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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Common Lip Diseases: A Clinical Guide is a comprehensive medical atlas designed to enhance the understanding and management of various labial pathologies. This guide is specifically tailored for dentistry students, dentists, and dermatologists, offering a clear and concise overview of common lip diseases, organized by etiology for easy reference.
The atlas covers a wide range of conditions, including infectious and inflammatory cheilitis, traumatic lip diseases, and systemic immunological disorders like lichen planus and pemphigus vulgaris. It also addresses labial manifestations of systemic diseases, vascular pathologies, and potentially malignant disorders such as squamous cell carcinoma. Additionally, the guide explores pigmented lesions and introduces innovative treatment protocols like phototherapy and photodynamic therapy.
Key Features
- Quick and easy-to-read medical reference
- Covers several conditions of the lips
- Several detailed images
- Case studies for understanding outpatient clinical practice
With its didactic approach, this atlas is an invaluable resource for medical professionals seeking to advance their basic knowledge in oral medicine.
Readership
Students and professionals in training in the fields of medicine, dentistry and dermatology.
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Seitenzahl: 262
Veröffentlichungsjahr: 2024
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PREFACE
Oral pathology is a specialized medical branch that is continuously evolving, thanks to the expansion of current knowledge and increasing clinical experience.
Progressive patient care in oral medicine requires a thorough knowledge of many disciplines of medicine and dentistry. Similarly, other related medical branches benefit from their understanding and insight into overall patient management. Therefore, a key aspect of this branch is that it bridges the gap between dentistry and medicine. For this reason, the authors have chosen the lip as the anatomical district of interest because, even today, there is no clarity on the relevance of the specialized medical figure. Often, patients do not know that it pertains to the oral cavity; therefore, the dentists specializing in oral pathology and often dermatologists, not being specialized in this anatomical field, do not have great expertise in these pathologies that also have manifestations in the mucous membranes of the oral cavity.
Therefore, the primary objective of this atlas is to provide the reader with a very didactic text that is easy to read and a quick reference that aims to update the most common pathologies of the oral cavity with lip manifestation.
Furthermore, the importance of the diagnosis of some pathologies, including actinic cheilitis, was underlined, due to the risk of neoplastic evolution. In the text, some lip manifestations of systemic immunological diseases have been extensively discussed, including lichen planus, erythema multiforme, pemphigus vulgaris, and vitiligo, which, if not diagnosed, can have very serious outcomes.
Finally, the last chapter is a brief overview of our outpatient clinical practice, based on the treatment of the most common lip diseases by phototherapy and photodynamic therapy (PDT), which are widely chosen by patients for their advantages over other surgical and pharmacological ablative therapies. We trust you will enjoy reading and using this little atlas as much as we enjoyed writing it.
Infectious and Inflammatory Cheilitis
Martina Salvatorina Murgia1,*,Cinzia Casu1,2,Germano Orrù1Abstract
A broad spectrum of infections can occur in the oral cavity. These can be classified according to the etiological agent in bacteria, viruses and fungi. The most common bacterial infections are more putative in the hard tissues of the teeth, the pulp organ and periodontal tissues. Fungal infections are caused by opportunistic fungi that are generally present in the oral microbiota. In the oral and perioral regions, they are mainly attributed to Candida albicans. As far as viral infections are concerned, the oral and perioral cavity can be infected with numerous viruses, each capable of determining a rather distinct clinical-pathological picture. Herpes viruses are the most common and, in most cases, cause local disease in the short term. Human papillomaviruses are responsible for clinically distinct, rosy-white, exophytic verruca-papillary lesions with a typical surface alteration that gives a granular or cauliflower appearance.
