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Ocular Infection with Orf Virus
OCULAR INFECTION WITH ORF VIRUS G. FREEMAN, M.D., A. J. BRON, F.R.C.S., AND B. JUEL-JENSEN, D.M., F.R.C.P. Oxford, England
Orf virus infection of the pericanthal eyelid skin and conjunctiva was diagnosed by electron microscopy. Orf is a paravaccinia virus responsible for contagious pustular dermatitis in sheep and goats. It occasionally affects humans. The patient was a farmwife who had recently handled lambs. She had a raised ulcerating lesion at the inner canthus, follicular conjunctivitis, and lymphadenopathy. Treatment with 35% idoxuridine in dimethylsulfoxide on the skin and 0.5% idoxuridine ointment on the conjunctiva led to resolution after three weeks. Orf virus is a member of the paravaccinia group of DNA viruses (Fig. 1) which causes a contagious pustular dermatitis in sheep and goats and probably in reindeer and musk ox.! In these animals there are ulcerative pustular lesions in the epidermal cells of the skin and mucous membranes, principally in young animals. It is a common disorder in sheep, and is found in farming communities. Lesions of the hands are common (Fig. 2) but ocular infection and involvement of other sites on the face are unusual.
CASE REPORT The patient, a 38-year-old fannwife, developed a painless red swelling medial to the inner canthus in mid-April 1982. This was treated by her general practitioner with ampicillin trihydrate orally and chloramphenicol drops to both eyes. The erythematous area continued to enlarge and the central aspect became ulcerated and crusted over. The right side of her face had been swollen for two days after the start of penicillin therapy. The eyelids were puffy and sticky in the mornings and there was a watery discharge. When she was examined on April 27,
Accepted for publication Feb. 9, 1984. From the Department of Ophthalmology (Drs. Freeman and Bron), and the Nuffield Department of Clinical Medicine (Dr. Juel-Jensen), University of Oxford, Oxford, England. Reprint requests toA. J. Bron, F.R.C.S., University of Oxford, Nuffield Laboratory of Ophthalmology, Walton St., Oxford 0X2 6AW, England.
1982, there was an ulcerated, crusted area approximately 8 mm across at the base of the nose, close to the medial canthus (Fig. 3). The lesion was relatively nontender. The punctum was normal, there was no discharge on sac pressure, and the conjunctiva was injected. The patient's visual acuity was R.E.: 20/20 and L.E.: 20115 without correction. The right preauricular and submandibular lymph nodes were enlarged. It was established that the patient had recently had direct contact with newborn lambs at a neighboring farm. An anerobic bacterial infection was suspected. Cultures were taken from the base of the skin lesion and inoculated onto blood and chocolate agar and Robertson's meat medium. These grew only commensal organisms. The provisional diagnosis was orf. This was based on the resemblance of the facial lesion to orf lesions found more often on other parts of the body. The diagnosis was confirmed by electron microscopy of scrapings of the skin lesions. Paired herpes simplex virus and varicella roster virus titers showed no rise. The patient was hospitalized and kept in isolation. Idoxuridine 35% in dimethylsulfoxide was applied to the skin lesions every two hours and idoxuridine 0.5% ointment was applied five times daily to the right eye. When the patient was examined on April 3D, the facial swelling had regressed but the right preauricular lymph node was still swollen. The medial canthal lesion had become nodular and had an ulcerated center although crusting was no longer present. The lesion was 6.25 mm high and 5 mm wide at this time. The medial aspects of both eyelids were swollen, more so than central and lateral areas. There was also a hyperemic swelling on the plica semilunaris measuring 4 x 2 mm. The caruncle was hyperemic and there was florid follicular conjunctivitis with a marked papillary response and some follicles on the upper tarsal conjunctiva. The right cornea was clear. Fluorescein dye showed a limbal inflammation in the form of oval, nonstaining elevations concentric with the corneosclerallimbus and causing thinning of the overlying tear film (Fig. 4). The pupillary reaction
©AMERICAN JOURNAL OF OPHTHALMOLOGY 97:601--004, 1984
601
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AMERICAN JOURNAL OF OPHTHALMOLOGY
MAY, 1984
Fig. 1 (Freeman, Bron, and Juel-Jensen). Orfvirus from a human source (x 100,(00). was normal, as were the ophthalmoscopic findings. The left eye was unremarkable except for mild follicular changes in the lower eyelid conjunctiva, accompanied by distinct grade 1 papillary changes in the upper tarsal conjunctiva. As antiviral therapy had been initiated, no further smears were taken. When the patient was examined again on May 5, the lesion medial to the canthus had regressed remarkably. The preauricular lymph node was still palpable and non tender. The Iimbal inflammation had cleared, although there was still mild follicular change inferiorly with papillary changes on the superior tarsal conjunctiva. The bulbar conjunctival nodule was no longer present. The administration of idoxuridine ointment was decreased to three times daily. On May 20, the skin lesion could no longer be detected. The papillary changes on the superior conjunctiva remained, but the inferior follicles had been replaced by diffuse papillae. Treatment with idoxuridine was discontinued. At a final examination on July 22, all the lesions had healed.
