PHYSICIANS' DESK REFERENCE - Allergy/Hypersensitivity to Fluoride:

"In hypersensitive individuals, fluorides occasionally cause skin eruptions such as atopic dermatitis, eczema or urticaria. Gastric distress, headache and weakness have also been reported. These hypersensitivity reactions usually disappear promptly after discontinuation of the fluoride."
SOURCE: PHYSICIANS' DESK REFERENCE, 1994, 48th Edition, p. 2335-6.

ESTIMATED INCIDENCE - Allergy/Hypersensitivity to Fluoride:

"One percent of our cases reacted adversely to the fluoride. By the use of placebos, it was definitely established that the fluoride and not the binder was the causative agent. These reactions, occurring in gravid women and in children of all ages in the study group affected the dermatologic, gastro-intestinal and neurological systems. Eczema, atopic dermatitis, urticaria, epigastric distress, emesis, and headache have all occurred with the use of fluoride and disappeared upon the use of placebo tablets, only to recur when the fluoride tablet was, unknowingly to the patient, given again. When adverse reactions occur, the therapy can be readily discontinued and the patient or parent advised of the fact that sensitivity exists and the element is to be avoided as much as possible."
SOURCE: Feltman R, Kosel G. (1961). Prenatal and postnatal ingestion of fluorides - Fourteen years of investigation - Final report. Journal of Dental Medicine 16: 190-99.

CASE REPORTS - Feltman (1956) Dental Digest:

Out of the 601 cases in the adult group, six have shown undesirable side effects from the fluoride supplement. Five out of the 495 children have presented evidence of undesirable reactions. This is 1 per cent incidence of side effects...

Case 1

The patient was a seven-year old white child with an itchy skin rash, headache, epigastric distress, generalized weakness, and listlessness. Her discomfort was such that most of her time in school was spent in the nurse's room. When the tablets were withdrawn, symptoms disappeared but returned again when therapy was reinstituted. Again withdrawal resulted in disappearance of symptoms. The patient has been symptom free since. The parents of this child refused to allow further experimentation.

Case 2

A report from a physician concerning an experience with a white male child, two and a half years of age when treatment was instituted, states: "Beginning in his first year of life, after an episode of measles, the child developed an atopic dermatitis, at first, involving the entire skin of the body and with usual treatment receding to a controllable state. He was placed on fluoride, 1 milligram, every day. Approximately three days after ingestion of the daily dose, he developed a generalized vesicular type of rash associated with marked pruritus. Upon cessation of the drug, the rash markedly improved in ten days when he was again placed on the fluoride which again resulted with a rash of the same general appearance. After this second episode the use of fluoride was terminated."

Case 3

A 23-year-old well-oriented primipara in the fourth month of pregnancy was admitted to the prenatal clinic on January 7, 1955. She was placed on fluoride tablets, one daily, slowly dissolved in the mouth. After one week the drug was stopped because she developed a rash on her face. The rash looked like chapped blotches of various sizes and shapes, it was scaly and itchy, and covered the entire forehead, right cheek, and chin. The rash did not occur on the left cheek or chin.

Fluoride discontinued - The patient's face cleared up in three days on discontinuing the fluoride. Upon resuming the tablets the rash recurred in two days, this time accompanied by nausea. Tablets were again withdrawn and symptoms disappeared. Two weeks later the patient returned to the clinic and was directed to take the tablets again.

Development of Serious Symptoms - The patient took the tablets for three days, the rash reappeared and she developed serious symptoms including vomiting with blood showing in the vomitus. The fluoride description was discontinued. The patient then continued an uneventful pregnancy and delivered a healthy baby.

General Conclusions from Case Histories

The cases described indicate that certain patients react unfavorably to fluoride therapy. Whether the fluorine acts as an allergen after short term use or whether the fluorine acts as an intoxicant after many months of use, is unknown and should be determined.

Possible Association with Allergy - It has been reported that cases of fluorine intoxication occur in persons with a history of allergy. It is emphasized that a lower threshold in tolerance to drugs in allergic patients must be reckoned with. (10)

Termination of Undesirable Effects Simple - Whatever the mechanism involved it is simple to terminate the undesirable reaction of fluoride dosage by discontinuing the ingestion of the tablets. If the source of the fluoride is the public water supply, the problem is more complicated.

Additional Investigation Needed - Much has yet to be learned and understood regarding the metabolism and physiologic actions of this element and its salts.

SOURCE: Feltman R. (1956). Prenatal and postnatal ingestion of fluoride salts: A progress report. Dental Digest 62: 353-357.

