Glossodynia

ELSEVIER

Journal of the European Academy of Dermatology and Venereology 7 (1996) 207-227

Continuing

medical education

Glossodynia Giuseppe Hautmann, Emiliano Panconesi * Department

of Dermatology,

Uniuersity

1. Introduction The term “ glossodynia” (GD) is derived from the Greek “glossa” for tongue, and “odyne” for pain. The earliest references are attributed to Buisson (1854), Schwimmer (1886) and Magitot (1887) [l--3], but perhaps one very good definition is that of Oppenheim [4] who wrote in 1913 of a . . . “ paraesthesia, particularly a burning and prickling sensation on the tongue extending perhaps to adjacent membranes. It may be continuous, paroxysmal, and may even disturb the sleep . . . . Nothing is found on examination”. Although investigators agree on the normal appearance of the tongue, opinions differ on what constitutes GD. Fox [5] restricts the term to those cases with a psychogenic or idiopathic cause, but others [6-91, like us, include cases with an identifiable cause. The International Association for the Study of Pain (IASP) definies GD as a “burning pain in the tongue, involving the tip and lateral borders of glossal mucosa, palate, lips, and other buccal mucosa often associated with odd taste, dry mouth, uncomfortable bite or denture intolerance” [lo]. We prefer to consider GD as a symptom, according to the definition of the IASP, without specifying the eventual presence of clinical signs and, thus, the tongue may or may not present a

* Corresponding author. Clinica Dermatologica, Via Alfani, 37, 50121 Florence, Italy.

of Florence,

Florence,

Italy

normal appearance. GD is not a disease sui generis, but a symptom. In the scientific literature a variety of terms are used to describe similar symptoms, such as glossopyrosis, pain in the tongue, burning tongue, orodynia, burning mouth syndrome, glossalgia, stomatodynia, oral dysesthesia and even “oral galvanism”. Generally, these terms describe symptoms of an unexplained, prolonged sensation of pain and/or burning in the mouth. The so-called syndrome of “oral galvanism” describes a situation of chronic pain or atypical taste sensations in the mouth due to metal taste and galvanic currents caused by metal (mainly amalgam and non-precious alloys) used in dental work. In spite of what appears to be an etiology, the syndrome has characteristics similar to those of GD and can often be considered as a variant [ll-161.

2. Incidence and clinical characteristics The true incidence of GD is unknown: in fact, this is partly due to the lack of unanimity concerning the definition, and partly due to the fact that subjects with GD present to a variety of specialists (dentists, dermatologists, neurologists, psychiatrists, otorhinolaryngologists), with different patterns of presentation to each speciality. The age of initial onset is usually between 40 and 60 years; it appears only rarely before the age of 30 years, and never in children or adolescents.

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The typical GD patient is a middle-aged woman. Nearly all investigators report a strikingly higher percentage of women suffering from the syndrome, up to 90%. Symptoms usually occur in more than one site of the mouth, with the tongue as the most common site of sensation. Other areas include lips, palate, buccal mucosa, upper and lower denturebearing tissues, throat and pharyngeal cavity 117-291. The prevalence of oral sites at which a burning sensation occurs has been reported to be: tip of tongue (78%), anterior two-thirds of tongue (58%), ventral side of tongue (17%), posterior third of tongue (1 l%), floor of mouth (13%), anterior third of hard palate (49%), posterior two-thirds of hard palate (26%), soft palate (6%), orophatynx (13%), mucosal portion of lower lip (24%), mucosal portion of upper lip (18%), lower alveolar ridges (25%), upper alveolar ridges (24%) and buccal mucosa (14%) 1281.The patient may complain of pain despite the absence of any observable lesion on the tongue or elsewhere in the mouth. The surface of the tip of the tongue is often smooth and atrophic from constant rubbing against the front teeth. The symptoms are often poorly localized. Characteristically, the pain does not interfere with eating or sleeping and usually occurs only during the day [30]. A sour or bitter taste often accompanies the burning. Patients with chronic GD commonly describe all of the physicians and dentists consulted previously and the unsuccessful treatments prescribed [3 11. Most patients suffer from the syndrome for a long time, ranging from months up to 18 years [23,25,28]. The onset was reported to be gradual for 63% of the subjects and sudden for the others 1281. Although many patients tend to relate the onset of symptoms to previous dental procedures (up to 70%) (e.g., extractions) or to a previous illness (up to lo%), up to 57% could not relate it to any prior event.

3. Etiology Several causes have been proposed as possible etiologic factors for GD including local irritation by environmental factors, such as denture base, oral parafunction, deficiency states, hormonal changes occurring in menopause, change in salivary composi-

tion, candidiasis, and diabetes. Nevertheless, studies conducted comparing GD patients with age and sexmatched control subjects have provided little support for some of the earlier proposed etiologic factors, such as dentures, oral habits, candidiasis, nutritional deficiency. Furthermore, different sensory modalities (tests of touch, two-point discrimination, warmth scaling, and oral stereognostic ability) have showed no significant differences between the two groups [28]. Moreover, GD may be associated with a wide variety of clinical conditions which can be classified etiologically (Table 1). Although it is not uncommon for several conditions to be implicated (and consequently diagnosis and management can be complicated), we point out that the importance of systemic problems as a cause of GD (for example anemia or nutritional deficiencies) is, in view of all those authors concerned with such patients, almost always overrated. Table 1 presents a possible etiological classification of GD and we will discuss each item below. Our classification makes a distinction between “glossodyna syndrome” (GDS) and “glossodynia disease” (GDD). With the term “GD syndrome” we mean that glossodynia is a symptom that accompanies another well-defined illness (we may also use the term “symptomatic glossodynia”), with clinical and histological features that may be present at the onset of the glossodynic symptomatology or may present later. The term “GD disease” refers to a picture that is characterized only by the subjective glossodynic symptom without any other signs of disease for the entire duration of the disease. Obviously, this distinction between GD syndrome and GD disease is an attempt to clarify the possible etiopathogenesis of this still unclear symptom. Very careful follow-up is necessary to verify whether the patient has GD syndrome or GD disease. In fact, as mentioned below, the clinical features of well-known diseases may present some years after the onset of the glossodynic symptom. So, we believe that in most cases a follow-up of about 3 years must be done before establishing if the glossodynic symptom is a manifestation of GD disease (idiopathic GD) or an accompanying symptom of a disease (GD syndrome). Nevertheless, the suggested 3 years of follow-up were arbitrarily established by us. (1) Denture factors are commonly implicated.

