Hypersensitives – Topical Effects

Summation Allergic/Hypersensitive Reactions to Topical Fluorides:

Ever since fluoride toothpastes were introduced in the mid 1950s, case reports have been published in the scientific literature documenting the occurrence of allergic/hypersensitive reactions (primarily of the skin) resulting from the use of topical fluorides. These reactions include: perioral dermatitis; stomatitis, and urticaria.

The evidence of inflammtory skin disorders in humans from topical application of fluoride is supported by carefully controlled studies on animals. When topical fluoride has been applied to the skin of rabbits or rats, inflammation has been repeatedly noted, particularly, if not only, when the skin is cut or damaged prior to the application.

However, despite the fact that many dermatologists consider fluoride toothpaste a common cause of perioral dermatitis; the dental community – to the best of FAN’s knowledge – has yet to organize or publish any comprehensive research investigating this issue.

Excerpts from the Scientific Literature Allergic/Hypersensitive Reactions to Topical Fluorides in Humans: (back to top)

“[F]luorides easily pass through the mouth’s mucous membrane but do not cross the skin barrier. This would explain the lack of response of ordinary p-tests. Anyway, in cases of benign aphthosis, replacing toothpaste with normal soap is not such a difficult test. Of course, not all benign recurrent aphthoses respond favorably to this test, but because of its simplicity, it would be unwise not to try it. In cases of fluoride intolerance it would also be important to eliminate, among other items, salts and beverages enriched with fluoride compounds from the family diet…”
SOURCE: Brun R. (2004). Recurrent Benign Aphthous Stomatitis and Fluoride Allergy. Dermatology 208: 181″It is my understanding that dermatologists frequently recommend that their patients with perioral dermatitis discontinue use of toothpastes with pyrophosphates and/or fluorides, citing that these are the most frequent causes.”
SOURCE: McCaffery K. (2003). Fluoride and dermatitis. Journal of the American Dental Association 134: 1166.

“Discontinuing use of strong topical steroid lotions, or toothpastes containing fluoride or pyrophosphates, seems to reduce the symptoms of perioral dermatitis… [I]f this is the case, these patients need to be educated about other preventive measures to prevent tooth decay.”
SOURCE: Fuchs SS. (2003). Fluoride and dermatitis. Journal of the American Dental Association 134: 1167.

“This preliminary study demonstrates that tacrolimus 0.075% ointment may be effective for patients with steroid-induced rosacea, when combined with avoidance of topical steroid use, as well as avoidance of other agents known to aggravate rosacea (caffeine, spicy foods, alcohol, hot fluids, and fluoride).”
SOURCE: Goldman D. (2001). Tacrolimus ointment for the treatment of steroid-induced rosacea: a preliminary report. Journal of the American Academy of Dermatology 44: 995-8.

“7 hours after the 3rd application, a very severe disseminated acute urticaria and facial angioedema appeared, requiring hospital admission… The clinical features and patch tests do not allow a distinction to be made between immunological and non-immunological contact urticaria. Nevertheless, the case confirms that, in some atopic patients, painting the teeth with sodium fluoride can lead to severe and potentially dangerous reactions.”
SOURCE: Camarasa JG, et al. (1993). Contact urticaria from sodium fluoride. Contact Dermatitis 28: 294

“A patient is reported who had a suggestive but not proved exacerbation of dermatitis herpetiformis from a dental fluoride treatment, presumably through both local and systemic absorption. It seems reasonable that fluorides can produce a reaction similar to the one well established for their close relatives, the iodides. Physicians caring for persons with dermatitis herpetiformis should be aware of this possibility.”
SOURCE: Bovenmyer D. (1985). Aggravation of dermatitis herpetiformis by dental fluoride treatments. Journal of American Academy of Dermatology 12: 719-720.

