Professional Documents
Culture Documents
19
Alphavirus
In Finland, Sindbis virus infection is transmitted by the Culiset
396
a
mosquito. An eruption of multiple, erythematous, 24 mm
papules with a surrounding halo is associated with fever and
prominent arthralgias. The eruption and symptoms resolv
e
over a few weeks. Histologically, the skin lesions show a
perivascular lymphocytic infiltrate with large atypical cells
,
simulating lymphomatoid papulosis. CD30 does not stain the
large cells, however, allowing their distinction.
Chikungunya virus is transmitted by the Aedes mosquit
o.
Chikungunya is from the Makonde language of subSaharan
Africa and means that which bends up, describing the char
acteristic stooped posture due to the joint symptoms of
the
disease. It is endemic in Africa, India, Sri Lanka, Southe
ast
Asia, the Philippines, Hong Kong, and the islands of the Indian
Ocean. The incubation period is 27 days. The patient present
s
Papovavirusgroup
occur in the oral, penoscrotal, and less commonly the axillary cant percentage of patients with Chikungunya virus infection
affects the ar regions. These may be preceded by intense erythema and pai (approaching 100% of those with a rash), and are rare in
n
patients with dengue. Neutropenia is seen in 80% of dengue
ms, upper tr in the affected area. Following acute Chikungunya infection,
patients and only 10% of Chikungunya patients. A positive
tourniquet test does not distinguish these two infections, but
unk, and fac hyperpigmentation of the skin may occur.
A
bullous
eruption
may
occur
in
acute
Chikungunya
virus
thrombocytopenia is more common in dengue (85%) as com
e. It can be c
infection. Ninety percent of those with a bullous eruption are pared with Chikungunya (35%).
onfluent and under 1 year of age, and most of the severe bullous eruption
BandyopadhyayD,etal:MucocutaneousfeaturesofChikungunyafever:
islands of sp cases occur in children under the age of 6 months. Seventeen astudyfromanoutbreakinwestBengal,India.IntJDermatol2008;
aring can be percent of children develop a vesiculobullous component t 47:1148.
seen. It appe o
BorgheriniG,etal:OutbreakofChikungunyaonReunionIsland:early
ars by the se their eruption, compared to only 3% of adults. There is a clinicalandlaboratoryfeaturesin157adultpatients.ClinInfecDis
2007;44:1401.
cond day of n
the fever in initial exanthem, followed in hours or days by flaccid or tense BottieauE,etal:Feverafterastayinthetropics.Medicine2007;
more than nonhemorrhagic blisters that rupture easily. Nikolskys sign is 86:18.
half of patie positive. The genitalia, palms, and soles are spared. There is a ChenTC,etal:Denguehemorrhagicfevercomplicatedwithacute
idiopathicscrotaledemaandpolyneuropathy.AmJTropMedHyg
nts, and in close resemblance to toxic epidermal necrolysis (TEN) and up
2008;78:8.
another 20 to 80% of the total body surface area may become denuded.
delaC,SierraB,etal:Race:ariskfactorfordenguehemorrhagic
%
High titers of virus are recovered from blister fluid (in excess
fever.ArchVirol2007;152:533.
on the third of what is present in blood). Biopsy demonstrates an intr DelGiudiceP,etal:SkinmanifestationsofWestNilevirusinfection.
or fourth d a
Dermatol2005;211:348.
ay; only ab epidermal blister with acantholytic cells freefloating in the DionisioD,etal:Epidemiological,clinicalandlaboratoryaspectsof
sandflyfever.CurrOpinInfectDis2003;16:383.
out onefifth blister cavity. These patients are managed like burn patients
GonzalezD,etal:Classicaldenguehemorrhagicfeverresultingfrom
develop the and most recover. Skin grafting is usually not required.
eruption aft The diagnosis of Chikungunya virus infection is made b twodengueinfectionsspaced20yearsormoreapart:Havana,
dengue3epidemic,20012002.IntJInfectDis2005;5:280.
