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Koplik spots and a purpuric eruption associated with parvovirus B19 infection
Journal of the American Academy of Dermatology
466 Brief communications
Koplik spots and a purpuric eruption associated with parvovirus B19 infection Lydia M. Evans, MD, Marc E. Grossman, MD, and Neal Gregory, MD, MPH New York, New York Acute human parvovirus B 19 infection in the adult may not be readily recognized if the cutaneous findings are other than the classic "slapped-cheek" appearance of erythema infectiosum (fifth disease). We present a patient with a febrile illness associated with arthralgias and an unusual skin eruption of nonthrombocytopenic, nonvasculitic purpura followed by the development of Koplik spots and a morbilliform eruption, who had documented acute parvovirus B 19 infection. CASE REPORT A 26-year-old woman had a 4-day history of a pruritic eruption and a 3-day history of symmetric arthralgia of the hands, wrists, shoulders, elbows, and knees. Lowgrade fever and mild pharyngitis developed the day before. She denied having measles as a child and was unable to recall her immunization history. Physical examination revealed warm, indurated, bright red-purple, purpuric plaques on the buttocks, surrounded by I to 2 mm red-purple purpuric papules (Fig. 1). A similar lesion was present on the mons pubis. Petechiae were scattered on the trunk and extremities, concentrated on the volar wrists and ankles. Her temperature was 39.8° C. There was tender bilateral inguinal adenopathy. The white blood cell count was 3300/mm3, and the platelet count was 238,000/mm3; prothrombin and partial thromboplastin times were normal. Liver chemistry values were normal except for a lactate dehydrogenase value of 265 D/dl (normal range 90 to 200 DidO, erythrocyte sedimentation rate was 3 mm/hr, and chest roentgenography and electrocardiography were normal. Skin biopsy specimens of the purpuric plaque on the buttocks and a petechial lesion on the leg showed a mononuclear cell perivascular infiltrate with extravasated erythrocytes. There was no evidence of vasculitis, thrombosis, or organisms. The patient was treated with acetaminophen. The next day (day 5) petechiae developed on the palms, From the Department of Dermatology, Columbia Presbyterian Medical Center. Reprint requests: Lydia M. Evans, MD, Department of Dermatology, Columbia Presbyterian Medical Center, 622 W. 168th St., New York, NY 10032.
16/54/36912
soles, and hard palate and became more numerous on the trunk and extremities. On day 6, multiple Koplik spots were noted on the posterior buccal mucosa bilaterally and on the lower anterior gingiva. A diffuse morbilliform eruption developed on the trunk and extremities with minimal involvement of the face on day 7. Three days later, all signs and symptoms had resolved. Blood and urine bacterial cultures were negative, as were throat, rectal, and urine viral cultures. Cervical gonococcal cultures and vaginal cultures for Staphylococcus aureus were negative. Viral titers were negative for echovirus 4 and 9 (titers <1:8). Titers of 1:8 for echovirus 11 and 30 suggested infection at some indeterminate time in the past. Measles acute and convalescent titers were both IgM < 1: 10, IgG I :20, also documenting past infection. Acute titers for parvovirus B19 were positive for IgM and negative for IgG. Convalescent titers drawn 4 weeks later were positive for both IgM and IgG, confirming an acute parvovirus B 19 infection. DISCUSSION
Human parvovirus B19 is a small, single-stranded DNA virus that was identified in serum samples from asymptomatic blood donors in 1975. 1 It has been associated with erythema infectiosum (fifth disease), 2 polyarticular arthralgias and arthritis,3, 4 hydrops fetalis and fetal death, 5 and aplastic crisis in patients with hemoglobinopathies. 6 The most common manifestation of parvovirus B19 infection is fifth disease,? which generally occurs in children. Fifth disease is characterized by prominent erythematous plaques on the malar eminences, the classic "slapped cheeks," and lacelike erythema on the extensor surfaces and buttocks. Epidemiologic studies of parvovirus B19 infections have demonstrated that adults may have no eruption or only a blotchy lacelike erythema on the extremities and less often on the trunk. 4 "Slapped cheeks" are generally not observed. The exanthem in adults may be preceded by flu-like symptoms of fever, sore throat, mya1gias, and lymphadenopathy. Symmetric polyarthralgia ofthe hands, wrists, knees, and ankles occur in up to 80% of adults and affect women more often than men.? Arthropathy may
