Background

Warts are benign proliferations of skin and mucosa caused by the human papillomavirus
(HPV). Currently, more than 100 types of HPV have been identified. Certain HPV types tend
to infect skin at particular anatomic sites; however, warts of any HPV type may occur at any
site. The primary clinical manifestations of HPV infection include common warts, genital
warts, flat warts, and deep palmoplantar warts (myrmecia). Less common manifestations of
HPV infection include focal epithelial hyperplasia (Heck disease),[1] epidermodysplasia
verruciformis, and plantar cysts. Warts are transmitted by direct or indirect contact, and
predisposing factors include disruption to the normal epithelial barrier.
Treatment is difficult, with frequent failures and recurrences. Many warts, however, resolve
spontaneously within a few years even without treatment.
A small number of high-risk HPV subtypes are associated with the development of
malignancies, including types 6, 11, 16, 18, 31, and 35. Malignant transformation most
commonly is seen in patients with genital warts and in immunocompromised patients. HPV
types 5, 8, 20, and 47 have oncogenic potential in patients with epidermodysplasia
verruciformis.

Pathophysiology
Warts can affect any area on the skin and mucous membranes. The HPV virus infects the
epithelium, and systemic dissemination of the virus does not occur. Viral replication occurs in
differentiated epithelial cells in the upper level of the epidermis; however, viral particles can
be found in the basal layer.

Epidemiology
Frequency
International
Warts are widespread in the worldwide population. Although the frequency is unknown,
warts are estimated to affect approximately 7-12% of the population. In school-aged children,
the prevalence is 10-20%. An increased frequency also is seen among immunosuppressed
patients and meat handlers.

Mortality/Morbidity
Common warts are usually asymptomatic, but they may cause cosmetic disfigurement or
tenderness. Plantar warts can be painful, and extensive involvement on the sole of the foot
may impair ambulation. Malignant change in nongenital warts is rare but has been reported
and is termed verrucous carcinoma.[2, 3, 4] Verrucous carcinoma is considered to be a slowgrowing, locally invasive, well-differentiated squamous cell carcinoma that may be easily
mistaken for a common wart. It can occur anywhere on the skin but is most common on the
plantar surfaces. Although this type of cancer rarely metastasizes, it can be locally
destructive.

Race
Although warts may affect any race, common warts appear approximately twice as frequently
in whites as in blacks or Asians.[5] Focal epithelial hyperplasia (Heck disease) is more
prevalent among American Indians and Inuit.[1]

Sex
Male-to-female ratio approaches 1:1.

Age
Warts can occur at any age. They are unusual in infancy and early childhood, increase in
incidence among school-aged children, and peak at 12-16 years.[6]

History
HPV is spread by direct or indirect contact. It can resist desiccation, freezing, and prolonged
storage outside of host cells. Autoinoculation also may occur, causing local spread of lesions.
The incubation period for HPV ranges from 1-6 months; however, latency periods of up to 3
years or more are suspected.

Physical
Physical findings for different types of nongenital warts are as follows:

Common warts: Common warts also are termed verruca vulgaris. They appear as
hyperkeratotic papules with a rough, irregular surface. They range from smaller than 1
mm to larger than 1 cm. They can occur on any part of the body but are seen most

commonly on the hands and knees (see image below).

Common wart on the hand.
Filiform warts: Filiform warts are long slender growths, usually seen on the face
around the lips, eyelids, or nares.
Deep palmoplantar warts (myrmecia)[7] : Deep palmoplantar warts also are termed
myrmecia. They begin as small shiny papules and progress to deep endophytic,
sharply defined, round lesions with a rough keratotic surface, surrounded by a smooth
collar of calloused skin (see the image below). Because they grow deep, they tend to
be more painful than common warts. Myrmecia warts that occur on the plantar surface

usually are found on weight-bearing areas, such as the metatarsal head and heel.
When they occur on the hand, they tend to be subungual or periungual.

Plantar warts.

Flat warts: Flat warts also are termed plane warts or verruca plana. They are
characterized as flat or slightly elevated flesh-colored papules that may be smooth or
slightly hyperkeratotic. They range from 1-5 mm or more, and numbers range from a
few to hundreds of lesions that may become grouped or confluent. These warts may
occur anywhere; however, the face, hands, and shins tend to be the most common
areas. They may appear in a linear distribution as a result of scratching or trauma
(Koebner phenomenon). Regression of these lesions may occur, which usually is
heralded by inflammation.

Butcher's warts: Butcher's warts are seen in people who frequently handle raw meat.
Their morphology is similar to common warts, with a higher prevalence of
hyperproliferative cauliflowerlike lesions. They are seen most commonly on the
hands.

Mosaic warts: A mosaic wart is a plaque of closely grouped warts. When the surface
is pared, the angular outlines of tightly compressed individual warts can be seen.
These usually are seen on the palms and soles.

Focal epithelial hyperplasia (Heck disease)[1] : Focal epithelial hyperplasia, also

termed Heck disease, is an HPV infection occurring in the oral cavity, usually on the
lower labial mucosa. It also can be seen on the buccal or gingival mucosa and rarely,
on the tongue. The lesions appear as multiple flat-topped or dome-shaped pink-white
papules. They usually are 1-5 mm, with some lesions coalescing into plaques. They
are seen most frequently in children of American Indian or Inuit descent.

Cystic warts (plantar epidermoid cysts): A cystic wart appears as a nodule on the
weight-bearing surface of the sole. The nodule usually is smooth with visible rete
ridges but may become hyperkeratotic. If the lesion is incised, cheesy material may be
expressed. The etiology of these lesions is uncertain. One theory is that a cyst forms,
originating from the eccrine duct, and secondary HPV infection occurs. Another
theory is that the epidermis infected with HPV becomes implanted into the dermis,
forming an epidermal inclusion cyst.

Causes
Warts are caused by HPV, which is a double-stranded, circular, supercoiled DNA virus
enclosed in an icosahedral capsid and comprising 72 capsomers. More than 100 types of HPV
have been identified. Note the following wart types and HPV types:

Common warts - HPV types 2 and 4 (most common), followed by types 1, 3, 27, 29,
and 57

Deep palmoplantar warts (myrmecia) - HPV type 1 (most common), followed by

types 2, 3, 4, 27, 29, and 57

Flat warts - HPV types 3, 10, and 28

Butcher's warts - HPV type 7 (although some data suggest the association may be
weak)

Focal epithelial hyperplasia (Heck disease) - HPV types 13 and 32

Cystic warts - HPV type 60

Laboratory Studies
The diagnosis of warts is made primarily on the basis of clinical findings.
Immunohistochemical detection of HPV structural proteins may confirm the presence of
virus in a lesion, but this has a low sensitivity. Viral DNA identification using Southern blot
hybridization is a more sensitive and specific technique used to identify the specific HPV
type present in tissue. Polymerase chain reaction may be used to amplify viral DNA for
testing. Although HPV may be detected in younger lesions, it may not be present in older
lesions.

Procedures
Paring of warts may reveal minute black dots, which represent thrombosed capillaries. Obtain
a biopsy if doubt exists regarding the diagnosis.

Histologic Findings
Histologic findings for various types of nongenital warts are as follows:

Common warts: Histopathologic features of common warts include digitated

epidermal hyperplasia, acanthosis, papillomatosis, compact orthokeratosis,
hypergranulosis, dilated tortuous capillaries within the dermal papillae, and vertical
tiers of parakeratotic cells with entrapped red blood cells above the tips of the
digitations. Elongated rete ridges may point radially toward the center of the lesion. In
the granular layer, HPV-infected cells may have coarse keratohyaline granules and
vacuoles surrounding wrinkled-appearing nuclei. Koilocytic (vacuolated) cells are
pathognomonic for warts.
Deep palmoplantar warts (myrmecia): Deep palmoplantar warts appear similar to
common warts except that most of the lesion lies deep to the plane of the skin surface.
This endophytic epidermal growth often has the distinctive feature of polygonal,
refractile-appearing, eosinophilic, cytoplasmic inclusions composed of keratin
filaments, forming ringlike structures. Basophilic nuclear inclusions and basophilic
parakeratotic cells loaded with virions may be in the upper layers of the epidermis.
Flat warts: Flat warts resemble common warts on light microscopy; however, the
features tend to be muted. Cells with prominent perinuclear vacuolization around
pyknotic, strongly basophilic, centrally located nuclei may be in the granular layer.
These may be referred to as "owl's eye cells."

Butcher's warts: Butcher's warts have prominent acanthosis, hyperkeratosis, and

papillomatosis. Small vacuolized cells with centrally located shrunken nuclei may be
seen in clusters within the granular layer rete ridges.

Filiform warts: Filiform warts may appear similar to common warts but tend to have
prominent papillomatosis.

Focal epithelial hyperplasia (Heck disease): Focal epithelial hyperplasia is

characterized by a hyperplastic mucosa with thin parakeratotic stratum corneum,
acanthosis, blunting and anastomosis of rete ridges, and pallor of epidermal cells as a
result of intracellular edema. Some areas may have prominent keratohyaline granules,
and some vacuolated cells may be present.

Cystic warts: A cyst filled with horny material characterizes cystic warts. The wall is
composed of basal, squamous, and granular cells. Many of the epithelial cells may
have large nuclei and clear cytoplasm with eosinophilic inclusion bodies. The cyst
may rupture, resulting in a foreign body granuloma

Medical Care
Multiple modalities are available for the treatment of warts, but none is uniformly effective.[8,
9]
Start with the least painful, least expensive, and least time-consuming methods. Reserve the
more expensive and invasive procedures for refractory extensive warts. Immunosuppressed
individuals often are refractory to wart treatments. Various treatment methods are available.

Benign neglect
Providing no treatment at all is certainly safe and cost effective. Consider this as an option,
since 65% of warts may regress spontaneously within 2 years. Without treatment, however,
patients risk warts that may enlarge or spread to other areas. Treatment is recommended for
patients with extensive, spreading, or symptomatic warts or warts that have been present for
more than 2 years.

Topical agents
Salicylic acid is a first-line therapy used to treat warts.[10] It is available without a prescription
and can be applied by the patient at home. Cure rates from 70-80% are reported.
British, nonblinded, randomized controlled trial compared treatment of plantar warts with
50% salicylic acid topical (Verrugon) applied daily with cryotherapy with liquid nitrogen (up
to 4 treatments 2-3 wk apart). The study found no significant difference between the
treatments in clearance of the plantar warts at 12 weeks and again at 6 months.[11] The lesser
cost of the salicylic acid topical treatment made it more cost-effective than the liquid nitrogen
treatment.
Several topical agents are available that can be applied by trained personnel in a physician's
office. Cantharidin is an extract of the blister beetle that causes epidermal necrosis and
blistering. Dibutyl squaric acid, also known as squaric acid dibutyl ester (SADBE), and
diphencyclopropenone (DCP) are contact sensitizers. Trichloroacetic acid is a caustic
compound that causes tissue necrosis. Podophyllin is a cytotoxic compound used more

commonly in the treatment of genital warts. Aminolevulinic acid (ALA) is a photosensitizer

that has been successfully used topically in combination with blue light to treat flat warts.[12]
Several prescription medications have proven beneficial in treating warts. These can be
applied at home by the patient. Imiquimod is an immune response modifier approved for the
treatment of genital warts. Reports indicate successful treatment of common warts.[13]
Cidofovir is an antiviral agent used for the treatment of cytomegalovirus infection in HIV
patients. Reportedly, in 2 patients with recurrent persistent common warts in whom multiple
standard therapies were not responsive, the warts were resolved using topical cidofovir gel
applied 1-2 times per day. This remains an investigational drug for warts.[14]
Podophyllotoxin is a purified ingredient of podophyllin. Since it tends to work better on
mucosal surfaces, it is used primarily to treat genital warts. Little information is available
regarding treatment of nongenital warts with this medication.
5-Fluorouracil is a topical chemotherapeutic agent primarily used to treat actinic keratoses. It
has been reported to be effective in treating warts when used under occlusion daily for up to 1
month. It has been used in children.[15]
Tretinoin is a topical retinoic acid that primarily is used to treat acne. It has been successful in
treating flat warts.

Intralesional injections
When warts are persistent and refractory to topical agents, consider intralesional injections as
an alternative.
Intralesional immunotherapy using injections of Candida, mumps, or Trichophyton skin test
antigens has been shown to be effective in the treatment of warts, with reports of success in
up to 74% of patients.[16]
Bleomycin is a chemotherapeutic agent that inhibits DNA synthesis in cells and viruses. Cure
rates have ranged from 33-92%.[17, 18]
Interferon-alfa is a naturally occurring cytokine with antiviral, antibacterial, anticancer, and
immunomodulatory effects. Cure rates of 36-63% have been reported.

Photodynamic therapy
In one study, photodynamic therapy with topical 5-aminolevulinic acid applied to the warts,
followed by photoactivation with red 633-nm light-emitting diodes at 2- to 3-week
intervals resulted in 68% improvement.[19] .