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Table 1 A possible etiological classification of “glossodynia”

Table 1 (continued)

(I) Glossodynia syndrome (symptomatic glossodynia)

(II) Glossodynia disease (idiopathic glossodynia)

Denture factors ill-fitting dentures dental plaque residual monomer irritant

Psychological cancerophobia debility-induced neurosis depression

Deficiency states Iron Vit. B12 Folate Vit. B2 (riboflavine) Vit. B6 (pyridoxine) Zinc

Idiopathic

Endocrine disorders diabetes myxedema sex steroid hormones menopause Neurologically mediated disorders referred from tonsils/teeth neuropathy of the lingual nerve glossopharyngeaf neuralgia esophageal reflux Menopause Xerostomia diabetes scleroderma Sjogren’s syndrome systemic lupus erythematosus radiation therapy chemotherapy pharmacologic agents over-the-counter products caffeine alcohol dws latrogenic mouthwash pharmacologic agents Skin diseases with oral involvement and oral diseases lichen planus erythema multiforme candidiasis herpes virus infections aphthous stomatitis pemphigus vulgaris benign migratory glossitis squamous cell carcinoma

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There have been reports of ill-jitting dentures in 50% of cases [S]. Dental plaque and a high monomer content in the denture have also been suggested as contributing factors [7]. In the absence of macroscopic change, the exact mechanism is unclear. It is probable that the pressure exerted by the dentures on the underlying mucosa causes minimal changes in the sensorial nerve ending fibers, resulting in previously non-noxious stimuli producing a burning sensation [32]. For Brightman, muscular tension plays an important role [33] and McCabe and Basker report two cases attributable to the irritant effect of the high monomer content of dentures [34]. (2) It is well known that macroscopic changes in the tongue (swelling of the tongue, papillary atrophy, surface ulceration) can occur as a result of deficiencies of iron, folic acid or vitamin B12, but it is less well appreciated that a prodromal GD can precede any macroscopic change. Similarly, inadequate riboflavine, pyridoxine and zinc have all been described as causes of GD [35-371. Iron d&iency. The most common cause of anemia is iron deficiency [38]. An estimated 9% of women in the United States between the ages of 25 and 44 suffer from iron deficiency [39]. The prevalence of this deficiency among women is related to the increased need for iron during pregnancy and menstruation [40]. Burning or soreness of the tongue is reported to occur in about 39% of these cases [41]. Iron deficiency may result from inadequate dietary iron intake, malabsorption, blood loss, or rarely intravascular hemolysis with hemoglobinuria. Typically, the tongue of an anemic patient will exhibit papillary atrophy (filiform and fungiform papillae) and a smooth surface; progressively, the dorsal surface of the tongue becomes smooth and glistening. The tongue atrophy may be patchy or

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generalized. Candidiasis and angular cheilitis are common findings, but rarely do leukoplakia or superficial erosions develop. These tongue manifestations must be differentiated from those found in course of pernicious anemia, geographic anemia, atrophic lichen planus, atrophic glossitis of tertiary syphilis and other malnutrition disorders. The patient with iron deficiency also may experience fatigue and weakness, anorexia, headache, pallor of skin and mucosae. About 7% of patients with iron-deficiency anemia will develop Plummer-Vinson syndrome [41]. The syndrome is marked by the presence of dysphagia caused by an esophageal stricture or web, koilonychia (spoon-shaped nails), and glossitis [42]. Early recognition and treatment is important because patients with Plummer-Vinson syndrome have a 10% risk of developing esophageal carcinoma [43]. The diagnosis of iron deficiency is based on several available laboratory tests. A peripheral blood smear will show hypochromic, microcytic erythrocytes. Plasma ferritin will be less than 40 pg/lOO ml, and trasferrin saturation will be less than 10% [43,44]. Iron deficiency is generally corrected with oral administration of ferrous sulfate, 300 mg 3 times/day. Folic acid deficiency. Folic acid deficiency is usually the result of insufficient dietary intake. It is estimated that up to 20% of pregnant women suffer from this deficiency [45]. Other patients at risk include alcoholics, hemodialysis patients, the elderly, and patients taking certain drugs, such as phenytoin and oral contraceptives, that interfere with the absorption and storage of folate in tissues [41,46,47]. Malabsorption states, such as tropical and non-tropical sprue, also can cause folic acid deficiency [48]. Complaints of persistent GD occur in up to 90% of these cases [40]. The glossal changes related to folic acid deficiency are indistinguishable from those caused by deficiency of vitamin B12 [49]. Thus, the clinician may observe glossitis with papillary atrophy; there are reports of early glossal swelling with pallor followed by atrophy of filiform papillae and reddening of the fungiform papillae. Sometimes, there are aphthous-like ulcerations 148,501. As the deficiency persists, the dorsal surface of the tongue may develop a typical bald, shiny, smooth, raw appearance. The patient with folic acid deficiency commonly

presents macrocytic anemia, that resembles pemicious anemia. However, intrinsic factor is not absent in macrocytic anemia [38,49,51]. Folic acid deficiency treatment consists of 0.1-30 mg/day folic acid administered orally. Inappropriate administration of folic acid can mask the progression of vitamin B12 deficiency, and even exacerbate existing vitamin B12 deficiency, because it is not uncommon for a patient to present both folic acid and vitamin B12 deficiencies [52,53]. Vitamin B12 deficiency. The most common cause of vitamin B12 deficiency is pernicious anemia [41]. This is a megaloblastic anemia, usually caused by a gastric mucosal defect that decreases the synthesis of intrinsic factor, which is required for intestinal uptake of vitamin B12. Other less frequent causes of pernicious anemia are total gastrectomy, pancreatic dysfunction, parasitic diseases and diseases of the ileum, all of which interfere with vitamin B12 absorption and antibodies against transcobalamin. Less common than acid folic deficiency, pernicious anemia is typically an affliction of the elderly [54] and is probably the result of an autoimmune process [55]. It occurs in all races, without sex predilection, usually after the 30th year of age. Symptoms may include GD, neurologic abnormalities, tingling and numbness of the extremities, weakness, difficulty in walking, pallor, malaise, lassitude, weight loss, gastrointestinal upset 1561. Burning sensation of the tongue and taste loss are early symptoms. In fact, signs and symptoms related to the tongue are estimated to occur in 50-60% of cases of pernicious anemia. The tongue may show glossitis and varying degrees of papillary atrophy (filiform and fungiform papillae) 156,571. Initially, only the tip and lateral margins of the tongue are red and atrophic; if left untreated total papillary atrophy, which results in a smooth, bald, and fiery-red surface, can occur. Dorsal surface lobulations, generalized surface ulcerations and dysgeusia also may occur [57]. Laboratory tests generally reveal macrocytic anemia (mean corpuscular volume greater than 100 pm3), a low serum assay of vitamin B12 (less than 100 pg/ml) and absence of intrinsic factor as determined by the Schilling test [54], that measures urinary excretion of radioactive vitamin B12 (administered first without intrinsic factor and then with intrinsic factor). In pernicious anemia, urinary excre-

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tion of radioactive B12 without intrinsic factor will be less than 5% [45]. Treatment consists of regular parenteral administration of vitamin B12 every 2 months for life [51,54,57]. The oral signs and symptoms of the disease may resolve 48 h after the first adminstration of vitamin B12. Although it is generally accepted that these patients are at greater risk for developing carcinoma of the stomach 157,581, there are also studies that report no increased incidence of carcinoma of the stomach in patients with pernicious anemia [59]. Less common B-complex deficiencies. Niacin deficiency initially may occur as an enlargement of the papillae on the tip and margins of the tongue [50,60]. Glossal reddening, swelling, and noticeable discomfort may occur: persistence of the deficiency can lead to total papillary atrophy that creates a smooth, bald, and beefy red glossal surface [61]. A common complication is Vincent’s infection, a necrotizing infection of the gingiva 1601.Measurement of urinary excretion of methylated metabolites of nicotinic acid does not provide unequivocal evidence of deficiency. Therefore, the diagnosis of niacin deficiency is largely based on clinical findings. Riboflavin (vitamin B2) deficiency may result in seborrheic dermatitis, cornea1 vascularization and, in advanced stages, keratitis and oral lesions. The most frequent oral manifestation is angular cheilitis, which may be unilateral or bilateral. The lips appear dry and cracked. There may be swelling of the fungiform papillae and a granular glossal surface. A continued deficiency may lead to papillary atrophy and irregular areas of surface denudation [60]. Generally, the color of the tongue is magenta or purple-red color. This vitamin deficiency is marked by urinary excretion less than 50 pg/day of riboflavin [47]. Treatment of vitamin B2 (deficiency consists of 10 mg/day riboflavin administered orally. The main symptom of pyridoxine (vitamin B6) deficiency is a painful, swollen, purplish tongue. The swelling can either blot out the structure of the filiform papillae, or papillary atrophy can occur. Thus, the tongue’s rich vascularity, rapid cellular turnover rate, intimate contact with microorganisms, and exposure to physiologic trauma make it an early indicator of many nutritional deficiencies. To further complicate the clinical picture, the individual patient

