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ORAL MUCOUS MEMBRANE CONTACT DERMATITIS
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CONTACT DERMATITIS
ORAL MUCOUS MEMBRANE CONTACT DERMATITIS Derek H. Jones, MD, and Vincent S. Beltrani, MD
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Oral mucous membrane contact dermatitis (or contact stomatitis) is relatively rare. In general, the mucosa is more resistant to primary irritants, and is not as readily sensitized as the skin. The oral mucosa is also constantly bathed in saliva, which washes sensitizers from the mucosal surface and prevents adequate contact. Furthermore, abundant mucosal vasculature allows for rapid absorption and clearing of allergens. Nevertheless, contact reactions can occur on the oral mucous membrane. Contact sensitivity has been described as a factor in recurrent oral ulceration43,32 and oral lichenoid reactions.52As with other types of contact dermatitis, allergic contact dermatitis may be difficult to distinguish from irritant contact dermatitis, and it may also mimic oral changes of vitamin deficiency, certain anemias, uremic stomatitis, and candidiasis.I8 Although the prevalence of allergic contact sensitivity in the mouth is unknown, a number of substances have been reported to cause oral symptoms.
CLINICAL PRESENTATIONS In a recent review of patients referred for patch testing because of oral symptoms, Shah et a147found mouth/lip swelling, tingling/burning,
From the Department of Dermatology, Columbia-Presbyterian Hospital (DHJ, VSB), and the Department of Dermatology, College of Physicians & Surgeons of Columbia University (VSB), New York, New York
IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA
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VOLUME 17 NUMBER 3 * AUGUST 1997
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and local anesthetic reactions to be the most common presenting complaints of patients with positive patch test results. The clinical presentation of contact dermatitis in the mouth is dependent upon the offending substance and the duration of contact. The oral symptoms may include numbness, aguesia (loss of taste), and burning sensation^,^^, 35, 29 which are often more prominent than the physical signs. Itching is a rare symptom of contact stomatitis. Objectively, changes may be barely visible or may vary from a mild erythema to a fiery red color, with or without edema. Vesiculation of the oral mucosa is rarely seen because vesicles rupture quickly to form erosions. Oral lichen planus2 and other lichenoid reactions characterized by white patches may be seen with allergens that have persistent contact with the mucosa, such as compounds used in dental appliances and hardware (Figs. 1A and B). In rare instances of marked edema, difficulty in swallowing and breathing may occur. Allergic mucosal dermatitis is often accompanied by a perioral contact dermatitis, which manifests as an eczematoid eruption characterized with the more typical pruritus, erythema, and scale affecting the lips and adjacent skin. As a general rule, once the oral mucosa has been sensitized, the skin is sensitized as well; however, it has been reported that sensitization of the oral mucosa with dinitrochlorobenzene actually increases skin t ~ l e r a n c e . ~ ~ CHEMICAL AND TRAUMATIC INJURY
The oral mucosa is relatively resistant to thermal injury, although hot foods or liquids may cause mild to severe burns of the oral mucus characterized by erosions or bullae. A distinctive cause of a circular lesion seen on the palate is the "pizza burn," caused by the adhesion of hot pizza to the palate. A variety of chemicals may accidentally burn the mouth, such as household lyes, gasoline siphoned from a car, pipetted caustic agents, or chemicals inadvertently applied during dental treatment (phenol, silver nitrate, nitric acid). Strong caustics will cause tissue necrosis that appears clinically as white Aspirin placed next to a "sore" tooth is a common cause of an irritant dermatitis or mucosal u1cer.lo Undiluted Shohl's solution (9.8% sodium citrate and 14% citric acid) may also cause direct irritation of the oral mucosa, especially in patients with poor oral hygiene or in debilitated patients who have trouble swall0wing.4~ Ammonia that is liberated from the action of bacterial urease on salivary urea in patients with renal failure can present with a uremic stoma ti ti^.^^ Leukoplakia or hyperplastic white patches (leukedema) of
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Figure 1. A and B, A 14-year-old female developed extensive leukedema of entire buccal mucosa and gingiva 4-6 weeks following the applications of a nickel-containing orthodontic device. Patch tests revealed a 1 reaction to cobalt and nickel. Buccal mucosal biopsy showed leukedema, without an inflammatory infiltrate.
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the mucosa may result from prolonged irritation from ill-fitting dentures or dental appliances (braces).
Allergic Contact Stomatitis A wide range of allergens may be responsible for oral and perioral symptoms. The most common allergens identified, however, may be divided into four main groups:
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1. Allergens contained in dental and mouth-care products 2. Food additives (flavorings and antioxidants) 3. Metals used in dental restorations 4. Rubber chemicals in examination gloves
DENTAL AND MOUTH-CARE PRODUCTS
Mouthwashes are medicated liquids used for cleansing the mouth for therapeutic or cosmetic purposes, and like dentrifices, may contain alcohol, flavorings, antiseptics, and preservatives. The abrasives in dentrifice’s are not sensitizers. The allergens in mouthwashes and dentrifices that have been implicated in allergic stomatitis include formaldehyde, mercurial antiseptics, benzalkonium chloride, dichlorophene (G-1l), antibiotic agents, flavorings, fluorides and coloring agents. Cinnamon flavorings, particularly cinnamic aldehyde, and peppermint are probably the most common cause of allergic stomatitis from dentrifices, and they are included in many These patients will present with a burning oral sensation, a stomatitis, and frequently with a perioral dermatitis.41 Chemical injury of the oral mucosa may be caused by undiluted mouthwashes of perborate of hydrogen peroxide. Denture cleansers may contain acids, alkali, or oxygenating compounds which may cause chemical burns or ”store teeth” dermatitis of the mouth if dentures are not thoroughly rinsed after soaking1 Despite the widespread use of corticosteroids on the mucous membranes of the respiratory tract, mucosal contact sensitivity has apparently been uncommon; however, since the introduction of new corticosteroids, such as tixocortol pivalate and budesonide, mucosal contact sensitivity has been reported. Stomatitis and pharyngitis due to budesonide in a bronchial inhaler has been Another report noted tixocortol pivalate in oral lozenges caused an allergic contact stomatitis.h
ALLERGIC STOMATITIS CAUSED BY METALS
Allergic contact stomatitis due to orthodontic metal is rare. There are a number of reports of contact stomatitis due to metal in patients with dental plates, crowns, or other orthodontic material^,^^ and oral lichen planus has been associated with mercury in amalgam fillings.5R, 33, 2h The metals used in dentistry that have been responsible for contact dermatitis include mercury, chromate, nickel, gold, cobalt, beryllium, and palladium. Of these metals, mercury has most often been implicated as a producer of allergic reaction^.'^