er the fifth y
HochedezP,etal:Chikungunyainfectionintravelers.EmerInfDis2006;
day of the i detecting virusspecific IgM in the serum. Confirmation is
12:1565.
llness. Ecch with seroconversion over the next several months, with devel HochedezP,etal:Managementoftravelerswithfeverandexanthema,
ymoses may opment of virusspecific IgG. PCRbased methods may detect
notablydengueandChikungunyainfections.AmJTropMedHyg
appear durin viral genome in the blisters or serum during the acute illness. 2008;87:710.
g the acute il It may be quite difficult to differentiate dengue fever from
InanadarAC,etal:CutaneousmanifestationsofChikungunyafever:
observationsmadeduringarecentoutbreakinSouthIndia.IntJ
lness. Aphth Chikungunya fever, since they are both endemic in the same
Dermatol2008;45:154.
ouslike ulcer geographic regions, and their clinical symptoms and labora
ItodaI,etal:Clinicalfeaturesof62importedcasesofdenguefeverin
ations can tory findings are quite similar. Arthralgias occur in a signifi
Japan.AmJTropMedHyg2006;75:470.
Papovaviruses are doublestranded, naked DNA viru
LupiO,TyringSK:Tropicaldermatology:viraltropicaldiseases.JAm
AcadDermatol2003;49:979.
Martyn-SimmonsCL,etal:Afloridskinrashinareturningtraveller.
Clin
ExpDermatol2007;32:779.
NicolettiL,etal:Chikungunyaanddenguevirusesintravelers.Emer
InfecDis2008;14:177.
PistoneT,etal:ClusterofChikungunyavirusinfectionintravelers
returningfromSenegal,2006.JTravMed2009;16:286.
Radakovic-FijanS,etal:DenguehemorrhagicfeverinaBritishtravel
guide.JAmAcadDermatol2002;46:430.
RajapakseS,etal:AtypicalmanifestationofChikungunya
infection.
TransRSocTropMedHyg2009;Aug26(Epubaheadofprint).
RobinS,etal:Severebullousskinlesionsassociatedwith
Chikungunya
virusinfectioninsmallinfants.EurJPediatr2009Aug19(Epubahead
ofprint).
SaadiahS,etal:Skinhistopathologyandimmunopathologyarenotof
prognosticvalueindenguehaemorrhagicfever.BrJDermatol
2008;
158:836.
SimonR,etal:Anemergingrheumatismamongtravelersreturned
from
IndianOceanislands:reportof47cases.Medicine2007;86:
123.
SinghS,etal:DenguefeverandKawasakidisease:aclinicaldilemma:
RheumatolInt2009;29:717.
SolignatM,etal:ReplicationcycleofChikungunya:areemerging
arbovirus.Virology2009;Sep2(Epubaheadofprint).
SolomonT:Flavivirusencephalitis.NEnglJMed2004;351:370.
ThomasEA,etal:Cutaneousmanifestationsofdengueviralinfection
in
Punjab(northIndia).IntJDermatol2007;46:715.
ValassinaM,etal:AMediterraneanarbovirus:theToscana
virus.J
Neurovirol2003;9:577.
Papovavirusgroup
ses char
acterized as slowgrowing. They replicate inside the
nucleus.
Because they contain no envelope, they are resista
nt to drying,
freezing, and solvents. In addition to the huma
n papilloma
viruses (HPVs), which cause warts, papillomaviruse
s of rabbits
and cattle, polyomaviruses of mice, and vacuolatin
g viruses of
monkeys are some of the other viruses in this grou
p.
Warts(verruca)
There are more than 100 types of HPV. The genome
of HPV
consists of early genes (E1, E2, E4, E5, E6, and E7),
two late
genes (L1 and L2), and in between an upstrea
m regulatory
region (URR). L1 and L2 code for the major and min
or capsid
proteins. A new HPV type is defined when there is l
ess than
90% DNA homology with any other known type in t
he L1 and
E6 genes. Viruses with 9098% homologies are
classified as
subtypes. The gene sequences from HPVs throu
ghout the
world are similar. Most HPV types cause specifi
c types of
warts and favor certain anatomic locations, suc
h as plantar
w
a
r
Verruca vulgaris
Common warts are a significant cause of concern and frustra
tion on the part of the patient (Figs 1943 and 1944).