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commonly suffers from multiple nutritional deficiencies [62]. Therefore, it is not advisable to diagnose a specific nutritional deficiency on clinical impression alone. (3) GD may be a symptom in course of endocrine disorders. In fact, Michael reports hypothyroidism (which, when it is congenital, may provoke macroglossia, enamel dysplasia, delayed eruption of teeth) as an endocrine cause of a burning tongue but does not propose a feasible explanation [63]. The oral effects of diabetes mellitus include xerostomia, GD, cheilitis, a reduction in salivary flow, an increase in the glucose concentration in saliva, benign migratory glossitis, a painless enlargement of the parotid glands, an increase in the incidence and severity of periodontal disease, caries, fungal and bacterial infections, taste change and delayed wound healing [64]. Any one or a combination of these signs and symptoms may indicate diabetes. In their study of 142 patients with symptoms of burning, dryness, or gingival tenderness, Brody et al. [65] found that 35% [50] patients had glucose-tolerance curves indicative of diabetes. This incidence is at least 5 times greater than the estimated incidence in the general population. Another study by Chinn et al. [66] found that 27% (12 subjects) of 45 patients with symptoms of burning, dryness or gingival tenderness had abnormally high 2 h glucose-tolerance levels. These results may be contrasted with those of Zegarelli’s study [67] of 57 GD patients, none of whom presented hyperglycemia. Moreover, the dehydration caused by diabetes also affects the salivary glands; in fact, it has been found that true xerostomia exists in diabetics [68]. Xerostomia predisposes the oral cavity to all irritations that saliva presents. Oral sensory disorders, such as altered taste (dysgeusia) or tactile response, difficulty in speech, and dysphagia, all occur as the result of a decrease in saliva. Other problems such as dental caries, periodontal disease and mucositis occur commonly [69,70]. For denture wearers such involvement in the oral mucosal barrier may lead to denture irritation and painful ulcerations which heal slowly. All of these complications lead to considerable oral morbidity. However, in Grushka’s study [28] the cause and effect relationship between xerostomia and GD was not substantiated since xerostomia was found to occur after the onset of the GD.

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Another common finding in patients with diabetes mellitus is an asymptomatic bilateral enlargement of the parotid glands [71]. This phenomenon does not appear to be influenced by the duration of diabetes, and in certain cases the enlargement precedes the onset of diabetes. The cause of this enlargement is unclear, but it may be a compensatory mechanism that results from xerostomia secondary to dehydration in diabetes. Patients’ sialograms invariably result normal, and histopathologic examination reveals fatty infiltration of the interstitium with normal acini and ducts [72]. GD may occur secondary to diabetic neuropathy and microangiopathy. The neuropathic and microangiopathic manifestationsof diabetesmay occur in the genetically prediabetic patient who has minimal glucose intolerance and none of the classic symptomsof diabetes[64]. Also, patients with glucose intolerance and the classic symptoms of diabetes have neuropathic and microangiopathic manifestations that may result in GD. In a case report by Oles [73] a patient presented with GD while in a prediabetic state that was characterized by reactive hypoglycemia. The patient’s symptomsdisappearedafter changesin diet. The symptoms were thought to be caused by localized microangiopathy to the lingual nerve that was not severe enough to cause neuropathy. The combination of microangiopathy and hypoglycemia resulted in the neuropathic symptomsof GD. Finally, several mechanismshave been suggested to account for GD in diabetesmellitus. It may be just an oral manifestation of peripheral neuropathy or microangiopathy (or the combination of these two factors) or be attributed to the increasedincidence of oral candidiasis in diabetics. Alternatively, it has been suggestedthat the lack of insulin may produce a catabolic processwithin the mucosa in responseto previously insignificant trauma [74]. Moreover, hormones in saliva and oral tissues affect overall dental and oral mucosa health. Evidence of a relationship between oral symptoms and sex steroid hormone activity comes from several sources [75-771. Although the evidence is not conclusive, the data demonstrate a strong association between these hormones and some oral symptoms, including GD. The concentration of steroid hormones in the saliva is in proportion to blood levels. Because the majority (90-98%) of plasma sex

steroids are bound, or inactive, changes in the unbound, or active, hormone may not be measurableby clinically available hormone assays.Hormone concentrations in the saliva reflect the unbound, or active, hormone levels in the serum. Sex steroid, such as androgen, estrogen, or progesterone, and cortisol levels in saliva fluctuate with diurnal and menstrual alterations, and the oral tissues are affected by the salivary as well as systemic levels of these hormones. Sex steroids have been detected bound to receptorsin the gingiva, parotid glands, and minor salivary glands following administration of triturated hormones. Thus, the presence of these receptors suggests hormone action taking place in the oral tissues. Testosterone stimulates oral epithelial growth through receptors located within the oral tissues, particularly in the gingiva. Phenytoin provokes an increase in testosterone receptor sites that induce gingival hyperplasia. Inflamed gingivae in both men and women metabolize testosterone.However, when the gingivae are healthy, testosteroneis metabolized only in men [77,78]. Testosteroneincreasesprotease activity and inhibits calcification, thereby decreasing inflammation; however, it also stimulates fibroblast and leukocyte migration that may contribute to inflammation [77,78]. It has also been demonstratedthat progesterone has the ability to augment the exudative leukocyte migration stimulated previously by local factors within the oral environment [79]. In humans, elevated serum progesteroneconcentrations accompany periodontal inflammation in men and women [78]. In women, progesterone causes a change in gingival microflora and microvasculature. Increased serum progesteroneduring pregnancy or oral contraceptive use causesa 50-fold increase in Bacteroides species (Bacteroides intermedium, in particular) [80,81]. The organism causes GD and gingivitis, and it is most abundant during the second trimester of pregnancy, when gingivitis scores are highest. Elevated progesterone increases androgen metabolism to the more active form and may stimulate epithelial growth [78]. Estrogen and progesteroneregulate prostanoid synthesis in oral tissues. Estradiol stimulates prostacycline formation and leukotriene production, and progesterone prevents the formation of these two inflammatory mediators [82]. Regarding salivary levels

