Farmer’s Lip – Causes, Symptoms, Treatment

Farmer’s Lip/Actinic cheilitis is cheilitis (lip inflammation) caused by long term sunlight exposure. Essentially it is a burn and a variant of actinic keratosis which occurs on the lip.[rx] It is a premalignant condition,[x] as it can develop into squamous cell carcinoma (a type of mouth cancer).

“Sailor’s Lip,” or actinic cheilitis (AC), is a precursor of squamous cell carcinoma (SCC) found on the lips. Similar to actinic keratosis, actinic cheilitis is a premalignant lesion caused by chronic sun exposure. It is most common on the lower lip along the vermillion border. Given SCC on the lips is considered a high-risk form of skin cancer with an 11% chance of metastasis compared to 1% for other body locations, it is essential to recognize and appropriately manage these potentially malignant precursory lesions.

Actinic cheilitis, also known as solar cheilosis, farmer’s lip, or sailor’s lip, is a reaction to long-term sun exposure on the lips, primarily the lower lip. The lip is especially susceptible to UV radiation because it has a thinner epithelium and less pigment. Some believe actinic cheilitis represents a type of actinic keratosis and is therefore premalignant. Others believe it is a form of in-situ squamous cell carcinoma. Regardless, the literature is in agreement that its presence indicates an increased risk for invasive squamous cell carcinoma.

Pathophysiology

Those with fair skin have less melanin and innately less protection against UV rays. The physical properties of the lips, such as their shape and being a transition area from oral mucosa to skin with thinner epithelium, less sebaceous glands, and less melanin, contribute to less protection and increased exposure to UV radiation. Chronic exposure to UV light damages tumor suppressor gene p53 resulting in uncontrolled replication of defective cells, which is a common gene mutation found with increasing frequency as actinic cheilitis and actinic keratoses undergo malignant transformation to SCC. Although actinic cheilitis can affect both the upper and lower oral cutaneous mucosa, more light from the sun hits the lower lip, making this area especially prone to sun damage and an increased number of skin cancers.

Causes of Farmer’s Lip

Actinic cheilitis results from the sun or UV radiation exposure. Additional risk factors include increased age, especially over 60 years, Fitzpatrick I and II skin types, genetic abnormalities affecting pigmentation such as albinism, working more than 25yrs outdoors, or a history of nonmelanoma skin cancer (NMSC). There has been conflicting evidence as to whether alcohol and smoking independently increase the risk of AC.AC is caused by chronic and excessive exposure to ultraviolet radiation in sunlight.

Risk factors include

  • Outdoor lifestyle – e.g. farmers, sailors, fishermen, windsurfers, mountaineers, golfers, etc.[rx] This has given rise to synonyms for this condition such as “sailor’s lip” and “farmer’s lip”.[rx] The prevalence in agricultural workers in a semi-arid region of Brazil is reported to be 16.7%.[rx]
  • Light skin complexion – the condition typically affects individuals with lighter skin tones,[rx] particularly Caucasians living in tropical regions.[rx] In one report, 96% of persons with AC had phenotype II according to the Fitzpatrick scale.[rx]
  • Age – AC typically affects older individuals, and rarely those under the age of 45.
  • Gender – the condition affects males more commonly than females. Sometimes this ratio is reported as high as 10:1. Additional factors may also play a role, including tobacco use, lip irritation, poor oral hygiene, and ill-fitting dentures.[rx]

Symptoms of Farmer’s Lip

AC almost always affects the lower lip and only rarely the upper lip, probably because the lower lip is more exposed to the sun. In the unusual cases reported where it affects the upper lip, this may be due to upper lip prominence. The commissures (corners of the mouth) are not usually involved.[rx][rx]

  • Affected individuals may experience symptoms such as a dry sensation and cracking of the lips.[rx] It is usually painless and persistent.
  • The appearance is variable. White lesions indicate hyperkeratosis. Red, erosive or ulcerative lesions indicate atrophy, loss of epithelium, and inflammation. Early, acute lesions may be erythematous (red) and edematous (swollen). With months and years of sun exposure, the lesion becomes chronic and may be grey-white in color and appear dry, scaly, and wrinkled.[rx]
  • There is thickening whitish discoloration of the lip at the border of the lip and skin. There is also a loss of the usually sharp border between the red of the lip and the normal skin, known as the vermillion border. The lip may become scaly and indurated as AC progresses.
  • When palpated, the lip may have a texture similar to rubbing the gloved finger along with sandpaper.[rx]
  • AC may occur with skin lesions of actinic keratosis or skin cancer elsewhere, particularly on the head and neck[rx] since these are the most sun-exposed areas. Rarely it may represent a genetic susceptibility to light damage (e.g. xeroderma pigmentosum or actinic prurigo).[rx]

