Infections of the Oral Mucosa PDF

Infections of the oral mucosa Dr. Ghada Haroun M.Med.Sci-Diagnostic oral pathology  Viral infections Bacterial infections Fungal infections 1. Viral infections disease virus Herpetic stomatitis; primary and recurrent herpes simplex- type...

Infections of the oral mucosa Dr. Ghada Haroun M.Med.Sci-Diagnostic oral pathology  Viral infections Bacterial infections Fungal infections 1. Viral infections disease virus Herpetic stomatitis; primary and recurrent herpes simplex- type 1(mainly), and less commonly- type 2 Chickenpox and shingles varicella zoster herpangina Coxsacki A Hand, foot, and mouth disease Coxsacki A Infectious mononucleosis Epstein-Barr virus (EBV) Measles paramyxovirus hairy leukoplakia EBV Viral warts Human papilloma virus (HPV) Oral manifestations of HIV infection Human immune deficiency virus (HIV) Mumps paramyxovirus Influenza Influenza virus Herpetic stomatitis: The most common viral infection of the mouth Caused by HSV- type 1(mainly), and 2 Primary infection is usually subclinical, but may manifest as herpetic gingivostomatitis Herpetic gingivostomatitis: Mainly in children and young adults Incubation period: 5 days Fever and malaise Numerous small vesicles on any part of oral mucosa Vesicles rupture and become secondarily infected Regional lymphadenitis Gingiva is erythematous and edematous Circumoral crusting due to coagulation of exudates  Extra oral lesions may be seen, particularly in children Herpetic Whitlow:-infection of finger and nail bed; painful and can be transmitted to the eyes by rubbing Histopathology: Intraepihelial blister; it results from distention and rupture of virally infected cells and coalescence of these disrupted cells Ballooning degeneration: the virally infected cells become swollen, with eosinophilic and large vesicular nuclei Multinucleated giant cells Lamina propria shows variable inflammatory infiltrate which may extend to the epithelium Recurrent herpes infection: Affects one of three who have had primary infection Symptoms are localized with no systemic illness Herpes labialis is the most common form Prodromal symptoms; numbness and itching followed by clusters of vesicles Vesicles rupture with in short time and become crusted Heals with in a week Recurrent intraoral herpes occurs occasionally, and affects gingiva or hard palate Pathogenesis of recurrent herpes: Following primary infection the virus become latent in the sensory ganglion of trigeminal nerve Reactivating factors involve: stress, common cold, trauma, uv light, menstruation, and immunosuppression These factors alter the latency of the virus resulting in its migration along the sensory nerves to the nerve endings The virus will then replicate with in the epithelium of the lips, skin or oral mucosa resulting in recurrent herpes Can be very severe in HIV or immunocompromized patients Chickenpox and herpes zoster: Both chickenpox and herpes zoster are caused by varicella-zoster (VZ) VZ is a DNA virus similar in morphology to herpes simplex virus Oral lesions of chickenpox can be found any where on the oral mucosa; particularly, soft palate and fauces Oral lesions may precede the characteristic skin rash, and present in form of ulcers Histopathology: examination of an intact vesicle shows cytopathic effects indistinguishable from those of Herpes simplex Herpes zoster: It is the recurrent form of chickenpox Repeated attacks of zoster is uncommon Following primary infection by chickenpox; the virus becomes latent in the sensory ganglia Reactivation of the virus may be spontaneous or due to immunosuppression The lesions are localized to the distribution of sensory nerves Unilateral vesicular eruptions Prodromal symptoms start up to 2 weeks as sever pain and numbness When the trigeminal nerve is involved; the ophthalmic division is the most commonly affected Involvement of second and third divisions of trigeminal nerve, results in toothache like pain followed by vesicular eruptions along the distributions of one or more branches of trigeminal nerve  The vesicles may be entirely intraoral, where they rapidly rupture and ulcerate The course of the disease is about two weeks Post herpetic neuralgia is the most distressing complication Ramsy Hunt syndrome : Due to involvement of facial and auditory nerves by Herpes Zoster: Facial paralysis Painful vesicular