nostrils, eyes, and, occasionally, udders. These lesions progress through the vesicular and pustular stages to become ulcerated and crusted over in three to four weeks." Recovery is usually uneventful. Recently a live virus vaccine has been used to immunize lambs and kids.! The
DISCUSSION
Orf, also known as contagious ecthyma of sheep or contagious pustular dermatitis, is a disease that most often affects sheep. It produces papules around the mucous membranes, particularly the lips,
Fig. 2 (Freeman, Bron, and Juel-Jensen). Typical orf lesions on the hand.
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Fig. 3 (Freeman, Bron, and [tiel-jensen). Left, Orf lesion at the medial canthus at the first examination. Right, Healed lesions ten days later.
same virus may he responsible for bovine papular stomatitis in cattle." Human infection usually occurs only in people whose occupations bring them into close contact with live stock. Thus, veterinarians, sheep ranchers, farmers, and occasionally laboratory workers! are at risk. The virus is usually acquired by direct inoculation but can be transferred from pastures and on clothing." As the virus is heat-resistant, it can be propagated years later from dried crusts of saliva. The diagnosis can be made by electron microscopic examination of scrapings from lesions or by a complement-fixation test." Human-to-human transmission, although it has been reported, is unusual." In humans, the incubation time is three to seven days; then, a maculopapular lesion erupts at the site of infection, usually the arm or hand. Often only one lesion is present, although multiple inoculations do occur. This progresses to a raised red nodule with an ulcerated summit. If it is mistaken for a pustule and incised, no purulent material is found. The nodule progresses rapidly to a papillomatous stage in four to six weeks and finally regresses without scarring in six to eight weeks." Pain and inflammation are usually slight. Occasionally systemic involvement in the form of lymphangitis, lymphadenopathy, erythema multiforme, and secondary bacterial infection occurs.
A survey of human orf infection between 1975 and 1981 reported 344 cases involving skin lesions." Of these, 142 were related to contact with sheep, 36 with cows or calves, and two with goats. Infections of the face or ear were reported in nine cases. Although blindness has been reported in human orf infection, possibly from secondary bacterial disease.! ocular involvement appears to be rare. Our patient had been helping with new lambs before her infection. Interestingly, the canthal and conjunctival lesions were the only ones to develop, and although it is possible that her finger contacted the virus first and then spread it to the ocular region, it is also possible that infection occurred directly while she was carrying a lamb.
Fig. 4 (Freeman, Bron, and Juel-Jensen). Follicular limbal inflammation demonstrated with fluorescein (arrows).
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AMERICAN JOURNAL OF OPHTHALMOLOGY
In previous cases 6,8-13 treatment has consisted either of waiting for the lesions to regress spontaneously or excision. Antibacterial antimicrobials are of no use except in cases of proven secondary bacterial infection. In our patient, treatment with idoxuridine resulted in prompt resolution of both conjunctival and skin lesions. The limbal inflammation and skin nodule had completely regressed 21 days after treatment began. Vaccinia virus is a member of the Poxviridae family and belongs to the same subfamily, chordopoxvirinae as orf but to a different genus (Orthopoxvirus in the case of vaccinia and Parapoxoirus in the case' of orf.2 Idoxuridine is effective in the treatment of vaccinial lesions of the eye and skin in human and rabbit infections'v" and has been used previously in the treatment of orf. ACK."IOWLEDGMENT
T. Lee, of the Department of Virology, John Radcliffe Hospital, Oxford, provided Figure 1. REFERENCES 1. Falk, E.: Parapoxvirus infections of reindeer and musk ox associated with unusual human infections. Br. J. Dermatol. 99:647, 1978. 2. Naano, J. H.: Comparative Diagnosis of Viral Diseases. New York, Academic Press, New York, 1977, vol. 1, pp. 299 and 300.