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of steroid hormones, Vittek et al. [83] measured low levels of testosterone in women with periodontitis. In men with periodontitis high levels of estradiol and low levels of progesterone were measured. Estrogen stimulates synthesis of salivary peroxidase and an increase in inflammatory products. Different relative concentrations of progesterone either augment or suppress some effects of estrogen [84]. Estrogen metabolism that occurs in oral tissues results in the formation of an estrogen that is more potent. In inflamed tissues this leads to a three-fold increase in estrogen potency, and metabolism of progesterone proceeds more rapidly [85]. Low oral tissue concentrations of estrogen stimulate prostanoid synthesis, but high concentrations suppress this synthesis [79]. Prostanoid synthesis is also suppressed when estrogen and progesterone are combined. Therefore, the effect of estrogen depends on its concentration in the tissue and the relative concentrations of other sex steroids. In animal studies, estrogen suppresses oral inflammation, and when combined with physiologic levels of progesterone, inflammation is suppressed even more, regardless of local factors. Thus, oral inflammation and GD may sometimes occur during puberty, pregnancy, menses, and therapy with hormones (especially oral contraceptive agents), and other medications, such as phenytoin. Alterations of the oral environment result from fluctuations of plasma and salivary sex steroids. The ratio of the sex steroids to one another and their absolute concentrations determine the amount of prostanoid and peroxidase production and salivary flow. These relationships are obviously complex and are not readily predictable. (4) In regard to neurologically related disorders, Sluder considered tonsillitis as the source of a painful tongue and this was supported by Montgomery and Culver who also regarded any form of dental pathology as having a contributory role 186,871. They suggested that the condition was reflex-mediated, rather than a direct extension of the inflammatory response. Although disorders of the lingual and glossopharyngeal nerve can produce GD, the nature of the different disorders varies. Trauma to the lingual nerve has been reported following mandibular fracture, removal of a submandibular calculus, difficult third molar extraction and laceration of the lateral border

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of the tongue during dental procedures [33]. The quality of the resultant GD is non-specific. Glossopharyngeal neuralgia, however, is characterized by its paroxysmal nature and pain, affecting not only the tongue but the entire distribution of the nerve, too [88]. It can be elicited by stimulation of trigger zones in the tonsils, pharyngeal wall, base of the tongue and ear. Several authors report the association between gastric hyperacidity and a burning tongue [89-911. It has been postulated that there is a neurologically mediated reflex involving stimulation of the lower esophagus, the nucleus of the vagus nerve in the fourth ventricle, and the trigeminal nerve [89]. That there is direct stimulation of the mucosa has been confirmed by Morelli, who produced GD by causing a moderate hyperacidity, and relieved it by administering alkalis [90]. (5) Since 1945 it has been considered that “a definite relationship appears to exist between the transitional period in a woman’s life and the local manifestation of a general condition called burning mouth” [92]. Several authors have confirmed the strong link between menopause and GD [93,94]. The pathogenesis has been thought to be a reduction in estrogen levels, but it has been found that, although replacement therapy has a systemic effect as shown by the epithelial, oral and vaginal smears (see above), the symptom remains [95]. These authors seem to conclude that, behind the evident role played by the plasma and salivary levels of sex steroids, a psychogenic element, not directly related to hormonal levels, is involved. (6) The nature of the fluid in which the tongue bathes can also be responsible for GD. The fluid component of saliva acts primarily to protect the oral epithelium from drying, but it also acts as a mechanical cleansing solution that aids in the removal of food, cellular debris, and microorganisms. The fluid is the vehicle for the glycoproteins and mucoids that form a protective coating. These proteins add lubrications to minimize the abrasive action of foods, aid in speech, provide a buffer to neutralize acids, encourage antibacterial activity, and aid in the remineralization of the teeth. Any changes in saliva quantity or quality will affect these functions. A change in quantity also will affect a change in quality; therefore, as salivary flow

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diminishes, all protective functions are reduced. The most obvious effect on the individual is a decrease in the lubrication of affected tissues and an increase in friction that may present as a burning sensation or GD. Normally the saliva contains essential electrolytes, glycoproteins, antimicrobial enzymes and other important factors. In the healthy mouth, copious amounts of saliva lubricate and protect the oral mucosa by cleaning, regulating acidity, maintaining the integrity of the teeth and destroying bacteria. When the normal oral environment is altered by a decrease in salivary flow or a modification of salivary composition, the probability of caries, periodontal disease, mucositis, and many other serious oral problems increases. Dry and cracking oral mucosa and soft tissues, ulcerations, opportunistic bacterial infections, glossodynia, periodontal atrophy and deterioration, and extreme difficulty in lubricating, tasting, masticating, and swallowing certain foods are among the many manifestations of xerostomia [961011. In addition, a decrease in saliva alters the efficient removal of normally growing organisms, reduces the buffering and antibacterial activity and alters the mechanical removal of debris which, if not removed, provides a medium for organisms. All of these changes alter the microflora of the oral cavity and allow the proliferation of unwanted organisms, such as Candida albicans which, when its growth is left unchecked, may be implicated in the mucosal discomfort of GD. Currently, however, the amount of saliva loss needed to cause GD is not known; therefore, when a patient complains of GD, xerostomia as a cause should be high on the list of possible causes. Xerostomia is a term used to define a subjective clinical condition of a less than “normal” amount of saliva, but the amount that constitutes “abnormal” is not defined. Xerostomia is a common complaint of geriatric patients. A decrease in the quantity and composition of saliva elicits a multitude of problems in elderly patients. We believe that a xerostomic subject complains almost always of a burning sensation. Xerostomia may result from several chronic systemic diseases, such as diabetes, and autoimmune disorders, such as scleroderma, systemic lupus erythematosus, Sjiigren’s syndrome. Radiation therapy and chemotherapy for cancer treatment also may

lead to varying degrees of xerostomia. In addition, xerostomia may be induced by pharmacologic therapy that includes tranquilizers, antihistamines, diuretics, anti-Parkinson agents, sedatives, and analgesics [102,103]. Xerostomia caused by radiation therapy has been studied extensively, as has xerostomia resulting from Sjbgren’s syndrome. In both of these conditions the damage to the salivary glands may be complete and irreversible. The amount of saliva loss caused by pharmacologic agents, on the other hand, varies quantitatively, depending on the pharmacologic agent, its dosage, the time interval between dosages, and the effect on the individual, since these drugs affect neither the neural pathway of secretion nor the glandular structure itself. Their quantitative variations make pharmacologic agents a difficult group to study, although they are probably the most common cause of xerostomia, especially in the elderly [104]. The primary mechanism of action of drugs that cause xerostomia involves interference with the parasympathetic pathways of the autonomic nervous system. These pathways contain chiefly cholinergic fibers which, when stimulated, cause an increase in the salivary secretions. Anticholinergic agents, there-

Table 2 Drugs with possible xerostomic side effects Analgesic mixtures Anticonvulsants Antiemetics Antihistamines Antihypertensives Antinauseants Anti-Parkinson agents Antipruritics Antispasmotics Appetite suppressants Cold medications Diuretics Expectorants Muscle relaxants Psychotropic drugs central nervous system depressants dibenzoxazepine derivatives phenotiazine derivatives monoamine oxidase inhibitors tranquilizers - major tranquilizers - minor Sedatives

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Table 3 Medications with xerostomic side effects (from the 20 medications most frequently prescribed in 1986 in the USA) * Triamterene with hydrochloride Acetaminophen Cimetidine Alprazolam Propanolol hydrochloride Furosemide Ibuprofen Atenolol Diazepam Metaprolol tartrate Propoxyphene napsylate and acetaminophen * From: Top 200 drugs of 1986. Pharmacy Times 1987;32-40.

fore, are the primary cause of a reduction in salivary flow. Alpha- and beta-adrenergic receptors in the sympathetic nervous system also contribute to flow, so alpha- or beta-blockers will have some effect on the amount of saliva secreted but much less so than anticholinergic agents.. Beta-adrenergic blockers appear to affect primarily the protein content of saliva. Although the effects appear to be reversible on removal of the offending agents, no studies have been done to determine if permanent changes occur with long-term use of certain pharmacologic agents in man. Table 2 lists some medications with possible xerostomic side effects. Some of these groups overlap with others in terms of their pharmacologic agents; however, the grouping illustrates the different indications for which a drug with xerostomic side effect may be prescribed. Regardless of why they are prescribed, the practitioner must be aware of xerostomic side effects so that if the patient develops GD, the medications can be evaluated. Of the 20 medications most frequently prescribed in 1986 in the United States [105], at least 11 have some xerostomic side effects (Table 3). Moreover, it is even more difficult to evaluate non-prescription medications than prescription medications because patients often do not consider these drugs to be medications and therefore will not list them in their medical history. Nevertheless, if the patient does list an over-the-counter medication, it is difficult to find the additional information on side effects. Three groups of over-the-counter medications have great potential for abuse, precisely because they are non-prescription and may be used