INTRODUCTION
Patients with oral viral infections are a common finding in outpatient clinical practice. Both primary and secondary or recurrent injuries can be extremely painful and debilitating, especially in patients with systemic diseases. The most common of the viral lesions is herpes simplex virus (HSV) infection. Secondly, oral lesions associated with the human papillomavirus stand out. HPV-associated oral lesions include verruca vulgaris, focal epithelial hyperplasia, and condyloma acuminate. Bacterial infections of the oral cavity can be divided into non-odontogenic and odontogenic. The most common odontogenic infections are caries, gingivitis, periodontitis, endodontic infections, dental abscesses and pericoronitis. Bacteria present in dental plaque are the most common cause of odontogenic infections. Oral candidiasis is the most commonly encountered superficial oral fungal infection. In fact, about 70% -80% of fungal infections are caused by Candida albicans, a fungus normally present in the flora of the digestive and vaginal tract of humans. Other Candida species, such as C. glabrata and C. tropicalis, represent approximately 5% and 8% of those reported. Therefore, this chapter focuses on the infectious pathologies of the labial mucosa
most frequently encountered in outpatient clinical practice: herpetic and HPV-related viral infections and Candida albicans fungal infections.
Herpes Simplex Infections
Primary Herpetic Gingivostomatitis
Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) represent a group of nine double-stranded DNA herpesvirus (HSV) species belonging to the Herpesviridae family [1]. The first type mainly infects the orofacial region, and the second type infects the genital area. HSV-1 is globally endemic, but recent studies in the literature report that it is becoming more common than HSV-2 as a cause of genital mucosal infections in young women [2, 3].
Primary oral HSV-1 infection is characterized by a productive infection and lytic activity directed against epithelial cells and limited to the viral entry site. The resulting local inflammatory process, possibly enhanced by bacterial co-infections, leads to the development of primary herpetic gingivostomatitis after an incubation ranging from 2 to 20 days [4]. A vesicular rash develops on the affected area, the vesicles of which very quickly result in very painful confluent ulcers. The typical red color is due to the hypervascularization of the underlying connective tissue that occurs as a result of inflammation, while pain is related to the loss of integrity of the epithelial barrier with consequent exposure of the underlying sensory nerve endings [4]. Initial lesions gradually increase in diameter, favoring the formation of coalescing central ulcerations due to the exposure of the lamina propria and underlying connective tissue [5]. The ulcerations are covered with yellow-gray pseudomembranes. Adjacent lesions can fuse to form irregular ulcerations [5]. Primary herpetic gingivostomatitis is often accompanied by local lymphadenopathy. The lesions can appear on the skin, vermilion and oral mucosa. Intra-oral lesions can affect the palatal, lingual, gingival mucosa and, less frequently, the pharyngeal (with pharyngotonsillitis) and nasal (with rhinitis) mucosa (Fig. 1) [5, 6]. Clinically, there is widespread gingival edema. Ulcers gradually heal in about 10-14 days in the absence of scarring [7, 8]. Perioral lesions occur in three-quarters of patients with primary herpetic gingivostomatitis affecting the lips, cheeks and chin [7]. Occasionally, ocular (ocular herpes or herpetic keratoconjunctivitis) and digital (herpetic whitlow) infections may also occur [9]. The development of primary herpetic gingivostomatitis is often preceded by generic, non-pathognomonic signs and symptoms, such as fever, chills, nausea, loss of appetite, lethargy, irritability, general malaise, and headache. Sometimes, prodromal symptoms are the only signs of primary HSV-1 infection, and sometimes, they can be so mild (or even absent) that those affected do not remember it [4]. Older adults who develop primary herpetic gingivostomatitis usually show mild lesions and an absence of lymphadenopathy. In contrast, primary herpetic gingivostomatitis among young adults is statistically more severe [10]. Primary herpetic gingivostomatitis is generally mild or asymptomatic since productive infection (i.e., viral replication) and lytic activity are minimal [4]. Peaks in incidence occur during childhood (between 5 and 6 years) and adolescence in developing countries, whereas in rich nations, the incidence is more frequent in adulthood (between 20 and 40 years) [11]. Less frequently, clinically severe forms of primary herpetic gingivostomatitis may occur, in which purpuric macular rashes and arthralgia are present. Intraoral symptoms include dysphagia and odynophagia, which may be severe enough to require hospitalization [12].