eruptions on the external auditory meatus of the ipsilateral year Tinnitus, deafness, vertigo Loss of taste sensation Herpangina: Caused by Coxsackie A virus (RNA –virus) Most commonly in children Sudden onset of mild illness; fever, malaise, anorexia, sore throat Vesicles on the palate, tonsils, and uvula Vesicles rupture leaving small ulcers Symptoms resolve within 3 days Some times confused with primary herpes; however, herpes is gingivostomatitis, whereas herpangina is an oropharyingitis Hand, foot and mouth disease: Caused by coxasckie virus A Mainly in children Transmitted by close association e.g: household Small (2-8 mm) ulcers on : Oral: gingiva, tongue, palate, buccal mucosa Skin: palms of hands , and soles of feet Spontaneous remission with in 2 weeks Infectious mononucleosis (glandular fever): Caused by Epestein-Barr virus (EBV)_ a member of herpes virus Mainly in teenagers and young adults Transmitted by kissing; hence called kissing disease Fever, pharyngitis, enlarged lymph nodes Long lasting malaise; for months or more Oral fondings: Non specific Petechial hemorrhage at junction of hard and soft palate Ulceration of oral mucosa Pericoronitis Enlarged submandibular lymph nodes Investigations: Testing acute serum for IgM antibodies to EBV capsid antigen Mono-spot slide test Pauel- bunnell test N.B: EBV is also associated with: Burkitts lymphoma Nasopharyngeal carcinoma Hairy leukoplakia Measles: Mainly in children In developed countries:- mild, with low mortality In developing countries:- severe with high mortality Prodromal symptoms resemble common cold accompanied by oral lesions called Koplik’s spots Koplik’s spots:  Mainly on buccal mucosa opposite the molar teeth  Pin-point bluish white spots against erythematous background.  Range from few numbers to several hundred  Disappear after the skin rash develops three to four days later  May result in gangrenous stomatitis in malnourished patients Mumps: Acute epidemic infection caused by Mumps virus (paramyxovirus) The commonest cause of salivary gland enlargement. Most common in children Spread by direct contact with infected saliva. Incubation period is 2-3 weeks after exposure. Fever, malaise and sudden enlargement of one or more saliv.gl, mainly parotid.  the swelling subsides gradually over 6 weeks. In adults; other internal organs my be involved, like ovaries, testis, CNS and pancreas. Orchitis (inflammation of testis) is a common complication in adult males resulting in infertility Recurrence is rare. Cytomegalovirus (CMV); Belongs to herpes group Pathogenic in immunocompromized individuals Subclinical infection is common Oral manifestations: non specific ulceration Asymptomatic involvement of salivary gland, but in some patients may cause acute sialadenitis May play a role in cyclosporine associated gingival hyperplasia Strongly associated with xerostomia in AIDS patients 2. Bacterial infections: Acute necrotizing ulcerative gingivitis ( ANUG)- Vincent angina: Relatively uncommon in developed countries, and usually associated with HIV infection In developing countries it occurs almost exclusively in children related to malnutrition Regarded as an endogenous, opportunistic poly-microbial infection-mostly fuso-bacteria and spirochetes  Signs and symptoms:  Sudden onset of crater-like (punched out) ulceration of interdental papilla and gingival margin  the ulcers are covered by greyish-green pseudomembrane surrounded by linear erythema  Bleeding, pain, and soreness  Halitosis and bad (metallic) taste  Increased salivation  Fever, malaise, and cervical lymphadenopathy Histopathology: Epithelial destruction and its replacement by pseudomembrane composed of: fibrin, necrotic epithelial cells, RBC and WBC, cell debris and bacteria Gram stain of the pseudomembrane shows: fuso-spirochetal complex N.B:  A persisting form of ANUG is associated with HIV infection  ANUG is an important factor in the development of cancrum oris Noma (cancrum oris): Also known as gangrenous stomatitis Sever, rapidly developing gangrene of orofacial tissues and jaws Almost exclusively in developing countries Mostly in malnourished and immunocompromised children Most cases are preceded by ANUG, followed by rapid spread to orofacial tissues Histological and bacteriological features are similar to those of ANUG Actiomycosis: The causative organism: actinomyces