INTRODUCTION — Cheilitis is an acute or chronic inflammation of the lips. It usually involves the lip vermilion and the vermilion border, but the surrounding skin and the oral mucosa may also be affected [1]. Common symptoms include erythema, dryness, scaling, fissuring, edema, itching, and burning.
Cheilitis may be caused by a multiplicity of endogenous or exogenous factors, the most common of which are atopic dermatitis, contact irritants or allergens, chronic sun exposure, and infection [2]. Secondary involvement of the lips can occur in many cutaneous and systemic disorders, such as lichen planus, lupus erythematosus, autoimmune bullous diseases, Crohn disease, sarcoidosis, and nutritional deficiencies.
This topic will review the clinical manifestation, diagnosis, and treatment of primary lip diseases. An overview of oral lesions in adults and children and the oral manifestations of cutaneous and systemic diseases are discussed separately.
●(See "Oral lesions".)
●(See "Soft tissue lesions of the oral cavity in children".)
●(See "Oral lichen planus: Pathogenesis, clinical features, and diagnosis".)
●(See "Overview of cutaneous lupus erythematosus", section on 'Mucosal manifestations'.)
●(See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus".)
●(See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)
●(See "Cutaneous manifestations of sarcoidosis".)
ECZEMATOUS CHEILITIS — Eczematous cheilitis is the most common type of lip disease. It presents with dryness, scaling, erythema, and fissuring of the lips. The inflammation may extend to the perioral skin or, less frequently, to the oral mucosa. Pruritus and burning are frequent symptoms.
Eczematous cheilitis may be due to endogenous factors (eg, atopic dermatitis) or may be caused by exogenous factors (eg, contact irritants or allergens) [3]. Multiple contributing factors may coexist in some patients.
Irritant contact cheilitis — Irritant contact cheilitis is the most common inflammatory lip disorder, typically affects the upper and lower lip, and can extend onto the cutaneous lip [1,4,5]. Chronic lip licking is a major cause, particularly in young children (picture 1D). Other causes include environmental factors (eg, cold, low humidity, wind, occupational exposure to irritants), irritants in lip cosmetics or oral hygiene products, or foods.
Allergic contact cheilitis — Allergic contact cheilitis is a delayed-type hypersensitivity reaction to allergens that come in contact with the lips. Women are more commonly affected than men, likely due to a heavier exposure to allergens from lipsticks, lip balms, sunscreens, makeup products, or nail polish [3-10]. Other causes of allergic contact cheilitis include oral hygiene products, such as toothpastes and mouthwash, and certain foods, such as mango, citrus fruit, and cinnamon [3-5,8,9].
Although fragrances, Myroxylon pereirae, and nickel remain the most frequent cosmetic sensitizers identified by patch testing in patients with allergic contact cheilitis [11], many other ingredients that are unique to lip and oral hygiene products can also cause allergic cheilitis [12]. Examples are ricinoleic acid (also known as castor oil) found in most lipsticks for its ability to dissolve pigments, resins (eg, colophony, shellac), drug and cosmetic dyes, preservatives (eg, methylisothiazolinone), ozonated olive oil, propolis (a bee product found in many lip-care products), cera alba (bee wax), carmine, lanolin, linalool, sunscreens (eg, benzophenones), and copolymers [4,11,13-17]. (See "Common allergens in allergic contact dermatitis".)
Patients typically present with an erythematous, scaly eruption that involves both lips and often extends beyond the vermilion border to involve the perioral skin (picture 1A) [4]. Edema, fissuring, vesiculation, and superficial ulceration can also be seen (picture 1B).
Symptoms include pruritus, burning, and tenderness. Depending upon the allergen source and exposure patterns, eczematous lesions may also be present in other body areas, providing a clue to the diagnosis.
Atopic cheilitis — Cheilitis is common in patients with atopic dermatitis or a history of atopic disease. The clinical manifestations include erythema, dryness, scaling, and fissuring (picture 1C). The clinical appearance may be indistinguishable from irritant or allergic cheilitis.
Diagnosis — The evaluation of the patient presenting with eczematous cheilitis involves the following:
●A general skin examination that includes the oral mucosa for signs of atopic dermatitis or other skin diseases that may involve the lips.
