Zdroj: P. A. Reichart, H. P. Philipsen: Color atlas of dental medicine. Oral pathology. Thieme. Stuttgart, New York. 2000.
The defence from the foreign agents (in particular from microbial antigens) is a necessary prerequisite for the existence of any individual. The first encounter with the antigen activates the innate non-specific immune mechanisms capable of reacting very quickly (within minutes to hours). This non-specific immunity is predominantly mediated by the complement system and phagocytes (phagocytosis) and manifests as an inflammatory reaction. This encounter of the organism with a foreign protein leaves a permanent information “stored” in the organism, which allows this agent to be recognized and deactivated at any future contact. Specific antibodies are produced – specific immunity, reaching a maximum after 2-3 weeks and then declining. The above described process represents the so-called primary immune response. With every subsequent contact with the antigen, the antibodies are produced sooner and in greater quantities, which is called secondary immune response. The result of such immune response may however not be always positive as it can lead (if pathological reactions occur) to development of a disease. As far as mucosal diseases are concerned, the pathological manifestations may include the immune system oversensitivity (allergies), autoimmune damage of the tissues and/or states of immunodeficiency.
Over the last decades, the number of individuals with allergic reaction to various substances they encounter over the course of their lives grows. Allergy represents overreaction of the immune mechanisms. That oversensitivity may be humoral (anaphylactic type reaction, cytotoxic type and oversensitivity of immune complexes) or cellular (cell-mediated oversensitivity).
Type 1 – anaphylaxis: this term describes a reaction between an antigen and an IgE antibody. Degranulation of phagocytes and basophils occurs, followed by a release of vasoactive histamine-like substances, SRS. IgG antibodies also participate in the reaction with the antigen – this complex activates the complement, anaphylactogenic components of which, namely C3a and C5a, facilitate/support the release of histamine. Anaphylactic shock then represents an example of such a reaction (in dentistry, this most commonly occurs after administration of anaesthetics, ATBs or other substances).
Type 2 – cytotoxic type: Formation of the bond between the antibodies and cellular antigen leads to activation of the complement, disruption of the cellular membrane and cytolysis. This mechanism leads to autoimmune haemolytic anaemia or drug-induced purpura.
Typ 3 – oversensitivity of immune complexes: the antigen-antibody bond leads to formation of pathological complement-activating immune complexes. The result of the reaction depends on the ratio between the antigen and antibodies. If the antibodies are in excess, an Arthus type reaction (necrosis) occurs on the site of the antigen entry into the organism. If the antigen is in excess, the circulating immune complexes penetrate the vascular wall and result in vasculitis (e.g. in systemic lupus erythematodes).
Typ 4 – cellular: this reaction is sometimes called tuberculin-type reaction (as the TBC Mantoux reaction represents this type). It sets in later, the antigen first binds to so-called antigen presenting cells (APC) and sensitizes the T-lymphocytes. They proliferate and differentiate into subpopulations of regulatory (suppressor and helper T-cells) and executive (cytotoxic T lymphocytes), capable of killing the target cells. The regulatory subpopulation of the helper T-cells produces lymphokines that can damage the tissue by themselves (an example of such reaction is contact dermatitis.
Allergic reactions on the oral mucosa develop after sensitization with an antigen suddenly, manifesting as erythema, oedema, blisters or erosions. Epithelial desquamation, crevices or fissures (sometimes even haemorrhagic) appear in the vermilion zone. Those changes are clinically variable and non-specific, the patient subjectively complains about burning or pain. The oral symptoms can be accompanied by lesions on the skin in the adjacent areas.
Typical manifestations of the allergic reaction of the 1st type include the allergic drug-induced stomatitis and allergic angioedema. The allergic reaction of the 4th type results in the development of a contact allergic reaction (allergic eczema).
The clinical picture of drug-induced stomatitis with allergic etiopathogenesis can be polymorphic (and similar to stomatitides of other etiologies such as EEM or herpetic gingivostomatitis). The inflammation is usually turbulent with a lot of exudate and usually affects larger areas of the oral mucosa in various locations (the gingiva is however only rarely affected). In the forefront of the clinical picture, there is an acute inflammation with infiltration of the oral mucosa, which may be catarrhal and/or accompanied by blisters and by a subsequent development of erosions or even ulcerations. The coating of the tongue is typically thickened, moist and whitish, the discoloration can however be modified by previous treatment (it may be e.g. whitish to brown due to ATB treatment). Drug-induced stomatitis can also have the clinical picture of anaphylactic reaction with urticaria-like skin manifestations; oedema with infiltration of lips, macroglossia and possibly inspiratory stridor (laryngeal oedema) can appear on the face, in the oral cavity and/or on the larynx. In the field of dentistry, the biggest role in this respect is played by anaesthetics and antibiotics, which can bring about even a systemic reaction (anaphylactic shock). A targeted and meticulous taking of the patient history is usually crucial for establishing the correct diagnosis.
Many drug-induced stomatitides are however not caused by allergic reactions but result from other pathogenic mechanisms (toxic or non-allergic immunopathological reaction, microbial dysbalance, etc.).
Th.: In stomatitis of allergic etiology, the short-term use of antihistamines or corticosteroids is indicated. Local therapy is limited to washing the mouth with herbal infusions.
Allergic angioedema results from an allergic reaction of the 1st type, usually in association with hypersensitivity to a certain food or drug. It usually develops rapidly, the tissue is soft, non-inflammatory, the site of the reaction is painless and well-circumscribed, regressing spontaneously within several hours to days. The face, especially eyelids and lips, are typically affected, other regions include the oral mucosa (angioedema of the oropharynx can lead to suffocation!), the GIT, limbs or genitals. Typically, swelling of the skin and subcutaneous tissues or mucosa and submucosal tissues is observed.
Congenital (hereditary) angioedema is similar in appearance, the underlying cause is however conditioned by the disruption of the complement system. A C1 inhibitor defect leads to an unregulated activation of the components of the complement, to the release of anti-inflammatory substances and development of an oedema. Drug-induced angioedema can develop in patients using ACE inhibitors.
Contact allergies developing on the lips and oral mucosa after a direct contact of the mucosa with certain substances are relatively commonplace. They can be induced by some components of food (nuts, fruits, additives, preservatives), cosmetic products (lipsticks) or materials used during dental procedures (eugenol, acrylic and epoxy resins, silicone and eugenol impression materials, some metals used in dentistry, in particular nickel). Such allergies can also result from the use of oral hygiene preparations (toothpastes, mouthwashes), some local treatment agents (propolis) and mucosal antiseptics. A contact allergic reaction can also appear after a contact of the oral cavity with latex (gloves, dental dam), which can be prevented by the use of unsaturated latex materials (containing vinyl and nitrile rubber). Clinically and histologically, mucosal oedema with intraepithelial blisters and a marked leukocyte infiltration is observed.
Th.: Elimination of the allergen, short-term administration of antihistamines or corticosteroids. Local therapy could, if an unsuitable preparative is used, lead to an aggravation of the condition and is therefore not recommended.