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Mercury Probably the most common contact with mercury in the general population occurs from mercury amalgam dental fillings. Lichenoid lesions of the mouth have been reported as a result of allergy to mercury contained in amalgam dental fillings.2' Clinically the lesions appear as hyperplastic white patches in the mouth, and frequently occur at the mucosal site in contact with the filling. In addition to localized lesions of the oral mucosa, mercury from amalgams has been incriminated as the cause of generalized dermatitis in mercury-sensitive individual^.'^ This generalized dermatitis is thought to be related to mercury vapor that is liberated during the preparation and insertion of dental fillings. Once the filling is completely inserted, however, the amount of mercury liberated in comparison to the preparation and insertion process is Nonetheless, there are reports noting the disappearance of chronic eczema upon removal of mercury-containing amalgams.48 In a recent study of the relationship of oral lichenoid lesions to mercury-containing amalgams, 21 of 91 patients studied had positive patch test reactions to mercury.34 Of these 21 patients, 18 had oral lichenoid lesions adjacent to mercury filling whereas three patients had neither amalgam fillings nor oral lesions. In 15 of the 18 symptomatic patients, the amalgam fillings were removed and replaced with nonmercuric fillings. After a mean follow-up of 3.2 years, seven patients had achieved a complete cure whereas six had marked improvement, and two had no change. Gots and F ~ r t r n a n nreported ~~ that allergic reaction of the skin to mercury that is detected during routine tests is not due to the effect of amalgam fillings.Z4Gaul reported three patients with mercury dermatitis in whom epidermal sensitivity to mercury was demonstrated, but no irritation was noted in the mouth adjacent to amalgam dental fillings.22 Another recent study has documented mercury in macrophages in lesional and nonlesional skin adjacent to mercury-containing amalgam, giving further evidence to support a mechanism for allergic contact dermatiti~.~ Additionally, immediate and sometimes persistent urticaria1 reactions have been described in association with mercury dental restor a t i o n ~ .Therefore, ~' in mercury-sensitive individuals with persistent oral lesions, urticaria or eczematous dermatitis, it may be justifiable to replace amalgam filling with gold or nonmetallic fillings. Shah et a147and the author (VSB) have each had a patient who had unilateral jaw pain for years on the side of their mouth, where mercury amalgam fillings were present. They both reported a metallic taste in the mouth. Both patients reacted to mercury and ammoniated mercury on patch testing. Upon removal of the amalgam, the author's patient
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became symptom-free, and has remained symptom-free three years later. (Shah’s patient did not have the filling removed.) There exists a cadre of physicians who, under the guise of a “fashionable” title of ”clinical ecology” profess as ”alternative medicine” an amalgam disease. The issue has received extensive coverage in the lay as well as the medical media. They have created confusion regarding the terms mercury allergy, mercury burden and intoxication, and amalgam allergy, the understanding of which is crucial in the consideration of this controversy. The amalgam disease has been introduced as a term to identify patients who typically ascribe a variety of subjective symptoms to their amalgam fillings. When these physicians make the aforementioned diagnoses, they demand removal of all dental amalgam. Although dental amalgam is the most important source of mercury burden in the general population, occupational exposure to mercury within established exposure limits reaches levels much higher without evidence of intoxication. Current literature lacks sound evidence of a role for amalgam in human disease other than allergy.5,37
Nickel
Allergic contact stomatitis and cheilitis can occur from nickel-plated instruments used in dental procedures. Nickel-sensitive individuals can present with allergic stomatitis, perleche, and erosions resembling aphthous ulcers by holding needles, pins, bobby pins, coins, keys, and other objects in and near the mouth.”, 60 Nickel is the most common cause of allergic contact dermatitis. Five patients with nickel sensitivity on patch testing had small nickel plates glued to the oral mucosa for 7 days. All five developed lesions at the site that were clinically and histologically consistent with contact dermatiti~.~~ Nickel-containing metal alloys are widely used for dental prostheses and orthodontic appliances; however, a recent study noted that nickelsensitive patients are not at greater risk of developing oral symptoms or lesions when wearing intraoral orthodontic appliance^.^"
Other Metals Pins containing chrome-cobalt combination to fasten porcelain teeth to acrylic dentures may produce stomatitis in persons sensitized to cobalk8 Gold is becoming increasingly recognized as an allergen, and a case has been described where gingival mucosa in contact with a gold filling
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sloughed and sites of previous contact with gold jewelry flared.I2 In Shah et a l ’ evaluation ~ ~ ~ of 47 patients, only one patient reacted to gold (sodium theosulfatoarate). This patient experienced tingling on the oral mucosa immediately adjacent to new dental crowns. Metal was showing on the crowns that contained gold. Symptoms resolved after the crowns were removed. Sensitization to gold should be considered as a possible cause of allergic contact stomatitis, as well as a pathogenic or triggering factor in oral lichen p l a n u ~ . ~ ~ Because of the high cost of gold, alloys containing nickel, cobalt, chromium, copper, palladium, and beryllium are being used. Contact dermatitis of the oral mucosa has rarely been associated with these latter compounds.
DENTAL IMPRESSION COMPOUNDS These preparations may contain a variety of substances, of which resin is most likely to cause sensitization.’*Fluxes which contain borax, boric acid, silica and potassium fluoride are strong irritants. Modern bonding adhesive materials may contain acrylic monomers and epoxy resins and hardeners that may cause allergic reactions. Resins are adhesive materials used in a wide variety of dental reconstructive procedures, including pit and fissure sealant, orthodontic adhesives, glazes, veneers, and repair kits for porcelain-fused-to-metal restorations, root canal sealers, and temporary crowns. Resins and bonding adhesives contain acrylic monomers which must be polymerized by either heat (ultraviolet or visible light) or cold curing. Unpolymerized monomers and other components of bonding adhesives may cause allergic reactions of the oral mucosa or urticaria, although such events are considered rare.” Unpolymerized material in the cured resin may be leached out by saliva, water, soda water, and alcohol. In general, coldcured resins are much more likely to cause allergic contact dermatitis on the oral mucosa. Allergic reactions to these binding materials may occur in the patient, the operator, or office personnel. Widespread dermatitis has been reported to occur in a resin-sensitive patient after dental treatment with a resin-containing p r o d ~ c t . ~ Scutan, an epimine plastic used for temporary crowns and bridges, contains methyl-p-toluene, and has been linked to untoward mucosal reaction in individuals sensitive to this compound on patch tests.54 Additionally, allergic reactions of the mucosa have been attributed to methyldichlorobenzene sulfonate 0.1% in dibenzyltoluol present in impregum, an impression rubber material used for construction of crowns and bridges. It is usually in contact with the oral mucosa only briefly.
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ANTISEPTICS AND PRESERVATIVES IN ORAL MEDICATIONS
A wide variety of potential sensitizers may be present in antiseptics and preservatives added to certain dentrifices, mouthwashes, topical oral medications, and anesthetics. Sensitizers in dentrifices may produce cheilitis and circumoral dermatitis. Elimination of dentrifices containing specific preservatives or cosmetics is a difficult problem, as there is no law to impel manufacturers of toothpastes to indicate the presence of a preservative in their products.l8These include dichlorophene (G-4) (most common), formaldehyde, merthiolate, phenylmercuric nitrate, ethylenediamine hydrochloride, parabens (a rare sensitizer), hexachlorophene (Gll), sodium perborate, and quaternary ammonium compounds. Iodoform contained in a ribbon gauze used for packing in dental procedures may cause an allergic stomatitis,%as can hexetidine contained in garg l e ~Allergic . ~ ~ reactions to antibiotic compounds used intraorally may be due to the antibiotic or the flavoring or coloring agents. SURFACE OR TOPICAL ANESTHETICS
Benzocaine is a common and potent sensitizer found in many oral topical medications, including mouthwashes and gargles. The use of benzocaine-containing oral sprays may produce immediate-type "anaphylactic" IgE-mediated severe reactions in benzocaine-sensitive individuals. Symptoms may include angioedema of the mouth and larynx, wheezing, urticaria, syncope, and hypotension progressing to vascular collapse. Patch testing with local anesthetics does not reveal the immediate anaphylactic-type reaction. Benzocaine-sensitive individuals can be tested with the anesthetic intradermally or by "prick-test" to detect the presence of IgE antibodies. Benzocaine cross-reacts with para-aminobenzoic acid (PABA) compounds (i.e., procaine, tetracaine, etc.) and these related substances should also be avoided. Anesthetics containing the amide linkage, such as lidocaine (Xylocaine),can be used in benzocaine-sensitive patients.