●Assessment of personal or family history of atopic disease (atopic dermatitis, allergic rhinitis, asthma).
●A detailed history that reviews the exposure to irritants or allergens (eg, cosmetics, sunscreens, foods, hobbies, instruments, dental hygiene products).
●Patch testing to assess for allergic contact cheilitis.
●Biopsy should be considered when standard treatments are not effective or in patients with persistent, painful, bleeding, hyperkeratotic, or eroded findings.
Patch testing is an essential investigation in patients with suspected allergic contact cheilitis. Testing should include standard series of allergens, as well as extended series for cosmetics and possibly the patient's personal products. The North American Contact Dermatitis Group (NACDG) has shown that more than one-half of patients referred for patch testing for cheilitis have positive patch test results, and almost one-quarter were not detected with the standard NACDG tray, emphasizing the need for expanded testing to adequately assess patients suspected of allergic cheilitis [11]. (See "Patch testing", section on 'Selection of allergens'.)
The diagnosis of allergic contact cheilitis is confirmed based on a relevant patch test reaction (see "Patch testing", section on 'Determining the clinical relevance'). Relevant patch test reactions are detected in 30 to 65 percent of patients tested with standard and supplementary series of allergens [4,5,10].
Patients with negative patch tests are often diagnosed with irritant contact cheilitis or atopic cheilitis. However, since multiple factors can be responsible for lip inflammation, the differentiation between the various types of eczematous cheilitis may be difficult in many cases. In a series of 75 patients with lip dermatitis, 49 patients had a sole diagnosis of allergic contact cheilitis and 26 had at least one additional diagnosis, with irritant contact cheilitis being the second most common diagnosis [4].
Treatment — Removal of the causative irritant or allergen from the patient's environment is the mainstay of treatment of irritant or allergic contact cheilitis. Patients should be advised to avoid potential irritants that can be found in lip balms, such as flavors, fragrances, preservatives, propolis, lanolin, and other potential allergens. (See "Management of allergic contact dermatitis in adults", section on 'Allergen avoidance'.)
Topical corticosteroids are helpful in reducing inflammation and pruritus. Low- to medium-potency corticosteroids (groups 4 to 6 (table 1)) can be applied twice a day for one to two weeks. Simple emollients, such as plain petrolatum, can be liberally used in combination with topical corticosteroids.
Prolonged use of topical corticosteroids may cause atrophy, which can exacerbate irritant cheilitis. Off-label use of topical calcineurin inhibitors (pimecrolimus or tacrolimus) may be used as an alternative to topical corticosteroids for long-term use [18].
ORAL RETINOID-ASSOCIATED CHEILITIS — Systemic retinoids, such as etretinate and isotretinoin, cause dryness, scaling, erythema, and fissuring of the lips in nearly all patients [19,20]. The mouth commissures can also be involved. The severity of cheilitis is dose dependent. Any other medication that produces dry mouth can result in drying of the lips as well. Treatment is symptomatic and consists of bland lip moisturizers and emollients. Complete remission occurs shortly after drug discontinuation.
ACTINIC CHEILITIS — Actinic or solar cheilitis is a premalignant disorder of the lip caused by chronic sun exposure [1,21-23]. It is most common in geographic areas with a hot, dry climate, in outdoor workers, and in light-skinned individuals [1,23-27]. The clinical features, diagnosis, and management of actinic cheilitis are discussed separately. (See "Actinic cheilitis".)
ANGULAR CHEILITIS — Angular cheilitis, also known as perlèche, is an acute or chronic inflammation of the skin and contiguous labial mucosa located at the lateral commissures of the mouth. It typically presents with erythema, maceration, scaling, and fissuring at the corners of the mouth (picture 2A-B). Lesions are most often bilateral and may be painful.
Angular cheilitis is caused by excessive moisture and maceration from saliva and secondary infection with Candida albicans or, less commonly, Staphylococcus aureus [28-30]. Angular cheilitis may occur at any age without sex predilection but is especially common in older individuals wearing dentures. Predisposing local factors include wearing orthodontic appliances or ill-fitting dentures, sicca symptoms (dry mouth), intraoral fungal infection, poor oral hygiene, and age-related anatomic changes of the mouth due to reduced vertical facial dimensions [28,31-33].
