A. Case study
A mother took her 2-year-old daughter to see the 4th doctor regarding her persistent eczema. She had generalized eczema that did not have a specific pattern throughout the day and was only partially controlled by medication. The clinical history revealed that the child was exclusively breastfed from birth and that solid foods were introduced at the age of 6 months. Within a few weeks of this, the child developed a rash over her whole body. This was diagnosed as eczema by a pediatrician, and topical creams were prescribed. As she grew older, the eczema grew worse. She was placed on more medication. At the time of the 4th consultation, she was on 2 types of antihistamine and 2 types of steroid cream. Her general practitioner had done blood tests, but all serum-specific IgE levels were normal. It was not known whether total IgE had been done. She was placed on a low-allergenic diet with oral challenges, but this could not determine any cause. The mother suspected that additives aggravated the eczema. She began excluding these from her daughter's diet, and the symptoms improved slightly. Now the child was eating mainly homemade foods and few processed or pre-prepared foods. According to the mother, there was no other apparent cause or aggravation of the persisting skin reaction.

THOUGHT PROCESS
Could additives be causing the eczema?
It is possible. The mother stated that the exclusion of additives from her daughter's diet improved her condition. But it was clear that something else contributed to the symptoms. What were the options for further investigation?
a. Question the mother about the family history of allergy.

b. Question the mother about non-food factors in the child's environment (e.g., exposure to house dust mite, pets, smoke, perfumes, fabric softeners) that could aggravate her condition.

c. Investigate whether the child was exposed to (and perhaps reacting to) additives that the mother was not aware of. For example, the mother might consider sausage to be free of additives, but in actual fact most sausages are not.

d. Redo blood tests, or do skin prick tests.

e. Redo a low-allergenic diet with oral challenges, or do an elimination diet.

INTERVENTION:
a. The mother had light asthma, and the father hay fever; both to environmental allergens. This constituted a family history of allergy, but there was no known food allergy. The likelihood that the child had a food allergy was therefore lower.

b. There was no indication that any environmental factor had an effect on the child's condition. The mother had already made some changes in the house environment.

c. A detailed diet history was taken, but there were no indication that the child was ingesting any additives.

d. There was no reason to redo the serum-specific IgE tests, as the results would not have changed in such a short period of time-unless new allergens were tested for. There was, however, no hint as to which allergens could be relevant in this case. In some cases, it might be worth redoing serum-specific IgE tests as the results may change over time (some patients may develop tolerance to an allergen, while others may have been in the process of developing an allergy when the original IgE test came up negative, and still others may develop a totally new allergy). A total IgE test would be helpful in determining whether the child had an IgE-mediated reaction at all.

Can skin prick tests be done on an eczema patient? Only if the patient's forearm is clear of eczema. Otherwise, the skin could have a falsely positive reaction because of its sensitivity. Also, the patient must have been off antihistamines and steroid creams for a period of at least 7-10 days. If not, the test results could be falsely negative, with the medication preventing an immune response. The child's forearm was free of eczema at that time. She was not using topical creams on that area but was on a low dose of antihistamines.

The doctor decided to do a skin prick test for potato. This decision was based on recent evidence that potato is a more relevant allergen than was previously thought. Children under a year of age can develop an allergy to potato, as it is usually one of the first solids included in an infant's diet. The child in question had first developed the reaction at the time of the introduction of solids. The mother could not say that she had ever noticed an association between her daughter eating potato and the aggravation of her eczema. The child, however, enjoyed eating potato and ate it on a regular basis. The skin prick test was done using fresh raw potato. Within minutes, the child's arm started to itch. Not only did she react to the skin prick test, but she also developed papules (solid elevated lesion usually <10 mm) in the area of contact with potato (see picture below). Potato was thus identified as a possible major contributing factor in the eczema. The next step was to exclude this food from the diet to see whether the symptoms improved.

Potato (raw and cooked) was excluded from the child's diet, and her symptoms improved dramatically. The improvement was so great that she no longer needed medication. e. A low-allergenic diet was to be the next step if the exclusion of potato did not improve the child's symptoms. Even though it had been done before, it was not certain that it had been done properly.

TIP for Allergy Advisor users: In the case of a patient with suspected potato allergy, the Allergy Advisor database offers a quick reference to all the information that could be helpful in the assessment and management of such a patient: background information on potato (such as its various uses, which track "hidden allergen" and non-food exposure), the allergens that have been identified in potato, symptoms of IgE-mediated and other types of reactions to potato that have been reported in medical literature, possible cross-reactions with other foods, a list of other foods that belong to the same family as potato, and the references that were used for the above information.