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improperly, in particular laxatives, cold and allergy products, and weight control products. All laxatives have the potential for causing xerostomia because of the dehydrating effect of long-term use. Patients suspected of having anorexia nervosa need to be evaluated for this type of abuse. Selfmedication for colds and the symptoms of allergies is common. Included in this group are the decongestants, whether oral, topical, or nasal, antitussives, expectorants, and analgesics. All of these drugs may contain agents with powerful xerostomic side effects. Many over-the-counter weight control products contain phenylpropanolamine hydrochloride and caffeine, both of which have xerostomic side effects [106]. Less used medications with xerostomic side effects are the antidiarrheal agents, some of which contain a belladonna alkaloid, or anticholinergic, in doses equivalent to 0.6-1.0 mg of atropine sulfate, and the anti-helmintic products used to treat worms such as metronidazole. Caffeine and alcohol are not generally considered drugs, but they are, in fact, pharmacologic agents with xerostomic side effects and are found in a number of prescription preparations. Caffeine is also found in many everyday beverages and foods. Alcohol, besides being a beverage, is also an ingredient in many pharmacologic preparations. Some vitamin products contain from 1.5 to 18% alcohol. The subject with xerostomia who perceives a bad taste in the mouth may try to alleviate it with mouthwash, but such products usually contain a large amount of alcohol and will aggravate an existing problem. The alcoholic or the heavy social drinker may suffer from noticeable xerostomia. Smoking also dries the oral mucosa and aggravates an existing problem. Moreover, drugs such as marijuana or cocaine have severe xerostomic side effects, but it may be difficult to get the individual to admit to use of these drugs, which makes the task of tracking down xerostomia as the cause of glossodynia more difficult. The major clinical manifestations of xerostomia include dryness and burning of the tongue and other areas of the oral mucosa. Other complaints may include loss of taste, alteration in taste (increased salty and metallic taste), and thick, frothy, or sparse saliva [107-1091. Often the tongue sticks to the palate or cheeks, interfering with speech and causing clicking noises. GD is usually a major problem for

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xerostomic patients and it may become severe: the tongue characteristically appears fissured and lobulated and is usually erythematous, with partial or complete surface depapillation. Hypogeusia or dysgeusia are frequently associated with xerostomia and depapillation, together with decreases in or abnormalities of the taste buds, or all of these conditions [97,110-l 121. Sometimes, the xerostomic subject’s mouth appears moist, but it actually lacks normal salivary pooling and whole saliva. In other cases, the mucosa is totally desiccated and glazed, with generalized desquamation and multiple lesions [98,100,112-1141. Mucositis and GD are common conditions that are complicated by secondary infections with streptococci, other bacteria, or Can&u albicuns. These complications may affect 7080% of all xerostomic patients. Chapped lips and angular cheilitis or cheilosis are frequent findings and are most evident in subjects with removable dental prostheses [ 100,lO 1,115]. Generally, the susceptibility to caries is increased in xerostomic patients, particularly in the cervical and root surface areas. Absence of protective components, such as IgA, antibacterial enzymes, immunoglobulins, lubricating glycoproteins, increases the incidence of caries in these subjects, and there is reduced clearance of food debris and plaque from the oral cavity, resulting in acceleration of gingivitis and periodontal disease [lOO,lOl]. Another common finding in xerostomic patients is thin, atrophic, friable, marginal gingivae. Many subjects experience accentuated gingival recession, with alveolar bone loss. Lack of salivary glycoproteins or inadequate moisture and lubrication, as well as other compositional alterations in the saliva, may explain partially this phenomenon. In particular, the decrease in proline-rich proteins in both whole and parotid saliva may contribute to these important changes [116,117]. Especially the integrity of the epithelial barrier is affected. Basker et al., and subsequently Powell, noted that xerostomia can produce a burning sensation [7,118]. GD is found in about 64% of the general xerostomic population [119]. Among patients with primary Sjijgren’s syndrome the prevalence is 88%. Among patients with secondary Sjiigren’s syndrome (with systemic lupus erythematosus) the prevalence is 88% [120]. (7) There has also been suggested an iatrogenic

cause of GD. Bergenholtz and Hanstrom [121] showed that the proprietary mouthwash Oraldene, which contains 0.1% hexetidine, can produce GD. We have already mentioned both the possible role of phenytoin in inducing GD and the pharmacologic agents that may have xerostomic side effects as a cause of GD (see above). (8) GD may also be the result of any one of a number of oral lesions. Such lesions include lichen

planus, benign migratory glossitis, erythema multiforme, aphthous stomatitis, candidiasis, herpes virus infections, and squamouscell carcinoma [ 1221. Recently some authors suggested a possible psychogenic etiology for GD. A thorough clinical workup should be done initially to determine whether a local or systemic cause is involved (see above). If local and systemic factors are ruled out and it is possible to exclude a GD syndrome (symptomatic GD) then inquiries need to be made to determine positive evidence of a psychogenic cause. Nevertheless, one must keep in mind that also a subject with a symptomatic burning mouth syndrome may experience psychic discomfort due to possible somatopsychic rebound. In fact, the symptom of GD has long been a medical problem and has given rise to a wide range of differential diagnostic considerations. Despite this, the fact that it might also point to a disorder of psychiatric relevance is not known well enough, although Albert [123] speculated that psychiatric disturbance could be a possible contributory factor as long ago as 1885. Although GD is a condition familiar to virtually all general practitioners, dentists and medical specialists, there are very few publications considering the symptom of burning tongue on a general, non-specialist basis. Marxkors and Muller-Fahlbusch [124], who wrote a monograph dealing with psychogenic artificial denture intolerance (a symptom related to GD), were the first authors to go beyond the dental, intemistic and allergological aspects and give considerations to the important psychiatric aspects of the condition. Maier [125] published a report on 8 patients with “vital disorders of the oral region (glossodynia)” which occurred within the framework of an endogenous depression. In these patients, the basic depressive syndrome faded into the background compared to the glossodynia. In one study of 150 cases of

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psychogenic GD, it was found that involvement most frequently implicates multiple locations and involvement at a single location is rare [ 126,127]. Regarding denture problems, Marxkors and Muller-Fahlbusch found in their series that the diagnosis “psychogenic denture intolerance” masked depression in 57% of cases,neurotic developments in 21%, abnormal psychic reactions in 19%, and schizophrenia in 3%. True denture intolerance is only very rarely seen I:O be the cause of GD. However, the fitting of dentures, or some other dental or medical intervention, often triggers or exacerbates the condition [ 1241. Baurle and Schoenberger[128] submitted 100 patients with GD to patch testing for suspectedallergic stomatitis, with negative findings in all cases. For this reason, the authors drew attention to the lack of clinical relevance of allergens in the etiology of GD. Such patch testing, the,ymaintained, could be considered superfluous, and denture replacement usually resulted in no decisive improvement in the symptomatology. They concluded that “the time spent on patch testing should rather be employed for a carefully conducted interview of the patient, or else an attempt should be made to convince the patient that the condition is possibly psychiatric in origin, thus preparing the ground for further psychiatric diagnostic evaluation” [ 1281. With respect to the premorbid personality of patients with GD, Haneke [ 1291reported that almost all appearednervous or even tense, and many appeared to be anxious and introverted, depressed or even lachrymose. Almost half of the patients associated the onset of their complaints with medical or dental treatments. Gottwald and Haneke 11301noted that these subjects appear “psycho-vegetatively” labile and depressive in mood. In general, however, it should be noted that individuals with GD are usually not recognized immediately by non-psychiatrists as having psychiatric/psychological problems. In 1984, Cossidente and Sarti, reviewing the “psychiatric syndromes with dermatologic expression”, believed that GD should be included in the sphere of the hypochondrias and the so-called phobias [131]. They agree with Obermayer [ 1321,considering GD a phobi’c syndrome similar to cancerophobia. Obermeyer cites Ziskind and Moulton [133], who point out that the psychological basis of the

