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Papular-purpuric gloves and socks syndrome in HIV-positive patients
Papular-purpuric gloves and socks syndrome in HIV-positive patients Giovanni Ghigliotti, MD,a Giovanni Mazzarello, MD,b Anna Nigro, MD,a Flavio Fusco, MD,b Valerio Del Bono, MD,b and Roberto De Marchi, MDa Genoa, Italy Three HIV-positive women showed clinical signs of papular-purpuric gloves and socks syndrome and serologic evidence of acute Parvovirus B19 infection. The course of the disease was complicated by anemia and persistent skin lesions, probably related to inadequate immune response. Because anemia in AIDS patients may be due to many causes, the history of recent Parvovirus B19 infection is helpful in suggesting the etiologic diagnosis. (J Am Acad Dermatol 2000;43:916-7.)
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arvovirus B19 (B19) has been considered as a possible etiologic agent of papular-purpuric gloves and socks syndrome (PPGSS), a pruritic eruption of erythema, edema, and purpura involving predominantly the hands and feet.1 This report describes 3 HIV-positive women with PPGSS because of B19.
CASE REPORTS Case 1 A 45-year-old heterosexual HIV-positive woman had a fever (temperature, 38.5°C), headache, and drowsiness, and an extremely pruritic acral rash developed. Physical examination showed erythematous macules and erythemato-edematous papules and plaques mainly involving hands and feet (Fig 1). At the onset of PPGSS, her CD4 cell count was 7/µL (1%). Serum was tested by enzyme-linked immunosorbent assay (ELISA) for B19 IgM and IgG. IgM was positive (1+) on day 5 and (2+) on day 17; IgG was negative on day 5 and positive (1+) on day 17. In the 2 weeks after the appearance of the eruption, her hemoglobin dropped from 11.2 to 8.4 g/dL, and remained low during the follow-up. Her bone marrow showed a reduced number of erythroid cells with the presence of giant pronormoblasts, suggestive of B19 infection. The cerebrospinal fluid (CSF) showed signs of an aseptic meningitis. Polymerase chain reaction for This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Division of Dermatology,a S Martino Hospital, and I Clinic of Infectious Diseases,b University of Genoa. Reprint requests: Giovanni Ghigliotti, Division of Dermatology, S Martino Hospital, L.go R. Benzi, 10 I-16132, Genoa, Italy. Copyright © 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/4/103263 doi:10.1067/mjd.2000.103263
916
B19 in the CSF was negative. PPGSS spontaneously resolved with desquamation after 3 weeks, whereas the hemoglobin levels remained low for the next 45 days, when we lost the patient to follow-up. Case 2 A 36-year-old heroin-addicted HIV-positive woman had a fever and asthenia, and pruritic erythema and edema of the feet and hands developed. Her CD4 cell count was 158/µL (20%), hemoglobin 9.4 g/dL, and hematocrit 29.5%. Her previous hemoglobin was 11.8 g/dL with hematocrit 33.6%. ELISA testing of her serum for B19 IgM was positive on day 4 and +/– on day 30; IgG was positive on day 4 and remained positive on day 30. Her skin rash healed after 4 weeks with desquamation. The anemia resolved within 8 weeks. Case 3 A 33-year-old heroin-addicted HIV-positive woman had pruritic palmar and plantar erythema and edema develop, and a headache, night sweats, and fever (temperature, 39°C). She was taking fluconazole for oral candidiasis and the antiretroviral agents zidovudine and didanosine. Her CD4 cell count was 6/µL (6%). Anti-B19 IgM was positive ++ on day 2 and +++ on day 14 after the onset of PPGSS. IgG was negative on day 2 and positive on day 14. No anemia was found. Her bone marrow was unaffected. PPGSS resolved after 4 months with desquamation, whereas pruritus persisted for 8 months. It is interesting to note that patients 2 and 3 were friends and next-door neighbors and patient 3 had the PPGSS develop 15 days after patient 2.