Systemic agents

Systemic agents that have been used to treat warts include cimetidine, retinoids, and
intravenous cidofovir.
Cimetidine is a type-2 histamine receptor antagonist commonly used to treat peptic ulcer
disease. Because of its immunomodulatory effects at higher doses, cimetidine was considered
a possible treatment for warts; however, results have varied. Double-blind placebo-controlled
studies have shown no benefit.[20]
Retinoids are synthetic vitamin A analogs that may help with extensive disabling
hyperkeratotic warts in immunocompromised patients. They may help alleviate pain and
facilitate the use of other treatments. Retinoids also have helped reduce the number of lesions
in immunosuppressed renal transplant patients. The limiting side effects include liver
function abnormalities, increased serum lipid levels, and teratogenicity.
Two reports have described intravenous cidofovir used for the treatment of extensive,
disfiguring, and refractory warts. This should be used with caution because of the risk of
nephrotoxicity.[21, 22]

Alternative treatments
Several alternative treatments have been reported as successful in treating warts, including
adhesiotherapy, hypnosis, hyperthermia, garlic, and vaccines.[23, 24]
Adhesiotherapy is performed by applying duct tape to the wart daily. This method is painless
and inexpensive and has reports of good success.
Hypnosis has been used to treat refractory warts.[25] Several published studies have
documented the success of hypnotherapy. Cure rates have been reported from 27-55%, with
prepubertal children more likely to respond than adults. Patients in whom hypnotherapy fails
may respond to hypnoanalysis for warts.
Hyperthermia involves immersing the involved surface in hot water (113F) for 30-45
minutes, 2-3 times per week.
Propolis is a resin that has been reported to be significantly more effective than Echinacea or
placebo as an immunomodulating treatment for common and planar warts.[26]
Raw garlic cloves have been demonstrated to have antiviral activity. This can be rubbed onto
the wart nightly, followed by occlusion.[27]
Tea tree oil possesses antimicrobial properties and when applied topically has also been
reported as successful.[28]
Vaccines currently are in development.

Surgical Care
Cryosurgery [29]

Liquid nitrogen (-196C) is the most effective method of cryosurgery. Apply liquid nitrogen
using a cotton bud applicator or cryospray to the recommended 1-2 mm rim of normal skin
tissue around the wart. Repeat every 1-4 weeks for approximately 3 months, as needed. Warn
patients about pain and possible blistering after treatment.
Use with caution on the sides of fingers, since it can injure underlying structures and nerves.
Other side effects may include scarring, ulceration, or pigment alteration. In addition, rarely
cryosurgery can result in a central clearing with an annular recurrence of the wart
surrounding the treated area, known as a "doughnut wart." Cure rates of 50-80% have been
reported. Paring the wart, in addition to 2 freeze-thaw cycles, has been a valuable adjunct to
cryosurgery for plantar warts.[30]

Lasers
This is an expensive treatment, and is reserved only for large or refractory warts. Multiple
treatments may be required. Local or general anesthesia may be necessary. A potential risk of
nosocomial infection also exists in health care workers, since HPV can be isolated in the
plume and can be inhaled.[31]
Carbon dioxide lasers have successfully treated resistant warts; however, the procedure can
be painful and leave scarring. One retrospective study revealed a cure rate of 64% at 12
months with carbon dioxide lasers.[32]
The flashlamp-pumped pulse dye laser targets the blood vessels that feed warts and has
shown mixed results in treating warts, with decreased risk of scarring and transmission of
HPV in the smoke plume.[33]
Nd:YAG laser may be used for deeper, larger warts.

Electrodesiccation/curettage and surgery

Although electrodesiccation and curettage may be more effective than cryosurgery, it is
painful, more likely to scar, and HPV can be isolated from the plume. Avoid using surgical
excision in most circumstances because of the risks of scarring and recurrence.

Medication Summary
The goals of pharmacotherapy are to reduce morbidity and prevent complications. In addition
to the medications listed below, propolis is a brownish resinous waxy material collected by
honeybees from the buds of trees and used as a cement and used at 500 mg/day until warts
resolve or until 3 mo, whichever occurs first.
Dibutyl squaric acid/diphencyclopropenone has also been used. Contact sensitizers induce
allergic contact dermatitis, causing a localized inflammation and immune response. Apply
solution in light-shielded accessible location (eg, arm) to achieve initial sensitization; repeat
until reaction occurs; apply to warts q1-2weeks.

Keratolytic agents

Class Summary
Cause cornified epithelium to swell, soften, macerate, and then desquamate.

Salicylic acid 17% (Compound W, Duofilm), or 40% pad (Curad Mediplast)

Available OTC in 5-40% concentration and in a variety of vehicles, including creams, paints,
gels, karaya gum, impregnated plasters, collodion, or sodium carboxycellulose tape. Lactic
acid may be a second ingredient in some wart varnishes. By dissolving the intercellular
cement substance, salicylic acid desquamates the horny layer of skin. Therapeutic effect may
be enhanced by removal of surface keratin prior to application. Apply topically qd/bid for
several weeks.
View full drug information

Podofilox (Condylox)

Podofilox is a purified ingredient of podophyllin and, therefore, is less irritating. Available by

prescription and can be applied by patient at home. A 0.5% purified solution may be applied
topically bid for 3 consecutive days, repeat qweek, not exceed 4 weeks
View full drug information

Podophyllum resin (Podocon-25)

Resin extract derived from May Apple plant that contains several cytotoxic compounds. Has
a powerful irritant effect and must be used with caution. Works better on mucosal surfaces
than keratinized surfaces and is therefore more commonly used for treatment of genital warts.
Trained personnel must apply topically because of adverse effects; may be left on skin for 1-6
h before washing.

Cantharidin

Dried extract of blister beetle (also termed Spanish fly). Causes epidermal necrosis and
blistering. Apply 0.7% solution sparingly with wooden end of cotton-tipped applicator in
physician's office, and allow to completely dry; do not cover area with bandage after
application; repeat application at 3- to 4-wk intervals may be required.
View full drug information

Trichloroacetic acid (Tri-Chlor)

Caustic compound that causes immediate superficial tissue necrosis. Available as 80%
solution that is painted onto lesions in physician's office; apply after excess keratotic debris is
pared; repeat therapy qweek prn until wart is cured.

Immunomodulators
Class Summary
Stimulate the release of key factors that regulate the immune system.[34]
View full drug information

Imiquimod (Aldara)

Induces secretion of interferon alpha and other cytokines; FDA approved for treatment of
genital warts in adults; reports indicate success in treatment of common warts in children. A
5% gel applied daily for 3 days/week; may apply hs and wash off after 6-10 h; twice-daily
administration for nongenital warts reported, but irritation may be increased.
View full drug information

Interferon alfa 2b (Intron A)

Naturally occurring cytokine with antiviral, antitumor, and immunomodulatory actions;

intralesional administration more effective than systemic administration and associated only
with mild flulike symptoms. Treatments may be required for several weeks to months before
beneficial results are seen. Consider this treatment as third line, and reserve it for warts
resistant to standard treatments.
View full drug information

Pegylated interferon alfa-2a (Pegasys)

PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. It is
predominantly metabolized by the liver. Has immunomodulatory actions; intralesional
administration more effective than systemic administration and associated only with mild
flulike symptoms. Treatments may be required for several weeks to months before beneficial
results are seen. Consider this treatment as third line, and reserve it for warts resistant to
standard treatments.
View full drug information

5-Fluorouracil (Efudex, Carac, Fluoroplex)

Topical chemotherapeutic agent that is approved to treat actinic keratoses and superficial
BCC; has been found more successful in treatment of flat warts than plantar and common
warts. Apply 5% solution or cream daily for up to 1 mo; may be used under occlusion, but
risk of irritation increases.

Antineoplastics, Antibiotic
Class Summary
Inhibit cell growth and proliferation.
View full drug information

Bleomycin

Cytotoxic polypeptide that inhibits DNA synthesis in cells and viruses. Has affinity for HPVinfected tissue and induces vascular changes that result in epidermal necrosis. Has been
beneficial in treating resistant warts. Reserve as a third-line treatment when standard
therapies have failed. Inject 0.5-1 U/mL solution directly into wart; not to exceed 1.5
U/treatment; less painful administration involves placing 1 mg/mL gtt onto wart and pricking
it into wart with needle.

Histamine H2 receptor antagonists

Class Summary
Type 2 histamine receptor antagonist commonly used to treat peptic ulcer disease; due to
immunomodulatory effects at higher doses, has been used as treatment for warts. Results
have been variable, and double-blinded, placebo-controlled studies have shown no benefit.
View full drug information

Cimetidine (Tagamet)

Believed to have immunomodulatory effects at higher doses. May administer 20-40 mg/kg
PO qd divided q6h; not to exceed 2400 mg/day.

Retinoid-like Agents
Class Summary

May be helpful in immunocompromised patients with extensive disabling hyperkeratotic

warts. May help alleviate pain and facilitate use of other treatments. In addition, retinoids
have helped reduce the number of lesions in immunosuppressed renal transplant patients.
Topical retinoids may be useful in treating flat warts.
View full drug information

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotrel)

Synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid); structurally
related to vitamin A. Approved for severe nodular acne but has also been helpful in certain
keratinization disorders.
A US Food and Drug Administrationmandated registry is now in place for all individuals
prescribing, dispensing, or taking isotretinoin. For more information on this registry, see
iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted
and potentially dangerous adverse effects during a course of isotretinoin therapy. May
administer 0.5-2 mg/kg/d PO divided bid with food.

Topical Skin Products

Class Summary
Products that become cytotoxic following exposure to light may be beneficial.
View full drug information

5-Aminolevulinic acid topical 20% solution (Levulan Kerastick)

Topical porphyrin available as Levulan Kerastick. To be applied topically to warts and kept
under occlusion for 5h, then exposed to red light-emitting diodes or other suitable red or blue
light source.

Prognosis
Approximately 65% of warts disappear spontaneously within 2 years. When warts resolve on
their own, no scarring is seen. However, scarring can occur as a result of different treatment
methods. Growth of periungual or subungual warts may result in permanent nail dystrophy.
Treatment failures and wart recurrences are common, more so among immunocompromised
patients. Normal appearing perilesional skin may harbor HPV, which helps explain
recurrences.

Patient Education

Alert patients to the risk factors for transmission of warts. These include trauma or
maceration of the skin, frequent wet work involving hands, hyperhidrosis of feet, swimming
pools, and nail biting. Butchers and slaughterhouse workers also are at increased risk for
developing warts.
Alert patients that some warts may require multiple treatments and may be resistant to several
treatment modalities. In addition, some warts may regress spontaneously without treatment.
For excellent patient education resources, visit eMedicineHealth's Skin Conditions and
Beauty Center. Also, see eMedicineHealth's patient education articles Warts and Plantar
Warts.

Overview
Palmoplantar keratoderma (PPK) constitutes a heterogeneous group of disorders
characterized by thickening of the palms and the soles of individuals who are affected. In
recent years, speculation has arisen that a molecular genetic classification system will replace
the traditional, clinically based, descriptive systems. Consequently, the authors of this review
present each disorder according to traditional schemes and offer molecular and genetic
insights into each.
The PPKs can initially be divided based on whether they are inherited or acquired. Focusing
on the inherited PPKs, initial classification is into 3 distinct clinical patterns of epidermal
involvement.
The first is diffuse PPK, which is uniform involvement of the palmoplantar surface. This
pattern is usually evident within the first few months of life. The second is focal PPK, which
consists of localized areas of hyperkeratosis located mainly on pressure points and sites of
recurrent friction. The third is punctate keratoderma, which features multiple small,
hyperkeratotic papules, spicules, or nodules on the palms and soles. These tiny keratoses may
involve the entire palmoplantar surface or may be restricted to certain locations (eg, palmar
creases).
The keratodermas can then be further subdivided based on whether only an isolated
keratoderma is present or whether other skin findings are present and/or other organs are
involved.
The first subclassification is simple keratoderma, which is isolated PPK. The second is
keratodermas with associated features such as lesions of nonvolar skin, hair, teeth, nails, or
sweat glands and/or with abnormalities of other organs.
Acquired forms are divided into keratoderma climactericum, keratoderma associated with
internal malignancy, PPK due to inflammatory and reactive dermatoses, PPK caused by
infections, drug-related PPK, and systemic diseaseassociated PPK.

Diffuse Hereditary PPK

Diffuse types without associated features

Epidermolytic PPK (Vorner PPK)

o Synonyms for epidermolytic PPK (EPPK) include diffuse Vorner disease and
PPK cum degeneratione granulosa. In some ethnic groups, this form is the
most common type of hereditary PPK. It has an estimated prevalence of at
least 4.4 cases per 100,000 population in Northern Ireland. It is inherited in an
autosomal dominant fashion. Onset occurs in the first few months of life, but
the disease is usually well developed by age 3-4 years.
o

Clinical features are very similar to diffuse nonepidermolytic PPK (NEPPK).

A well-demarcated, thick, yellow hyperkeratosis is present over the palms and
soles. An erythematous band is frequently present at the periphery of the
keratosis. The surface is often uneven and verrucous. Finally, it is usually
nontransgredient, with a sharp demarcation of the lesions at the wrists.