Fig. (1)) Herpetic lesions in the vesicular phase involving all the intraoral mucous membranes in a young patient.Herpes Labialis
Herpes labialis is the most common recurrence in immunocompetent individuals. Recurring extra-oral herpes can affect any site along the sensory area innervated by the trigeminal nerve, including the skin of the nasal pyramid, chin, or cheek, although the vermilion and mucocutaneous lip junction is the most commonly involved [13]. The first clinical symptom is a vesicular rash. Subsequently, these vesicles give rise to irregularly shaped coalescing ulcers (Figs. 2 and 3). After about 3-4 days, the lesion evolves into the crusted phase with consequent healing in the absence of scarring within 1-2 weeks [8]. The average area affected is 70 (range 4-250) mm2; in most cases, it is less than 100 mm2. The average duration of the lesion is 7 (range 2-16) days. Peak pain occurs at the onset, then gradually recedes until it disappears after 4-5 days. Virus transmission is at a peak immediately after the rupture of the vesicles, which then persists for 2-3 days and can also continue after the resolution of clinical signs. Herpes labialis can coexist with recurrent herpetic stomatitis [4]. Usually, an average of three to four episodes occur per year. Recurrent cold sores are more common in women than men and in younger individuals [14]. Reactivation can be triggered by various factors such as emotional or physical stress, trauma, iron deficiency, ultraviolet light exposure [15], and dental procedures [14], as well as by important immunodeficiency states such as in HIV patients, especially in cases of injury highly relapsing and therapy-refractory herpes [15]. For this reason, the dentist must obtain the patient’s detailed medical history so that, where necessary, they can encourage the patient to carry out the appropriate investigations.
Fig. (2)) Herpetic lesions in the crusty phase in the right hemi-lip.The standard diagnosis of herpetic infection is based on the patient's clinic and medical history. However, a confirmatory laboratory diagnosis is necessary if the clinical characteristics are atypical, especially in cases of recurrent herpetic lesions that are refractory to therapy. For this reason, in case of suspected immunodeficiency, a careful medical history must be obtained by the dentist, who can encourage the patient to carry out appropriate investigations.
Fig. (3)) Young girl with herpes labialis of the upper lip in the vesicular stage.A great variety of investigations can confirm the diagnosis; however, those based on cytological and tissue culture techniques have now been flanked by more accurate and potentially cheaper molecular biological methods. In the presence of clinical lesions, the examination can be completed with the direct evaluation of the virus through culture or molecular examination. The laboratory test for HSV-1 / HSV-2 can be performed through the use of microscopic [16-18], cultural [19], serological [20] and molecular methods [21]. Historically, direct light microscopy of patient samples has been widely used for its simplicity [22]. However, the use of viral culture has significantly improved diagnostic sensitivity [23]. The latter has further increased over time with the addition of modified culture methods and molecular assays. The management of herpetic infections is related to the frequency, severity and distribution of lesions as well as the presence of systemic pathologies that can aggravate their course. Topical nucleoside antivirals are the standard treatment of recurrent herpes labialis, both in terms of reduction of healing time and symptoms [24]. Valaciclovir, in particular, is more effective than acyclovir, especially in reducing healing times [24]. However, the most serious adverse effects of antiviral agents are nephrotoxicity [25] and neurotoxicity, especially in patients with prior renal disease [26, 27]. Rare cases of thrombocytopenia have also been described [28]. For this reason, in recent years, photo-stimulating therapies have been tested, which have shown excellent results both in vitro and in vivo [29]. In fact, photo-stimulating therapies do not present side effects, so they can be applied in immunosuppressed patients or with systemic diseases [29]. Although a great variety of parameters for LLLT is reported in the literature, it is characterized by non-thermal irradiation, with wavelengths considered biostimulants in a range between 380 and 780 nm and with power between 1-10 J / cm2 [30]. Numerous studies in the literature confirm that LLLT is effective in the treatment of relapsing herpetic lesions [31], even in comparison with acyclovir [32]. Furthermore, photodynamic therapy, which makes use of specific photosensitizers, has given numerous positive results in the treatment of herpetic lesions [33-36]. Dye sensitizers are mainly porphyrrinoid compounds, including chlorine, bacteriochlorin, phthalocyanines and related structures [37]. Their great advantage, related to the absence of side effects, is the ability to tightly bind only to infected cells and not to healthy ones [37-39].