CASE REPORTS - Waldbott (1958) International Archives of Allergy:

Case no. 1... This patient had had a tendency to allergic nasal disease, to gastro-intestinal and bladder disturbances due to food and other allergy... A 1:10 dilution of 1% NaF in horse serum reproduced diarrhea, nasal obstruction, edema of both eyes and general pruritus within a few minutes, lasting for about 24 hours. Control tests with horse serum and with a weaker solution of NaF had no effect, whatsoever. The tests were made (2/23/56) in another allergist's office (Dr. C.M.). On July 14, 1956, I produced the same results within 10 minutes with a 0.1% aqueous solution of sodium fluoride (.1 mg).

Case no. 3. An 8-year-old girl gave a history since infancy, of abdominal pains associated with anorexia, frequent pyelitis and pruritus vulvae. Since early 1956 she had intermittently spastic pains and paresthesias in legs and arms. She consulted me because of seasonal upper respiratory allergy... 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... Only 16% of the test dose of fluoride was recovered in the urine of a 137 mg. calcium diet; 17% on a daily calcium intake of 3.3 grams (7/1/57).

Case no. 4. Mrs. H.S., age 33, consulted me because or urticaria present intermittently for about 2 years; it had gradually become more severe in recent weeks. It was not related to food, season of the year, menses or ingestion of drugs. It was associated with pains in arms and legs, ulcers in the mouth, spastic abdominal pains, diarrhea and nausea, polyuria and dysuria, paresthesias in both arms and hands, bilateral frontal headaches radiating into the occipital region, loss of memory, inability to concentrate. In recent months, the patient had several episodes of syncope without apparent cause. She had had a mild sinus disease for about ten years.

On examination as an in-patient at Harper Hospital she exhibited a generalized papulous urticaria involving trunk and all extremities. Except for slight tenderness in the left lower quadrant and some muscular weakness in both hands, the examination was negative. Laboratory tests were unrevealing.

After having avoided fluoride water for 2 weeks, the patient was given, 2 days before the test, 6.8 mg. of F as NaF and another 6.8 mg. on the day of the test. The first dose caused no ill effect. However, within 30 minutes after she had taken the second dose she developed a severe outbreak of urticaria, cephalgia, paresthesias in legs and hands. She became lethargic and developed pain in the epigastric region followed by spastic pain in the lower abdomen. These symptoms began to clear in about one hour... Only 3.6 percent of the total test dose of 6.8 mg. of F was recovered in the urine within 24 hours.

Case no. 5. Mrs. B.M., 50-year-old white female, consulted me because of generalized urticaria present since December, 1952, usually worse on arising. In addition, she complained of severe headaches, paresthesias in arms and hands, pains in legs and edema of both ankles, ulcers in the mouth, pain in the lower spine.

Typical urticarial lesions were present on trunk and extremities; there was limitation in motion in the lower spine. Laboratory and biochemical studies were entirely normal, except for a sedimentation rate of 67 mm per hour. There was X-ray evidence of sclerotic changes of the lower spine. An allergic survey including extensive intradermal tests failed to detect anything significant. On 6/10/57 the patient while being kept on a low (137 mg.) calcium diet was given a placebo test of 300 cc. of distilled water. It caused no ill effect. On June 12th 2 mg. NaF (.9 mg. F) in 300 cc. of distilled water was administered. The patient was not aware that the water contained fluoride. She had previously had similar tests (glucose tolerance and urea clearance). Within 20 minutes she developed a generalized urticaria associated with cough and pain in the gastric region followed by marked flatulence in the abdomen.

This test was repeated on June 18th, after placing the patient on a high calcium (2 gms.) diet to which 1.3 gms. of calcium lactate had been added. The patient experienced the same symptoms as had occurred subsequent to the above-described test. Urticaria dominated the picture.

Since eliminating fluoridated water for drinking and cooking foods all symptoms have subsided.

Case no. 6. Mrs. N.S., 29 years-old, consulted me on 10/7/57 because of a dermatitis in the suprapubic area and at the adjoining parts of both thighs. This had been present for 3 1/2 months during the past two weeks. She also complained of paresthesias in arms and legs, of severe frontal headaches associated with blurring of the eyes, dizziness and fainting spells, pain and stiffness in the lower spine, mild arthritic symptoms migratory in character, affecting practically every joint.