B. More information:
Despite worldwide consumption of potato, allergy to potato is reported to be uncommon, and allergy to potato pollen even more uncommon. But the condition is probably underdiagnosed as we understand from recent literature.¹ Adverse reactions to potato seem to be more prevalent in atopic individuals, especially in birch pollen-sensitive individuals.²

Allergens in potato
Potato's biochemical composition includes proteins, glycoproteins and alkaloids (including solanine).1 One study reported that potato flour and starch are not allergenic.³ The study, however, did not evaluate the heat-stability of potato allergens. This opinion should therefore be reviewed, based on recent findings.

Potato contains many proteins, consisting of amino acid sequences. Some of the sequences (or whole proteins) are seen as hostile by the body, which mounts immune responses against them. In other words, they are allergens. In potato, only a few of the known allergens have as yet been characterised,³ namely Sol t 1, Sol t 2, Sol t 3.0101, Sol t 3.0102, and Sol t 4.^4,5,6 Potato-allergic individuals may be allergic to all the allergens or only to one or a few.

Cooked potato is usually well tolerated. Adverse reactions to both raw and cooked potato, however, have been documented.⁷ This is because both heat-labile and heat-stable allergens can be present.^7,8 Some people can eat and handle cooked potatoes without adverse reactions, but not raw potatoes.² This difference would be due to the presence of a heat-labile allergen.

Among the allergens identified, most of the focus has been on Sol t 1 (also known as patatin). It is reported to be a significant IgE-binding protein in children with a positive skin-specific IgE to raw potato, and it appears to be a relevant allergen in atopic dermatitis. There are conflicting reports on the heat-stability of this allergen, but it has been found partially stable to digestion.⁹

Potato belongs to the family Solanaceae. Other members of the family include tomato, cherry, eggplant, melon, pear, paprika, bell pepper, cayenne pepper, red pepper, tobacco, and chili.¹ Cross-reactivity can be strong within the same family, but there does not seem to be a strong cross-reactivity within this family. Potato and tomato, however, both contain the allergen patatin, and this may explain some of the cross-reactivity between these foods. Patatin has not been found in other members of the family.

Homology means "similarity" in the amino acid sequences of the proteins. The homology of an allergen in a plant (or animal) with another allergen in another plant (or animal) is expressed as a percentage. The higher the percentage, the more likely cross-reactivity will occur between the items. Patatin has 60% homology with a patatin-like allergen, Hev b 7, present in latex. In other words, the amino acid sequences in patatin are 60% similar to the amino acid sequences in Hev b 7.5,10 Patatin is thus a major cross-reactive protein in latex-associated potato allergy and appears to be relevant for atopic dermatitis. In other words, if a person reacts to patatin (in potato) specifically, he or she may, because of cross-reactivity, react to Hev b 7 (in latex) as well. But the cross-reactivity between Hev b 7 and patatin appears to be restricted mainly to latex-sensitized adults, suggesting a different mechanism of sensitization in children with atopic dermatitis.9 More on sensitisation below.

Potato contains other proteins that may cause adverse reactions, including the panallergen profilin,^11,12 and a chitinase (also a panallergen).¹³ Chitinase was identified as present in the potato plant, but its role as an allergen in the potato tuber specifically has not been defined. It is not even clear whether the chitinase is present in the tuber itself, as opposed to other parts of the plant. Adverse reactions have been reported to chitinase in other plants.

IgE reactions to potato
Reactions to potato can occur as a result of the ingestion of potato¹, the inhalation of finely dispersed particles of raw potato^2,14 or the inhalation of the plant pollen.¹ Skin reactions are most often caused by handling potato, and other reactions by the ingestion of potato.

Reactions have been reported to raw and cooked potatoes. As noted above, some people can eat and handle cooked potatoes without adverse reactions, but not raw ones.^2,15

The onset of allergic reactions to potato differs among individuals.⁷ Immediate, late and delayed reactions have been reported to both raw and cooked potato.^7,16 This may indicate that both IgE-mediated and other activation pathways are involved.¹⁶

In adult patients with pollen allergy, allergy to raw potato is associated mainly with Oral Allergy Syndrome. These patients seem to react to an allergen present in potato that is similar to an allergen in the pollen of birch, grass and mugwort.