VZV-associated Oral Lesions
Primary varicella-zoster virus (VZV) infection in serum-negative individuals is known as chickenpox and typically affects preschool children [40, 41]. Secondary disease or reactivation of the virus is known as herpes zoster (HZ) or shingles [42, 43]. Structurally, VZV is very similar to HSV, consisting of a DNA core, a protein capsid, and a lipid coat [43]. Furthermore, the ability of the virus to remain quiescent in the sensory ganglia after primary infection for an indeterminate period of time is a common feature [43]. The early manifestations of chickenpox are pharyngitis, rhinitis, fever and asthenia. An itchy rash then appears on the face, trunk, and extremities [44]. Maculopapular lesions result in vesicles, pustules and crusted eruptions [45]. Oral manifestations, which may precede cutaneous ones, consist of small whitish vesicles that evolve in ulcers, typically in the palate and attached gingiva [46-48]. The diagnosis of chickenpox is mainly clinical [45]. Viral or serological investigations are rarely prescribed. Therapy is essentially symptomatic. Furthermore, antivirals are not routinely indicated [45]. As regards the clinical manifestations of HZ, they include multiple vesicular eruptions extending up to the midline, with a metameric distribution, which evolve into ulcers and prolonged erythema (Fig. 4). Prodromal symptoms include fever, general malaise, and pain in the involved dermatome [49, 50]. If the trigeminal nerve is affected, there may be involvement of the oral tissues and the overlying ipsilateral skin. Intraoral lesions appear as diffuse ulcerations extending up to the midline [51, 52]. The involvement of the facial and acoustic nerves determines the onset of Ramsay Hunt Syndrome [53]. Again, the diagnosis is mainly based on clinical aspects. In doubtful cases, cytological and culture tests are useful [54]. The elective therapy is based on the administration of high doses of aciclovir, especially in immunosuppressed patients [54]. Supportive therapy with antipyretics and painkillers is useful [54].
HPV-associated Oral Lesions
Verruciform Xanthoma
Verruciform xanthoma is a rare benign mucocutaneous lesion [55-57]. Its etiology is unknown, although trauma, inflammation and immune system alterations have been proposed [58]. Verruciform xanthoma is a well-circumscribed lesion with a granular or papillary appearance [58]. The dimensions range from 2 mm to more than 2 cm [58, 59]. The surface may be exophytic or depressed, occasionally crateriform (Fig. 5). Keratinization's degree determines its color, which can vary from white to red [60, 61]. According to a recent study, the female: male ratio is 1.06:1 [62]. The most common locations are the gingiva (51.2%), palate (19.3%) and tongue (9.4%) [63]. Associations with other pathologies have been reported in the literature, including discoid lupus erythematosus, pemphigus vulgaris, dystrophic epidermolysis bullosa, lichen planus, Snuff Dipper keratosis and CHILD syndrome [64]. The diagnosis is confirmed by histopathological examination [62]. However, several cases of labial verruciform xanthoma are described in the literature [63, 65-67]. Differential diagnosis includes squamous papilloma, verruca vulgaris, fibroma, leukoplakia and squamous cell carcinoma [62, 66-68]. Surgical excision is the treatment of choice [68].
Fig. (4)) Initial aspect of varicella-zoster infection involving the upper lip.Condyloma Lata
Oral condyloma lata is one of the many manifestations of secondary syphilis [69, 70]. The clinical manifestations are papillary or polypoid, exophytic and sometimes friable lesions [69-71]. Sometimes, condyloma lata can look like an ulcer [56]. The surface is generally lobed or smooth. Palatal, lip and tongue localizations are described in the literature [72, 73]. A peculiar feature of this manifestation is the absence of painful symptoms [69-71]. The general medical history can be conclusive in these cases, especially in the presence of risky sexual behavior or positivity to other sexually transmitted diseases. Serological testing remains the gold standard for diagnosis; the most prescribed is the Venereal Disease Research Laboratory (VDRL) test [69, 70]. In addition, FTA-ABS (Fluorescent Treponemal Antibody Absorption) is used as a confirmation test associated with VDRL [69, 70]. Treatment consists of the administration of systemic antibiotic drugs [72, 73].
Fig. (5)) Verruciform xanthoma of the lower lip (courtesy of Dr. Treville Pereira, Mumbai, India).Human Papillomavirus Infection Lesions
Human papillomaviruses (HPV) are double-stranded DNA viruses with no envelope that preferentially infect epithelial cells [74, 75]. There are numerous viral subtypes, some of which cause benign lesions commonly known as warts; others, defined as high risk (HPV 16 and HPV 18), cause some cancers of the oral cavity [76] and cervix [77]. The HPV-related lesions of the oral cavity include squamous papilloma, condyloma acuminatum and multifocal epithelial hyperplasia.