Volume 27 Number 3 September 1992
Brief communications 467
Fig. 1. Purpuric plaque over the buttocks surrounded by 1 to 2 mm purpuric papules. occur with or without an exanthem and lasts for approximately 10 days, although joint pains have been rarely reported to persist for months. The fever, arthralgias, and lymphadenopathy experienced by our patient are well-recognized manifestations of parvovirus B19 infection in adults, but her exanthem and enanthem are not. Unusual purpuric, petechial, and pseudopustular eruptions have been rarely reported in adults and children with parvovirus Bl9 infection. 8-l2 Not surprisingly, purpuric and petechial eruptions have occurred in patients with aplastic crisis,8, 10 but similar eruptions have also been reported in a few patients without thrombocytopenia or coagulopathy.8-12 The accentuation of petechiae on the wrists and ankles, combined with the patient's age at immunization (if she was indeed immunized), led to consideration of atypical measles in the initial differential diagnosis. The development of Koplik spots on the sixth day of her illness, which are not seen in atypical measles, followed by a morbilliform eruption suggested the possibility of an unusual presentation of classic measles. Koplik spots have been considered to be pathognomonic of measles. 13 However, the patient had neither conjunctivitis nor coryza, and her morbilliform eruption first developed on the trunk with relative sparing of the face. Acute and convalescent titers did not confirm a recent paramyxovirus infection. Koplik spots in echovirus 9 infection is mentioned in the second and third editions of Mandell's Principles and Practice of Infectious Diseases, 13,14 but no documentation for this assertion can be found. 15 We have been unable to locate any previous reports of Koplik spots associated with parvovirus B 19 infection.
REFERENCES 1. Cossart YE, Yield AM, Cant B, et al. Parvovirus-like particles in human sera. Lancet 1975;1:72-3. 2. Anderson MJ, Jones SE, Fisher-Hoch SP, et al. Human parvovirus: The cause of erythema infectiosum (fifth disease)? [Letter]. Lancet 1983;1:1378. 3. Reid TM, Reid TMD, Brown T, et al. Human parvovirusassociated arthritis: a clinical and laboratory description. Lancet 1985;1:422-5. 4. Woolf AD, Campion GV, ChishickA, et al. Clinical manifestations of human parvovirus B19 in adults. Arch Intern Med 1989; 149:1153-6. 5. Anand A, Gray ES, Brown T, et al. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 1987;316: 183-6. 6. Rao KRP, Patel AR, Anderson MJ, et al. Infection with parvovirus-like virus and aplastic crisis in chronic hemolytic anemia. Ann Intern Med 1983;98:430-2. 7. Bialecki C, Feder HM Jr, Grant-Kels JM. The six classic childhood exanthems: a review and update. J AM ACAD DERMATOL 1989;21:891-903. 8. LeFrere n, Courouc AM, Muller JY, et al. Human parvovirus and purpura. Lancet 1985;2:730. 9. Conway SP, Cohen BJ, Field AM, et at A family outbreak ofParvovirus Bl9 infection with petechial rash in a 7-yearold boy. J Infect 1987;15:110-2. 10. Mortimer PP, Cohen P J, Rossiter MA, et al. Human parvovirus and purpura. Lancet 1985;2:730-1. 11. Naides 8J, Piette W, Veach LA, et at Human parvovirus B19 induced vesiculopustular skin eruption. Am J Med 1988;64:968-72. 12. Loong CL, Coyle PV, Anderson MJ, et at Human serum parvovirus associated vasculitis. Postgrad Med J 1986; 62:493-4. 13. Mandell GL, Douglas RG Jr, Bennett JE, cds. Principles and practice of infectious disease. New York: John Wiley & Sons, 1985:816. 14. Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practice of infectious disease. New York: John Wiley & Sons, I 990:1281, 1370. 15. Annunziato D. Koplikspots and echo 9 virus [Letter]. N Y State J Med 1987;87:667.
