Content uploaded by Marcos Tadashi Kakitani Toyoshima
Author content
All content in this area was uploaded by Marcos Tadashi Kakitani Toyoshima on Nov 13, 2014
Content may be subject to copyright.
Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
www.bjid.com.br
62 BJID 2006; 10 (February)
Papular-Purpuric “Gloves and Socks” Syndrome
Caused by Parvovirus B19 Infection in Brazil: A Case Report
Marcos Tadashi Kakitani Toyoshima
1
,
1
Department of Internal Medicine of University of São Paulo
Lilian Walsh Keller
2
, Maria Luisa Barbosa
2,3
School of Medicine,
2
Institute of Biomedical Sciences, University
and Edison Luiz Durigon
2
of São Paulo,
3
Adolfo Lutz Institute; São Paulo, SP, Brazil
Papular-purpuric “gloves and socks” syndrome (PPGSS) is a novel, rare, self-limiting dermatosis
caused by human parvovirus B19. It consists of pruritic edema and erythema of the hands and feet in
a gloves-and-socks distribution, and it is associated with oral lesions and fever. We present a case of
PPGSS in a 22-year-old Brazilian woman. Clinical and laboratory evaluation, including serological
tests, PCR and gene sequencing, confirmed the presence of human parvovirus B19.
Key Words: Dermatosis, gloves and socks, parvovirus B19, PCR, sequencing
Received on 22 Novermber 2005; revised 21 January 2006.
Address for correspondence: Dr. Marcos Tadashi Kakitani
Toyoshima – Rua Professor Antonio Prudente, 41 apto. 506 –
Liberdade – São Paulo – SP – Brazil. Zip code: 01509-010. Telephone:
55-11-3207-3840. E-mail: mtkt@terra.com.br
The Brazilian Journal of Infectious Diseases 2006;10(1):62-64.
© 2006 by The Brazilian Journal of Infectious Diseases and Contexto
Publishing. All rights reserved.
Parvovirus B19 (B19) was discovered by Yvonne Cossart,
an Australian virologist working in London in 1975; it was
first linked to a disease by John Pattison in 1981 [1]. Parvovirus
B19 is until recently the only member of the large Parvoviridae
family that has been directly associated with human infection
[1,2]. Infection with B19 is distributed worldwide and has been
associated with a broad spectrum of clinical syndromes that
vary with the age and clinical conditions of the host [1,3].
Papular-purpuric “gloves and socks” syndrome (PPGSS) is a
novel, rare, self-limiting dermatosis caused by B19.
We described
a case of PPGSS that occurred in a healthcare
professional with acute parvovirus B19 infection.
Case Report
A 22-year-old woman, a nurse technician, was admitted
to
the emergency department of “Hospital Universitário” of the
University of São Paulo with a 3-day history of ecchymosis
on the left hand index finger and daily fever (39.0
o
C) that did
not decrease with dipirone. Several purpuric papules rapidly
developed on the palms, back of her hands and feet. These
lesions were not pruriginous. The patient was previously
healthy with no preceding upper respiratory tract infection,
no abdominal pain or diarrhea, and no joint pain or swelling.
There was no history of blood transfusion, or foreign travel.
On admission, the physical examination showed multiple
purpuric skin lesions on the dorsa and palms of both hands
and on the feet. These skin lesions were petechial and
marginated on the wrists and the ankles. The patient was
febrile (40.0
0
C) and in good general condition. No peripheral
lymph nodes, liver or spleen enlargements were present.
Multiple erythematous macules and papules could be seen
on the hard palate. No signs of meningeal irritation were seen.
The initial vital signs were a pulse of 124/min, 39.7
o
C, 120/
80mmHg blood pressure and a respiratory rate of 20/min.
Initial laboratory tests revealed mild leukopenia (4,500/
mL, with a differential count of 3% unsegmented neutrophils,
73% segmented neutrophils, 16% lymphocytes, 720
lymphocytes, 6% eosinophils and 2% monocytes) and
thrombocytopenia (106 X 10³ platelets/mL). Renal and hepatic
functions, serum electrolytes (sodium, potassium, and
calcium) and coagulation tests were within normal ranges. No
alteration was observed in abdominal ultrasonography. The
patient was admitted for further diagnostic investigation.
One day after she had been interned, petechiae affected
wrists, ankles and the distal third region of the legs. At the
same time, oral enanthema with small painful vesicles appeared.