Normally, the immune system can distinguish between „its own“ and „foreign“ antigens. It has a broad capacity and spectrum and can react basically against any molecule or cell. Although the capability of react to its own antigens exists in most people, they usually induce no reaction (anergy or tolerance), which implies the participation of mechanisms capable of preventing or suppressing autoimmune responses. Besides, the autoreactive T and B lymphocytes (just like auto-antibodies) are relatively often found also in people who are not suffering with any autoimmune disease, which suggests that the immunological reactivity is not a sufficient condition for development of an autoimmune disease on itself (we speak of autoimmune disease only if the disease leads to tissue damage). Mechanisms that are assumed to participate in prevention/suppression of the autoimmune response include inactivation or deletion (a type of chromosomal aberration) of autoreactive T and B cells (the forbidden clone theory), active suppression of the cells or cytokines, idiotypic/anti-idiotypic interactions and immunosuppressive adrenal hormones (glucocorticoids).
If, however, the suppressive mechanisms prove insufficient, a reactivity against organism’s own antigens can appear and lead up to the development of autoimmune diseases that can be either organ-specific (diabetes, thyroiditis, pemphigus, pemphigoid) or systemic (non-specific) such as the systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) that can result in multiorgan damage. The pathogenesis of the autoimmune diseases can primarily involve autoantibodies (e.g. haemolytic anaemia), immunocomplexes (SLE), cellular immunity (e.g. multiple sclerosis) or a combination of humoral and cellular immunity (e.g. RA). Joint action of several co-factors playing important roles in development of such diseases are assumed: genetics (e.g. HLA associations), gender and age. Properties of the individual antigens and the way in which they are presented to the immune system are also important. Some infections, e.g. EB virus (Epstein-Barr virus) or mycoplasma infections, can induce the production of autoantibodies in otherwise healthy patients. Some medications such as procainamide (used e.g. in treatment of some types of cardiac arrhythmias) or toxic substances such as mercury(II)chloride or polyvinylchloride can induce autoimmune reactions. Various such diseases can manifest in the oral cavity, in particular pemphigus, pemphigoid, SLE, Sjögren syndrome, etc.
Pemphigus is a chronic autoimmune blistering disease affecting skin and mucosa. Based on the clinical, histopathological and immunological criteria, four basic forms of the disease can be distinguished: pemphigus vulgaris, p. vegetans, p. foliaceus a p. erythematosus (Senear-Usher’s syndrome).
This, the most common, disease in this group is characterized by the production of antibodies against membrane antigens of keratocytes and their intercellular substance, which leads to a disruption of intercellular junctions, acantholysis and formation of intraepithelial blisters. It affects both sexes evenly, mostly between 50 and 60 years of life but it can develop at any age. In most patients (approx. 90 %), the oral mucosa is affected and in approximately 50 % of all patients with this disease, it begins in the mouth! The manifestations can remain limited to the oral mucosa for many months to years. In addition to the oral mucosa, however, mucosa in the genital region and conjunctiva can be also affected.
Clinical picture: The disease can begin at any spot of the healthy, non-inflamed skin or mucosa by formation of blisters with clear fluid. The contents of the blister gradually grow turbid, becoming yellowish to haemorrhagic. The blisters are of varying sizes, often merging and when breaking, painful erosions develop that can spread into the adjacent areas. The eruptions often manifest in waves and after a time (of various duration), the process can become systemic. The generalized form of the disease affecting organs is a very serious disease with a high risk of mortality, often due to complications associated with the immunosuppressive therapy. On the oral mucosa, erosions are more commonly found than blisters, which is caused by the fact that the roof of the blister is easily torn down and on examination, only the erosion remains. The mucosa is usually oedematous but bears no signs of inflammation (the lower degree of inflammatory symptoms is an important sign for differential diagnosis). The erosions can develop anywhere in the oral cavity but they are most commonly found on the mucosa of the soft palate, buccal mucosa and mucosa of the lower lip. In the vermilion zone, yellowish crusts formed by drying of the exudate on the surface of the erosions can be observed. A typical sign of pemphigus is the way it spreads, i.e., intraepithelial spreading into the periphery; a pressure applied by a finger followed by pulling the finger along the normal skin, the surface layer of epidermis gets separated (Nikolski’s sign I). When applying pressure of the finger on the surface of the bulla, its content is pushed under the surface layer of the adjacent epidermis and the blister increases (Nikolski’s sign II). The erosions heal very slowly, the epithelised areas may be slightly atrophic with hyperpigmentation.
Dg.: Discovery of an acantholytic intraepithelial blister during histological examination. Immunofluorescence examination (IF) revealing IgG antibodies and the C3 component of the complement in the intercellular space or circulating antibodies in the serum. An assay for desmoglein 3 can be also performed using ELISA; the presence of desmoglein is specific for pemphigus vulgaris. In the smear from the blister floor, acantholytic cells can be found (Tzanck’s test).
Th.: Systemic administration of corticosteroids in high doses, potentially combined with other immunosuppressants. The therapy and treatment itself including follow-ups must be done in specialized departments of dermatology-venereal diseases. The treatment requires frequent clinical and laboratory follow-ups.
Locally: corticosteroids in orabase or mouthwash, local ATBs.
Dif. dg.: Bullous pemphigoid, EEM, bullous drug-induced eruptions. In the oral cavity, erosive lichen planus, persisting aphthae, Behçet disease, benign familial chronic pemphigus (Hailey-Hailey, a histologically identical hereditary form with a chronic course, which is however significantly less aggressive).
This subtype of pemphigus vulgaris forms soft, moist, dark red wart-like vegetations, on the periphery of which isolated blisters are almost always found. Those vegetations represent a major proliferation of some excoriations. In the oral cavity, they predominantly appear in the area of the corners of the mouth. They are frequently invaded by C. albicans as a secondary infection.
Dg., dif. dg. and th.: Same as in p. vulgaris.
This disease represents a superficial, less serious form, which however has a prolonged course. It appears only rarely. It is characterized by subcorneal localization of acantholytic blisters. Due to this localization, we can only rarely see the intact blisters but rather eroded and crust-covered patches. The lesions can be most commonly found in the hair, face, trunk and in the seborrhoeic areas of the body. Oral mucosa is only rarely affected (small, superficial erosions).
This superficial type of pemphigus is also rare, has a mild course and usually a good prognosis. The disease is characterized by erythematous eruption similar to lupus erythematosus, with which it can coexist (as well as with myasthenia gravis or thymoma). Oral mucosa is only very rarely involved, if so, we can see only superficial erosions.
This rare autoimmune disease has been only recently described. This type of pemphigus manifests by lesions on both skin and mucosa in individuals with cancer, most commonly leukaemia and lymphomas. The clinical picture is characterized by a) polymorphic skin lesions, often manifesting as papulosquamous eruptions b) painful erosions resistant to treatment, often affecting the lower lip, c) persisting erosions of the conjunctiva.
This chronic autoimmune disease affects predominantly the mucosa and results in epithelial atrophy. It usually affects middle-aged and older individuals. A genetic predilection with participation of the HLA complex gene (a greater frequency of the HLA-B12 antigen) has been proposed as a possible etiology.
Clinical picture: Most commonly, the oral mucosa and conjunctiva are affected, followed by nasopharyngeal and esophageal mucosa and the anal region. Skin lesions appear only in 20-40 % of patients. In the oral cavity, the disease mostly affects the gingiva, offering the clinical picture of desquamative gingivitis; other parts of the mucosa can however be affected. Similar to pemphigus, intact blisters can be only rarely found and only the erosions or secondary scarring are usually observed! If eyes are affected, the cornea can be damaged, which can result in blindness. Lesions on GIT mucosa often lead to the formation of strictures.