Diagnosis of Farmer’s Lip

Biopsy w/ H&E is recommended for persistent suspicious lip lesions to rule out invasive skin cancer. Basic histopathology for actinic cheilitis would be:

  • Hyperkeratosis: thickening of stratum corneum
  • Solar elastosis:  loss of eosin staining, accumulation of irregular thick elastic fibers and tangled fibrillin
  • Epithelial dysplasia (mild-moderate): disordered maturation of epidermal cells, loss of rete ridges, variable cytological atypia
  • Perivascular inflammation: inflammatory cells around the blood vessels
  • Severe dysplasia: increase in dyskeratosis, keratin pearls, drop-shaped projections, and nuclei related changes such as mitoses and pleomorphism indicate the progression of dysplasia and increased malignant transformation.

History and Physical

  • Persistent white plaque with “sandpapery” feel on the lips
  • Most commonly lower lip
  • Blurring of the vermillion border between the cutaneous and mucosal lip
  • Usually asymptomatic/painless, but may have burning, numbness, pain
  • Eventually, plaque may become indurated, scaly and ulcerate as lesion progresses
  • Outdoor laborers: sailors, farmers, construction workers, lifeguards
  • Fitzpatrick I-II fair-skinned individuals

Evaluation

Actinic cheilitis is a diagnosis made from clinical and histopathology evaluation. It is essential to distinguish between cheilitis (benign inflammation),  premalignant actinic cheilitis, and squamous cell carcinoma. Skin biopsy is the golden standard regarding the evaluation of a persistent suspicious lesion on the lip. Many lesions initially thought to be premalignant actinic cheilitis on exam were found to be SCC upon histological evaluation, which indicates providers are not able to entirely make the diagnosis clinically, and biopsy is helpful when evaluating these lesions. While not required to make a diagnosis, one article suggests evaluating patients with electron microscopy helps to assess further the ultrastructural changes found in AC lesions, their potential for malignant transformation, and ensure they are diagnosed and managed correctly.

  • Physical exam – persistent white/erythematous thickening sandpapery skin on the lower lip
  • Labwork – for lesions that are new, symmetric, in young patients, found in patient’s with darker skin types, or individuals without a history of chronic sun exposure where skin cancer is less likely, consider first ruling out reversible causes such as those with a vitamin deficiency/infectious/contact/irritant etiology (Chart 1)
  • Skin biopsy – skin biopsy is recommended for persistent lesions
  • Electron Microscopy – hyperkeratosis, mild acanthosis, Perivascular lymphocytic infiltrate around glandular ducts

Treatment of Farmer’s Lip

MEDICAL OPTIONS

  • Topical treatments (ie, chemotherapeutic versus immunotherapy)
  • Topical 5-Fluourouracil
  • Imiquimod
  • Trichloroacetic Acid Peel 50%
You Might Also Read  How Can I Insure Blau Syndrome

SURGICAL

  • Localized shave removal
  • Vermilionectomy

PHYSICAL MODALITIES

  • Cryotherapy
  • Electrosurgery
  • CO2 laser resurfacing
  • Er:YAG laser resurfacing
  • Photodynamic therapy (PDT)
  • Dermabrasion

Treatment of actinic cheilitis should depend on the size, location, and severity of the lesion, along with the patient’s other comorbidities. The goal of therapy is to reduce the risk of malignant transformation from AC to SCC while maintaining functionality and cosmesis of the lips. A variety of therapies targeted at removing the dysplastic epithelium have been used to manage AC, including both surgical and medical options.

Surgical/destructive options for treatment include excisional vermilionectomy, cryotherapy, electrocautery, and pulse-dye or CO2 laser. However, these procedures are invasive, and patients may experience adverse effects such as pain, delayed healing, infection, scarring, edema, and paresthesias.

Non-surgical treatments for AC include topical therapies such as 5-fluorouracil, imiquimod, trichloroacetic acid, ingenol mebutate, diclofenac, phototherapy, topical DNA enzyme repair creams, photoprotection, and curettage with methyl aminolevulinate cream/daylight PDT. Many of the topical treatments cause adverse effects such as inflammation, crusting, and pain, which may reduce patient compliance.

A systemic review and meta-analysis of 283 patients showed surgically treated lesions compared to medically managed lesions had a higher remission rate (92.8% vs. 65%) and lower recurrence rates (8.4 vs. 19.2%) than non-surgical treatment. Dermoscopy has been used to aid with diagnosis and monitor treatment management in patients undergoing topical treatment.