Histologically, keratinocytes show epidermolysis, hyperkeratosis, acanthosis,

and papillomatosis. Perinuclear vacuolization and large keratohyalin granules
are seen. Cellular breakdown in the spinous and granular cell layers sometimes
leads to blister formation. Several biopsy specimens may be required to
confirm the changes because they may be subtle and patchy.

Keratin 1 and keratin 9 mutations have been reported. The keratin 1 mutations
appear to be associated with a milder form of EPPK.[1]

Treatment includes salicylic acid, 50% propylene glycol in water under plastic
occlusion several nights per week, and lactic acid and urea-containing creams
and lotions; all have been shown to be helpful. Mechanical debridement with a
blade also may be useful. Oral retinoid therapy has had variable effects and
may not benefit patients with certain genotype profiles, such as K1 mutations.

Nonepidermolytic PPK (Unna-Thost PPK)

o

Synonyms include diffuse Unna-Thost disease and PPK diffusa circumscripta.

Diffuse NEPPK is inherited in an autosomal dominant fashion. The condition
may manifest in the first few months of life but is usually well developed by
age 3-4 years. It is another common type of hereditary PPK.

Clinically, even, waxy, thick, well-demarcated hyperkeratosis is present over

the palms and soles. A red band is frequently present at the periphery of the
keratosis. It is usually nontransgredient, with a sharp demarcation of the
lesions at the wrists. Aberrant keratotic lesions may appear in the dorsum of
the hands, feet, knees, and elbows. The dorsa of the fingers may be involved
with a sclerodermalike thickening of the distal digit. A cobblestone
hyperkeratosis of the knuckles may be seen. Nails may be thickened.

Although not always distinguishable, some clinical features may help

differentiate EPPK from NEPPK. NEPPK may have a waxy appearance,
compared with the dirty appearance of EPPK. Hyperhidrosis and pitted
keratolysis may be present with NEPPK. Finally, with NEPPK, secondary
dermatophyte infections, resulting in maceration and peeling, are common.

Histologic findings include orthokeratotic hyperkeratosis associated with

hypergranulosis or hypogranulosis and moderate acanthosis. Changes are

nonspecific and common to many varieties of keratoderma. An absence of

epidermolysis differentiates it from EPPK.

Molecular biology features include linkage to type II keratin locus on band

12q11-13, corresponding to a keratin 1 gene mutation.

Treatment includes salicylic acid, 50% propylene glycol in water under plastic
occlusion several nights per week, and lactic acid and urea-containing creams
and lotions; all have been shown to be helpful. Mechanical debridement with a
blade may also be useful. Oral retinoid therapy has had variable effects.
Treatment with an antifungal agent is beneficial if dermatophyte infection
coexists with the NEPPK.

Mal de Meleda[2]
o

A synonym is keratosis extremitatum hereditaria trangrediens et progrediens.

Mal de Meleda is an autosomal recessive disease. Onset occurs in early
infancy, but the condition is rare. The prevalence is 1 case per 100,000
population. Initially, it was described in inhabitants of the Adriatic Island of
Meleda.

Clinical features include diffuse, thick keratoderma with a prominent

erythematous border. Lesions spread onto the dorsa of the hands and the feet
(transgredient). Constricting bands are present around the digits and can result
in spontaneous amputation. Well-circumscribed psoriasislike plaques or
lichenoid patches may be present on the knees and the elbows. Patients may
have severe hyperhidrosis, possibly accompanied by malodor. Secondary
bacterial and fungal infections are common. Perioral erythema; periorbital
erythema and hyperkeratosis; nail changes (eg, koilonychia, subungual
hyperkeratosis); and lingua plicata, syndactyly, hair on the palms and the
soles, high-arched palate, and left-handedness are other clinical features.

Histologic findings include orthokeratosis and normogranulosis without

epidermolysis.

Molecular biology features include mutations in the gene encoding SLURP-1

found on band 8q24.3. Proteins of the SLURP family have been implicated in
transmembrane signal transduction, cell activation, and cell adhesion.

Treatment is with oral retinoid therapy.

Nagashimi-type PPK[3]
o

This condition is inherited in an autosomal recessive fashion. Onset of disease

occurs between birth and age 3 years. To date, all 19 cases have been reported
in Japan.

Clinically, the disease was initially described as a milder form of mal de

Meleda. Some classify this keratosis as its own distinct entity, with
involvement of other sites, including the elbows and knees, being common.
Hyperhidrosis and tinea pedis infection are associated features.

Molecular biology studies in one case did not find any mutations in the gene
encoding SLURP-1.

Progressive PPK (Greither disease)

o

A synonym is transgrediens et progrediens PPK. This is inherited in an

autosomal dominant fashion. Onset occurs in early infancy but may occur later
in childhood.

Clinically, diffuse PPK extends onto the dorsa of the hands and the feet
(trangredient), with characteristic involvement of the Achilles tendon. Scaly
plaques may be found on the elbows, knees, and flexural areas. Hyperhidrosis
and intrafamilial phenotypic variation are common. Pseudoainhum formation
with amputation of the digits has been described.

Histologic features include epidermolysis of the granular cell layer. Lipidladen corneocytes may be seen.

Molecular biology features include mutations in the gene encoding keratin 1.[4]

Treatment includes emollients, topical retinoids, keratolytics, and topical

steroids.

Diffuse types with associated features

Mutilating PPK (Vohwinkel syndrome)

o Synonyms include PPK mutilans and keratoderma hereditaria mutilans.
Mutilating PPK is inherited in an autosomal dominant fashion. Onset occurs in
infancy.
o

Clinically, this condition manifests in infants as a honeycomblike keratosis of

the palms and the soles. It becomes transgredient during childhood. Laterforming, constricting, fibrous bands appear on the digits and can lead to
progressive strangulation and autoamputation. Starfish-shaped keratosis may
occur on the knuckles of the fingers and toes, which is a characteristic feature
of this disorder. Alopecia, hearing loss, spastic paraplegia, myopathy,
ichthyosiform dermatosis, and nail abnormalities are associated. Cases of
epithelioma cuniculatum have been reported.

Histologic findings include hyperkeratosis, acanthosis, and a thickened

granular cell layer with retained nuclei in the stratum corneum.

Molecular biological studies have confirmed that the most common mutation
found in Vohwinkel syndrome involves the gene encoding connexin 26. This
subtype is associated with hearing loss. In contrast, a mutation in the gene for
loricrin is associated with mutilating keratoderma and ichthyosis but not
deafness.

Treatment includes oral retinoids.

Also see Vohwinkel Syndrome.

Bart-Pumphrey syndrome

A synonym is PPK with knuckle pads, leukonychia, and deafness. It is

inherited in an autosomal dominant fashion. Onset occurs in infancy.

Clinically, all neonates are hearing impaired from birth and develop diffuse
PPK in childhood. Leukonychia and hyperkeratoses over the joints of the hand
also appear.

Molecular biological studies include a new mutation in the gene that encodes
connexin 26, which explains the clinical overlap with Vohwinkel syndrome.

Diffuse NEPPK and sensorineural deafness

o

This condition is inherited in an autosomal dominant fashion.[5]

Clinical features include diffuse palmoplantar hyperkeratosis in association

with slowly progressive, bilateral, high-frequency hearing loss (onset in early
childhood). Deafness precedes the skin changes (onset in mid childhood).

Molecular biology features include a connexin 26 mutation (different domains

than those mutated in Vohwinkel syndrome). In addition, a mitochondrial
point mutation has been demonstrated as the cause of this phenotype, making
this the only type of keratoderma associated with a mutation in mitochondrial
DNA (serine tRNA).

PPK with sclerodactyly (Huriez syndrome)

o

PPK with sclerodactyly is inherited in an autosomal dominant fashion. Onset

occurs in infancy.

Clinical features include red, atrophic skin on the dorsal hands and feet at
birth. Diffuse, mild keratoderma is more marked on the palms than the soles.
Other clinical features are sclerodactyly and nail abnormalities (hypoplasia,
fissuring, ridging, koilonychia). PPK with sclerodactyly is also associated with
aggressive squamous cell carcinoma in areas of atrophic skin.

Histologic findings include acanthosis, accentuation of the granular layer, and

orthokeratosis; Langerhans cells are almost completely absent in the affected
skin. Under electron microscopy, dermoepidermal junctions and desmosomes
are normal; however, dense bundles of tonofilaments are seen in the epidermal
layer. The granular layer shows large, coarse, clumped keratohyalin.

Molecular biologic findings include a mutation in the gene mapped to 4q23.

Hidrotic ectodermal dysplasia (Clouston syndrome)

o

This syndrome is an autosomal dominant disorder.

Clinical features include diffuse papillomatous PPK (especially over pressure

points of the palms and soles), dystrophic nails, and hypotrichosis. Thickened,
hyperpigmented skin may also appear over the small and large joints,
including the knuckles, elbows, and knees. Thickened, severely dystrophic
nails develop, but they may be normal at birth. Universal sparsity of hair
involves the scalp, eyebrows, eyelashes, and axillary and genital regions.

Sensorineural deafness, polydactyly, syndactyly, clubbing of fingers, mental

retardation, dwarfism, photophobia, and strabismus are associated.
o

Clouston syndrome is mapped to 13q11. One form can be caused by mutation

in the gene encoding connexin 30. Ultrastructural studies of the hair of these
patients demonstrate disorganization of hair fibrils with loss of the cuticular
cortex.

Mutilating PPK with periorificial keratotic plaques (Olmsted syndrome)

o

Most cases of this condition are sporadic, with the exception of one report of
an autosomal dominant pattern of inheritance. Onset occurs in the first year of
life.

Clinically, PPK begins focally in infancy and then becomes diffuse and severe.
Later findings include flexion deformities and constriction of the digits,
sometimes leading to spontaneous amputation. Progressive, well-defined
perioral, perianal, and perineal hyperkeratotic plaques are present, as is
onychodystrophy. Alopecia, deafness, nail dystrophy, and dental loss may be
associated. Squamous cell carcinoma and malignant melanoma have
developed in the areas of PPK.

Histologic findings include hyperkeratosis without parakeratosis and mild

acanthosis.

Abnormal expression of keratin 5 and 14 has been reported.

Treatment includes oral and topical retinoids. Full-thickness excision and skin
grafting has also been reported to result in clinical improvement.

PPK with periodontitis (Papillon-Lefvre syndrome)

o

This condition is inherited in an autosomal recessive fashion. The frequency of

PPK with periodontitis is 4 cases per 1 million population. The male-to-female
ratio is equal. Onset occurs between the first and fifth years of life. A variant,
Haim-Munk syndrome, features, in addition to PPK and periodontitis,
arachnodactyly, acroosteolysis, and onychogryphosis.

Clinically, diffuse transgredient PPK may be observed, typically developing

within the first 3 years of life. Punctiform accentuation, particularly along the
palmoplantar creases, may be seen. Unless treated, periodontosis results in
severe gingivitis and loss of teeth by age 5 years. No significant correlation
has been demonstrated between the level of periodontal infection and the
severity of skin affections, which supports the concept that these major
components of this syndrome are unrelated to each other. Patients exhibit
increased susceptibility to cutaneous and systemic infections. Scaly,
psoriasiform lesions are often observed over the knees, elbows, and
interphalangeal joints. Finally, patients may have malodorous hyperhidrosis.
Reports from 2008 indicate a high prevalence of malignant melanoma in
Japanese patients with Papillon-Lefvre syndrome.[6]

Histologic findings include hyperkeratosis with irregular parakeratosis and

moderate perivascular infiltration. Electron microscopic features include

lipidlike vacuoles in corneocytes and granulocytes, a reduction in

tonofilaments, and irregular keratohyalin granules.

Molecular biology findings include mutations in the gene for cathepsin C,

mapping to 11q14-q21, which are responsible for this syndrome.[7] Cathepsin C
is a lysosomal protease known to activate enzymes that are vital to the body's
defenses.

Treatment includes oral retinoids for the PPK. Elective extraction of involved
teeth may prevent excess bone resorption. Appropriate antibiotic therapy may
be required for periodontitis and recurrent cutaneous and systemic infections.
Treatment with acitretin starting at an early age shows promise towards
allowing patients to have normal adult dentition.

Diffuse NEPPK with woolly hair and arrhythmogenic cardiomyopathy (Naxos

disease)
o

This condition is inherited in an autosomal recessive fashion.

Clinically, a diffuse, nontransgredient keratoderma with an erythematous

border appears during the first year of life. Woolly (dense, rough, and bristly)
scalp hair is present at birth. Cardiac disease, manifested by arrhythmias, heart
failure, or sudden death, becomes evident during and after late puberty. Other
cutaneous manifestations include acanthosis nigricans, xerosis, follicular
hyperkeratosis over the zygoma, and hyperhidrosis.

Histologic findings include hyperkeratosis, hypergranulosis, and acanthosis.