Dg.: Histological examinations will reveal non-specific ulcerations with chronic inflammatory cellularization. Immunohistochemistry will prove the presence of deposits of IgG, IgA, IgM and C3 component of the complement in the basal membrane. BP 180 and BP 230 proteins, laminin 5, integrin and Type VII collagen can be detected using immunoblotting, which helps differentiate the benign mucosal pemphigoid from the bullous pemphigoid, epidermolysis bullosa acquisita and systemic bullous lupus erythematosus. In the case of benign mucosal pemphigoid, BP 180, BP 230 protein and Type VII collagen are detected.
Dif. dg.: pemphigus, erosive OLP, recurrent aphthae, Behçet disease
Th.: Systemic administration of corticosteroids that can be supplemented with other immunosuppresives. In mild forms, a local therapy with topical steroids may be sufficient.
Bullous pemphigoid is probably the most common blistering disease affecting elderly individuals, usually over 60 years of age. The circulating antibodies in this autoimmune disease attack the antigens of the stratum lucidum of the basal membrane, which triggers the complement cascade and formation of subepidermal blisters.
Clinical picture: The blisters begin to form on only vaguely circumscribed erythematous patches or (less often) on the normal skin. After the blisters burst, erosions with a tendency of spreading into the periphery appear. The oral mucosa is affected only rarely, usually only secondarily, after the cutaneous manifestations. The course of the disease is prolonged, with spontaneous remissions and good prognosis. Nikolski’s sign is absent, the Tzanck’s test is negative.
Dif. dg.: Pemphigus vulgaris, dermatitis herpetiformis Duhring, EEM. Unlike in the benign mucosal pemphigoid, Type VII collagen is not detected in immunoblotting; BP 180 and BP 230 are however present.
Th.: Systemic administration of corticosteroids.
This disease is a chronic dermatitis associated with gluten-sensitive enteropathy, which can however remain asymptomatic. An association with HLA antigens (HLA-B8, DR3 and DR7) has been proved in up to 90 % of patients. It can occur at any age (even in children), it however manifests mostly between 20-50 years of age with men being affected more often.
Etiopathogenetically, the disease is caused by an incorrect response of the immune system on gluten antigens (gluten Ags); of the complex of antigens, gliadin appears to be the most important. A chronic inflammatory reaction with production of IgA antibodies against gliadin occurs in the small intestine. Through an alternative pathway, the complement cascade is activated, the chemotactic factors are produced and leukocytes immigrate into the papillae of corium. After the death of these cells, their enzymes are released, epidermal cells separate from the corium and a subepidermal blister is formed.
Clinical picture: Symmetrical papulovesicular eruptions appear on the skin – most commonly, above limb extensor muscles and in the sacral region. The manifestations are profoundly itching, their intense scratching often leads to the formation of excoriations or crusts. The oral cavity is affected in 10-20 % of patients, usually only secondarily, after the primary manifestations on the skin appeared. The most common structure in the oral cavity are macropapules; vesicles or erosions similar to aphthous ulcers can however also appear. The palate, tongue and buccal mucosa are more commonly affected than gingiva, lips or tonsils. In 10-20 % of patients, the enteropathy manifests clinically.
Dg.: Histological proof of subepidermal blister, a direct proof of IgA antibodies against smooth muscle reticulin by immunofluorescence.
Th.: Gluten-free diet, sulfones and sulfapyridines.
This term describes a group of rare diseases causing easy formation of intra-and subepidermal blisters on the skin and oral mucosa.
The disease, also known as the “butterfly disease”, is a rare congenital disease further dividing into several subtypes.
Clinical picture: The blisters on the skin as well as on mucosa arise spontaneously or only upon application of slight pressure or friction. After the blisters break, painful open lesions appear. During healing, scars and contractures appear.
This rare blistering disease causing subepidermal blisters usually affects adults over 50 years of age. The pathogenesis may include both inflammatory and non-inflammatory mechanisms, including immune ones.
Clinical picture: The manifestations of the disease are very diverse, especially in the first stages when they can mimic almost any other blistering disease. Gradually, however, the typical picture with extreme skin fragility develops, which is combined with traumatic formation of blisters and erosions healing by scars. Most commonly, the manifestations affect the dorsum of the hands and extensor surfaces of the limbs. In one third of patients, erosions with subsequent scarring appear in the oral cavity as well, rarely also in the larynx and in the esophagus.
Dg.: It is very difficult to distinguish it from pemphigoid – both diseases form subepidermal blisters and in the region of the basal membrane, they accumulate IgG and C3 component of the complement. Indirect immunofluorescence assay can help distinguish those diseases – in EBA, the circulating immunocomplexes bind to the sublamina densa while in pemphigoid, they bind to the lamina lucida of the basal membrane. In differential diagnosis, immunoblotting can be used and if Type VII collagen is found but not BP 180 and BP 230 proteins, EBA can be distinguished from both the bullous and benign mucosal pemphigoids.
Th.: Difficult; a combination of corticosteroids and cytostatics is used (however, resistance to therapy is a typical characteristics of the disease).
Lupus erythematosus is a chronic inflammatory autoimmune disease with a variable spectrum of clinical manifestations, from isolated mucocutaneous lesions to their combination with systemic manifestations. The etiopathogenesis remains poorly understood, the most likely explanation involves a failure of regulatory mechanisms responsible for autotolerance.
DLE is the most common chronic form of the disease. Its course is slow, manifestations are in particular in the orofacial region, on the scalp and/or external ears but can also appear elsewhere on the skin. The cutaneous manifestations are especially apparent on the exposed parts of the body and typically include livid papules and patches with a marked follicular hyperkeratosis. In the centres of the foci, firmly adherent scales are formed. When the scales are removed, keratin plugs reaching down to the mouths of the follicles can be found on their bottom. The patches are well circumscribed and separated from the surrounding healthy skin; where the disease is advanced, skin atrophy and teleangiectasia may develop (clown’s face).
Erythema centrifugum is a characteristic symptom, typically localized above the root of the nose where it forms a well-known butterfly-like pattern with itching and burning. The oral mucosa in DLE is affected in approximately 15-25% of patients, usually together with skin lesions, although rare cases where only the oral mucosa is affected can also occur. LE manifests on the oral mucosa as discoid atrophic plaques, which are red in the centre. The lesions are well circumscribed with whitish edges, slightly elevated above the surrounding mucosa. In the centre of the enanthema, teleangiectasia, erosions or even ulcerations may occur. The buccal mucosa is most commonly affected, followed by lower lip, palate, gingiva and tongue. Intraoral manifestations are very similar to lesions occurring in oral lichen planus. A sign that may help in distinguishing LE from oral lichen planus is a netlike pattern of the edges of LE lesions (while the whitish colour of lichen lesions is rather continuous).
Laboratory testing: Various antibodies can be detected in the serum (antibodies against DNA, histons, non-histon RNA-bound proteins or against the nuclear membrane antigens). Immunofluorescence methods can help detect subepidermally deposited immunoglobulins.
