Skin-Colored Lesions



Skin-Colored Lesions


Peter J. Lynch



“Skin colored” refers to those lesions whose color is of the same hue as the patient’s surrounding normal skin. Thus, in a darkly pigmented person, skin-colored lesions would be brown. Likewise, skin-colored lesions on a pink or red mucosal surface will also be pink or red. Skin-colored lesions may be benign or malignant.


Genital Warts

Genital warts are caused by infection with human papillomavirus (HPV). They are common benign neoplasms that are significant because of (a) their transmissibility, (b) the association of some HPV types with the development of malignancy, and (c) our current inability to eradicate latent HPV from infected tissue. In contrast with herpes simplex virus (HSV) where there are two viral types, HSV1 and HSV2, there are over 200 HPV types (1).


Clinical Presentation

Most anogenital HPV infections occur at a subclinical (asymptomatic) level and only a small percentage (about 10%) of those infected will develop clinical lesions in the form of genital warts and precancerous lesions (2). Asymptomatic anogenital infection due to HPV is extremely common. Most sexually active individuals will become infected at least once in their lifetime (3). Moreover, about 20% of women in their late teens and early twenties have molecular evidence of HPV DNA infection (4). This rate decreases with age, declining to about 5% in older women. Not surprisingly, the rates are even higher in special groups such as prisoners, patients who attend a sexually transmitted disease (STD) clinic, and men who have sex with men. The few studies carried out in men show great variability, but the average prevalence appears similar to that in women. The prevalence of symptomatic anogenital infection (anogenital warts and precancerous lesions) is approximately 0.1% to 5%in men and women worldwide (5). These data suggest that HPV infection represents the most common STD worldwide (2).

HPV infection is quite transmissible, and the major risk factor for acquisition of the virus relates to sexual activity. Specifically, the risk of infection correlates best with number of past sexual partners and the acquisition of a recent, new sexual partner (2). Most HPV transmission occurs by way of vaginal and anal intercourse, but other forms of sexual activity with skin-to-skin contact also result in high transmission rates. In contrast, among children with anogenital warts, most transmission occurs through nonsexual contact (6). Condom use and male circumcision appear to decrease the risk of transmission.

There are four major morphologic variants of genital warts. Those found in persistently moist areas tend to be skin colored and filiform (e.g., tall and narrow) with or without a brushlike tip (Fig. 5.1). This variant is appropriately termed “condylomata accuminata” and, strictly speaking, is the only variant for which this term should be used. The second variant occurring in the anogenital area is verruca vulgaris (common warts) (Fig. 5-2). These are skin colored and similar in appearance to hand warts. They are about as wide (5 to 10 mm) as they are tall and typically have palpable, if not visible, surface roughness due to the presence of scale. They are located on the drier aspects of the anogenital tissue. Smooth-surfaced, flat-topped papules (wider than they are tall) represent the third variant (Fig. 5.3). These are usually 3 to 15 mm in diameter but individual lesions may coalesce to form slightly elevated plaques several centimeters or more in diameter. They can occur on either moist or dry surfaces. While often skin colored, these flat-topped warts may also be pink, red, brown, or black. Large globular warts, 2 to 4 cm in diameter, correspond to the fourth variant (Fig. 5.4). They have a smooth, but often cauliflower-like surface and are skin colored, pink, or red in hue. This type of lesion is often termed a giant condyloma or Buschke-Lowenstein tumor.

Genital warts occur most often in individuals between the ages of 16 and 25 years. Although genital warts are usually asymptomatic, they occasionally produce itching and irritation. The number and size of lesions in an infected individual presumably depend on the immunologic resistance that the host can mount against the infecting virus. Thus, some individuals with very good immune response may have only a few small lesions that disappear spontaneously or respond readily to treatment. Other patients exhibit numerous small and large lesions that are very resistant to almost all attempts at therapy.







FIG. 5.1. These closely set warts are long with pointed tips, the filiform morphology called condylomata acuminata. Because they are wet, these tips have stuck together.