Molecular biology findings include a mutation in the plakoglobin gene,

mapping to 17q21, which is responsible for Naxos disease. Plakoglobin is an
important component of cell-to-cell and cell-to-matrix adhesion complexes of
many tissues, including the skin and cardiac junctions. It also plays a role in
signaling in the formation of desmosomal junctions. Mutations in the
plakoglobin gene may lead to detachment of the cardiac myocytes, resulting in
myocyte death. Plakoglobin mutations may also lead to desmosomal junction
fragility in hair shafts, explaining the clinical phenotype of woolly hair.

Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK)

Focal Hereditary PPK

Focal PPK without associated features

Focal EPPK
o Synonyms include keratosis palmoplantaris nummularis and hereditary painful
callosities. This condition is inherited in an autosomal dominant manner.
Onset occurs within the first 2 years of life.[8]
o

Clinical features include nummular keratotic lesions, mainly located on plantar

pressure points. This condition is also painful.

Histologic features include local epidermolytic hyperkeratosis.[9, 10]

Molecular genetic findings have not yet been reported.

Striate PPK
o

Synonyms include Brnauer-Fuhs-Siemens syndrome, Wachter-type focal

NEPPK, and PPK areata/striata. Striate PPK is inherited in an autosomal
dominant fashion. Onset occurs in infancy or in the first few years of life.

Clinical features include marked variability in phenotypic expression. Hands

may show minimal callous formation, or, changes may be undetectable in
individuals with sedentary occupations. Friction-associated trauma from
manual labor results in a striate pattern of PPK over the palmar aspects of the
digits (islands of linear hyperkeratosis). Increased skin fragility may lead to
skin splitting following trauma. Nails and hair may be involved.

Histology demonstrates acanthosis and an increased granular layer.

Molecular biology findings include mutations in desmosomal proteins, which

have been implicated in this disorder, including desmoglein 1 on 18q11-12 and
the desmoplakin gene on 6p21. Desmosomal function is very important in
areas prone to repeated friction. Mutations in keratin 1 and keratin 16 are also
associated with striate PPK.

Treatment includes oral retinoids.

Focal type with associated features

PPK associated with esophageal cancer (Howell-Evans syndrome)

o Synonyms include tylosis esophageal cancer and focal NEPPK with
carcinoma of the esophagus. This condition is inherited in an autosomal
dominant fashion.
o

Clinically, focal PPK develops at age 5-10 years. The PPK is limited to the
pressure points on the balls of the feet, with later mild involvement on the
palms. Patients have an increased susceptibility to developing carcinoma of
the esophagus in the fifth decade of life. Two variants, one with a late onset of
PPK and a higher risk of esophageal carcinoma and another with an early
onset and a benign course, have been described. Oral leukokeratosis and
follicular keratosis are often present.

Histologic findings include acanthosis, a prominent granular cell layer, and

hyperkeratosis in the palms and soles. Patients have thickened sweat ducts of
the dermis, with the lumen often occluded by a hyperplastic epithelium.

The tylosis esophageal cancer gene (TOC) is localized to a small region on

band 17q25, a region frequently deleted in persons with sporadic squamous
cell esophageal tumors.

Oculocutaneous tyrosinemia (Richner-Hanhart disease)

o

Synonyms include tyrosinemia type II. Oculocutaneous tyrosinemia is

inherited in an autosomal recessive fashion.

Clinical features include focal, painful PPK development in childhood or

adolescence. Occasionally, hyperkeratotic lesions develop on the elbows,
knees, and tongue. Patients have hyperhidrosis and bullous lesions.
Photophobia and herpetiform corneal erosions often appear in infancy and can
lead to corneal ulcerations, scarring, and glaucoma. Tyrosine crystal deposits
can be seen during slit-lamp examination. Mental retardation develops,
especially if patients are not treated.

Histologic findings include acanthosis with hyperkeratosis and

hypergranulosis. Under electron microscopy, keratinocytes contain clumped
tonofilament with adherent globoid keratohyalin granules and intracellular
needle-shaped tyrosine crystalline inclusions can be found.

Molecular biology features include at least 15 mutations in the gene encoding

tyrosine aminotransferase at band 16q22.1-q22.3. Deficiency of the enzyme
tyrosine aminotransferase leads to increased levels of serum and urinary
tyrosine and phenolic acid metabolites of tyrosine.

Treatment includes early institution of a low-phenylalanine and low-tyrosine

diet.

Pachyonychia congenita, types I and II[11]

o

This condition is inherited in an autosomal dominant manner; however, a rare

autosomal recessive pattern is also observed.

Clinical features include localized areas of hyperkeratosis on the palms and

the soles, typically found on pressure points and weightbearing areas of the
palms and soles. Patients have discoloration and thickening of the nails, which
may be striking. Follicular hyperkeratosis, angular cheilitis, oral
leukokeratosis, hyperhidrosis, and hoarseness may develop.

Type 1 is the Jadassohn-Lewandowsky type and is the most prevalent type of

pachyonychia congenita. It is characterized by severe focal PPK, possibly with
blistering. Type 2 is the Jackson-Lawler type. The focal PPK is milder in type
2 than in type 1. Natal or neonatal teeth and multiple pilosebaceous cysts
(steatocystoma multiplex) are also present and help distinguish this type from
type 1.

Histologic features include hyperkeratosis with alternating orthokeratosis and

parakeratosis. Large keratohyalin granules are present. Under electron
microscopy, these granules appear as perinuclear keratin aggregates.

Molecular biology findings for the Jadassohn-Lewandowsky type include a

keratin 16 gene mutation and keratin 6a gene mutations. The Jackson-Lawler
type is associated with keratin 17 and keratin 6b gene mutations.

Treatment includes emollients and keratolytics in mild cases and oral retinoids
in more severe disease. Surgical excision of severely deformed nails offers a
temporary solution, but nail dystrophy recurs. Injection of botulinum toxin has
shown relief for hyperhidrosis and pain.

Also see Pachyonychia Congenita.

Striate PPK with woolly hair and left-sided dilated cardiomyopathy (Carvajal-Huerta
syndrome)
o

This condition is inherited in an autosomal recessive pattern. Both this disease

and Naxos disease are autosomal recessive, whereas most of the hereditary
dilated cardiomyopathies are autosomal dominant.

Clinical features include the appearance of striate PPK during early infancy.
Left ventricular cardiomyopathy begins in adolescence and occasionally leads
to early heart failure. Woolly hair is present at birth. Striated lichenoid
keratoses of the flexures, follicular keratoses on the elbows and knees, and
clubbing of the nails have been described. Skin fragility, characterized by
transient vesicles and blisters on the trunk and extremities, is another clinical
feature.

Histologic features include spongiform edema with large intercellular spaces,

clustering of desmosomes at infrequent sites of keratinocyte adhesion, and
perinuclear localization of keratin in suprabasal keratinocytes, which have all
been demonstrated by immunohistochemistry studies, suggesting the presence
of a collapsed intermediate filament network.

Molecular biology findings include homozygous mutations of the gene

encoding desmoplakin, which maps to 6p24 and is the most abundant protein
of the desmosome.

Punctate Hereditary PPK

Punctate PPK without associated features

Punctate keratosis of the palms and soles (Buschke-Fischer disease)[12]

o Synonyms include keratosis punctata palmaris et plantaris, Buschke-FischerBrauer disease, and keratosis papulosa. The prevalence is 1.17 cases per
100,000 population. This condition is inherited in an autosomal dominant
manner, although sporadic cases have been reported. The age at onset is
variable, between 10 and 70 years.
o

Clinically, asymptomatic, tiny, hyperkeratotic papules are present on the

palmoplantar surface. Lesions are uncommon in childhood and usually
manifest after age 20 years. This condition is not associated with
hyperhidrosis. Patients commonly report pruritus. Most individuals lack
associated features; however, spastic paralysis, ankylosing spondylitis, and
facial sebaceous hyperplasia have been reported. An association with
gastrointestinal and pulmonary malignancy is possible.

Histologic findings include substantial compact hyperkeratosis over a distinct

area of epidermis, hypergranulosis, the presence of a cornoid lamella, and the
absence of epidermal dyskeratosis or hydropic change, which help
differentiate this condition from porokeratosis.

Molecular genetic studies have not yet identified specific genes involved,
although linkage analyses have mapped the disease between bands 15q22.2
and 15q22.31.

Treatment includes keratolytics, topical salicylic acid, mechanical

debridement, excision, and topical and systemic retinoids.

Punctate keratosis of the palmar creases

o

Punctate keratosis of the palmar creases occurs most commonly in African

American patients aged 15-40 years. An autosomal dominant inheritance
pattern has been suggested.

Clinical features include small, round depressions filled with conical

keratinous plugs, which typically occur on the creases of the palms, fingers,
and, less commonly, on the soles. The lesions are aggravated by friction, and,
occasionally, they may be painful.

Histologic features include hyperkeratosis and parakeratosis.

Treatment may include keratolytics and topical retinoids.

Acrokeratoelastoidosis
o

Synonyms include acrokeratoelastoidosis of Costa. Acrokeratoelastoidosis is

usually sporadic, although familial cases suggest an autosomal dominant
pattern of inheritance. Onset usually occurs before the second or third decade
of life.

Clinical features include round or oval, shiny, firm, yellowish papules that can
appear umbilicated. These papules are distributed along the marginal border of
the palms, soles, and/or digits and can also be seen in the space between the
thumb and forefinger, on the anterior surface of the lower legs, and over the
knuckles and nail folds. The papules are usually asymptomatic.

Histologic features include focal hyperkeratosis and elastorrhexis

(fragmentation and a decreased number of elastic fibers in the reticular
dermis).

No treatment is usually required for acrokeratoelastoidosis because lesions are

asymptomatic. However, methods to remove the lesions for cosmetic
purposes, including liquid nitrogen, salicylic acid, and topical tretinoin, have
largely been unsuccessful.

Focal acral hyperkeratosis

o

Focal acral hyperkeratosis is usually sporadic, but familial cases suggest an

autosomal dominant pattern of inheritance. Onset peaks in the third decade.
Some believe this entity is a variant of acrokeratoelastoidosis.

Clinically, the lesions are identical to those of acrokeratoelastoidosis. It has an

insidious onset in childhood, reaching a maximum in early life. Initial reports
suggested a predilection for those of African origin, but subsequent reports
have refuted the importance of ethnicity. Associated findings may include

hyperhidrosis, a gradual increase in the number and size of the lesions, and
rapid progression during pregnancy.
o

Histologic features include focal hyperkeratosis, but no decrease or

fragmentation of dermal elastic fibers is reported.

Topical treatments have been unsuccessful, although oral retinoids have been
partially effective in long-term treatment.

Punctate PPK with associated features

Rare single-pedigree syndromes

o Cystic eyelids, punctate PPK, hypotrichosis, and hypodontia (Sch pf-SchulzPassarge syndrome)
o

Punctate PPK with ankylosing spondylitis

Punctate PPK with facial sebaceous hyperplasia

Punctate PPK with spastic paralysis

PPK with lipomata

Acquired PPK

Keratoderma climactericum
o Synonyms include Haxthausen disease. Onset occurs in women of menopausal
age.
o

Clinically, pressure areas on the soles are initially affected. Erythema and
hyperkeratosis with fissuring make walking painful. Transgrediens is absent.
Pruritus is minimal. Later in the course of the disease, palmar involvement is
seen as discrete and centrally confined hyperkeratosis. Many patients are
obese and hypertensive. A role for estrogen therapy has been proposed and is
supported by the timing of onset and the response to topical and systemic
estrogens. However, reports indicate that patients have normal hormone
profiles. Some cases may represent a form of eczema or psoriasis.

Histologic features include compact orthokeratotic hyperkeratosis,

hypergranulosis, irregular acanthosis with alternating thick and thin
interpapillary ridges, and spongiosis with exocytosis of lymphocytes. In the
dermis, a lymphocytic infiltrate is present around the upper dermal vessels.

Treatment includes topical estradiol 0.05% ointment or 25-40% urea.

Keratoderma associated with internal malignancy

o

Keratoderma is associated with malignancy as a paraneoplastic phenomenon

and as a manifestation of malignancy predisposition. Skin changes tend to
precede discovery of the neoplasm by a few months, and metastasis is usually
present at diagnosis. Keratodermas have been associated with carcinomas of
the esophagus, lung, breast, stomach, pancreas, kidney, bladder, and colon.

Acrokeratosis paraneoplastica of Bazex is associated with squamous cell

carcinoma of the upper gastrointestinal tract. The condition affects white men
aged 40 years and older. Psoriasiform changes of the fingers and the toes with
nail dystrophy extend to involve the palms, soles, limbs, and trunk. The
paraneoplastic nature of the condition is supported by a tendency for both the
time course and the skin involvement to parallel the extent of tumor. The skin
may clear with the removal of the tumor, but relapses occur with tumor
regrowth and cervical metastasis. Also see Acrokeratosis Neoplastica.

Tripe palms (acanthosis palmaris) is a distinct cutaneous paraneoplastic

syndrome most often associated with malignancy of the stomach or lung. The
palms are diffusely thickened, with a velvety texture and ridged appearance.
Malignant tripe palms persists, with less than one third of patients responding
to tumor therapy. Tripe palms is also associated with bullous pemphigoid,
psoriasis, and exfoliative dermatitis.

