Actinic cheilitis

INTRODUCTION — Actinic cheilitis, also called "solar cheilitis" or "solar cheilosis," is a premalignant disorder of the lip caused by chronic sun exposure [1-6]. It is most common on the lower lip in persons with light skin type, in outdoor workers, and in geographic areas with high ultraviolet irradiation [1,4,7-10]. Actinic cheilitis shares a common pathogenesis with actinic keratosis. However, the risk of progression to squamous cell carcinoma (SCC) appears to be higher for actinic cheilitis than for actinic keratosis [1]. (See "Actinic keratosis: Epidemiology, clinical features, and diagnosis".)

This topic will discuss the clinical features, diagnosis, and management of actinic cheilitis. Actinic keratosis and other forms of cheilitis are discussed separately. Other premalignant oral lesions are also discussed separately.

●(See "Actinic keratosis: Epidemiology, clinical features, and diagnosis".)

●(See "Cheilitis".)

●(See "Oral lesions", section on 'Oral potentially malignant disorders'.)

EPIDEMIOLOGY AND RISK FACTORS — Actinic cheilitis is most common in geographic areas with high ultraviolet irradiation, in outdoor workers, and in persons with light skin types. Males are more frequently affected than females [11,12]. Reported prevalence rates among individuals with high levels of occupational exposure to ultraviolet radiation (eg, fishermen, farmers) range from 10 to 40 percent [7,8,13,14]. Chronic exposure to solar radiation is the main risk factor for actinic cheilitis. In a Spanish, multicenter study including 410 patients aged ≥45 years with actinic cheilitis, independent risk factors for actinic cheilitis were outdoor working for >25 years, age ≥60 years, light skin phototype, and personal history of nonmelanoma skin cancer [15].

Actinic cheilitis may occur at an early age in patients with genetic conditions associated with increased susceptibility to solar damage (eg, xeroderma pigmentosum, oculocutaneous albinism) [1,16-18].

CLINICAL FEATURES — Actinic cheilitis initially presents as a persistent area of dryness and desquamation, typically located on the lower lip, which is likely to receive more ultraviolet radiation exposure than the upper lip (picture 1E) [19]. On palpation, these lesions have a characteristic "sandpapery" feel to the touch.

Atrophic changes, blurred demarcation of the vermilion border, erythema, edema, hyperkeratotic (leukoplakia-like) plaques, ulceration, and crusting may be seen in more advanced lesions (picture 1A-D). Lesions are usually solitary, but multiple or diffuse lesions can occur.

Other signs of actinic skin damage, including actinic keratoses, solar lentigines, and elastosis, are commonly noted in patients with actinic cheilitis [20].

DIAGNOSIS — The diagnosis of actinic cheilitis is mainly based on clinical examination and history. A skin biopsy may be needed in select cases to rule out squamous cell carcinoma (SCC) [1].

Clinical — The diagnosis of actinic cheilitis is, in most cases, clinical. Features suggestive of actinic cheilitis include persistent lip dryness and desquamation; hyperkeratotic plaques; focal or diffuse, atrophic changes; blurring of vermilion border; erosions; or ulceration (picture 1A-E). A history of chronic sun exposure, particularly in outdoor workers (eg, farmers, fishermen, construction workers), supports the clinical diagnosis.

Biopsy — A lip biopsy is not routinely performed in patients with a history of chronic sun exposure and early, obvious changes of actinic cheilitis (eg, persistent dryness and scaling of the lip, characteristic "sandpapery" feel to the touch, mild atrophy). However, a biopsy is warranted in patients presenting with hyperkeratotic (leukoplakia-like) or nodular areas, with or without erosions or ulceration, that are suspicious for SCC.

Since microscopic changes suggestive of SCC may not occur homogeneously in the involved area, a single punch biopsy may not be an accurate method for precise diagnosis [21]. Rather, an elliptical incision biopsy in the thickest part of the lesion is preferred.

Histopathology — Histopathologic changes of actinic cheilitis include acanthosis, hyperkeratosis, focal areas of atrophy, and a variable degree of architectural changes and keratinocyte atypia (picture 2) [22]. A dermal, inflammatory infiltrate predominantly composed of lymphocytes, with occasional plasma cells and eosinophils, can also be seen. Solar elastosis is a frequent and important secondary finding [23].

