Red & White Lesions PDF

Red & White Lesions May Bilal Assoc. Prof. of Oral Medicine, Periodontology, Oral Diagnosis & Radiology  Aim Recognition the different types of white and red lesions.  Intended Learning Outcomes Identify th...

Red & White Lesions May Bilal Assoc. Prof. of Oral Medicine, Periodontology, Oral Diagnosis & Radiology  Aim Recognition the different types of white and red lesions.  Intended Learning Outcomes Identify the etiology, clinical features, principles of diagnosis, treatment and prognosis of different white and red lesions. Distinguish between the different forms these lesions. Choose the different tools and investigations for diagnosis and treatment of white and red lesions.  Content Systemic lupus erythematosus Candidiasis Etiology Clinical and histopathologic features Investigations & differential diagnosis Treatment Systemic L.E. SYSTEMIC LUPUS ERYTHEMATOSUS ◼ Definition: ◼ SLE is an auto immune disease of unknown etiology, characterized by a variety of immunologic disorders which result in multisystem involvement with varied clinical presentation. ◼ Any organ can be involved e. g. joints, kidneys, heart, lungs, etc. ◼ Etiology: ◼ The etiology is exactly unknown, but it may be attributed to: ◼ 1) Immunologic factors: ◼ Autoantibodies arise as a result of polyclonal activation of B- lymphocytes in an environment where there is impaired function of T- suppressor lymphocytes (Ts). ◼ The autoanibodies include antinuclear, antierythrocytes, antithrombocytes, antiphospholipids, antilymphocyte antibodies (mainly T-lymphocytes) and anticytoplasmic antibodies, circulating anticoagulant are found in the patient's serum and tissue. ◼ The autoantibody may be: ◼ i. Directed against RBCs, WBCs, platelets and coagulation factors and is responsible for hematological features i.e. anemia, leukopenia, thrombocytopenia and clotting disorders. ◼ ii. Autoantibodies may combine with antigen (chiefly nucleic acid) and immune complex is formed, which can activate the complement and attract neutrophils and macrophages. ◼ Failure to eliminate the immune complex by phagocytic system result in their accumulated in the circulation leading to vasculitis and tissue damage of any organ e.g. liver, lung, kidney, heart, CNS, skin... ◼ 2) Genetic factors: ◼ Relatives of SLE patient have demonstrated a high incidence of low autoantibody titer and immune deficiency (Ts and C2) and this is greater among identical twins. ◼ Patients with HLA DR3 & DR4 gene are at risk of developing SLE. ◼ 3) Hormonal factors: ◼ The high prevalence of SLE among women of reproductive age suggest that female hormones may modify the immune response. ◼ Abnormal estradiol metabolism has been reported in both male and female patients. ◼ Disturbance is estrogen-progesterone balance in women may precipitate disease flare as in pregnancy or pre-menstruation. ◼ In some women, the combined oral contraceptive pill may precipitate SLE. ◼ Estrogen enhances anti-DNA antibody formation. ◼ 4) Infection: ◼ Viral like particles have been detected in tissues of SLE patients and it may initiate the abnormal immune response. ◼ 5) Drug induced: ◼ Many drugs have been listed in the etiology of lupus like syndromes e.g. phenytoin, quinidine, methyldopa. ◼ The drug induced features of LE suggest hypersensitivity mechanism that may involve alteration of DNA nucleoprotein and subsequently auto-antibody production. ◼ Clinical Features: ◼ SLE is predominantly a disease of young women, there is female predominance of 10:1 and has higher incidence among blacks. ◼ ◼ SLE is serious cutaneous systemic disorder which is characteristic by repeated remission and exacerbation. ◼ American Rheumatism Association proposed a revised set of criteria for the classification of SLE. ◼ This classification is based on 11 criteria and requires that the patient exhibits four or more criteria either serially or simultaneously, during any interval of observation in order to be diagnosed positively. ◼ Diagnostic Criteria: ◼ 1) The cutaneous manifestation may be widely spread over the body, occurring usually as erythematous, edematous, macules with patchy and coalescent distribution. (butterfly) ◼ The lesions tend to be bilateral and widespread in SLE. ◼ 2) Discoid scaly rash is less common. ◼ 3) Photosensitivity ◼ Associated skin lesions: ◼ Alopecia: may be patchy or diffuse