Specific infections of the oral mucosa

Specific infections of the oral mucosa

1. Introduction:

Küffer divides infections into two groups:

• Non-specific infections whose appearance does not suggest any particular germ, and which are most often related to polymorphic oral flora;
• Specific infections, whose clinical and/or histological appearance suggests a well-defined bacterium.

2. Definition  

“A specific infection is a disease always determined by the same cause and sensitive to the same drugs. It is a fairly rare pathology, due to a specific germ, not belonging to the commensal flora. These are therefore exogenous germs which do not live in the oral cavity.” 

• 3. Clinical study:

3.1. Tuberculosis (TB):

• Tuberculosis (TB): a major global health problem.
• TB: one of the top 10 causes of death worldwide. 
• Leading cause of death from an infectious agent (before HIV/AIDS).

WHO (2023):

• TB: 10.6 million new cases / year (in 2022) including 

* 5.83 million men, 

* 3.49 million women and 

* 1.27 million children.

• TB 🡪 1.4 million deaths / year in 2022 including 167,000 HIV-positive subjects.
• TB: all countries.

Algeria (WHO 2020):

• TB: 20,980 new cases reported [new and relapse]
• Pulmonary TB: 6,714 cases: 32%. 
• Extrapulmonary TB: 14,266 cases: 68%.
• 61% Men
• 38% Women
• 1% children aged 0 to 14 years.
• TB: chronic bacterial infection.
• TB: notifiable disease.
• Pathogen: Mycobacterium Tuberculosis (MBT) complex bacteria (Koch’s bacillus).
• Discovered by Robert Koch in 1882 .  
• TB: +++ pulmonary (not in Algeria).
• Extrapulmonary TB: 1/3 cases (Coulon and Piette 2008).
• Primary oral mucosal TB: rare. 
• TB: +++ HIV + patients .

3.1.1. Pathogenesis 

Modes of contamination: 

• The pathogen is often Mycobacterium Tuberculosis Hominis, contamination occurs via airborne saliva droplets or Pflügge droplets.
• Caused by Mycobacterium tuberculosis , which is spread through the air, for example when people with tuberculosis cough.  
• Local inoculation by inhalation of bacillus dust (nasal, etc.),
• Endogenously from a pulmonary focus,
• Inoculation by scratch lesion,
• Inoculation via the blood (pulmonary) or lymphatic (mucous membrane) route from a recognized focus. 
• Lymphatic diffusion results in tuberculous cervical adenopathies.

• Sometimes TB is caused by  Mycobacterium Tuberculosis Bovis and contamination occurs through the digestive tract by ingestion of raw milk. 
• There are other routes of skin or mucous membrane contamination. 
• BK, after entering through the air, spreads throughout the body: this is the primary tuberculosis infection. 
• BK is sought in sputum, gastric tube fluids, and serous fluids. 
• Contagion: Only one patient in whom BK has been identified by direct examination of sputum is contagious. He ceases to be contagious after two weeks of treatment. 

MBT Survival: 

• Dust: 90 – 120 days; 
• Carpet: 70 days; 
• Expectoration: 6 – 8 months (cool, dark place). 

 [Dr F Squinazi Hygiene Laboratory of the City of Paris 2007].

3.1.2. CLINIC  

3.1.2.1. Primary oral infection 

• This is the most frequent extra-pulmonary form: 61%.
• Usual form: that of children, between 8 and 10 years old, with moderate impairment of the general condition. It is characterized by a triad: 
• CHANCRE, ADENOPHTHIA, ACCOMPANYING SIGNS. 

Chancre is a superficial ulceration. 

• When it is located at the level of the gingival festoon, it is an ulceration or semilunar erosion, oval in shape, painless. It can be located at the level of the mucous hood. At the level of the bottom of the vestibule, it presents as a “book leaf”  
• The bottom of the ulceration is granular, raspberry-colored; the base is soft. The edges are thinned and the surrounding mucosa is more or less red and edematous. 