It is difficult to directly compare efficacy across the numerous treatment options available for actinic cheilitis since many of the published studies, the severity of actinic cheilitis, and treatment regimens are not consistent or controlled across studies. However, the following options may be an option when deciding management for actinic cheilitis.

Laser treatment: preferred non-surgical intervention (efficacy 93%, low recurrences)

  • CO2 Laser: 10600 nm
  • Erbium Laser: 2940 nm
  • Adverse effects: pain, hypertrophic scarring (managed with corticosteroids)

Vermilionectomy/Surgical excision – preferred treatment for severe/refractory cases (efficacy near 100%, low recurrences).

  • Adverse effects: pain, delayed healing, infection, scarring, edema, paresthesias, may be cosmetically disfiguring compared to other treatment options

Topical Treatments – preferred treatment for patients with large areas of sun damage or those preferring medical intervention

  • Various treatment regimens studied, examples range from applying to affected area once daily for 1 to 4 weeks depending on patient’s tolerability (Efficacy for 5-FU at one week 69%, increased to 91% efficacy at four weeks)
  • Adverse effects: pain, crusting, inflammation, reduced patient compliance

  • Summary of Topical Options and Their Mechanism of Action

    • 5-FU: impairs pyrimidine thymidine synthesis and DNA replication
    • Imiquimod: nucleoside analog and immunostimulator
    • Ingenol mebutate: induces cell death and neutrophil-mediated antibody-dependent immune response to clear tumors
    • Trichloroacetic acid: induces cell necrosis
    • Diclofenac: anti-inflammatory, induces apoptosis by inhibiting COX 1 and COX2

Phototherapy – while actinic cheilitis results from by UV light damaging epithelial DNA, light therapy at an increased intensity level that causes reactive oxygen species to destroy damaged skin cells and was found to be an effective treatment in some cases (efficacy 68%,12% recurrences). Efficacy increases when used in conjunction with other treatment options, including topical treatments.

  • Adverse effects include pain, recurrence

Cryotherapy – liquid nitrogen physically destroys abnormal cells

  • Adverse effects include pain, crusting, scarring, reduced efficacy compared to other treatment options

Electrocautery/Curettage – physical destruction of the abnormal cells

  • Adverse effects include pain, scarring

Photoprotection – reduce the progression

  •  Dependent on patient compliance

Optimal Therapeutic Approach for this Disease

Cryosurgery is a simple procedure that can be performed to effectively treat localized actinic damage. Cryosurgery works at both the cellular and vascular level to induce necrosis of the epidermis. To be effective, it commonly requires multiple freeze-thaw cycles of liquid nitrogen to the dysplastic areas. It is a good option for localized areas of actinic damage and can be performed by most physicians. Attachments can be used to avoid unnecessary treatment of uninvolved mucosa and/or skin. It is a quick and inexpensive procedure. No local anesthetic is required.

The potential side effects that result are swelling, blistering, ulceration, pain both during and after the procedure, hypo/hyperpigmentation, scarring, and potential induction of herpes labialis. One clinical study reported a 96% cure rate after the treatment of actinic cheilitis with cryosurgery.

Electrosurgery and localized shave removal are also effective options for discrete areas of actinic cheilitis. Both procedures involve the destruction or removal of clinically involved areas of actinic damage. A local anesthetic is required. Shave removal provides a histologic evaluation to confirm that the dysplastic area has been completely removed. Electrosurgery uses electrical current to cause destruction of the localized area of actinic damage.

You Might Also Read  Actinic Keratoses - Causes, Symptoms, Treatment

Potential side effects experienced with both procedures are edema, pain, dyschromia, scarring, prolonged healing time, and potential activation of herpes labialis. No serious side effects are associated with these modalities and both are relatively simple and inexpensive. One study showed similar clinical results when comparing electrodessication with CO2 ablation, but electrodessication was shown to have an increased healing time for complete reepithelialization.

Carbon dioxide (CO2) laser ablation is one of the most effective treatments for extensive actinic cheilitis. The CO2 laser emits infrared light at a 10,600-nm wavelength that targets water resulting in the disruption of the cell membrane and cell death. The epidermis is ablated with the laser treatment, resulting in effective clearance of all dysplastic epithelial changes. Coagulation occurs with every pass of the laser and a moist gauze can be used to remove the char in order to evaluate the depth of treatment.

Previous studies have reported that the super pulsed mode has fewer potential side effects than the continuous waveform. The super pulsed mode reduces the potential for collateral damage by concentrating the energy into rapid pulses with adequate cooling between pulses. The ultra pulsed mode has also shown to be an effective way of delivering powerful, rapid pulses for successful treatment with minimal collateral damage. Expected wound healing time and potential for scarring are decreased with these methods.

