Ispaghula

Code: k72
Latin name: Plantago psyllium/Plantago ovata
Family: Plantaginaceae
Common names: Ispaghula, psillium, psyllium

Occupational allergen

A food and pharmaceutical ingredient, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Ispaghula, more commonly known as psyllium or psillium, is a natural hydrophylic mucilloid obtained from the seed husk of plants of the Plantago genus of weeds, which are native to the Mediterranean region and the Near East and are cultivated there and in the south-western US. Since 1500, it has been used as a bulk laxative, functioning through its high water-binding capacity.

Seed produced from Plantago ovata is known in trading circles as white or blonde psyllium, Indian plantago, or Isabgol. Plantago seed, known commercially as black, French, or Spanish psyllium, is obtained from P. psyllium, also known as P. arenaria. India dominates the world market in the production and export of psyllium. (1)

P. ovata is an annual herb that grows to a height of 30-46 cm. Plants flower about 60 days after planting. The seeds are enclosed in capsules that open at maturity. P. ovata has small seeds; 1 000 seeds weigh less than 2 grams. (1)

Psyllium-containing laxatives are used by 4 million Americans daily, (2) and usage is also widespread in other parts of the industrialised world. Dietary supplements for the management of hypercholesterolemia and for prevention of colon cancer make up additional uses for this plant fibre.

Psyllium has been added to breakfast cereal as a cholesterol-lowering agent. (3)

Allergen Description

No allergens from this plant have yet been characterised.

The allergens in psyllium appear to be proteins derived from the inner seed endospore and embryo rather than from the husk itself. (2) Results of one study indicated that the commercial-grade husk, endosperm, and embryo contained similar antigens. Extracts of all 3 seed components contained antigens that bound IgE antibodies in the sera of 11 psyllium RAST-positive individuals. The findings suggest that other contaminating seed components, rather than the husk itself, are primarily responsible for the allergenicity of commercial-grade psyllium husk powder. (4)

In a study evaluating the prevalence of P. ovata seed allergy among health care workers in geriatric care homes, IgE-binding proteins of 17, 20, 25, 32-34, 54, 73-77, and > 97 kDa were identified. (5)

Potential Cross-Reactivity

A close phylogenetic relationship exists between P. ovata (psyllium) and P. lanceolata (English plantain); both are members of the same genus in this family. (6, 7) While most cross-reactivity studies between P. ovata seed and P. lanceolata pollen allergens suggest a lack of cross-reactivity, at least one showed the existence of immunologic cross-reactivity between P. ovata seed and P. lanceolata pollen. (8) A recent study reported that “mild” cross-reactivity existed between P. ovata seed and P. lanceolata pollen was observed.

The major allergen of English plantain, Pla l 1, displays significant sequence homology with the major olive pollen allergen Ole e 1. But Pla l 1 was not detected in psyllium or melon extracts. (9)

Clinical Experience

The first case of allergic reaction to psyllium seed was described as early as 1941. (10) Since then, a great variety of allergic symptoms have been reported to the seed and dust of ispaghula, including asthma and/or rhinitis, pruritis of mouth and eyes, diarrhoea, vomiting, nausea, tachycardia, hypotension, cough, angioedema, abdominal cramping, wheezing, and urticaria. (11) Acute bronchospasm associated with inhalation of psyllium hydrophilic mucilloid has also been described, (12) as well as eosinophilia. (13)

Three risk groups for hypersensitivity to psyllium have been described: consumers who consume psyllium laxatives; pharmaceutical workers who handle P. ovata seeds in the manufacture of laxatives; and health care professionals who prepare psyllium laxatives for their patients. (14)

Anaphylaxis has been reported. (15, 16, 17) There has been a case of immediate allergic reaction after ingestion of a dietary bar containing psyllium. (18)

Cases of anaphylactic reaction have been reported in all risk groups after ingestion of laxative or breakfast cereals containing P. ovata seed. (16, 19, 20, 21) In most of those subjects, sensitisation occurred by inhalation of P. ovata seed dust in the workplace.

Anaphylaxis may occur following the first ingestion of psyllium, as described in a woman who experienced severe laryngeal oedema and fatal anaphylaxis following ingestion of a psyllium-containing product for the first time. She had previously worked as a nurse assistant preparing psyllium bulk laxatives for years. Serum-specific IgE was strongly positive for psyllium only, and negative for the remaining 21 ingredients of the ingested food product. Her serum tryptase level was elevated, indicating mast cell degranulation. (22)

Psyllium hydrophilic mucilloid was added to breakfast cereals for cholesterol-lowering effects. A number of studies subsequently reported adverse reactions to the cereal. A 60-year-old woman with no prior history of psyllium ingestion developed anaphylactic symptoms after eating a psyllium-containing cereal. Her only previous exposure was dispensing a psyllium-containing laxative as a nurse. Skin-prick test was positive for psyllium. (23) Sensitisation occurred by inhalation in the absence of symptoms (rhinitis, asthma) and her first hypersensitivity reaction was that of anaphylaxis by ingestion.