israielli Other species that might be associated; A. viscosus, and A. naeslundi Neck and the submandibular region are the most common areas Multiple foci of chronic suppuration Presents with painless firm swellings which eventually soften with pus discharging through multiple sinuses Abscesses tend to point onto the skin rather than the mucosa with marked fibrosis of the surrounding tissues  Source of infection is endogenous, and could be: tooth socket, or infected root canal Almost always confined to the soft tissue, but can cause osteomyelitis Histopathology :  Granulomatous inflammation surrounded by granulation and fibrous tissues  Pus from actinomycotic abscess contains meshes of gram +ve filament of actinomyces, with superficial radiating gram –ve filaments  The organisms may be seen clinically in the pus as “sulfur granules”. Syphilis: Caused by spirochaetes treponema palledum primary syphilis: (chancre) Clean based, shallow, painless ulcer, with induration of the surrounding tissues the ulcer is mainly genital, but in some patient may be found on oral mucosa, particularly ;the lips. Enlargement of the regional lymph nodes Chancre heals spontaneously with in few weeks, followed by secondary syphilis after about six weeks Histopathology: granulation tissue with abundant mononuclear inflammatory cells infiltrates, mainly; plasma cells Secondary syphilis: After about six weeks of the primary syphilis Skin rash is the predominant feature, and may be accompanied by oral lesions orally:- o Diffuse erythema o Characteristic mucosal patches which represent necrotic slough covering areas of chronic inflammation o Patches may coalesce to form a lesion of an irregular out line called: snail-track ulcer o Occasionally, papillary lesions that may resemble viral papillomas arise during this time and are known as condylomata lata. Histopathology: Numerous spirochetes may be demonstrated by silver stain Tertiary syphilis: A gumma may occur on the tongue or palate Begins as an indurated swelling which may become necrotic and ulcerated to form deep painless ulcer H/P: gumma consists of central mass of coagulative necrosis surrounded by granulation tissues infiltrated by chronic infl. cells and occasional giant cells. Spirochetes are very scanty or absent.  Atrophic glossitis due to endarteritis obliterance Syphilitic leukoplakia, with greater frequency of tongue cancer; however, tertiary syphilis is nowadays considered a rare factor in oral cancer Congenital syphilis: 1. Dental defects 2. Eighth nerve defect 3. Ocular keratitis 4. Saddle nose (dished face) 5. Other bone and organ defects Oral manifestations of congenital syphilis: 1. Hutchinson incisors; (screw driver –incisors):- affect the developing permanent incisors, mainly the maxillary central incisors. The teeth are tapered with central notch at the incisal edge 2. Moon’s molars or mulberry molars: usually the first permanent molar; characterized by defective cusps, hypoplastic occlusal surface, and round globular masses of hard tissues producing their mulberry appearance Tuberculosis: Caused by mycobacteria, mainly ; mycobacterium tuberculosis Common in developing countries Oral lesions can be either: 1. Primary lesion –less common 2. Secondary to pulmonary tuberculosis by coughing of infected sputum -more common Signs and symptoms: Fever, malaise, and anorexia Night sweating Cervical lymphadenitis. Parotid lymph nodes may be also involved Orally: Chronic, painless undermined ulcer covered by grayish-yellow slough; mainly on the tongue. Diagnosis: Clinical symptoms Positive Tuberculin test Histopathology and demonstration of acid fast bacilli Bacterial culture from sputum or tissue to identify mycobacteria PCR- to isolate bacterial DNA Histopathology: Formation of granulomas Granuloma is described as aggregation of epitheloid histocytes, lymphocytes , and multinucleated giant cells. Granulomas of T.B often show caseous necrosis The multinucleated giant cells have characteristic (horse shoe) arrangement of their nuclei; such cells are called (langhanse cells) special acid fast stain should be used to demonstrate tuberculus bacilli; like (Zeihl- Neelsen stain) Leprosy: Caused by mycobacterium leprae Two forms of infection; lepromatous leprosy, or tuberculoid leprosy In lepromatous type; humoral immunity predominates In tuberculoid type; cell mediated immunity