The exact settings and handpieces will depend on the CO2 laser being used, but one will generally aim for a setting of 18W and one to two passes, depending on the extent of involvement. We use the Sharpton Silktouch CO2 laser mode with a setting of 18W. One study reported using the Paragon 50 short-pulsed CO2 laser with the Parascan Handpiece for one pass with settings of 18W (360mJ/cm2), 20% overlap in a 7×3.5-mm rectangular pattern.

Multiple studies have shown that the CO2 is extremely effective at treating actinic cheilitis and posttreatment biopsies have confirmed complete clearance. The procedure is performed under local anesthetic and nerve blocks. The ablation of the epithelium can result in 1-2 weeks of downtime with the need for frequent soaks and the application of petroleum-based emollients.

The potential risk for infection and activation of herpes labialis is greater than with previously mentioned treatment methods. It may be prudent to place those treated on a prophylactic antibiotic and antiviral treatment (ie, valacyclovir or acyclovir). Other potential side effects include edema, pain during and after the procedure, dyschromia, scarring, paresthesias, and delayed wound healing.

When compared to surgical vermilionectomy, CO2 laser ablation results are less operator dependent, do not result in lip contour irregularities or changes, involve less downtime, are less likely to cause difficulty eating, and will not result in postoperative complications like dehiscence and hematoma formation. CO2 ablation for actinic cheilitis can be performed in conjunction with Mohs surgery when there is an invasive squamous cell carcinoma with surrounding actinic damage.

Erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation has recently been discussed as a potential treatment for actinic cheilitis. The Er: YAG laser emits infrared light at a 2940-nm wavelength that targets water and also leads to the destruction of the cell membrane and ablation of the epidermis. Although there is little in the literature at this time, the mechanism of action is similar to the CO2 ablation and therefore appears to be a good treatment option.

The following settings were reported in a recent case series report. A combination of an ablative (1J/cm2, with a variable pulse width up to 400 microseconds) passes and coagulation (<1J/cm2, with pulse width between 2-35 ms) pass was used. The treatment consisted of: a 4-mm spot 100-micrometer ablation and two 4-mm spot combined 100-micrometer ablation and 100-micrometer coagulation passes. Additional passes (up to four) were performed in focal areas that showed clinical persistence. The final endpoint was a visualization of the normal dermal surface.

This series showed high cure rates of up to 84.8% with low morbidity and excellent cosmetic results. Aftercare and potential side effects are similar to those discussed above with CO2 ablation.

Vermilionectomy is by far the most successful treatment for actinic cheilitis because it not only surgically removes the dysplastic area but also allows for histologic confirmation of clear margins and no invasive component. One study in the literature found no clinical or histologic recurrences at 4 years for those cases of actinic cheilitis treated with vermilionectomy. Despite its high cure rates, this procedure is often not the first line because it is operator dependent and an increased risk of morbidity is associated with the procedure.

Surgical vermilionectomy is often reserved for severe actinic cheilitis or done intraoperatively in cases where an invasive squamous cell carcinoma has been removed and surrounding actinic damage is noted. Vermilionectomy involves surgically resecting the full-thickness atypical epithelium either down to the orbicularis oris muscle (simple vermilionectomy) or includes removal of muscle and glans (modified vermilionectomy). After the removal of the dysplastic epithelium, a labial mucosa advancement flap is performed.

Potential postoperative complications associated with this procedure are hematoma, dehiscence, functional impairment, asymmetry and contour distortion, scarring, and paresthesias.

Topical treatments with chemotherapy and immunotherapy (topical 5-fluorouracil and imiquimod) have been successful at treating actinic cheilitis as they offer a non-surgical option for field treatment. Both are potentially effective treatments, but they are limited by the low rate of patient compliance.

5-fluorouracil (5-FU) is an antimetabolite that inhibits thymidylate synthetase, an enzyme necessary for the production of DNA and RNA. Neoplastic cells are known to have an increased rate of mitosis and are therefore preferentially targeted. The disruption of metabolic activity leads to cell death and the destruction of dysplastic cells. There are different regimens suggested but the most effective for 5-FU has been shown to be twice daily application to the area for 2-4 weeks. The length of treatment varies based on the clinical response.

You Might Also Read  What Is Blau Syndrome, Causes, Treatment

Patients will experience an inflammatory reaction with edema, oozing, and likely ulceration or erosion formation. These symptoms can occur throughout the treatment course and can be decreased with a topical steroid application. Reactions can be severe and intolerable for patients because of the duration of treatment and impact on the ability to eat, drink, and speak.