and is often guide to disease activity. ◼ Raynaud's phenomenon; is a common manifestation and characterized by pallor or cyanosis and tingling of toes and fingers on exposures to cold or emotion due to paroxysmal vasospasm. ◼ Skin ulcers secondary to vasculitis. ◼ 4) Oral ulcers ◼ 5) Serositis-inflammation of serous tissue: (a) Pleuritis-lining lung (b) Pericarditis-lining heart (c) Peritonitis-lining abdomen. ◼ 6) Renal disorder. ◼ a. Persistent proteinuria. ◼ b. Cellular casts (erythrocytes and leukocytes). ◼ c. Nephritis. ◼ 7) Musculoskeletal: ◼ Non-deforming arthritis ◼ Arthralgia-joint pain, polyarthritis (migratory as in rheumatic fever) and myositis-ms. inflam. ◼ 8) Cardiopulmonary: ◼ Pericarditis may occur often in association with pleurisy or inflammation in sheet like layers covering lung. ◼ A localized myositis of the diaphragm may result in the so called "shrinking lung syndrome" with diminution of lung volume and normal gas transfer. ◼ Circulating immune complex cause endothelial damage to heart valves and initiate fibrin-platelets deposition at the site of injury which can act as nidus for bacterial colonization during bacteremia. ◼ Damage of heart valves is called Libman-Sacks endocarditis. ◼ Antibiotic prophylaxis should be considered for all patients with SLE undergoing dental procedures associated with transient bacteremia. ◼ 9) Immunologic disorder: ◼ a. Positive LE cell ◼ b. False positive STS (serologic test for syphilis) ◼ c. Anti dsDNA antibody ◼ d. Circulating antibodies to platelets and other blood cells ◼ 10) Neurologic disorder: ◼ a. Seizures ◼ b. Psychosis ◼ c. Cerebrovascular accident ◼ 11) Hematological: ◼ Hemolytic anemia and autoimmune thrombocytopenia may precede the development of other disease features by many years. ◼ Anemia and leukopenia are common features of disease activity. The latest diagnostic criteria for SLE were developed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) in 2019. These criteria are designed to be highly sensitive and specific, and they require a positive antinuclear antibody (ANA) test as an obligatory entry criterion in addition to weighted criteria. Patients with a score of 10 or more points are classified as having SLE. ◼ SLE can produce a wide variety of clinical features depending on the organs which are affected. ◼ The classic picture is that of young woman with fever, malaise, anemia, joint pain, skin rashes and weight loss. ◼ In renal involvement, about 22% of patients progress to end stage require hemodialysis or transplantation. ◼ Oral Manifestation: ◼ It is seen in 10-20% of patients but rarely an early features. ◼ Common sites: buccal mucosa, gingival tissues, lip, palate and alveolar ridge. ◼ 1) The oral manifestations of SLE may be similar to those described for DLE but with little keratinization. ◼ Lip lesions : ◼ Consists of a central atrophic area with small white dots surrounded by a keratinized border composed of small radiating striae. ◼ Mucositis, glossitis and angular cheilosis have been reported. ◼ 2) Erythematous patches on the oral mucosa, superficial erosion, or ulceration are induced by vasculitis secondary to immune complex formation and complement activation. ◼ 3) Oral mucosa may reveal pallor, petechia, secondary infection or bleeding, this is attributed to autoantibodies against RBCs, platelets, WBCs & clotting factors. ◼ 4) 2ry infection by candida may be seen. ◼ About 30% of the patients complain of xerostomia & soreness as a part of Sjogren's syndrome. (kerato conjunctivitis sicca – xerostomilargement of parotid gland). - Temporomandibular disorders causing pain. ◼ Desquamative gingivitis. ◼ Oral lesions of SLE may be confused with oral lichen planus and can be differentiated by histopathological and direct immunofluorescent findings. ◼ Oral LE lesions would respond less rapidly than OLP to the usual topical steroid treatment. ◼ Histopathologic Findings: ◼ The histologic appearance of both SLE and DLE are nearly similar but differing only in degree of certain finding. ◼ The histopathological features reveals: ◼ 1. Hyperorthokeratosis or hyperparakeratosis with areas of atrophic epithelium. ◼ 2. Acanthosis. ◼ 3. Hydropic degeneration of the basal cell layer. ◼ 4. Vascular dilatation with edema of the upper dermis or submucosa are characteristic features. ◼ 5. Diffuse infiltration of lymphocytes. There