An anaphylactic reaction was reported to the psyllium-containing cereal Heartwise. (24) In another study, of the 20 women evaluated with reported allergic reactions to Heartwise, all but 6 were nurses. Previous exposures to psyllium included ingestion or dispensing of psyllium-containing products. Symptoms developed shortly after small amounts of the cereal were ingested, and most commonly included moderate to severe wheezing, throat and chest tightness, and urticaria. All the women required medical therapy, 11 (55%) in an emergency room. It was concluded that individuals sensitised by occupational exposure to psyllium dust are at high risk for allergic reactions to ingested psyllium-containing products. (19)

Another study reports the case of a 38-year-old female nurse who ingested a bowl of Heartwise, and 25 minutes later developed severe systemic anaphylaxis manifested by hypotension, a feeling of constriction in the throat, hoarseness, dyspnoea, wheezing, generalised pruritus, urticaria, and vomiting. (20)

In general, allergic reactions to psyllium have been described as an occupational hazard among nurses and pharmaceutical workers who handle psyllium-containing laxatives. A 39-year-old female dialysis nurse had a 3-year history of nasal and eye symptoms from exposure to psyllium. She took a psyllium bulk laxative for constipation and developed flushing, tachycardia, urticaria, angioedema, laryngeal edema, and lightheadedness. An epicutaneous skin test and radioallergosorbent test for psyllium were both strongly positive. A 42-year-old female nurse with a history of asthma had allergic nasal and eye symptoms while dispensing psyllium. She received a prescription for crystallised psyllium, took it by mouth, and developed immediate flushing, tachycardia, urticaria, and angioedema. With subsequent ingestion of psyllium she also had severe wheezing, lightheadedness, and loss of consciousness. A psyllium epicutaneous skin test was strongly positive. (25) It has been widely shown that occupational exposure to a psyllium-based powdered laxative in nurses may result in asthma and or rhinitis. (26, 27, 28, 29, 30, 31)

The personnel of 4 chronic care hospitals were evaluated by means of a questionnaire, and skin-prick tests with psyllium and various inhalants administered to 193 of 248 (78%) of the workers who agreed to participate. Seventy-five subjects (39%) had a history of respiratory symptoms in regular life and/or respiratory symptoms and/or rhinoconjunctivitis after handling psyllium. Six (3%) showed skin reactivity to psyllium. Increased specific IgE antibodies were found in 20 of 162 of the sera that were tested (12%). In the second part of the study, a histamine inhalation challenge was performed on 70 of 75 (93%) of the subjects with a history suggestive of asthma and/or occupational asthma and/or skin reactivity to psyllium. Twenty (29%) had significant bronchial hyperresponsiveness. The 6 subjects with a history suggestive of occupational asthma (n=3) and/or asthma (n=6) and/or positive skin test results to psyllium (n=6) had significant bronchial hyperresponsiveness and increased specific IgE levels. They all underwent specific inhalation challenges with psyllium in the laboratory. Four developed bronchospastic reactions (2 immediate and 2 dual reactions). It was concluded, with the inclusion of 4 cases initially reported in the year preceding the trial, that the prevalence of IgE sensitisation to psyllium was between 5 (skin testing) and 12% (increased specific IgE levels). (32)

Of 743 surveyed health care workers who prepared psyllium laxatives for patients, 136 (18%) reported allergic events. Thirty-four of these employees (5%) reported shortness of breath, wheezing, or hives within 30 minutes after preparing psyllium laxatives. (33)

A recent evaluation of the prevalence of psyllium-seed allergy among health care workers in geriatric care homes found the prevalence of sensitisation and clinical allergy to psyllium seed in the exposed group to be 13.8% and 8.6%, respectively. All the sensitised subjects had a positive prick test (8 of 58;13.8%) but only 4 (6.9%) of them were positive for specific IgE (> 0.35 kU/l). Five out of the 8 sensitized health care workers reported allergic symptoms on or after handling laxatives containing psyllium seed. All had rhinoconjunctivitis, and asthma was suspected in in 2 individuals. Asymptomatic sensitisation had occurred in 3 subjects. One subject with respiratory symptoms from psyllium had also experienced 2 anaphylactic reactions after ingestion of laxatives containing psyllium seed. (5)

Occupational asthma has been described in pharmaceutical workers and nurses. (34) Differing degrees of psyllium allergy were reported in 3 nurses. The reactions ranged from sneezing to chest congestion and wheezing. Allergy to psyllium may be brand-related: 2 did not report further symptoms when the brand was changed, suggesting that the granular form is less likely to result in allergy than the powdered form. (35)

There is a report of 5 nurses aged 31-55 years having a history of asthmatic symptoms after exposure to psyllium that they prepared and distributed to patients. One subject – exposed for only 1 minute to the psyllium powder – experienced a severe immediate bronchospastic reaction, which required intubation for 3 hours; but she had complete functional recovery thereafter. Four of the 5 tested subjects had an immediate skin reaction to a commercial psyllium extract. All had IgE antibodies to psyllium. Inhalation challenges with psyllium caused isolated immediate (1 subject) and dual (3 subjects) reactions. (36)

With the recognition of the importance of psyllium as an occupational allergen, precautionary steps have been instituted; this may have contributed to a reduction in the reports of adverse reactions to this allergen.