There is a high rate of patient noncompliance seen because of these side effects. Treatment can be associated with pain and sun sensitivity, and it may be prudent to do antiviral prophylaxis if patients have a history of herpes labialis. Previous studies have shown that histologic dysplasia is likely to recur within a few years of treatment.

Imiquimod cream is an immune stimulator that is believed to cause an upregulation of proinflammatory cytokines, through Toll-like receptor 7, resulting in cellular apoptosis of dysplastic cells. It has also been effectively used to treat subclinical actinic damage. There are many different treatment regimens performed with 5% imiquimod, varying from 3-5 times a week for 3-16 weeks. A small study showing successful histologic clearance, applied imiquimod 3 times a week for 4-6 weeks, and showed no evidence of clinical recurrence in 3 months.

Imiquimod 3.75% cream is a relatively new formulation that has shown similar efficacy as the imiquimod 5% cream for the treatment of actinic keratoses. This 3.75% cream has a shorter treatment course and is able to treat a larger surface area. The recommended treatment regimen is the daily application of the cream for 2 weeks, a 2-week nontreatment period, and then an additional 2-week treatment cycle.

The potential side effects of imiquimod treatment are similar to treatment with 5-FU. Patients can expect erythema, edema, discomfort, oozing, and potential ulceration or erosion formation. Compliance is an issue with this medication because of these side effects and the impact on daily activities (ie, eating, drinking, talking). As with 5-FU treatment, there is usually good cosmetic outcome with minimal risk of scarring. Antiviral prophylaxis should be considered in those with a history of herpes labialis. A potential link between imiquimod treatment and aphthous ulcer formation has been reported.

PDT is becoming a more commonly used procedure to treat actinic damage. The literature shows anywhere from 50-90% response rate with this treatment. It involves applying a photosensitizing agent, ie, 5-aminolevulinic acid ( 5-ALA) or methyl-ester 5-aminolevulinic acid (MAL), to the affected area and activating it with a specific light source. Proliferating cells preferentially take up the photosensitizing agent. The light source converts it to Protoporphyrin IX, leading to radical oxygen species formation and cell death. These changes occur in more actively dividing cells, therefore targeting the dysplastic cellular areas.

In order to perform the treatment, the area must first be lightly curetted to remove the scale and allow for better penetration of the photosensitizing agent. After hemostasis is achieved, the 5-ALA or MAL is then applied and occluded for 2-4 hours. The area is then exposed to either a blue light source (417nm) for activation of the 5-ALA or a red light source (650nm) for the activation of the MAL.

For PDT using 5-ALA, the exposure to blue light is for 16 minutes and 40 seconds, with a total light source of 10J/cm2. For MAL treatment, the exposure to red light for 8 minutes and 40 seconds with a total light source of 37J/cm2 has been successfully used. A total of 2-5 sessions every 2-4 weeks is recommended.

Potential side effects include localized pain and burning during and after the treatment, edema, blistering, crusting, photosensitivity, and reactivation of herpes labialis. Overall, the side effects are generally milder and more tolerable than some of the other treatments. Good cosmetic results and functionality have been reported.

Dermabrasion is a procedure that uses a diamond fraise tip to mechanically remove the surface of the epithelium. It has recently been reported to be an effective treatment for actinic cheilitis. It can be used intraoperatively after the removal of an invasive SCC of the lip to treat the surrounding actinic damage. One to two passes with a fine pear-shaped diamond fraise tip is used to remove the epithelium. The endpoint is a visualization of the dermis with a dull appearance and pinpoints bleeding.

The device should rotate toward the orifice to avoid any irregularities and feathering should be performed along the cutaneous border to avoid lip margin scarring. Re-epithelialization takes about 1-2 weeks. Topical wound care with emollients (ie, petrolatum) should be performed until re-epithelialization is complete.

Potential side effects include minimal discomfort, swelling and edema, crusting, and potential herpes labialis reactivation. Benefits include less downtime and potential for scarring than when compared to CO2 ablation, good cosmetic outcome, and quick and easy low-cost treatment that is less operator dependent.

Trichloroacetic Acid (TCA) 50% chemical peels nonselectively destroy both the epithelium and superficial dermis. Although the literature is limited, it has not shown this method to be very successful. One small study showed initial clinical improvement of all patients, but at 1 year, 70% had a clinical recurrence and 100% had a histologic recurrence of dysplasia. Reepithelialization can take 1-3 weeks. Potential side effects include mild discomfort, crusting, edema, and herpes labialis reactivation.

References