PPK due to inflammatory and reactive dermatoses

o

Chronic hand dermatitis is characterized by marked irritation, scaling, and

fissuring. Causes may include atopic dermatitis, irritant contact dermatitis, or
allergic contact dermatitis.

Psoriasis may manifest as diffuse hyperkeratosis or as scaly plaques with a

scalloped margin.

Keratoderma blennorrhagica (Reiter syndrome) occurs in 30% of patients with

Reiter syndrome. Lesions are compact, and the sole of the foot is the typical
site of involvement.

Pityriasis rubra pilaris is associated with red-orange thick scale on the palms
and soles with sharp borders. Usually, follicular papules with surrounding
erythema are present, often on the dorsal proximal phalanges (see Pityriasis
Rubra Pilaris).

Callosities develop in response to repeated trauma over bony prominences.

Lichen planus may cause an erythematous, scaly PPK or a punctate, yellow,

warty keratosis. PPK and nail dystrophy have been seen in lichen nitidus.

Aquagenic keratoderma[13, 14]

o

Synonyms include acquired aquagenic PPK, transient reactive

papulotranslucent acrokeratoderma, and aquagenic syringeal acrokeratoderma.
Onset occurs during the second decade of life.

Clinically, within minutes of immersion in water, translucent whitish papules

and plaques appear on the palms and, less commonly, on the soles. A burning
sensation and edema of the hands may also occur simultaneously. The lesion
resolves minutes to hours after drying of the affected skin. Hyperhidrosis may
be associated with the condition.

Histologically, the epidermis and dermis may be normal or mild

orthohyperkeratosis, hypergranulosis, acanthosis, or dilated eccrine ostia may
develop.

Treatment includes 20% aluminum chloride hexahydrate, which has shown

significant clinical improvement in signs and symptoms. Other options include
12% ammonium lactate cream, 20% acid salicylic in petroleum jelly, 10%
urea cream, and botulinum toxin injections.

PPK caused by infections

o

Dermatophytes manifest as hyperkeratosis affecting the soles, toe webs, and

sides of the feet. Hyperhidrosis increases itching and malodor.

Human papillomavirus may form confluent exuberant masses on the palms

and the soles, mimicking keratoderma.

Syphilis may manifest as a diffuse, symmetric keratoderma or papular PPK.

Leprosy can manifest as glove-and-stocking anesthesia, predisposing patients

to infection, ulceration, and hyperkeratosis. Tuberculosis, especially miliary
tuberculosis, may cause hyperkeratosis of the palms and soles.

Encrusted scabies may progress into strikingly hyperkeratotic and/or crusted

lesions on palmar surfaces.

Drug-related PPK
o

Chronic arsenic exposure can lead to multiple, irregular, warty keratotic

lesions on the palms and soles. Onset of the keratoses may occur 10-30 years
after ingestion

Drug hypersensitivity may result from agents such as glucan, verapamil,

quinacrine, etodolac, mepacrine, proguanil, mexiletine, methyldopa, lithium,
venlafaxine, gold, tegafur, fluorouracil, bleomycin, hydroxyurea, practolol,
and doxorubicin.

PPK may rarely occur as an adverse reaction to the influenza vaccine.[15]

Systemic diseaseassociated PPK

o

Myxedema is associated with distinctive features that include its response to

treatment and the severity and verrucosity of the hyperkeratosis, with diffuse
involvement of the plantar surface and more limited involvement of the palms.
The mechanism is unclear; however, it has been postulated that inhibition of
carotene conversion to vitamin A by thyroxine deficiency may cause
hyperkeratosis. Mild relief is achieved with thyroid hormone replacement.

Diabetes mellitus features include discrete plantar keratosis under the

metatarsal arch and the great toe.

Chronic lymphedema and other circulatory disorders such as acrocyanosis and

livedo reticularis have been associated with keratoderma.

Cutaneous T-cell lymphoma features diffuse hyperkeratosis accompanied by

subungual hyperkeratosis and nail dystrophy, which is typical of Szary
syndrome.

Diets lacking protein energy and vitamin deficiency have been implicated in
PPK with associated fissuring.

Syndromes With PPK as an Associated Feature

Basal cell nevus syndrome

Bullous congential ichthyosiform erythroderma

Cantu syndrome - Hyperkeratosis-hyperpigmentation syndrome

Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome

Cole disease - Guttate hypopigmentation and punctate PPK

Congenital nonbullous ichthyosiform erythroderma

Darier disease

Ectodermal dysplasia with skin fragility

Epidermodysplasia verruciformis

Epidermolysis bullosa herpetiformis (Dowling-Meara type)

Erythrokeratoderma variabilis

Familial pityriasis rubra pilaris

Hystrixlike ichthyosis-deafness (HID) syndrome

Ichthyosis hystrix of Curth-Macklin

Ichthyosis vulgaris

Incontinentia pigmenti

Keratitis, ichthyosis, and deafness (KID) syndrome

Lamellar ichthyosis

Progressive symmetric erythrokeratoderma

Schpf-Schulz-Passarge syndrome - PPK with hidrocystomas, hypodontia and

hypotrichosis

Sjgren-Larsson syndrome

Treatment & Management

Treatment of all types of hereditary and nonhereditary keratodermas is difficult. The most
common therapeutic options only result in short-term improvement and are frequently
compounded by unacceptable adverse effects. Treatment tends to be symptomatic and may
vary from simple measures (eg, saltwater soaks, paring) to topical keratolytics, systemic
retinoids, or reconstructive surgery with total excision of the hyperkeratotic skin followed by
grafting. The mainstays of treatment include the following:

Topical keratolytics (eg, salicylic acid 5%, lactic acid 10%, urea 10-40%) are useful in
patients with limited keratoderma.
Topical retinoids (eg, tretinoin) are effective, but treatment is often limited by skin
irritation.

Consider potent topical steroids with or without keratolytics in dermatoses with an

inflammatory component.

Oral retinoids are effective, especially in some hereditary PPKs such as mal de
Meleda, Papillon-Lefvre syndrome, and erythrokeratoderma variabilis. Most
hereditary PPKs require long-term treatment. Results indicate that acitretin is
comparable to etretinate. Intermittent therapy should be attempted whenever possible.
To limit unacceptable long-term adverse effects, the optimal dosage of acitretin in
adults is 30-35 mg/d (0.5-1 mg/kg/d for adults and 0.5 mg/kg/d for children).
Treatment of women of childbearing age results in long-term potential teratogenic
effects. The maintenance dose can be reduced to 25 mg/d. Caution is advised if the
patient has an epidermolytic form because large erosions may occur with retinoid
therapy. Some patients with KID syndrome have had worsening keratitis with
retinoids. Patients should be started on a low dose, and the dose should be carefully
increased to avoid flaring the disease and/or causing erosions.

Specific therapies dependent on the PPK type may be used. Psoralens and ultraviolet
A (PUVA) or re-PUVA (a combination of oral retinoids and PUVA) may be indicated
in persons with PPK secondary to psoriasis or eczema. Patients with oculocutaneous
tyrosinemia may benefit from dietary restriction of phenylalanine and tyrosine.
Improvement has been seen in persons with nonhereditary PPK after oral 1-alpha, 25dihydroxyvitamin D-3.

Careful selection of footwear and treatment of fungal infections are important.

Dermabrasion may permit increased penetration of topical agents, and carbon dioxide
laser treatment may be beneficial in persons with limited keratodermas.

For severe and refractory keratoderma, consider surgery. Total excision of

hyperkeratotic skin followed by grafting has been successful in a number of cases.

Paraneoplastic keratodermas are generally refractory to local treatment and may only
respond to removal of the underlying neoplasm.

Molluscum Contagiosum

Background

Molluscum contagiosum virus causes a benign viral infection that is largely (if not
exclusively) a disease of humans. Molluscum contagiosum virus causes characteristic skin
lesions consisting of single or, more often, multiple, rounded, dome-shaped, pink, waxy
papules that are 2-5 mm (rarely up to 1.5 cm in the case of a giant molluscus) in diameter.
The papules are umbilicated and contain a caseous plug. See the images below for examples.
(See Presentation and Workup.)

Note the central umbilication in these classic lesions of

molluscum contagiosum.
Approximately 10% of patients
develop eczema around lesions. Eczema associated with molluscum lesions spontaneously

subsides following removal.

Larger lesions may have several
clumps of molluscum bodies rather than the more common single central umbilication. This

may make them difficult to recognize as molluscum contagiosum.

Molluscum contagiosum on the right axilla.
Molluscum contagiosum virus is an unclassified member of the Poxviridae family. It cannot
be grown in tissue culture or eggs; it has been grown in human foreskin grafted to athymic
mice but has not been transmitted to other laboratory animals. (See Etiology.)
Through restrictive endonuclease analysis of the genomes of isolates, molluscum
contagiosum virus types I-IV have been identified. In a study of 147 patients, molluscum
contagiosum virus I caused 96.6% of infections, and molluscum contagiosum virus II caused
3.4%; however, no relationship was observed between virus type and lesional morphology or
anatomical distribution.[1] Molluscum contagiosum viruses III and IV are rare. In patients with
human immunodeficiency virus (HIV) infection, molluscum contagiosum virus II causes
most infections (60%).
Bateman first described the disease in 1817, and Paterson demonstrated its infectious nature
in 1841. In 1905, Juliusburg proved its viral nature. Infection follows contact with infected
persons or contaminated objects, but the extent of epidermal injury necessary is unknown.
Lesions may spread by autoinoculation.

Complications
Complications of molluscum contagiosum include irritation, inflammation, and secondary
infections. Lesions on eyelids may be associated with follicular or papillary conjunctivitis.
Bacterial superinfection may occur but is seldom of clinical significance. (See Prognosis,
Treatment, and Medication.)
Cellulitis is an unusual complication of molluscum contagiosum in patients who are HIV
infected.[2] Secondary infection with Staphylococcus aureus has resulted in abscess formation,
whereas Pseudomonas aeruginosa can cause necrotizing cellulitis.

Etiology
Transmission
The molluscum contagiosum virus may be inoculated along a line of minor skin trauma (eg,
from shaving), resulting in lesions arranged in a linear pattern (see the image below). This
process, termed autoinoculation, can also result from manipulation of lesions by the patient.
Autoinoculation is different from the Koebner phenomenon, which is also called an

isomorphic response. In the Koebner phenomenon, new lesions develop along a line of
trauma and the etiology of the underlying condition is unknown. Psoriasis and lichen planus
are examples of skin conditions that commonly koebnerize.

In a patient who had preexisting molluscum contagiosum, the

virus was inoculated along a line of minor skin trauma, resulting in the development of the 3
new lesions.
Molluscum contagiosum virus transmission through direct skin contact between children
sharing a bath and between athletes sharing gymnasium equipment and benches has been
reported. An association between school swimming pool use and molluscum contagiosum
infection has also been reported.[3, 4]
Three distinct disease patterns are observed in 3 different patient populations: children, adults
who are immunocompetent, and patients who are immunocompromised (children or adults).
The prognosis and therapy are different for each of these groups.
Molluscum contagiosum is most common in children who become infected through direct
skin-to-skin contact or indirect skin contact with fomites, such as bath towels, sponges, and
gymnasium equipment. Lesions typically occur on the chest, arms, trunk, legs, and face.
Hundreds of lesions may develop in intertriginous areas, such as the axillae and intercrural
region (see the image below). Lesions may rarely occur on the mucous membranes of the lip,
tongue, and buccal mucosa. The palms are spared. Patients with atopic dermatitis may
develop large numbers of lesions.

Molluscum lesions may become quite numerous in intertriginous areas.

This child has autoinoculated lesions to both inner thighs.
In adults, molluscum contagiosum most commonly is a sexually transmitted disease (STD).
Healthy adults tend to have few lesions, which are limited to the perineum, genitalia, lower
abdomen, or buttocks. Molluscum contagiosum in healthy children and adults is usually a
self-limited disease.

Widespread, persistent, and atypical molluscum contagiosum may occur in patients who are
significantly immunocompromised or have acquired immunodeficiency syndrome (AIDS)
with low CD4 T-lymphocyte counts (see the images below). Molluscum contagiosum may be
the presenting complaint in patients with AIDS. Molluscum contagiosum virus infection in
immunocompromised patients may be particularly resistant to therapy. Other opportunistic
infections in these patients may closely resemble molluscum contagiosum.

Molluscum contagiosum rarely occurs on the face in an adult

unless the patient is infected with HIV. When molluscum contagiosum occurs in individuals
infected with HIV, facial lesions are common and frequently numerous.

Molluscum contagiosum lesions in individuals infected with

HIV may number in the hundreds. In addition, they may become quite large and prominent.

Multiple papules on the face of a man with HIV.