Anaphylaxis was reported in a 69-year-old nurse after psyllium ingestion; she presented with generalised body swelling, flushing and urticaria. She had experienced recurrent rhinitis and asthma related to psyllium exposure for the past 15 years while dispensing laxatives to patients. The diagnosis of psyllium hypersensitivity was established by a positive psyllium puncture-skin test, an elevated psyllium-specific IgE level in serum, and a confirmatory soluble-antigen competitive inhibition test. (37)

Occupational allergy to psyllium, however, extends far beyond the immediate clinical setting and includes not only pharmaceutical manufacturing but cosmetics, fireworks, food, carpet and other textile manufacturing, hairdressing, printing, mining, and pharmaceutical research. Psyllium is a broadly important occupational allergen giving rise to asthma and rhinitis. (38, 39, 40) The risk of sensitization to psyllium appears to be higher with laxatives in powder form than with granulated forms or with laxatives that produce fewer airborne particles. (38) In general, psyllium seed sensitisation occurs after inhalation of psyllium seed powder, the particles of which can be as small as 2µm. (41)

Exposure to psyllium dust in a pharmaceutical factory resulted in chest tightness/wheeze, nasal, ocular or skin symptoms in 48 of 92 exposed workers. While symptoms were not incapacitating in the majority (n=44) of these, 1 worker required antihistamines and 3 others experienced severe respiratory symptoms when exposed to the dust. It was concluded that handling psyllium produces a moderate irritant effect in most exposed people, but that sensitisation to the dust can provoke severe respiratory symptoms. (42)

Of 140 employees of a psyllium-producing company, 39 had a history suggestive of occupational asthma; 23 of 120 (19%) showed a positive skin prick test to psyllium, and 31 of 118 (26%) had increased specific IgE antibodies; 39 (32%) workers had at least 1 of these 2 features. (43)

In a cross-sectional study of 125 workers engaged in the manufacture of bulk laxatives based on psyllium husks and senna pods, skin-prick tests with extracts revealed that 7.6% were allergic to psyllium and 15.3% to senna. Four (3.2%) cases of occupational asthma were identified. (44)

Occupational asthma occurred in a 19-year old male involved in the processing of psyllium, who reported an irritating cough on getting up in the morning. (45)

Sixteen workers with normal nonspecific bronchial reactivity (NSBR) had been previously diagnosed with occupational asthma caused by high-molecular-weight agents: flour in 7 workers, psyllium in 5, and guar gum in 4. They were re-challenged after they had been removed from exposure to these agents for a mean of 5.7 years, no longer showed evidence of persisting asthma, and had a normal lung function. The authors concluded that specific bronchial reactivity to high-molecular-weight agents persists in most cases despite a normalisation of NSBR, and that this persistence is associated with a persistence of specific immunisation to the agents in question. (46)

However, psyllium is not exclusively an occupational allergen. Two years after initiating regular psyllium-containing laxative use, a 40-year-old woman presented with a pruritic macular, papular, and urticarial rash involving the entire body, including the palms, soles and oropharynx, and sparing only the face. There was an associated sensation of chest and throat tightness and lip swelling. The signs and symptoms resolved upon discontinuance of the psyllium and recurred immediately after the patient initiated a challenge test. RAST for psyllium-specific IgE was positive. (2) Anaphylaxis following ingestion of a laxative containing psyllium has been described in two studies. Skin test for psyllium was positive, and specific IgE elevated for psyllium seed. (16, 17)

A 31-year-old atopic woman, who handled a laxative containing P. ovata seeds at home, is reported to have developed asthma as a result. Psyllium may act as a potent inhalant allergen capable of eliciting asthma symptoms not only in an occupational context but also in a domestic environment, affecting consumers of this laxative or others who handle it. (6)

b. Other reactions

Pharmacobezoars, bezoars comprised of medications, are unusual entities. Psyllium preparations are reported to cause bezoars. (47)

