White & Red Oral Lesions PDF

Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK White & Red Lesions of the Oral Mucosa Useful dermatological, clinical and pathological terms: Macule: A macule is a change in the surface color of skin or mucosa without elevation or depression, non-palpable, well or ill-d...

Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK White & Red Lesions of the Oral Mucosa Useful dermatological, clinical and pathological terms: Macule: A macule is a change in the surface color of skin or mucosa without elevation or depression, non-palpable, well or ill-defined variously sized, but generally less than 5-10mm (or less than 1cm) in diameter. Its color might be red due to increased vascularity or inflammation, or pigmented due to the presence of melanin, hemosiderin, and foreign materials (including the breakdown products of medications). A good example in the oral cavity is the melanotic macule. Patch: A patch is a large macule equal to or larger than 5-10mm (or larger than 1cm) in diameter. Patch may have some surface change such as fine scale or wrinkling; however, the lesion itself still not palpable. Papule: Is a circumscribed solid elevation (slightly domed or flat-topped) of the skin or mucosa with no visible fluid, varying in size from pinhead to less than 5-10mm (or less than 1cm) in diameter. Plaque: Described as either a broad papule or confluence of papules equal to or greater than 10mm (or larger than 1cm). Alternatively defined as an elevated, plateau-like lesion that is greater in its diameter than its depth. Nodule: A nodule is morphologically similar to a papule that it is also a palpable spherical or dome shaped lesion less than 10mm (or less than 1cm) in diameter. However, it is differentiated by being centered deeper within the subcutaneous or submucosal tissue (Endophytic) or protrude above/outward (within the dermis or mucosa) (Exophytic). A good example of an oral mucosal nodule is a fibroma. Tumor: similar to nodule but larger than 10mm (or larger than 1cm) in diameter. Blister: Is a small skin or mucosal elevation containing body fluid (serous, lymph, serum, plasma, blood or pus). 1 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Vesicle: A vesicle is a small blister, circumscribed, fluid-containing, epidermal or mucosal elevation generally less than 5-10 mm in diameter (less than 1cm). The fluid content is clear serous fluid. Bulla: A bulla is a large blister, rounded or irregularly shaped containing clear serous or purulent fluid. Its size is larger than 5-10mm (greater than 1cm). Pustule: A pustule is a small elevation (blister) of the skin or mucosa containing cloudy or purulent material (pus) usually consisting of necrotic inflammatory cells. They appear yellow, white or red. Telangiectasia: Represents an enlargement of superficial blood vessels to the point of being visible. (Commonly known as “spider veins”). Purpura: These are reddish to purple discolorations caused by blood leaking from blood vessels into the tissue. These lesions do not blanch when pressure is applied and are classified by size as petechiae (less than 0.3 cm), purpura (0.4–0.9 cm), or ecchymosis (greater than 1 cm). Scale: Dry or greasy laminated masses of keratin that represent thickened stratum corneum. Crust: Dried sebum (sebaceous secretion), pus, or blood usually mixed with epithelial and sometimes bacterial debris. 2 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK The oral cavity lined by oral mucosa, which is composed of Oral Epithelium & Sub-mucosa According to its function, the oral mucosa is divided into: 1. Masticatory mucosa 2. Lining mucosa 3. Specialized mucosa Why lesions appear white? Mucosal lesions appear white due to: 1. Increased thickness of epithelial coverage 2. Abnormal keratinization of non-keratinized epithelial surfaces (metaplasia) such as keratinization of non-masticatory (lining) mucous membrane of the oral cavity 3. Hyperkeratosis, which is increased or excessive production of keratin 4. Imbibition of fluid (water, saliva) by the upper layer of mucosa 5. Tissue necrosis Why lesions appear red? Mucosal lesions appear red due to: 1. Thinning of epithelial coverage (erosion, atrophy) 2. Reduced epithelial keratinization 3. Abnormal cell turnover during