predominates Oral lesions occur almost exclusively in lepromatous type, and have been reported in 50% of patients. Sites: palate, anterior gingiva, and tongue Present as nodular inflammatory masses, which tend to ulcerate and heal with fibrosis Oral lesions are usually secondary to nasal involvement Facial deformity in case of lesions involving nasomaxillary complex Gonorrhea: A venereal disease caused by Niesseria gonorrhea (N.G) Oral mucosa is considered resistant to gonoccal infections Orophryngeal infections have been reported in homosexuals Oral manifestations vary from generalized stomatitis and painful erythema to vesiculations and ulcerations Dysphagia and difficulty in speaking Reiter syndrome: Though to be predisposed by N.G In males at age of 20-35yrs Triade of arthritis, conjunctivitis, and urethritis Orally: erythema of lips, gingiva, and B.M. and purpuric spots on the palate Acute streptococcal stomatitis: Fever, malaise, and anorexia Submandibular lymphadenopathy Orally: generalized erythema, and acute gingivitis Could be secondary to viral infection Scarlet fever: Caused by group A, beta hemolytic streptococci Bacteria elaborate an erythrogenic toxin that attacks blood vessels and produce the characteristic skin rash Affects children between 3 and 12 yrs. Oral manifestations: oErythema and edema of tonsils, pharynx, soft palate, and tongue o the tongue become red, edematous, with hyperplasia of fungi form papillae ( Strawberry tongue) 3. Fungal infections Mostly due to candida Candida albicans is the principle species in oral infection Other less frequently associated species : c. glabrata, c. tropicalis, c. krusei, and c. parapsilosis C. albicans are commensal organisms in mouth, throat, large bowels, and vagina carriage rate is higher in newborns, pregnancy, smoking, denture wearers, and some medical conditions e.g: D.M So, the isolation of candida from lesion in these sites is not enough to make diagnosis, but should be considered together with clinical findings N.B: Candida is considered to have a direct relation with lesion if hyphae are present in the smear or the histological section, while the presence of yeasts alone is not a confirmatory evidence Predisposing factors:  Local: Mucosal trauma Denture (appliance) wearing, and denture hygiene Tobacco  Age: neonates, old age  Drugs: Broad spectrum antibiotics, corticosteroid, and immunosuppressant drugs  Xerostomia  Systemic diseases: Iron deficiency anaemia Megaloblastic anaemia Acute leukaemia D.M HIV and AIDS Other immune deficiency states  Pathogenesis: The exact mechanism is still obscured; however, the following has been considered: Hydrolytic enzymes; like proteinases, and lipases Toxins, which are antigenic, stimulate the immune response in the affected tissue, resulting in tissue damage; either directly or as a result of delayed type hypersensitivity reaction Classification of oral candidiasis: Group 1: candidiasis confined to oral mucosa Acute: o Acute pseudomembranous (thrush) o Acute atrophic (erythematous) Chronic o Chronic atrophic (denture stomatitis) candiasis o Candida associated with angular chaelitis o Chronic hyperplastic candidiasis Group 2: oral manifestation of generalized candidiasis o Chronic mucocutaneous candidiasis 1. Acute pseudomembranous candidiasis (thrush): Associated with prior local disturbance or systemic illness. Predisposing factors: oAntibiotics, corticosteroids, and immunosuppressive drugs oDiabetes oBlood dyscresia oMalignancy, and immunodeficiency oIn 5% of new born oIn 10% of elderly and debilitated patients Clinical features: Thick white coating on the oral mucosa (pseudomembrane) The coating can’t be wiped away (albeit with difficulty in some cases) leaving a red and often bleeding base. May occur on any mucosal surface of the mouth Vary in size from drop- like areas to confluent plaques covering a wide area. Histopathology: Epithelium is hyperplastic, parakertinized, with superficial necrosis The necrotic superficial layer of epithelium is infiltrated by candidal hyphae and yeasts, as well as, neutrophile leukocytes Neutrophils may aggregate forming micro-abscesses Candidal hyphae appear as weakly basophilic threads in haematoxylene and eosin stain, but seen more clear by special staining such as periodic acid -Shiff (PAS) stain. Lamina propria is infiltrated by chronic inflammatory