Adenopathy is located in the cervical, submaxillary or jugular region.

• It is unilateral and cold, painless and increases in volume progressively. It is generally a polyadenopathy of 2 or 3 nodes. 
• These lymph nodes are hard at first then become thickened and progress to fluctuation within 5 to 6 weeks.
• Then the fistulization lets out a greenish pus, poorly bound. The suppuration can last 1 year to 18 months.
• All this happens without inflammatory signs: it is the cold abscess.
• Accompanying signs are discreet: pallor, asthenia, anorexia, night sweats
•  Accelerated sedimentation rate 

Then comes the turn of the skin tests: the intradermal reaction (IDR) to tuberculin becomes strongly positive. The skin reacts by the formation of small subcutaneous papules.

– In 90% of cases, the primary infection heals spontaneously.

– In 5% of cases, BK spreads through the bloodstream and causes infectious foci that can remain latent and reactivate following immunodeficiency. 

– In the other 5% of cases, the BK remains localized in the lungs and neighboring tissues: lymph nodes.  

TB:

• Immunocompetent subject 🡪 +++ formation of granulomas in infected tissues + cell-mediated hypersensitivity.
• HIV + subject : Opportunistic disease 🡪 more moderate cellular immune response, granulomatous or not, +++ extrapulmonary involvement + atypical pulmonary involvement. 

Specific infections of the oral mucosa

3.1.2.2. Chronic progressive tuberculosis 

• This form presents as an extremely painful ulcer. The edges are thin, detached and the vegetative surface is slightly hollow and covered with a yellowish-gray exudate. The surrounding tissues are inflamed but not hardened.
• This lesion is found in patients with pulmonary involvement. BK inoculation occurs through a wound or pre-existing mucosal erosion.
• The preferred site is lingual (back of the tongue), followed by the lips, the jugal mucosa and the floor.

3.1.2.3. Cutaneous-mucosal TB 

• The ulceration is located on the tongue, lips, gums or palate.
• It begins with a yellow spot that flakes and gives an oval ulceration with detached edges, an irregular base, covered by a yellowish coating; the base is always soft. The ulceration is surrounded by an inflammatory zone.
• We find yellow tubercles, these are the Trélat grains which are clusters of BK. 
• Tuberculous gumma or cold abscess: this is a firm nodule, most often lingual, which develops into softening then fistulization and release of pus rich in BK.
• Tuberculous lupus: common in adolescents. Oral lupus coexists with cutaneous facial lupus: it is a purplish plaque on the mucosa that takes a vegetative, mammary form. Each nipple is called a lupus tubercle or lupoma. The lupoma evolves towards softening, fistulization and leaves a retractile scar.

3.1.2.4. Bone TB    

• BK reaches the bone by proximity from soft tissues or by hematogenous route with predilection for spongy tissue.
• The localization is mainly maxillary or malar taking the form of osteitis with elimination of sequestra.

3.1.2.5. TB of the salivary glands:

• Mainly affects the parotid glands. 
• Can be presented in the form of:

– A swelling that adheres to the skin, softens and ulcerates, causing facial paralysis. 

• Or a well-defined nodule located in the upper part of the parotid gland without general signs.

• The evolution is towards softening and fistulization.
• The treatment is surgical and medical.   

3.1.3. Diagnosis  

3.1.3.1. Positive diagnosis 

– It is necessary to find the symptomatic triad (chancre, adenopathies, accompanying signs).

– It is necessary to look for family, school or animal contagion such as the ingestion of raw milk.

– Serological tests must be carried out, and repeated if the reactions are negative. 

• The diagnosis is mainly guided by the biopsy, and is based on the isolation of the BK, as soon as the anatomopathological examination reveals giant-cell inflammation with or without caseous necrosis, TB should be considered. 
• Sometimes BK is observed on histological sections by Ziehl-Neelsen staining which uses fuschin to highlight acid-alcohol resistant bacilli: BAAR.