STOMATITIS CAUSED BY DENTURES
When examining the oral cavity of a person wearing complete dentures, physicians should remember they are observing the changes caused by the prosthesis itself as well as the relevant oral changes associated with the aging edentulous patient. Oral mucosa does not respond in the same manner as skin to everyday wear and tear. Mucosa
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demonstrates a low tolerance to injury or i r r i t a t i ~ nMany . ~ ~ patients with denture stomatitis are unaware that they have the condition, as it is frequently asymptomatic. Others may report a burning or itching sensation of the mucosa. The inflammation occurs more frequently in the maxillary arch, and the tissue of the maxillary mucosa that is actually in contact with the denture base may become extremely erythematous. Although allergy to dentures is frequently implicated as the cause of inflammatory changes beneath prosthetics, usually the reactions are due simply to trauma from poorly fitting dentures. Fortunately, true allergy to the materials in denture bases is rare. Clinically, the allergic reaction resembles the generalized inflammation of oral tissues associated with denture wear; however, allergic reactions of the mucosa may be caused by denture-base material, denture cleansing materials, or denture fixing preparation^.'^ Compounds in denture materials that may cause allergic stomatitis include resin monomers, hydroquinone (used as an inhibitor or stabilizer contained in the acrylic monomer resin), benzoyl peroxide, dimethyl-p-toluidine (a polymer which is an initiator of the cold-curing process), and metha~rylate.~" Cold-cured dentures are more likely to produce allergic dermatitis of the oral mucosa than are heat-cured dentures.lS A positive patch test is required to establish the diagnosis of denture-base allergy. Patch testing with the denture should be avoided. Similarly, applying denture fillings under a Finn chamber should be avoided, as pressure from the hard particulate matter frequently causes a nonspecific irritation of the skin. Patch testing should be performed with the liquid monomer or individual components of the dentures in solution or in petrolatum. Positive patch test reactions to a single component of dentures cannot be interpreted if the dentures have been heatcured. There is a "denture sore mouth" syndrome that occurs predominantly in women, and for which no cause has been identified. Studies have demonstrated no causal role for allergy to dentures, heat trapped under the dentures, or infections with Candida.59It may be that psychological factors, such as stress or as yet unidentified "other" factors, may be causing the symptoms. The space under the dentures tends to trap food and promotes an ideal environment for the growth of Candida.5" Oral candidiasis may contribute to symptoms of soreness and burning in denture wearers, and such individuals do not usually have candidal infections at other body sites. A potassium hydroxide (KOH) examination of tissue scraped from involved mucosa can be most helpful when the broad hyphi of Candida are present. Positive cultures from the mouth are less reliable because of the nonpathogenic presence of yeast in the mouths of many people.
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RUBBER CHEMICALS IN GLOVES
With the mandate of universal precautions by the Occupational Safety and Health Administration (OSHA), anyone who has direct patient involvement or who works with blood products must wear gloves.61Even outside the healthcare field, gloves are a probable primary sensitizing vehicle for the majority of the population, and all are constantly exposed to natural rubber latex (NRL) through the use of protective wear. It is not surprising that the population is now susceptible to NRL allergies. NRL products are encountered with examination and surgical gloves, catheters, and dental dams. A wide spectrum of symptoms have been associated with NRL allergy, from pruritus, eczematous eruptions, contact dermatitis (stomatitis), urticaria, asthma, angioedema, and anaphylaxis. The recent reports of severe anaphylactic reactions with fatalities compel physicians in all specialties to be cognizant of, and prepared to deal with, the clinical ramifications of an immediate type I allergic reaction to NRL protein. Patients with NRL allergy typically present with symptoms that suggest the diagnosis of diffuse or patchy eczema on the contact area (of a dental dam, or surgical gloves), often accompanied by itching, redness, vesicles, and sores. Like all allergic contact reactions, the type IV response to NRL can develop anywhere from minutes to hours after exposure, and may persist for several weeks after initial contact.28 Although a delayed reaction to the chemical additives is the predominant immunologic response with NRL exposure, NRL can also induce immediate hypersensitivity. Predisposed individuals, usually atopics, are most susceptible to these type I reactions. The clinical manifestations of these reactions are highly variable, depending on the primary route of exposure, the amount of bioavailable antigen, and the individual’s allergic potential. A common factor in the most severe reactions with generalized urticaria, hypotension, and anaphylactic shock has been the direct exposure of body tissue or mucous membranes to NRL products during surgery. Mucous membranes provide ideal conditions for elution and absorption of the protein allergens.44 The diagnosis of NRL sensitivities is based on carefully taken histories. Both environmental and certain genetic factors have been well defined as elements of risk in NRL allergies. Occupational exposure is a significant risk factor for healthcare workers or anyone who routinely wears NRL gloves on the job. The greatest risk, however, is among children with a history of multiple surgeries, with the highest incidence reported among children with spina bifida.39Atopy is an important indicator of potential problems. Of surgeons and nurses studied in Finland, 67% of the type I positive individuals were atopic whereas only 17.4% of the nonsensitized people had an atopic history.53Crossreactivity also plays a potential role in the development of NRL allergy.
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Bananas, avocados, chestnuts, kiwi, passion fruit, fig, papaya, and numerous other foods have produced symptoms in NRL-sensitive individuals.44Conversely, subjects allergic to those foodstuffs have experienced adverse reactions after contact with NRL. Patients with a history of allergic reactions to latex should be aware of the potential for allergic reactions to these foods, and individuals with such food allergies may have a significant risk for developing NRL sensitivity. Concomitant immediate and delayed allergy was previously considered unusual, but combined reactions are now being reported more freq~ently.~ Patch testing may verify a delayed allergy to rubber chemicals whereas an immediate allergy to latex remains undetected. The skin-prick test is most reliable for diagnosing immediate allergic reactions, and NRL sensitivity is no exception. There is no standard NRL antigen available in the United States, but it is available in Europe and Canada. Variations in office-based antigen extraction methods and source materials prevent direct comparisons, but may be valuable in individual sites, especially when the extraction is made from the NRL source being used. Management and Prevention of NRL Allergy
Once the diagnosis of NRL allergy is made or suspected, the physician must help the patient avoid latex exposure (more than 20,000 consumer items contain NRL).Z7Preoperative medications have been used with "at risk" latex-sensitive patients; however, the efficacy of premeditation has not been established. Despite appropriate H1 plus H2 antagonists (the authors recommend doxepin 25 mg 1 hour before exposure) and systemic prednisone (60 mg 6-8 hours prior to surgery), anaphylaxis has been documented in patients with known latex hypersensitivity. Tosi et a1 have reported the successful use of premedications in latex-allergic patients with spina bifida, but not without vigorous efforts to provide a latex-free environment. An anaphylaxis protocol should be available in all medical facilities. Epinephrine should be administered at the earliest sign of the systemic catastrophe, plus the availability of equipment to maintain a patent airway may be life-saving. Prompt summoning of emergency medical technician (EMT) services and transference to a hospital is recommended. DIFFERENTIAL DIAGNOSIS OF ALLERGIC CONTACT STOMATlTlS
The increasing awareness on the part of dermatologists and dentists of the distress suffered by patients afflicted with mucosal disease be-
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hooves us to establish a correct diagnosis to develop an effective program of therapy. Many different conditions of the oral mucosa have a superficially similar clinical appearance (i.e., that of a white plaque). Thus, a careful history is paramount in leading to the suspicion of a ”contact” stomatitis. The differential diagnosis includes precancerous and cancerous lesions; viral and fungal infections; aphthous stomatitis; oral lichen planus; vesiculobullous disease, such as pemphigus vulgaris; Stevens-Johnson syndrome; oral hairy leukoplakia in the immunocompromised (HIV-infected)host; and the Melkerson-Rosenthal syndrome.4*
DIAGNOSIS OF ORAL CONTACT DERMATITIS (STOMATITIS)
Clues in the patient’s history and physical examination should raise the possibility of a contact dermatitis (stomatitis). A mucosal biopsy is a diagnostic procedure that will identify an inflammatory (spongiotic) dermatosis, but it is nonspecific. More importantly, a biopsy will rule out other considerations in the differential diagnosis.