is perivascular collection of lymphocytes. ◼ 6. Basophilic degeneration of collagen and elastic fibers. ◼ In SLE, the inflammatory features are more prominent, while DLE tends to have more pronounced degenerative and collagenous changes. ◼ SLE exhibit histopathologic changes in the oral lesion that are identical with DLE but with lack of keratinization. Histopathological and direct immunofluorescence findings in cutaneous lupus erythematosus; superficial perivascular infiltration with lymphocytes and basal vacuolization, superficial and deep perivascular lymphocytic infiltration ◼ Immunofluorescent Testing: ◼ Direct immunofluorescent technique is performed by incubating a biopsy specimen of the lesion with a fluorescein - conjugated antiglobulin and the slide examined in the ultraviolet microscope, this may reveal: ◼ 1. With immunoglobulin antisera (IgG, IgM, IgA antisera): ◼ Positive reaction which appear as granular linear deposits at the level of basement membrane zone, 100% positive for SLE and 70% positive for DLE. ◼ 2. With anti fibrinogen and anticomplement (C3) antisera: ◼ Positive reaction i.e. granular, linear deposits along the basement membrane zone. ◼ Biopsies from uninvolved skin when subjected to immunofluorescent testing reveal positive reaction (90%) in SLE and negative reaction in DLE. ◼ This is called Lupus band test. Lupus band test: is a diagnostic procedure used to detect deposits of immunoglobulins and complement components along the dermoepidermal junction in patients with lupus erythematosus. This test is particularly helpful in distinguishing between systemic lupus erythematosus and cutaneous lupus: 1.In SLE, the lupus band test will be positive in both involved and uninvolved skin. 2.In cutaneous lupus, only the involved skin will be positive. The LE cell test is an another diagnostic tool used in SLE. Lupus Erythematosus (LE) Cells are neutrophils that have engulfed lymphocyte nuclei coated with and denatured by antibodies to nucleoprotein. 1.LE cells are not usually found in peripheral blood but can be observed in other bodily fluids like synovial fluid, cerebrospinal fluid, and pericardial and pleural effusions from patients with SLE. 2.LE cells are positive in 50%-75% of individuals with acute disseminated SLE. 3. Positive reactions are also seen in other conditions like rheumatoid arthritis, scleroderma, and other disease. 4. While the presence of LE cells is indicative of SLE, their absence does not exclude the disease. Typical LE cell consists of neutrophilic granulocyte distended by large structureless pink staining granular inclusion body which compresses the nucleus against the cell membrane, leaving only thin rim of visible cytoplasm. Other Laboratory Diagnostic Tests of SLE: 1.Antinuclear Antibody (ANA) Test: (indirect immunofluorescent antinuclear antibody test using rat's kidney or liver substrate) 1. ANA are autoantibodies that target the nuclei of cells. 2.Approximately 98% of people with SLE have a positive ANA test result. 3.The ANA test is the most commonly and most sensitive screening test for confirming the diagnosis of SLE. Indirect Immunofluorescence Test for ANA identify ANA staining patterns and titers. Staining Patterns: Common ANA staining patterns include nuclear (e.g., homogeneous, fine speckled, coarse speckled), cytoplasmic, and mitotic. Titer of ANA: Titers above 1:80 are considered positive, and higher titers (≥ 1:640) suggest SLE, especially when other clinical manifestations are observed. 2. Anti-Double-Stranded DNA (anti-dsDNA) Antibodies: 1.These antibodies specifically target double-stranded DNA to determine if there are antibodies to the genetic material in the cell. 2.They are specific for diagnosing SLE and their presence is highly associated with SLE and may detect disease activity. 3. Anti-Smith (anti-Sm) Antibodies: 1.These antibodies are directed against small nuclear ribonucleoproteins (snRNPs). 2.Their presence is strongly linked to SLE. 3.Anti-Sm antibodies are part of the diagnostic criteria for SLE. 4. Antiphospholipid Antibodies: 1.These antibodies target phospholipids and are associated with clotting disorders. 2.Highly specific but not very sensitive for diagnosis. 