VERRUCAE, CURRENT

TREATMENT REGIMES

KERWIN TALBOT

OUTLINE

• BIOLOGY OF WARTS

• EPIDEMIOLOGY

• DIFFERENTIAL DIAGNOSIS

• TREATMENT FACTORS

• TREATMENTS BRIEF SUMMARY OF THE LARGE VARIETY OF

TREATMENTS IN-DEPTH EXAMINATION OF THE HIGHER EVIDENCE

BASED TREATMENTS

• DISCUSSION

• CONCLUSION

BIOLOGY OF WARTS

• CUTANEOUS VIRAL WARTS, CAUSED BY THE HUMAN PAPILLOMA VIRUS

• (HPV)

• DNA VIRUSES, WHICH INFECT EPITHELIAL CELLS

• MINOR ABRASIONS AND INFECTIONS FREQUENTLY SERVE AS CONDUITS

FOR HPV

• REMAIN DORMANT WITHOUT VISIBLE DISEASE

• THE MOST COMMON INFECTIONS ARE WITH HPV TYPE 1,2, 4, 37 AND 57 ON THE HANDS AND FEET.

EPIDEMIOLOGY

OVERALL PREVALENCE OF WARTS OF 32.8/1000 IN THE 15 TO

74 YEARS AGE RANGE.

• YOUNGER GENERATION- HIGHER PREVALENCE

VIRAL ACTIVITY LIKELY DEPENDS ON:

• IMMUNE STATUS

• RESPONSE OF THE INFECTED INDIVIDUAL

SEROCONVERSION AFTER NATURAL INFECTION IS :

• RELATIVELY SLOW

• VIRAL LOAD

• PERSISTENT INFECTION

• RECURRENCE AFTER CLINICAL CURE IS OFTEN DUE TO LATENT VIRUS VERSUS REINFECTION

DIFFERENTIAL DIAGNOSIS

WARTS ARE IDENTIFIED BY: A CHANGE IN THE REGULAR PAPILLARY SKIN LINES WITH INDEPENDENT VASCULAR SOURCES.

HPV CAN MASQUERADE AS:

• A SEBORRHEIC KERATOSIS,

• CALLUS,

• CORN,

• EPIDERMAL NEVUS,

• MOLLUSCUM CONTAGIOSUM OR SQUAMOUS CELL CARCINOMA.

IS IT IMPORTANT TO KEEP THESE IN MIND- IF UNSURE HISTOLOGICAL EXAMINATION MAY NEED TO BE PERFORMED.

INDICATIONS FOR WART TREATMENT

• DEVELOPED BY THE AMERCIAN ACADEMY OF DERMATOLOGY

1) THE PATIENT’S DESIRE FOR THERAPY,

2) SYMPTOMS OF PAIN, BLEEDING, ITCHING OR BURNING,

3) DISABLING OR DISFIGURING LESIONS,

4) LARGE NUMBERS OR LARGE SIZES OF LESIONS,

5) THE PATIENT’S DESIRE TO PREVENT THE SPREAD OF WARTS

TO UNBLEMISHED SKIN OF SELF OR OTHERS, AND

6) AN IMMUNOCOMPROMISED CONDITION.

TREATMENT FACTORS

WHEN CHOOSING A TREATMENT

• AGE

• SITE OF INFECTION,

• SIZE,

• NUMBER AND TYPES,

• IMMUNOLOGICAL STATUS,

• TREATMENT AVAILABILITY,

• COST,

• PATIENT’S DESIRE FOR THERAPY,

• ABILITY TO ADHERE,

• PAIN TOLERANCE.