Laboratory exams showed an erythrocyte sedimentation rate
of 58 mm per hour and 28 mg C-reactive protein/dL. We
alternated dipirone and acetaminophen to reduce the fever.
Four pairs of blood cultures (aerobic and anaerobic Bactec®)
were collected after admission, and all the results were
negative.
On the third day of admission, petechiae could be seen up
to the thighs, especially on the right thigh. The vesicles with
hematic crusts in the oral cavity and on the lips were so painful
that it was difficult for the patient to open her mouth and eat.
The leukocyte and platelet counts reached their lowest level:
2.8x10
3
/mL (280 lymphocytes) and 83x10³/mL, respectively.
After seven days of illness, the exanthema started to recede
and they were limited to the wrists. It was the first day without
fever. There was not complete remission of purpura; a few
crusts on the lips were still painful.
Serological tests were performed during hospitalization.
Serology for viral hepatitis A, B and C, syphilis, Epstein-Barr
virus, rubella, enterovirus, toxoplasmosis, Chagas disease,
HIV and cytomegalovirus, excluded recent
infections. A serum
sample was collected for dengue serology on the seventh
day of illness, with a negative result. We then considered the
possibility of papular-purpuric “gloves and socks” syndrome,
whose principal etiological agent is human parvovirus B19.
www.bjid.com.br
BJID 2006; 10 (February) 63
The ELISA test for B19 virus was positive for IgM and IgG
antibody using a commercial assay (Biotrim Inc.). The
presence of B19 DNA were first screened by a nested
polymerase-chain-reaction assay for amplification of the NS1
encoding region, with external primers designed P1 and P6
and internal primers P2 and P5 [4]. Phylogenic analysis of the
VP2 gene indicated that the Br572 B19 strain from this Brazilian
patient had a high degree of homology with other published
B19 sequences [5] (Figure 1).
Eleven days after admission, the patient was discharged
in good condition, without fever for five days, along with
complete regression of the rash and the enanthema.
A new laboratory exam was made after two months; the
results returned to normal. The platelet and leukocyte counts
were 201X10³/mL and 5.6X10³/mL (1960 lymphocytes),
respectively. The C-reactive protein was less than 5 mg/dL
and the coagulogram was normal. Serological tests showed
negativity for anti-B19 IgM and no B19 DNA was detected by
PCR analysis.
Discussion
Most cases of parvovirus B19 infection are asymptomatic.
The most common clinical presentations include
dermatological involvement, such as erythema infectiosum
(or fifth disease), hematological findings such as transient
aplastic crisis or chronic anemia in the immunocompromised
host, rheumatological manifestations, such as arthritis without
joint destruction, and if infection occurs during pregnancy,
B19 may lead to miscarriage or hydrops fetalis [2].
Although parvovirus B19 is usually transmitted by the
respiratory route, administration of contaminated blood and
plasma-derived products, particularly clotting factors, can also
result in transmission [2]. It is mildly contagious and infection
may occur sporadically or in epidemics. Hospital workers have
not been found to be at high risk of infection during endemic
periods. However, hospital acquisition and transmission have
been reported after exposure to patients with acute infection.
Serological or DNA evidence of B19 has been reported in
some patients with necrotizing vasculitis, Kawasaki’s disease,
Henoch-Schönlein purpura, giant-cell arteritis, hepatitis and
myocarditis [1]. The papular-purpuric “gloves and socks”
syndrome is a rare manifestation of B19 infection.
Harms et al. first described the clinical features of PPGSS
in 1990 [6], but the etiological association with HPV B19 became
known in 1991, when IgM anti-B19 was detected in a patient’s
serum [7]. Most cases of PPGSS occur in young adults, and it
equally affects men and women, during spring and summer
seasons [8,9]. Likely other manifestations, the reasons for
this predominance are unknown.
The clinical manifestations of PPGSS consist of
progressive painful and pruritic symmetric swelling and
erythema of the hands and feet in a gloves-and-socks
distribution, and association with oral lesions and fever.
Lesions extend to the wrists and ankles. Exanthema may be
less frequently involved, including on the cheeks, elbows,
knees, the inner side of thighs, and buttocks. Mucosal
involvements can include petechiae on the hard palate,
vesiculopustules on the hard and soft palates, pharyngeal
erythema, small erosions on the oral mucosa, and swollen
lips. Lymphadenopathy is a common feature, but it was not
present in our patient. Laboratory findings include leukopenia,
anemia, thrombocytopenia and elevated liver enzyme levels.
The erythrocyte sedimentation rate and C-reactive protein
level are infrequently increased [8,10,11]. We observed a
prominent lymphopenia in our patient.