Patch Testing is the Gold Standard for Identification of a Contact Allergen
There is no need to test the oral mucosa directly; whenever the oral mucosa is sensitized, so is the skin.16 The paradox of patch testing lies in its deceptive simplicity. Although the application of antigens for patch testing is rather simple, antigen selection and patch test interpretation can be difficult. It requires extensive knowledge and sufficient e~perience.~ All patients should be tested to a ”standard” series and to selected preservatives and antigens relevant to the clinical Always test nonstandardized antigens on three controls if it is positive on the patient. After patch tests are interpreted, the data must be reviewed and the clinical relevance must be ascertained. Experience and textbook references are essential in unraveling the puzzle. Product labels must be carefully reviewed, and further data can be obtained from the manufacturer.
THERAPY OF ALLERGIC STOMATITIS
Optimal therapy of all contact dermatitides require identification of the offending antigen and its elimination from contact with the patient.
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In most cases, prompt removal of the specific contact allergen or irritant is all that is necessary to effect a cure.
Local Therapy
For swelling of the lips or edema of the oral mucosa, the application of ice cold water compresses or sucking on ice chips is helpful. Painful erosions or ulcers may be sprayed with aerosolated steroids (Aerobid [Forest Pharmaceuticals, St. Louis, MI], Azmacort M [Poulenc-Rorer Pharmaceuticals, Collegeville, PA]) 2 to 3 times a day. If the lesions are painful, lidocaine (Xylocaine viscous) may be applied. Seven or eight sprays of aerosolized epinephrine (Primetine Mist [Whitehall-Robins Healthcare, Madison, NJ], Medihaler-Epi [3M Pharmaceuticals, St. Paul, MN]) directly into the oral cavity can be helpful in relieving rapidly progressing angioedema of the tongue, uvula, and epiglottis (concomitantly with systemic therapy).
Systemic Therapy
In the more uncomfortable patient, oral prednisone (0.5-1 .O mg/ kg/d) may be required for 10 to 20 days after removal of the allergen. Antihistamines are only helpful for type I (urticaria1 or angioedematous) reactions.
References 1. Abramson A: Causes of stomatitis. Medical World News June 28, 1974; 19. 2. Alanko K, Kanerva L, Jolanki R, et al: Oral mucosal diseases investigated by patch testing with a dental screening series. Contact Dermatitis 34263-267, 1996 3. Belsito D V Contact urticaria caused by rubber: Analysis of seven cases. Contact Dermatitis 8:61-66, 1990 4. Beltrani VS, Beltrani VP: Contact dermatitis. AM Allergy Asthma Immunol 78:160-
175,1997 5. Berglund A, Molin M: Mercury vapor release from dental amalgam in patients with symptoms allegedly caused by amalgam fillings. Eur J Oral Sci 10456-63, 1996 6. Bircher AJ, Pelloni F, Langauer MS, et al: Delayed hypersensitivity reactions to corticosteroids applied to mucous membranes. Br J Dermatol 135:310-313, 1996 7. Bolewska J, Holmstrup P, Moller-Madsen B, et al: Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med 19:3942, 1990 8. Brendlinger DL, Tarsitano JJ: Generalized dermatitis due to sensitivity to a chromecobalt removable partial denture. J Am Dent Assoc 81:395-397, 1970 9. Bruze M: Systemically induced contact dermatitis from dental resin. Scand J Dent Res 102376-378, 1994 10. Cohen L Ulcerative lesions of the oral cavity. Int J Dermatol 19:62-64, 1980
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11. Davidson WM, Sheinis EM, Sheperd SR: Tissue reaction to orthodontic adhesives. Am J Orthod 82:502-505, 1982 12. Elgart ML, Higdon RS: Allergic contact dermatitis to gold. Arch Dermatol 103:649652, 1971 13. Fernstreom AEB: Mercury allergy with eczematous dermatitis due to silver amalgam fillings. Br Dent J 113:20&211, 1962 14. Fisher AA: Allergic sensitization of the skin and oral mucosa to acrylic denture materials. JAMA 156238-242, 1954 15. Fisher AA: Allergic sensitization of the skin and oral mucosa to acrylic resin denture materials. J Prosthet Dent 6:600-604, 1956 16. Fisher AA: Contact stomatitis, glossitis, and cheilitis. Otolaryngol Clin North Am 7827-830, 1974 17. Fisher AA: Allergic reactions due to metals used in dentistry. Cutis 14:797-802, 1974 18. Fisher AA: Contact stomatitis. Dermatol Clinic 5:4:709-717, 1987 19. Fisher AA, Shapiro A: Allergic eczematous contact dermatitis due to metallic nickel. JAMA 161:717-720, 1956 20. Frykholm KO: On mercury from dental amalgam: Its toxic and allergic effects and some comments on occupational hygiene. Acta Odonto Scand 22(suppl 15):230-242, 1957 21. Garioch J, Todd P, Lamey P-J, et al: The significance of a positive patch test to mercury in oral disease. Contact Dermatitis 23:301-305, 1990 22. Gaul LE: Immunity of the oral mucosa in epidermal sensitization to mercury. Arch Dermatol 93:4548, 1966 23. Gonzalo GMA, Bobadilla GP: Cutaneous-mucosal allergic contact reaction due to topical corticosteroids. Allergy 50:833-836, 1995 24. Gots H, Fortmann I: Can amalgam fillings cause a mercury sensitization of the skin? Haut Geschlectskr 26:34-37, 1959 25. Gruskin SE, Tolman DE, Wagoner RD: Oral manifestations of uremia. Minn Med 53:495499, 1970 26. Haberman A, Pratt M, Storrs FJ: Contact dermatitis from beryllium in dental alloys. Contact Dermatitis 28:157-162, 1993 27. Hamann CP: Natural rubber latex protein sensitivity in review. Am J Contact Dermatitis 44-21, 1993 28. Hamann CP, Sullivan KM: Natural rubber latex hypersensitivities. In Charlesworth EN (ed): Cutaneous Allergy. Cambridge, Blackwell Science, pp 155-208, 1997 29. Helton J, Storrs F: The burning mouth syndrome: Lack of a role for contact urticaria and contact dermatitis. J Am Acad Dermatol 31:201-205, 1994 30. Hochman N, Zalkind M: Hypersensitivity to methyl methacrylate: Mode of treatment. J Prosthet Dent 77:93-96, 1997 31. Jolly M: White lesions of the mouth. Int J Dermatol 5:719-721, 1977 32. Jolly M, Moule AJ, Freeman S: Amalgam related chronic ulceration of oral mucosa. Br Dent J 160:434437, 1986 33. Laeijendecker R, vanJoost T Oral manifestations of gold allergy. J Am Acad Dermatol 30~205-209, 1994 34. Laine J, Kalimo K, Forsell H, et al: Resolution of oral lichenoid lesions after replacement of amalgam restorations in patients allergic to mercury compounds. Br J Derm 126:lO15, 1992 35. Lamey P-J, Lamb AB, Hughes A, et a1 Type 3 burning mouth syndrome: Psychological and allergic aspects. J Oral Pathol Med 23216-219, 1994 36. Lowney ED: Unresponsiveness to a contact sensitizer in man. J Invest Dermatol 51:411, 1968 37. Lubbe J, Wuthrich B: Amalgam allergy and amalgam controversy. Scweiz Med Wochenschr 126:661-665, 1996 38. Maurice PDL, Hopper C, Rycroft R, et a!: Allergic contact stomatitis and cheilitis from iodoform used in a dental dressing. Contact Dermatitis 18:114-117, 1988 39. Meeropol E, Kelleher R, Bell S, et al: Allergic reactions to rubber in patients with myelodysplasia. N Engl J Med 323:1072, 1990