MAY, 1984
3. Andrews, c.. Pereira, H. C., and Wilde, P.: Viruses of Vertebrates. London, Balliere Tindall, 1978, p. 369. 4. PHLS Communicable Disease Surveillance Centre and Communicable Diseases (Scotland) Unit: Orf paravaccinia infections, British Isles, 1875-81. Epidemiological report. Br. Med. J. 284:1958, 1982. 5. Moore, R. ~l.: Human orf in the United States, 1972. J. Infect. Dis. 127:731, 1973. 6. Dalton, A. J.: Orf. A report of 19 human cases and clinical and pathological observations. J.A.M.A. 204:657, 1968. 7. Johannessen, J. V., Krogh, H. K., Solberg, 1., Dalen, A., van Wyngaarden, H., and Johansen, B.: Human orf. J. Cutan. Pathol. 2:265, 1975. 8. Wilkinson, J. D.: Orf. A family with unusual complications. Br. J. Dermatol. 97:447, 1977. 9. joensen, H. D., and Block, D.: Human ecthyma contagiosum (orf) in the Faroe Islands. Acta Pathol. Microbiol. Scand. 82:3ll, 1974. 10. Hodgson-lones, J. S.: Orf in London. Br. Med. J. 1:79, 1951. II. Hall, M.: Orf in Britain, letter. Br. Med. J. 2:420, 1976. 12. Sweeney, E. C., and Woolfson, M.: Human ecthyma contagiosum (orf). Irish J. Med. Sci. I:ll2, 1978. 13. Steijman, A. J.: Viral diseases. In Craernes: Principles and Practice of Clinical Pharmacology and Therapeutics. London, Churchill-Livingstone, 1980, pp. ll52 and ll53. 14. Kaufman, H. E., Nesbum, A. B., and Maloney, E. D.: Cure of vaccinia infection by 5 iodo-2'deoxyuridine. Virology 18:567, 1962. 15. Calabresi, P., McCollum, R. W., and Welsh, A. D.: Suppression of infections resulting from a deoxyribonucleic acid virus (vaccinia) by systemic administration of 5-iodo-2'-deoxyuridine. Nature 1971:767, 1963. 16. [uel-jensen, B. E.: The chemotherapy of viral disease. Br. J. Hosp. Med. 10:402, 1973.
Orf virus infection of the pericanthal eyelid skin and conjunctiva was diagnosed by electron microscopy. Orf is a paravaccinia virus responsible for contagious pustular dermatitis in sheep and goats. It occasionally affects humans. The patient was a farmwife who had recently handled lambs. She had a raised ulcerating lesion at the inner canthus, follicular conjunctivitis, and lymphadenopathy. Treatment with 35% idoxuridine in dimethylsulfoxide on the skin and 0.5% idoxuridine ointment on the conjunctiva led to resolution after three weeks. Orf virus is a member of the paravaccinia group of DNA viruses (Fig. 1) which causes a contagious pustular dermatitis in sheep and goats and probably in reindeer and musk ox.! In these animals there are ulcerative pustular lesions in the epidermal cells of the skin and mucous membranes, principally in young animals. It is a common disorder in sheep, and is found in farming communities. Lesions of the hands are common (Fig. 2) but ocular infection and involvement of other sites on the face are unusual.
CASE REPORT The patient, a 38-year-old fannwife, developed a painless red swelling medial to the inner canthus in mid-April 1982. This was treated by her general practitioner with ampicillin trihydrate orally and chloramphenicol drops to both eyes. The erythematous area continued to enlarge and the central aspect became ulcerated and crusted over. The right side of her face had been swollen for two days after the start of penicillin therapy. The eyelids were puffy and sticky in the mornings and there was a watery discharge. When she was examined on April 27,
Accepted for publication Feb. 9, 1984. From the Department of Ophthalmology (Drs. Freeman and Bron), and the Nuffield Department of Clinical Medicine (Dr. Juel-Jensen), University of Oxford, Oxford, England. Reprint requests toA. J. Bron, F.R.C.S., University of Oxford, Nuffield Laboratory of Ophthalmology, Walton St., Oxford 0X2 6AW, England.