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syndrome is “ sexual frustration and maladjustment prior to the menopause,with an increase in sexual anxiety at the approach of the menopause”. Cossidente and Sarti point out that, in general, sentiments of fear and guilt are present in patients with GD. In their opinion, the pain, therefore, representsat times the threat of danger or the means to make amends. For these authors, GD is sometimes a depressive equivalent, i.e., a somatic sign of maskeddepression [131]. Zaiden hypothesizesthat GD symbolizes the fear of death (above all expressed as fear of cancer) localized in particular in the oral cavity that, being the site of food introduction, is directly connected with the preservation of life [ 1321. From a deep-psychological point of view, the mouth and tongue region is of considerable significance from the earliest age onwards. In the infant, apart from the skin, the mouth is the “primary site of social contact”, and the tongue is the first mediator of infantile object relationship. In adulthood, too, this area plays a central role in the intake of food, alcohol, coffee, tea and use of tobacco, and also in the sexual sphere. Suppressedfeelings and emotions and buried conflicts find expression in oral symptoms, in particular during sleep, but also during the day, in such symptomsas “oral habits” (grinding of teeth or bruxism, movementsof the mouth). According to Haneke [134] particular oral habits not infrequently lead to muscular tension, aches and temporo-mandibular joint syndromes. These “pain dysfunction syndromes” may give rise to the sensation of burning of the tongue. The intimate relationship between the personality structure of patients with GD and the temporo-mandibularjoint syndrome (Costen’s syndrome), which often has a psychogenetic etiology, is well known. In 1984, Feinman et al. [135] described two facial pain syndromes,possibly psychogenic in origin, Costen’s syndrome or ‘ ‘ facial arthromyalgia’ ’ and atypical facial pain. There have been suggestionsof an association with masked or atypical depression, and some investigators consider antidepressantsan effective treatment of such pain. In one study 160 GD patients submitted to a psychodiagnostic questionnaire survey showing that in these subjects(only 10% of whom were male and whose averageage was 60 years) the state of anxiety

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and trait anxiety scores were clearly higher than the average scores of healthy subjects, but lower than the average recorded for psychiatric out-patients [ 1351. The corresponding depression scores (state and trait> were higher than those of in-patients suffering from somatic diseases, but much lower than those of depressed psychiatric patients. The scores for neuroticism and neurosomatic lability were considerably higher than the mean scores observed in the general population. Thus, subjects with GD have been found to score higher than the normal population on state and trait anxiety, depression, somatic reactions to stress and neuroticism [25]. In another study 39% of the study population was found to suffer from clinically significant anxiety and 13% from depression [22]. Another study evidenced psychiatric disorders in 44% of GD patients compared with only 16% in a control group [20], and in a series of 10 treated GD patients, 7 presented a pathologic personality disorder and 3 a mild psychiatric disorder [136]. The psychopathologic profile of subjects with GD basically resembles the psychological distress reported for other chronic pain populations [137-1391. For example, the psychopathologic profile of the GD patient shows elevations in scales of somatization and depression resembling the elevations reported for a general chronic pain population in the United States [137]. The relative elevation in the scales of somatization and depression is evident when GD patients are compared with other groups of dental patients, such as dental phobics who have been treated successfully for their dental fear (0.94 vs. 0.63 on the somatization scale, 0.93 vs. 0.70 on the depression scale) [ 1401; their psychopathological profile is higher for all parameters than that of a general, healthy population of dental patients. Although such comparisons should be carried out with care (differences in population characteristics, socio-cultural contexts, research design, etc.), it seems that the increased psychological distress of the GD patient is associated with the chronic pain condition. This is in agreement with Grushka et al. [I81 who point out some psychopathology in GD patients. In this latter study the personality profiles of GD patients show elevations in some personality characteristics (e.g., depression, anger, anxiety, etc.), changes that tend to increase with pain. The psychological findings in GD patients may be

either the consequence of the chronic pain condition or its cause. Many of these patients often live alone, and their psychologic distress is significantly associated with the marital status. A relatively high percentage report having had psychiatric or psychological treatment in the past and/or present. All of the patients who reported having had such treatment initiated it over 5 years before the study (conducted by Eli et al.), whereas the GD symptoms in most of the patients began l-3 years before this study. Thus, it is possible that personal distress plays a role in the development of the syndrome. However, the possibility that some patients may have developed psychologic distress after the onset of symptoms and initiated treatment as a result cannot be overlooked. Today it is generally accepted that syndromes involving prolonged chronic pain, such as GD, indeed, are closely associated with increased psychological distress in the individual. For example, a significant excess in adverse life events has been found before the onset of low-back pain [141]. In fact, chronic pain (like GD) and depression seem to be closely related. Ott and Ott [ 1261 conducted a study on 13 1 GD patients submitting them to a careful examination that included a neurological work-up, detailed psychiatric interview and numerous psychological tests (Achievement Test for Endogenous Depression, Multiple Choice Vocabulary Test measuring verbal intelligence, Erlangen Depression Scale, AnxietyAggression Scale, Scale for General Somatic Symptoms, Scale for Vegetative Functional Disorders, Abbreviated Pain Scale, Self-Rating Scale for State of Wellbeing, Self-Rating Anxiety Scale, Self-Rating Depression Scale). Particular attention was paid to psychosomatic and psychopathologic disorders. The finding that 73% of GD patients are female contrasts with earlier reports [137,138] in which it is stated that about 90% of the patients are women. The author concludes saying that post-menopausal women in particular may develop the symptoms of GD. The probability of depression being the causal factor is high, so the treatment with antidepressants would appear to make good sense; Ott and Ott observed 49.2% of the patients were diagnosed as depressive (8.2% major depression, 41% minor depression): these data may justify treatment with antidepressant drugs. Finally, quite often, GD is a somatic manifesta-

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tion of a psychological illness that may range from life stress reactions with anxiety or minor depression, or both, to major depression. Both organic and psychogenic factors may be obviously present; for example, a patient with candidiasis may also have major depression. Moreover, there may be a genuine cancerophobia [142,143]. Cancerophobia is common in patients with GD and it is one of the hypochondriacal disorders. Patients with hypochondrias are preoccupied with the convinction that they are incurably ill with a specific disease. The physician should ask about fear of cancer, because many patients may not voluntarily express their intense fears and convinctions unless this information is elicited directly. Also, patients should be asked if a close friend or relative has had oral cancer, for obvious reasons.

