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eMedicine Journal
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Emergency Medicine
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Dermatology
Warts, Genital Synonyms, Key Words, and Related Terms: human papillomavirus, HPV, sexually transmitted disease, STD, condyloma acuminatum, papilloma acuminatum, papilloma venereum, pointed condyloma, pointed wart, venereal wart, verruca acuminata, genital warts, papovaviruses, HPV infection |
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Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Pictures | Bibliography
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| AUTHOR INFORMATION | Section 1 of 12 |
Authored by A Antoine Kazzi, MD, Chief of Service, Department of Emergency Medicine, Medical Director of the Emergency Unit, American University of Beirut
Coauthored by Rasha A Hindiyeh, BS, Emergency Medicine, University of California, Irvine School of Medicine
A Antoine Kazzi, MD, is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, California Medical Association, and Society for Academic Emergency Medicine
Edited by Jeffrey Glenn Bowman, MD, MS, Consulting Staff, Department of Emergency Medicine, Mercy Springfield Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Mark W Fourre, MD, Program Director, Department of Emergency Medicine, Maine Medical Center, Associate Clinical Professor, Department of Surgery, University of Vermont School of Medicine; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
| Author's Email: | A Antoine Kazzi, MD | |
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| Editor's Email: | Jeffrey Glenn Bowman, MD, MS |
eMedicine Journal, January 18 2007, VOLUME 8,
Number 1
| INTRODUCTION | Section 2 of 12 |
Background: Genital warts are an epidermal manifestation attributed to the epidermotropic human papillomavirus (HPV). More than 75 types of double-stranded HPV papovaviruses have been isolated thus far. Many have been linked directly to an increased neoplastic risk in men and women.
Approximately 90% of all genital warts are related to HPV types 6 and 11 (HPV-6, HPV-11). These are the least likely to have neoplastic potential.
Thirteen HPV types (ie, 33, 35, 39, 40, 43, 45, 51-56, 58) have a moderate risk for neoplastic conversion; HPV-16 and HPV-18 are considered high risk. This picture is complicated by the proven coexistence of many types in the same patient (10-15%), lack of adequate information on the oncogenic potential of many other types, and ongoing identification of additional HPV-related clinical pathology. For example, bowenoid papulosis, seborrheic keratoses, and Buschke-Lowenstein tumors—previously parts of the differential diagnosis of genital warts—all have been linked to HPV infections.
Pathophysiology: HPV invades cells of the basal layer of the epidermis, penetrating skin and mucosal microabrasions in the genital area.
A latency period of months to years may ensue. Following that period, viral DNA, capsids, and particles are produced. Host cells become infected and develop the morphologic atypical koilocytosis of genital warts.
Most frequently affected are the penis, vulva, vagina, cervix, perineum, and perianal area. These mucosal lesions occasionally can be found in the oropharynx, larynx, and trachea. HPV-6 even has been reported in other uncommon areas (eg, extremities).
Multiple simultaneous lesions are common and may involve subclinical states as well as different anatomic sites. Subclinical infections have an infectious and oncogenic potential.
Consider the possibility of sexual abuse in pediatric cases; however, remember that infection by direct manual contact or, rarely, by indirect transmission from fomites may occur. Additionally, passage through an infected vaginal canal at birth may cause respiratory lesions in infants.
Frequency:
Mortality/Morbidity: Mortality is secondary to malignant transformation to a carcinoma. This oncogenic potential, which is rare with HPV-6 and HPV-11 (the most commonly isolated viruses), reportedly triples the risk of genitourinary cancer among infected males.
Sex: Both sexes are susceptible to infection. Overt disease may be more common in men (reported in 75% of cases); however, infection may be more prevalent in women.
Age: Prevalence is greatest in persons aged 17-33 years, with a peak incidence in persons aged 20-24 years.
| CLINICAL | Section 3 of 12 |
History:
Physical:
Causes:
| DIFFERENTIALS | Section 4 of 12 |
Other Problems to be Considered:
Darier disease
Hailey-Hailey disease
Neoplasia
Nevi
Pearly penile papules
Vulvar neurofibromatosis
Vulvar vestibular papillae
| WORKUP | Section 5 of 12 |
Other Tests:
| TREATMENT | Section 6 of 12 |
Emergency Department Care:
Consultations:
| MEDICATION | Section 7 of 12 |
Do not administer the following medications in the ED. These agents are listed strictly for educational purposes and to help readers understand and manage potential complications.
Warts generally regress spontaneously within months or years. Remove genital or laryngeal warts, however, because of the possibility of malignant transformation.