There have been many reports of adverse reactions in adults handling or peeling raw potatoes. Most reports were of housewives and workers in the potato industry (i.e., occupational allergy). Symptoms reported include rhinoconjunctivitis, asthma, contact urticaria, atopic dermatitis, angioedema and immediate finger itching upon handling raw potato.^{2,6,14,24,25,26,27}But there have also been reports of children with reactions, ranging from contact urticaria^15,19 to anaphylaxis,^14,23 due to contact with raw potato.

How does sensitization occur?
The literature has shown both primary and secondary sensitization to potato.

a. Primary sensitization:
In children, as discussed above, sensitization is probably not latex-associated. White potato is a very common ingredient in the diet of Western countries, and in its cooked form it is one of the first solid foods introduced into a child's diet, usually around the age of 4-6 months.¹⁶ Because there are reports of children of less than a year of age developing adverse reactions to cooked potatoes,²⁸ it is proposed that sensitization can occur this early.

Sensitization can occur early in life but present with symptoms only later. Also, the symptoms that a person presents with can worsen with time. There was a case of an 11-year-old girl, exclusively breast-fed for her first 4 months, who developed anaphylactic symptoms after ingestion of cooked potato at 5 months of age, when she was fed potato for the first time. Subsequently, she developed urticaria, angioedema, and respiratory and systemic symptoms on contact with potatoes, ingestion of potatoes, and exposure to cooking potatoes or potato pollen.¹

b. Secondary sensitization:
It is proposed that, in some adults, initial sensitization to potato occurs by exposure to latex. Thereafter, Hev b 7-specific antibodies detect homologous regions in potato patatin to mediate potato allergy. It is suggested that the molecular basis of atopic dermatitis and acquired latex-fruit syndrome are different and should be carefully compared.⁹

An interesting example of secondary sensitization via primary sensitization was reported: A woman experienced adverse reactions to potato, tomato and latex. She worked with raw potatoes and tomatoes for years, without any adverse effects, until she started wearing rubber gloves. It may be that her allergy to latex arose secondarily via primary sensitization to potato and tomato.10

Unexpected exposure to potato

• Cooked potato can be dried and made into a powder and used as a thickener, or it can be added to cereal flours that are ingredients of bread, cookies, etc.

• Potatoes may be used for medicinal purposes:

• The leaves are said to be antispasmodic.


• A juice made from the tubers is used to treat peptic ulcers. But excessive doses of
  potato juice can be toxic.


• Raw and cooked potatoes have many functions as topical applications, e.g., for
  rheumatic joints, swellings, skin rashes, haemorrhoids, burns, scalds, and swollen
  gums.

If a person reacts to contact with potato, there are possible non-food exposures he or she should be aware of. For example:

• The potato is a source of starch for sizing cotton and making industrial alcohol, and for many other purposes in industry.


• Ripe potato juice is an excellent cleaner of silks, cottons and woolens. The water in which potatoes have been boiled can be used to clean silver and to restore a shine to furniture.


• Emollient and cleansing facemasks are made from potatoes and used to treat hard, greasy and wrinkled skin.

Other reactions to potato
a. Sulphites:
Skinned Potatoes or pre-cut French fries may be dipped in a sulphite or metabisulphite solution to prevent browning. The sulphite may trigger asthma in susceptible individuals.^29,30

b. Solanine (also known as Solasonine or Solanidine):
Solanine is a glycoalkaloid and a naturally occurring toxicant in plants that are members of the Solanaceae family. Solanine is present at low levels in the great majority of commercial varieties of potatoes and tomatoes available, but the substance can accumulate to high levels in greened (with green skin from exposure to light), stored or damaged potatoes. If ingested in large amounts, solanine may cause poisoning in humans and farm animals. Acute poisoning, including gastro-intestinal and neurological disturbances, may occur. Most individuals have a low serum level of solanine at any point in time and, according to the World Health Organization, the normal level of solanine in potatoes, 20-100 mg per kg of potatoes, is not of toxicological concern.^31,32

compiled by Karen du Plessis B.Sc. Diet. karen@allergyadvisor.com Food & Allergy Consulting & Testing Services (FACTS) PO Box 565 Milnerton 7435 South Africa