In men, most genital lesions involve the shaft of the penis and, less frequently, the glans, foreskin, scrotum, groin, and periurethral or intraurethral area. Perianal and anal warts occur more commonly in men who have sex with men but also can develop in heterosexual men. In women, genital warts occur most commonly around the vaginal introitus, the vulvar vestibule, and surrounding anogenital skin. Fifty percent of women with vulvar warts have evidence of cervical HPV infection. Women may develop perianal warts, and, not surprisingly, their presence at this site is especially likely in those who practice receptive anal intercourse.




Management

As noted above, genital warts may resolve spontaneously, especially in children and young adults. This resolution, if it is to occur, takes an average of several months. Contrarily, those warts containing high-risk HPV types and those occurring in immunosuppressed patients are likely to remain in place indefinitely. In spite of the potential for resolution, most anogenital warts should be treated to reduce contagion occurring through sexual activity. This is particularly important because it is not possible to determine clinically which warts contain foci of dysplastic change. However, it is extremely important to note that treatment only eradicates visible lesions; latent virus remains in place indefinitely. This leads to high recurrence rates regardless of the type of treatment used.

Before considering treatment options, clinicians should consider whether or not biopsy of one or more lesions should be undertaken. As indicated above, flattopped warts (regardless of color) and large globular warts should be biopsied because of the possibility that in situ or invasive SCC may be present. Shave biopsy is acceptable for flat-topped warts, whereas shave excision is preferred for large globular warts because of the greater risk of sampling error in these large lesions. Filiform lesions and those mimicking hand warts (see above) may be treated without biopsy due to the very low likelihood that dysplasia will be present.

Multiple approaches to treatment are available (8,9). Treatment needs to be individualized for each patient as no single therapy is universally preferable. One of the first priorities in the treatment process is the education of patients regarding the contagious aspects of the viral infection, the likelihood of recurrence after therapy, and, in some instances, the potential for malignant transformation. After this has been accomplished, input from the patient should be sought as to whether the treatment is to be undertaken by the patient (patient-based therapy) or by the clinician (clinician-based therapy).

There are three prescription-only medications available for patient-based therapy: application of 0.5% podofilox, 3.75% or 5% imiquimod, or 15% sinecatechins, green tea polyphenon E (Veregen). Podofilox (Condylox) solution or gel is applied to the warts twice daily for 3 days followed by 4 days without treatment. This can be carried out for 4 weeks and is contraindicated for use during pregnancy. Imiquimod 5% cream (Aldara) cream is applied once daily three times per week on alternate days for up to 16 weeks. Imiquimod 3.75% (Zyclara) is applied once daily, for up to 16 weeks. Sinecatechins 15% ointment (Veregen) is applied three times per day for up to 16 weeks. Adverse effects of redness, burning, pain, and erosion occur with all four of these products. Clearance rates (about 50%) and recurrence rates (about 25% to 35%) are similar for all four medications (9).

Clinician-based therapy can be either medical or procedural. Two medical approaches are available. With the first, 25% podophyllin is applied to the warts once weekly or every other week. This approach is uncommonly used today due to nonstandardized podophyllin preparations, highly variable cure rates, and significant problems with irritation and pain. With the second, trichloroacetic acid or bichloroacetic acid (both 80% to 90%) can be applied very carefully in the office at 2- or 3-week intervals. Clearance rates of 70% to 80% have been reported, but recurrence rates are similar to those with patient-based therapy as described above (9). Burning on application is troublesome for patients, and ulcer formation is possible if too much is applied. Nevertheless, it is a reasonable approach when the warts are relatively nonkeratotic and the number and size of the lesions are small.

Clinician-based procedural therapy includes cryotherapy, electrosurgical destruction, laser destruction, and surgical excision. With cryotherapy, liquid nitrogen is sprayed (or applied with cotton-tipped applicators) at 2- to 3-week intervals. Electrosurgical destruction (electrofulguration, electrodessication) is carried out under local anesthesia. Other electrosurgical approaches using loop excision or a bipolar Bovie-type apparatus can also be used. Laser therapy, generally with a CO2 laser, can also be considered, but the cost of this equipment, and thus the cost of such treatment, is very high. Surgical excision is most often accomplished with a tangential shave or scissors-snip technique; rarely, elliptical excision might be considered. All three of these ablative approaches result in clearance rates of somewhat over 80% to 90%, but recurrence rates remain quite high. Drawbacks to procedural
therapy include the requirement for local anesthesia, the possibility of secondary infection, and potentially long healing times.