Squamous Papilloma
Oral squamous papillomas are common lesions [74]. They occur more frequently in adults [78, 79], however, children can also be affected [80-82]. All the sites of the oral cavity can be involved; the most frequent are the tongue, the palate, the lips and the labial commissures (Fig. 6) [83]. The clinical symptoms are an exophytic lesion with a typical “cauliflower” appearance [84]. They can be sessile or pedunculated, pinkish-white in color [85]. They generally have a diameter of less than 1 centimeter and are asymptomatic. In most cases, they are single lesions, more rarely multiple [85]. Diagnosis is initially clinical, confirmed by histopathological examination following excisional biopsy. Differential diagnoses include giant cell fibroma, papillary squamous cell carcinoma, condyloma acuminatum, multifocal epithelial hyperplasia, and verruciform xanthoma [85]. Verruciform xanthoma may be clinically very similar to squamous papilloma but typically occurs in the adherent gingiva and edentulous alveolar ridges [55]. The inflammatory papillary hyperplasia differs because it is always characterized by a cause-effect relationship (for example, incongruous prosthesis) [86]. The condyloma acuminata is usually larger and sessile, pinkish-red in color, depending on the degree of keratinization [84]. The classic treatment involves surgical excision [74]. However, laser excisions are described in the literature [82, 87-90], especially in pediatric patients [91]. A recent retrospective study found that recurrence rates for squamous oral papillomas treated with a surgical scalpel and two different lasers (CO2 or Er, Cr; YSGG) are low in all treated cases [92].
Fig. (6)) Squamous papilloma on the lip commissure in an adult woman. The typical whitish color is due to the marked keratinization of the lesion cells.Condyloma Acuminatum
Condyloma acuminatum is an infectious lesion that typically involves the anogenital region but which can also be observed in the oral cavity [93, 94]. This lesion is etiologically related to HPV virus subtypes 6 and 11 [93]. Clinically, small pink nodules appear at the onset and then tend to merge. Subsequently, a papillary, exophytic and sessile lesion appears (Fig. 7) [93, 95]. It is often associated with HIV-positive patients, reflecting the opportunistic and sexually transmitted nature of the infection [96]. The lips are often involved [95, 97]. Differential diagnosis includes focal epithelial hyperplasia, vulgar wart, Heck’s disease and condyloma lata [98]. Diagnosis is based on clinical and histopathological examination. However, PCR sequencing of the tissue sample for HPV detection and identification of its specific genotype is required to make the definitive diagnosis. The classic treatment involves their surgical removal [99]. Relapses are quite common, occurring in 20-30% of cases in the same area or in other locations [99].
Fig. (7)) Flat condyloma acuminatum in the lower lip in a young man.Multifocal Epithelial Hyperplasia (Heck’s Disease)
Multifocal epithelial hyperplasia (Heck's disease) is an endemic, rare, asymptomatic and benign oral disease. This condition is common in certain geographic areas of Central America [100, 101]. Children and adolescents are more frequently affected, although cases have been reported in adulthood [102]. There are numerous etiological hypotheses, including local irritating factors and vitamin deficiencies [103]. PCR-based studies have shown that genotype 13 and, to a lesser extent, genotype 32 are frequently detected in these lesions [103-105]. Clinically, multiple lesions ranging in size from 1 to four mm are detectable. These have a papular appearance and a color similar to the surrounding mucosa (Fig. 8). The lesions are asymptomatic and soft on palpation [106]. The diagnosis is initially clinical and then confirmed by histopathological examination [106]. Differential diagnoses include condyloma acuminatum, Cowden syndrome, tuberous sclerosis, molluscum contagiosum and multiple squamous papillomas [102]. Treatment is generally unnecessary because Heck’s disease tends to regress spontaneously and is asymptomatic. For aesthetic reasons, lesions can be removed by surgical excision or laser [107]. However, long-term follow-up is necessary [103].