3.Although not specific to SLE, their presence can suggest the possibility of SLE. ◼ 5. Immune complexes: although tissue damage is mediated by immune complexes, the presence of circulating complexes is of limited use in assessing disease activity. ◼ 6. Complement Level: ◼ The serum complement is frequently reduced in the presence of active disease because of increased utilization due to immune complex formation, reduced synthesis or combination of both factors. ◼ C3 and C4 decreased during the disease activity. ◼ C2 deficiency predispose to SLE. ◼ 7. ESR and C. reactive protein: ◼ In most of the chronic inflammatory diseases, CRP rises in direct proportion to ESR. ◼ This is not specific in case of SLE, where despite ESR above 100 mm/ hour, the CRP remain less than 1 ug/ litre. (Normal after 1 hour → 4 mm. in male and 8 mm in female). ◼ Treatment of DLE: Topical Steroids: Medicated mouthwashes and topical creams or gels containing steroids, such as triamcinolone dental paste, are commonly used to reduce inflammation and pain. Topical Anesthetic Agents: Gels or rinses containing benzocaine can provide relief from pain and discomfort. Saltwater and Baking Soda Rinses: These can soothe oral lesions and promote healing. Antimalarial Drugs: Such as hydroxychloroquine can manage symptoms and reduce flare-ups. NSAIDs: can manage pain and inflammation. Corticosteroids: Prednisone and other systemic corticosteroids are often prescribed to control severe inflammation. Immunosuppressive-Drugs: like azathioprine, methotrexate, cyclophosphamide, cyclosporine, and mycophenolate mofetil can be used to suppress the immune system and reduce inflammation. ◼ Treatment of SLE: ◼ The same treatments as DLE, in addition to: Steroid Nasal Sprays: These can be used as an alternative to topical applications for treating oral lesions. ◼ Hydroxychloroquine: Recommended at a dose not exceeding 5 mg/kg real body weight. ◼ Glucocorticoids: During chronic maintenance treatment, glucocorticoids should be minimized to less than 7.5 mg/day and, when possible, withdrawn Immunomodulatory Agents: Early initiation of agents like methotrexate, azathioprine, and mycophenolate can help in decreasing the dose of glucocorticoids and improvement. Belimumab and Rituximab : Considered as an added therapy for persistent active or flared diseases and threating refractory cases. They are both monoclonal antibodies. Some patients may respond well to long term with NSAIDs or combined NSAIDs with a very low dose of corticosteroids taken on alternate days. ◼ Dental Implication of S.L.E.: ◼ 1. There is an excessive bleeding tendency due to marked platelets deficiency or coagulation disorders so platelet count, PT and PTT should be undertaken before any surgical interference. ◼ 2. Prophylactic antibiotic cover is necessary in S.L.E. because bacteremia in these patients is dangerous and the patients are liable to develop infective endocarditis. ◼ 3. Avoid penicillin and sulfonamide and non steroid ant-inflammatory drugs as much as possible since these drugs may cause deterioration of the disease. ◼ Avoid tetracyclines, it may cause photosensitivity rashes. ◼ 4. Avoid any dental surgery as possible since it may cause exacerbation of the condition. ◼ 5. Since these patients are on long term steroids, atrophy of the adrenal gland may occur, and adrenal crisis may develop. ◼ These patients are liable to severe infections due to immunosuppressive therapy. ◼ 6. Anemia, heart failure and renal disease may complicate the dental treatment. Oral Candidiasis ◼ Candidiasis is a general term of diseases produced by candida species, and entails colonization, superficial infection (thrush), moderate invasion (candida leukoplakia) deep invasion (CMCC). ◼ Oral candidiasis is a specific endogenous infection caused by yeast like fungus called candida albicans. ◼ Not only the oral mucosa is involved, but candida albicans can invade GIT, RT, vagina and blood stream (fungaemia). ◼ The etiology of tissue alteration produced by Candida albicans is not known but it may be attributed to: ◼ I) Toxins produced by c. albicans: ◼ a. Direct effect of toxins on the tissues. ◼ b. Toxin may act as antigen, stimulating immune response or delayed hypersensitivity reaction and tissue damage is due to lymphokines. ◼ II) C. albicans produce proteinase and lipase enzymes: ◼ This enzymatic break down of the infected epithelium induces the candidal lesions. ◼ Candida albicans is found normally in healthy mouth in low concentration and in adult