Social
ViralDiseases
397
19
Fig.19-44 Verruca,nailbiterwithperiungualwarts.
398
Papovavirusgroup
lesions with
Common warts may occur anywhere on the skin, apparentl
similar surfa y
ce character spreading from the hands by autoinoculation. In nail bite
(e.g. seborrh rs,
eic kerato
warts may be seen on the lips and tongue, usually in t
sis). In som he
e instances, middle half, and uncommonly in the commissures. Digitate or
a single wafiliform warts tend to occur on the face and scalp, and present
rt (mother as single or multiple spikes stuck on the surface of the skin.
wart) appea
Fig.19-45 Verrucaplana,atopicdermatitisinfectedwithnumerous
Pigmented warts
rs
flatwarts.
and grows sl Pigmented warts have commonly been reported in Japan.
owly for a lo They appear on the hands or feet, and resemble common war
ng time, and ts
or plantar warts, except for their hyperpigmentation. They are
then suddenl
caused by HPV4, 65, and 60. The pigmentation is due to
y many
melanocytes in the basal cell layer of the HPVinfected tissue,
new warts er
which contain large amounts of melanin. This is proposed to
upt. On the s
be caused by melanocyte blockade or the inability of the
urface of the
melanocytes to transfer melanin to the HPVinfected cells.
wart, tiny bl
ack dots
Flat warts (verruca plana)
may be visib
HPV3, 10, 28, and 41 most often cause flat warts. Children
le, represent
and young adults are primarily affected. Sun exposure appears
ing thrombo
to be a risk factor for acquiring flat warts. They are common
sed, dilated
on swimmers and on the sunexposed surfaces of the face and
capillaries.
lower legs. Flat warts present most typically as 24 mm flat
Trimming t
topped papules that are slightly erythematous or brown on
he surface
pale skin and hyperpigmented on darker skin. They are gener
keratin mak
ally multiple and are grouped on the face, neck, dorsa of the
es the cap
hands, wrists, elbows, or knees (Fig. 1945). The forehead,
illaries mor
cheeks, and nose, and particularly the area around the mouth
e
and the backs of the hands are the favorite locations. In men
prominent a
who shave their beards and in women who shave their legs,
nd may be u
numerous flat warts may develop as a result of autoinocula
sed as an ai
tion. A useful finding is the tendency for the warts to
d in diagnosi
Koebnerize, forming linear, slightly raised, papular lesions.
s. Warts do
Hyperpigmented lesions occur, and when scarcely elevated,
not have d
may be confused with lentigines or ephelides. Plaquelike
ermatoglyph
lesions may be confused with verrucous nevus, lichen planus,
ics (fingerpr
and molluscum contagiosum. When lesions occur only on the
int folds), a
central face and are erythematous, they can be easily confused
s opposed t
with papular acne vulgaris. Of all clinical HPV infections, flat
o
warts have the highest rate of spontaneous remission.
calluses, in
which these
Plantar warts (verruca plantaris)
lines are acc
HPV1, 2, 4, 27, and 57 cause plantar warts. These warts gener
entuated.
ally appear at pressure points on the ball of the foot, especially
over the midmetatarsal area. They may, however, be any
where on the sole. Frequently, there are several lesions on one
foot. Sometimes they are grouped or several contiguous warts
Flat warts
fuse so that they appear as one. Such a plaque is k
Fig.19-46 Myrmecia.