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40. Merk H, Ebert L, Goerz G: Allergic contact dermatitis due to the fungicide hexitidine. Contact Dermatitis 8:216-218, 1982 41. Miller RL, Gould AR, Bernstein ML: Cinnamon-induced stomatitis venenata. Oral Surg Oral Med Oral Pathol 73:708-711, 1992 42. Miles DA, Rogers RS: Disorders affecting the oral cavity. Dermatol Clin 14:2-22, 1996 43. Nolan A, Lamey P-J, Milliken KA, et al: Recurrent aphthous ulceration and food sensitivity. J Oral Pathol Med 20:473475, 1991 44. Reeve CM, VanRoekel NB: Denture sore mouth. Dermatol Clin 5:681-686, 1987 45. Rietschel RL, Fowler JF: Mucous membrane contact dermatitis. In Fisher AA (ed): Contact Dermatitis. Baltimore, Williams & Wilkins, 1995 46. Sainio EL, Kanerva L: Contact allergens in toothpastes and a review of their hypersensitivity. Contact Dermatitis 33:lOO-105, 1995 47. Shah M, Lewis FM, Gawdrodger DJ: Contact allergy in patients with oral symptoms: A study of 47 patients. Am J Contact Dermatitis 7146-151, 1996 48. Sidi E, Casalis J: Les intolerance's de a1 Muqueuse Buccale. Presse Med 59:730-733,1951 49. Staikaer L, Menne T: Nickel allergy and orthodontic treatment. Eur J Ortho 12284289, 1990 50. Taaffe A, Riggott JM: Aetiological factors in denture stomatitis. Br J Dermatol 1073841, 1982 51. Thomson J, Russell JA: Dermatitis due to mercury following amalgam dental restoration. Br J Dermatol 82292-296, 1970 52. Todd P, Garioch J, Lamey P-J, et al: Patch testing in lichenoid reactions of the mouth. Contact Dermatitis 23:300-301, 1990 53. Turjanmaa K Incidence of immediate allergy to latex gloves in hospital personnel. Contact Dermatitis 17:270-276, 1987 54. Van Groeningen G, Nater Jl': Reactions to dental impression materials. Contact Dermatitis 1:373-375, 1975 55. VanJoosst T, VanUlsen J, VanLoon LAJ: Contact allergy to denture materials in the burning mouth syndrome. Contact Dermatitis 18:97-99, 1988 56. VanLoon LAJ, VanElsas PW, Van Joost T, et al: Contact stomatitis and dermatitis to nickel and palladium. Contact Dermatitis 11:292-296, 1984 57. Veien NK, Borchorst E, Hattel T, et a1 Stomatitis or systemically-induced contact dermatitis from metal wire in orthodontic materials. Contact Dermatitis 30:210-213, 1994 58. Vilaplana J, Romaguera C, Cornellana F: Contact dermatitis and adverse oral mucous membrane reactions related to the use of dental prostheses. Contact Dermatitis 30:8084, 1994 59. Wakkers-Garritsen BG, Timmer LH, Nater JP: Etiologic factors in the denture sore mouth syndrome: An investigation of 24 patients. Contact Dermatitis 1:337-340, 1975 60. Wilson HT: Nickel dermatitis. Br J Dermatol 67:291-295, 1955 61. Wrangsjo K IgE-mediated Latex Allergy and Contact Allergy to Rubber in Clinical Occupational Dermatology. Stockholm, National Institute of Occupational Health, 1993
Address reprint requests to Vincent S . Beltrani, MD 29 Fox Street Poughkeepsie, NY 12601
CONTACT DERMATITIS
ORAL MUCOUS MEMBRANE CONTACT DERMATITIS Derek H. Jones, MD, and Vincent S. Beltrani, MD
1
Oral mucous membrane contact dermatitis (or contact stomatitis) is relatively rare. In general, the mucosa is more resistant to primary irritants, and is not as readily sensitized as the skin. The oral mucosa is also constantly bathed in saliva, which washes sensitizers from the mucosal surface and prevents adequate contact. Furthermore, abundant mucosal vasculature allows for rapid absorption and clearing of allergens. Nevertheless, contact reactions can occur on the oral mucous membrane. Contact sensitivity has been described as a factor in recurrent oral ulceration43,32 and oral lichenoid reactions.52As with other types of contact dermatitis, allergic contact dermatitis may be difficult to distinguish from irritant contact dermatitis, and it may also mimic oral changes of vitamin deficiency, certain anemias, uremic stomatitis, and candidiasis.I8 Although the prevalence of allergic contact sensitivity in the mouth is unknown, a number of substances have been reported to cause oral symptoms.
CLINICAL PRESENTATIONS In a recent review of patients referred for patch testing because of oral symptoms, Shah et a147found mouth/lip swelling, tingling/burning,
From the Department of Dermatology, Columbia-Presbyterian Hospital (DHJ, VSB), and the Department of Dermatology, College of Physicians & Surgeons of Columbia University (VSB), New York, New York
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and local anesthetic reactions to be the most common presenting complaints of patients with positive patch test results. The clinical presentation of contact dermatitis in the mouth is dependent upon the offending substance and the duration of contact. The oral symptoms may include numbness, aguesia (loss of taste), and burning sensation^,^^, 35, 29 which are often more prominent than the physical signs. Itching is a rare symptom of contact stomatitis. Objectively, changes may be barely visible or may vary from a mild erythema to a fiery red color, with or without edema. Vesiculation of the oral mucosa is rarely seen because vesicles rupture quickly to form erosions. Oral lichen planus2 and other lichenoid reactions characterized by white patches may be seen with allergens that have persistent contact with the mucosa, such as compounds used in dental appliances and hardware (Figs. 1A and B). In rare instances of marked edema, difficulty in swallowing and breathing may occur. Allergic mucosal dermatitis is often accompanied by a perioral contact dermatitis, which manifests as an eczematoid eruption characterized with the more typical pruritus, erythema, and scale affecting the lips and adjacent skin. As a general rule, once the oral mucosa has been sensitized, the skin is sensitized as well; however, it has been reported that sensitization of the oral mucosa with dinitrochlorobenzene actually increases skin t ~ l e r a n c e . ~ ~ CHEMICAL AND TRAUMATIC INJURY
The oral mucosa is relatively resistant to thermal injury, although hot foods or liquids may cause mild to severe burns of the oral mucus characterized by erosions or bullae. A distinctive cause of a circular lesion seen on the palate is the "pizza burn," caused by the adhesion of hot pizza to the palate. A variety of chemicals may accidentally burn the mouth, such as household lyes, gasoline siphoned from a car, pipetted caustic agents, or chemicals inadvertently applied during dental treatment (phenol, silver nitrate, nitric acid). Strong caustics will cause tissue necrosis that appears clinically as white Aspirin placed next to a "sore" tooth is a common cause of an irritant dermatitis or mucosal u1cer.lo Undiluted Shohl's solution (9.8% sodium citrate and 14% citric acid) may also cause direct irritation of the oral mucosa, especially in patients with poor oral hygiene or in debilitated patients who have trouble swall0wing.4~ Ammonia that is liberated from the action of bacterial urease on salivary urea in patients with renal failure can present with a uremic stoma ti ti^.^^ Leukoplakia or hyperplastic white patches (leukedema) of
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Figure 1. A and B, A 14-year-old female developed extensive leukedema of entire buccal mucosa and gingiva 4-6 weeks following the applications of a nickel-containing orthodontic device. Patch tests revealed a 1 reaction to cobalt and nickel. Buccal mucosal biopsy showed leukedema, without an inflammatory infiltrate.