healing 4. Blood leakage into surrounding tissue due to trauma 5. Vasodilation during inflammation and vascular proliferation in tumor (neoplasm) 6. As part of dysplasia (premalignant and malignant) 3 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Classification of White and Red lesions 1. Normal variation: I. Leukodema II. Fordyce’s granules III. Linea alba IV. Morsicatio 2. Developmental: I. White spongy nevus II. Median rhomboid glossitis 3. Traumatic: I. Traumatic keratosis II. Nicotinic stomatitis (Stomatitis nicotina) III. Papillary hyperplasia of the palate 4. Infective: I. Candidiasis (Candidosis) II. Syphilis III. Measles or Rubeola 5. Blood dyscrasias: I. Anemia II. Plummer Vinson syndrome III. Vitamin A deficiency 6. Drugs: I. Chemical burn (Aspirin & other medications) II. Drug reactions: a. Lichenoid drug reaction b. Stomatitis venenata c. Stomatitis medicamentosa 7. Dermatological: I. Lichen planus II. Lupus erythematosus III. Psoriasis 8. Premalignant: I. Leukoplakia II. Erythroplakia III. Submucous fibrosis 9. Malignant: Squamous cell carcinoma 10. Miscellaneous: I. Oral skin graft II. Geographic tongue III. Coated tongue 4 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Leukodema It’s a variation of the normal oral mucosa. Appears as a greyish-white milky film on the buccal mucosa and soft palate, especially in dark skinned people (Negros) and heavy smokers. It represents a normal anatomical variation that can be accentuated by smoking. It’s asymptomatic & found on routine oral examination. It cannot be removed with tongue blade. D.D: Lichen planus, Leukoplakia, Frictional keratosis & White spongy nevus Diagnosis: 1. Clinical appearance 2. Stretching test (disappears by stretching) 3. Histopathology when premalignancy or malignancy suspected Treatment: Reassurance Fordyce’s granules They are common congenital lesions seen mostly in elder patients occasionally in young adults. Fordyce’s granules represent ectopic sebaceous glands. Mostly found on the buccal mucosa and the lips (labial mucosa). Commonly, they are soft, asymptomatic, and symmetrically distributed yellowish-creamy spots with few millimeters in diameter. Sometimes appear as clumps of spots or small white- yellowish sub-mucosal patches. Diagnosis: 1. Clinical appearance 2. Biopsy (if another lesion suspected) Treatment: Reassurance Linea alba Is a horizontal white line on the buccal mucosa at the level of the occlusal plane extending from the mouth commissure to the posterior teeth. It is a very common finding and is most likely associated with pressure or frictional irritation (as in bruxism), or sucking trauma from the facial (labial, buccal) surfaces of the teeth (negative pressure such as during sucking or heavy shisha/ pipe smoking). 5 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Clinical features: 1. Linea alba buccalis usually present bilaterally and may be pronounced in some individuals. 2. It is more prominent in individuals with reduced overjet of posterior teeth. 3. It is often scalloped and restricted to dentulous areas. Treatment: 1. No treatment (Reassurance). It may disappear spontaneously 2. Remove the cause (example Bite plate in bruxism) 3. If not disappear, then apply Keratolytic agent (Tretinoin®, Retinol®, “Retin A” 0.025% Gel or Cream) Morsicatio Morsicatio (also known as “morsicatio mucosae oris”) refers to biting or nibbling of the oral mucosa. Common sites for this habitual nibbling include the lateral borders of the tongue (morsicatio linguarum), buccal mucosa (morsicatio buccarum), and labial mucosa (morsicatio labiorum). The patient may or may not be aware of the habit & the lesion (asymptomatic), some clinicians have suggested an association with stress or psychological disorders. The chronically traumatized mucosa develops a white to red-white plaque/patch with a rough, ragged, or macerated appearance. Sometimes, the patient can remove thread-like shreds of keratin from the surface. Accompanying ulcerations or erosions is also possible on continuous biting/nibbling. Diagnosis: The characteristic clinical presentation is sufficient for the diagnosis, although biopsy may be performed if there is uncertainty. Microscopic examination shows a thickened, shredded keratin layer. 