– Culture on Löwenstein medium takes 8 weeks to be positive.

– The tuberculin IDR is often difficult to interpret in people vaccinated with the bacillus Calmette-Guérin (BCG). It is often positive. It is only of value if the person is not vaccinated, or if they are phlyctenular, or if the diameter of the induration zone is increased by more than 0.5 mm compared to a previous IDR.

– A negative IDR in case of immunodeficiency has no value.

– Finally, lung lesions will be investigated by radiology and pulmonary CT scan.

Latent tuberculosis: 

Interferon  -Gamma Release Assays  ( IGRAs ) are diagnostic tests for latent tuberculosis infection. 

The QuantiFERON® test assesses the strength of the body’s immune response against TB by measuring the production of a defense molecule (interferon gamma) in the blood by leukocytes exposed to tuberculosis antigens.

3.1.3.2. Differential diagnosis: Will be done with:

– Squamous cell carcinoma 

– Syphilis

– Lymphomas. 

– Centrofacial malignant granuloma (T/NK cell lymphoma). 

– Traumatic ulceration.

– Large aphthous ulcers,

– Systemic mycoses,

– Actinomycosis,

– Wegener’s granuloma,

– Eosinophilic ulceration.

3.1.4. Treatment 

3.1.4.1. Preventive: 

• Vaccination / Bacillus Calmette-Guérin (BCG).
• Boiling raw milk,
• Fight against bovine TB,
• Isolation of infected subjects. 

3.1.4.2. Curative: Based on anti-tuberculosis polychemotherapy.

• ^First- line anti-tuberculosis drugs (rifampycin, pyrazinamide, isoniaside and ethambutol).
• Cure is achieved in the majority of cases of TB due to strains sensitive to anti-tuberculosis drugs. 
• The combination classically used is triple therapy:

– Rifampicin 10 mg/Kg + Isoniazid 4 to 5 mg/Kg + Pyrazinamide 25 mg/Kg to which Ethambutol 15 mg/Kg can be added.

• Treatment is continued for 2 to 3 months with triple therapy, then extended for 4 to 6 months with dual therapy (Isoniazid + Rifampicin).
• Any abnormal development should lead to suspicion of resistance or the occurrence of neoplastic disease in a weakened area. It is therefore necessary to perform a biopsy. 

In case of resistance to 2nd line anti-tuberculosis ^drugs   :

• Oral forms: ethionamide, cycloserine, p. aminosalicylic acid.
• Injectable forms: Kanamycin, amikacin, capreomycin, viomycin.
• Recently: quinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin.).
• In HIV + 🡪 rifamycin derivatives: rifabutin, rifapentine (long-acting: 1 dose/week).

Specific infections of the oral mucosa

3.2. Syphilis: 

3.2.1. General  

3.2.1.1. Definition  

• It is a treponematosis due to Treponema pallidum or Pale Treponema described in 1905 by Fritz Schaudinn and Erich Hoffman. 
• Treponema pallidum: It is a Gram-negative bacterium of the spirochete family. It has the shape of a spiral which allows it to propel itself by rotating around its central axis. 
• Sexually transmitted infection requiring mandatory notification.
• There is congenital syphilis with vertical transmission: from mother to child and acquired syphilis with horizontal transmission.

3.2.1.2. Contamination and contagiousness 

• Treponema pallidum enters the body through unaffected mucous membranes or abraded skin.
• The contagion is almost always venereal and direct, most often genital but also oral and anal. 
• The germ passes into the lymphatic system and blood. It multiplies every 30-33 hours. The patient becomes contagious during the incubation period. 
• After contamination, the condition develops in 2 phases:

• Early (primary-secondary-latency syphilis).
• Late (beyond 2 years tertiary and visceral syphilis). 