Th.: For treatment of oral lesions, local application of steroids in orabase paste. Systemic treatment includes steroids and antimalarial drugs.
SLE is a typical example of a multisystemic autoimmune disease affecting internal organs. Skin symptoms may or may not be present. The disease can be acute, with rapid onset, or chronic, initially latent disease with tendency to recur. Many internal organs can be affected, including those of cardiovascular and gastrointestinal system, followed by lungs, kidneys, joints and nervous system. The disease is often accompanied with general symptoms such as fever, loss of weight and lymphadenopathy. The presence of butterfly-like exanthema (butterfly rash) in the face, affliction of kidneys (glomerulonephritis) and presence of antinuclear factors are important for diagnosis. The oral mucosa is affected in 30-45 % of patients. Extensive painful erosions or ulcers, surrounded by a white or red zone are observed. Petechiae, haemorrhages (due to thrombocytopenia) and xerostomia are often present. A less common manifestation is represented by white hyperkeratotic lesions that may be difficult to distinguish from other white lesions in the oral cavity. This is especially true in subacute stages when the systemic symptoms may be missing or only slightly expressed. The palate, lips and buccal mucosa are the most commonly affected sites.
Laboratory proof: See DLE.
Th.: Due to the serious nature of the disease, systemic steroids, antimalarial drugs, immunosuppressants or, if necessary, plasmapheresis.
Psoriasis is a relatively common chronic disease affecting mostly the skin – it only rarely affects the oral mucosa. If oral symptoms are present, it is almost exclusively accompanied by parallel serious skin problems, which makes the diagnosis, to a certain degree, easier. The pathogenesis of psoriasis has not yet been fully explained, it is assumed that disorders of the normal epidermal development play a role, leading to epidermal hyperproliferation, alterations in skin cells maturation, vascular and inflammatory changes. Psoriasis is genetically determined, polygenic heritability has been suggested. Various provoking factors may trigger the onset of the disease, including various infections, mechanical or chemical injury to the skin, stress, smoking and many others.
The skin lesions are most commonly present in the areas of extensor muscles over joints (particularly elbows and knees), in the lumbar region, scalp and nails. The skin is thickened, dry, scaly, silvery white. Several types of psoriasis (annular, circinate, guttate, nummular and pustular) can be distinguished according to the morphology of skin lesions. On the oral mucosa, the clinical picture of psoriasis is both rare and variable. Whitish, dry desquamating patches can be observed in the vermilion zone that can lead to pinpoint bleeding. Whitish round patches can be found on the buccal mucosa where the desquamation is obviously not present due to maceration. The tongue often shows smooth patches lined with whitish hyperkeratotic filiform papillae. Ring-like lesions on the sides and bottom of the tongue may resemble the annular form of cutaneous psoriasis. The changes on the oral mucosa do not cause any subjective problems. Interestingly, the clinical and histopathological picture of psoriasis and geographic tongue are similar, which leads some authors to a conclusion that the geographic tongue is in fact a mucosal manifestation of psoriasis.
Th.: Mucosal problems of psoriasis do not need any treatment, they regress spontaneously and faster than changes on the skin that are subject to a complex therapy by dermatologists (PUVA, steroids, methotrexate, cyclosporine, retinoids).
A significant role in pathogenesis of this chronic disease is probably played by HTLV-1 viruses affecting lacrimal, salivary and other exocrine glands, reducing the secretion of these glands. This disease predominantly affects women in their 4th to 5th decades of life and is characterized by xerostomia and dry keratoconjunctivitis. New clinical, serological and genetic criteria ere applied to distinguish two forms of the disease: primary and secondary. The Sjögren syndrome (SS) is considered primary if it is not accompanied by disorders of the connective tissue (collagenosis) and secondary if it coexists with a disease of the connective tissue such as rheumatoid arthritis, SLE, polymyositis, primary biliary cirrhosis, thyroiditis or vasculitis. Besides symptoms of the eye (keratoconjuctivis sicca) and joints (progressive polyarthritis often develops), symptoms can also occur in the oral cavity – in particular insufficient salivation, making swallowing of solid foods and speaking difficult. The xerostomia manifests especially on the lingual mucosa where atrophy of both filiform and fungiform papillae can be observed, which may lead up to the clinical picture of smooth tongue. The oral mucosa can be erythematous, dry with desquamation of the superficial epithelial layers, often accompanied by angular cheilitis and increased tendency to developing caries of teeth. Parotic glands may be enlarged in some patients. The prognosis is uncertain, Sjögren syndrome is (along with helicobacter-associated gastritis and Hashimoto’s thyroiditis) considered a precancerosis of the B-MALT lymphoma (mucosa-associated lymphoid tissue lymphoma).
Dg.: Sialometry (Škach’s test) is used for determining the production of saliva. Ultrasound, scintigraphy and sialography can also be employed, as well as lab tests for various antibodies. Biopsy of minor salivary glands from the lower lip should be performed to search for signs of mononuclear infiltrate with periductal distribution in patients with primary SS and with perivascular distribution in patients with secondary SS. Reduced secretion of salivary glands can be also determined by an ophthalmologist using Schirmer’s test or using specific staining (Bengal red). See Fig. 9 for overview of criteria for establishing diagnosis of the Sjögren syndrome.
Th.: Treatment is symptomatic, includes receiving of every piece of food along with liquid (in particular dry foods), maintaining a strict oral hygiene (prevention of the increased tendency to caries) stimulation or substitution of saliva production and protection of conjunctiva with artificial tears. If the Sjögren syndrome represents a manifestation of a systemic disease, its treatment forms a part of the complex therapy.
Dif. dg.: Chronic interstitial sialoadenitis, affecting the submandibular salivary gland, can have similar symptoms in the oral cavity. It is associated with parenchymal sclerotization with a marked lymphocytic infiltration (it is often misdiagnosed as neoplasia – so-called. Küttner’s tumour).
Lichen planus is a chronic inflammatory disease of unclear etiology with a likely immunopathological etiology. It occurs as lichen ruber planus on the skin, as oral lichen planus in the oral cavity and it can also manifest on other mucosal surfaces. So-called „lichenoid lesions“ (or „lichenoid reactions“) are very similar in appearance and can be either of contact origin (dental materials) or represent manifestation of induced reactions (antidiabetic, antihypertensive drugs or NSAIDs). The chronic form of the chronic graft versus host disease (GVHD) is of similar appearance, it is also possible to consider chronic hepatopathy.
To distinguish a typical oral lichen planus (OLP) from an oral lichenoid lesion (OLL), clinical and histopathological criteria were set by WHO (1973, further modified in 2003). The clinical criteria for OLP require a presence of bilateral lesions that can be more or less symmetrical and the presence of lacy, reticulated structure. Erosive, atrophic, bullous and plaque-like lesions are only accepted as a subtype providing the reticulated lesions are present. Histopathological criteria for establishing OLP diagnosis require the presence of a band-like lymphocytic infiltrate below the basal membrane (hydropic degeneration of basal layer cells) and the absence of epithelial dysplasia. If either clinical or histopathological criteria are not met, the changes on the mucosa are termed as OLL.