Case reports have detailed molluscum contagiosum eruptions in areas that were treated with
tacrolimus 0.1% (Protopic).[5, 6, 7]

Infection
The molluscum contagiosum virus replicates in the cytoplasm of epithelial cells, producing
cytoplasmic inclusions and enlargement of infected cells. This virus infects only the
epidermis. Infection follows contact with infected persons or contaminated objects, but the
extent of necessary epidermal injury is unknown. The initial infection seems to occur in the
basal layer, and the incubation period is usually 2-7 weeks. This is suggested by the fact that,
although viral particles are noted in the basal layer, viral deoxyribonucleic acid (DNA)
replication and the formation of new viral particles do not occur until the spindle and granular

layers of the epidermis are involved. Infection may be accompanied by a latent period of as
long as 6 months.
Following infection, cellular proliferation produces lobulated epidermal growths that
compress epidermal papillae, while fibrous septa between the lobules produce pear-shaped
clumps with the apex upwards. The basal layer remains intact.
Cells at the core of the lesion show the greatest distortion and are ultimately destroyed,
resulting in large hyaline bodies (ie, molluscum bodies, Henderson-Paterson bodies)
containing cytoplasmic masses of virus material. These bodies are present in large numbers
and appear as a white depression at the center of fully developed lesions. Occasionally, the
lesions can progress beyond local cellular proliferation and become inflamed with attendant
edema, increased vascularity, and infiltration by neutrophils, lymphocytes, and monocytes.
As with other poxviruses, molluscum contagiosum virus does not appear to develop latency
but evades the immune system through the production of virus-specific proteins. Cellmediated immunity is most important in modulating and controlling the infection. Children
and patients with HIV infection generally have more widespread lesions. Prevalence of
molluscum contagiosum virus in patients with HIV may be as high as 5-18%, and the severity
of infection is inversely related to the CD4 T-lymphocyte count. More extensive and resistant
infections also are noted in patients receiving prednisone and methotrexate.
The virus is not strongly immunogenic, as it infrequently induces antibody formation.
Specific antibodies have been found in approximately 80% of patients and in about 15% of
control subjects. A role for humoral immunity in regression of lesions is not established.
Reinfection is common.

Viral characteristics
Molluscum contagiosum is a viral disease caused by a DNA poxvirus and is largely, if not
exclusively, a disease of humans. It is an unclassified member of the Poxviridae family (ie,
poxviruses).
The poxviruses are a large group of viruses with a high molecular weight. They are the
largest animal viruses, only slightly smaller than the smallest bacteria, and are just visible
using light microscopy. They are complex DNA viruses that replicate in the cytoplasm and
are especially adapted to epidermal cells. They cannot be grown in tissue culture or eggs.
Molluscum contagiosum virus has been grown in human foreskin grafted to athymic mice but
not in other laboratory animals.
Humans are the host for the following 3 types of molluscum contagiosum virus:

Orthopoxvirus - This resembles variola (smallpox) and vaccinia, which are ovoid (300
x 250 nm)
Parapoxvirus - These are orf and milkers nodule viruses, which are cylindrical (260
x 160 nm)
Unclassified (with features that are intermediate between those of the orthopox and
parapox groups) - These are intermediate in structure (275 X 200 nm); they include
molluscum contagiosum virus and tanapox

The primary structure and coding capacity of molluscum contagiosum virus was determined
by Senkevich et al.[8] Analysis of the molluscum contagiosum virus genome has revealed that
it encodes approximately 182 proteins, 105 of which have direct counterparts in
orthopoxviruses.
Restriction endonuclease analysis of the genomes has identified 4 types. Molluscum
contagiosum virus I and molluscum contagiosum virus II have genomes of 185 kilobases (kb)
and 195 kb, respectively. Molluscum contagiosum virus III and IV are very rare.
No relationship between virus type and lesional morphology or anatomical distribution is
known. Molluscum contagiosum virus encodes an antioxidant protein (MC066L),
selenoprotein, which functions as a scavenger of reactive oxygen metabolites and protects
cells from damage from ultraviolet (UV) light and peroxide. The particular role of this
protein is not known.
In one study, type I caused 96.6% and type II caused 3.4% of infections in 147 patients, but
no relationship was observed between virus type and lesional morphology or anatomic
distribution.[1]

Epidemiology
Occurrence in the United States
Molluscum contagiosum is a common infection throughout the United States and accounts
for approximately 1% of all skin disorders diagnosed. Data reported from 1969-1983 by the
National Disease and Therapeutic Index Survey show an increasing number of patient visits.
The prevalence rate in patients with HIV is reported to be 5-18%, and, if the CD4 cell counts
are less than 100 cells/L, the prevalence of molluscum contagiosum is reported to be as high
as 33%.

International occurrence
The molluscum contagiosum virus occurs throughout the world, and its incidence in most
areas is not reliably known. It is more prevalent in tropical areas. In Mali, molluscum
contagiosum is among the most frequent dermatoses in children, with an incidence of 3.6%.[9]
In Australia, an overall seropositivity rate of 23% is reported.[10] The lowest antibody
prevalence was in children aged 6 months to 2 years (3%), and seropositivity increased with
age to reach 39% in persons aged 50 years or older.
Childhood molluscum contagiosum is common in Papua New Guinea, Fiji, and certain parts
of Africa. During a regional outbreak in East Africa, it was estimated that 17% of the village
population and as many as 52% of children older than age 2 years developed lesions.
Epidemiologic studies suggest that transmission may be related to poor hygiene and climatic
factors such as warmth and humidity.

Race- and sex-related demographics

During a US longitudinal study performed from 1977-1981, 2-4 times as many cases were
found in whites than in persons of other races.[11] Whether the noted difference was secondary

to differences in access to medical care, other socioeconomic factors, or genetic

predisposition is unclear.[12]
Several studies have shown that males are affected by molluscum contagiosum more
commonly than are females. Data from STD clinics in England and Wales revealed that more
than twice as many men as women were diagnosed with the infection.

Age-related demographics
Molluscum contagiosum is rare in children younger than age 1 year, perhaps because of
maternally transmitted immunity and a long incubation period; otherwise, incidence seems to
reflect exposure to others. The greatest incidence is in children younger than age 5 years and
in young adults. The peak among the pediatric age group correlates with casual contact,
whereas the peak in young adults correlates with sexual contact.[13, 14]
Spread of the virus among households is common in warm climate countries where children
are lightly dressed and in close contact with one another and where personal hygiene may be
poor. The age of peak incidence is reported to be 2-3 years in Fiji and 1-4 years in the Congo
(formerly Zaire). In New Guinea, the annual infection rate for children younger than age 10
years was found to be 6%.
In cooler climates, spread within households is less common, and infection is more common
at a later age. Use of school swimming pools is correlated with childhood infections, with a
peak incidence in children aged 10-12 years in Scotland and 8 years in Japan. Prevalence
appears to be increasing in all age groups.

Prognosis
The prognosis in molluscum contagiosum is generally excellent because the disease is usually
benign and self-limited. Spontaneous resolution generally occurs by 18 months in
immunocompetent individuals; however, lesions have been reported to persist for as long as 5
years. In healthy patients, treatments are usually effective, although lesions can be disfiguring
and may produce anxiety in the patient, family, and daycare facility or school.
Recurrences occur in as many as 35% of patients after initial clearing. The significance of
these recurrences is unknown. They may represent reinfection, exacerbation of ongoing
disease, or new lesions arising after a prolonged latent period.
The disease often becomes generalized in patients who are infected with HIV or are
otherwise immunocompromised. A direct correlation has been found between increasing
severity of the disease and lower CD4 counts. The duration of infection is uncertain in
populations with HIV infection and in populations that are otherwise immunocompromised
(eg, patients who have undergone renal transplant), because molluscum contagiosum may not
be self-limiting in these cases.

Morbidity and mortality

Molluscum contagiosum is generally a benign and self-limited infection. For the most part,
morbidity is caused by temporary adverse cosmetic results. Morbidity is higher in

immunocompromised patients because they tend to have more lesions and more widespread
infection. Most lesions resolve with no permanent residual skin defect; however, occasional
lesions may produce a slightly depressed scar. This may represent deeper skin damage in
lesions that were particularly inflammatory or secondarily infected. Involvement of the
margin of the eyelids may produce keratoconjunctivitis. No mortality has been associated
directly with the molluscum contagiosum virus.

Patient Education
Before attempting any therapy, educate the patient or parents in-depth about the diagnosis,
prognosis, risk of autoinoculation or infection of others, therapeutic options, and risks of
therapy.[15, 16] More than 1 treatment session is frequently required. Providing this information
at the first clinical visit is particularly important when treating benign lesions, such as those
of molluscum contagiosum and common warts. A few extra minutes of explanation at this
stage can prevent or mitigate numerous problems and questions during later visits.[17]
When lesions fail to respond to initial therapy, a temptation to be overzealous in treatment
may occur. Patients and families are more understanding and less likely to demand aggressive
therapy when reasonable goals and limitations of therapy are thoroughly discussed.
Stress the benign nature of this ubiquitous disease to the patient and his or her parents.
Limiting physical contact with infected areas of skin and good handwashing may reduce
transmission. Instruct the patient to avoid scratching, which may result in autoinoculation.
Keeping children out of school is not necessary; however, discourage physical contact and
sharing of clothes and towels. In smaller children in whom physical contact is more difficult
to prevent, keeping infected areas covered with clothing is reasonable. Cover exposed lesions
with tape or an adhesive bandage. Infection of other children cannot be completely prevented.
Because the disease is extremely common and of very little clinical significance, the decision
to limit infected children from daycare centers must be approached on a case-by-case basis.
In adolescent and adult patient populations, this disease is usually sexually transmitted.
Encourage safe sex and abstinence; however, whether condoms and other barrier methods
provide adequate protection against transmission is unclear.
Emphasize that not all STDs are as benign as molluscum contagiosum virus (eg, herpes
simplex, gonorrhea, chlamydia, HIV). Stress adherence to abstinence until lesions resolve. In
the patient with multiple sexual partners or other risk factors, HIV testing is strongly
recommended. Note that not all cases in adults are sexually transmitted. This diagnosis can
cause significant relationship stress.
For patient education information, see the Skin Conditions and Beauty Center, as well as
Molluscum Contagiosum.

History
Molluscum contagiosum is usually asymptomatic; however, individual lesions may be tender
or pruritic. In general, the patient does not experience systemic symptoms, such as fever,
nausea, or malaise.

The patient may recall contact with an infected sexual partner, family member, or other
person. Patients who report having multiple sexual partners or unprotected sex have an
increased risk of infection. Contact may be reported in children sharing a bath or in athletes
sharing gymnasium equipment and benches. Parents may report recent exposure to other
children affected with molluscum contagiosum at school, camp, or public recreational
facilities (eg, gymnasiums, swimming pools).
If the patient has skin conditions that disrupt the epidermal layer, molluscum tends to spread
more rapidly.
The patient may notice new lesions developing along a scratch in areas of involved skin.
Patients with atopic dermatitis may have more extensive disease and may have a positive
family history of atopy (eg, eczema, asthma, hayfever). Children frequently have active
atopic dermatitis.
A report detailed an eruption of molluscum contagiosum in a patient who had undergone a
renal transplant.[18] Case reports have detailed molluscum contagiosum eruptions in areas that
were treated with tacrolimus 0.1% (Protopic).[5, 6, 7]
Duration of the individual lesion and of the attack varies. Although most cases resolve
without therapy within 6-9 months, some persist for 3-4 years. Individual lesions seldom
persist more than 2 months.
Patients with HIV or those receiving prednisone, methotrexate, or other immunosuppressive
medications may have more extensive and resistant infections.

Patients infected with HIV

Patients generally have a low CD4 count, with the severity of infection being inversely
related to the count.
Patients who are poorly compliant or noncompliant with highly active antiretroviral therapy
(HAART) for the treatment of HIV are at an increased risk, as are patients who have multiple
sexual partners. The frequency of unprotected sex also increases the risk of transmission.

Physical Examination
Lesions are discrete, nontender, flesh-colored, dome-shaped papules that show a central
umbilication (which is more apparent when the lesion is frosted with liquid nitrogen). (See
the image below.)

Presented here are the classic umbilicated papules of molluscum

contagiosum lesions on the cheek of a child. Facial lesions occur frequently in children,
although lesions generally are few.
Lesions are usually 2-5 mm (rarely up to 1.5 cm in the case of giant molluscus) in diameter
and may be present in groups or widely disseminated. Immunocompetent children and adults
usually have fewer than 20 lesions. Larger lesions may have several distinct clumps of
molluscum bodies (see the image below). Beneath the umbilicated center is a white, curdlike
core that contains molluscum bodies. Some lesions become confluent to form a plaque
(agminate form).

Larger lesions may have several clumps of molluscum bodies

rather than the more common single central umbilication. This may make them difficult to
recognize as molluscum contagiosum.
Lesions may be located anywhere; however, a predilection for the face, trunk, and extremities
is observed in children and a predilection for the groin and genitalia is observed in adults.
Lesions are seldom found on the palms and are rarely documented on the soles, oral mucosa,
or conjunctiva.
Distribution is influenced by the mode of infection, type of clothing worn, and climate. In
sexually active individuals, the lesions may be confined to the penis, pubis, and inner thighs
(see the image below). Widespread and persistent molluscum contagiosum may occur in
patients with AIDS and may be the presenting complaint.