COMMENT We report 3 cases of PPGSS due to B19 occurring in HIV-positive patients. In 1991, B19 was proposed as a possible etiologic agent of PPGSS, and this has
J AM ACAD DERMATOL VOLUME 43, NUMBER 5
Ghigliotti et al 917
been confirmed in subsequent reports.2,3 In immunocompetent patients, PPGSS is a benign dermatosis. Arthralgias, adenopathy, transient anemia, leukopenia, thrombocytopenia, abnormal coagulation time, cold agglutinins, and elevation of liver enzymes tests are described.2,4,5 However, the disorder is self-limited and heals without sequelae.5 In immunosuppressed patients, B19 is known to cause chronic anemia and pancytopenia.6 The lack of an adequate immune response may lead to viral persistence. Viral persistence might explain the complications noted in our patients; case 3 had prolonged cutaneous lesions and pruritus and cases 1 and 2 had persistent anemia. Anemia is frequently observed in HIV-positive patients. It may be due to opportunistic infections, drugs, neoplasms, inappropriately low erythropoietin production, or immunologic consequences of the HIV infection itself.7 In addition to B19, measles virus,8 coxsackie B6,9 cytomegalovirus,10 hepatitis B virus,11 Epstein-Barr virus,12 and human herpesvirus 613 have been reported to cause PPGSS. However, in AIDS patients, B19 should also be taken into consideration and, if anemia is present, the study of the bone marrow morphology should be performed to demonstrate signs of Parvovirus infection. Persistent Parvovirus infection can be successfully treated with immunoglobulin infusions.6 REFERENCES 1. Bagot M, Revuz J. Papular-purpuric “gloves and socks” syndrome: primary infection with parvovirus B19? J Am Acad Dermatol 1991;25:341. 2. Halasz CL, Cormier D, Den M. Petechial glove and sock syndrome caused by parvovirus B19. J Am Acad Dermatol 1992;27: 835-8. 3. Bessis D, Lamaury I, Jonquet O, Segondy M, Janbon F. Human parvovirus B19 induced papular-purpuric “gloves and socks” syndrome. Eur J Dermatol 1994;4:133-4. 4. Castanet J, Taillan B, Garnier G, Ragoin O, Ortonne JP, Dujardin P. Gloves and socks papular purpura associated with antiphospholipid antibodies. Presse Med 1993;22:1747. 5. Leger F, Callens A, Machet MC. Parvovirus B19 primo-infection and cold agglutinins. Ann Dermatol Venereol 1997;124:257-9. 6. Frickhofen N, Abkowitz JL, Safford M, Berry JM, Antunez-deMayolo J, Astrow A, et al. Persistent B19 Parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS. Ann Int Med 1990; 113:926-33. 7. Scadden DT, Zon LI, Groopman JE. Pathophysiology and management of HIV-associated hematologic disorders. Blood 1989; 74:1455-63.
Fig 1. Erythematous macules and papules on right foot.
8. Perez-Ferriols A, Martinez-Aparicio A, Aliaga-Boniche A. Papular-purpuric “gloves and socks” syndrome caused by measles virus. J Am Acad Dermatol 1994;30:291-2. 9. Harms M, Feldmann R, Saurat JH. Reply. J Am Acad Dermatol 1994;30:292. 10. Carrascosa JM, Bielsa I, Ribera M, Ferrandiz C. Papular-purpuric “gloves and socks” syndrome related to cytomegalovirus infection. Dermatology 1995;191:269-70. 11. Guibal F, Buffet P, Mouly F, Morel P, Rybojad M. Papular-purpuric gloves and socks syndrome with hepatitis B infection. Lancet 1996;347:473. 12. Drago F, Parodi A, Rebora A. Gloves-and-socks syndrome in a patient with Epstein-Barr virus infection. Dermatology 1997; 194:374. 13. Ruzicka T, Kalka K, Diercks K, Schuppe HC. Papular-purpuric “gloves and socks” syndrome associated with human herpesvirus 6 infection. Arch Dermatol 1998;134:242-4.
P
arvovirus B19 (B19) has been considered as a possible etiologic agent of papular-purpuric gloves and socks syndrome (PPGSS), a pruritic eruption of erythema, edema, and purpura involving predominantly the hands and feet.1 This report describes 3 HIV-positive women with PPGSS because of B19.
CASE REPORTS Case 1 A 45-year-old heterosexual HIV-positive woman had a fever (temperature, 38.5°C), headache, and drowsiness, and an extremely pruritic acral rash developed. Physical examination showed erythematous macules and erythemato-edematous papules and plaques mainly involving hands and feet (Fig 1). At the onset of PPGSS, her CD4 cell count was 7/µL (1%). Serum was tested by enzyme-linked immunosorbent assay (ELISA) for B19 IgM and IgG. IgM was positive (1+) on day 5 and (2+) on day 17; IgG was negative on day 5 and positive (1+) on day 17. In the 2 weeks after the appearance of the eruption, her hemoglobin dropped from 11.2 to 8.4 g/dL, and remained low during the follow-up. Her bone marrow showed a reduced number of erythroid cells with the presence of giant pronormoblasts, suggestive of B19 infection. The cerebrospinal fluid (CSF) showed signs of an aseptic meningitis. Polymerase chain reaction for This supplement is made possible through an educational grant from Ortho Dermatological to the American Academy of Dermatology. From the Division of Dermatology,a S Martino Hospital, and I Clinic of Infectious Diseases,b University of Genoa. Reprint requests: Giovanni Ghigliotti, Division of Dermatology, S Martino Hospital, L.go R. Benzi, 10 I-16132, Genoa, Italy. Copyright © 2000 by the American Academy of Dermatology, Inc. 0190-9622/2000/$12.00 + 0 16/4/103263 doi:10.1067/mjd.2000.103263
916
B19 in the CSF was negative. PPGSS spontaneously resolved with desquamation after 3 weeks, whereas the hemoglobin levels remained low for the next 45 days, when we lost the patient to follow-up. Case 2 A 36-year-old heroin-addicted HIV-positive woman had a fever and asthenia, and pruritic erythema and edema of the feet and hands developed. Her CD4 cell count was 158/µL (20%), hemoglobin 9.4 g/dL, and hematocrit 29.5%. Her previous hemoglobin was 11.8 g/dL with hematocrit 33.6%. ELISA testing of her serum for B19 IgM was positive on day 4 and +/– on day 30; IgG was positive on day 4 and remained positive on day 30. Her skin rash healed after 4 weeks with desquamation. The anemia resolved within 8 weeks. Case 3 A 33-year-old heroin-addicted HIV-positive woman had pruritic palmar and plantar erythema and edema develop, and a headache, night sweats, and fever (temperature, 39°C). She was taking fluconazole for oral candidiasis and the antiretroviral agents zidovudine and didanosine. Her CD4 cell count was 6/µL (6%). Anti-B19 IgM was positive ++ on day 2 and +++ on day 14 after the onset of PPGSS. IgG was negative on day 2 and positive on day 14. No anemia was found. Her bone marrow was unaffected. PPGSS resolved after 4 months with desquamation, whereas pruritus persisted for 8 months. It is interesting to note that patients 2 and 3 were friends and next-door neighbors and patient 3 had the PPGSS develop 15 days after patient 2.