6 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Treatment: 1. No treatment (Reassurance) 2. Stop or abstain the habit and the lesion will disappear spontaneously 3. To remove the cause, Bite plate or habit breaker may be constructed 4. If not disappear; then apply a Keratolytic agent (Tretinoin®, Retinol®, “Retin A” 0.025% Gel or Cream) White sponge nevus White sponge nevus (Cannon's disease) is a developmental keratotic lesion inherited as an autosomal dominant trait (mutation in the keratin genes), affects the mouth and other mucosal surfaces. It appears from infancy to adolescence. Affected mucosa appears white thickened, folded or corrugated lesions with spongy soft texture. White sponge nevus is asymptomatic, in the oral cavity it involves the buccal mucosa and floor of the mouth usually bilaterally. Other mucosal surfaces may be affected such as vagina, anus and nasal cavity. Diagnosis: 1. Clinical appearance 2. Positive family history 3. When confused with leukoplakia, biopsy is indicated to confirm the diagnosis Treatment: Reassure the patient that the condition is benign. If it causes extreme discomfort, surgical excision and grafting can be performed. Median rhomboid glossitis (MRG) Described as rhomboid, diamond or rounded area of depapillation in the midline of the dorsum of the tongue at the junction of the anterior 2/3 and posterior 1/3 anterior to the V-shaped circumvallate papillae. The lesion is asymptomatic and seen in adults. Mostly appear as a red depapillated area; however, alternatively it may be white. 7 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK It may have a nodular appearance, or flat/slightly depressed area. In some cases, it may appear nodular fibrous with epithelial hyperplasia. MRG location on the tongue suggests that it may be developmental, represents a remnant of the tuberculum impar; however, as it is not commonly seen in children this suggestion is no longer accepted. It has now been recognized that MRG is often associated with candida. Diagnosis: 1. Clinical appearance 2. Swab and culture to demonstrate candidal hyphae (Gram stain) 3. Biopsy is indicated to rule out carcinoma when suspected Treatment: 1. Reassurance 2. When candidal hyphae detected, the lesion treated with topical antifungal medication 3. If the lesion remains, follow up (for any enlargement or change) is indicated Traumatic keratosis (Frictional Keratosis) It refers to an isolated area of thickened whitish oral mucosa that is related to an identifiable local irritant and resolves following elimination of the irritant. It's usually found in association with denture clasps, rough edges of a denture, orthodontic brackets, sharp edges of restorations, broken teeth, on the lips of heavy cigarette smokers and buccal mucosa opposite to the molar teeth. Early cases appear grayish- white, later becomes dense, firm and white. Diagnosis: Demonstrate the irritant factor & Biopsy (if suspected) Treatment: Reassurance & Remove the irritant (cause). If not disappear; Keratolytic agent might be used (Tretinoin®, Retinol®, “Retin A” 0.025% Gel or Cream). 8 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Nicotinic stomatitis (stomatitis nicotina) It's a specific lesion that develops on the palate of heavy cigarette, pipe and cigar smokers. Palatal mucosa appears as grayish white, thickened and/or fissured. Focal thickening occurs around the orifices of the palatal minor salivary glands which appear as white, umbilicated nodules with red centers (orifices of the minor S. Gs) due to heat generation, sometimes may be stained brown by deposits of tar. Diagnosis: History, Clinical examination & Biopsy (if malignancy suspected) Treatment: 1. Stop smoking & lesion resolves within weeks 2. Follow up the patient Papillary hyperplasia of the palate Appears in denture wearers especially those wearing ill-fitting denture or rocking denture. The lesion is asymptomatic discovered by clinical examination, sometimes painful (symptomatic). The palatal mucosal lesion appears as polypoid, granulated erythematous elevations. Diagnosis: history and clinical appearance. Biopsy if suspected. Treatment: 1. Reassure the patient that the lesion is benign 2. In early cases the lesion will resolve with relief of the denture or construction of a new well-fitting denture 3. In advanced cases, surgical excision may be required (and biopsied). 