“We decided to conduct a study of the possible role of fluoride toothpaste in the development of PD (perioral dermatitis) when one of our patients noted dramatic improvement after switching from a fluoride to a nonfluoride toothpaste… She remained free of lesions for approximately three months, at which point we asked her to resume use of fluoride toothpaste. Within a few days she experienced an exacerbation of PD (perioral dermatitis) that resolved completely when she stopped using the fluoride toothpaste. Table 2 presents the results of the double-blind crossover phase of the study… [T]he data seem to support our hypothesis that fluoride-containing dentrifices play a role in the development of PD (perioral dermatitis). Six of the fourteen patients who completed the study experienced exacerbations of PD while using the fluoride-containing toothpaste but not while using the nonfluoride. Two patients reported mild reactions with both the fluoride and nonfluoride toothpastes, and six patients experienced no reaction with either toothpaste.
SOURCE: Mellette JR, et al. (1983). Perioral dermatitis. Journal of the Association of Military Dermatologists 9: 3-8. **Click here to read the full paper**

“In two patients receiving [topical fluoride] therapy a papulonodular eruption developed, similar to the recognized halogenodermas. These cases may help to increase awareness of this entity.”
SOURCE: Blasik LG, Spencer SK. (1979). Fluoroderma. Archives of Dermatology 115:1334-5.

“Since its description in 1957… perioral dermmatitis (PD) has continued to be a perplexing entity. Many causes have been postulated, including sunlight sensitivity, birth control pills, emotional stress, fluorinated steroid creams, Candida albicans, and rosacea. We have gathered clinical and historical data implicating fluoride dentrifices as an important etiologic factor in this dermatosis… For the past eighteen months, we have been conducting a clinical study with the assumption that in some patients, fluoride dentrifices cause or aggravate perioral dermatitis. The clinical and historical evidence gathered has been impressive in support of this hypothesis.”
SOURCE: Mellette JR, et al. (1976). Fluoride tooth paste: A cause of perioral dermatitis. Archives of Dermatology 112: 730-731. **Click here to read the full paper**

“I recently received a note from Emery Kocsard, MD, of Sydney, Australia, who has had an interest in perioral dermatitis and who has published an article on that subject. In his article, he anticipated the possible relevance of fluorinated toothpastes and fluoridated corticosteroids to the perioral dermatitis problem. In his note, he reported that, since reading my letter to the editor, he had treated approximately 50 patients with fluoride-related perioral dermatitis; in all cases, the condition responded favorably after the discontinuance of the use of fluorinated toothpastes.”
SOURCE: Saunders MA. (1976). Fluoride toothpaste as a cause of acne-like eruptions. Archives of Dermatology 112: 1033-1034.

“Recognizing the fact that fluoride toothpastes are the prevalent type of dentrifice and that my findings could be a mere coincidence, I requested, nevertheless, that these patients switch, on a trial basis, from their fluoride toothpastes to a nonfluoride-containing toothpaste. Within a period varying from two to four weeks, approximately one half of the patients thus observed cleared of their previously persistent acne-like eruption… Several of the patients, who were concerned about the dental health factors relative to fluoride and its exclusion, requested to resume use of a fluoride toothpaste despite assurances that fluoride in water and dental treatments should be sufficient for good dental health and protection. These patients were then allowed to resume use of a fluoride toothpaste. Without exception, each developed the same distribution of acne-like eruption that had previously occurred.”
SOURCE: Saunders MA. (1975). Fluoride toothpastes: A cause of acne-like eruptions. Archives of Dermatology 111: 793. **Click here to read the full paper**

“Mr. E. H., age 48, consulted one of us on May 9, 1961, because of giant urticaria of one month’s duration. The lesions involved mainly hands and feet and at times the entire body surface. At the first visit the lips and gums showed a marked edema. The lesions usually occurred about one hour after breakfast. The patient had been using a fluoridated toothpaste at that time… He was asked to discontinue the fluoride toothpaste and not to take any medication. Three days later, be reported having had only a single hive and slight residual pruritus. Six days later (May 18), he was completely free of symptoms.” (NOTE: This patient consented to a double-blind test to determine if fluoride toothpaste was in fact the cause. The double-blind test confirmed that the patient did in fact have an allergic reaction to fluoride.)
SOURCE: Shea JJ, et al. (1967). Allergy to fluoride. Annals of Allergy 25:388-91. **Click here to read the full paper**