OLP is associated with disorders of epithelial keratinization (hyperkeratosis) causing the whitish discoloration of the mucosa. Mucosal changes often (in about 25 % of cases) constitute the only manifestation of this disease. Oral mucosal manifestations occur in 50 % of patients with skin lesions. Individuals of all races can be affected, the disease is more common in females and the highest prevalence (approx. 70 %) falls within the age category of 30-60 years. The etiopathogenesis is not fully explained, although more recent findings suggest the role of autoimmune mechanisms. This theory is supported by the occurrence of OLP as a disease associated with various autoimmune conditions as well as by the presence of cytotoxic lymphocytes, Langerhans cells and expression of HLA class II antigens (DR) or by increased expression of some adhesion molecules (ICAM-1 or VCAM-1) by keratinocytes or squamous epithelial cells.
Clinical picture: small, flat polygonal papules form on the skin, initially red (hence the term lichen ruber planus) and gradually turning into purplish colour. Sites of predilection include the skin on flexors of the forearm and wrist, sacral region, back, lateral sides of the neck, less commonly distal thirds of the lower leg.
The basic structure on the oral mucosa is a shiny, flat, whitish papule. The papules can be isolated or form groups, thus creating whitish oval patches (lichen annularis). On the buccal mucosa, porcelain-like whitish reticulated patches that can be also arranged in a garland-like pattern (lichen reticularis) are more common. Whitish bands radially project from white lesions on the vermilion zone. Besides the most common reticular form, papular and plaque form of the disease (also with a character of white lesion), atrophic, erosive, ulcerative or bullous (erythematous appearance or form ulcers covered with white fibrin pseudomembrane. Occurrence of lesions in the oral cavity can be associated with lesions in the genital area (vulvo-vagino-gingival syndrome).
The course of the disease can be asymptomatic, a chronic course with remissions and exacerbations is however more common. On the skin, patients mostly complain about itching of various intensity while on the oral mucosa, the complaints are rather about burning sensation and irritation after contact with usual diet. Erosive and bullous forms can be painful. Diagnosis of lichen is relatively simple if the lesions have their typical appearance, it can be however (and often is) mistaken for leukoplakia in clinical practice (especially if the lesions form continuous whitish plaques).
Histology: Hyperkeratosis, hypergranulosis, irregular acanthosis, hydropic degeneration of basal cells and the presence of apoptotic cytoid Civatte bodies can be found. The lichenoid band-like inflammatory infiltrate below the basal membrane is formed by lymphocytes and histiocytes. Immunofluorescence can reveal predominantly linear deposits of fibrinogen along the dermoepidermal junction. The cytoid bodies are usually positive for IgM.
Th.: No causal therapy is available, symptomatic (usually local) treatment can bring relief –administration of corticoids in an oral paste/mucoadhesive patch; if need be, depot injections of corticoids can be applied. Corticoid treatment can be augmented with levamisole; levamisole monotherapy is also a suitable option in patients who cannot use corticoids (Won et al., 2009). If lesions are asymptomatic, the therapy is not necessary. Non-irritating food is recommended, along with inert (baby) toothpastes; the use of alcohol containing mouthwashes should be avoided. Washing the mouth with lukewarm sage infusions is often soothing.
Dif. dg.: The presence of isolated lichen papules on the edge of the patches is a sign important for differential diagnosis (immunohistological methods provide reliable diagnosis). Similar manifestations include so-called lichenoid allergic reactions, graft versus host reaction, or mucosal reaction to formaldehyde-releasing substances. Lesions with whitish margins can develop in lupus erythematodes; the rare manifestations of psoriasis in the oral cavity can resemble the annular form of lichen. The prognosis with a view of survival is relatively favourable (malignant transformation occurs in only approx. 2 % of patients, usually those with more serious, erosive forms of disease, the prognosis toward full recovery is however unfavourable.
This kind of lesions is probably the most common type of manifestations of intolerance of both metallic and non-metallic dental materials. Whitish lesions of reticular appearance are typical, mostly occurring on the buccal mucosa, less commonly on other sites (labial, lingual mucosa), always on the site of contact with the dental material (note that when the mouth is open during examination, points of contact differ from those when the mouth is closed!). The edges are indistinct, the surrounding mucosa is often intensely erythematous, the mucosa can be sensitive (but not painful).
Drug-induced lichenoid reactions of the oral mucosa occur most commonly during treatment with antihypertensives, non-steroidal antirheumatic drugs and antidiabetic drugs (so-called Grinspan’s syndrome, i.e., combination of diabetes mellitus, lichen planus and essential hypertension). In HIV-positive individuals, such lesions can occur during treatment with zidovudine and ketoconazole. The chronic form of the graft versus host disease can be of similar appearance, as well as some chronic hepatopathies.
EEM is a systemic chronic inflammatory disease of the skin and mucosa with acute exacerbations. The term is considered rather as a descriptive term unrelated to the etiology and nature of the affliction. EEM develops in genetically predisposed individuals as a result of an immune reaction to external factors. The etiology includes an allergic component (although the disease is not considered allergy) and manifests as eruption of papules or pustules on the skin and changes on the mucosa of the oral cavity (only skin, only mucosa, or both can be affected). EEM is often associated with the use of some drugs (ATBs, barbiturates), local cosmetic products (toothpastes, mouthwashes lipsticks), or can be associated with a post-infection reaction (herpes, streptococci). A seasonal occurrence with maxima in spring and autumn is typical, as well as the predilection to young people (particularly men). EEM starts usually with brick-red sharply circumscribed spots on the skin, later developing into blisters, usually arranged in (often concentric) circles. The itching exanthema is often notably symmetrical, blisters can be large and covered (after bursting) with a thick haemorrhagic crust. Extensive mucosal erosions covered with fibrin pseudomembranes can manifest suddenly anywhere in the oral cavity. In the vermilion zone, haemorrhagic crusts can develop. They are accompanied by major subjective complaints and worsening of the patient’s overall condition (in particular idiopathic forms can be fatal). The disease has a tendency to recur and deeper defects are associated with risk of developing secondary infections. It is often associated with hypersalivation, bad breath and heavy coating of the tongue.
Apart from changes in the peripheral blood count (leukocytosis and lymphopenia), other internal and immunological examinations usually reveal only minimum deviations from normal.
Histology: mucosal necroses, vacuolar degeneration of the basal layer and/or subepithelial blisters are found.
Th.: Therapy is based on the use of (non-steroidal) anti-inflammatory drugs that can be combined with ATB mouthwashes. If the disease progresses to a serious condition, short-term application of corticoids is recommended, ideally with patient hospitalization.
One of the clinical forms of the erythema multiforme is Stevens-Johnson’s syndrome, manifesting on the mucosa more than on the skin. This serious bullous form of the disease has a particular predilection for the vermilion, which is combined with complaints of conjunctiva, urethra, perianal region and genitals. The syndrome is most commonly drug-induced (ATBs – sulfonamides, antiepileptics, carbamazepine), or resulting from a post-infection reaction (herpes).