9 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Candidiasis (Candidosis) It is the most common oral fungal infection in humans. Represent classic opportunistic infections caused by Candida albicans. Candida albicans is a component of the normal oral flora with as many as 30-50% of people carrying the organism in their mouths without clinical manifestations. The commensal Candida albicans becomes pathogenic when appropriate predisposing factors exist such as: 1. Acidic saliva 2. Xerostomia 3. Nocturnal denture wearing 4. Heavy smokers 5. Mal-nutrition & mal-absorption syndrome 6. Prolonged use of antibiotics 7. Steroid therapy 8. Radiotherapy (7, 8, 9, 10 & 11 considered Immune-compromised) 9. Chemotherapy 10. HIV infection 11. Endocrine abnormalities 12. Diabetes mellitus 13. Vitamins’ deficiencies 14. Age (elders & infants) 11 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Pseudomembranous candidiasis (Thrush): It's an acute candidal infection, characterized by: 1. Development of soft friable adherent creamy white plaques (pseudo- membranes) on the oral mucosa 2. Distinctive feature of these plaques is that they can be wiped off easily by scrapping them with a tongue blade leaving an erythematous area (bleeding raw mucosa) 3. Most commonly occur on the palate (soft & hard), buccal mucosa, labial mucosa & tongue. Angle of the mouth may be associated (angular stomatitis/ angular cheilitis) 4. Symptoms: Burning sensation & abnormal taste (metallic taste) Diagnosis: 1. History: If any adult male/female patient (not infant, not elder) who develops thrush without an apparent cause; HIV infection or other immunological disturbances should be suspected. However, any form of candidiasis can be secondary to HIV infections 2. Clinically: Presence of the pseudo-membranes, which can be removed by scrapping 3. Laboratory Investigations: a) +ve swab and culture on Sabouraud's dextrose agar to see the colonies b) PAS stain (Periodic Acid Schiff stain) and Gram-stain demonstrate the candidal hyphae Neonatal thrush: Due to: Milk fermentation, Immaturity of the immune response, Acquired during passage through birth canal. 11 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Treatment of Thrush & other Oro-Pharyngeal Candidiasis: # Correction of systemic background or underlying causes # Antifungal therapy, including: I. Topical (Most commonly used): 1. Nystatin (Mycostatin®, Nystat®): *Pastilles/Lozenges 100000 IU 1×4/daily for 1-2 weeks for both adults and children above 5 years old (continue up to 7 days after disappearance of clinical infection). The lozenge held in mouth after meal for 15-30 minutes to dissolve by saliva then swallowed (not for chewing). *Suspension/Drops 100000 IU 1×4/daily after meal for 1-2 weeks (continue up to 7 days after disappearance of clinical infection). *Topical cream (oral gel Nystatin acis®/Mundgel® Germany) (ointment) 100000 IU apply to the affected areas 3-4 times/day after meal for 1-2 weeks (continue up to 7 days after disappearance of clinical infection). Side Effects: It is the best antifungal to treat oral candidiasis; however, may cause nausea and vomiting with high doses. 2. Miconazole: Topical Oral Gel (Daktarin®) (Micogel®), each gram of the gel contains 20 mg of miconazole. Apply to the affected areas 3-4 times/day after meal for 1-2 weeks (continue up to 7 days after disappearance of clinical infection). Side Effects: Interacts with anticoagulants (such as warfarin). Avoid in pregnancy and liver diseases. 3. Amphotericin B (Fungizone®): *Oral suspension 100 mg/ml 3-4 times/day after meal for 1-2 weeks (continue up to 7 days after disappearance of clinical infection). *Lozenge 10mg (slowly dissolves in mouth) 3–4 times/day after meals for 2 weeks (continue up to 7 days after disappearance of clinical infection). 