C. Comments by our editors

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D. References

1. Castells, MC, Pascual, C, Estaban, M, Ojeda, JA. Allergy to white potato. J Allergy Clin Immunol 1986;78:1110-1114.
2. Quirce S, Diet Gomez ML, Hinjosa M, Cuevas, et al. Housewives with raw potato-induced bronchial asthma. Allergy 1989;44:532-536
3. R. Wahl, Susanne Lau, et al. IgE-mediated Allergic Reactions to Potatoes. Int Arch Allergy Appl Immunol 1990:92:168-174.
4. Seppala U, Majamaa H, Turjanmaa K, Helin J, Reunala T, Kalkkinen N, Palosuo T. Identification of four novel potato (Solanum tuberosum) allergens belonging to the family of soybean trypsin inhibitors. Allergy 2001;56(7):619-26.
5. Seppala U et al. IgE reactivity to patatin-like latex allergen, Hev b 7, and to patatin of potato tuber, Sol t 1, in adults and children allergic to natural rubber latex. Allergy 2000;55:266-73.
6. Seppala U, Alenius H, Turjanmaa K, Reunala T, Palosuo T, Kalkkinen N. Identification of patatin as a novel allergen for children with positive skin prick test responses to raw Potato. J Allergy Clin Immunol 1999;103(1 Pt 1):165-71
7. Majamaa H, Seppala U, Palosuo T, Turjanmaa K, Kalkkinen N, Reunala T. Positive skin and oral challenge responses to potato and occurrence of immunoglobulin E antibodies to patatin (Sol t 1) in infants with atopic dermatitis. Pediatr Allergy Immunol 2001 Oct;12(5):283-8.
8. Iliev D, Wuthrich B. Occupational protein contact dermatitis with type I allergy to different kinds of meat and vegetables. Int Arch Occup Environ Health 1998 Jun;71(4):289-92.
9. Schmidt MH, Raulf-Heimsoth M, Posch A. Evaluation of patatin as a major cross-reactive allergen in latex-induced potato allergy. Ann Allergy Asthma Immunol 2002 Dec;89(6):613-8.
10. Tavadia S, Morton CA, Forsyth A. Latex, potato and tomato allergy in a restaurateur. Contact dermatitis 2002:47:109.
11. Ebner C, Hirschwehr R, Bauer L, Breiteneder H, Valenta R, Ebner H, Kraft D, Scheiner O. Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin). J Allergy Clin Immunol 1995;95(5 Pt 1):962-9
12. van Ree R, Voitenko V, et al. Profilin is a cross-reactive allergen in pollen and vegetable foods. Int Arch Allergy Immunol 1992;98(2):97-104.
13. Verburg JG, Smith CE, Lisek CA, Huynh QK. Identification of an essential tyrosine residue in the catalytic site of a chitinase isolated from Zea mays that is selectively modified during inactivation with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide. J Biol Chem 1992;267(6):3886-93.
14. Nater JP, Zwartz JA. Atopic allergic reactions due to raw potato. J Allergy 1967 Oct;40(4):202-6.
15. Delgado J, Castillo R, Quiralte J, Blanco C, Carrillo T. Contact urticaria in a child from raw Potato. Contact Dermatitis 1996;35(3):179-80
16. De Swert LF, Cadot P, Ceuppens JL. Allergy to cooked white potatoes in infants and young children: A cause of severe, chronic allergic disease. J Allergy Clin Immunol 2002 Sep;110(3):524-35.
17. Ortolani C, Ispano M, Pastorello E, Bigi A, et al. The Oral Allergy Syndrome. Ann Allergy 1988;61:47-52
18. Ortolani C, Ispano M, Pastorello EA, Ansoloni R, et al. Comparison of results of skin prick tests (with fresh foods and RAST in 100 patients with oral allergy syndrome. J Allergy Clin Immunol 1989;83:683-690
19. Meynadier J, Meynadier JM, Guilhou JJ. [Contact urticaria in atopic patients. Apropos of 2 cases] Ann Dermatol Venereol 1982;109(10):871-4.
[Article in French]
20. Sabbah A. Food allergy in childhood asthma [French]. Allerg Immunol (Paris) 1990;22(8):325-31.
21. Caffarelli C, Cataldi R, Giordano S, Cavagni G. Anaphylaxis induced by exercise and related to multiple food intake. Allergy Asthma Proc 1997;18(4):245-8
22. Caffarelli C, Giovanni C, Giordano S, et al. Reduced pulmonary function in multiple food-induced, exercise-related episodes of anaphylaxis. J Allergy Clin Immunol 1996;98:762-765
23. Beausoleil JL, Spergel JM, Pawlowski NA. Anaphylaxis to raw potato. Ann Allergy Asthma Immunol 2001;86(1):68-70.
24. Jeannet-Peter N, Piletta-Zanin PA, Hauser C. Facial dermatitis, contact urticaria, rhinoconjunctivitis, and asthma induced by potato. Am J Contact Dermat 1999 Mar;10(1):40-2.
25. Larko O, Lindstedt G, Lundberg PA, Mobacken H. Biochemical and clinical studies in a case of contact urticaria to potato. Contact Dermatitis 1983 Mar;9(2):108-14.
26. Gomez Torrijos E, Galindo PA, Borja J, Feo F, Garcia Rodriguez R, Mur P. Allergic contact urticaria from raw Potato. J Investig Allergol Clin Immunol 2001;11(2):129
27. Peter JN, et al. Contact urticaria from potatoes. Contact Dermatitis 1999;10(1):40-42.
28. Hannuksela M, Lahti A. Immediate reactions to fruits and vegetables. Contact Dermatitis 1977;3(2):79-84
29. Taylor SL, Bush RK, Selner JC, Nordlee JA, Wiener MB, Holden K, Koepke JW, Busse WW. Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma. J Allergy Clin Immunol 1988;81(6):1159-67
30. Steinman HA, Le Roux M, Potter PC. The incidence of Sulfite sensitivity in South African asthmatic children. SAMJ 1993;83:387-390
31. Badowski P, Urbanek-Karlowska B. Solanine and chaconine: occurrence, properties, methods for determination. [Polish] Rocz Panstw Zakl Hig 1999;50(1):69-75.
32. Harvey MH, Morris BA, McMillan M, Marks V. Measurement of potato steroidal alkaloids in human serum and saliva by radioimmunoassay. Hum Toxicol 1985;4(5):503-12.