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the mucosa may result from prolonged irritation from ill-fitting dentures or dental appliances (braces).
Allergic Contact Stomatitis A wide range of allergens may be responsible for oral and perioral symptoms. The most common allergens identified, however, may be divided into four main groups:
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1. Allergens contained in dental and mouth-care products 2. Food additives (flavorings and antioxidants) 3. Metals used in dental restorations 4. Rubber chemicals in examination gloves
DENTAL AND MOUTH-CARE PRODUCTS
Mouthwashes are medicated liquids used for cleansing the mouth for therapeutic or cosmetic purposes, and like dentrifices, may contain alcohol, flavorings, antiseptics, and preservatives. The abrasives in dentrifice’s are not sensitizers. The allergens in mouthwashes and dentrifices that have been implicated in allergic stomatitis include formaldehyde, mercurial antiseptics, benzalkonium chloride, dichlorophene (G-1l), antibiotic agents, flavorings, fluorides and coloring agents. Cinnamon flavorings, particularly cinnamic aldehyde, and peppermint are probably the most common cause of allergic stomatitis from dentrifices, and they are included in many These patients will present with a burning oral sensation, a stomatitis, and frequently with a perioral dermatitis.41 Chemical injury of the oral mucosa may be caused by undiluted mouthwashes of perborate of hydrogen peroxide. Denture cleansers may contain acids, alkali, or oxygenating compounds which may cause chemical burns or ”store teeth” dermatitis of the mouth if dentures are not thoroughly rinsed after soaking1 Despite the widespread use of corticosteroids on the mucous membranes of the respiratory tract, mucosal contact sensitivity has apparently been uncommon; however, since the introduction of new corticosteroids, such as tixocortol pivalate and budesonide, mucosal contact sensitivity has been reported. Stomatitis and pharyngitis due to budesonide in a bronchial inhaler has been Another report noted tixocortol pivalate in oral lozenges caused an allergic contact stomatitis.h
ALLERGIC STOMATITIS CAUSED BY METALS
Allergic contact stomatitis due to orthodontic metal is rare. There are a number of reports of contact stomatitis due to metal in patients with dental plates, crowns, or other orthodontic material^,^^ and oral lichen planus has been associated with mercury in amalgam fillings.5R, 33, 2h The metals used in dentistry that have been responsible for contact dermatitis include mercury, chromate, nickel, gold, cobalt, beryllium, and palladium. Of these metals, mercury has most often been implicated as a producer of allergic reaction^.'^
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Mercury Probably the most common contact with mercury in the general population occurs from mercury amalgam dental fillings. Lichenoid lesions of the mouth have been reported as a result of allergy to mercury contained in amalgam dental fillings.2' Clinically the lesions appear as hyperplastic white patches in the mouth, and frequently occur at the mucosal site in contact with the filling. In addition to localized lesions of the oral mucosa, mercury from amalgams has been incriminated as the cause of generalized dermatitis in mercury-sensitive individual^.'^ This generalized dermatitis is thought to be related to mercury vapor that is liberated during the preparation and insertion of dental fillings. Once the filling is completely inserted, however, the amount of mercury liberated in comparison to the preparation and insertion process is Nonetheless, there are reports noting the disappearance of chronic eczema upon removal of mercury-containing amalgams.48 In a recent study of the relationship of oral lichenoid lesions to mercury-containing amalgams, 21 of 91 patients studied had positive patch test reactions to mercury.34 Of these 21 patients, 18 had oral lichenoid lesions adjacent to mercury filling whereas three patients had neither amalgam fillings nor oral lesions. In 15 of the 18 symptomatic patients, the amalgam fillings were removed and replaced with nonmercuric fillings. After a mean follow-up of 3.2 years, seven patients had achieved a complete cure whereas six had marked improvement, and two had no change. Gots and F ~ r t r n a n nreported ~~ that allergic reaction of the skin to mercury that is detected during routine tests is not due to the effect of amalgam fillings.Z4Gaul reported three patients with mercury dermatitis in whom epidermal sensitivity to mercury was demonstrated, but no irritation was noted in the mouth adjacent to amalgam dental fillings.22 Another recent study has documented mercury in macrophages in lesional and nonlesional skin adjacent to mercury-containing amalgam, giving further evidence to support a mechanism for allergic contact dermatiti~.~ Additionally, immediate and sometimes persistent urticaria1 reactions have been described in association with mercury dental restor a t i o n ~ .Therefore, ~' in mercury-sensitive individuals with persistent oral lesions, urticaria or eczematous dermatitis, it may be justifiable to replace amalgam filling with gold or nonmetallic fillings. Shah et a147and the author (VSB) have each had a patient who had unilateral jaw pain for years on the side of their mouth, where mercury amalgam fillings were present. They both reported a metallic taste in the mouth. Both patients reacted to mercury and ammoniated mercury on patch testing. Upon removal of the amalgam, the author's patient
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became symptom-free, and has remained symptom-free three years later. (Shah’s patient did not have the filling removed.) There exists a cadre of physicians who, under the guise of a “fashionable” title of ”clinical ecology” profess as ”alternative medicine” an amalgam disease. The issue has received extensive coverage in the lay as well as the medical media. They have created confusion regarding the terms mercury allergy, mercury burden and intoxication, and amalgam allergy, the understanding of which is crucial in the consideration of this controversy. The amalgam disease has been introduced as a term to identify patients who typically ascribe a variety of subjective symptoms to their amalgam fillings. When these physicians make the aforementioned diagnoses, they demand removal of all dental amalgam. Although dental amalgam is the most important source of mercury burden in the general population, occupational exposure to mercury within established exposure limits reaches levels much higher without evidence of intoxication. Current literature lacks sound evidence of a role for amalgam in human disease other than allergy.5,37
Nickel
Allergic contact stomatitis and cheilitis can occur from nickel-plated instruments used in dental procedures. Nickel-sensitive individuals can present with allergic stomatitis, perleche, and erosions resembling aphthous ulcers by holding needles, pins, bobby pins, coins, keys, and other objects in and near the mouth.”, 60 Nickel is the most common cause of allergic contact dermatitis. Five patients with nickel sensitivity on patch testing had small nickel plates glued to the oral mucosa for 7 days. All five developed lesions at the site that were clinically and histologically consistent with contact dermatiti~.~~ Nickel-containing metal alloys are widely used for dental prostheses and orthodontic appliances; however, a recent study noted that nickelsensitive patients are not at greater risk of developing oral symptoms or lesions when wearing intraoral orthodontic appliance^.^"
Other Metals Pins containing chrome-cobalt combination to fasten porcelain teeth to acrylic dentures may produce stomatitis in persons sensitized to cobalk8 Gold is becoming increasingly recognized as an allergen, and a case has been described where gingival mucosa in contact with a gold filling
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sloughed and sites of previous contact with gold jewelry flared.I2 In Shah et a l ’ evaluation ~ ~ ~ of 47 patients, only one patient reacted to gold (sodium theosulfatoarate). This patient experienced tingling on the oral mucosa immediately adjacent to new dental crowns. Metal was showing on the crowns that contained gold. Symptoms resolved after the crowns were removed. Sensitization to gold should be considered as a possible cause of allergic contact stomatitis, as well as a pathogenic or triggering factor in oral lichen p l a n u ~ . ~ ~ Because of the high cost of gold, alloys containing nickel, cobalt, chromium, copper, palladium, and beryllium are being used. Contact dermatitis of the oral mucosa has rarely been associated with these latter compounds.
