190 Part I Disorders Presenting in the Skin and Mucous Membranes 638 Part III Diseases Due to Microbial

638 Part III Diseases Due to Microbial Agents

Skin Tag ICD-9: 701.9 ICD-10: L91.8 Human Papillomavirus Infections

A skin tag is a very common, soft, skin-colored
or tan or brown, round or oval, pedunculated
papilloma (polyp) (Fig. 9-53); it is usually
constricted at the base and may vary in size from
>1 mm to as large as 10 mm. Occurring in the
middle aged and elderly.
Histologic findings include a thinned epidermis and
a loose fibrous tissue stroma.
Usually asymptomatic but occasionally may
become tender following trauma or torsion and
may become crusted or hemorrhagic.
More common in females and in obese patients
and most often noted in intertriginous areas
(axillae, inframammary, groin) and on the neck and
eyelids.
ICD-9: 079.4 ICD-10: B97.7
It occurs in acanthosis nigricans and metabolic
syndrome.
May be confused with a pedunculated seborrheic
keratosis, dermal or compound melanocytic nevus,
solitary neurofibroma, or molluscum contagiosum.
Lesions tend to become larger and more
numerous over time, especially during pregnancy.
Following spontaneous torsion, autoamputation
can occur.
Management is accomplished with simple
snipping with scissors, electrodesiccation, or
cryosurgery.
Synonyms: Acrochordon, cutaneous papilloma,
soft fibroma.
HPV are ubiquitous in humans, causing:
Subclinical infection
Wide variety of benign clinical lesions on skin
and mucous membranes.
Cutaneous and mucosal premalignancies
(Table 27-1): Squamous cell carcinoma in situ
(SCCIS); invasive SCC
More than 150 types of HPV have been identified
and are associated with various clinical lesions and
diseases. Papillomaviruses infect all mammalian
species as well as birds, reptiles, and others.
Cutaneous HPV infections occur commonly in
the general population:
Common warts: Represent approximately 70%
of all cutaneous warts, occurring in up to 20%
of all school-age children.
Butchers warts: Common in butchers, meat
packers, fish handlers.
Plantar warts: Common in older children
and young adults, accounting for 30% of
cutaneous warts.
Flat warts: Occur in children and adults,
accounting for 4% of cutaneous warts.
Oncogenic HPV can cause SCCIS and invasive
SCC with host defense defects.
Epidermodysplasia verruciformis (EDV).
Anogenital HPV infections.
External genital wart: most prevalent sexually
transmitted infection (see Section 30).
Squamous Cell Carcinoma. Some HPV types
have a major etiologic role in the pathogenesis of
in situ as well as invasive SCC of the anogenital
epithelium.
During delivery, maternal genital HPV infection
can be transmitted to the neonate, resulting in
anogenital warts and respiratory papillomatosis
after aspiration of the virus into the upper
respiratory tract.

TABLE 27-1 CORRELATION OF HUMAN PAPILLOMAVIRUS TYPE WITH DISEASE

Disease Associated HPV Types

Plantar warts 1,* 2, 4, 63

Myrmecia 60
Common warts 1,* 2,* 4, 26, 27, 29, 41, 57, 65, 77
Common warts of meat handlers 1, 2,* 3, 4, 7,* 10, 28
Flat warts 3,* 10,* 27, 38, 41, 49, 75, 76
Intermediate warts 10,* 26, 28
Epidermodysplasia verruciformis 2,* 3,* 5,* 8,* 9,* 10,* 12,* 14,* 15,* 17,* 19, 20, 21, 22, 23, 24, 25,
36, 37, 38, 47, 50
Condyloma acuminatum 6,* 11,* 30, 42, 43, 44, 45, 51, 54, 55, 70
Intraepithelial neoplasias
Figure 9-53. Skin tags Soft skin-colored and tan pedunculated papillomas. These are very common in the elderly Unspecified 30, 34, 39, 40, 53, 57, 59, 61, 62, 64, 66, 67, 69, 71
obese and are obligatory lesions in acanthosis nigricans, as in this patient. Low-grade 6,* 11,* 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 74
High-grade 6, 11, 16,* 18,* 31, 33, 34, 35, 39, 42, 44, 45, 51, 52, 56, 58, 66,
Cervical carcinoma 16,* 18,* 31, 33, 35, 39, 45, 51, 52, 56, 58, 66, 68, 70
Laryngeal papillomas 6,* 11*
Focal epithelial hyperplasia of Heck 13,* 32*
Conjunctival papillomas 6,* 11,* 16*
Others 6, 11, 16, 30, 33, 36, 37, 38, 41, 48, 60, 72, 73

*Most common associations.