DIFFERENTIAL DIAGNOSIS — The clinical and histopathologic differential diagnosis of actinic cheilitis includes:

●Squamous cell carcinoma of the lip – Actinic cheilitis with severe, cytologic atypia and an intense, inflammatory infiltrate may be difficult to differentiate from squamous cell carcinoma (SCC). Moreover, changes of SCC may be focal and go undetected in inadequate biopsy specimens, such as those obtained by small punch biopsy. If vermilionectomy is performed as treatment, serial sections of the entire specimen should be examined. Keratinocytic dysplasia involving the full thickness of the epidermis with atypical, pleomorphic cells indicates SCC in situ. Invasive SCC typically shows dysplastic keratinocytes involving the full thickness of the epidermis and dermal invasion. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Diagnosis'.)

●Lupus erythematosus – Atrophic actinic cheilitis may resemble discoid lupus erythematosus clinically and histologically (picture 3). However, the presence of vacuolization of the basal layer; follicular plugging; and patchy, periappendageal infiltrate differentiates lupus erythematosus from actinic cheilitis. (See "Overview of cutaneous lupus erythematosus", section on 'Discoid lupus erythematosus'.)

●Lichen planus – Lip involvement of lichen planus typically shows a reticular, white pattern (picture 4) and is usually associated with oral buccal mucosal lesions. On histologic examination, lichen planus shows damage of basal keratinocytes with multiple apoptotic cells (Civatte bodies) and a band-like, lymphocytic infiltrate in the upper dermis. (See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis".)

●Other primary lip diseases – Several inflammatory lip diseases, such as plasma cell cheilitis, cheilitis glandularis, and cheilitis granulomatosa, may share clinical features with actinic cheilitis (picture 5A-C). Histologic examination of a lip biopsy clarifies the diagnosis. (See "Cheilitis".)

MANAGEMENT — There is no general consensus on the management of actinic cheilitis. Treatments that are commonly used include topical medications (eg, topical fluorouracil, imiquimod), destructive therapies (eg, liquid nitrogen, electrodessication, chemical peels, laser therapy, photodynamic therapy [PDT]), and surgery (vermilionectomy) [24-35]. Evidence for the efficacy of these treatments is limited to a few small, randomized trials and several uncontrolled clinical studies [24,31,36].

The choice of treatment is made in the individual patient, based upon the extent and severity of the disease, clinical experience, and patient preference. Our approach is described below (algorithm 1).

General measures — Reinforcing the use of sun protection measures, including wearing a wide-brimmed hat and using lip balms containing broad-spectrum sunscreens multiple times per day, is of key importance in the ongoing management of patients with actinic cheilitis. Cessation of tobacco use, both smoked and smokeless, should also be encouraged.

Focal mild to moderate actinic cheilitis — Observation and conservative treatments, including lip sunscreens and sun avoidance, are reasonable choices for the motivated patient with mild actinic cheilitis (focal erythema, desquamation, and/or atrophy of the vermilion border) who is willing to commit to regular follow-up visits to monitor for possible progression and adhere to daily sunscreen application to the lips (algorithm 1).

If a decision is made to treat, we suggest cryotherapy with liquid nitrogen for focal lesions of mild to moderate cheilitis [31]. Cryotherapy is widely available, rapid, inexpensive, and can be performed without local anesthesia. Adverse effects of cryotherapy include pain, edema, and scarring.

In cases of incomplete clearance at three to six months, retreatment with additional cryosurgery or initiation of topical field therapy may be undertaken. (See 'Topical "field therapy"' below.)

There is little direct evidence supporting the use of cryotherapy for the treatment of actinic cheilitis [31]. In one study, 37 patients with 53 histologically confirmed actinic cheilitis lesions of the lower lip were treated with liquid nitrogen using the paintbrush technique [37]. Recurrence was noted after two and three years of follow-up in two patients, of whom one developed squamous cell carcinoma (SCC).

Multifocal or diffuse mild to moderate actinic cheilitis

Topical "field therapy" — For patients with multifocal or diffuse mild to moderate actinic cheilitis, we suggest field therapy with topical fluorouracil or imiquimod as first-line therapy (algorithm 1):

●Topical fluorouracil – Fluorouracil 1% or 5% cream is applied twice a day for two to four weeks. Adverse effects of treatment include pain, erythema and edema of the lips, erosions, and ulcerations [26]. Although topical fluorouracil has the potential to treat subclinical disease in adjacent areas ("field therapy"), the discomfort associated with treatment may cause poor adherence to treatment in many patients. Recurrence after treatment with topical fluorouracil has been reported.