466 Brief communications
Koplik spots and a purpuric eruption associated with parvovirus B19 infection Lydia M. Evans, MD, Marc E. Grossman, MD, and Neal Gregory, MD, MPH New York, New York Acute human parvovirus B 19 infection in the adult may not be readily recognized if the cutaneous findings are other than the classic "slapped-cheek" appearance of erythema infectiosum (fifth disease). We present a patient with a febrile illness associated with arthralgias and an unusual skin eruption of nonthrombocytopenic, nonvasculitic purpura followed by the development of Koplik spots and a morbilliform eruption, who had documented acute parvovirus B 19 infection. CASE REPORT A 26-year-old woman had a 4-day history of a pruritic eruption and a 3-day history of symmetric arthralgia of the hands, wrists, shoulders, elbows, and knees. Lowgrade fever and mild pharyngitis developed the day before. She denied having measles as a child and was unable to recall her immunization history. Physical examination revealed warm, indurated, bright red-purple, purpuric plaques on the buttocks, surrounded by I to 2 mm red-purple purpuric papules (Fig. 1). A similar lesion was present on the mons pubis. Petechiae were scattered on the trunk and extremities, concentrated on the volar wrists and ankles. Her temperature was 39.8° C. There was tender bilateral inguinal adenopathy. The white blood cell count was 3300/mm3, and the platelet count was 238,000/mm3; prothrombin and partial thromboplastin times were normal. Liver chemistry values were normal except for a lactate dehydrogenase value of 265 D/dl (normal range 90 to 200 DidO, erythrocyte sedimentation rate was 3 mm/hr, and chest roentgenography and electrocardiography were normal. Skin biopsy specimens of the purpuric plaque on the buttocks and a petechial lesion on the leg showed a mononuclear cell perivascular infiltrate with extravasated erythrocytes. There was no evidence of vasculitis, thrombosis, or organisms. The patient was treated with acetaminophen. The next day (day 5) petechiae developed on the palms, From the Department of Dermatology, Columbia Presbyterian Medical Center. Reprint requests: Lydia M. Evans, MD, Department of Dermatology, Columbia Presbyterian Medical Center, 622 W. 168th St., New York, NY 10032.
16/54/36912
soles, and hard palate and became more numerous on the trunk and extremities. On day 6, multiple Koplik spots were noted on the posterior buccal mucosa bilaterally and on the lower anterior gingiva. A diffuse morbilliform eruption developed on the trunk and extremities with minimal involvement of the face on day 7. Three days later, all signs and symptoms had resolved. Blood and urine bacterial cultures were negative, as were throat, rectal, and urine viral cultures. Cervical gonococcal cultures and vaginal cultures for Staphylococcus aureus were negative. Viral titers were negative for echovirus 4 and 9 (titers <1:8). Titers of 1:8 for echovirus 11 and 30 suggested infection at some indeterminate time in the past. Measles acute and convalescent titers were both IgM < 1: 10, IgG I :20, also documenting past infection. Acute titers for parvovirus B19 were positive for IgM and negative for IgG. Convalescent titers drawn 4 weeks later were positive for both IgM and IgG, confirming an acute parvovirus B 19 infection. DISCUSSION
Human parvovirus B19 is a small, single-stranded DNA virus that was identified in serum samples from asymptomatic blood donors in 1975. 1 It has been associated with erythema infectiosum (fifth disease), 2 polyarticular arthralgias and arthritis,3, 4 hydrops fetalis and fetal death, 5 and aplastic crisis in patients with hemoglobinopathies. 6 The most common manifestation of parvovirus B19 infection is fifth disease,? which generally occurs in children. Fifth disease is characterized by prominent erythematous plaques on the malar eminences, the classic "slapped cheeks," and lacelike erythema on the extensor surfaces and buttocks. Epidemiologic studies of parvovirus B19 infections have demonstrated that adults may have no eruption or only a blotchy lacelike erythema on the extremities and less often on the trunk. 4 "Slapped cheeks" are generally not observed. The exanthem in adults may be preceded by flu-like symptoms of fever, sore throat, mya1gias, and lymphadenopathy. Symmetric polyarthralgia ofthe hands, wrists, knees, and ankles occur in up to 80% of adults and affect women more often than men.? Arthropathy may