High malignant potential.
Note: Additional information on new HPV types can be found on the HPV Sequence Data Base through the
Internet (hpv-web.lanl.gov).
Section 27 Viral Diseases of Skin and Mucosa 639 640 Part III Diseases Due to Microbial Agents

Etiology HPV type. HPV are normally grouped accord-

Papillomaviruses are double-stranded DNA
viruses of the papovavirus class, which infect
most vertebrate species with exclusive host
and tissue specificity. Infections are restricted
squamous epithelia of skin and mucous mem-
branes. Clinical lesions induced by HPV and
their natural history are largely determined by
ing to their pathologic associations and tis-
sue specificityeither cutaneous or mucosal.
Mucosal-associated HPV can be further sub-
grouped according to their risk of malignant
transformation. New types of HPV are defined
as possessing <90% homology to known types
in six specified early and late genes.

Human Papillomavirus: Cutaneous Diseases

Certain human HPV types commonly infect
keratinized skin.
Cutaneous warts are:
Discrete benign epithelial hyperplasia with
varying degrees of surface hyperkeratosis.
Manifested as minute papules to large
plaques.
Figure 27-12. Verruca vulgaris: thumb A 25-year-old male with hyperkeratotic, verrucous papules on the dorsal
Lesions may become confluent, forming a mosaic.
thumb. The dark points represent thrombosed capillaries. The lesion resolved with electrodessication, having failed to
The extent of lesions is determined by the immune respond to cryosurgery.
status of the host.

dots (thrombosed capillaries). As with palmar tain acute types and in lesions over sites of
warts, normal dermatoglyphics are disrupted. pressure (metatarsal head).
Epidemiology Plantar Warts (Verruca Plantaris) Return of dermatoglyphics is a sign of resolu- Mosaic warts: Confluence of many small warts.
Early small, shiny, sharply marginated pap- tion of the wart. Warts heal without scarring. Kissing warts: lesion may occur on opposing
Transmission. Skin-to-skin contact. Minor Therapies such as cryosurgery and electrosur- surface of two toes (Fig. 27-17). Plantar foot,
trauma with breaks in stratum corneum facili- ule (Fig. 27-16) plaque with rough hyper-
keratotic surface, studded with brown-black gery can result in scarring at treatment sites. often solitary but may be three to six or more.
tates epidermal infection. Tenderness may be marked, especially in cer- Pressure points, heads of metatarsal, heels, toes.
Demography. Host defense defects are associ-
ated with an increased incidence of and more
widespread cutaneous warts: HIV disease, iat-
rogenic immunosuppression with solid organ
transplantation.
Epidermodysplasia Verruciformis. Autosomal-
recessive hereditary disorder. Acquired EDV-
like lesions seen in HIV disease.