E. CPD Questions (South Africa, Australia)

This CPD session is now closed. Please contact karen@allergyadvisor.com for more information.

PLEASE ANSWER ALL THE QUESTIONS
(There is only one correct answer per question.)
1. Which of the following is not true regarding allergy to potato?
(a.) Some individuals react to only raw potato but not to cooked.
(b.) Some individuals react to only cooked potato but not to raw.
(c.) Some individuals react to both raw and cooked potato.

2. Which of the following is not true regarding the potato allergen, Patatin?
(a.) It is also known as Sol t 1.
(b.) It appears to be a relevant allergen in atopic dermatitis.
(c.) It is not clear whether it is present in the potato tuber.
(d.) It is a major cross-reactive protein in latex-associated potato allergy.

3. Which of the following is not a potato allergen, i.e., does not cause an allergic reaction?
(a.) The panallergen profilin
(b.) Solanine
(c.) Sol t 2
(d.) Patatin

4. Choose the correct answer: Reactions to potato can occur as a result of:
(a.) The ingestion of potato
(b.) The handling of potato
(c.) The inhalation of the plant pollen
(d.) All of the above

5. True or false: The onset of allergic reactions to potato can be immediate, late or delayed.
(a.) True
(b.) False

6. Which of the following is not an example of proposed sensitisation to potato in potato allergic individuals?
(a.) When potato is given as one of the first solid foods introduced in the child's diet, usually around the age of 4-6 months.
(b.) Initial exposure and allergy to latex, leading to the development of an allergy to potato thereafter.
(c.) Prolonged exposure to potato by handling the raw product in the work situation (food industry).
(d.) Initial allergy to potato and tomato lead to sensitisation to latex thereafter.

7. True or false: Sulphite sensitive individuals may react to commercial pre-skinned potatoes or pre-cut French fries.
(a.) True
(b.) False

8. Which of the following is not true regarding solanine in potatoes:
(a.) It occurs naturally in members of the Solanaceae family.
(b.) It is usually present at low levels that are not of toxicological concern.
(c.) It can accumulate to high levels when the potato is cooked.
(d.) Symptoms to solanine include gastrointestinal and neurological disturbances.

Answers

1. b. Some individuals react to only cooked potato but not to raw.
2. c. It is not clear whether it is present in the potato tuber.
3. b. Solanine
4. d. All of the above
5. a. True
6. d. Initial allergy to potato and tomato lead to sensitisation to latex thereafter.
7. a. True
8. c. It can accumulate to high levels when the potato is cooked.

Index