Parvovirus B19 is the principal etiological agent of PPGSS.
Other viral agents, such as cytomegalovirus, measles virus,
coxsackie B6, Epstein-Barr, rubella, human herpes virus types
6 and 7, and hepatitis B have been associated with this
syndrome [11, 12, 13]. Parvovirus B19 can be demonstrated as
the etiological agent by seroconversion after performing viral
serological tests, or B19-DNA can be identified by PCR in the
serum or in cutaneous biopsy specimens [11].
In several B19-related PPGSS cases, B19-specific IgM
antibody was not detected in the serum at the time of the
initial clinical features [13]. In our case, the serological test
was positive for B19-specific IgG and IgM; the nested-PCR
detected B19 DNA, as also found in other cases [11,12,14].
The nucleotide sequence of our isolate, when compared with
other genotypes, confirmed the presence of B19; the genomic
variability in the region encoding VP2 differ by conspicuously
little in their sequences [5].
Parvovirus B19 infection can be associated with a wide
spectrum of human illnesses that range from an asymptomatic
condition to life-threatening disease, but the full spectrum of
this virus-induced disease is not totally defined. To summarize,
PPGSS is a rare cause of dermatosis, and parvovirus B19 is
Figure 1. Dendrogram showing the genetic relation of the BR
572 isolate of parvovirus B19 based on the VP2 coding region,
compared with other parvoviruses
Papular-Purpuric “Gloves and Socks” Syndrome
www.bjid.com.br
64 BJID 2006; 10 (February)
the principal etiological agent. This infection is usually brief
and self-limiting, and it can affect previously healthy patients.
References
1. Young N.S., Brown K.E. Parvovirus B19. N Engl J Med
2004;350:586-97.
2. Wiss K., Brown T.J. Parvovirus B19. In: Tyring S.K.
Mucocutaneous manifestations of viral diseases. New York:
Marcel Dekker, Inc., 2002.
3. Anderson M.J. Parvoviruses as Agents of Human Disease. Prog.
Med Virol 1987;34:55-69.
4. Durigon E.L., Erdman D.D., Gary G.W., et al. Multiple primer
pairs for polymerase chain reaction (PCR) amplification of human
parvovirus B19 DNA. J Virol Methods 1993; 44:155-65.
5. Erdman D.D., Durigon E.L., Wang Q.Y., Anderson L.J. Genetic
diversity of human parvovirus B19: sequence analysis of the
VP1/VP2 gene from multiple isolates. J Gen Virol
1996;77:2767-74.
6. Harms M., Feldmann R., Saurat J.H. Papular-purpuric “gloves
and socks” syndrome. J Am Acad Dermatol 1990;23:850-4.
7. Bagot M., Revuz J. Papular-purpuric “gloves and socks”
syndrome: primary infection with parvovirus B19? J Am
Acad Dermatol 1991;25:341-2.
8. Borradori L., Cassinotti P., Perrenoud D., et al. Papular-
purpuric “gloves and socks” syndrome. Int J Dermatol 1994;
33:196-7.
9. Veraldi S., Rizzitelli G., Scarabelli G., et al. Papular-purpuric
“glove and socks” syndrome. Arch Dermatol 1996;132:975.
10. Alfradley A, Aljubran A, Hainau B, Alhokail A. Papular-purpuric
“gloves and socks” syndrome in a mother and daughter. J Am
Acad Dermatol. 2003;48:941-4.
11. Sklavounou-Andrikopoulou A., Lakovou M., Paikos S., et al.
Oral manifestations of papular-purpuric ‘gloves and socks’
syndrome due to parvovirus B19 infection: the first case
presented in Greece and review of the literature. Oral Dis
2004;10:118-22.
12. Passoni L.F., Ribeiro S.R., Giordani M.L., et al. Papular-
purpuric “gloves and socks” syndrome due to parvovirus
B19: report of a case with unusual features. Rev Inst Med
Trop Sao Paulo 2001;43:167-70.
13. Smith P.T., Landry M.L., Carey H., et al. Papular-purpuric
gloves and socks syndrome associated with acute parvovirus
B19 infection: case report and review. Clin infect Dis
1998;27:164-8.
14. Aractingi S., Bakhos D., Flageul B., et al. Immunohistochemical
and virological study of skin in the papular-purpuric gloves
and socks syndrome. Br J Dermatol 1996;135:599-602.
Papular-Purpuric “Gloves and Socks” Syndrome