vagina. ◼ The persistence of c. albicans in the mouth and vagina is due to symbiotic relationship with lactobacillus acidophilus, this organism appears to favor the persistence of the yeast but its acid production limits its proliferation. ◼ Immunity and candidiasis: ◼ The source of candidal infection is usually the, normal host flora. ◼ Intact mucosal barrier (normal epithelial shedding), is the major nonspecific host defense mechanism. ◼ Immunity to candidiasis is mainly cellular involving neutrophils, macrophages, lymphocytes (mainly T cells) and probably natural killer cells. ◼ (1) Phagocytes: ◼ Neutrophils have strong candidacidal activity. ◼ Neutrophils contain microbicidal proteins which can resist candidal invasion and ingest the yeast (phagocytosis). ◼ Neutropenia or defective neutrophilic function predispose to candidal invasion. ◼ (2) T-lymphocytes: ◼ These cells control of chronic candidiasis by manufacturing and releasing lymphokines. ◼ Defective cell mediated immunity predispose to invasive mucosal disease. ◼ (3) Salivary IgA act as first line of defense against acute candidiasis. ◼ Salivary IgA affects the adherence of C. albicans to oral mucosal epidermal cells. ◼ (4) Serum antibody and nonspecific factors like complement while possessing anticandidal activity, appear to play less significant role. ◼ The fungi are not susceptible to direct killing by antibody and complement. ◼ Predisposing factors: ◼ C. albicans is a poor pathogenic fungus, of low virulence and non-contagious and in order to induce a disease it should penetrate or invade the epidermis. ◼ This penetration may be very superficial or moderate or deep. ◼ In order to penetrate or invade the tissue certain local and or systemic factors should operate in favor of the fungus.  such as Down’s syndrome ☻Newborn infant, old age patients & ☻ Excessive use of antiseptic pregnancy and contraceptive pills mouth washes, or topical antibiotics ◼ Clinical Features: ◼ Oral candidiasis can produce a variety of clinical features; Nonkeratotic (pseudomembranous), keratotic, erythematous or combination. 1. Acute candidiasis 2. Chronic candidiasis Pseudomembranous Pseudomembranous candidiasis e. g. thrush candidiasis e. g. AIDS Erythematous (atrophic) Erythematous (atrophic) candidiasis or candida candidiasis associated lesion: Denture stomatitis Angular cheilitis Median rhomboid glossitis Hyperplastic candidiasis: Candidal leukoplakia Chronic mucocutaneous candidiasis ◼ 1) Acute candidiasis ◼ a. Acute pseudomembranous candidiasis: ◼ Clinical features: ◼ Age: ◼ This form of candidiasis can be seen in newly born infants (2-3 days old) as well as in children. ◼ Adults and older age group who are immuno- compromised are commonly affected. ◼ Signs: ◼ The lesions appear as raised, white, soft, gelatinous or creamy adherent plaques. ◼ It may be isolated patches, or it may grow centrifugally and merge to form diffuse white patches. ◼ Oral lesion may be localized or diffuse, depending on the patient's body resistance. ◼ If the host resistance is high the lesion tends to be localized, if the host resistance is impaired or not active the lesion tends to be diffuse. ◼ The pseudomembranous white patches may be surrounded by erythematous band. ◼ Wiping away the pseudomembrane with a cotton tipped applicator (with difficulty), will reveal an erythematous, eroded or ulcerated surface which is often tender. ◼ The oral lesion may develop at any site in the mouth. ◼ Symptoms: ◼ The oral lesion is generally painless or associated with minimum symptoms. ◼ The lesion will become painful as the pseudo- membrane is removed or torn away. ◼ The lesion may extend on circumoral tissue or may spread to the pharynx and esophagus which my lead to feeding problem especially in infants. ◼ Histopathology: ◼ There is localized inflammatory reaction with erosion of the surface epithelium. ◼ The mucosa is covered by pseudomembrane which consists of desquamated epithelial cells, keratin fragments, fibrin, food debris, polymorphonuclear leukocytes and bacteria, all matted together and attached to the oral mucosa by the hyphae of candida albicans. ◼ The superficial epithelial cells (pseudomembrane) are separated by inflammatory cells from the deeper epithelium. ◼ b. Acute atrophic "erythematous“ candidiasis ◼ The acute atrophic candidiasis is induced via: ◼ 1) If thrush persists