In older individuals, the loss of vertical dimension of the mouth due to recession of the alveolar ridges or edentulous state leads to drooping of the corners of the mouth, drooling, and retention of saliva in the creases [1,28,32]. Drooling, thumb sucking, and lip licking are frequent causes of angular cheilitis in young children [28,31-33].
Less common causes in both adults and children include nutritional deficiencies, such as B9 (folic acid), zinc, B6 (pyridoxine), B2 (riboflavin), or B3 (niacin) deficiency. Other causes include type 2 diabetes, Sjögren's disease, immunodeficiency, irritant or allergic reactions to oral hygiene products or denture materials, and medications causing dryness and xerostomia (eg, isotretinoin, acitretin) [19,29,34,35].
Diagnosis — The diagnosis of angular cheilitis is usually straightforward. A potassium hydroxide (KOH) preparation from lesions and oral mucosa may be needed to confirm or rule out Candida infection. In patients with recalcitrant cheilitis, a lesion swab for bacterial and fungal culture should be obtained.
Treatment — The management of angular cheilitis involves the control of local predisposing factors and treatment of fungal or bacterial superinfection. General measures to reduce moisture pooling at the corners of the mouth include:
●Improving denture fit and cleaning
●Maintaining optimal oral hygiene
●Treating sicca symptoms (dry mouth) (see "Treatment of dry mouth and other non-ocular sicca symptoms in Sjögren’s disease", section on 'Treatment of dry mouth')
●Use of barrier creams (eg, zinc oxide paste) or petrolatum
For patients with positive KOH preparation, we suggest topical antifungal therapy with azole (eg, miconazole, clotrimazole) ointment. The topical antifungal is applied two times per day for one to three weeks and repeated as necessary. For patients with associated Candida stomatitis, clotrimazole troches (one 10 mg troche dissolved slowly five times daily for two weeks) or oral fluconazole (100 mg per day for one to two weeks) may be beneficial. (See "Oropharyngeal candidiasis in adults".)
Staphylococcal infection can be treated with topical mupirocin ointment. Topical mupirocin is applied two times a day for 7 to 14 days.
Once cleared, a barrier cream or petrolatum applied nightly can help protect the skin from moisture. However, recurrence of angular cheilitis is common [36].
EXFOLIATIVE CHEILITIS — Exfoliative cheilitis is an uncommon, chronic, superficial, inflammatory disorder of the lips characterized by hyperkeratosis, desquamation, and crusting of the lips [37]. Some patients describe this condition as chronic chapped lips. The etiology is unknown, although cases due to repeated licking or biting of the lips have been reported.
Exfoliative cheilitis is a diagnosis of exclusion after other types of cheilitis with similar clinical appearance, such as eczematous or actinic cheilitis, have been ruled out. Treatment is difficult. There are isolated reports of successful treatment with topical corticosteroids or topical tacrolimus in combination with lip moisturizers [37-39]. Antidepressants have been reported as beneficial in a few cases associated with a habit tic [40,41]. A case report has shown that excimer laser therapy and narrowband ultraviolet B (NBUVB) phototherapy were effective in two patients with recalcitrant disease [42]. Carbon dioxide (CO2) laser has also been reported to treat exfoliative cheilitis [43].
PLASMA CELL CHEILITIS — Plasma cell cheilitis is a rare, benign, inflammatory condition presenting with a well-defined, indurated, or eroded erythematous plaque most often located on the lower lip [1,44-47]. It shares clinical and histopathologic features with Zoon balanitis and similar lesions affecting other mucosal sites, such as the vulva (Zoon vulvitis), gingiva, oral mucosa, and upper respiratory tract [46,48-50]. (See "Vulvar lesions: Differential diagnosis of vesicles, bullae, erosions, and ulcers" and "Balanitis in adults".)
Diagnosis and differential diagnosis — The diagnosis of plasma cell cheilitis is based upon the examination of a lip biopsy. Histology shows in the upper dermis a dense, band-like lichenoid infiltrate predominantly composed of mature plasma cells (picture 3) [46,47,51]. Associated findings include capillary dilation, erythrocyte extravasation, hemosiderin deposits, and mild epidermal spongiosis.