cells 2. Acute atrophic (erythematous) candidiasis: Mainly seen on the tongue Appears following prolonged therapy with antibiotic or corticosteroid Antibiotics alter the oral micro flora allowing the resistant strains like candida to flourish. This condition is referred as (antibiotic sore tongue) Present as red, often, painful, areas resemble thrush but without the pseudomembrane In some patients may occure when the pseudomembrane is shed Histopathology: Thin atrophic non keratinized epithelium Occasional candida hyphae infiltrating the superficial layers Chronic inflammatory cells in both the epithelium and the c.t The appearance is similar to that of pseudomembrane except the pseudomembrane Chronic atrophic candidiasis (denture stomatitis): Common and usually asymptomatic Found in 50% of denture wearers, more frequently in women Regarded as being secondary candidal infection due to poor denture hygiene and ill fitting denture Almost in the upper denture; may be because it fits more closely compared to the lower one Erythema and oedema of the covered mucosa, with clear line of demarcation Can also be seen under orthodontic appliance Three patterns of inflammation: 1. Localized: pin point areas of erythema 2. Diffuse: generalized areas of erythema 3. Chronic inflammatory papillary hyperplasia Pathogenesis: Poor denture hygiene and wearing denture during night High carbohydrate diet predisposes to infection The micro-pores and irregularities of the fitting surface of the denture provide a suitable environment for retention and growth of the organism A delayed hypersensitivity response to candidal antigen is thought to contribute to inflammation Histopathology: Epithelium may show hyperplasia or atrophy, and being either para- keratinized or non-keratinized Leukocytic infiltration of the epithelium with formation of micro- abscess at the superficial layer Sub-epithelial chronic inflammatory cell infiltration Invasion of epithelium by candidal hyphae is not a feature of this condition Angular cheilitis: A multifactorial disease of infectious origin Predominantly in denture wearers Seen in 30% of patients with denture stomatitis, and less frequently with other types of candidiasis Also caused by staphylococcus aureus or ,less frequently, by beta- hemolytic streptococci Present as erythema and fissuring at the corners of the mouth Deep folds of skin at the corners of the mouth which may result from decreased occlusal dimension in old age, or due to incorrectly designed or old denture  Skin fold predispose to infection by local maceration of the keratinized layers of the skin due to continual witting by saliva Other predisposing factors: nutritional deficiency ;particularly, iron, folic acid and vitamin B12 Chronic hyperplastic candidiasis: Referred to as candidal leukoplakia Present as white patch which is clinically indistinguishable from leukoplakia Dense, opaque white patches with nodular surface can’t be removed by scrapping, but fragments can be dethatched Smear examination of these fragments reveals candidal hyphae which can help in diagnosis in some cases there is erythematous areas with in the white patches giving rise to speckled leukoplakia  Buccal mucosa is the most common site, just beneath the commissures of the lips Present as roughly triangular, often bilateral white plaques tapering posteriorly, and often associated with angular cheilitis Tongue and palate may be involved Usually associated with tobacco smoking, denture wearing, and occlusal friction Histopathology: Epithelial para-keratosis, hyperplasia, and acanthosis The superficial para-keratinized layer is edematous and infiltrated by neutrophils which aggregate forming micro-abscesses Candidal hyphae penetrate the parakeratin at right angle, but never penetrate deeper to the prickle cell layers Prickle cell layer is infiltrated by acute and chronic inflammatory cells Lamina propria is infiltrated by mix of chronic inflammatory cells, mainly; plasma cells Areas of atrophic epithelium may be present, giving rise to the speckled erythematous appearance seen clinically  Chronic hyperplastic candidiasis is considered to be a premalignant lesion, and epithelial dysplasia is seen in 50% of cases Candida species can generate carcinogens such as nitrosamines, and the severity of dysplasia and malignant transformation is higher in speckled