and the pseudomembrane is torn away and lost, the resulting clinical feature is known as acute atrophic candidiasis. ◼ 2) Occasionally acute atrophic candidiasis may occur following the administration of antibiotic where oral lesions begins to appear on 5th day and this is known as antibiotic stomatitis and / or glossitis. ◼ The latter should be suspected if there is bad taste and sore mouth and throat during the convalescent period of the illness in patients who has had antibiotic treatment. ◼ 3) Steroid therapy may induce the same clinical picture as that induced by antibiotic. ◼ Clinical features: ◼ Signs: ◼ The oral lesions resembling thrush in which the pseudomembrane is removed and has the following features: ◼ The oral mucosa appears red, atrophic with painful eroded areas which may be localized or diffuse. ◼ Few white flecks of thrush (minimum evidence of pseudomembranous formation) may be seen. ◼ Angular cheilitis may be present ◼ Tongue; when affected it reveals papillary atrophy (antibiotic glossitis, if there is history of antibiotic administration). ◼ Symptoms: ◼ Oral symptoms are marked compared with thrush because of the numerous erosions and intense inflammation. ◼ Oral lesions tend to be localized with systemic antibiotic and diffuse with topical antibiotic mouth rinse ◼ A similar picture of generalized redness and soreness of the oral mucosa is the typical feature of candidiasis associated with xerostomia. ◼ Histologically: ◼ Thin atrophic epithelium covering. ◼ Candidal hyphae & spores penetrating the superficial cells. ◼ Infiltration of inflammatory cells within and beneath the epithelium. ◼ 2) Chronic candidiasis ◼ A. Chronic pseudomembranous candidiasis (AIDS) ◼ B. Chronic atrophic candidiasis or candida associated lesion: Denture stomatitis Angular cheilitis Median rhomboid glossitis ◼ Denture Stomatitis: ◼ It is commonly seen in relation to the upper jaw because: ◼ 1) The nature of retention of upper denture by negative pressure leads to deficient access of salivary antibodies (IgA). ◼ 2) The intimate contact between upper denture and palatal mucosa facilitate adherence of C. albicans to denture bearing area. ◼ 3) Inadequate cleaning of the fitting surface of the denture. ◼ 4) Wearing of the denture day and night. ◼ 5) Delayed hypersensitivity reaction to C-albicans antigen is believed to contribute to the inflammation. ◼ It is uncommon with lower denture, due to nature of retention leading to constantly flushing with salivary flow. whose mechanical cleansing effect and candidal antibodies prevent infection. ◼ DSM is seen more in females than males, this may be due to self infection, via the vagina. ◼ Clinical features: ◼ Signs: ◼ a. The whole oral mucosa of the denture bearing area up to the crest of the ridge is diffusely inflamed, brightly erythematous with pebbly to velvety surface and small sized sporadic white flecks. ◼ b. Occasionally this feature may appear in the form of small patches. ◼ c. The palatal inflammation may be associated with papillary hyperplasia. ◼ d. Angular cheilitis is seen in 70 % of cases of denture stomatitis. ◼ These clinical features persist for years as the denture is worn and in the absence of treatment. ◼ Symptoms: ◼ The symptoms are usually absent, but occasionally there may be soreness, or burning sensation which is reported during period of exacerbation. ◼ Histopathology: ◼ The normal orthokeratin layer of the palatal epithelium is replaced by parakeratotic cells. ◼ The epithelium may show hyperplasia or atrophy. ◼ Chronic inflammatory cell infiltration in the corium. ◼ Angular cheilitis: ◼ Angular cheilitis is characterized by soreness, erythema, maceration, ulceration and fissuring affecting the lip commissure. ◼ In other cases, there may be cracking, bleeding or prominent crusting, in such case there may be mixed staphylococcus and candidal infection. ◼ Etiology: ◼ A. Candidal infection associated with denture stomatitis is the most common cause. ◼ B. Elderly patients with reduced vertical dimension or the presence of deep skin folds at the angle of the mouth, the saliva may collect in skin fold at the angle of the mouth and C. albicans soon colonizes the wet skin. ◼ C. Angular cheilitis may be seen in individuals who habitually lick their lips and moisten the skin with saliva. The skin is fissured and erythematous. ◼ D. Nutritional