**Oral Pathology module** **Major infections of the mouth and** **face** DENT4217 **A/Prof Omar Kujan** BDS DipOPath MDSc MFDS RCPS FHEA FRCPath FFOMP(RCPA) PhD  **Acknowledgement** of country**Artist: Dr Richard Barry Walley OAM** The University of Western Australia acknowledges that its campus is situated on Noongar land, and that Noongar people remain the spiritual and cultural custodians of their land, and continue to practise their values, languages, beliefs and knowledge.  **Learning outcomes** 1. Describe common bacterial, viral and fungal oral infections 2. Outline the pathology of common bacterial, viral and fungal oral infections Bacterial infections  **Oral Actinomycosis** * Actinomycosis is a chronic, suppurative infection caused by _Actinomyces sp_. Although common in the past, it has become rare. * Half of all cases affect the face and neck. * Clinically, men are predominantly affected, ages 30 and 60 years. * Chronic soft tissue swelling near the angle of the jaw in the upper neck is the usual complaint * Pain is minimal. * The usual clinical features are a persistent subcutaneous collection of pus or a sinus, unresponsive to conventional, short courses of antibiotics. **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** 5   **Oral Actinomycosis** * **Actinomyces israelii** is a long filamentous Gram-positive bacterium, not a fungus as its name suggests * This single, complete loculus was from an early case of actinomycosis that followed dental extraction. * The colony of actinomyces with its paler staining periphery (a ‘sulphur’ granule) is in the centre; around it is a dense collection of inflammatory cells surrounded by proliferating fibrous tissue.  **Tuberculosis** Tuberculosis is the second most common cause of death from a single infectious agent worldwide, after HIV/AIDS. Oral lesions are noted in less than 5% of patients with pulmonary tuberculosis Occurs in the second to fourth decades of life and presents as an ulcer of the oral mucosa, a mass or osteolytic lesions within the jawbones, with some patients exhibiting tuberculous lymphadenitis (scrofula) and salivary gland involvement **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA**  Mycobacterium tuberculosis, a facultative intracellular bacterium.  **SYPHILIS** Syphilis is a chronic bacterial disease that is endemic in low- and middle- income countries, and those in economically depressed neighborhoods. More than 5 million new cases of syphilis are diagnosed every year. If left untreated, it can lead to irreversible neurological and cardiovascular complications. 91% of all cases occur in men, and it is closely linked with HIV infection **Types** * Primary syphilis (chancre) * Secondary syphilis * Tertiary syphilis * Congenital syphilis  **Pathobiology** The spirochete responsible for this disease is *Treponema* *pallidum*. **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA**    Image of oral lesions associated with viral infections.  THE UNIVERSITY OF **WESTERN** **AUSTRALIA** Herpesviruses are DNA viruses that are mostly: - transmitted in saliva. - characterised by latency. - reactivated during immunosuppression. - cause more severe disorders in patients with compromised immunity, HIV, cancer patients and those immunosuppressed after organ grafts. Herpesvirus Types - Herpes simplex type 1 (HSV-1) - Herpes simplex type 2 (HSV-2) - Herpes varicella-zoster (VZV) - Epstein-Barr virus (EBV) - Cytomegalovirus (CMV) - Human herpesvirus type 6 (HHV-6) - Human herpesvirus type 7 (HHV-7) - Human herpesvirus type 8 (HHV-8) **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** **Herpesvirus Type** **HHV-1** Herpes simplex virus-1 Alpha virus **HHV-2** Herpes simplex virus-2 Alpha virus **HHV-3** Varicella-zoster virus Alpha virus **HHV-4** Epstein-Barr virus Gamma virus **HHV-5** Cytomegalovirus Beta virus **HHV-6** Beta virus **HHV-7** Beta virus **HHV-8** Kaposi sarcoma herpesvirus Gamma virus **Disease Manifestation** Oral cavity: Primary herpetic gingivostomatitis and recrudescent herpes stomatitis or herpes labialis Genital herpes, eczema herpeticum, herpes whitlow, herpes gladiatorum, ocular herpes, herpes encephalitis, dis- seminated infection Although usually found on skin and mucosa below the waist (genital herpes), may also be found in the mouth with lesions identical to those of HSV-I, neonatal infection, herpetic whitlow (also see HHV-1 above) Oral cavity: Primary infection exhibits oral ulcers; recrudescent infection is facial or oral shingles along the distri- bution of the trigeminal nerve and is usually unilateral Primary infection is chickenpox; skin shingles are common on the trunk Oral cavity: Hairy leukoplakia occurs in patients with HIV/AIDS, organ transplant recipients, or other immuno- compromised hosts, as well as those on immunosuppressive agents; non infrequently occurs in the healthy host Epstein-Barr virus mucocutaneous ulcer in immunosuppressed or immunosenescent host Infectious mononucleosis, Burkitt lymphoma, central nervous system lymphoma, diffuse large B-cell lymphoma, NKT lymphoma, immunodeficiency-associated lymphoproliferative disorder, Hodgkin lymphoma, plasmablastic lymphoma, nasopharyngeal carcinoma, leiomyosarcoma, follicular dendritic cell sarcoma Oral cavity: Penetrating oral ulcers; organism may be a bystander noted in other ulcerative lesions Infectious mononucleosis-like syndrome, retinitis, gastroenteritis, hepatitis, pneumonitis No documented oral findings Roseola infantum, exanthema subitum No documented oral findings Roseola infantum, exanthema subitum Oral cavity: Kaposi sarcoma Skin and visceral Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease, diffuse large B-cell lymphoma  **Herpes simplex virus** The primary clinical infection with HSV • Usually caused by HSV-1 • Seen mainly between the ages of 2 and 4 years. • Increasingly seen in older patients. • In teenagers, sometimes due to HSV-2 transmitted sexually and mainly cause oropharyngeal soreness. **Predisposing factors** •Herpes simplex virus is contracted from infected saliva or other body fluids after 4-7 days of incubation •Close contact with infected individuals •HSV-1 can cause oral and oropharyngeal infection (above belt) •HSV-2 can cause severe oropharyngeal infection usually via orogenital or oro-anal sexual contact. •Patients with immune defects are liable to infections. Diagram illustrating HHV infection process: - Physical examination (depicts epithelial tissue with infected cells) - Neuronal latency leading to ganglion - Virus labeled "HHV" binds to receptor on host cell - Entry via endocytosis - Viral propagation inside host cell - Release through cell lysis Includes labels: - "Physical examination" - "Neuronal latency" → "Ganglion" - "HHV" - "Receptor" - "Endocytosis" - "Propagation" - "Release" - "lysis" University logo: The University of Western Australia  **HERPES SIMPLEX VIRUS** THE UNIVERSITY OF WESTERN AUSTRALIA **Primary herpetic gingivostomatitis** - common herpesvirus infection in the first three decades of life - fever, malaise, and sore throat, followed by an acute onset of multiple, painful, clustered, and subsequently coalescent ulcers on any mucosal surface, but frequently on the lip mucosa, tongue, and gingiva 18   **HERPES SIMPLEX VIRUS** **Herpes labialis** on the lip (fever blisters or cold sores) is the most common presentation with less common sites being the keratinized mucosa of the hard palatal mucosa and attached gingiva. There are painful, 2- to 3-mm clustered and coalescent ulcers with scalloped borders often induced by injury (e.g., sunburn) or trauma (e.g., dental procedures)   **Primary varicella-zoster virus** • This infection causes vesicles on erythematous skin and also in the mouth that rupture to form ulcers. • Reactivation of VZV tends to occur in older adults, in immunocompromised hosts, and in those on biological therapies such as tumor necrosis factor inhibitors   **Pathobiology** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** HSV and VZV are DNA viruses that are cytotoxic to epithelial cells. After primary infection, latency is established in sensory ganglia and peripherally at mucosal sites. Reactivation of HSV either leads to asymptomatic shedding, which is the primary means of transmission, or results in painful lesions, referred to as recrudescence.   **HAIRY LEUKOPLAKIA** - caused by the Epstein-Barr virus (EBV) - occurs most commonly in immunocompromised individuals, especially those with HIV/ AIDS with low CD4 counts and in organ transplant recipients. - Healthy patients, usually older adults, possibly due to immunosenescence - Clinically appears a white, painless, linear lesion or plaque, usually on the lateral border of tongue, and cases are usually bilateral. Classically, white linear lesions run perpendicular to the long axis of the tongue **THE UNIVERSITY OF WESTERN AUSTRALIA**   **Pathobiology** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** EBV establishes latency in peripheral memory B lymphocytes and one theory proposes that these B lymphocytes migrate to the lamina propria or to the oral epithelium where EBV undergoes productive replication resulting in hairy leukoplakia.   **HUMAN PAPILLOMAVIRUS–RELATED** **BENIGN LESIONS** THE UNIVERSITY OF WESTERN AUSTRALIA Squamous papilloma, verruca vulgaris, condyloma acuminatum, and Heck disease (focal epithelial hyperplasia) • Young patients present as painless, exophytic, papillary/verrucous or papular, white or pink, sessile, or pedunculated growths on the mucosa. • Squamous papilloma: This is often seen on the soft palate and hard palatal mucosa, tongue or gingiva and may be white/keratotic or mucosal-colored, and is only a few millimeters in size 24  **Histopathology** Squamous papilloma   Histological images with cellular detail and tissue morphology. No text present.   **HUMAN PAPILLOMAVIRUS–RELATED** **BENIGN LESIONS** THE UNIVERSITY OF WESTERN AUSTRALIA **Verruca vulgaris:** This is often on the gingiva, lips, and palatal mucosa and is almost always white/keratotic, and is only a few millimeters in size 27  **Histopathology** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** Verruca vulgaris 28   **HUMAN PAPILLOMAVIRUS–RELATED** **BENIGN LESIONS** **29** **THE UNIVERSITY OF** **WESTERN** **AUSTRALIA** **Condyloma acuminatum:** This is usually seen in immunocompromised patients as single or multiple papular or papillary lesions that are mucosal-colored and usually 1 cm in size or larger **29**  **Histopathology** THE UNIVERSITY OF WESTERN AUSTRALIA 30    **<font color="#3166d1">HUMAN PAPILLOMAVIRUS–RELATED</font>** **<font color="#3166d1">BENIGN LESIONS</font>** **<font color="#1F497D">THE UNIVERSITY OF</font>** **<font color="#1F497D">WESTERN</font>** **<font color="#1F497D">AUSTRALIA</font>** Heck disease: There are multiple papules/nodules or papillary lesions (less common), several millimeters in size, but may coalesce to form larger lesions on the mucosa of the lips and tongue, often seen in the first and second decades of life. It occurs in up to 13% of those living in crowded South and Central America conditions. It is also common in Africa, the Middle East, in patients with HIV/AIDS, and sporadically in North America. The condition tends to regress with age when lesions begin in childhood. 31  Histological images of tissue samples (no text or figure labels).   <p style="text-align: right;"><b><span style="font-size: 8px;">THE UNIVERSITY OF</span></b></p> <p style="text-align: right;"><b><span style="font-size: 14px;">WESTERN</span></b></p> <p style="text-align: right;"><b><span style="font-size: 14px;">AUSTRALIA</span></b></p> <p><b>Fungal infections</b></p> **CANDIDOSIS (CANDIDIASIS)** * Some 50% of the normal population harbor Candida albicans as a normal oral commensal (without disease) and are termed “Candida carrieres”. * C. albicans resides particularly on the posterior dorsum od tongue. * Candida carriage is more frequent in * Women * People: * of blood group O and with non-secretion of blood antigens in saliva * of high carbohydrate diets causing acidic saliva * with xerostomia * on broad spectrum antimicrobial use * who wear dental appliances * who smoke tobacco * who are immunocompromised (HIV, malnutrition, diabetes) * who are hospitalised 34 **CANDIDOSIS (CANDIDIASIS)** •Candidiasis (candidosis) is the state when candida species cause lesions (host defences are compromised). •C. albicans is the only common cause of oral fungal or yeast infection. •Symptomatic candidiasis presents as mainly: •White lesions (thrush, candidal leukoplakia and chronic mucocutaneous candidiasis) in which hyphal forms are common. •Red lesions (denture-related stomatitis, median rhomboid glossitis, erythematous candidiasis) in which yeasts forms predominate. 35 **Factors PREDISPOSING to ORAL CANDIDIASIS** * Local factors influencing oral immunity or ecology include: - Xerostomia - Smoking - Broad-spectrum antimicrobials - Corticosteroids - Dental appliances - Irradiation involving the mouth or the salivary glands * Systemic immune defects, such as those caused by: - Extremes of age - Malnutrition - Cytotoxic chemotherapy - Immune T-cell defects (HIV infection, lymphoma, leukemia, cancer and PMNL defects, diabetes and immunosuppressant drugs) - Anemia 36 and here are the different crops of this image to help you see better, use these only as hints:  Microscopic image of filamentous bacteria stained with acid-fast technique.  **Thrush** * Acute pseudomembranous candidiasis * It is termed because the white flecks resemble the appearance of the breast of the of the bird of that name   Oral cavity with white plaque-like lesions on erythematous mucosa.  **ACUTE ATROPHIC CANDIDIASIS** • Acute atrophic candidiasis presents as a red patch of atrophic or erythematous raw and painful mucosa, with minimal evidence of the white pseudomembranous lesions observed in thrush. • Antibiotic sore mouth, a common form of atrophiccandidiasis, should be suspected in a patient who develops symptoms of oral burning, bad taste, or sore throat during or after therapy with broad-spectrum antibiotics. • Patients withchronic iron deficiency anemia may also develop atrophic candidiasis  **Chronic hyperplastic candidiasis** * Candidal leukoplakia is considered a chronic form of oral candidiasis in which firm white leathery plaques are detected on the cheeks, lips, palate, and tongue. (persistent white lesion) characterized histologically by parakeratosis and chronic intrepithelial inflammation with fungal hyphae invading the superficial layers of the epithelium.  No text is present in the provided image.  **Angular Cheilitis** * Angular cheilitis is chronic inflammation affects both commissure of the lips * Common * Occurs mostly in adults * It is predisposed by “3Ds” * Denture-wearing, denture related stomatitis and disorders (dry mouth, tobacco smoking) * Deficiency states (deficiency anemias, iron deficiency, hypovitaminosis (B), malabsorption states or eating disorders, zinc deficiency, immunity disorders) * Disorders where the lip anatomical relationship are changed (reduced vertical dimension)   There is no text in this image.  **Denture-related Stomatitis** **Aetiology and Pathogenesis** * Candida proliferates in the dental plaque, dental appliance surface and on the mucosa. * Absence of symptoms * Chronic erythema and edema of the mucosa that contacts the fitting surface of the denture * Uncommon complications which include: * Angular stomatitis * Papillary hyperplasia in the palate  **Histopathology** THE UNIVERSITY OF **WESTERN** **AUSTRALIA**     Illustration of a group of diverse students observing and interacting with red circular creatures resembling cells or bacteria, some using tools and instruments, under a banner labeled "ENTER HERE!".