VERRUCAE (WARTS)
Verrucae are one of the most frequently encountered viral infections in humans. They are capable of causing disease in any individual, but severe infections seem to be more likely in those who are immunocompromised. Warts can affect any cutaneous surface, and unique wart subtypes are more prone to cause disease in different clinical locations. By far the most important aspect of infection with the human papillomavirus (HPV) is the ability of the virus to cause malignant transformation. This malignant potential is specific to certain subtypes and is especially a concern in women, who are at risk for cervical cancer. Most cases of cervical cancer can be traced to prior infection with certain HPV strains. In June 2006, the U.S. Food and Drug Administration approved the use of a prophylactic HPV vaccine in prepubertal girls. The vaccine is a recombinant quad-rivalent vaccine against HPV types 6, 11, 16, and 18. Types 16 and 18 are believed to have been responsible for up to 70% of cervical cancers.
Clinical
Findings: Verruca vulgaris, also called the common wart, is the most prevalent wart that infects the human. It can
be located on any cutaneous surface. These warts often appear as small papules
with a rough surface studded with pinpoint, dark purple to black dots. These
dots represent the thromboses of the tiny capillaries within the wart. Most
warts are between 5 mm and 1 cm in diameter, but some can become quite large
and encompass much larger areas of the skin. The coalescence of multiple warts
into one larger wart is called mosaic warts. These are most commonly seen on
the plantar aspect of the foot. Verruca vulgaris can come in many sizes and
shapes. Most lesions spontaneously resolve within a few years. A good rule of
thumb is that 50% of verrucae will disappear spontaneously in 2 years. Many
distinctive clinical forms of warts exist.
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| HUMAN PAPILLOMAVIRUS (HPV) INFECTION |
The filiform
wart is represented by a small verrucal papule with finger-like projections
extruding from the base of the papule. The projections are typically 1 to 2 mm
thick and 4 to 7 mm long. They are commonly found on the face. The flat wart is
frequently encountered and manifests as a 3- to 5-mm, flat papule with a slight
pink to red to purple coloration. Flat warts are frequently seen on the legs of
women and in the beard region of men, and they can be arranged in a linear
pattern if the warts are spread during the act of shaving. Flat warts have been
found to be highly associated with HPV types 3 and 10.
Plantar
warts (myrmecia) are seen on the plantar aspect of the foot and are caused for
the most part by HPV types 1, 2, and 4. They are deep-seated papules and
plaques that may coalesce into large mosaic warts.
The warts
are well defined and characteristically interrupt the skin lines. This is in
contrast to a callus, in which the skin lines are retained, and this sign can
be used to differentiate the two conditions. Plantar warts can cause pain and
discomfort if they are located in areas of pressure such as the heels or across
the skin underlying the metatarsal heads. Palmar warts are very similar to
plantar warts and have the same clinical appearance.
Subungual
and periungual warts, a subclassification of palmar/plantar warts, are found
around and under the nail apparatus. These warts can cause nail dystrophy and
pain on grasping of objects. They tend to affect more than one finger and can
be more difficult to treat than the common wart. Long-standing periungual or
subungual warts that have a changing morphology should be biopsied to rule out
malignant transformation into a squamous cell carcinoma. This is not infrequently encountered,
and a high clinical suspicion should be used when investigating these types of
warts. Ring warts are seen after various treatments of common warts, most
frequently after liquid nitrogen therapy. The central portion of the wart
resolves, leaving a ring-shaped or donut-shaped wart with central clearing.
These warts can become larger than the wart originally treated.
Condylomata
acuminata (genital warts) are often considered to be the most common form of
sexually transmitted disease in the United States. These warts typically begin
as small, flesh-colored to slightly hyper-pigmented macules and papules. As
they grow, they take on an exophytic growth pattern and have often been
compared with the appearance of cauliflower. The warts may stay small and
localized, or they may grow to enormous size, leading to difficulty with
urination and sexual intercourse. Females with cervical genital warts are
asymptomatic and may not realize they are infected. Routine gynecological
examinations and Papanicolaou smears are the only reliable way to diagnosis
cervical warts. Diagnosis is extremely important, because cervical warts are
the number one cause of cervical cancer.
Histology:
Skin
biopsies of wart tissue show the pathognomonic cell called the koilocyte. This cell,
when present, is highly specific and sensitive for HPV infection. It is a
keratinocyte with a basophilic small nucleus and a surrounding clear halo.
There are few to no keratohyalin granules in the koilocyte. Other findings
include varying amounts of hyperkeratosis, acanthosis, and striking
papillomatosis.
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| CONDYLOMATA ACUMINATA (GENITAL WARTS) |
Pathogenesis:
Warts
are caused by infection with HPV, of which more than 150 subtypes are known to
cause human disease. They are small viruses with no lipid envelope, and they
can stay viable for long periods. HPV has a double-stranded, circular DNA. A
variety of subtypes are able to affect different regions of the body. HPV is
capable of infecting human epithelium, including the keratinized skin and the
mucous membranes. It gains entry through slightly abraded skin or mucous
membranes. The virus does not actively infect the outer stratum corneum but
rather the stratum basalis cells. Like most viruses, HPV can produce early and
late gene products. The early genes encode various proteins necessary for replication.
These early gene products also play a role in malignant transformation of the
infected cell. The exact mechanism is not completely understood. The late genes
produce capsid proteins. At least eight early genes are present, and two late
genes are included in the viral DNA.
Treatment:
Common
warts can be treated in a number of ways. Approximately 50% of the lesions spontaneously resolve.
The others may or may not respond to therapy. This lack of universal treatment
response is frustrating to patient and physician alike. Many destructive
therapies are available, including liquid nitrogen cryotherapy, salicylic acid,
trichloracetic acid, cantharidin, podophyllin, and bleomycin. Immunotherapy can
be used to induce an immunological response; these options include imiquimod,
interferon, squaric acid, and Candida skin test antigen. No single therapy appears to work
better than any other, and patients often need to undergo a variety of
treatments until they find one that works.
Genital
warts should be treated with imiquimod or one of the destructive methods to
decrease the risk of transmission. Women who are sexually active should undergo
routine gynecological screening. The advent of the HPV vaccine may lead to a d
creased incidence of
genital warts and cervical cancer.