1982, there was an ulcerated, crusted area approximately 8 mm across at the base of the nose, close to the medial canthus (Fig. 3). The lesion was relatively nontender. The punctum was normal, there was no discharge on sac pressure, and the conjunctiva was injected. The patient's visual acuity was R.E.: 20/20 and L.E.: 20115 without correction. The right preauricular and submandibular lymph nodes were enlarged. It was established that the patient had recently had direct contact with newborn lambs at a neighboring farm. An anerobic bacterial infection was suspected. Cultures were taken from the base of the skin lesion and inoculated onto blood and chocolate agar and Robertson's meat medium. These grew only commensal organisms. The provisional diagnosis was orf. This was based on the resemblance of the facial lesion to orf lesions found more often on other parts of the body. The diagnosis was confirmed by electron microscopy of scrapings of the skin lesions. Paired herpes simplex virus and varicella roster virus titers showed no rise. The patient was hospitalized and kept in isolation. Idoxuridine 35% in dimethylsulfoxide was applied to the skin lesions every two hours and idoxuridine 0.5% ointment was applied five times daily to the right eye. When the patient was examined on April 3D, the facial swelling had regressed but the right preauricular lymph node was still swollen. The medial canthal lesion had become nodular and had an ulcerated center although crusting was no longer present. The lesion was 6.25 mm high and 5 mm wide at this time. The medial aspects of both eyelids were swollen, more so than central and lateral areas. There was also a hyperemic swelling on the plica semilunaris measuring 4 x 2 mm. The caruncle was hyperemic and there was florid follicular conjunctivitis with a marked papillary response and some follicles on the upper tarsal conjunctiva. The right cornea was clear. Fluorescein dye showed a limbal inflammation in the form of oval, nonstaining elevations concentric with the corneosclerallimbus and causing thinning of the overlying tear film (Fig. 4). The pupillary reaction
©AMERICAN JOURNAL OF OPHTHALMOLOGY 97:601--004, 1984
601
602
AMERICAN JOURNAL OF OPHTHALMOLOGY
MAY, 1984
Fig. 1 (Freeman, Bron, and Juel-Jensen). Orfvirus from a human source (x 100,(00). was normal, as were the ophthalmoscopic findings. The left eye was unremarkable except for mild follicular changes in the lower eyelid conjunctiva, accompanied by distinct grade 1 papillary changes in the upper tarsal conjunctiva. As antiviral therapy had been initiated, no further smears were taken. When the patient was examined again on May 5, the lesion medial to the canthus had regressed remarkably. The preauricular lymph node was still palpable and non tender. The Iimbal inflammation had cleared, although there was still mild follicular change inferiorly with papillary changes on the superior tarsal conjunctiva. The bulbar conjunctival nodule was no longer present. The administration of idoxuridine ointment was decreased to three times daily. On May 20, the skin lesion could no longer be detected. The papillary changes on the superior conjunctiva remained, but the inferior follicles had been replaced by diffuse papillae. Treatment with idoxuridine was discontinued. At a final examination on July 22, all the lesions had healed.
nostrils, eyes, and, occasionally, udders. These lesions progress through the vesicular and pustular stages to become ulcerated and crusted over in three to four weeks." Recovery is usually uneventful. Recently a live virus vaccine has been used to immunize lambs and kids.! The
DISCUSSION
Orf, also known as contagious ecthyma of sheep or contagious pustular dermatitis, is a disease that most often affects sheep. It produces papules around the mucous membranes, particularly the lips,
Fig. 2 (Freeman, Bron, and Juel-Jensen). Typical orf lesions on the hand.
VOL. 97, NO..5
OCULAR INFECTION WITH ORF VIRUS
603
Fig. 3 (Freeman, Bron, and [tiel-jensen). Left, Orf lesion at the medial canthus at the first examination. Right, Healed lesions ten days later.
same virus may he responsible for bovine papular stomatitis in cattle." Human infection usually occurs only in people whose occupations bring them into close contact with live stock. Thus, veterinarians, sheep ranchers, farmers, and occasionally laboratory workers! are at risk. The virus is usually acquired by direct inoculation but can be transferred from pastures and on clothing." As the virus is heat-resistant, it can be propagated years later from dried crusts of saliva. The diagnosis can be made by electron microscopic examination of scrapings from lesions or by a complement-fixation test." Human-to-human transmission, although it has been reported, is unusual." In humans, the incubation time is three to seven days; then, a maculopapular lesion erupts at the site of infection, usually the arm or hand. Often only one lesion is present, although multiple inoculations do occur. This progresses to a raised red nodule with an ulcerated summit. If it is mistaken for a pustule and incised, no purulent material is found. The nodule progresses rapidly to a papillomatous stage in four to six weeks and finally regresses without scarring in six to eight weeks." Pain and inflammation are usually slight. Occasionally systemic involvement in the form of lymphangitis, lymphadenopathy, erythema multiforme, and secondary bacterial infection occurs.