The choice of which medical or procedural approach is taken depends on patient preference and on the experience level of the clinician. For most patients, I prefer electrosurgical destruction or removal with either scissors-“snip” or tangential shave excision. If bleeding persists, it can be stopped with very light electrosurgery to the base. These two approaches are time honored and inexpensive and do not depend on patient compliance. Moreover, only a single clinic visit is generally necessary and the patient leaves the clinic with the knowledge that he or she is free of most or even all of the visible lesions. Of course, if the number and/or size of the warts are large, staged eradication at monthly intervals may be necessary.

Anogenital warts in children present a special problem because of the concern that sexual abuse may have taken place. However, for children under the age of 2, it is very unlikely that the transmission occurred through sexual contact. Anogenital warts in these very young children may have arisen through normal parental contact or by way of contagion from an infected birth canal. A greater level of concern exists for those over the age of 4, and, in any case, inquiry by an experienced clinician or by other skilled interviewers must be carried out for all children with anogenital warts.

The best approach for genital warts is to prevent them from occurring in the first place. During the last decade, three HPV vaccines have been FDA approved in the United States. These include a bivalent vaccine (Cervarix) that is directed toward the two most common HPV types associated with the development of malignancy, HPV 16 and HPV 18, and a quadrivalent vaccine (Gardasil) that protects against HPV 16 and 18 and also HPV 6 and HPV 11. The latter two types are the most common HPV types causing benign anogenital warts. Finally, a 9-valent vaccine (Gardasil-9) covers, in addition to the 4 HPV types mentioned above, 5 additional HPV types (HPV 31, 33, 45, 52, and 58) that are responsible for a sizeable number of cervical malignancies and a smaller number of anogenital malignancies occurring at other sites. The bivalent vaccine is recommended only for females, whereas the other two vaccines are recommended for both men and women (2).

All three vaccines are administered by way of three intramuscular injections administered over a 6-month period of time with the second and third injections given 2 and 6 months after the first dose. Although three doses are recommended, there is evidence that even one or two doses result in surprising good protection (10). All three vaccines are preferably given before sexual debut because the vaccines have no efficacy against HPV types once they have been acquired and are present as either latent or clinically visible infection. The FDA allows for vaccination at 9 years of age and the Advisory Committee on Immunization Practices (ACIP) recommends vaccination at age 11 or 12 (2). Catch-up vaccination (to offer protection against those HPV types that have not as yet been acquired) is recommended for 13- to 21-year-old males and 13- to 26-year-old females who have not been vaccinated earlier (2). Unfortunately, the cost of all three vaccines remains high for individuals living in those countries where vaccinations are not covered by the government or health insurance. For instance, the cost in the United States for the three-dose regimen is about $500 (10).

Safety of these vaccines is excellent with no serious safety concerns having so far been detected (2,10). Vaccination is not recommended for pregnant women but may be given safely to those who are immunosuppressed. The efficacy of HPV vaccination is excellent. When vaccines are given to those with no evidence of previous HPV infection (HPV-naïve group), there is 95% to 100% prevention of HPV-related malignancy (11). And when the quadrivalent vaccine is administered to the HPV-naïve group, there is almost 100% protection against the development of anogenital warts as well (11). This protection lasts at least 10 years (10). Unfortunately, in the real world, the low prevalence of vaccination and the lateness in life with which vaccines are often administered limit the efficacy to appreciably lower protection rates.



Molluscum Contagiosum

Infection with molluscum contagiosum virus (MCV) is common and self-limited. It can be viewed as more of a nuisance than a threat to health or well-being. A review of the subject was published in 2013 (12).