Clinical Manifestation
Common Wart or Verruca Vulgaris
Firm papules, 110 mm or larger (Figs. 27-
1127-15), hyperkeratotic, clefted surface,
with vegetations. Isolated lesion, scattered
discrete lesions. Occur at sites of trauma:
hands, fingers, and knees. Palmar lesions dis-
rupt the normal line of fingerprints. Return of
fingerprints is a sign of resolution of the wart.
Characteristic red or brown dots, best visual-
ized with dermatoscope, are pathognomonic,
representing thrombosed dermal papilla capil-
lary loops.
Linear arrangement: inoculation by scratching.
Annular warts: at sites of prior therapy.
Butchers warts: large cauliflower-like lesions A B
on hands of meat handlers.
Filiform warts have relatively small bases, Figure 27-11. Verruca vulgaris on face A 3-year- Figure 27-13. Verruca vulgaris: hands A 20-year-old immunosuppressed male with nephrotic syndrome. Multiple
extending out with elongated cap (Fig. 27-11). old boy with common wart on the moustache area. verrucae on the (A) dorsum and (B) palm of the hand.
Section 27 Viral Diseases of Skin and Mucosa
Figure 27-14. Periungual warts A 77-year-old male with extensive periungual warts. He was depressed and picked
at periungual skin folds created portal of entry for HPV. Lesions resolved with hyperthermia.
Flat Warts (Verruca Plana)
Sharply defined, flat papules (15 mm); flat
surface; the thickness of the lesion is 12 mm
(Fig. 27-18). Skin-colored or light brown.
Round, oval, polygonal, linear lesions (inocu-
lation of virus by scratching). Occur on face,
beard area (Fig. 27-19), dorsa of hands, and
shins.
Epidermodysplasia Verruciformis
Autosomal-recessive condition. Flat-topped
papules. Tinea versicolor-like lesions, particu-
larly on the trunk. Color: skin-colored, light
brown, pink, hypopigmented. Lesions may
be numerous, large, and confluent. Seborrheic
keratosis-like and actinic keratosis-like lesions.
Linear arrangement after traumatic inocula-
tion. Distribution: face, dorsa of hands, arms,
legs, anterior trunk (Fig. 27-20). Premalignant
and malignant lesions arise most commonly on
face. SCC: in situ and invasive.
Host Defense Defects
(HIV disease, iatrogenic immunosuppres-
sion). HPV-induced warts are common (Fig.
27-21) and may be difficult to treat success-
fully. Some have atypical histologic features
641
and may progress to in situ and invasive
SCC.
Human Papillomavirus:
Oropharyngeal Diseases
HPV infects mucosal epithelial cells of the
mouth, nose, and airways (Fig. 27-21). Oral
infections may be subclinical or cause benign
or malignant oral neoplasms. In respiratory
or laryngeal papillomatosis, HPV 6 and 11 are
acquired during vaginal delivery and cause
warts of the oropharynx and upper airways.
Laryngeal lesions cause major morbidity. SCC
occurs in some persons.
Human Papillomavirus:
Anogenital Infections
See Section 30, Sexually Transmitted Diseases.
Differential Diagnosis
Verruca vulgaris molluscum contagiosum, seb-
orrheic keratosis, actinic keratosis, keratoacan-
thoma, SCCIS, invasive SCC.
Verruca plantaris callus, corn or keratosis,
exostosis.
642 Part III Diseases Due to Microbial Agents
sunlight.
Figure 27-15. Giant warts on hand and forearm.
A 51-year-old female with recalcitrant warts on hands
for 2 years. Immunodeficiency was suspected but not
detected.
Verruca plana, syringoma (facial), mollus-
cum contagiosum.
Epidermodysplasia verruciformis pityriasis
versicolor, actinic keratoses, seborrheic kera-
toses, SCCIS, basal cell carcinoma.
Laboratory Findings
Dermatopathology. Acanthosis, papillomatosis,
hyperkeratosis. Characteristic feature is foci of
vacuolated cells (koilocytosis), vertical tiers of
parakeratotic cells, and foci of clumped kerato-
hyaline granules.
Diagnosis. Usually made on clinical findings.
With host defense defects, HPV-induced SCC
at periungual sites or anogenital region should
be ruled out by lesional biopsy.
Course
In immunocompetent individuals, cutaneous
HPV infections usually resolve spontaneously,
without therapeutic intervention. With host
defense defects, cutaneous HPV infections may
be very resistant to all modalities of therapy.
With EDV, lesions first occur at 57 years of
age and increase in numbers progressively,
becoming widespread in some. About 3050%
of individuals with EDV develop malignant
cutaneous lesions on areas of skin exposed to
Treatment
Goal. Aggressive therapies, which are often
quite painful and may be followed by scarring,
Figure 27-16. Verruca plan-
taris: plantar feet A 71-year-
old male with chronic lymphatic
leukemia. Large and painful on
pressure, warts are seen on the
plantar feet and toes. Multiple
warts were also present on the
fingers. After many failed thera-
peutic modalities, he was suc-
cessfully treated with electron
beam radiation.
Section 27 Viral Diseases of Skin and Mucosa 643 644 Part III Diseases Due to Microbial Agents
Figure 27-17. Extensive verrucae A 49-year-old male with HIV disease has confluent warts
on the hands and feet. The large warts on opposing toes are referred to as kissing warts.
Figure 27-19. Filiform and flat warts A 38-year-old male with HIV disease has a conflu-
ence of lesions on face and beard area. Lesions resolved after successful antiretroviral therapy.
are usually to be avoided because the natural
history of cutaneous HPV infections is for spon-
taneous resolution in months or a few years.
Plantar warts that are painful because of their
location warrant more aggressive therapies.
Patient-Initiated Therapy. Minimal cost; no/
minimal pain.
For Small Lesions. 1020% salicylic acid and
lactic acid in collodion.
For Large Lesions. 40% salicylic acid plaster for
1 week, then application of salicylic acidlactic
acid in collodion.
Imiquimod Cream. At sites that are not thickly
keratinized, apply half-strength three times per
Figure 27-18. Verruca plana A 12-year-old male kidney transplant recipient. Multiple brown week. Persistent warts may require occlusion.
keratotic papules are seen on the forehead and scalp. Hyperkeratotic lesions on palms/soles should
be debrided frequently; Imiquimod used alter-
nately with a topical retinoid such as tazaro-
tene topical gel may be effective.
Hyperthermia for Verruca Plantaris. Hyperther-
mia with hot water [45C (113F)] immersion
for 20 minutes or three times weekly for up to
16 treatments is effective in some patients.
Clinician-Initiated Therapy. Costly, painful.
Cryosurgery. If patients have tried home thera-
pies and liquid nitrogen is available, light cryo-
surgery using a cotton-tipped applicator or
cryospray, freezing the wart and 12 mm of
surrounding normal tissue for approximately
30 seconds, is quite effective. Freezing kills the
infected tissue but not HPV.
Cryosurgery is usually repeated about every
4 weeks until the warts have disappeared.
Painful.
Section 27 Viral Diseases of Skin and Mucosa
Figure 27-20. EDV-like flat warts on chest A 44-year-old male with HIV disease had extensive flat wart-like lesions
on face, neck, trunk, abdomen.
Electrosurgery. More effective than cryosur-
gery, but also associated with a greater chance
of scarring. EMLA cream can be used for an-
esthesia for flat warts. Lidocaine injection is
usually required for thicker warts, especially
palmar/plantar lesions.
CO2 Laser Surgery. May be effective for recalci-
trant warts, but no better than cryosurgery or
645 646 Part III Diseases Due to Microbial Agents
electrosurgery in the hands of an experienced
clinician.
Surgery. Single, nonplantar verruca vulgaris:
curettage after freon freezing; surgical excision
of cutaneous HPV infections is not indicated in
that these lesions are epidermal infections.
Figure 27-21. Multiple oral condylomata in
HIV disease. Lesions resolved with antiretroviral
B
therapy.
Section 9 Benign Neoplasms and Hyperplasias 159