12 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Side Effects: On prolong use in sever/deep cases; Amphotericin B may cause thrombophlebitis, anorexia, nausea, vomiting, fever, headache, weight loss, anemia, hypokalemia, nephrotoxicity, hypotension, arrhythmias, etc. 4. Clotrimazole (Mycelex®): *Gel (15g, 30g) or Cream (1%) apply to the affected area 2-3 times for 3-4 weeks *Solution (1%) 3–4 times daily for 2 weeks minimum *Troche-lozenge (10mg) (slowly dissolves in mouth) 3–4 times/day after meals for 2 weeks (continue up to 7 days after disappearance of clinical infection). Side Effects: Allergic reactions are rare but serious including blistering, rash, burning/itching sensation, (redness, swelling and oozing of face, tongue, and throat), severe dizziness, and breathing difficulties. 5. Others: Gentian violet 1% (Crystal violet) (Triarylmethane antiseptic dye) (not antifungal but has a desirable effect against Candidiasis). Apply 3–4 times/day after meals for 1-2 weeks (continue up to 7 days after disappearance of clinical infection). II. Systemic (for adults mostly in resistant cases and immune- compromised patients): 1. Ketoconazole (Nizoral®): 200mg-400mg tablets taken once or twice daily with food for 2 weeks (depending on the severity and response to treatment). Side Effects: May cause nausea, vomiting, rashes, pruritus, and liver damage. Interacts with anticoagulants. Contraindicated in pregnancy and liver diseases. 2. Itraconazole (Sporanox®): 100mg capsules once or twice daily after meal for 2 weeks depending on the case. Should be taken 1-2 hours before or after antiacids because it needs stomach acid to dissolve. Side Effects: Interacts with anticoagulants. Contraindicated in pregnancy and liver diseases. May cause nausea, neuropathy, and rash. 13 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK 3. Fluconazole (Diflucan®): 50–100 mg capsules once daily for 2–3 weeks Tablets once daily 200mg on first day then 100mg once daily for 2–3 weeks IV solution (200mg/100ml) once daily for 2–3 weeks Side Effects: Interacts with anticoagulants. Contraindicated in pregnancy and liver & renal diseases. May cause nausea, diarrhea, headache, rash, liver dysfunction. Erythematous candidiasis: I. Acute atrophic candidiasis or antibiotic sore mouth Mostly follows a course of broad-spectrum antibiotics. However; could be found in: 1. AIDS & immunocompromised patients 2. Prolonged use of systemic and local steroids 3. Iron deficiency anemia 4. Misdiagnosed with the raw areas of thrush after the white pseudo- membranes have been scraped off Clinically characterized by: 1. Burning sensation 2. The affected mucosa appears red For instance, when the tongue is affected, it may be associated with diffuse loss of the filiform papillae resulting in a reddened (erythematous) bald tongue Treatment: 1. Treat the underlying condition (e.g. Stop or change the antibiotic) 2. Antifungal (topical & if not respond change to systemic) 14 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK II. Central papillary atrophy of the tongue or Median rhomboid glossitis MRG is usually asymptomatic and chronic. It presents as a well- demarcated erythematous zone with smooth or papulated surface. Treatment: Topical Antifungal III. Chronic multifocal candidiasis This is a form of chronic candidal infection involving multiple areas in the mouth. Areas involved: Tongue (as MRG), angle of the mouth (as Angular cheilitis), in addition to the hard & soft palate. Palatal lesions appear red (erythematous) Treatment: Antifungal (systemic) IV. Angular cheilitis or Perlèche Angular cheilitis (Angular stomatitis, Angular Cheilosis, Perlèche). It's a bilateral chronic inflammation of the corner (commissure) of the mouth Characterized by erythema, fissuring and scaling. Typically seen in elders with reduced vertical dimension; however, may occur in other age groups. Smoking might predispose for Angular cheilitis. Microbiological investigations revealed that the lesion is caused by both Candida albicans and Staphylococcus aureus Treatment: 1. Identify the predisposing factors 2. Topical antifungal &/ topical antibiotic such as fusidic acid cream (Fucidin®) 3-4 times/day for 1-2 weeks 3. Increase the vertical dimension if needed (for example restore vertical dimension and occlusion with a prosthesis or correct a faulty prosthesis) 15 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK V. Chronic atrophic candidiasis or Denture associated stomatitis It occurs in denture wearing patients, especially those wearing a well- fitting denture overnight. The denture isolates the underlying or bearing mucosa from the protective/washing action of