Recurrent aphthae (stomatitis aphtosa, habitual aphthae, benign aphthae, recurrent aphthous ulcers, RAS) are the most common stomatitis, affecting a quarter to a fifth of worldwide population, without a predilection to a certain age or sex. Many theories about the origin of the disease have been developed, none of which has however been confirmed so far and the cause of the disease has therefore not been satisfactorily explained. At present, we rather speak of predisposing factors than about etiological factors, such as:
heredity – the theory about involvement of genetic factors is backed by the familial occurrence with an incidence rate of 50 % in first degree relatives. Some associations between the development of aphthae and some HLA molecules have also been suggested..
age –the disease mostly occurs in childhood and puberty; a first manifestation after 35 years of age is relatively rare, the disease is almost non-existent in elderly, toothless patients.
immunopathological conditions – it is currently assumed that disorders and dysregulations of the immune system play a significant role in the development of the disease. Immunological studies report that the destruction of the epithelial cells of the oral cavity during recurrent aphthae appears to be a terminal stage of an immunopathological process, the course of which is known but reasons are not. The immune system is probably activated through production of activating cytokines (such as TNF-a, IL-1, IL-6) by keratinocytes of the oral mucosa as well as by Langerhans cells, dendritic cells and lymphocytes. Chemotactic stimulation leads to a transfer of immunocompetent cells to the site of the lesion-to-be where lytic enzymes are released, which leads to the necrosis. The reason for marking some epithelial cells for destruction by the local immune reaction is however not known.
infections – the autoimmune cross-reaction theory based on the similarity of oral streptococcal antigens with mucous structures has been rejected. However, it is generally assumed that some conditionally pathogenic oral microorganisms that contaminate existing mucosal defects have a secondary effect and may deteriorate the progression of the disease.
endocrine effects – hormonal imbalance during the menstrual cycle is expected to play a major role (exacerbation of aphthae during the menstrual cycle), unambiguous results are however not available.
psychological effects – aphthae may possibly recur through the neuroendocrine pathway.
local factors – aphthae often develop on the previously injured oral mucosa (cheek biting, injury caused by food or tools). The assumption of traumatic etiology is supported by the facts that the aphthae form at sites of frequent injuries to the oral mucosa and that aphthae are almost non-existent in toothless patients or at sites with continuous keratinization (gingiva, hard palate).
systemic diseases (including GIT diseases, hypovitaminoses, sideropenic anaemia, neutropenia) – when lesions resembling recurrent aphthae are found in patients with systemic diseases, it is better to use the terms “aphthous-like ulcers” or “aphthoid ulcerations”.
Classification: Aphthae can be counted among a group of diseases characterized by a loss of tissue by erosion/ulceration. Depending on the course of the disease, they can be classified as transient (spontaneously healing within approx. 3 weeks) and persisting form (healing longer than 3 weeks). The disease occurs in three principal clinical forms:
minor aphthous ulcers (aphthosis minor) – the most common form of the disease (approx. 80 % of all cases). The first manifestation is usually in the childhood, predominantly in women. Familial occurrence is common,
major aphthous ulcers (periadenitis mucosa necrotica recurrens) – a less common form (approx. 10-15 % of cases), always preceded in the patient’s history by the occurrence of minor aphthae. The appearance is atypical, it is usually a larger (over 1 cm) and deeper (can penetrate up to the submucosa) solitary defect with marked inflammatory changes in the surroundings of the ulcer. It occurs most commonly on the sides of the tongue, in some cases on the buccal or labial mucosa. Healing takes a long time (months) and often results in scarring.
herpetiform type – the rarest form (less than 10 %). Clinically, it is similar to the herpetic gingivostomatitis, but the affliction of gingiva and systemic symptoms are absent. Recurrences are rare, remissions often last for many years.
The common finding in all forms is the primary mucosal defect – the aphthous ulcer. Macroscopically, it presents as an oval or round erosion with the base covered with a yellowish-grey fibrin coating and a distinct red margin. The size can be anywhere from a couple of millimetres up to several centimetres. In larger defects, a collateral oedema of adjacent soft tissues and regional lymphadenitis can be observed. Alteration of the patient’s general condition is rare. Hyperesthesia can occur during the process of developing of the aphthous ulcer, replaced with intense pain in the erosion stage (possibly caused by the irritation of the nerve endings by released inflammatory mediators – IL-1, PGE2). Aphthae are mostly formed sporadically with various time intervals between exacerbations (sometimes even several years), they can however also present as multiple ulcers (several unhealed ulcers are present at any given moment).
Dif. dg.: The site of the ulcers helps distinguish them, especially from herpetic infections.
Most commonly, aphthae develop in the non-keratinizing parts of the oral mucosa, in particular on the labial and buccal mucosa in the vestibulum, on the sides of the tongue, on the oral floor, soft palatine mucosa and palatine arches. Recurrent aphthae are usually well circumscribed, with an inflammatory margin (unlike herpetic efflorescences that occur in groups and have irregular margins).
Distinguishing minor aphthous stomatitis from other diseases of the oral cavity is usually not difficult due to its typical appearance, localization of the manifestations and typical course of the disease with remissions and recurrences.
Major aphthosis can be clinically misdiagnosed as various other diseases that manifest in the oral cavity by forming deeper defects.
Herpetiform aphthae are probably the one form of recurrent aphthous stomatitis that is the most difficult to diagnose correctly. It must be especially distinguished from: viral stomatitis, autoaggressive diseases such as pemphigus or pemphigoid, secondary stage of syphilis, and toxic/allergic reactions.
Laboratory examination: Routine and specific immunological lab tests (such as ASCA IgA, ASCA IgG and ANCA antibodies) are performed to exclude celiac disease, Crohn’s disease, ulcerative colitis, Behçet’s syndrome, clinical neutropenia, vitamin B12 deficiency and EEM. To exclude herpetic etiology, serological tests detecting anti-herpes simplex virus antibodies (IgM and IgG) can be used.
Th.: No specific therapy is available. Establishing the correct diagnosis followed by treatment of the disease rather than of other similar diseases is of utmost importance. The treatment is largely symptomatic and aims at reducing patient’s subjective discomfort, acceleration of the healing of the mucosal defects, reduces the development of new manifestations; moreover, it can help prolong the period between exacerbations.
Local therapy: It is indicated in patients at the time of the acute manifestations, aiming to reduce the patient’s discomfort and speeding up the healing of efflorescences that have already developed. Local therapy can be administered in every patient with any form of recurrent aphthae. Local anaesthetics, antiseptics. ATBs, anti-inflammatory drugs, bioadhesives, mucoprotectives and other substances non-specifically supporting healing and epithelisation of the lesions (as well as their combinations) can be used.
Local anaesthetics: For topical superficial application, both ester (procaine derivatives – 1 % tetracaine, 20 % benzocaine) and amide type (2-10 % lidocaine) anaesthetics in the form of sprays, gels or solutions are used. Lauromacrogol – a drug with anaesthetic and sclerotizing effect – can be also applied. When prescribing local anaesthetics, it is necessary to inform the patients about the possible toxicity (hence, it is necessary to use them only when necessary, especially before meals) and about the risk of injury of the insensitive mucosa by mechanical or thermal irritation.
Antiseptics: CHX or hexetidine, triclosan, benzydamine. Usually, a short-term application (5-10 days) in the form of solutions or gels is prescribed. Care must be taken regarding possible interaction with lauryl sulphate (present in most toothpastes) and to apply the anaesthetic only for 30-60 minutes after cleaning the teeth. A long-lasting adhesion to the oral mucosa is a significant advantage of chlorhexidine (possessing marked antibacterial, antiviral and antifungal effects) as it allows rinsing the mouth only twice a day. Hexetidine blocks, by means of competitive inhibition, the synthesis of thiamid diphoshate – a coenzyme necessary for life processes of microorganisms – and such disruption of glycolytic processes helps reduce microbial decay of remnants of food in the oral cavity. It is used in the form of solution or oral spray three times a day.