deficiency "Perleche" e.g. vit. B complex, folate and iron deficiency. ◼ E. In minority of cases it is due to staphylococcus infection spread from anterior nares. ◼ Angular cheilitis can be seen with any type of intraoral candidiasis and this is the only feature which they all share in common. ◼ Angular cheilitis is occasionally seen in isolation, then it is likely to be staphylococcus or streptococcus rather than candida. ◼ Median Rhomboid glossitis; ◼ The median rhomboid glossitis appears as a smooth pink rhomboid area, devoid of lingual papillae, the surface may be depressed or raised and is always asymptomatic. ◼ It is found anterior to the circumvallate papillae and has a rhomboid outline. ◼ In the past this was attributed to developmental anomalies of the tongue, secondary to persistence of tuberculum impar. ◼ However, this lesion may be a form of chronic atrophic candidiasis. ◼ C. Chronic Hynerplastic Candidosis (Candidal leukoplakia) ◼ Candidal leukoplakia appears as a thick, white leathery plaque of irregular thickness, with rough or nodular surface, and is difficult to differentiate it from leukoplakia, because clinically they are identical. After elimination of yeast (by antifungal drug) the hyperplastic ◼ Biopsy using special stains epithelium persists (PAS) and antibody studies (leukoplakia). are employed to differentiate both lesions. ◼ The white patch is frequently Chronic Plaque- Type Candidiasis seen as a triangular patch on the buccal mucosa adjacent to lip commissure which tapers posteriorly. ◼ The lesions are usually of bilateral distribution. ◼ In some cases, erythematous areas are located within the Chronic Nodular Candidiasis white patches producing a feature of speckled leukoplakia. ◼ Candidal leukoplakia is often associated with angular cheilitis. ◼ Similar clinical features are seen in CMCC. ◼ Most patients are men of middle age or over and many are heavy smokers. ◼ Candidal leukoplakia is considered to be premalignant lesion. ◼ Histopathology ◼ The histopathology of this lesion differs from leukoplakia in that the epithelium is always parakeratinized (hyperparakeratosis). ◼ Candidal invasion of the epithelium may reach the edge of stratum spinosum and mitotic activity is often increased leading to acanthosis. ◼ Dysplastic changes may be prominent. ◼ Areas of atrophic epithelium associated with lack of surface keratinization may be seen. ◼ There is chronic inflammatory infiltration in the underlying corium. ◼ Chronic Mucocutaneous Candidosis (CMCC) ◼ CMCC is a rare group of candidiasis characterized by deep candidal invasion of the epidermis & may reach the corium. ◼ It induces inflammatory hyperplastic response and granulomatous reaction. ◼ CMCC involve the skin, scalp, nails and mucous membranes. ◼ The development of CMCC is attributed to secretory IgA deficiency, structural defect of epidermis, defect in cellular immunity & reduced serum candidacidal activity. ◼ CMCC even if mild, it persists and responds poorly to topical treatment with nystatin or amphotericin but may respond to imidazole antifungal drugs. ◼ Once the treatment is discontinued the organism rapidly reappears, since immunological defects may be found. ◼ Oral mucosa is involved in all cases of CMCC & in most cases appears similar to chronic hyperplastic candidiasis & affect any part of the oral mucous membrane ◼ Diagnosis of candidosis: ◼ 1. Case history. ◼ 2. Clinical examination of the lesion. ◼ 3. Special investigation: ◼ Bacterial smear for direct microscopic examination. ◼ Demonstration of the fungus by direct scraping from the lesion. ◼ The yeast is gram positive in stained films. ◼ Bacterial culture using Sabouraud's modified agar with Chloramphenicol and incubated at 30 C° or room temperature on which the bulk of oral bacteria fails to grow. ◼ The colonies appear white and have bad odor because they ferment sugar. ◼ High candidal antibody titer in serum and saliva. ◼ 4. Resolution by antifungal drugs. ◼ Treatment of oral candidiasis: ◼ The underlying predisposing factors should be eliminated or corrected, so topical or parentral antibiotics and corticosteroids should be stopped if possible. ◼ Poorly fitted dentures should be replaced and oral hygiene must be improved. ◼ Diabetes should be controlled, and search is made for other systemic diseases. ◼ Antifungal agents are the drugs of choice in