●Imiquimod – Imiquimod is an alternative to topical fluorouracil for the treatment of multifocal or diffuse mild to moderate actinic cheilitis. Imiquimod 5% cream is applied to the involved area three times per week for four to six weeks. Imiquimod 2.5% or 3.75% cream is used on a schedule of daily application for two weeks, rest period for two weeks, and then another two weeks of daily application. Adverse effects included erythema, induration, erosions, and ulcerations.

We typically reassess patients three to six months after starting treatment. Persistent lesions and thickened/hyperkeratotic areas should be biopsied and further treatment planned, based on histopathologic findings. (See 'Biopsy' above.)

There is very limited evidence from small, observational studies supporting the efficacy of topical fluorouracil and imiquimod for actinic cheilitis [24]. Indirect evidence for their efficacy is derived from studies in patients with actinic keratosis of the skin [36].

In a small study comparing different treatment modalities (ie, topical fluorouracil, chemical peel, lip shave, laser therapy) in patients with actinic cheilitis involving >50 percent of the lower lip, recurrence was observed in 7 of 10 patients treated with topical fluorouracil after a median follow-up time of 50 months [35]. In a series of 15 patients with actinic cheilitis treated with topical imiquimod, all patients showed clinical clearing four weeks after discontinuing treatment [38].

Photodynamic therapy — Photodynamic therapy (PDT) is a treatment option for patients who do not tolerate topical fluorouracil or imiquimod. However, its efficacy appears to be relatively low [39-41] (see "Photodynamic therapy"):

●In a systematic review of 15 case series including 242 patients with actinic cheilitis treated with PDT, 139 of 223 patients (62 percent) had complete clinical response at 3 to 30 months, and 57 of 121 patients (47 percent) demonstrated histologic cure 1.5 to 18 months after treatment [39]. In a subsequent report of 16 patients treated with two sessions of methyl aminolevulinate (MAL)-PDT with a similar rate of clinical clearing, none achieved histologic cure [42].

●A similar clinical response rate with PDT (69 percent) was reported in a subsequent systematic review that included 239 patients [24]. Of note, a complete clinical response was reported in 19 of 23 patients (83 percent) treated with daylight PDT.

Ablative laser-assisted PDT may be more effective than standard PDT for the treatment of actinic cheilitis. In a small comparative study, 33 patients with actinic cheilitis were treated with a single session of ablative fractional laser (AFL) therapy immediately followed by MAL-PDT or with two sessions of MAL-PDT one week apart [43]. At 12 months, the complete clinical and histologic response rates were 85 and 29 percent in the AFL plus MAL-PDT and MAL-PDT only groups, respectively.

Severe actinic cheilitis — For patients presenting with severe, diffuse actinic cheilitis with hyperkeratotic (leukoplakia-like) or nodular areas, ulceration, or fissuring, treatment options include laser ablation and surgical excision (algorithm 1).

The choice between these approaches is based on the grade of dysplasia assessed by pretreatment histopathologic examination (see 'Biopsy' above):

●For patients with severe actinic cheilitis without evidence of high-grade dysplasia or cancer on biopsy, we suggest laser ablation with carbon dioxide (CO₂) laser or erbium:yttrium aluminum garnet (Er:YAG) laser rather than surgical excision or topical therapies. Adverse effects of laser ablation include a prolonged healing time and post-treatment hypo- or hyperpigmentation.

●For patients with severe actinic cheilitis with evidence of high-grade dysplasia, surgical excision (vermilionectomy) followed by defect repair by primary closure or mucosal advancement flap is the treatment of choice [44,45]. In contrast with laser ablation, vermilionectomy allows for the histopathologic examination of the entire vermilion and margins as well as the detection of occult SCC not identified by a previous biopsy [21]. The procedure may be associated with significant postoperative complications, including bruising, wound dehiscence, partial flap necrosis, scarring, and loss of normal lip contour [31]. (See "Treatment of stage I and II (early) head and neck cancer: The oral cavity", section on 'Lip (squamous cell carcinoma)'.)

A few studies, mainly case series, have evaluated the efficacy of laser ablation and surgical excision for actinic cheilitis:

●In a systematic review and meta-analysis of nine observational studies and one randomized trial (283 patients) comparing surgical (vermilionectomy or laser therapy) and nonsurgical (imiquimod, topical diclofenac, PDT) treatments for actinic cheilitis, the weighted remission rate among 122 patients treated with surgical excision or laser therapy was 93 percent (95% CI 85.5-96.5 percent), with a weighted recurrence rate of 8.4 percent (95% CI 4.5-15.1 percent) [46]. For nonsurgical therapies, the weighted remission and recurrence rates were 66 and 19 percent, respectively. However, these results must be interpreted with caution because the included studies were small, and none of them directly compared surgical versus nonsurgical therapies.