The differential diagnosis includes [44-46]:
●Allergic contact cheilitis (picture 1A-B) (see 'Allergic contact cheilitis' above)
●Actinic cheilitis (picture 4A-C) (see "Actinic cheilitis")
●Lichen planus (picture 5) (see "Oral lichen planus: Pathogenesis, clinical features, and diagnosis")
●Squamous cell carcinoma (picture 6) (see "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis", section on 'Cutaneous squamous cell carcinoma of the lip')
●Syphilis (picture 7) (see "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV")
Treatment — Treatment of plasma cell cheilitis is difficult. Potent topical corticosteroids and intralesional corticosteroids have been used in a few patients with variable results [47,52,53]. Other treatments that have been reported as beneficial in individual patients include topical calcineurin inhibitors [45,46], topical cyclosporine [54], oral griseofulvin [51], topical antibiotics [55], excimer laser therapy [56], and brachytherapy [57].
CHEILITIS GLANDULARIS — Cheilitis glandularis is a rare, chronic, inflammatory disease involving the minor salivary glands of the lower lip [58-60]. It is usually seen in males in their 40s, but young individuals and females may also be affected. The cause is unknown, but several factors appear to play a role, including chronic sun exposure, factitial cheilitis, atopy, infection, poor oral hygiene, and tobacco use [1,59,61,62].
Cheilitis glandularis typically presents with enlargement and eversion of the lower lip, which shows numerous pin-sized orifices from which mucous saliva can be easily squeezed. Patients describe tenderness and bumpiness of the lip as well as the presence of a sticky substance that dries on the lips.
Three types of cheilitis glandularis have been described: simple, superficial suppurative, and deep suppurative type [62]. In the more severe suppurative form, the dilated ostia of the minor salivary glands on the vermilion area exude a mucopurulent fluid; superficial ulceration and crusting may also be present [63]. Secondary infection can lead to ulceration, abscess, and drainage [59]. Squamous cell carcinoma arising in the context of cheilitis glandularis has been reported in a few patients [58,59,62-64].
Diagnosis — The diagnosis of cheilitis glandularis is made clinically, based upon the clinical finding of a swollen lip with dilated salivary gland ostia exuding a mucous substance. Papules and nodules can be felt upon palpation.
The histopathology is nonspecific and may reveal salivary gland hyperplasia, duct ectasia, and a dermal inflammatory infiltrate composed of lymphocytes, plasma cells, and histiocytes [64]. However, a biopsy may be helpful in ruling out other types of cheilitis and squamous cell carcinoma.
Treatment — Numerous therapies have been used for cheilitis glandularis, including systemic antibiotics; topical, intralesional, or systemic corticosteroids; topical calcineurin inhibitors; and surgical excision of the vermilion [1,58-62,65,66]. However, evidence of efficacy is limited to individual case reports and small case series.
For patients with mild disease, topical corticosteroids and sunscreen products may be helpful [67]. Vermilionectomy with dissection of the enlarged minor salivary glands may be required for patients with severe disease [1,58-61,65,67].
CHEILITIS GRANULOMATOSA — Cheilitis granulomatosa, also known as Miescher's cheilitis, is a persistent, idiopathic, nontender swelling of one or both lips [68]. It is considered a manifestation of orofacial granulomatosis, a non-necrotizing granulomatous inflammatory disorder characterized by persistent or recurrent soft tissue enlargement, oral ulceration, and a variety of orofacial features, in the absence of systemic granulomatous disorders such as Crohn disease or sarcoidosis [69-72].
Cheilitis granulomatosa is rare. It primarily affects young adults but can occur at any age, without sex predilection [69,73]. The etiology is unknown. Many factors, including allergy to foods (eg, cinnamon, sodium benzoate), genetic predisposition, infection, and atopy, have been implicated [69,74-76].
Clinical manifestations — The first manifestation of disease is often an intermittent swelling of the upper or lower lip that mimics angioedema [77]. The initial episodes typically resolve in hours to days. As the disease progresses, the episodes increase in duration and lead to persistent swelling that may involve both lips, resulting in functional disability and cosmetic disfigurement (picture 8A-C).