Clinical presentation

Molluscum contagiosum is a common infection that occurs primarily in children. Incidence rates can be as high as 20% of children in lesser developed countries but are lower elsewhere. In children ages 1 to 4, the incidence rates in the United Kingdom and North America appear to be about 0.1% and 1.5% per year (13). The point prevalence rate for children worldwide averages about 3% (13). Children with atopic dermatitis (“eczema”) and those who are frequent swimmers seem to be predisposed
to acquire the infection (13). Spread among family members is possible but occurs infrequently (12). Adults account for only a minority of all MCV infections. The majority of these occur in sexually active young adults. Those who are immunosuppressed either by illness or through immunosuppressive therapy are predisposed to more frequent infection and more numerous and larger lesions (12). Infection rates are similar between males and females (12,13). Transmission occurs primarily by skin-to-skin contact and is facilitated by damage to the epidermal barrier layer.






FIG. 5.12. Skin-colored, dome-shaped papules are typical of mollusca contagiosa, and one of these lesions has the classic dell (arrow).

The lesions of molluscum contagiosum are skin colored, pink, white, or, occasionally, translucent hemispherical papules 3 to 10 mm in diameter (Fig. 5.12). Rarely, and mostly in immunocompromised patients, giant lesions are encountered. Immunocompetent patients generally have 15 to 50 lesions at any one time. Most of the lesions develop on keratinizing epithelial skin, but they rarely also occur on mucous membranes. The skin surrounding lesions is usually normal in appearance, but redness and eczematous changes may occur circumferentially. Sometimes, in the resolution stage, the lesions develop brisk, red inflammation (Fig. 5.13).

The papules of molluscum contagiosum characteristically have a central depression or umbilication. However, many lesions, especially early and small lesions, lack this feature (Fig. 5.14). Although this umbilication may not be seen in every lesion, a careful examination usually shows at least some umbilicated lesions. Sometimes, the papules of molluscum contagiosum mimic vesicles, thus accounting for the lay term “water warts” (Fig. 5.15). Molluscum contagiosum is typically asymptomatic, but some patients may experience low-grade pruritus. Lesions in children may be found anywhere on the skin, but most often, the trunk is affected. Lesions in adults, because of sexual transmission, are most commonly located on the mons, the medial thighs, and the buttocks. They are less often found on the penis and on the labia.






FIG. 5.13. Sometimes, mollusca become inflamed and crusted, suggesting initiation of an immunologic reaction that heralds clearing.



Management

In immunocompetent patients, untreated individual lesions of molluscum contagiosum resolve spontaneously over a matter of 1 to 3 months. But “seeding” of virus into surrounding skin or at distant sites occurs such that new lesions develop while old ones are resolving. The total duration of the infection, at least in children, averages 12 to 30 months (12). In immunocompromised persons, the number of lesions is larger and the variability in size is greater. Spontaneous resolution takes much longer and may not occur at all. On this basis, it seems prudent to check the HIV status in adults who develop lesions that are larger, more numerous, or last more than several months.

All of the treatments currently available are problematic in one way or another. Specifically in the review by Chen et al., the authors note that “no evidence based consensus has been reached on best treatment” (12,13). For this reason, most clinicians advise “watchful waiting” rather than active therapy for pediatric patients. For adults and patients who insist on treatment, both medical and procedural approaches are possible. The most commonly used medical treatments include cantharidin, trichloroacetic acid, imiquimod, and potassium hydroxide (KOH). The first two are applied in the office by the clinician, but the latter two can be used at home.

Cantharidin 0.9% solution is applied very carefully to prevent contact with the normal surrounding skin. Special care must be taken if cantharidin is used in intertriginous areas as the retained sweat can allow unwanted spread of the applied solution. For lesions in the anogenital area, it is useful to apply a loose bandage over the treated lesions to prevent spread of the cantharidin due to friction and retained sweat. Many clinicians advise that the cantharidin be washed off 6 to 8 hours after application, but I have not found it necessary to do so. A blister develops at the cantharidin application site within 24 hours, and the lesion is eventually sloughed off 4 or 5 days later when the blister roof peels away. Two to three office visits for repeat application are usually necessary. It is painless when initially applied, and for this reason, it is generally the treatment of choice for infants and children. Mild pain and irritation may occur later. Clearance rates for individually treated lesions is excellent and patient satisfaction is quite good (14,15).