Molluscum contagiosum on the shaft of the penis. Molluscum

contagiosum in the genital region of adults is most commonly acquired as a sexually
transmitted disease.
Molluscum contagiosum may be randomly associated with other lesions, such as epidermal
cysts, nevocellular nevi, sebaceous hyperplasias, and Kaposi sarcoma. Pseudocystic
molluscum contagiosum, giant molluscum contagiosum, and molluscum contagiosum
associated with other lesions are responsible for frequent clinical misdiagnosis.
Other characteristics of molluscum contagiosum to consider include the following:

Intertriginous areas - Hundreds of lesions may develop in intertriginous areas, such as

the axillae and intercrural region
Atopic dermatitis - Patients with atopic dermatitis occasionally develop large numbers
of lesions, which are confined to areas of lichenified skin

Eczema - Approximately 10% of patients develop eczema around the lesions, with
this being attributed to toxic substances produced by the virus or to a hypersensitivity
reaction to the virus; eczema that is associated with molluscum lesions subsides
spontaneously following removal (see the first image below)

Inflammatory changes - These result in suppuration, crusting, and eventual resolution

of the lesion; this inflammatory stage does not usually represent secondary infection
and seldom requires antibiotic therapy (see the second image below)

Approximately 10% of patients develop eczema

around lesions. Eczema associated with molluscum lesions spontaneously subsides

following removal.
After trauma, or spontaneously after
several months, inflammatory changes result in suppuration, crusting and eventual
resolution of the lesion. This inflammatory stage does not usually represent secondary
infection and seldom requires antibiotic therapy.
Disfiguring lesions may occur in patients with the following conditions:

AIDS - Facial and perioral molluscum contagiosum are most commonly observed as a
manifestation of HIV infection, particularly in homosexual men with HIV[19] ; at the
time of molluscum contagiosum diagnosis, the CD4 count is low
Immunocompromise - Lesions are especially common and extensive on the face and
neck

Sarcoidosis

Lymphocytic leukemia

Congenital immunodeficiency

Selective immunoglobulin M (IgM) deficiency

Thymoma

Treatment with prednisone and methotrexate

Disseminated malignancy

Refractory atopic dermatitis

Diagnostic Considerations
The cutaneous manifestations of other opportunistic infections, such as cutaneous
cryptococcosis, histoplasmosis, and aspergillosis, may mimic molluscum contagiosum and
must be ruled out in immunocompromised hosts. (See the images below.)

This lesion of cutaneous coccidioidomycosis could be

included among the differential diagnoses of molluscum contagiosum.

This keratoacanthoma could be included among the

differential diagnoses of molluscum contagiosum.
Molluscum contagiosum may be randomly associated with other lesions, such as epidermal
cysts, nevocellular nevi, sebaceous hyperplasias, and Kaposi sarcoma. Pseudocystic
molluscum contagiosum, giant molluscum contagiosum, and molluscum contagiosum
associated with other lesions are responsible for frequent clinical misdiagnoses.
Infection of children through sexual abuse is possible; however, to a greater extent than
warts, molluscum contagiosum virus is quite common on the genital, perineal, and
surrounding skin of children.[20, 21] Regard abuse as unlikely, unless other suspicious features
are present.
Histologic or microscopic confirmation of molluscum contagiosum is indicated in patients
who are immunocompromised because several life-threatening opportunistic infections may
clinically mimic molluscum contagiosum.
Conditions to consider in the differential diagnosis of molluscum contagiosum include the
following:

Keratoacanthoma
Verruca vulgaris (warts)

Eccrine poroma

Epidermal cyst

Foreign body granuloma

Lichen planus

Flat warts (verruca plana)

Pyoderma

Perforating disorders (all very rare in children) to consider in the differential diagnosis of
molluscum contagiosum include the following:

Acquired reactive perforating dermatosis of renal failure

Kyrle disease

Perforating serpiginous elastoma

Perforating folliculitis

Verrucous perforating collagenoma

Perforating granuloma annulare

Differential diagnoses to consider in patients with AIDS include the following:

Cutaneous cryptococcus[22] - Cutaneous cryptococcus presents as molluscumlike

eruptions (on the face, it often has a very dramatic appearance); the patient may have
few or no other symptoms associated with cryptococcal meningitis
Cutaneous coccidioidomycosis

Cutaneous histoplasmosis

Cutaneous aspergillosis

Differential Diagnoses

Basal Cell Carcinoma

Condyloma Acuminatum

Cryptococcosis

Keratosis Pilaris

Milia

Pearly Penile Papules

Pyogenic Granuloma

Surgical Treatment of Basal Cell Carcinoma

Varicella-Zoster Virus

Approach Considerations

In most instances, a diagnosis is easily established because of the distinctive, central

umbilication of the dome-shaped lesion. Pseudocystic molluscum contagiosum, giant
molluscum contagiosum, and molluscum contagiosum associated with other lesions
may be more difficult to diagnose clinically.

If diagnosis is uncertain, lesions may be biopsied. Characteristic intracytoplasmic

inclusion bodies (molluscum bodies, or Henderson-Paterson bodies) are seen on
histologic examination findings.

Express the pasty core of a lesion by crushing the lesion between 2 microscope slides
and staining it to reveal the particulate virions, which are present in abundance. Firm
compression between the slides is required to release the virions with the stain in
place. The use of crystal violet, safranin, and ammonium oxalate in 10% ethanol; the
Papanicolaou test; or Wright, Giemsa, or Gram stains can reveal the virions that make
up the Henderson-Paterson bodies.

Measure serum antibodies by complement fixation, tissue culture neutralization,

fluorescent antibody, and gel agar diffusion techniques; however, they are not well
standardized and are seldom used except in research protocols.

Polymerase chain reaction (PCR) assay can be used to detect and categorize
molluscum contagiosum virus in skin lesions.

Molluscum contagiosum virus cannot be grown in tissue culture; however, Buller et al

demonstrated molluscum contagiosum virus replication in an experimental system
using human foreskin grafted to athymic mice.[23]

Evaluate the patient for other sexually transmitted diseases (STDs) because sexually
active patients may acquire other concomitant venereal diseases, such as syphilis and
gonorrhea. Always consider testing for HIV infection in patients with facial lesions.

Squash preparation

Squash preparation is microscopic examination of cellular exudate. The cellular

material contained within the central umbilication may be extracted manually,
flattened between 2 microscope slides, and stained. Microscopic examination of this
preparation reveals the Henderson-Paterson bodies.

Histologic Findings

Lesions in molluscum contagiosum have a characteristic histopathology.[24] The

prototypical hematoxylin and eosin (H&E)stained histologic section in this disease
reveals a cup-shaped indentation of the epidermis into the dermis (as seen in the
images below). Downward proliferation of the rete ridges with envelopment by the
connective tissue forms the crater.

This low-power view of a molluscum contagiosum

lesion shows the classic cup-shaped invagination of the epidermis into dermis. The
Henderson-Paterson bodies are identified readily and stained purple to red in this

image.
Low-power histopathologic examination
reveals an overall cup-shaped appearance.
Within the region of the indentation, the epidermis appears thickened (acanthosis),
possibly measuring up to 6 times the thickness of the surrounding, uninvolved skin,
and the cornified layer typically is disintegrated. The striking feature is the presence
of intracytoplasmic, eosinophilic, granular inclusions within the keratinocytes of the
basal, spinous, and granular layers of the epidermis.

These inclusions, the Henderson-Paterson bodies, can measure 35m in diameter.

Ultrastructural studies have shown that these bodies are membrane-bound sacs that
contain numerous molluscum contagiosum virions. The viral particles increase in size
as they progress up toward the granular layer, causing compression of the nucleus to
the periphery of the infected keratinocytes. The surrounding dermis is relatively
unremarkable. Intact lesions show little or no inflammatory change. (See the images
below.)

This is a medium-power view of a molluscum

contagiosum lesion. Magnification allows better demonstration of the
intracytoplasmic molluscum bodies (staining purple-pink) within the keratinocytes.

Lesions of molluscum contagiosum have a

characteristic histopathology. Lobules containing hyalinized molluscum bodies, also

known as Henderson-Paterson bodies, are diagnostic.

This molluscum contagiosum body is an intracytoplasmic inclusion body. Notice in
the image that the keratinocyte nuclei are displaced to the periphery of the cell and
that the intracytoplasmic inclusions have a granular quality.

Cytoplasmic viral inclusions become progressively

larger toward the epidermal surface (hematoxylin and eosin, 200X)

Viral particles have a dumbbell-shaped appearance.

Courtesy of Alvin Zelickson, MD.
In nonprototypical cases of molluscum contagiosum, in which intradermal rupture of
molluscum bodies occurs, an intense, inflammatory dermal infiltrate consisting of
lymphocytes, histiocytes, and occasional foreign bodytype, multinucleated giant
cells may be observed. Rarely, metaplastic ossification may occur. Exceptionally, the
inflammatory dermal infiltrate may be intense enough to simulate a cutaneous
lymphoma (pseudolymphoma)

Approach Considerations
In healthy patients, molluscum contagiosum is generally self-limited and heals spontaneously
after several months. Individual lesions are seldom present for more than 2 months. Although
treatment is not required, it may help to reduce autoinoculation or transmission to close
contacts and improve clinical appearance.
Intervention may also be indicated if lesions persist. Therapeutic modalities include topical
application of various medications, radiation therapy, and/or surgery. Each technique may
result in scarring or postinflammatory pigmentary changes. Frequently, multiple treatment
sessions are necessary because of the recurrence of treated lesions and/or the appearance of
new lesions by autoinoculation. The benefit of therapy must exceed the risk.

Therapeutic options for molluscum contagiosum can be divided into broad categories,
including the following:

Benign neglect
Direct lesional trauma

Antiviral therapy

Immune response stimulation

Choice of therapy
The most appropriate therapeutic approach largely depends on the clinical situation. In
healthy children, a major goal is to limit discomfort, and benign neglect or minor, direct
lesional trauma is appropriate. In adults who are more motivated to have their lesions treated,
cryotherapy or curettage of individual lesions is effective and well tolerated.
In immunocompromised individuals, molluscum contagiosum may be very extensive and
difficult to treat. The goal may be to treat the most troublesome lesions only. In severe cases,
these patients may warrant more aggressive therapy with lasers, imiquimod, antiviral therapy,
or a combination of these. Of course, effective antiretroviral therapy in patients with AIDS
makes therapy of molluscum contagiosum much more effective.
The US Food and Drug Administration (FDA) has approved none of the topical or
intralesional agents for treatment of molluscum contagiosum.
In a study of the treatment of molluscum contagiosum in children, Hanna et al determined
that curettage was the most efficacious therapy. The investigators conducted a prospective,
randomized trial that compared the efficacy and adverse effects of 4 recognized treatments of
molluscum contagiosum in 124 children.[25] One group was treated with curettage, a second
with cantharidin, a third with a combination of salicylic acid and lactic acid, and a fourth with
imiquimod.
Curettage was found to be the most efficacious treatment and had the lowest rate of side
effects. However, it must be performed with adequate anesthesia and is a time-consuming
procedure. Cantharidin had moderate complications due to blisters and was slightly less
effective. The topical keratolytic used was too irritating for children. Topical imiquimod was
more effective than cantharidin but is expensive, and an optimum treatment schedule has yet
to be reported.

Follow-up
Repeat examination is recommended 2-4 weeks after treatment. Retreatment often is
necessary. Consider combination therapy in patients whose lesions respond poorly.

Activity
Instruct the patient to avoid activities or sports involving physical contact between infected
areas of skin and exposed skin of other participants.

Deterrence and prevention

Most cases in adolescents and adults are secondary to sexual contact. Abstinence and careful
selection of sexual partners are important. Whether condoms are effective in preventing
spread is unclear. Good personal hygiene is important in limiting transmission.
Autoinoculation may result from trauma, such as shaving or the manipulation of lesions by
the patient.

Pharmacologic Therapy
Clinical success has been reported with the use of the following topical agents, which may act
as irritants, stimulating an immunologic response:

Imiquimod cream - An immune response modifier approved for the treatment of

external genital and perianal warts in adults, imiquimod cream has been reported to be
effective in the treatment of molluscum contagiosum[26, 27] ; imiquimod cream may be
used in conjunction with cantharidin[28]
Cantharidin - Several studies report that cantharidin, a chemovesicant that can be used
in combination with imiquimod, is effective in treating molluscum contagiosum; to
test the patient's response to therapy, treat only a few lesions on the initial visit[28]

Tretinoin - This agent has reportedly been successful in the treatment of small
molluscum contagiosum lesions

Bichloracetic acid

Trichloroacetic acid

Salicylic acid

Lactic acid

Glycolic acid

Silver nitrate

Tretinoin, cantharidin, and imiquimod may be dispensed to the patient with application
instructions and close follow-up, although some recommend application in the office.
Bichloracetic acid, trichloroacetic acid, salicylic acid, lactic acid, glycolic acid, and silver
nitrate must be applied in the office by the physician.
Topical podophyllotoxin 0.5% cream self-administered twice daily for 3 weeks has been
reported effective in a placebo-controlled, double-blind study.[29]
Reports have suggested that subcutaneous interferon alfa administered intralesionally may be
useful in immunocompromised children.
A case report noted the efficacy of topical cidofovir in the treatment of disseminated
molluscum in immunodepressed patients.[6] Cidofovir diphosphate was reported to inhibit
molluscum contagiosum virus DNA polymerase activity.[30]

Benign Neglect
Leaving mollusca to spontaneously resolve is often reasonable,[31] especially in young
children for whom freezing or curettage may be painful and frightening. The dictum primum
non nocere (first do no harm) has a special significance in children with minor, self-limited
conditions. Many physicians refuse to treat children with small numbers of mollusca.
Lesions on the eyelids and central face may be particularly distressing to parents and patients.
When possible, treat lesions at other locations first, with the hope that the treatment may
stimulate the facial lesions to spontaneously resolve. When facial lesions require treatment,
the best option is to treat them frequently with minor physical trauma. (See the image below.)