Cheilitis granulomatosa is in most cases an isolated finding. When associated with recurrent facial palsy and/or lingua plicata (fissured tongue), it is referred to as Melkersson-Rosenthal syndrome (picture 9) [72,78]. (See "Bell's palsy: Pathogenesis, clinical features, and diagnosis in adults" and "Salivary gland swelling: Evaluation and diagnostic approach", section on 'Processes that may mimic salivary gland enlargement'.)
Diagnosis and differential diagnosis — The examination of a lip biopsy is necessary for the diagnosis. However, granulomatous inflammation is not invariably present, especially in the early stages of the disease, and histology may only show edema, a perivascular infiltrate of lymphocytes and plasma cells, and lymphangiectasia [79]. Granulomas, if present, are noncaseating, small, and scattered; contain Langerhans giant cells (picture 10); and are indistinguishable from those seen in sarcoidosis or orofacial manifestations of Crohn disease. Chest radiograph and colonoscopy can also help evaluate and differentiate this from sarcoidosis and Crohn disease. Allergic contact dermatitis can be assessed through patch testing [80].
The diagnosis of cheilitis granulomatosa is thus frequently one of exclusion. Other diseases with oral or facial involvement that must be ruled out include:
●Angioedema – In the early stage of disease characterized by intermittent lip swelling, cheilitis granulomatosa should be differentiated from angioedema. A history of atopy or current therapy with an angiotensin-converting enzyme (ACE) inhibitor or calcium channel blocker should alert the practitioner to the possibility of angioedema. (See "An overview of angioedema: Clinical features, diagnosis, and management".)
●Crohn disease – Oral localizations of Crohn disease, including labial, intraoral, or gingival swelling (picture 11), cobblestoning of the oral mucosa, oral ulcers, and tag-like mucosal lesions, are uncommon. In exceedingly rare cases, they can be the initial manifestation of the disease [81,82]. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults" and "Clinical presentation and diagnosis of inflammatory bowel disease in children".)
●Sarcoidosis – Sarcoidosis involving the lips (picture 12) may be clinically and histologically indistinguishable from cheilitis granulomatosa. However, in sarcoidosis, ACE levels are often elevated, and bilateral hilar lymphadenopathy may be present. (See "Clinical manifestations and diagnosis of sarcoidosis".)
●Foreign body reaction – A foreign body reaction to injectable dermal fillers should also be considered in the differential diagnosis of cheilitis granulomatosa. The foreign material can be identified on histologic examination, based upon the unique host response induced by each material [83]. (See "Injectable soft tissue fillers: Overview of clinical use".)
●Infection – In rare cases, tuberculosis or histoplasmosis may present with orofacial localization [84-86]. Cutaneous leishmaniasis and leprosy have also been reported to mimic granulomatous cheilitis [87]. (See "Cutaneous manifestations of tuberculosis", section on 'Tuberculosis cutis orificialis' and "Diagnosis and treatment of disseminated histoplasmosis in patients without HIV" and "Pathogenesis and clinical manifestations of disseminated histoplasmosis".)
●Allergic contact dermatitis – Allergic contact dermatitis typically affects both lips. A detailed history of exposures to potential allergens and patch testing can help in the diagnosis.
Treatment — Treatment of cheilitis granulomatosa is difficult, with complete remission uncommon [80,88]. Multiple therapies, alone or in combination, have been reported as successful in individual patients. Examples include topical, intralesional, and systemic corticosteroids [80,89-93]; antibiotics, such as minocycline [94], roxithromycin [95], and metronidazole [96]; clofazimine [97]; dapsone [98]; thalidomide [99]; anti-tumor necrosis factor (TNF) agents [100-102]; methotrexate [103]; and surgery [104]. A trial of a cinnamon- and sodium benzoate-free diet has been suggested, based on the hypothesis that type I and IV hypersensitivity to these agents may have a role in the pathogenesis of cheilitis granulomatosa [75,76].
Topical or intralesional corticosteroids are used in most cases as first-line therapy [70]. Intralesional corticosteroids have been reported as effective in reducing lip swelling in several case reports and case series, though recurrence is common [80,89-93]. In a retrospective study of 22 patients with orofacial granulomatosis, intralesional injections of triamcinolone acetonide 40 mg/mL once a week for three consecutive weeks was effective in reducing lip swelling at up to 48 months after treatment [92].