SUMMARY OF TREATMENTS Treatment categories Treatment Folk and alternative treatments

• Folklore • Hypnosis/Suggestive Therapy• Garlic Extracts• Duct Tape

Destructive therapy • Surgical Removal by Curettage or Cautery• Salicylic Acid• Cantharidin• Cryotherapy• Exothermic Patches• Ultrasound Hyperthermia• Radiofrequency Ablation• Microwave Treatment• Infrared Coagulation• Carbon Dioxide (CO2) Laser• Pulsed Dye Laser• Photodynamic Therapy

SUMMARY OF TREATMENTS Treatment categories Treatments

Virucidal Therapy • Glutaraldehyde• Formaldehyde• Formic Acid• Antiviral Drugs

Antimitotic Therapy • Bleomycin• Retinoids• Podophyllin• Podophyllotoxin

Immunotherapy • Oral Zinc Sulphate• Contact Sensitizers• Intralesional Injection of Interferon• 5-Fluorouracil (5-FU)

Combination Therapies • 5-FU + Salicylic Acid• Cryotherapy + Podophyllotoxin• SA + cryotherapy

TREATMENT SPECIFICS Treatment type

Treatment Cost Reported efficacy

Reported pain

Reoccurrence Side effects

Alternative remedies

Duct tape Low High* 85% Low Not reported None (allergy)

Destructive Surgical High* High* 65-85%

Low High -30% Scarring

Silver nitrate Low* Mod43%

Low* Mod 15% Clinical burns Irreversible tissue staining

Salicylic acid Low* Mod-high 70%

Low -mod Low Localised burns Contact dermatitis

Cryotherapy Traditional   Aggressive

 Mod*  Mod*

 Low-mod 30% Mod 50%

 Mod  Mod-high*

 Low   Low

 Blistering and pain* (44%)  Increase risk and severity (64%)

Virucidal therapy

Formalin (aqueous solution)

Low* Mod-high 60-67%

Low Low Sensitivity*

Immunotherapy

Oral zinc sulphate Low* High 87% Low Not reported Minimal

Combination therapies

Salicylic acid and cryotherapy

Mod* High 50-100%

Mod-high Low Clinical burnsBlistering Pain

TREATMENTS

Clinical recommendationEvidence rating

Topical salicylic acid therapy is recommended A

Cryotherapy is not recommended over salicylic acid for treatmentAggressive is recommended over traditional

A

Surgical is only recommended over salicylic acid in case by case basis B

Sliver nitrate is recommend for patients with low pain tolerance and children and facial areas

B

Formalin has found to be effective, pain less and have minimal side effects B/C

There is poor evidence to recommend pulsed dye laser therapy B

KEY RECOMMENDATIONS FOR PRACTICE

TREATMENTS SALICYLIC ACID (SA)

• KERATOLYTIC THERAPY

• OVER-THE-COUNTER- 17% SALICYLIC ACID

• THERAPEUTIC- UP TO 80% SOLUTION.

ADVANTAGES:

• CONVENIENCE, MINIMAL EXPENSE, NEGLIGIBLE PAIN AND REASONABLE EFFECTIVENESS.

DISADVANTAGES:

• REQUIRE WEEKS TO MONTHS OF TREATMENT, AND THE PATIENT COMPLIANCE

RECOMMENDED METHOD:

• HIGHER CONCENTRATION – BETTER RESULTS WITH 60%,

• OCCLUSIVE DRESSING,

• OFF-LOADING PADDING MINIMISED PAIN IN WEIGHT BEARING AREAS

• 1 WEEK WITH TREATMENT ON, TREAT EVERY 2 WEEKS – BEST RESULTS

SA THERAPY SHOULD REMAIN AS THE RECOMMENDED FIRST-LINE THERAPY

TREATMENTS CRYOTHERAPY

• AGGRESSIVE CRYOTHERAPY TO BE SIGNIFICANTLY MORE EFFECTIVE THAN GENTLE/TRADITIONAL.

• CRYOTHERAPY TECHNIQUES CAN VARY• APPLICATION MODE, - NO DIFFERENCE BETWEEN PEN OR SPRAY

• FREEZE TIMES- AGGRESSIVE OVER TRADITIONAL/ GENTLE

• INTERVALS BETWEEN TREATMENTS- EVERY 2 WEEKS

• DEBRIDEMENT IMPORTANT

ADVANTAGES: EFFECTIVE, EASY, ACCESSIBLE (OVER COUNTER)

DISADVANTAGES: HYPOPIGMENTATION/ HYPERPIGMENTATION, INFECTION RISK, VASCULAR STATUS

CRYOTHERAPY, RECOMMENDED AS A SECOND-LINE THERAPY OR AS A COMBINATION TREATMENT.