• After inoculation, the incubation period is clinically and biologically silent for about 20 days.
• 3.2.2. Clinical study 
• 3.2.2.1. Acquired syphilis  
• 3.2.2.1.1. Primary syphilis  
• The primary lesion is represented by the inoculation chancre which appears after an incubation of 14 to 28 days. 
• At the labial and oral mucosal level, the lesion is a pink macule that transforms into a papule and ulcerates. This ulceration is initially smooth, painless and well-limited. After 8 days, it becomes suggestive. Unique, painless and indurated at its base, it persists for 3 to 5 weeks, but even after healing, the induration persists.
• At the lingual level, the appearance is less typical, with deeper erosions or fissures.
• At the level of the tonsils, it can become covered with a false membrane reminiscent of diphtheria.
• Adenopathy is a satellite of the chancre. It can be bilateral; it has a very important diagnostic value. It is a polyadenopathy made up of 4 to 5 lymph nodes with one of them larger. They are hard, mobile, painless, non-adherent and not sensitive to the touch. They never suppurate.
• The differential diagnosis is made with herpes, traumatic ulceration, bullous diseases (Stevens-Johnson; Behçet), secondary syphilis.
• The evolution: 
• Without treatment, the chancre will heal in 5 to 6 weeks and will leave an indelible scar.
• With treatment, the chancre heals in 8 to 20 days. The lymphadenopathy disappears after 2 to 4 months.
• The induration and adenopathy persist for several months after the chancre has disappeared.
• 3.2.2.1.2. Secondary syphilis   
• Occurs 2 to 4 years after the onset of the disease.
• Oral mucosal involvement is extremely common. These lesions are maculopapular, 5 to 10 mm in diameter, with a central ulceration with a grayish background. The boundaries are clear, erythematous, round or oval in shape. These lesions are painless and may coalesce. They are contagious.
• They should be differentiated from herpes, aphthae, ulcerative stomatitis, agranulocytosis.
• There are few functional signs. The sites are the tongue which appears cracked; the corners of the lips may be the site of angular cheilitis.
• Adenopathies are present in the drainage areas.
• General and visceral manifestations: 
• These are fatigue, fever, pallor and headaches simulating flu syndrome. 
• Lymph node manifestations:
• These are mainly microadenopathies. 
• Mucosal manifestations: 
• These are early non-infiltrated mucous plaques, and later infiltrating papular and papulo-ulcerative lesions.
• All these lesions will regress and the disease will enter a latent, non-contagious phase. They will heal and then relapse immediately. 
• Skin manifestations: 
• Patchy hair loss may be observed.
• Roseola is a pale pink, erythematous patch on the limbs, soles and palms.
• Papular syphilides are round, red, infiltrated papules that occupy the entire surface of the body. They simulate psoriasis and regress within a few months, leaving pigmented spots. 
• They are often macerated, or even oozing when they are located in the folds. Highly contagious, they predominate on the face, palms of the hands, soles of the feet and around the orifices. They develop in successive attacks with general signs: fever, headaches, fatigue, liver damage, jaundice and bone pain.  
• Sometimes glomerulonephritis and decreased visual acuity are found.
• Then a period of latency sets in which can last several decades. Sometimes, syphilis can be latent from the outset.   
• 3.2.2.1.3. Tertiary syphilis  
• This is the granulomatous stage of the disease, the lesions constitute the “syphilitic gumma”.
• The obvious manifestations of the tertiary phase only appear late in about 10% of patients who are not or insufficiently treated.
• These manifestations are dominated by nervous syphilis (general paralysis, tabes or inexpressive facies, and sensory disorders) and ocular and vascular accidents.
• At the level of the bony palate, the lesions are destructive, leading to osteolysis with bone necrosis and extension to the floor of the nasal fossae: this is perforating disease.
• Mucosal manifestations are limited to syphilitic gummas. It is generally a nodule of 1 to 2 cm in diameter, unique and painless. It evolves in 4 phases (crudity – softening – ulceration – and repair).
• The evolution lasts 1 to 6 months.
• 3.2.2.2. Congenital syphilis  
• Concerns children born with syphilis. The disease was transmitted to them by their mother during pregnancy or childbirth.
• Typically, treponema does not cross the placental barrier until the fourth to fifth month of pregnancy.
• 3.2.2.2.1. Early syphilis: manifests during the 2nd ^year of life, affecting the skin and mucous membranes, bones, liver, spleen, kidneys, lungs and eyes.
• 3.2.2.2.2. Late syphilis: appears between 5 and 8 years of age and results in damage to the joints, nervous system, ears, teeth, etc. 
• 3.2.2.2. Positive diagnosis: based on clinical and biological examinations.
• Direct examination: 
•     It is of little use in oral localizations, due to the usual presence of spirochetes. Is done under a dark-field microscope. 
• Serodiagnostics: 
• The diagnosis of syphilis is essentially serological, and combines a treponemal test (specific): TPHA and FTA-abs, and another non-treponemal: Veneral Disease Research Laboratory (VDRL). 
• TPHA ( Treponema Pallidium Haemagglutination Assay ) is the first-line test ⁱⁿ   association with VDRL ( Venereal Disease Research Laboratory ),
• FTA-abs (indirect immunofluorescence or Fluorescent Treponema Antibody absorption test ).
• Histology: 
• Without being specific, it can be suggestive of secondary syphilis when the image shows a dermal inflammatory infiltrate where lymphocytes predominate, and especially plasma cells with involvement of the vessels.
• Silver staining (Wharthin-Starry) can reveal spirochetes 
• 3.2.2.5. Treatment  
• The treatment is done with slow-release penicillin. Do not forget to treat sexual partners.
• Single intramuscular injection of 2.4 million benzathine penicillin G (extencillin). In case of allergy to β lactams: one or more courses of cyclines. Each course lasts two weeks. It uses either tetracycline (500 mg per os 4 times per day) or doxycycline (100 mg per os morning and evening for 15 days).
• In case of allergy to β-lactams, cyclins are used, but they are contraindicated in pregnancy. In this case, macrolides can be used .
•  It takes approximately 1 year for VDRL serology to become negative in cases of primary syphilis and approximately 2 years in cases of secondary syphilis.
• Special areas: 