4. Conclusions: diagnosis and management When a patient has an unusual complaint and there seem to be few objective physical findings, the physician is challenged to provide an appropriate differential diagnostic workup. Obviously, the examiner’s bias can influence findings, especially when there is a major psychologic stressor like glossodynia. The simple process of giving a name to a symptom is often a major stress reliever; fear of the unknown can be worse than dealing with a chronic problem. The Greek word “odyne”, which means pain, has been used in medicine for many years to indicate localized discomfort. The aim of assessment of GD is the identification of correctable causes. We believe that the first step is to try to evaluate whether the subject with GD presents a symptomatic GD or an idiopathic GD (i.e., GD syndrome versus GD disease). We realize that this distinction may be very difficult or dangerous and in some cases it may be made only after many months (or even years) of follow-up. Table 4 presents a very basic outline for a preliminary screeening of the glossodynic subject. Obviously, a thorough history including psychological stress factors is essential (history of anxiety or depression). The examiner should investigate kindly on familial and social situations, possible cancerophobia, and if the burning mouth syndrome interferes with sleep,

Table 4 Basic outline for a preliminary subject

screening of the glossodynic

Pain directly associated with eating Pain with outset some time after eating Pain diminishing while eating

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+ Local cause + Myogenic or neurologic cause + Psychological cause

and ask frankly about possible depression (for example: “Do you feel down-hearted and blue? Do you feel hopeful about the future? Are you restless and can’t keep still? Do you get tired for no reason? Does your heart beat faster than usual? Do you have trouble sleeping at night? etc.). Glossodynia is sometimes a symptom of a complex systemic disease rather than a pathologic entity; thus a full otorhinolaryngological examination is required, with particular attention to any macroscopic changes in the mouth and oropharynx, and the state of the teeth. A general examination may reveal signs of systemic disorder. Even in the presence of an identifiable cause, there may be contributing and aggravating factors (such as psychological implications or intrapsychic conflicts), and further investigation is advisable. A bacteriological swab is easily taken, and a full blood count and film. To establish iron, folate or vitamin B12 deficiency, a hematologic screening that includes complete blood count, red cell, serum iron, vitamin B12, folate levels, serum zinc should be performed [144]. Although they are rarely required, specific tests for suspected niacin, pyridoxine and riboflavin deficiency are available in specialized centers. Although GD related to nutritional deficiency is statiscally uncommon, it is easily curable with replacement therapy. Identification of a vitamin deficiency through early oral symptoms can forestall development of serious and irreversible systemic and neurologic damage. Random blood sugar and thyroid function tests are easy and should probably be performed in every case. If the GD is thought to be related to the onset of the menopause, the existence of ovarian failure can be confirmed by measuring serum folliclestimulating hormone (FSH). An orthopantomogram may reveal dental pathology and a barium swallow

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will confirm or negate suspectedesophagealreflux. Finally, when there are dentures, a dental opinion may reveal an ill-fitting prosthesis, dental plaque or an irritant residual monomer. As mentioned above, the importance of generalized medical diseasesas a causeof GD, for example anemia or nutritional deficiencies, is almost always overrated. It is our opinion, in fact, that most subjects who report burning mouth syndrome present an idiopathic-psychogenic GD (GD disease), whereas few subjects present complaining of symptomatic GD. Nevertheless, we emphasize that the physician must not forget this possibility and should remember to prescribe specific testsand/or examinations.Table 5 presents a very short system for assessing GD syndrome. It may be useful to try to identify the causesof GD on the basis of the type of discomfort referred by the patients, as reported in Table 6. In Table 6 we present a possible diagnostic-therapeutic iter for the managementof the GD patient.

Table 5 A short system for assessing glossodynia Anamnesis General physical examination Laboratory tests (a) bacteriological swab (b> mycological tests (c) hematological tests full blood count and film random blood sugar serum iron serum vitamin B 12 serum folate serum zinc serum thyroxine serum follicle stimulating hormone (FSH) serum erythrocyte glutathione reductase activity (for assessment of riboflavine status) serum erythrocyte aminotransferase activity (for assessment of pyridoxine status) (d) radiological tests orthopantomogram barium swallow Dental examination

Table 6 Diagnostic therapeutic iter of glossodynic patient

HISTORY t OSJECTIVE

EXAMINATION

3 Alterauons v Diagnosis

a

Of oral muco*a v Systemic

Absence

medical

evaluation

of alterations

of oral mucosa

Psychiatric

evaluation

Patient

information

Antidepressants Psychotherapy

Persistenceof

burning

mouth

sensation reculTalt

followvp

Finally, it is worth note that the presence (or absence)of depression in chronic pain patients has been shown to affect the patient’s treatment response [145]. Therefore, early identification of any possible psychological factors may contribute significantly to the understanding and treatment of GD patients. In fact, several recent studies suggestthat GD patients can be divided into those responsiveto treatment and those who resist it. When the psychological profiles of cured versus non-cured patients are compared,the latter are found to be more unstable, apprehensive, and tense [146]. Management of the glossodynic patient should focus on correcting suspectedcausativefactors. Thus, one should eliminate the medications known to provoke or aggravatexerostomia. In the casesof symptomatic GD (GD syndrome) treatment is based essentially on correct therapy of the underlying disease. Thus, for example, antimycotic agents in the case of candidiasis, nutritional supplementsfor deficiency states,estrogen and hormonal replacementin endocrine disorders. Irritants, such as alcohol-based mouth-washes should be avoided, and pain, itching and stinging can be appropriately treated with topical anestheticagents(for example, diphenhydramine hydrochloride 12.5 mg/5 ml mixed with one tablespoonful of water, before each meal). An elixir of

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equal parts of diphenhydramine, kaolin and pectin retained for l-2 min and then expectorated, 30 min before meals [7], has been reported to give some relief. In the cases of GD disease (idiopathic glossodynia) or psychogenic CD as well as cases of GD syndrome which present an important somatopsychic rebound, psychoactive drugs may be also employed. First, however, we recommend that these subjects be reassured that there is no evidence of any important local or systemic disease, including malignancy. In their very recent comprehensive review of burning mouth syndrome, Huang et al. [7] suggest the use of amitryptiline (75-150 mg daily) and doxepin (7% 150 mg daily), the most commonly prescribed tricyclic antidepressants. We point out that as tricyclic antidepressants also have an anticholinergic effect they often induce xerostomia. Thus, we prefer to prescribe the newer serotonin uptake inhibitor antidepressants, such as fluoxetine or paroxetine, in presenting symptoms of depression or depression equivalents. Also pimozide (a neuroleptic drug), alone or in combination with antidepressants, has been reported effective [147]. However, no specific treatment recommendations except for psychotherapy are usually given. Unfortunately patients with psychosomatic symptoms are most often resistant to and may even be indignant about referrals to a psychiatrist. Their intense preoccupation with their symptoms often overshadows the underlying depression. With some depressed patients the same or other somatic symptoms reappear with each recurring depression. These patients are often unable to recognize the effects of the depressed mood, and they return to their doctors expecting a physical cause for the symptoms. Such patients commonly deny a depressed mood, even though it is evident to their doctor. This is known as “masked” depression or “smiling” depression. Depressed patients with GD require a comprehensive diagnosis that leads to the initiation of more specific treatment by the consulting doctor or treatment recommendations for the referring doctor, or both. Fortunately, the recent literature on psychogenic glossodynia focuses on the diagnosis of treatable depressive disorders. The “burning” is a symptom of the depression. If the depression is adequately treated the GD will subside. Kuffer 11271