COMMENT We report 3 cases of PPGSS due to B19 occurring in HIV-positive patients. In 1991, B19 was proposed as a possible etiologic agent of PPGSS, and this has
J AM ACAD DERMATOL VOLUME 43, NUMBER 5
Ghigliotti et al 917
been confirmed in subsequent reports.2,3 In immunocompetent patients, PPGSS is a benign dermatosis. Arthralgias, adenopathy, transient anemia, leukopenia, thrombocytopenia, abnormal coagulation time, cold agglutinins, and elevation of liver enzymes tests are described.2,4,5 However, the disorder is self-limited and heals without sequelae.5 In immunosuppressed patients, B19 is known to cause chronic anemia and pancytopenia.6 The lack of an adequate immune response may lead to viral persistence. Viral persistence might explain the complications noted in our patients; case 3 had prolonged cutaneous lesions and pruritus and cases 1 and 2 had persistent anemia. Anemia is frequently observed in HIV-positive patients. It may be due to opportunistic infections, drugs, neoplasms, inappropriately low erythropoietin production, or immunologic consequences of the HIV infection itself.7 In addition to B19, measles virus,8 coxsackie B6,9 cytomegalovirus,10 hepatitis B virus,11 Epstein-Barr virus,12 and human herpesvirus 613 have been reported to cause PPGSS. However, in AIDS patients, B19 should also be taken into consideration and, if anemia is present, the study of the bone marrow morphology should be performed to demonstrate signs of Parvovirus infection. Persistent Parvovirus infection can be successfully treated with immunoglobulin infusions.6 REFERENCES 1. Bagot M, Revuz J. Papular-purpuric “gloves and socks” syndrome: primary infection with parvovirus B19? J Am Acad Dermatol 1991;25:341. 2. Halasz CL, Cormier D, Den M. Petechial glove and sock syndrome caused by parvovirus B19. J Am Acad Dermatol 1992;27: 835-8. 3. Bessis D, Lamaury I, Jonquet O, Segondy M, Janbon F. Human parvovirus B19 induced papular-purpuric “gloves and socks” syndrome. Eur J Dermatol 1994;4:133-4. 4. Castanet J, Taillan B, Garnier G, Ragoin O, Ortonne JP, Dujardin P. Gloves and socks papular purpura associated with antiphospholipid antibodies. Presse Med 1993;22:1747. 5. Leger F, Callens A, Machet MC. Parvovirus B19 primo-infection and cold agglutinins. Ann Dermatol Venereol 1997;124:257-9. 6. Frickhofen N, Abkowitz JL, Safford M, Berry JM, Antunez-deMayolo J, Astrow A, et al. Persistent B19 Parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS. Ann Int Med 1990; 113:926-33. 7. Scadden DT, Zon LI, Groopman JE. Pathophysiology and management of HIV-associated hematologic disorders. Blood 1989; 74:1455-63.
Fig 1. Erythematous macules and papules on right foot.
8. Perez-Ferriols A, Martinez-Aparicio A, Aliaga-Boniche A. Papular-purpuric “gloves and socks” syndrome caused by measles virus. J Am Acad Dermatol 1994;30:291-2. 9. Harms M, Feldmann R, Saurat JH. Reply. J Am Acad Dermatol 1994;30:292. 10. Carrascosa JM, Bielsa I, Ribera M, Ferrandiz C. Papular-purpuric “gloves and socks” syndrome related to cytomegalovirus infection. Dermatology 1995;191:269-70. 11. Guibal F, Buffet P, Mouly F, Morel P, Rybojad M. Papular-purpuric gloves and socks syndrome with hepatitis B infection. Lancet 1996;347:473. 12. Drago F, Parodi A, Rebora A. Gloves-and-socks syndrome in a patient with Epstein-Barr virus infection. Dermatology 1997; 194:374. 13. Ruzicka T, Kalka K, Diercks K, Schuppe HC. Papular-purpuric “gloves and socks” syndrome associated with human herpesvirus 6 infection. Arch Dermatol 1998;134:242-4.