nown as a
mosaic wart. The soft, pulpy cores are surrounded
by a firm,
horny ring. Over the surface of the plantar wart, m
ost clearly
if the top is shaved off, multiple small black p
oints may be
s
e
en that represent dilated capillary loops within elongate Flat warts frequently undergo spontaneous remission,
d
so
dermal papillae. Plantar warts may be confused with corns o
therapy should be as mild as possible and potentially scarring
r
calluses, but have a soft central core and black or ble therapies should be avoided. If lesions are few, light cry
o
eding
points when pared down, features that calluses do not have. therapy is a reasonable consideration. Topical salicylic aci
d
The myrmecia type of verruca occurs as smoothproducts can also be used. Treatment with topical tretinoi
surfaced,
deep, often inflamed and tender papules or plaques, m n
once or twice a day, in the highest concentration tolerated to
ostly
on the palms or soles, but also beside or beneath the nails, produce mild erythema of the warts without frank dermatitis,
can be effective over several months. Tazarotene cream or gel
or,
less often, on the pulp of the digits (Fig. 1946). They are dis may also be effective. Imiquimod 5% cream used up to once a
tinctively domeshaped and much bulkier beneath the surfac day can be effective. If the warts fail to react initially to
the
e
than they appear. Myrmecia are caused by HPV1. They can imiquimod, tretinoin may be used in conjunction. Should this
fail, 5FU cream 5%, applied twice a day, may be very effec
be mistaken for a paronychia or digital mucinous cyst.
HPV60 causes a peculiar type of plantar wart called tive. Anthralin, although staining, could be similarly used for
its irritant effect. For refractory lesions, laser therapy in very
a
ridged wart because of the persistence of the dermatoglyphi low fluences or photodynamic therapy might be considere
d
cs
across the surface of the lesion. Typically, the warts are slig before electrodesiccation because of the reduced risk of scar
ring. Ranitidine, 300 mg twice a day, cleared 56% of refractory
htly
elevated, skincolored, 35 mm papules. They occur on non flat warts in one study. Cimetidine alone or with levamisole
weightbearing areas and lack the typical features of plantar may be considered. Topical immunotherapy with dinitrochlo
warts. HPV60 also causes plantar verrucous cysts, 1.52 cm, robenzene (DNCB), squaric acid, or dyphencyprone, or intra
epitheliumlined cysts on the plantar surface. These cysts te lesional Candida antigen injections, can be used on limite
d
nd
to occur on weightbearing areas, suggesting that H areas of flat warts. The induced dermatitis requires caref
ul
PV
infected epidermis is implanted into the dermis, forming the dose monitoring when treating facial lesions.
cyst. It is common to see ridged warts near plantar verrucou Common warts
s
Treatments for common warts involve two basic approaches:
cysts.
destruction of the wart and induction of local immune reac
Histologic features
tions (immunotherapy). Destructive methods are most co
Typical nongenital warts rarely require histologic confirm m
monly used as initial therapy by most practitione
a
rs.
tion. A biopsy may be useful in several settings, howevCryotherapy is a reasonable firstline therapy for most common
er.
warts. The wart should be frozen adequately to produce
Histology can be used to distinguish warts from corns a
and
blister after 1 or 2 days. This correlates with a thaw time of
other keratotic lesions that they resemble. This is enhanced 3045 s for most common warts. A sustained 10 s freeze with
by
a spray gun was found to be more effective than simply
immunoperoxidase staining for HPV capsid antigen. Cytologi freezing to obtain a 23 mm halo around the wart. Aggressive
c
cryotherapy can produce significant blistering and may be
atypia and extension into the dermis suggest the diagnosis complicated by significant postprocedural pain for several
of
days. BerthJones et al found that a single freezethaw cycle
an HPVinduced squamous cell carcinoma. There is a correla was as effective as two cycles. The ideal frequency of treatme
tion between HPV type and the histologic features of the warnt
t,
is every 2 or 3 weeks, just as the old blister peels off. A spray
allowing identification of the HPV types that cause specdevice, while more costly, is quicker, and cannot spread infec
ific
tious diseases (especially viral hepatitis) from one patient
lesions, a useful feature in the diagnosis of epidermodysplas to the next. Children may be frightened by such a devic
ia
399
e,
verruciformis, for example.
so a cottontipped swab is an option for them.