The CDC recommends keratolytic agents, antimitotic agents, and immune-response modifiers as alternative regimens to cryotherapy to treat external genital/perianal warts, vaginal warts, and urethral meatus warts.
Drug Category: Keratolytics -- These agents cause the cornified epithelium to swell, soften, macerate, and then desquamate.
| Drug Name | Podophyllum resin (Podocon-25, Podo-Ben-25, Podofin) -- Powdered mixture of resins removed from the May apple (mandrake) (Podophyllum peltatum linne). Cytotoxic agent used topically to treat genital warts. Arrests mitosis in metaphase, an effect it shares with other cytotoxic agents (eg, vinca alkaloids). Podophyllotoxin is the active agent, and its strength varies with the type of podophyllum resin used. American podophyllum contains a fourth the amount of Indian source. A cure rate of 20-50% can be expected if used as a single agent. |
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| Adult Dose | Sparingly apply 10-25% concentration onto lesions 1-2 times/wk; use 1 gtt at a time, allowing drying between gtt until area is covered Treat only intact lesions; wash treatment area 1-2 h after first application; in subsequent treatments, patient can wait 4-6 h before washing off agent |
| Pediatric Dose | Apply as in adults |
| Contraindications | Documented hypersensitivity; diabetes; impaired peripheral circulation; avoid use on mucous membranes, eyes, bleeding warts, moles, birthmarks, or unusual warts with hair |
| Interactions | None reported |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Powerful caustic and severe irritant; do not use if surrounding tissue is swollen or irritated; do not apply 25% solution near mucous membranes; do not use large amounts; avoid contact with cornea |
| Drug Name | Podofilox (Condylox) -- Topical antimitotic that can be chemically synthesized or purified from plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum). Treatment of anogenital warts results in necrosis of visible wart tissue. Exact mechanism of action is unknown. Genital warts are epidemiologically associated with cervical carcinoma. Slightly higher cure rates can be expected with podofilox than with podophyllin. Additionally, this agent is useful for prophylaxis. |
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| Adult Dose | 0.5% solution applied bid for 3 d and discontinued for 4 d; repeat this on-and-off cycle for up to 4 wk Use no more than 0.5 mL of solution or 0.5 g of gel qd; treat <10 cm2 of tissue qd Thoroughly wash hands after each application |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Avoid contact with eyes; if eye contact, immediately flush eye with copious quantities of water and seek medical advice; not for use on mucous membranes of genital area, including urethra, rectum, and vagina; do not exceed frequency of application or duration of usage; not recommended by itself for recurrent warts or perianal or genital mucous membranes (distinguishing between these conditions can be difficult); obtain histopathologic confirmation if the diagnosis is doubtful |
| Drug Name | Trichloroacetic (Tri-Clor), Dichloroacetic (Bichloracetic) acids -- Cauterizes skin, keratin, and other tissues. Although caustic, causes less local irritation and systemic toxicity than other agents in the same class. However, response is often incomplete and recurrences are frequent. |
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| Adult Dose | Paint on to lesions, avoiding uninvolved skin; can be used in anal areas; repeat q1-2wk; 3-4 treatments may be necessary Treated area requires no cleansing after several hours |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; not for use on premalignant or malignant lesions |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | External use only; restrict use to treatment areas only; if acid spilled on normal tissue or if too much applied, remove immediately and wash with water; sodium bicarbonate may be applied as a local antidote |
| Drug Name | 5-Fluorouracil (Efudex, Fluoroplex) -- Has antimetabolic, antineoplastic, and immunostimulative activity. Useful to prevent recurrence in patients who are immunocompromised if started within 4 wk of condyloma ablation. Mild local discomfort can be treated with cortisol cream. |
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| Adult Dose | 5% cream qd or periodically for 10 wk 1% cream bid for 2-6 wk |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; pregnancy |
| Interactions | None reported |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Incidence of inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction; avoid prolonged exposure to sunlight or UV radiation; increased absorption may occur through ulcerated or swollen skin; use care near eyes, nose, and mouth; wash hands immediately after application; prolonged use may result in erosive dermatitis and mucositis; additionally, there is a risk of developing vaginal adenosis and clear cell adenocarcinoma with this treatment; pain, pruritus, burning, irritation, inflammation, allergic contact dermatitis, and telangiectasia are possible adverse effects |
| Drug Name | Kunecatechins (Veregen) -- Botanical drug product for topical use consisting of extract from green tea leaves. Mode of action unknown but does elicit antioxidant activity in vitro. Indicated for topical treatment of external genital and perianal warts (condylomata acuminatum) in immunocompetent patients. |
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| Adult Dose | Apply topically tid; use approximately a 0.5-cm strand of ointment topically for each external genital or perianal wart |