A survey of human orf infection between 1975 and 1981 reported 344 cases involving skin lesions." Of these, 142 were related to contact with sheep, 36 with cows or calves, and two with goats. Infections of the face or ear were reported in nine cases. Although blindness has been reported in human orf infection, possibly from secondary bacterial disease.! ocular involvement appears to be rare. Our patient had been helping with new lambs before her infection. Interestingly, the canthal and conjunctival lesions were the only ones to develop, and although it is possible that her finger contacted the virus first and then spread it to the ocular region, it is also possible that infection occurred directly while she was carrying a lamb.
Fig. 4 (Freeman, Bron, and Juel-Jensen). Follicular limbal inflammation demonstrated with fluorescein (arrows).
604
AMERICAN JOURNAL OF OPHTHALMOLOGY
In previous cases 6,8-13 treatment has consisted either of waiting for the lesions to regress spontaneously or excision. Antibacterial antimicrobials are of no use except in cases of proven secondary bacterial infection. In our patient, treatment with idoxuridine resulted in prompt resolution of both conjunctival and skin lesions. The limbal inflammation and skin nodule had completely regressed 21 days after treatment began. Vaccinia virus is a member of the Poxviridae family and belongs to the same subfamily, chordopoxvirinae as orf but to a different genus (Orthopoxvirus in the case of vaccinia and Parapoxoirus in the case' of orf.2 Idoxuridine is effective in the treatment of vaccinial lesions of the eye and skin in human and rabbit infections'v" and has been used previously in the treatment of orf. ACK."IOWLEDGMENT
T. Lee, of the Department of Virology, John Radcliffe Hospital, Oxford, provided Figure 1. REFERENCES 1. Falk, E.: Parapoxvirus infections of reindeer and musk ox associated with unusual human infections. Br. J. Dermatol. 99:647, 1978. 2. Naano, J. H.: Comparative Diagnosis of Viral Diseases. New York, Academic Press, New York, 1977, vol. 1, pp. 299 and 300.
MAY, 1984
3. Andrews, c.. Pereira, H. C., and Wilde, P.: Viruses of Vertebrates. London, Balliere Tindall, 1978, p. 369. 4. PHLS Communicable Disease Surveillance Centre and Communicable Diseases (Scotland) Unit: Orf paravaccinia infections, British Isles, 1875-81. Epidemiological report. Br. Med. J. 284:1958, 1982. 5. Moore, R. ~l.: Human orf in the United States, 1972. J. Infect. Dis. 127:731, 1973. 6. Dalton, A. J.: Orf. A report of 19 human cases and clinical and pathological observations. J.A.M.A. 204:657, 1968. 7. Johannessen, J. V., Krogh, H. K., Solberg, 1., Dalen, A., van Wyngaarden, H., and Johansen, B.: Human orf. J. Cutan. Pathol. 2:265, 1975. 8. Wilkinson, J. D.: Orf. A family with unusual complications. Br. J. Dermatol. 97:447, 1977. 9. joensen, H. D., and Block, D.: Human ecthyma contagiosum (orf) in the Faroe Islands. Acta Pathol. Microbiol. Scand. 82:3ll, 1974. 10. Hodgson-lones, J. S.: Orf in London. Br. Med. J. 1:79, 1951. II. Hall, M.: Orf in Britain, letter. Br. Med. J. 2:420, 1976. 12. Sweeney, E. C., and Woolfson, M.: Human ecthyma contagiosum (orf). Irish J. Med. Sci. I:ll2, 1978. 13. Steijman, A. J.: Viral diseases. In Craernes: Principles and Practice of Clinical Pharmacology and Therapeutics. London, Churchill-Livingstone, 1980, pp. ll52 and ll53. 14. Kaufman, H. E., Nesbum, A. B., and Maloney, E. D.: Cure of vaccinia infection by 5 iodo-2'deoxyuridine. Virology 18:567, 1962. 15. Calabresi, P., McCollum, R. W., and Welsh, A. D.: Suppression of infections resulting from a deoxyribonucleic acid virus (vaccinia) by systemic administration of 5-iodo-2'-deoxyuridine. Nature 1971:767, 1963. 16. [uel-jensen, B. E.: The chemotherapy of viral disease. Br. J. Hosp. Med. 10:402, 1973.