DENTAL IMPRESSION COMPOUNDS These preparations may contain a variety of substances, of which resin is most likely to cause sensitization.’*Fluxes which contain borax, boric acid, silica and potassium fluoride are strong irritants. Modern bonding adhesive materials may contain acrylic monomers and epoxy resins and hardeners that may cause allergic reactions. Resins are adhesive materials used in a wide variety of dental reconstructive procedures, including pit and fissure sealant, orthodontic adhesives, glazes, veneers, and repair kits for porcelain-fused-to-metal restorations, root canal sealers, and temporary crowns. Resins and bonding adhesives contain acrylic monomers which must be polymerized by either heat (ultraviolet or visible light) or cold curing. Unpolymerized monomers and other components of bonding adhesives may cause allergic reactions of the oral mucosa or urticaria, although such events are considered rare.” Unpolymerized material in the cured resin may be leached out by saliva, water, soda water, and alcohol. In general, coldcured resins are much more likely to cause allergic contact dermatitis on the oral mucosa. Allergic reactions to these binding materials may occur in the patient, the operator, or office personnel. Widespread dermatitis has been reported to occur in a resin-sensitive patient after dental treatment with a resin-containing p r o d ~ c t . ~ Scutan, an epimine plastic used for temporary crowns and bridges, contains methyl-p-toluene, and has been linked to untoward mucosal reaction in individuals sensitive to this compound on patch tests.54 Additionally, allergic reactions of the mucosa have been attributed to methyldichlorobenzene sulfonate 0.1% in dibenzyltoluol present in impregum, an impression rubber material used for construction of crowns and bridges. It is usually in contact with the oral mucosa only briefly.
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ANTISEPTICS AND PRESERVATIVES IN ORAL MEDICATIONS
A wide variety of potential sensitizers may be present in antiseptics and preservatives added to certain dentrifices, mouthwashes, topical oral medications, and anesthetics. Sensitizers in dentrifices may produce cheilitis and circumoral dermatitis. Elimination of dentrifices containing specific preservatives or cosmetics is a difficult problem, as there is no law to impel manufacturers of toothpastes to indicate the presence of a preservative in their products.l8These include dichlorophene (G-4) (most common), formaldehyde, merthiolate, phenylmercuric nitrate, ethylenediamine hydrochloride, parabens (a rare sensitizer), hexachlorophene (Gll), sodium perborate, and quaternary ammonium compounds. Iodoform contained in a ribbon gauze used for packing in dental procedures may cause an allergic stomatitis,%as can hexetidine contained in garg l e ~Allergic . ~ ~ reactions to antibiotic compounds used intraorally may be due to the antibiotic or the flavoring or coloring agents. SURFACE OR TOPICAL ANESTHETICS
Benzocaine is a common and potent sensitizer found in many oral topical medications, including mouthwashes and gargles. The use of benzocaine-containing oral sprays may produce immediate-type "anaphylactic" IgE-mediated severe reactions in benzocaine-sensitive individuals. Symptoms may include angioedema of the mouth and larynx, wheezing, urticaria, syncope, and hypotension progressing to vascular collapse. Patch testing with local anesthetics does not reveal the immediate anaphylactic-type reaction. Benzocaine-sensitive individuals can be tested with the anesthetic intradermally or by "prick-test" to detect the presence of IgE antibodies. Benzocaine cross-reacts with para-aminobenzoic acid (PABA) compounds (i.e., procaine, tetracaine, etc.) and these related substances should also be avoided. Anesthetics containing the amide linkage, such as lidocaine (Xylocaine),can be used in benzocaine-sensitive patients.
STOMATITIS CAUSED BY DENTURES
When examining the oral cavity of a person wearing complete dentures, physicians should remember they are observing the changes caused by the prosthesis itself as well as the relevant oral changes associated with the aging edentulous patient. Oral mucosa does not respond in the same manner as skin to everyday wear and tear. Mucosa
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demonstrates a low tolerance to injury or i r r i t a t i ~ nMany . ~ ~ patients with denture stomatitis are unaware that they have the condition, as it is frequently asymptomatic. Others may report a burning or itching sensation of the mucosa. The inflammation occurs more frequently in the maxillary arch, and the tissue of the maxillary mucosa that is actually in contact with the denture base may become extremely erythematous. Although allergy to dentures is frequently implicated as the cause of inflammatory changes beneath prosthetics, usually the reactions are due simply to trauma from poorly fitting dentures. Fortunately, true allergy to the materials in denture bases is rare. Clinically, the allergic reaction resembles the generalized inflammation of oral tissues associated with denture wear; however, allergic reactions of the mucosa may be caused by denture-base material, denture cleansing materials, or denture fixing preparation^.'^ Compounds in denture materials that may cause allergic stomatitis include resin monomers, hydroquinone (used as an inhibitor or stabilizer contained in the acrylic monomer resin), benzoyl peroxide, dimethyl-p-toluidine (a polymer which is an initiator of the cold-curing process), and metha~rylate.~" Cold-cured dentures are more likely to produce allergic dermatitis of the oral mucosa than are heat-cured dentures.lS A positive patch test is required to establish the diagnosis of denture-base allergy. Patch testing with the denture should be avoided. Similarly, applying denture fillings under a Finn chamber should be avoided, as pressure from the hard particulate matter frequently causes a nonspecific irritation of the skin. Patch testing should be performed with the liquid monomer or individual components of the dentures in solution or in petrolatum. Positive patch test reactions to a single component of dentures cannot be interpreted if the dentures have been heatcured. There is a "denture sore mouth" syndrome that occurs predominantly in women, and for which no cause has been identified. Studies have demonstrated no causal role for allergy to dentures, heat trapped under the dentures, or infections with Candida.59It may be that psychological factors, such as stress or as yet unidentified "other" factors, may be causing the symptoms. The space under the dentures tends to trap food and promotes an ideal environment for the growth of Candida.5" Oral candidiasis may contribute to symptoms of soreness and burning in denture wearers, and such individuals do not usually have candidal infections at other body sites. A potassium hydroxide (KOH) examination of tissue scraped from involved mucosa can be most helpful when the broad hyphi of Candida are present. Positive cultures from the mouth are less reliable because of the nonpathogenic presence of yeast in the mouths of many people.
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RUBBER CHEMICALS IN GLOVES
With the mandate of universal precautions by the Occupational Safety and Health Administration (OSHA), anyone who has direct patient involvement or who works with blood products must wear gloves.61Even outside the healthcare field, gloves are a probable primary sensitizing vehicle for the majority of the population, and all are constantly exposed to natural rubber latex (NRL) through the use of protective wear. It is not surprising that the population is now susceptible to NRL allergies. NRL products are encountered with examination and surgical gloves, catheters, and dental dams. A wide spectrum of symptoms have been associated with NRL allergy, from pruritus, eczematous eruptions, contact dermatitis (stomatitis), urticaria, asthma, angioedema, and anaphylaxis. The recent reports of severe anaphylactic reactions with fatalities compel physicians in all specialties to be cognizant of, and prepared to deal with, the clinical ramifications of an immediate type I allergic reaction to NRL protein. Patients with NRL allergy typically present with symptoms that suggest the diagnosis of diffuse or patchy eczema on the contact area (of a dental dam, or surgical gloves), often accompanied by itching, redness, vesicles, and sores. Like all allergic contact reactions, the type IV response to NRL can develop anywhere from minutes to hours after exposure, and may persist for several weeks after initial contact.28 Although a delayed reaction to the chemical additives is the predominant immunologic response with NRL exposure, NRL can also induce immediate hypersensitivity. Predisposed individuals, usually atopics, are most susceptible to these type I reactions. The clinical manifestations of these reactions are highly variable, depending on the primary route of exposure, the amount of bioavailable antigen, and the individual’s allergic potential. A common factor in the most severe reactions with generalized urticaria, hypotension, and anaphylactic shock has been the direct exposure of body tissue or mucous membranes to NRL products during surgery. Mucous membranes provide ideal conditions for elution and absorption of the protein allergens.44 The diagnosis of NRL sensitivities is based on carefully taken histories. Both environmental and certain genetic factors have been well defined as elements of risk in NRL allergies. Occupational exposure is a significant risk factor for healthcare workers or anyone who routinely wears NRL gloves on the job. The greatest risk, however, is among children with a history of multiple surgeries, with the highest incidence reported among children with spina bifida.39Atopy is an important indicator of potential problems. Of surgeons and nurses studied in Finland, 67% of the type I positive individuals were atopic whereas only 17.4% of the nonsensitized people had an atopic history.53Crossreactivity also plays a potential role in the development of NRL allergy.