Patients with persistent and disfiguring lip swelling that is unresponsive to conservative treatment may benefit from reduction cheiloplasty, consisting of surgical excision of excess tissue [104].
LEISHMANIAL CHEILITIS — Primary mucocutaneous leishmaniasis may uncommonly present as cheilitis [105,106]. The initial presentation may be an erythematosus papule that gradually enlarges and then ulcerates or a persistent lip enlargement (macrocheilia). The diagnosis is often delayed and requires a high index of suspicion, as lesions can mimic a variety of infectious and noninfectious diseases, including herpes labialis, primary syphilis, cheilitis granulomatosa, basal cell carcinoma, and squamous cell carcinoma. Skin scraping or biopsy stained with Giemsa, culture, and polymerase chain reaction are used for diagnosis. (See "Cutaneous leishmaniasis: Clinical manifestations and diagnosis", section on 'Mucosal leishmaniasis'.)
SUMMARY AND RECOMMENDATIONS
●Definition – Cheilitis is an acute or chronic inflammation of the lips. It may be caused by a multiplicity of exogenous or endogenous factors, the most common of which are contact irritants or allergens, chronic sun exposure, infection, or atopic disease. (See 'Introduction' above.)
●Eczematous cheilitis – Eczematous cheilitis is the most common type of lip disease. It may be due to endogenous factors (eg, atopic dermatitis) or may be caused by exogenous factors (eg, contact irritants or allergens). Symptoms include dryness, scaling, erythema, and fissuring that may also involve the perioral skin (picture 1A, 1C-D). Treatment involves removal of irritants or allergens, mild to mid-potency topical corticosteroids, and lip emollients. (See 'Eczematous cheilitis' above.)
●Actinic cheilitis – Actinic or solar cheilitis is a premalignant keratosis of the lip caused by chronic sun exposure. It presents as a persistent area of dryness and scaling on the lower lip that progresses to atrophy, edema, erythema, ulceration, and crusting in more advanced lesions (picture 4A-C). Actinic cheilitis is discussed separately. (See "Actinic cheilitis".)
●Angular cheilitis – Angular cheilitis, also known as perlèche, is an acute or chronic inflammation of the skin and contiguous labial mucosa located at the lateral commissures of the mouth caused by excessive moisture and maceration from saliva and secondary infection with Candida albicans or, less commonly, Staphylococcus aureus (picture 2A-B). Predisposing factors include loss of vertical dimension of the mouth, wearing ill-fitting dentures, sicca syndrome, and poor oral hygiene. Treatment involves removal of predisposing factors, topical antifungals or antibiotics, and use of barrier creams. (See 'Angular cheilitis' above.)
●Plasma cell cheilitis – Plasma cell cheilitis is a rare, benign, inflammatory condition characterized by dense plasma cell infiltrates in the lips. It shares clinical and histopathologic features with similar conditions affecting other mucosal sites, such as Zoon balanitis and vulvitis. It presents with a well-defined, indurated, or eroded, erythematous plaque most often located on the lower lip. Treatment is difficult. Topical or intralesional corticosteroids may be of some benefit. (See 'Plasma cell cheilitis' above.)
●Cheilitis glandularis – Cheilitis glandularis is a rare, chronic, inflammatory disease involving the minor salivary glands of the lower lip. It typically presents with enlargement and eversion of the lower lip, which shows numerous pin-sized orifices exuding a viscous or mucopurulent fluid. Topical corticosteroids and sunscreen products may be beneficial in patients with mild disease. Vermilionectomy with dissection of the enlarged minor salivary glands may be required in severe cases. (See 'Cheilitis glandularis' above.)
●Cheilitis granulomatosa – Cheilitis granulomatosa, also known as Miescher's cheilitis, is characterized by a persistent, nontender swelling of the lips (picture 8A-C). It is an isolated finding in most cases; when associated with facial palsy and/or plicated tongue, it is referred to as Melkersson-Rosenthal syndrome (picture 9). Cheilitis granulomatosa must be differentiated from oral or facial localizations of other granulomatous diseases, including Crohn disease and sarcoidosis. Treatment is difficult. Topical or intralesional corticosteroids may be beneficial in reducing lip swelling. (See 'Cheilitis granulomatosa' above.)
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