NSAIDs (non-steroidal anti-inflammatory drugs): benzydamine and preparations containing salicylic acid. Benzydamine has anti-inflammatory, analgesic, anaesthetic and antimicrobial effects. In the oral cavity, it is applied at a 0.15 % concentration, 4-6 times a day. Salicylic acid: the mechanism of action lies in blocking cyclooxygenase – an enzyme participating in the synthesis of prostaglandin and other derivatives of arachidonic acid. It can be applied locally as a gel. It is less effective than benzydamine.
Corticosteroids: their use is limited to the treatment of defects that have already developed – in particular in the case of major aphthae (both systemic and local contraindications including viral, bacterial and fungal stomatitides must be considered). Prior to the application of the gel with corticosteroids (2-4 times per day), it is necessary to blot up the lesion and the surrounding mucosa. Depot injection of corticosteroids into the soft tissues surrounding the lesion can be considered in some cases, in particular in major aphthae (aphthosis major). This therapy must be however limited to specialized departments due to the possible local and systemic side effects.
Bioadhesives and mucoprotectives: cellulose hydrogels and polyacrylates are used to cover the lesion with a film, which relieves the pain. They can also serve as carriers of various treatment agents, which facilitates a longer exposure of the lesion to the active substances. A mucoprotective medication sucralfate has the capability to stick to the damaged mucosa and protect it, which accelerates epithelial regeneration, improves microcirculation and locally stimulates the GIT mucosa. Besides the therapy of erosive lesions of the esophagus, stomach or duodenum, it is also used in therapy of frequently recurring aphthae.
Other medications that can be individually used at specialized departments are preparations containing cyclosporine A, recombinant interferon alpha or prostaglandin E2.
Systemic therapy: It is only administered in some patients with aphthosis major, with herpetiform recurrent aphthae and with recurrent minor aphthae with severe attacks and many ulcers. The aim of the therapy is to relieve patients’ discomfort and to prevent recurrences. Substances for systemic administration include B vitamins (B1, B2, B3, B5, B6, B9, B12), for example so-called Škach’s vitamin therapy. This treatment method is based on bolus administration of preparations containing vitamins B6, B9 and B12 with intervals between treatments, for example using a scheme 3 weeks of bolus treatment – 3 weeks of no intervention – 3 weeks of bolus treatment – 6 weeks without intervention – 3 weeks of treatment. Vitamin B12 is administered intramuscularly (300 µg on alternate days), Pyridoxin 3x20 mg + folic acid 1x10 mg a day (active folate is preferred because the enzyme methylentetrahydrofolate reductase is defective in a high percentage of the population). Other drugs may be prescribed, including antihistamines, vasodilators, corticoids, immunosuppressants or immunostimulants, lysine and Fe-containing preparations. Most remedies for systemic administration (usually long-term use) are reserved for specialized departments and therefore do not need to be listed here.
Preventive measures and other therapy: Prevention of local trauma to the oral mucosa, modification of the diet, elimination of known allergens, avoiding stressful situations, laser or ultrasound therapy.
Some authors count Behçet’s syndrome (aphthosis maligna) among recurrent aphthae. Unlike the “normal” aphthae, however, Behçet’s syndrome is a serious systemic disease of unknown etiology. It develops from vasculitis and is associated, besides ulcerations in the oral cavity, with many extraoral manifestations. Similar to many other diseases, major criteria (recurrent ulceration in the oral cavity) and minor criteria (recurrent genital ulcerations, skin and eye lesions and formation of a pustule – pathergy – on the site of a puncture) apply. Some authors divide the disease according to the clinical picture into 3 types: mucocutaneous form (affecting the oral cavity, genitals, conjunctiva and skin), arthritic form and neuro-ocular form (affecting eyes and/or nervous system along with mucocutaneous or rheumatic complaints).
Th.: Combined (corticoids, cytostatics).
This disease counts among the so-called chronic aphthoses. In this disease, ulcerations similar to those observed in the oral cavity develop also in the stomach, bowels, in the genital area and respiratory tract. In addition, eyes or central nervous system can be affected. This disease is also one of systemic multiorgan diseases with only symptomatic treatment.
Any component of specific and/or non-specific immunity can be missing in the organism, only present in abnormally small amounts or not function properly. Common manifestations of immunodeficient disorders is lowering of the immune barrier resulting in increased susceptibility to infections with serious course reacting only to a limited degree to the usual antimicrobial therapy. If humoral immunity is compromised, suppurative (pyogenic) infections predominantly appear; if cellular immunity is affected, viral, fungal or parasitic infections are more common. Specific immunodeficiency conditions are categorized into primary and secondary types. Primary ones include for example DiGeorge syndrome (limited development of the thymus and parathyroid glands, resulting in T-cells deficiency and other disorders) or congenital (Bruton’s) X-linked agammaglobulinemia associated with an inability of the organism to produce immunoglobulins.
Secondary immunodeficiency conditions occur in some diseases (AIDS, malignant lymphomas), after intensive immunosuppressive, cytostatic or radiation therapy. Both humoral and cellular immunity are usually affected. From the dentist’s perspective, chronic mucocutaneous candidosis representing a combined disorder of both humoral and cellular immunity must be mentioned.
The Acquired Immune Deficiency Syndrome was first described in 1981. The HIV virus attacks especially CD4+ T-cells and macrophages. It multiplies inside them, destroys them and thus significantly reduces their levels in the body of the infected person. This decline gradually leads to the immune system failure, which manifests by recurrent infections and reduced anticancer immune response, which results in higher susceptibility to some types of tumours. The range of HIV manifestations is extremely wide and can coincide with many diseases of the oral mucosa of other etiologies. Infectious diseases of the oral cavity often appear already in the ARC (AIDS related complex) stage and are common once the full scale AIDS sets in. None of these manifestations however count among clinical criteria for diagnosing HIV infection. From both the diagnostic and epidemiological perspectives, the fact that the afflictions of the oral mucosa can clinically manifest months before other HIV symptoms poses a problem. The oral manifestations thus can represent the first clinical symptoms of the disease but none of those is specific for the HIV infection! Diseases of various etiologies can occur simultaneously in a single patient but this is usually only the case when the CD4+ T-cell count is below 200/mm3; in patients with higher values of the CD4+ T-cells (200-400/mm3), only one type of intraoral affliction is usually found.
Infectious diseases/complications of the oral mucosa in HIV positive patients can be categorized into viral, bacterial and fungal infections. The course of the diseases is usually atypical, prolonged, with frequent recurrences and often with coincidence of multiple infections (e.g. herpetic and fungal at the same time); their treatment is difficult.
Herpes viruses are the most common etiology of such diseases; papovaviruses or poxviruses can however also affect the mucosa. In HIV patients, the infections typically last longer and have a more serious course than in HIV negative individuals.
This disease is often more extensive with serious course. The healing takes usually longer, even if systemic antiviral therapy is administered.
Similar to the above, the disease is also usually more serious with longer duration, is always very painful and recurs more frequently. The disease can turn chronic. Acyclovir can be administered to prevent possible recurrences.