Cryotherapy
can be effective for periungual warts. Damage to the matrix is
The form of therapy used depends on the type of wart being unusual or rare, since periungual warts usually affect the
treated, age of the patient, and previous therapies use lateral nailfolds, not the proximal one. Complications of cryo
d and
therapy include hypopigmentation, uncommonly scarring
their success or failure. With any treatment modality at leas ,
t
and rarely, damage to the digital nerve from freezing too
2 or 3 months of sustained management by that meth deeply on the side of the digit. Patients with Fanconi anemia,
od is
cryoglobulinemia, poor peripheral circulation, and Raynaud
considered a reasonable therapeutic trial. Do not abandon a may develop severe blisters when cryotherapy is used to treat
ny
their warts. Doughnut warts, with central clearing and an
treatment too quickly. Since many nongenital warts will spo annular recurrence, may complicate cryotherapy.
n
Products containing salicylic acid with or without lactic acid
taneously regress, the treatment algorithm should allow are effective patientapplied treatments; these have an efficac
for
y
nonaggressive options and the patient should be offered the
Treatment
warts recurred.
Bleomycin has high efficacy and is an important treatment
for recalcitrant common warts. It is used at a concentra
tion
of 1 U/mL, which is injected into and immediately benea
th
the wart until it blanches. The multiple puncture techniq
ue
of Shelleydelivering the medication into the wart by
mul
tiple punctures of the wart with a needle through a drop of
bleomycinmay also be used, as may an air jet injector. For
small warts (less than 5 mm), 0.1 mL is used; 0.2 mL is used
for larger warts. The injection is painful enough to requir
e
local anesthesia in some patients. Pain can occur for up
to
1 week. The wart becomes black, and the black eschar sepa
rates in 24 weeks. Treatment may be repeated every 3 week
s,
but it is unusual for common warts to require more than one
or two treatments. Scarring is rare. Response rates vary
by
location, but average 90% with two treatments for
most
common, nonplantar warts, even periungual ones. Treatment
of finger warts with bleomycin may uncommonly be compli
cated by localized Raynaud phenomenon of treated finge
rs.
Bleomycin treatment of digital warts may rarely result in
digital necrosis and permanent nail dystrophy, so extrem
e
caution should be used in treating warts around the nailfolds.
Lymphangitis/cellulitis is a rare complication. In a patient
comparable to that of cryotherapy. After the wartaffected
ViralDiseases
19
400
Papovavirusgroup
Plantar warts
In general, plantar warts are more refractory to any form of
treatment than are common warts. Initial treatment usu
ally
involves daily application of salicylic acid in liquid, film,
or
plaster form after soaking. In failures, cryotherapy or cantha
ri
din application may be attempted, alone or in combination.
A
second freezethaw cycle is beneficial when treating
plantar
warts with cryotherapy. Bleomycin injections, laser thera
py,
or topical immunotherapy, as discussed above, may be used
in refractory cases. Surgical destruction with cautery or blun
t
dissection should be reserved for failures with nonscarri
ng
techniques, since a plantar scar may be persistently pa
inful.
CO2 laser may also result in plantar scars. Photodynami
c
therapy may be effective in some cases. The optimum phot
o
sensitizing agent and light source are unknown.
ViralDiseases
19
Papovavirusgroup
Fig.19-48 Genitalwarts,keratotictype.
Fig.19-50 Genitalwarts,bowenoidpapulosis.
Fig.19-51 GenitalBowensdisease.
402
Treatment
Because no effective virusspecific agent exists for the
treat
ment of genital warts, their recurrence is frequent. Treatmen
t
is not proven to reduce transmission to sexual partners or to
prevent progression to dysplasia or cancer. Specifically,
the
treatment of male sexual partners of women with genital wa
rts
does not reduce the recurrence rate of warts in these wome
n.
Therefore, the goals of treatment must first be discussed wit
h
the patient, and perhaps with his/her sexual partner.
Observation represents an acceptable option for some patie
nts
ViralDiseases
19
403
404