“[S]he had 3 local applications of a 2% solution of NaF by her dentist in the manner usually employed for caries prophylaxis. After the first and second treatments the oral mucosa became edematous and irritated for periods of about 4 days. Within an hour after the third application on 3/5/56, a cheilitis developed involving the entire anterior portion of the oral mucosa. This subsided gradually within a week. Local application of this solution to the oral muccous membranes for about 30 seconds produced marked injection and edema of the test area. An intradermal test with a 1% aqueous solution of NaF produced an erythematous reaction of the size of a 25 cent piece; one for horse serum and horse serum combined with NaF were negative. On 6/18/57 the patient was given as a placebo 300 cc. of distilled water without ill effect. The following day a test dose of 6.8 mg. of fluoride (as NaF) elicited within 20 minutes moderately severe vomiting.”
SOURCE: Waldbott GL. (1958). Allergic Reactions from Fluorides. International Archives of Allergy 12: 347-355. **Click here to read the full paper**

“Mrs. L.C.H., 62-year-old white, developed an ulcer in the mouth within three days after she started to use stannous fluoride tooth paste. During the following 10 days, additional lesions developed throughout the oral mucosa accompanied by severe spastic pains throughout the whole abdomen, flatulence, diarrhea and dryness in mouth, nose and throat… Her dentist (Dr. W.H.P.) having observed a similar case suggested to her that the tooth paste might have induced this condition. Upon eliminating it, the condition gradually subsided… On 12/13/56, saline solution was applied with a cotton swab beneath her tongue without ill effect. Thirty minutes later a cotton swab soaked in 1% NaF was used similarly. Within 5 minutes hyperemia, edema and pruritus developed in the test area followed by more extensive irritation in a large portion of the oral mucosa. A smear of the mucus from the area showed marked eosinophilia. The patient refused further tests with the fluoride tooth paste.”
SOURCE: Waldbott GL. (1958). Allergic Reactions from Fluorides. International Archives of Allergy 12: 347-355. **Click here to read the full paper**

“There is nothing specific in the appearance of the lesions (stomatitis) which would distinguish or differentiate them from any of the other common oral pathologic processes. I believe that if one were to describe the lesions, it would be as shallow, superficially ulcerated areas which tend to have a whitish exudate on the surface and surrounding areas. The worst lesion and, indeed, the earliest lesions, commenced on the buccal mucosa opposite the teeth – that is, in those areas which come in contact with the teeth. The tongue, hard palate, soft palate, floor of the mouth, gingival regions and oral pharynx also produced similar ulcerations. Indeed, the longer the patient had used the fluoride dentrifice, the more chance he had of showing general involvement of the entire oral and pharyngeal regions… Treatment of these lesions is rather simple in the early stages – namely, changing to a dentrifice which does not contain fluoride… Those patients who had repeated courses of fluoride testing proved to be very grave problems indeed. In fact, some of them became so resistant to clearing of the oral lesions that I began to wonder if the lesions had not become irreversible. Duration from the time we actually commenced trying to rid the patients of their lesions until actual improvement was noted, was, indeed, very prolonged in those who had three, four or more courses of fluoride testing. The period from partial clearing to complete clearing of the lesions was even more prolonged and uncertain.”
SOURCE: Douglas TE. (1957). Fluoride dentifrice and stomatitis. Northwest Medicine 56: 1037-1039.