Herpes simplex often spreads from the vermilion zone onto the facial skin, which can be affected to various degrees. The lesions can persist for a long time despite the therapy.
This disease also recurs frequently and in the oral cavity, it can lead even to osteonecrosis of the alveolar bone. Sometimes, multiple sensitive nerves can be affected or the lesions can be bilateral, which is extremely rare in HIV negative patients.
They can develop in patients with seriously reduced immunity and are considered a sign of imminent organ complications (e.g. CMV-retinitis). If they are among the first clinical signs of the immunodeficiency, they can be difficult to diagnose (histopathological verification is needed).
Formation of multiple mucosal papillomas with chronic course are relatively common in the oral cavity. The most common ones are the focal epithelial hyperplasia (HPV 13, 32) or condylomata (HPV 6, 11). The genitalia and perianal region are usually also affected (condylomata acuminata).
This manifestation of EBV infection manifests on the oral mucosa, most commonly on the tongue. The development of the hairy leukoplakia signifies a poor prognosis and progression of HIV-positivity into the AIDS stage. In more than 80 % of HIV patients who develop hairy leukoplakia, this progression occurs within 30 months of its development.
Those are usually infections with mixed flora, mostly anaerobic rods or cocci (Tanarella, Fusobacterium, Prevotella, Aggregatibacter and Parvimonas) and oral spirochetes (Treponema genus).
This gingival lesions are characterized by an intensive 2-3 mm wide erythematous band on the marginal gingiva accompanied by bleeding and formation of petechiae. Etiologically, this inflammation is associated with the presence of the microbial plaque in the oral cavity.
Th.: The therapy is based on a proper and thorough maintaining of the oral hygiene; chlorhexidine type antiseptics can also be used.
Dif. dg.: It histologically differs from the “normal” plaque-induced gingivitis in the absence of inflammatory infiltrate and multiplication of blood vessels in the submucosal connective tissue. The linear marginal erythema must also be distinguished from desquamative gingivitis present as a part of OLP or pemphigoid manifestation
This disease is described in detail in the chapter devoted to bacterial infections (see Chapter 5.4.1).
In HIV-positive individuals, deep painful mucosal defects appearing as ulcers often develop (histopathological and microscopic examination is necessary). It is not completely clear whether such ulcers develop as a result of microbial activity or if the microorganisms only secondarily colonize the defects of another etiology.
Th.: Local and systemic ATBs, mucosal anaesthetics before meals.
The oral manifestations of TBC in HIV-positive patients have not been sufficiently studied so far. They are however often associated with „multiple-drug resistant“ TBC. Syphilis is relatively frequent among HIV patients (coincidence due to identical routes of transmission). The overall clinical picture including mucosal changes can be in these patients modified by the immune disorder (lues maligna).
The agent responsible for development of this disease occurring probably only in HIV-positive patients, is Rochalimaea henselae (genus Rickettsia). It affects in particular the endothelial cells of the capillaries, smaller vessels in the skin and mucosa, or in the internal organs. In the oral cavity, those manifest as erythematous, soft knot-like indurations, which can appear in various sites. On the skins, the disease manifests as maculopapular exanthema that can be accompanied by ulcerations.
Th.: macrolide or tetracycline antibiotics.
Dif. dg.: This disease can be easily mistaken for Kaposi’s sarcoma (can only be distinguished done using histopathological examination or by immunofluorescence examination).
Recurrent candidosis is probably the most common pathology in the oral cavity in HIV patients. The spectrum of the fungal diseases is however wider and even deep, systemic mycoses can manifest there. In the countries with high numbers of HIV positive individuals and AIDS patients, the clinical spectrum of oral candidosis is much wider. The oral candidosis is a typical AIDS symptom of the oral cavity, with whitish margins and pseudomembranes that can develop on the gingiva as well. Symptoms of yeast infection can combine with other infectious and non-infectious pathological manifestations. Other yeasts that can be responsible for the fungal infections include Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatidis, Rhyzopus oryzae or R. arrhizus. We can also consider some other diseases of the oral cavity to represent manifestations of oral candidosis. These so-called „Candida-associated lesions” include besides prosthetic stomatitis also glossitis rhombica mediana a lingua villosa nigra.
Practically any of the above-mentioned forms of oral candidosis can manifest in HIV positive individuals. The candidosis often represents a part of a much broader affliction of the GIT and respiratory systems (esophageal candidosis is considered as a diagnostic criterion of the HIV infection). Pseudomembranous forms of candidosis can occur practically on any site of the oral mucosa including gingiva. The chronic atrophic, hyperplastic and erythematous form often lead to superficial but very painful ulcerations that are difficult to diagnose. In HIV-positive individuals, both nodular and papillary forms of the candida infections can occur, which are never present in HIV-negative patients.
Glossitis rhombica mediana (one of the candida-associated lesions) is also often present.
Th.: In particular, 3rd generation azole antimycotics (fluconazole etc.) are used. A combination of systemic fluconazole administration with local application of nystatin or CHXcan be administered. After successful treatment, a long-term preventive therapy with fluconazole is recommended.
Dif. dg.: Hairy leukoplakia.
Systemic mycoses usually manifest as solitary, painful ulcers with oedematous surroundings. Histoplasmosis, cryptococcosis, mucormycosis, geotrichosis and aspergillosis can all occur and usually signify poor prognosis. Candida dubliniensis has been recently shown to be also capable to cause oral candidosis in HIV-positive individuals.
The collapse of the cellular immunity, which is among other things responsible for anti-cancer defence, leads to a more common development of tumours in HIV-positive patients. The typical tumours include the Kaposi’s sarcoma, non-Hodgkin malign lymphomas and squamous cell carcinoma of the oral mucosa, in particular the tongue.
This is the most common tumour in AIDS patients, occurring in approximately 20 % of them. Currently, it is considered a disease of infectious origin caused by human herpes virus HHV-8. It affects primarily the skin, lymph nodes, organs and oral mucosa, with predilection to males (male:female ratio of approx. 8:1). Many papules, nodules and tumorous lesions with purple or livid discoloration appear on the skin. Oral mucosa is affected only in some patients, usually only after cutaneous manifestations of Kaposi’s sarcoma. It can however, in rare cases, primarily affect the oral mucosa. Lesions in the mouth can be solitary as well as multiple, usually forming red or red-brown macules or papules, later elevated plaques or small tumours that can ulcerate. Most commonly, gingiva and the oral floor are affected, followed by the tongue, lips and buccal mucosa.
Th.: Radiotherapy, interferon alpha, chemotherapy, surgical excision of small lesions is also possible.
Dif. dg.: Pyogenic granuloma, haemangioma, pigmented moles, malignant melanoma.
These represent the second most common malignant disease in HIV-positive individuals. Most lymphomas originate from B-cells and clinically manifest as inflammatory swelling that can ulcerate. Usually, it affects the gingiva and the palate.
This group includes many afflictions, the most common of which are lesions similar to aphthae (so-called aphthoid ulcerations), drug-induced reactions (ulcerative, lichenoid, toxic epidermolysis) and diseases of the salivary glands.
This disease affects salivary glands (parotid gland in particular). Its symptoms are similar to those of the Sjögren syndrome.