Lesions on the upper eyelid of a 3-year-old child.

More aggressive therapy may be required in patients in whom the extent of disease is
intolerable and in patients who are immunocompromised.

Direct Lesional Trauma

Takematsu et al reported that disruption of the epidermal wall of Henderson-Paterson bodies
induces acute inflammatory changes by activation of the alternative complement pathway on
exposure to the tissue fluids; furthermore, the Henderson-Paterson bodies release
proinflammatory cytokines and other neutrophil chemotactic factors upon decomposition. [32]
This supports the observation that minor trauma to molluscum lesions frequently produces an
inflammatory response and resolution of the lesion. The Henderson-Paterson bodies can be
ruptured and a local inflammatory response created by various forms of physical trauma and
caustic topical agents.
Various caustic agents have been shown to be effective in treating molluscum contagiosum.
Tretinoin, salicylic acid, and potassium hydroxide[33, 34] may be used. Cantharidin,[28, 35] silver
nitrate,[36] trichloroacetic acid, and phenol also are options. Children may tolerate therapy with
these agents better than curettage or cryotherapy. None of these caustic agents has been
approved by the FDA for treatment of molluscum contagiosum.

Tretinoin cream
Tretinoin cream 0.1% or gel 0.025% is applied daily. Apply it to a region of skin with
scattered lesions. It may produce eczema and may increase the number of lesions through
autoinoculation; however, a small amount of tretinoin may be applied to individual lesions
with the rough end of a broken toothpick. Rotate the toothpick, gently abrading the lesion and

increasing the inflammatory response produced by the tretinoin. Treat lesions every few days
until significant inflammation or resolution occurs.

Potassium hydroxide
Potassium hydroxide is a strong alkali that has long been known to digest proteins, lipids, and
most other epithelial debris of skin scrapings to identify fungal infections. Topical 10%
potassium hydroxide aqueous solution applied twice daily on each molluscum contagiosum
lesion until all lesions undergo inflammation and superficial ulceration may be effective in
clearing molluscum contagiosum in children.

Cantharidin
Cantharidin is a chemovesicant that is highly effective in treating molluscum contagiosum;
however, this agent has lost favor with some physicians because of concerns regarding its
safety. However, if cantharidin is used properly, it is very effective, safe, and well tolerated
by children.
In a study by Silverberg et al in which 300 patients were treated with cantharidin, 90% of
patients experienced complete clearing after an average of 2.1 visits. Blisters occurred at sites
of application in 92% of patients. Temporary burning, pain, erythema, or pruritus was
reported in 6-37% of patients. No major adverse effects were reported, and no patients
experienced secondary bacterial infection. A total of 95% of parents reported that they would
proceed with cantharidin therapy again.[37]
Cantharidin is not approved by the FDA for treatment of any condition; however, it has been
used safely and effectively by dermatologists for many years.[38, 39] It is listed as acceptable
therapy in the American Academy of Dermatology treatment guidelines for warts; however,
because it has never been approved by the FDA for use in humans, it is no longer marketed as
medical therapy in the United States. Cantharidin crystals and diluent can be purchased in the
United States, and many dermatologists continue to use it. Cantharidin solution for the
treatment of warts and molluscum is available in Canada and many other countries.

Salicylic acid
Seventeen percent salicylic acid in collodion (Compound W, Freezone, Wart-Off, Occlusal) is
commonly used in treating verruca vulgaris. In most patients, repeated application to
individual molluscum contagiosum lesions until an inflammatory response is generated is
effective therapy.

Physical trauma
Varying degrees of physical trauma to individual lesions are used and are frequently quite
successful. Physical trauma to individual molluscum contagiosum lesions can be performed
with cryotherapy, lasers, curettage,[40, 41] expression of the central core with tweezers, rupture
of the central core with a needle or a toothpick,[42, 43] electrodesiccation, shave removal, or
duct tape occlusion.[44]

Instruct the parents to tease out the firm, white core at the center of lesions using a clean
needle or a toothpick. The process of irritating the lesion usually causes it to inflame and
resolve within 1-2 weeks. This safe and easy approach can be performed by the patient's
parent, limiting the need for follow-up visits.
In an office setting, curettage of individual lesions is easy and very effective. With a sharp
curette and a quick firm motion, small, individual lesions can be removed completely, with
little or no bleeding. With practice and a sharp curette, the provider may perform this
procedure with little or no discomfort. Older children, adolescents, and adults usually tolerate
this procedure better.
Other simple mechanical methods, such as expression of the contents in the papule by
squeezing it with forceps held parallel to the skin surface or shaving off the lesions with a
sharp scalpel, are effective.
Lesions may also be treated with light electrodesiccation. At very low voltage settings,
anesthesia may not be required.
Cryotherapy is the first-line treatment for many physicians, particularly in adolescents and
adults. A brief freeze, which causes icing of the lesion and a thin rim of surrounding skin, is
usually adequate. Treatment is repeated at intervals of 2-3 weeks until all lesions resolve.
Achieve accurate spray of liquid nitrogen by using a disposable ear speculum. The small end
is placed against the skin, and liquid nitrogen is sprayed into the funnel created. Lesions also
may be treated with cotton-tip applicators chilled in liquid nitrogen and held against the
lesion until a small amount of frosting occurs. Cryotherapy is painful and the smoke that rises
off the cold applicator or the noise of the liquid nitrogen sprayer may be quite frightening to
younger children.
Pulsed dye laser (PDL) therapy has been shown to be more than 95% successful in treating
individual lesions with 1 treatment. PDL treatment of molluscum contagiosum has been used
successfully in patients with AIDS. A significant reduction in the number of molluscum
contagiosum lesions following a single treatment with the PDL can be attained. Treated areas
may remain disease-free for months. Although cost and availability are major limiting factors
for routine use, PDL therapy may be considered for treatment of extensive or resistant
lesions. It may also be valuable in immunocompromised individuals with extensive disease.
[45, 46, 47, 48, 49]

Treatment of molluscum contagiosum in patients with AIDS remains a challenge. The

combination of 2 or more therapeutic modalities, such as carbon dioxide laser, PDL, and
trichloroacetic acid, can be of much help to improve the quality of life of these patients.
The discomfort of curettage or other mechanical removal may be reduced. Lesions may be
sprayed with ethyl chloride until frosting has occurred and then scraped away with a curette.
The application of local anesthetic cream, EMLA (a eutectic mixture of 5% lignocaine and
prilocaine) or its equivalent, may permit painless treatment. The cream is best applied under
occlusion 1-2 hours before the planned procedure.

Immune Response Stimulation

Imiquimod cream, intralesional interferon alfa,[50] and topical injections of streptococcal

antigen[51] have been shown to be effective in treating patients with resistant molluscum
contagiosum. The high cost of these products limits their use to more extensive or resistant
infections. Imiquimod cream applied 3 times per week for 16 weeks is an option in severe
cases. The dosing schedule and length of treatment require further evaluation.[25, 27, 52, 53, 54, 55, 56,
57]

Imiquimod is a novel topical immune response modifier that is a potent inducer of

interferons. Various treatment regimens have been effective in treating molluscum
contagiosum. In children[58, 59] and in some patients with AIDS-associated molluscum
contagiosum,[60, 26] 1% cream applied 3 times daily or 5% cream applied at every bedtime for 4
weeks appears to be effective treatment.
A newer compound, Veregen,is a sinecatechin. Its true mechanism of action is unknown. It is
a botanical extract from green tea. The 15% ointment is applied topically 3 times a day. It is
FDA approved for topical therapy for external genital warts and perianal warts, but it is used
off label for molluscum as well as verruca plana.[61]

Antiviral Therapy
In immunocompromised patients, improvement of lesions has been observed in individual
patients treated with ritonavir, cidofovir (intravenous and topical),[62, 63] and zidovudine. Not
surprisingly, patients with AIDS and severe molluscum contagiosum improve with effective
antiretroviral therapy.

Medication Summary
Molluscum contagiosum usually resolves within months in people with a normal immune
system. Many treatments have been promoted for molluscum contagiosum. The common
goal of most treatment methods is the destruction of lesions and the development of a
localized inflammatory reaction. Extensive controlled studies have not been performed and
all treatments have advantages and disadvantages. A review for the Cochrane Database
examined the effects of several topical, systemic, and homeopathic interventions.[64]
Among the findings, the investigators determined that there was limited evidence for the
efficacy of sodium nitrite coapplied with salicylic acid compared with salicylic acid alone.
In addition, no statistically significant differences were found for topical povidone iodine
plus salicylic acid compared with either povidone iodine or salicylic acid alone
The investigators also found no statistically significant differences between treatment with
placebo and therapy with potassium hydroxide or between placebo treatment and systemic
treatment with cimetidine or calcarea carbonica, a homeopathic drug.
The authors concluded no single intervention has been shown to be convincingly effective in
treating molluscum contagiosum. However, various limitations were found in the studies
reviewed, and the investigators cautioned that small study sizes may have caused some
important treatment differences to be missed. None of the evaluated treatment options were
associated with serious adverse effects.

Keratolytic Agents
Class Summary
These agents inhibit cell growth and destroy infected cells. They are applied directly to
lesions. To decrease discomfort, treat a small number of lesions at each visit.
View full drug information

Salicylic acid (Compound W, Freezone, Wart-Off)

Salicylic acid produces desquamation and inflammation. Various liquid products that contain
17% salicylic acid as the caustic agent or as part of a mix of caustic agents used to treat
molluscum contagiosum and warts are available. Most of these products include an adhesive
such as collodion or a clear nail-polishlike material, which dries within seconds of
application. This helps to concentrate the caustic agent on the lesion and minimize spread to
the surrounding skin.
View full drug information

Tretinoin topical (Retin-A, Avita, Tretin-X)

Tretinoin is available in various bases and concentrations (0.025%, 0.05%, 0.1% cream;
0.01%, 0.025%, 0.1% gel; 0.05% solution). Applied to a region of skin with scattered lesions,
tretinoin may produce eczema and increase the number of lesions through autoinoculation.
However, a small amount of tretinoin may be applied to individual lesions with good effect.

Cantharidin

Cantharidin is a strong vesicant. It has not been approved by the FDA for the treatment of any
condition but has been safely and effectively used by dermatologists for years. In the
American Academy of Dermatology treatment guidelines for warts, it is listed as the secondline therapy following liquid nitrogen. However, because cantharidin has never been
approved by the FDA for use in humans, it is no longer marketed in the United States.
Cantharidin crystals and diluent can be purchased in the United States, and numerous
dermatologists continue to use it. Cantharidin solution for the treatment of warts and
molluscum is available in Canada and many other countries. The effectiveness results from
the exfoliation of the lesion as a consequence of cantharidin's vesicant action. The lytic action
does not go below the basement membrane of epidermal cells. As a result, unless the area
becomes secondarily traumatized or infected, no scarring from topical application occurs.

Topical Skin Products

Class Summary
These agents induce cytokines, including interferon. They are typically reserved for use in
patients with molluscum contagiosum that is refractory to cryotherapy or tretinoin.
View full drug information

Imiquimod 5% cream (Aldara, Zyclara)

Imiquimod induces the secretion of interferon alfa and other cytokines; its mechanisms of
action are unknown.

Antivirals, Other
Class Summary
Presumably, antiviral drugs may interfere with the ability of the molluscum contagiosum
virus to replicate. Because of their expense and adverse effect potential, consider these
products for use only in immunocompromised patients.
View full drug information

Cidofovir (Vistide)

Cidofovir is a selective inhibitor of viral DNA production in cytomegalovirus and other

herpes viruses. One case report showed improvement in 3 out of 3 patients with HIV and
extensive co-infection with molluscum contagiosum virus.
View full drug information

Ritonavir (Norvir)

Ritonavir is an antiretroviral protease inhibitor. In one case report, a patient with HIV and
intractable molluscum contagiosum had resolution of lesions after treatment.

Herbal Formulations
Class Summary

These agents are over-the-counter, herbal alternatives. It is essential to be aware, however,

that herbal formulations are not regulated by the FDA.

Australian lemon myrtle (Backhousia citriodora)

This is a 10% solution of essential oil of Australian lemon myrtle.[65]