Pyogenic Granuloma ICD-9: 686.1 ICD-10: L98.0

Pyogenic granuloma is a rapidly developing
vascular lesion usually following minor trauma.
This is a very common solitary eroded vascular
nodule that bleeds spontaneously or after minor
trauma. The lesion has a smooth surface, with or
without crusts and with or without erosion (Fig.
9-17A). It appears as a bright red, dusky red,
violaceous, or brown-black papule with a collar of
hyperplastic epidermis at the base (Fig. 9-17B)
and occurs on the fingers, lips, mouth, trunk, and
toes.
Histopathology: lobular aggregates of proliferating
capillaries with edema and numerous neutrophils.
Thus, pyogenic granuloma is neither pyogenic
(associated with bacterial infection) nor a
granuloma.
Treatment is surgical excision or curettage with
electrodesiccation at the base.
The importance of pyogenic granuloma is that
it can be mistaken for amelanotic nodular
melanoma, and vice versa.

A B

Figure 9-17. Pyogenic granuloma (A) This is a solitary vascular nodule of recent onset that bleeds spontaneously
or after minor trauma. The lesions usually have a smooth surface, with or without crusts and with or without erosion.
(B) On palms and soles, they have a typical collar of thickened stratum corneum at the base. This collar can best be seen
when viewed from the side, as is the case here.