Fig. (8)) Focal labial epithelial hyperplasia in a healthy 12-year-old Hispanic girl (courtesy of May Elgash, Oregon, USA).Bacterial Infections
Infectious diseases of the skin and oral tissues are common, often self-limiting, although they can sometimes lead to more serious complications [108, 109]. The most common etiological agent is Staphylococcus aureus (S. aureus) [108-110]. S. aureus is a gram-positive, facultative anaerobic cocci bacteria [111]. It can cause limited and localized infections (e.g., skin abscesses) or serious systemic infections (e.g., fatal pneumonia and sepsis), especially in immunocompromised patients [111]. Furthermore, some strains of S.aureus have developed resistance to beta-lactam antibiotics, which further complicates the management [112]. There are several cases of S.aureus labial infection described in the literature [113, 114]. Small localized infections are commonly encountered in daily clinical practice (Fig. 9). Treatment of S.aureus infections depends on the severity and the patient's immune status. Circumscribed purulent infections are treated with incision, drainage, and antibiotic therapy.
Fig. (9)) Small abscess in the right labial commissure in an elderly woman.Fungal Infections
Angular Cheilitis and Candidiasis
Angular cheilitis refers to an inflammatory pathology affecting the angle of the labial commissures, also called angular cheilosis, angular stomatitis and perlèche (Figs. 10-13) [115]. AC prevalence is 0.7% in the American population, and it is the most common fungal infection of the lips [116, 115]. The most clinical symptoms are extremely painful fissures with a tendency of local bleeding of one or both of the labial commissures involving mucous and skin [115]. Ulcers, scabs, erythema and maceration may be present [117]. Cheilitis can be further divided into dystrophic (nutritional or vitamin deficiencies), traumatic, and infectious [115]. The etiology includes many causes, such as the decrease in the vertical dimension due to lack or severe wear of the teeth or incongruous prostheses resulting in an overclosure [115, 118], presence of deep or physiological wrinkles [117], and retrognathic occlusion [115, 119]. It also occurs more frequently in patients who tend to lick their lips [119]. Nutritional deficiencies, for example, of zinc, vitamin B6 and iron, are also associated [120-122]. Angular cheilitis typically occurs in patients with pre-existing systemic conditions such as chronic hepatic failure [123], diabetes [124], celiac pathology [125], Crohn’s disease [126], and conditions that cause an increase in salivation [118, 127]. In addition, it can rarely be a drug-related complication [128, 129]. Also, hyposalivation also leads to a greater risk of developing angular cheilitis. In fact, a recent observational cross-sectional study carried out on 61 patients with Sjögren’s syndrome showed that prosthetic stomatitis and angular cheilitis were the most common lesions present [130]. Finally, angular cheilitis develops more frequently in patients with compromised immune status [131, 132], especially in pediatric HIV-infected patients [133]. As regards the specific microbiological flora for angular cheilitis, Candida albicans, Candida stellatoidea, Staphylococcus aureus and Streptococci are the most frequently detected species [133]. The therapeutic options are many: first of all, the first step involves obtaining an adequate medical history aimed at identifying the predisposing risk factors. Reduced vertical dimension (due to lack of teeth or incongruous prostheses) must be corrected. Any presence of physiological or other cause induced xerostomia should be treated through adequate dietary plans or salivary substitutes. Topical antifungal therapy is the most frequently prescribed treatment [117, 134]. However, numerous other therapies are described in the literature. For example, a recent study evaluated the topical application of ozonized olive oil in numerous oral soft tissue diseases including angular cheilitis with good results and no side effects [135]. Another very interesting study carried out on a single patient suffering from acute lymphoblastic leukemia with extremely painful angular cheilitis showed that combined treatment with antifungals and photodynamic therapy using a 660 nm diode laser and methylene blue as photosensitizer and low level laser therapy (LLLT) result in complete healing of the lesion, disappearance of pain and absence of side effects [136].
Fig. (10)) Angular cheilitis in a female patient present for about 6 months. Erythema, fissuring and desquamation of the commissure are highlighted. Fig. (11)) Angular cheilitis in a patient with significant reduction of the vertical dimension due to the lack of upper and lower molars. Fig. (12)) A 27-year-old girl affected by angular cheilitis in the left labial commissure. Fig. (13)) Pseudomembranous candidiasis in the oral mucosa in a 56-year-old patient.
