healed and depressed scars remained on both lids (fig. 2). There was loss of lashes in the middle third of the upper lid where the largest lesion had been and on two small areas of the lower lid. No permanent sequelae other than mild scarring was noted after two weeks. COMMENT
Certain observations might lead one to sus pect the correctness of the diagnosis in this case. The rapid abatement of the lid lesions was most unusual. The lack of a primary take on the arm and the late appearance of the lid lesions two weeks after the vaccina tion were not characteristic. A small primary take on the lid may have been present prior to this time, however, as the mother was not too certain about the date of its origin. At the time the patient was first seen her*e the lesions resembled those of a third to fourth day vaccinia. It is probable that the child became infected from contami nation by the brother's vaccinia. The appearance of the discrete, elevated, pustular lesions which later became umbilicated, was identical with that seen in vac cinia.8 The inoculation of this material upon a rabbit's thigh, causing the production of typical vaccinia, was confirmatory of the causative agent. Complement fixation and agglutination tests were not done due to the unavailability of the necessary antivaccinial serum.
341
SUMMARY AND CONCLUSIONS
A case of multiple vaccinia of the eyelids in a two-year-old boy, without a primary take elsewhere, is reported. In addition to methods of treatment previously advocated by others,3 aureomycin locally and parenterally was em ployed. The lesions abated in 72 hours and there was complete disappearance of the con dition in four days. This is a dramatic re covery compared to the usual 28- to 31-day course of untreated vaccinia.8 It is impossible to state definitely that aureomycin was the cause of the rapid sub sidence of this condition in view of the fact that other methods of treatment were used. Penicillin is not generally considered to possess potent antiviral action. It was used in this case as a precaution against secondary bacterial infection. The known value of aureomycin as a viricidal agent, however, lends credence to the assumption that it was effective against vaccinia. The use of aureomycin parenterally and locally appears to be a promising therapeutic measure in ocular vaccinia as a means of pre venting damaging sequelae which may even cause loss of vision. It is hoped that this re port will stimulate further investigation in order to determine the therapeutic effect of this antibiotic in ocular and other vaccinial complications. APO 438, c/o Postmaster, San Francisco.
REFERENCES
1. Atkinson, W. S., and Scullard, G. Vaccinia with ocular involvement. Arch. Ophth., 23:584-585, 1940. 2. : Arch. Ophth., 23:587, 1940. 3. : Arch. Ophth., 23 :590, 1940. 4. Morgan, H. J.: Medicine of the Year. Philadelphia, Lippincott, 1949, p. 5. 5. Schoenbach, E. B., and Bryer, M. S.: J.A.M.A., 139 :275, 1949. 6. Kneeland, Y., Rose, H. M., and Gibson, C. D.: Am. J. Med., 6:41, 1949. 7. Braley, A. E., and Sanders, M.: Aureomycin in ocular infections. A preliminary report J.A.M.A., 138:426-427,1948. 8. Stimson, P. M.: Common Contagious Diseases. Philadelphia, Lea, 1940, p. 287.