Volume 27 Number 3 September 1992
Brief communications 467
Fig. 1. Purpuric plaque over the buttocks surrounded by 1 to 2 mm purpuric papules. occur with or without an exanthem and lasts for approximately 10 days, although joint pains have been rarely reported to persist for months. The fever, arthralgias, and lymphadenopathy experienced by our patient are well-recognized manifestations of parvovirus B19 infection in adults, but her exanthem and enanthem are not. Unusual purpuric, petechial, and pseudopustular eruptions have been rarely reported in adults and children with parvovirus Bl9 infection. 8-l2 Not surprisingly, purpuric and petechial eruptions have occurred in patients with aplastic crisis,8, 10 but similar eruptions have also been reported in a few patients without thrombocytopenia or coagulopathy.8-12 The accentuation of petechiae on the wrists and ankles, combined with the patient's age at immunization (if she was indeed immunized), led to consideration of atypical measles in the initial differential diagnosis. The development of Koplik spots on the sixth day of her illness, which are not seen in atypical measles, followed by a morbilliform eruption suggested the possibility of an unusual presentation of classic measles. Koplik spots have been considered to be pathognomonic of measles. 13 However, the patient had neither conjunctivitis nor coryza, and her morbilliform eruption first developed on the trunk with relative sparing of the face. Acute and convalescent titers did not confirm a recent paramyxovirus infection. Koplik spots in echovirus 9 infection is mentioned in the second and third editions of Mandell's Principles and Practice of Infectious Diseases, 13,14 but no documentation for this assertion can be found. 15 We have been unable to locate any previous reports of Koplik spots associated with parvovirus B 19 infection.
REFERENCES 1. Cossart YE, Yield AM, Cant B, et al. Parvovirus-like particles in human sera. Lancet 1975;1:72-3. 2. Anderson MJ, Jones SE, Fisher-Hoch SP, et al. Human parvovirus: The cause of erythema infectiosum (fifth disease)? [Letter]. Lancet 1983;1:1378. 3. Reid TM, Reid TMD, Brown T, et al. Human parvovirusassociated arthritis: a clinical and laboratory description. Lancet 1985;1:422-5. 4. Woolf AD, Campion GV, ChishickA, et al. Clinical manifestations of human parvovirus B19 in adults. Arch Intern Med 1989; 149:1153-6. 5. Anand A, Gray ES, Brown T, et al. Human parvovirus infection in pregnancy and hydrops fetalis. N Engl J Med 1987;316: 183-6. 6. Rao KRP, Patel AR, Anderson MJ, et al. Infection with parvovirus-like virus and aplastic crisis in chronic hemolytic anemia. Ann Intern Med 1983;98:430-2. 7. Bialecki C, Feder HM Jr, Grant-Kels JM. The six classic childhood exanthems: a review and update. J AM ACAD DERMATOL 1989;21:891-903. 8. LeFrere n, Courouc AM, Muller JY, et al. Human parvovirus and purpura. Lancet 1985;2:730. 9. Conway SP, Cohen BJ, Field AM, et at A family outbreak ofParvovirus Bl9 infection with petechial rash in a 7-yearold boy. J Infect 1987;15:110-2. 10. Mortimer PP, Cohen P J, Rossiter MA, et al. Human parvovirus and purpura. Lancet 1985;2:730-1. 11. Naides 8J, Piette W, Veach LA, et at Human parvovirus B19 induced vesiculopustular skin eruption. Am J Med 1988;64:968-72. 12. Loong CL, Coyle PV, Anderson MJ, et at Human serum parvovirus associated vasculitis. Postgrad Med J 1986; 62:493-4. 13. Mandell GL, Douglas RG Jr, Bennett JE, cds. Principles and practice of infectious disease. New York: John Wiley & Sons, 1985:816. 14. Mandell GL, Douglas RG Jr, Bennett JE, eds. Principles and practice of infectious disease. New York: John Wiley & Sons, I 990:1281, 1370. 15. Annunziato D. Koplikspots and echo 9 virus [Letter]. N Y State J Med 1987;87:667.