The skin eruption was characteristic of a dermatitis with papulo-pustular lesions, showing many scratch marks. There was tenderness and limitation in motion in the lower spine, hyper-reflexia in both extremities; otherwise the examination was negative.

X-rays showed minor hypertrophic changes in the lower spine. Blood and urine studies were normal except for an increase in cholesterol esters (130.5 mg.%). Intradermal skin tests were inconclusive.

During the stay at Women's Hospital the lesions improved spontaneously without treatment.

On 10/10/57, the patient was given a placebo test dose of 300 cc. of distilled water. It had no ill effect. The following day she received 6.8 mg. of fluoride as NaF in the same amount of water. Within one hour the skin lesions which had practically subsided returned with marked vesiculation, oozing and severe pruritus. In addition she developed frontal headache, lethargy and minor episodes of syncope. The headaches began to subside after 5 to 6 hours; the skin started to improve during the following days.

This patient has been well without treatment following elimination of fluoride water.

SOURCE: Waldbott GL. (1958). Allergic Reactions from Fluorides. International Archives of Allergy 12: 347-355.

CASE REPORTS - Waldbott (1959) Acta Allergologica:

"On 2/11/58 she was given 300 cc of distilled water on the fasting state with no ill effect. On 2/14/58, 6.8 mg of F was administered as NaF in 300 cc of water. Within two hours parasthesias in arms and legs accompanied by generalized angioneurotic edema and marked pruritus developed. This was followed by arhralgia, particularly in lower spine and by edema in wrists, fingers, ankles and toes, by suprapubic pain and dysuria. During the following 3 days the urticaria and joint swellings increased in intensity; they subsided within a week... Following avoidance of fluoride water for drinking and cooking and of high fluoride foods such as tea and seafood, she was given three bottles of water, identical in appearance, labelled 1, 2, and 3. From each bottle she took 1 tablespoon for seven consecutive days. One bottle contained 1 mg F per tablespoon, the daily dose recommended for water fluoridation. Neither the patient nor the examiner knew which one of the 3 bottles contained F. Urticaria, paresthesias and muscular pains appeared after the third day 4/28/58 on the fluoride solution."

SOURCE: Waldbott GL. (1959) Urticaria due to fluoride. Acta Allergologica 13: 456-468.

CASE REPORTS - Shea (1967) Annals of Allergy:

SUMMARY: Six children and one adult exhibited various allergic reactions after the use of toothpaste and vitaimin preparations containing fluoride. The following conditions were encountered: Urticaria, exfoliative dermatitis, atopic dermatitis, stomatitis, gastro-intestinal and respiratory allergy.

Case Reports

The following cases deal with allergic reactions to fluoride containing vitamins and toothpastes:

Case 2: C.E.O., a seven-month-old female child, had been taking Tri-Vi-Flor daily for five weeks since January 4, 1966. About that time she developed an exudative, pruritic dermatitis on the neck, face and in the antecubital and retropopliteal areas accompanied by diarrhea, abdominal cramps and bloody stool. The parents noted that the cramps occurred exclusively, shortly after the afternoon feedings when the baby received the fluoride drops. The drug, therefore, was discontinued. The skin immediately began to clear up. Within one week the eruption had healed, no medication had been prescribed. The child has been in good health ever since.

Case 3: E.A., a 6-week-old female, bad been placed on Tri-Vi-Flor when she was three weeks old. During the 5th week of life, the mother noticed an acute erythematous, diffuse pruritic exanthema. She consulted one of us (SMC) on October 14, 1966, five days after the onset of the rash. The baby appeared seriously ill. An exfoliative dermatitis covered nearly the whole body surface. During the examination the child bad a dark brown bowel movement, suggestive of enteric bleeding. The urine contained numerous red cells. The blood count showed slight anemia, a leucopenia, a 10 per cent eosinophilia and a normal leucocyte-lymphocyte ratio. Benadryl (25 mg) was administered for symptomatic relief. Since S.M.G. had encountered two other cases of dermatitis due to Tri-Vi-Flor drops, they were discontinued. Within five days the exantherma disappeared. The baby was placed on Tri-Vi-Sol without fluoride and no further symptoms occurred.

Case 4: B.W., an 8-week-old female, presented an eczematoid eruption on the face and trunk. She had been on an evaporated milk formula and Tri-Vi-Flor since the second week of life, and on cereal since the third. As a therapeutic trial, the milk was discontinued and soybean broth substituted. When there was no improvement, the cereal was eliminated from the baby's diet. However, the dermatitis persisted with increasing severity. At that time the fluoride drops were discontinued. Within 3 days there was visible fading of the eczema. The child has since been on plain vitamin drops and has had no further illness.