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Bananas, avocados, chestnuts, kiwi, passion fruit, fig, papaya, and numerous other foods have produced symptoms in NRL-sensitive individuals.44Conversely, subjects allergic to those foodstuffs have experienced adverse reactions after contact with NRL. Patients with a history of allergic reactions to latex should be aware of the potential for allergic reactions to these foods, and individuals with such food allergies may have a significant risk for developing NRL sensitivity. Concomitant immediate and delayed allergy was previously considered unusual, but combined reactions are now being reported more freq~ently.~ Patch testing may verify a delayed allergy to rubber chemicals whereas an immediate allergy to latex remains undetected. The skin-prick test is most reliable for diagnosing immediate allergic reactions, and NRL sensitivity is no exception. There is no standard NRL antigen available in the United States, but it is available in Europe and Canada. Variations in office-based antigen extraction methods and source materials prevent direct comparisons, but may be valuable in individual sites, especially when the extraction is made from the NRL source being used. Management and Prevention of NRL Allergy
Once the diagnosis of NRL allergy is made or suspected, the physician must help the patient avoid latex exposure (more than 20,000 consumer items contain NRL).Z7Preoperative medications have been used with "at risk" latex-sensitive patients; however, the efficacy of premeditation has not been established. Despite appropriate H1 plus H2 antagonists (the authors recommend doxepin 25 mg 1 hour before exposure) and systemic prednisone (60 mg 6-8 hours prior to surgery), anaphylaxis has been documented in patients with known latex hypersensitivity. Tosi et a1 have reported the successful use of premedications in latex-allergic patients with spina bifida, but not without vigorous efforts to provide a latex-free environment. An anaphylaxis protocol should be available in all medical facilities. Epinephrine should be administered at the earliest sign of the systemic catastrophe, plus the availability of equipment to maintain a patent airway may be life-saving. Prompt summoning of emergency medical technician (EMT) services and transference to a hospital is recommended. DIFFERENTIAL DIAGNOSIS OF ALLERGIC CONTACT STOMATlTlS
The increasing awareness on the part of dermatologists and dentists of the distress suffered by patients afflicted with mucosal disease be-
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hooves us to establish a correct diagnosis to develop an effective program of therapy. Many different conditions of the oral mucosa have a superficially similar clinical appearance (i.e., that of a white plaque). Thus, a careful history is paramount in leading to the suspicion of a ”contact” stomatitis. The differential diagnosis includes precancerous and cancerous lesions; viral and fungal infections; aphthous stomatitis; oral lichen planus; vesiculobullous disease, such as pemphigus vulgaris; Stevens-Johnson syndrome; oral hairy leukoplakia in the immunocompromised (HIV-infected)host; and the Melkerson-Rosenthal syndrome.4*
DIAGNOSIS OF ORAL CONTACT DERMATITIS (STOMATITIS)
Clues in the patient’s history and physical examination should raise the possibility of a contact dermatitis (stomatitis). A mucosal biopsy is a diagnostic procedure that will identify an inflammatory (spongiotic) dermatosis, but it is nonspecific. More importantly, a biopsy will rule out other considerations in the differential diagnosis.
Patch Testing is the Gold Standard for Identification of a Contact Allergen
There is no need to test the oral mucosa directly; whenever the oral mucosa is sensitized, so is the skin.16 The paradox of patch testing lies in its deceptive simplicity. Although the application of antigens for patch testing is rather simple, antigen selection and patch test interpretation can be difficult. It requires extensive knowledge and sufficient e~perience.~ All patients should be tested to a ”standard” series and to selected preservatives and antigens relevant to the clinical Always test nonstandardized antigens on three controls if it is positive on the patient. After patch tests are interpreted, the data must be reviewed and the clinical relevance must be ascertained. Experience and textbook references are essential in unraveling the puzzle. Product labels must be carefully reviewed, and further data can be obtained from the manufacturer.
THERAPY OF ALLERGIC STOMATITIS
Optimal therapy of all contact dermatitides require identification of the offending antigen and its elimination from contact with the patient.
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In most cases, prompt removal of the specific contact allergen or irritant is all that is necessary to effect a cure.
Local Therapy
For swelling of the lips or edema of the oral mucosa, the application of ice cold water compresses or sucking on ice chips is helpful. Painful erosions or ulcers may be sprayed with aerosolated steroids (Aerobid [Forest Pharmaceuticals, St. Louis, MI], Azmacort M [Poulenc-Rorer Pharmaceuticals, Collegeville, PA]) 2 to 3 times a day. If the lesions are painful, lidocaine (Xylocaine viscous) may be applied. Seven or eight sprays of aerosolized epinephrine (Primetine Mist [Whitehall-Robins Healthcare, Madison, NJ], Medihaler-Epi [3M Pharmaceuticals, St. Paul, MN]) directly into the oral cavity can be helpful in relieving rapidly progressing angioedema of the tongue, uvula, and epiglottis (concomitantly with systemic therapy).
Systemic Therapy
In the more uncomfortable patient, oral prednisone (0.5-1 .O mg/ kg/d) may be required for 10 to 20 days after removal of the allergen. Antihistamines are only helpful for type I (urticaria1 or angioedematous) reactions.
References 1. Abramson A: Causes of stomatitis. Medical World News June 28, 1974; 19. 2. Alanko K, Kanerva L, Jolanki R, et al: Oral mucosal diseases investigated by patch testing with a dental screening series. Contact Dermatitis 34263-267, 1996 3. Belsito D V Contact urticaria caused by rubber: Analysis of seven cases. Contact Dermatitis 8:61-66, 1990 4. Beltrani VS, Beltrani VP: Contact dermatitis. AM Allergy Asthma Immunol 78:160-
175,1997 5. Berglund A, Molin M: Mercury vapor release from dental amalgam in patients with symptoms allegedly caused by amalgam fillings. Eur J Oral Sci 10456-63, 1996 6. Bircher AJ, Pelloni F, Langauer MS, et al: Delayed hypersensitivity reactions to corticosteroids applied to mucous membranes. Br J Dermatol 135:310-313, 1996 7. Bolewska J, Holmstrup P, Moller-Madsen B, et al: Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med 19:3942, 1990 8. Brendlinger DL, Tarsitano JJ: Generalized dermatitis due to sensitivity to a chromecobalt removable partial denture. J Am Dent Assoc 81:395-397, 1970 9. Bruze M: Systemically induced contact dermatitis from dental resin. Scand J Dent Res 102376-378, 1994 10. Cohen L Ulcerative lesions of the oral cavity. Int J Dermatol 19:62-64, 1980
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