Trichloroacetic acid 85% solution must be applied very carefully so that the solution does not run off of the papule onto normal skin. This approach is quite effective, but it is
somewhat painful at the time of application. Imiquimod may be used at home and the method in which it is used is identical to that described in the section above on genital warts. Home application reduces the number and expense of office visits, but this approach is accompanied by considerable discomfort and the duration of treatment is long enough to hamper patient compliance. Potassium hydroxide (KOH) can also be applied at home. It appears that 10% KOH solution and imiquimod are about equally effective, but KOH use seems to be accompanied by more adverse effects.

The most commonly used procedural approaches are cryotherapy and curettage. Liquid nitrogen cryotherapy is used in the same manner as is used for warts. A total freeze time of about 10 seconds is recommended and this can be obtained either in a single freeze or in a freeze-thaw-freeze cycle. It is moderately painful. Curettage, in which the lesion is scraped away with the edge of a skin curet, is also moderately painful, but the fact that visible treated lesions are completely removed leads to good patient satisfaction. Because of discomfort, both cryotherapy and curettage are best used when the number of lesions is small. As noted by Chen et al., in a randomized trial, comparing curettage with cantharidin and imiquimod, curettage was found to be the most efficacious and was associated with the fewest adverse effects (12).



Condyloma Latum

Condylomata lata (plural) is the name used for the flattopped papules and nodules that develop in the anogenital area during the secondary stage of syphilis. These lesions are uncommonly seen in conventional office practice but are, of course, encountered with some frequency in STD clinics. The primary coverage of syphilis is located in the section on “chancre” in chapter 11 on ulcers, and only the clinical presentation and therapy of condylomata lata will be covered here.

Condylomata lata are sharply demarcated, large (1- to 2-cm), flat-topped, moist, skin-colored or pink papules (Fig. 5.16). When the lesions are located on a moist or mucosal surface, they often exhibit a white surface because of retained moisture (Fig. 5.17). They are most commonly found on the vulva and the perianal area but can occur elsewhere on the genitalia and perigenital skin. As opposed to the other cutaneous lesions of secondary syphilis, the lesions of condylomata lata are teeming with spirochetes and pose a high risk for transmission to others. Condylomata lata are usually associated with other signs and symptoms of secondary syphilis such as fever, malaise, and generalized lymphadenopathy. Other skin findings of secondary syphilis such as
slightly scaly red papules on the trunk, brown-red palmar and plantar papules, white patches on the oral mucous membranes, and patchy hair loss may also be present.






FIG. 5.16. This small boy was misdiagnosed with genital warts; however, the very flat-topped morphology is classic for condylomata lata.






FIG. 5.17. The condylomata lata on wet skin often show a white surface.

Patients with condylomata lata almost always exhibit a positive a nontreponemal rapid plasma regain (RPR) or Venereal Disease Research Laboratory (VDRL) serologic test for syphilis. The only exceptions are those who are severely immunocompromised (e.g., HIV-AIDS) and those with such a high antibody titer that they exhibit the so-called prozone phenomenon. However, a positive nontreponemal test should be confirmed by a treponemal test such as the fluorescent treponemal antibody absorbed (FTA-ABS) test (16). However, note that there is controversy whether or not the order of these two types of tests should be reversed.

The lesions of condylomata lata can be confused with flat-topped HPV-induced warts and intraepithelial neoplasia of the vulva, penis, and scrotum. If there is any question about the correct identity, a serologic test for syphilis as well as a biopsy should be obtained. The treatment for secondary syphilis as recommended by the CDC is a single 2.4 million unit IM injection of benzathine penicillin G (Bicillin L-A) (16).

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Oct 30, 2018 | Posted by in Dermatology | Comments Off on Skin-Colored Lesions
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