●In a 2021 systematic review, four of the five included studies using CO₂ laser ablation did not report any recurrences [47]. Recurrence occurred in 13 percent of patients in one study that used a single-pass, modified protocol for CO₂ laser ablation. No recurrences were reported in four studies with 106 patients treated with surgical excision.

PROGNOSIS AND FOLLOW-UP — The risk of malignant transformation of actinic cheilitis into squamous cell carcinoma (SCC) is unknown. In one study, the estimated transformation rate was approximately 3 percent [48]. However, as patients with actinic cheilitis have an increased risk of developing lip cancer, regular clinical surveillance and repeated biopsies of suspicious areas are recommended.

PREVENTION — Strict and continued sun protection is an important aspect of preventing the progression of actinic cheilitis to squamous cell carcinoma (SCC) and the development of further disease. Sun protection measures include sun avoidance, wearing wide-brimmed hats, and daily use of lip products containing broad-spectrum sunscreens [6]. Smoking and chewing tobacco cessation is recommended. (See "Selection of sunscreen and sun-protective measures".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Actinic keratosis".)

SUMMARY AND RECOMMENDATIONS

●Actinic cheilitis, also called "solar cheilitis" or "solar cheilosis," is a premalignant disorder of the lip caused by chronic exposure to ultraviolet radiation. It occurs most frequently on the lower lip of light-skinned individuals with high levels of occupational sun exposure (eg, fishermen, farmers) and is more common in males than in females. (See 'Introduction' above and 'Epidemiology and risk factors' above.)

●Actinic cheilitis initially presents as a persistent area of dryness and scaling typically located on the lower lip (picture 1E). More advanced lesions show atrophy, blurred demarcation of the vermilion border, erythema, edema, ulceration, and crusting (picture 1A, 1C-D). (See 'Clinical features' above.)

●The diagnosis of actinic cheilitis is usually clinical. However, a biopsy may be necessary for ulcerated or crusted lesions that are suspicious for squamous cell carcinoma (SCC). (See 'Diagnosis' above and 'Biopsy' above.)

●Topical, destructive, or surgical therapies are used for the treatment of actinic cheilitis. The choice of treatment is made in the individual patient, based upon the extent and severity of the disease, clinical experience, and patient preference. Our approach is as follows (algorithm 1):

•We suggest cryotherapy with liquid nitrogen for patients with limited mild to moderate actinic cheilitis (Grade 2C). However, observation is a reasonable choice for the motivated patient with mild actinic cheilitis (focal erythema, desquamation, and/or atrophy of the vermilion border) who is willing to commit to regular follow-up visits to monitor for possible progression and adhere to daily sunscreen application to the lips. (See 'Focal mild to moderate actinic cheilitis' above.)

•For patients with multifocal or diffuse mild to moderate actinic cheilitis, we suggest field therapy with topical fluorouracil or imiquimod rather than photodynamic therapy (PDT) or laser therapy (Grade 2C). However, PDT is a treatment option for patients who do not tolerate topical fluorouracil or imiquimod. (See 'Multifocal or diffuse mild to moderate actinic cheilitis' above.)

•Patients with severe actinic cheilitis presenting with hyperkeratotic (leukoplakia-like) areas with or without ulceration should undergo a lip biopsy prior to treatment to determine the presence and grade of dysplasia and whether invasive SCC is present. (See 'Biopsy' above.)

•For patients with severe diffuse actinic cheilitis without evidence of high-grade dysplasia or cancer on biopsy, we suggest laser ablation with carbon dioxide (CO₂) laser or erbium:yttrium aluminum garnet (Er:YAG) laser rather than surgical excision or topical therapies (Grade 2C). Surgical excision (vermilionectomy), which allows for the histopathologic examination of the entire vermilion, is the treatment of choice for actinic cheilitis with high-grade dysplasia on biopsy. (See 'Severe actinic cheilitis' above and "Treatment of stage I and II (early) head and neck cancer: The oral cavity", section on 'Lip (squamous cell carcinoma)'.)

●As patients with actinic cheilitis have an increased risk of developing lip cancer, regular clinical surveillance and repeated biopsies of suspicious areas are recommended. Sun protection measures and tobacco smoking or chewing cessation are important aspects of lip cancer prevention. (See 'Prognosis and follow-up' above and 'Prevention' above.)