–  Pregnant women:  The risk is of course that of congenital syphilis. The treatment of syphilis is identical, for the same stage of the disease, to that recommended for non-pregnant women. Clinical and biological monitoring will be monthly. In the event of allergy to penicillin, the advice of a specialist is mandatory to choose between treatment with macrolide or desensitization to penicillin.

Specific infections of the oral mucosa

–  Treatment of syphilis in HIV-positive subjects:  

• HIV+ subject: syphilis: atypical cutaneous symptoms, was frequently and early complicated by severe visceral damage, particularly ocular and neurological, and above all could not respond to penicillin treatment according to the methods constantly effective in non-immunocompromised patients. 
• Today, this pessimistic view of things deserves to be qualified. Standard treatment with penicillin can certainly be used in cases of primary syphilis in HIV-positive subjects and probably in the course of secondary syphilis in the same subject. A study of the cerebrospinal fluid prior to treatment is proposed by some authors. 

Conclusion 

• Cervicofacial manifestations of tuberculosis and syphilis are not pathognomonic but can be indicative.
• For any oral lesion that cannot be labeled and is resistant to treatment, serology is required (tuberculin IDR, TPHA-VDRL, FTAabs), chest X-ray and, above all, a histological examination. 

Specific infections of the oral mucosa

  Cracked teeth can be healed with modern techniques.
Gum disease can be prevented with proper brushing.
Dental implants integrate with the bone for a long-lasting solution.
Yellowed teeth can be brightened with professional whitening.
Dental X-rays reveal problems that are invisible to the naked eye.
Sensitive teeth benefit from specific toothpastes.
A diet low in sugar protects against cavities.
 

Specific infections of the oral mucosa