saliva. It’s characterized by varying degrees of asymptomatic erythema localized to the denture bearing areas of a maxillary removable dental prosthesis. Smoking increases the susceptibility of this infection. Angular cheilitis maybe associated and may represent the chief complain. Previously, Denture stomatitis was thought to be attributed to allergy to denture base material or sensitivity to remnants of methyl-methacrylate monomer. Denture stomatitis is classified into three different types. Type I is limited to minor erythematous sites caused by trauma from/wearing the denture. Type II affects a major part of the denture-covered mucosa. In addition to the features of type II, Type III has a granular mucosa. The denture serves as a vehicle that accumulates sloughed epithelial cells and protects the microorganisms from physical influences such as mastication & salivary flow. The microflora is complex and may, in addition to C. albicans (main causative MO) contain bacteria from several genera, such as Streptococcus-, Veillonella-, Lactobacillus-, Prevotella- (formerly Bacteroides), and Actinomyces-strains. It is unknown to what extent these bacteria participate in the pathogenesis of denture stomatitis. Diagnosis: Appearance & clinical examination. Smear from denture base. Swab and culture Treatment: 1. Instruct the patient to stop wearing the denture for 1-2 weeks, meanwhile, soak the denture in 0.1 hypochlorite or chlorhexidine overnight, to eliminate C.albicans from the denture base 16 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK 2. Topical antifungal: Coat the denture with miconazole gel and wear it, then remove it, clean & scrub the base, and apply the gel again, this is done t.i.d for 1-2 weeks till the fungi eliminated & continue for a week after disappearance 3. In resistant cases, itraconazole or fluconazole may be given orally; however, topical treatment is safer (especially in elders) 4. When there is no response, underlying conditions should be inspected and treated such as iron deficiency anemia Note: Consider replacing the old denture with a new one after treatment. Chronic hyperplastic candidiasis or Candidal leukoplakia This type of chronic candidiasis affects adults of middle age or older. It is characterized by a white patch (plaque) that can’t be removed by scraping. The plaque has variable thickness & often rough or irregular in texture. The lesion may also be nodular with an erythematous background (mixed red and white areas) resulting in a speckled leukoplakia. Such lesions may have an increased frequency of epithelial dysplasia. It's most commonly found on: a. The buccal mucosa & may extend to the commissural mucosa b. Dorsum & latero-dorsal surfaces of the tongue c. Labial mucosa (less) Diagnosis: 1. Clinically: Appearance & non-scraped-off lesion 2. Biopsy: To confirm diagnosis and differentiate the lesion from idiopathic leukoplakia &/ erythro-leukoplakia or erythroplakia 17 Dr. Ahmed Salih Khudhur BDS, M.Sc., PhD. Newcastle University/UK Treatment: 1. Systemic antifungal such as fluconazole for several months 2. Unresponsive lesions need surgical excision and grafting with antifungal treatment to prevent recurrence if there are any remnants Mucocutaneous Candidiasis MCC Chronic mucocutaneous candidiasis syndromes are a rare group of candidiasis, which are difficult to manage. They are also considered as a rare group of immunological disorders. There are 4 main types of MCC: 1. Familial (limited) type 2. Diffused type (Candidal granuloma) 3. Endocrine candidiasis syndrome 4. Late-onset (Thymoma syndrome) Generally characterized by candidiasis of the mouth, nails, skin and other mucosal surfaces. Oral lesions appear as thick white plaques that can’t be scraped off. Treatment: Treat underlying conditions & immunity, and prescribe systemic antifungals given for several months Syphilis Tertiary syphilis: Syphilitic leukoplakia of the tongue may also develop during 3ry syphilis, which is a premalignant lesion. Atrophic glossitis may occur as well. Treatment: After confirmation of diagnosis by history, clinical examination & biopsy (to exclude idiopathic leukoplakia), treat the underlying cause syphilis (Antibiotics, particularly penicillin, tetracycline and erythromycin are also effective). 18