lesions Chronic mucocutaneous candidiasis (CMC): a rare group of disorders characterized by persistent superficial candida infection of mucosa, nails, and skin Oral lesions resemble those seen in chronic hyperplastic candidiasis The disorders in this group are classified in five groups: 1. Familial CMC candidiasis: appears in the first year of life Mild Inherited as autosomal recessive 2. Diffuse CMC candidiasis: Presents within the first five years of life Sporadic disease or autosomal recessive Sever oral candidiasis and severe skin involvement 3. Candidiosis endocrinopathy syndrome: Autosomal recessive or sporadic Presents at the second decade of life Chronic oral candidiasis is usually the first presenting feature, and may precede the endocrine symptoms by several years Endocrine symptoms involve: hypothyroidism, hypoparathyroidism, Addison disease, and diabetes mellitus 4. Late onset CMC : Mild, and mainly affect the oral mucosa In middle age or elderly who develop thymoma 5. CMC associated with primary immune deficiency and HIV infection: Chronic candidiasis may be a feature of immune deficiency Oral manifestations of deep visceral mycosis: Rare Mainly endemic or in association with immune deficiency Oral lesions are uncommon, and present as non specific ulceration Types:  Blastomycosis  Coccidoidomycosis  Cryptococcosis  Histoplasmosis  Paracoccidoidomycosis  mucormycosis HIV infection and AIDIS: Mode of transmission: blood and body fluids, sexual contact, or from mother to child (perinatal). Symptoms of acute HIV infection: fever, headache, skin rash, sore throat, and diarrhea. Following seroconversion, most patient remain a symptomatic for many years, but AIDS develops with time AIDS: persistent generalized lymphadenopathy, diarrhea, weight loss, and fatigue Opportunistic infections, Kaposi sarcoma, non-Hodgkin’s lymphoma Oral manifestations of HIV infection: Group 1: lesions strongly associated with HIV infection: 1. Candidiasis: the most common, and seen in 90% of AIDS pt.s 2. Hairy leukoplakia (EBV) 3. HIV associated periodontal diseases: HIV gingivitis (linear gingival erythema) Necrotizing ulcerative gingivitis HIV- periodontitis Necrotizing stomatitis 4. Kaposi sarcoma 5. non-Hodgkin’s lymphoma Group 2: lesions commonly associated with HIV infection: 1. Atypical ulceration (oropharyngeal) 2. Idiopathic thrombocytopenic purpora 3. Salivary gland disorders: Dry mouth Swelling of major salivary glands 4. Viral infections other than EBV: CMV HSV HPV VZV  Group 3: lesions possibly associated with HIV infection: 1. Bacterial infections other than gingivitis and periodontitis 2. Fungal infections other than candidiasis 3. Melanotic hyperpigmentation 4. Neurological disturbances: facial palsy , trigeminal neuralgia Hairy leukoplakia (HL): Asymptomatic Caused by EBV Most commonly on lateral borders of the tongue, bilaterally Presents as non removable white patches with variable size and surface characters Described as vertical white folds on the lateral surface of the tongue, with raised corrugated or hairy surface Some lesions may have a smooth flat surface The distribution of HL at the lateral borders may be because these are areas liable to trauma; thus allowing access for the virus from saliva to the prickle cells Histopathology; Epithelium is acanthotic and parakeratinized, with long finger like projections of the parakearatin, giving rise to the characteristic corrugated surface seen clinically Candidal hyphae can be seen in half of the cases, but it is considered a secondary rather than a causal Absence of inflammatory cells, both in epithelium and C.T Swollen, balloon cells with prominent cell boundaries and darkly staining nuclei surrounded by perinuclear vacuoles. These cells arrange as a band in the prickle cell layer beneath the parakeratin The balloon cells contain EBV and described as koilocyte-like cells Demonstration of EBV is essential to make diagnosis No evidence to suggest that HL is a premalignant References: Soames J.V and Southam J.C (1998),Oral Pathology, third(ed) Oxford university press Inc, Oxford Regezi JA, Sciubba JJ, Jordan RC (2012), Oral pathology clinical pathological correlations, sixth edition, Elsevier Saunders, St. louis Missouri Neville, BW, Damm DD, Allen CM. and Chi AC. (2016) Oral & Maxillofacial Pathology. 4th Edition, WB Saunders, Elsevier, Missouri,