TREATMENTS SILVER NITRATE

CAUTERIZING AGENT TO REMOVE TISSUE AND BLOOD VESSELS.

ANTIMICROBIAL ACTIVITY

METHOD RECOMMENDED

FOR 10% - EVERY OTHER DAY FOR APPROXIMATELY 1-2 MINUTES FOR THREE WEEKS WITH HEAVY DEBRIDEMENT

AS THE CONCENTRATION INCREASES 25%, 50% AND 75% THE DURATION BETWEEN APPLICATION CAN INCREASE AND LENGTH OF ADMINISTRATION SHORTEN.

INCREASED RISKS OF SIDE EFFECTS WITH INCREASED CONCENTRATIONS.

TREATMENTS POTASSIUM HYDROXIDE

POWERFUL CAUSTIC AGENT

KERATOLYTIC AGENT – MULTIPLE DERMATOLOGICAL USES

METHOD RECOMMENDED:

5% : ONCE NIGHTLY, FOR 4 WEEKS, WEEKLY HEAVY DEBRIDEMENT.

SIDE EFFECTS:

ITCHING, BURNING SENSATION, ERYTHEMA AND TEMPORARY DYSPIGMENTATIONS.

5% HAD A 77.6% CURE RATE AFTER 4 WEEKS

10% HAD A 88.9% CURE RATE AFTER 4 WEEKS

RECOMMENDED TO AVOID EYE CONTACT

TREATMENTS FORMALIN

DISRUPTING THE UPPER LAYERS OF THE EPITHELIAL CELLS

KILLING THE VIRIONS

METHOD RECOMMENDED:

DEBRIDEMENT, DAILY APPLICATION, FILING BEFORE APPLICATION, OCCLUDE WITH DRESSING.

SOAKS HAVE A HIGHER CURE RATE BUT ALSO INCREASED REPORTED SENSITIVITY.

RECOMMEND NOT TO INHALE SOLUTION / MASK DURING APPLICATION AS A PRECAUTION.

MINIMAL SIDE EFFECTS, COST AND PAIN

MODERATE TO HIGH REPORTED CURE RATES – EVIDENCE IS OLD.

TREATMENTS

USING A TECHNIQUE OF MULTIPLE WART PUNCTURES WITH A BIFURCATED NEEDLE

• IN STUDIES USED WITH ANOTHER TREATMENT,

• FOUND A HIGHER CLEARANCE RATE USING THIS TECHNIQUE,

• USED IN CONJUNCTION WITH LA / ANKLE BLOCK,

• CAUSES AN INFLAMMATORY RESPONSE – EVOKES AN IMMUNE RESPONSE.

TREATMENTS

• THIRD LINE TREATMENTS:

• BLEOMYCIN:

• ADVANTAGES:

• RESERVED FOR RECALCITRANT WARTS,

• DNA AND PROTEIN SYNTHESIS ARE INHIBITED, AND APOPTOSIS IS TRIGGERED.

• DISADVANTAGES:

• SIGNIFICANT SYSTEMIC DRUG EXPOSURE

• EXPENSIVE AND PAINFUL

• RAYNAUD’S PHENOMENON

DISCUSSION

• ENORMOUS VARIETY OF WART TREATMENT,

• CHOOSING THE BEST WART TREATMENT,

• OVER 6 MONTHS- RECALCITRANT

• REMISSION AND RECURRENCE

• INVASIVE METHODS - PAINFUL AND REQUIRE LONG RECOVERY

TOPICAL MANAGEMENT- DEPENDENT ON:

• PATIENT COMPLIANCE

• LONG APPLICATION PERIODS

CONCLUSION

• EVIDENCE TO SUPPORT THE USE OF SA

• CRYOTHERAPY- SECOND-LINE THERAPY/ ALTERNATIVE TREATMENT

• THIRD-LINE TREATMENTS

• TAILORED

• MORE HIGH-QUALITY EVIDENCE

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