Excerpts from the Scientific Literature Fluoride-Enhanced Inflammation of Skin in Animals: (back to top)

“Application of ammonium fluoride under an occlusive patch to the abdomen of a rabbit converts a simple scratch into a double row of sterile pustules. Sodium fluoride produces a similar response, but ammonium chloride does not produce pustules… It appears that tissue damage and the presence of fluorides result in the ‘sterile pustular response.’ This can be called ‘enhancement of inflammation.’ The concentration of fluoride used will not induce inflammation, but it will enhance inflammation… We are not stating that iodide, fluoride, and nickel necessarily enhance inflammation in identical ways, but there is no doubt that they all enhance the inflammatory response. The fact that each of these substances produces the pustular patch test in man indicates that the reaction is not limited to animals.”
SOURCE: Stone OJ, Willis CJ. (1967). Enhancement of inflammation by fluorides. Texas Reports on Biology and Medicine 25: 601-6.

“Scratches were made to the depth of the upper dermis on the abdomen of rabbits. The scratches were covered by patch tests for 18 hours with solutions of stannous fluoride or stannous chloride. Both these substances produced a destructive reaction with intraepidermal polymorphonuclear leukocyte pustules occurring on each side of the scratch. Stannous fluoride was destructive at lower concentrations than stannous chloride. When these substances were patch tested over non-traumatized tissue, no tissue damage occurred… We believe that the metals and halogens that produce pustule along the scratch are damaging the body’s defenses against the mediators of inflammation and are therefore exaggerating the early cellular phase of inflammation… Dentrifices (toothpastes) are not made for prolonged contact with tissue; however, even brief exposure might influence preexisting oral pathology. Further clinical observations on the effects of fluoride dentrifices on oral inflammation are indicated.”
SOURCE: Stone OJ, Willis CJ. (1968). The effect of stannous fluoride and stannous chloride on inflammation. Toxicology of Applied Pharmacology 13: 332-8.

“Topical and systemic administration or contact with fluorides has produced various forms of cutaneous reactivity. These studies, conducted wtih 150-400 g. Sprague-Dawley rats, investigated the effect of topical application of NaF to a shaved, epidermal abraded region (5 cm) of dorsal skin. After 24 hrs. NaF (1%) produced inflammation of the epithelial keratin and the formation of intraepidermal vesicles abundant in fluid, polymorphonuclear leukocytes, lymphocytes, and erythrocytes. Edematous subendothelial changes were noted with cellular hypochromicity. Electron microscopy revealed extensive mitochondrial vacuolization. The cutaneous vesicles persisted for approximately 7 days after NaF application. In rats treated wtih NaF (23) skin histamine levels were significantly (p <0.01) elevated above those for NaCl-treated, H20-treated, or shaved only rats. In non-abraded skin NaF did not produce either chemical or histological changes. No further increase in vesicle formation or histamine elevation was produced by prolonging the duration of topical application. The accumulation of histamine as a result of NaF-induced inhibition of diamine oxidase, or enzymes of the skin glycolytic pathway providing for increased Ca++ availability, may explain the present data.”
SOURCE: Essman EJ, Essman WB. (1979). Rat skin reaction to topical fluoride: metabolic and histological changes. Federation Proceedings 38: 1242.

“The topical application of sodium fluoride to abraded rat skin produced several morphological and biochemical effects. Related to the degranulation of dermal mast cells, skin histamine concentration was increased, fluorides were absorbed into the skin, and deposited mainly kin mitochondria. Dermal histamine binding was decreased for both H1 and H2 receptors with reduced binding sites, but epidermal adenyl cyclase was activated by fluorides. The response of the rat skin to fluorides involves a sequence of changes by which the potentiation of an inflammatory response also involves alterations in specific histamine receptors and a histamine-specific adenyl cyclase system.”
SOURCE: Essman EJ, Essman WB, Valderrama E. (1981). Histaminergic mediation of the response of rat skin to topical fluorides. Archives of Dermatological Research 271: 325-40.

Thanks to Fluoride Action Network.

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