| Pediatric Dose | <18 years: Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Not evaluated for urethral, intravaginal, cervical, rectal, or intra-anal human papilloma viral disease and should not be used to treat these conditions; avoid application to open wounds, eyes, and nose; wash hands before and after application; avoid sexual contact while ointment is on skin; may cause application site reactions, phimosis, inguinal lymphadenitis, urethral meatal stenosis, dysuria, genital herpes simplex, vulvitis, hypersensitivity, pruritus, pyodermitis, skin ulcer, erosions in the urethral meatus, and superinfection of warts and ulcers |
| Drug Name | Interferon alfa-n3 (Alferon N) -- Approved by the FDA for injection in refractory condyloma acuminata. The mechanism by which interferons exert antitumor activity is poorly understood. Direct antiproliferative action against tumor cells and modulation of the host immune response may play important roles. Recurrence rate of 20-40%, but the recurrence rate after successful treatment is lower than with other treatment modalities. Nevertheless, intralesional interferon is expensive and requires repeated office visits. |
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| Adult Dose | 250,000 U intralesionally twice weekly for a maximum of 8 wk; not to exceed 2.5 million U per treatment session |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity to mouse immunoglobulin, egg protein, or neomycin |
| Interactions | Potential risk of renal failure when administered concurrently with interleukin-2; theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Numerous adverse reactions may occur with IM administration, including myalgias, fever and chills, GI symptoms, transient leukopenia, thrombocytopenia, LFT abnormalities, and serum lipid abnormalities, as well as a theoretical risk of viral transmission with natural interferon products; viral symptoms abate with time, and all adverse effects resolve once therapy is stopped; viral symptoms can be treated with acetaminophen or NSAIDs in the interim; monitor periodically to determine if the patient is responding to treatment; if patient does not respond within 6 mo, discontinue treatment; if a response to treatment is seen, continue treatment until either no further improvement is observed or the laboratory parameters have been stable for about 3 mo (not known whether continued treatment after that time is beneficial); caution in debilitating cardiovascular disease, severe pulmonary disease, diabetes mellitus with ketoacidosis, coagulation disorders, severe myelosuppression, or seizure disorders |
| Drug Name | Imiquimod (Aldara) 5% cream -- Induces secretion of interferon alpha and other cytokines; mechanisms of action are unknown. |
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| Adult Dose | Apply 3 times/wk prior hs for 16 wk; leave on skin for 6-10 h, then wash treatment area with soap and water |
| Pediatric Dose | <12 years: Not established >12 years: Apply as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Precautions | Genital use: Not recommended for treatment of rectal, cervical, intravaginal, urethral, and intra-anal human papilloma infection; following surgery or drug treatment, do not use topical imiquimod until genital/perianal tissue is healed Actinic keratosis: Avoid exposure to sunlight or artificial tanning; regular use of sunscreen is encouraged; avoid contact with lips, eyes, or nostrils; common adverse effects include erythema, edema, vesicles, erosion or ulceration, weeping, exudate, flaking, scaling, dryness, and scabbing or crusting Basal cell carcinoma: Medical follow-up is essential to ensure cancer has responded adequately to treatment; may cause redness, swelling, and sore development at application site; may cause itching or burning |
| Drug Name | Papillomavirus vaccine (Gardasil) -- Quadrivalent HPV recombinant vaccine. First vaccine indicated to prevent cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal intraepithelial neoplasia grades 2 and 3) due to HPV types 6, 11, 16, and 18. Vaccine efficacy mediated by humoral immune responses following immunization series. |
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| Adult Dose | <26 years: 0.5 mL IM administered as 3 separate doses; administer second and third doses 2 and 6 mo after first dose, respectively >26 years: Not established |
| Pediatric Dose | <9 years: Not established >9 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Immunosuppressive therapies (eg, irradiation, antineoplastic agents, corticosteroids) may decrease immune response to vaccine |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Shake well before administering; administer in deltoid region of upper arm or in higher anterolateral thigh; individuals with impaired immune responsiveness (eg, HIV infection, neoplastic disease, currently taking immunosuppressive drugs) may not elicit antibody response; because of IM administration, do not administer to individuals with bleeding disorders (eg, thrombocytopenia, coagulation disorders, anticoagulant therapy); common adverse effects include pain, swelling, erythema, and/or pruritus at injection site and fever |
| FOLLOW-UP | Section 8 of 12 |
Further Outpatient Care:
In/Out Patient Meds:
Deterrence/Prevention:
Complications:
Prognosis:
Patient Education:
| MISCELLANEOUS | Section 9 of 12 |
Medical/Legal Pitfalls:
Special Concerns:
| TEST QUESTIONS | Section 10 of 12 |
CME Question 1: A 26-year-old woman who has been sexually active for 12 years and is 3 months pregnant presents with new onset, painless, cauliflowerlike genital lesions associated with pruritus and discharge. Which of the following is not useful in the ED workup of these lesions?