Case 6: C.P., female age 14 months, had been taking Tri-Vi-Flor drops regularly since 3 weeks of age. Shortly thereafter she started having a persistent diarrhea. At 8 weeks of age she developed what appeared to be pylorospasm, but a pylorotomy failed to relieve the gastric symptoms. At the age of 10 months she suffered from rhinorrhea, dyspnea, intermittent swelling of the salivary glands and submaxillary lymphadenopathy. These symptoms failed to respond to antihistamines and antibiotics. On December 5, 1965, the mother discontinued the drops. Within three days there was a marked improvement. The child has remained symptomfree since eliminating the drops.

Case 7: L.W., a 6-year-old girl, consulted one of us (GLW) on December 26, 1963, for an allergic survey because of what appeared to be gastro-intestinal allergy. She had been taking Poly-Vi-Flor, three to four drops daily, since early infancy. Her complaints were frequent nausea, vomiting, pains in the hypogastrium and episodes of abdominal cramps, diarrhea, headaches, and occasional bloody stools followed by fever, up to 104 degrees. These attacks occurred on an average of every ten days. The child failed to gain weight. At first the diagnosis of food allergy and/or chronic appendictis was considered but neither diagnosis was corroborated by x-rays and an allergic work-up. Since the gastro-intestinal episodes usually occurred within one-half hour of the ingestion of the fluoride drops, the medication was discontinued. Improvement began immediately and was followed by complete recovery.

SOURCE: Shea JJ, et al. (1967). Allergy to fluoride. Annals of Allergy 25:388-91.

CASE REPORTS - Grimbergen (1974) Fluoride:

Case M.R., female, age 28, (Code G-1) had experienced ulcers in the mouth, general pruritus, acneform lesions around the mouth and eyes for 12 days prior to the test. In the preliminary screening, the patient was taken off fluoridated water during which interval she had no complaints. In January 1973 immediately upon disappearance of her illness, the (double-blind) test was initiated. On the 12th day of employing bottle #1, the ulcers in the mouth recurred, whereupon the patient switched to distilled water exclusively. After a 5 day interval the ulcers had subsided and the patient resumed the test. Use of bottle #4 reproduced the symptoms. They recurred on the 8th day and lasted for 14 days. Ten days following the use of bottle #7 the symptoms recurred with general pruritus which lasted for 17 days. The recurrence of these minor symptoms correlated preciselly with the intake of fluoride water in bottles 1, 4, and 7.

An additional experiment was carried out by a participant of our panel (G.G.) who had not been ill prior to the test.

He consumed four glasses of water each of which contained 1 ppm fluoride (total of 1 mg fluoride per day) without any noticeable effect. Subsequently he drank four glasses of water with 2 ppm (total 2 mg fluoride per day) without experiencing any reaction. The following day he repeated the experiment with 3 ppm fluoride in water and four ppm the next day. At 5 mg of fluoride per day he experienced diarrhea and bloating in the abdomen. The day following the disappearance of these symptoms he took a glass of 20 ppm fluoride (total 5 mg per day). This induced a severe stomatitis which disappeared after 10 days. When he reduced the dose to 4 glasses of water each of which contained 4 ppm of fluoride, the intestinal symptoms returned in conjunction with dryness of the oral mucosal membranes. After these symptoms disappeared he consumed 4 glasses of water each containing 3 ppm fluoride. Again the symptoms appeared but did not recur after taking 4 glasses containing 2 ppm. This experiment suggests that if fluoride has already been stored in the system, the symptoms recur at a lower concentration than without prior fluoride intake. We name this phenomenon "charging effect."

SOURCE: Grimbergen GW. (1974). A double blind test for determination of intolerance to fluoridated water (preliminary report). Fluoride 7:146-152.

CASE REPORTS - Zanfagna (1976) Fluoride:

Case 2: Mrs. J.G. of Methuen, Mass. reported severe, allergic reaction in her 4 year-old son caused by ingestion of a fluoride tablet. Within minutes after taking a fluoride pill, sudden extreme edema of lips and tongue was followed promptly by severe periorbital edema and swelling in the pharynx and nasal passages, dypsnea and wheezing. Whereas no further data could be obtained on this case, the outbreak of this episode is so characteristic of allergic shock from fluoride that its report here is believed to be warranted.

SOURCE: Zanfanga PE. (1976). Allergy to fluoride. Fluoride 9: 36-41.