treatment of candidosis and these include; ◼ 1. Nystatin ◼ Nystatin suspension (100,000 u/ml), small amounts can be held in the patient's mouth for several minutes, four times a day, and for infants swab the lesion several times a day. ◼ Nystatin pastille (100,000 U) to be sucked four times a day, because nystatin has a bitter taste and unpleasant flavor. ◼ Vaginal tablets (100,000 U) containing lactose are more acceptable to treat oral moniliasis. The tablets are allowed to dissolve in the mouth four times a day. ◼ 2. Amphotericin ◼ It is a more powerful drug used as 10mg lozenges to be sucked q.d.s or in the form of 3% ointment to be applied several times a day or for intravenous administration for deep and systemic candidiasis. ◼ Nystatin and Amphotericin have similar chemical and biological properties and act primarily by local contact, by linking drugs to the fungal cell membrane. ◼ In doing so, holes form in the cell membranes which become unable to protect the normal fluid and electrolyte balance of the cell content. ◼ 3. Imidazole anti-fungal agents: ◼ They are effective against superficial as well as many deep and systemic mycosis and include: ◼ a. Miconazole: is available as 250 mg tablets, cream and oral gel. ◼ Gel is useful in angular stomatitis where there is mixed bacterial and fungal infection. ◼ b. Ketoconazole: available in 200 mg tablet to be used once daily. (Nizoral) ◼ It is used in chronic candidal leukoplakia or candidiasis in immunosuppressed patients. ◼ Ketoconazole is available also as a cream which is effective in angular stomatitis. ◼ Ketoconazole is contraindicated in acute liver diseases and in pregnancy. ◼ Ketoconazole need acid in the stomach to dissolve, so patient on antacids or histamine blockers should take the drug two hours after the antacid. ◼ c. Fluconazole: Since it interacts with some drugs (anticoagulants, cyclosporin, phenytoin and oral hypoglycemics) it should be used with caution. ◼ The dose is 100 mg /day. (Diflucan) ◼ d. Itraconazole: 100mg capsule once/day. (Sporanox) ◼ 4. In dealing with chronic atrophic candidosis, ◼ The patient's denture may be relined, and the occlusal abnormalities should be corrected, but it is better to supply a new denture. ◼ The denture should be left out of the patient's mouth as long as possible. ◼ At night the patient is advised to put his denture in cetrimide solution. ◼ During the day, nystatin cream is applied to the fitting surface of the denture t.d.s. ◼ Treatment of angular cheilitis must always involve treatment of denture stomatitis or any other intraoral candidal lesions. ◼ 5. Chlorohexidine rinse and gel have been proved to be effective in treatment of sore mouth and angular cheilitis. ◼ 6. Yoghurt and butter milk which contain culture of lactobacillus are useful adjuncts in the treatment of both oral and G.I.T moniliasis. ◼ Acute oral lesions respond rapidly to nystatin and amphotericin for a period of 7-10 days, and the therapy should continue 2 weeks after the clinical resolution of the lesion. ◼ Patients for whom predisposing factors can't be eliminated or corrected, will need prolonged or repeated treatment. ◼ In chronic oral candidiasis, the response to antifungal drugs is less dramatic and this is due to the underlying thick keratotic lesion or the presence of artificial denture, so antifungal drugs should be maintained 4 weeks at least. ◼ Treatment of candidal infection particularly in debilitated patients is undertaken to avoid: ◼ 1. Direct spread of the lesion to the pharynx. ◼ 2. Aspiration of pseudo-membrane (pneumonia- pulmonary candidiasis). ◼ 3. GIT thrush. ◼ 4. Blood stream dissemination is called monilial fungaemia with the development of monilial granuloma on the heart valves, lungs, kidneys and other organs.  References Glick M, Greenberg MS, Lockhart PB, CallacombeSJ, Burket’s Oral Medicine, 13thedition, John Wiley & Sons, Inc. Hoboken USA; 2021. Farah C S, Balasubramaniam R, Mc Cullough M J, Contemporary Oral Medicine, Springer, Switzerland, 2019. Ongole R: Textbook of Oral Medicine, Oral Diagnosis and Oral Radiology, 2nd edition, Elsvier, 2014. Laskaris G, Color Atlas of Oral Diseases in Children and Adolescents, Library of Congress, 2017. THANK YOU For any questions feel free to contact me by mail [email protected] Assoc. Prof. May Bilal Oral Medicine, Periodontology, Oral Diagnosis & Radiology