A: VDRL test or rapid plasma reagent test
B: Viral culture
C: Searching for more than one involved area during physical examination
D: Wet mount
E: Testing for gonorrhea and chlamydia
The correct answer is B: This patient has genital warts caused by epidermal infection with human papillomavirus (HPV). HPV does not grow well in culture.
CME Question 2: Which of the following interventions for genital warts generally is not appropriate in the ED setting?
A: Using pressure to stop any associated bleeding
B: Relief of urethral obstruction in those rare cases in which it may be present
C: Employing keratolytic agents, cryotherapy, curettage, or electrodesiccation
D: Searching for coexisting sexually transmitted diseases
E: Outpatient follow-up with obstetricians, gynecologists, or urologists
The correct answer is C: While symptomatic treatment of genital warts may be warranted, much of the indicated workup and treatment regimen is beyond the scope of the ED physician.
Pearl Question 1 (T/F): Genital warts are the most common sexually transmitted disease (STD).
The correct answer is True: Genital warts, caused by more than 75 types of the human papillomavirus, are the most common STD. Annual incidence of genital warts is 1%. Prevalence has been reported to exceed 50%, and a 4-fold or more increase in prevalence has been reported in the last 2 decades. The highest prevalence is among young adults in their third decade and in older teenagers.
Pearl Question 2 (T/F): Males are more susceptible to overt genital warts infection than females.
The correct answer is True: Both sexes are susceptible to infection. Overt disease may be more common in men (reported at 75% of cases); however, infection may be more prevalent in women.
Pearl Question 3 (T/F): Treatment of genital warts falls in the scope of the ED.
The correct answer is False: The workup, treatment regimens, and necessary follow-up for genital warts are beyond the scope of the ED. Reassurance and symptomatic relief of such problems as bleeding or urethral obstruction should be given. Evidence of coexistent sexually transmitted diseases should be sought and treated if found. Outpatient follow-up with urologists or gynecologists should be recommended as appropriate.
Pearl Question 4 (T/F): Virtually no medicolegal pitfalls are associated with genital warts.
The correct answer is False: Medicolegal pitfalls include (1) failure to inform the patient of the potential risk of malignant transformation of lesions; (2) failure to indicate the necessity for follow-up, even after treatment eradicates the lesions; (3) failure to indicate the possibility of subclinical and intravaginal or cervical lesions and the need to search for them; (4) failure to indicate treatment availability and follow up; (5) failure to inform the patient of the risk of HPV transmission to sexual partners and neonates; (6) failure to inform the patient of the necessity of treating partners; and (7) failure to search for immunosuppression in patients with treatment failures and recurrences.
| PICTURES | Section 11 of 12 |
| Caption: Picture 1. Genital wart in pubic area. | |
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| Caption: Picture 2. Genital wart in pubic area. | |
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| Caption: Picture 3. Genital wart in pubic area. | |
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| Caption: Picture 4. Genital wart in pubic area (close-up). Note the pearly appearance. | |
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| Caption: Picture 5. Warts, genital. Condyloma acuminatum. Courtesy of Tsu-Yi Chuang, MD, MPH. | |
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| Caption: Picture 6. Warts, genital. Small papilloma of the vulva. Courtesy of Tsu-Yi Chuang, MD, MPH. | |
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| Caption: Picture 7. Warts, genital. "Cauliflower" condyloma of the penis. Courtesy of Tsu-Yi Chuang, MD, MPH. | |
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| Caption: Picture 8. Warts, genital. Small papilloma on the shaft of penis. Courtesy of Tsu-Yi Chuang, MD, MPH. | |
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| Caption: Picture 9. Warts, genital. Small papilloma of the anus. Courtesy of Tsu-Yi Chuang, MD, MPH. | |
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| BIBLIOGRAPHY | Section 12 of 12 |
| NOTE: |
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| Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER |
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Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Pictures | Bibliography
|
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