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found that 60% of cases of psychogenic GD were associated with depression that responded to treatment with antidepressant medication, often within 2-3 weeks after beginning treatment. As with most medical problems, the patient expects a diagnosis and subsequent treatment for a physical, non-psychogenic condition. From a medical point of view, it is usually in the patient’s best interest that the psychologic cause be suggested by the clinician at the same time that physical causes are presented. However, too often this is not done, perhaps as the doctor is reluctant to offend or anger the patient. Nevertheless, it is very desirable that the clinician tell the patient that tension and depression can indeed have a biologic basis that causes physical symptoms such as tension headaches or nervous diarrhea. The clinician should emphasize that an effective treatment is available and that the symptoms are real and not being imagined. This approach is usually accepted by patients who are fervently searching for an explanation for and relief from their distress. In evaluating patients the referring physician should inquire directly about a history of depression in both the patient and the patient’s parents and siblings, as well as whether the patient is presently depressed and/or being treated for depression. Some patients will not give a history of their emotional illnesses or treatments unless they are asked directly because they believe it will bias the doctor unfairly in his diagnostic evaluation. Patients also should be asked if they have had other physical complaints that have been difficult to diagnose or treat. Patients with depression often have more than one “psychosomatic” symptom. Depression commonly is triggered by an actual or a threatened personal loss, such as a death of a spouse or serious disability or the loss of a job or job status. The physician should ask specifically if such an event preceded the onset of the glossodynia. As stated above, cancerophobia is sometimes present in patients with GD. If cancerophobia is a manifestation of major depression, usually it will respond to antidepressant medication. If the cancerophobia is a hypochondriacal symptom without considerable depression, it is often difficult to treat. In the latter situation, the physician should emphasize the lack of clinical findings and, with the assistance

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of the patient’s family, try to get the patient to accept a psychiatric consultation. Moreover, some patients with GD have anxiety disorders [ 127,129,134]. These are seen most commonly in patients with secondaryguilt, especially in patients with emotional conflicts over sexual practices. Frank discussion may help elicit pertinent information from some of these patients. If warranted, anxiolytic medications can be given for a limited time so that psychological dependencyon the medications is minimized. In such cases,benzodiazepine chlordiazepoxide has been reported to lead to complete remission in 15% and some relief in 52% of treated patients [7,148].

d) about 0.1% of dermatologic outpatients e) about 13% of psychosomaticdermatologic outpatients (5) Choose the right sentences: a) The age of onset of glossodynia is usually between 40 and 60 years. b) Glossodynia is a typical post-menopausaldisease, as the typical glossodynic patient is a middle-aged woman. c) Glossodynia is usually observed before the age of 30 years. d) Glossodynia is never seen in children, but sometimesin adolescents. e> Glossodynia has never been seen in children and adolescents.

Appendix Questions (1) The earliest references of glossodynia are attributed to: a) Magitot in 1854 b) Fox in 1859 c> Schwimmer in 1886 d) Buisson in 1854 e> Oppenheim in 1887 (2) Which of the following terms is less used to describe the glossodynic symptoms? a) stomatodynia b) pain in the tongue c) oral galvanism d) burning mouth syndrome e) glossalgia (3) Choose the right sentences. The syndrome of “oral galvanism” describes a situation of atypical taste sensationsin the mouth usually due to: a) pemphigus vulgaris b) metal taste c) aphthous diseases d) galvanic currents used in dental work e) all the previous items (4) The incidence of glossodynia is: a) about 10% of elderly people b) about 22% of post-menopausalwomen c) unknown

(6) The highest prevalence of oral sites at which a burning sensationoccurs is: a) ventral side of the tongue b) anterior two-thirds of the tongue c) floor of the mouth d) mucosal portion of lower lip e) tip of the tongue. (7) The onset of symptoms is: a) gradual for about two-thirds of cases b) gradual for about one-third of cases c) sudden for two-thirds of cases d) always related to previous dental extractions e) usually related to previous illness (8) Glossodynia is: a>generally due to a systemic problem b) often provoked by a yeast infection of the mouth c> a symptom of psychiatric disorders d) always associatedwith pernicious anemia e) none of the above. (9) Choose the right sentences. The diagnosis of glossodynia: a) is mainly histological b) requires a very careful follow up c> should tend to verify whether the patient has a GD syndrome or a GD disease d> is anamnestic e>is mainly clinical

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(10) Choose the wrong sentence.In the etiology of glossodynia. a> all the following items are wrong b) the pressure exerted by dentures may provoke minimal changes on the underlying mucosa, causing microscopic changes in the sensorial nerve ending fibers c> dental plaque has been suggested as a contributing factor high monomer content of dentures has been d) suggestedas a contributing factor 4 ill-fitting dentures factors have been always reported (11) Choose the right sentence. a> 9% of women in the United Statesbetweenthe ages of 30 and 52 suffer from iron deficiencies. b) 9% of women in the United Statesbetween the ages of 25 and 44 suffer from iron deficiencies. c) 9% of women in the United Statesbetween the ages of 25 and 44 suffer from folic acid deficiencies. d) 15% of women in the United States between the ages of 30 and 52 suffer from folic acid deficiencies. e) 13% of women in the United States between the ages of 25 and 44 suffer from iron deficiencies. (12) Choose the right sentence. a) macrocytic anemia is commonly present in patients with vitamin B12 deficiency b) pernicious anemia is a typical manifestation of Plummer-Vinson syndrome c) pernicious anemia is a microcytic anemia, causedby a gastric mucosal defect d) pernicious anemia is a megaloblastic anemia, causedby a gastric mucosal defect, and is the major causeof vitamin B 12 deficiency e) folic acid deficiency provokes pernicious anemia (13) Pyridoxine deficiency: a) is characterizedby a not painful, atrophic, red tongue b) is associatedwith folic acid deficiency

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c) is characterizedby a painful, swollen, purplish tongue d> is usually iatrogenic e) affects up to 20% of pregnant women (14) The term “xerostomia” indicates: a) a subjective clinical condition of a less than normal amount of saliva b) an histological feature, characterized by the atrophy of salivary glands cl an objective condition, with 30% reduction of the normal amount of saliva d) an objective condition, with 60% reduction of the normal amount of saliva e) a qualitative alteration of saliva (15) Choose the wrong sentence.Xerostomia is provoked by: a) corticosteroids b) diabetes c> diuretics and some psychotropic agents d) connective tissue disorders e) caffeine, often associatedwith alcoholic beverages (16) Xerostomia a) is often complicated by dryness and burning of the tongue b) is sometimes associated with hypogeusia or dysgeusia c) may be accompaniedby bacteria or Candida albicans infections in 70 to 80% of cases d> appearscharacteristically with fissurated, lobulated and erythematoustongue e> all the above are right (17) Complete the sentence.According to Marxkors and Muller-Fahlbush a) glossodynia has always a psychogenic etiology b) the diagnosis of psychogenic denture intolerance masks depressionin 57% of cases c) the diagnosis of psychogenic denture intolerance masks schizophrenia in 57% of cases d) the diagnosis of psychogenic denture intolerance masks neurotic developments in 19% of cases e> the diagnosis of psychogenic denture intolerance masks abnormal psychic reactions in 3% of cases

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(18) Usually, the psychopathologic profile of the GD patient: a) differs from the psychological distressreported for other chronic pain populations b) shows elevations in scalesof anger and anxiety c) shows elevations in scalesof somatization and depression d) shows elevations in scale of somatization, but not in depression e) shows elevations in scale of depression, but not in somatization. Answers 1) d 2) c

3)bandd 4) c 5)aande 6) e 7) a 8) e 9)bandc 10) e 11) b 12) d 13) c 14) a 1.9 a 16) e 17) b 18) c

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