Compiled by Dr Harris Steinman harris@allergyadvisor.com

References

  1. Psyllium. Wikipedia. http://en.wikipedia.org/wiki/Psyllium. Accessed 25 July 2011.
  2. Freeman GL. Psyllium hypersensitivity. Ann Allergy. 1994;73(6):490-2.
  3. Bell LP, Hectome K, Reynolds H, etc. Cholesterol-lowering effects of psyllium hydophilic mucilloid. J Am Med Assoc 1989;261:3419-23.
  4. Arlian LG, Vyszenski Moher DL, et al. Antigenic and allergenic analysis of psyllium seed components. J Allergy Clin Immunol 1992;89(4):866-76.
  5. Bernedo N, García M, Gastaminza G, Fernández E, Bartolomé B, Algorta J, Muñoz D. Allergy to laxative compound (Plantago ovata seed) among health care professionals. J Investig Allergol Clin Immunol 2008;18(3):181-9.
  6. Aleman AM, Quirce S, Bombin C, Sastre J. Asthma related to inhalation of Plantago ovata. [Spanish] Med Clin (Barc) 2001;116(1):20-2.
  7. Morgan MS, Arlian LG, Vyszenski-Moher DL, Deyo J, Kawabata T, Fernandez-Caldas E. English plantain and psyllium: lack of cross-allergenicity by crossed immunoelectrophoresis. Ann Allergy Asthma Immunol 1995;75(4):351-9.
  8. Rosenberg S, Landay R, Klotz SD, Fireman P. Serum IgE antibodies to psyllium in individuals allergic to psyllium and English Plantain. Ann Allergy 1982;48:294-8.
  9. Calabozo B, Duffort O, Carpizo JA, Barber D, Polo F. Monoclonal antibodies against the major allergen of Plantago lanceolata pollen, Pla l 1: affinity chromatography purification of the allergen and development of an ELISA method for Pla l 1 measurement. Allergy 2001;56(5):429-35.
  10. Ascher MS. Psyllium seed sensitivity. J Allergy 1941;12:607-9.
  11. Drewes AM. Allergy to psyllium seed. [Danish] Ugeskr Laeger 1985;147(48):3909-10.
  12. Gross R. Acute bronchospasm associated with inhalation of psyllium hydrophilic mucilloid. [Letter] JAMA 1979;241(15):1573-4.
  13. Nelson AM, Taubin HL, Frank HD. Eosinophilia associated with psyllium hydrophilic colloid ingestion. [Letter] JAMA 1980;243(4):329-30.
  14. Hinojosa M, Dávila I, Zapata C, Cuesta J, Quirce S. Asma ocupacional inducido por semillas de Plantago ovata en trabajadores de la industria farmaceútica. Revista Española de Alergología e inmunología Clínica 1990;5:139-45.
  15. German A, Aregall S, Boada L, Tomas S. Anaphylactic shock following the ingestion of a laxative. [Spanish] [Letter] Med Clin (Barc) 1995;104(14):559.
  16. Zaloga GP, Hierlwimmer UR, Engler RJ. Anaphylaxis following psyllium ingestion. J Allergy Clin Immunol 1984;74(1):79-80.
  17. Suhonen R, Kantola I, Bjorksten F. Anaphylactic shock due to ingestion of psyllium laxative. Allergy 1983;38(5):363-5.
  18. Bouvier P, Buffiere I, Jouglard J, Cottin C, Pollini J. Immediate allergic reaction after ingestion of a dietary bar containing psyllium. [French] [Letter] Presse Med 1993;22(4):173.
  19. James JM, Cooke SK, Barnett A, Sampson HA. Anaphylactic reactions to a psyllium-containing cereal. J Allergy Clin Immunol 1991;88(3 Pt 1):402-8.
  20. Drake CL, Moses ES, Tandberg D. Systemic anaphylaxis after ingestion of a psyllium-containing breakfast cereal. Am J Emerg Med 1991;9(5):449-51.
  21. Rubira N, Valero A, Amat P, Elices A, Llunch M, Malet A, Bartolomé B. Asma ocupacional y anafilaxia por semillas de Plantago ovata. Alergol Inmunol Clin 2000;15:96-9.
  22. Khalili B, Bardana EJ Jr, Yunginger JW. Psyllium-associated anaphylaxis and death: a case report and review of the literature. Ann Allergy Asthma Immunol 2003;91(6):579-84.
  23. Lantner RR, Espiritu BR, Zumerchik P, Tobin MC. Anaphylaxis following ingestion of a psyllium-containing cereal. JAMA 1990;264(19):2534-6.
  24. Kaplan MJ. Anaphylactic reaction to "Heartwise". [Letter] N Engl J Med 1990;323(15):1072-3.
  25. Sussman GL, Dorian W. Psyllium anaphylaxis. Allergy Proc 1990;11(5):241-2.
  26. Schwartz HJ, Arnold JL, Strohl KP. Occupational allergic rhinitis reaction to psyllium. J Occup Med 1989;31(7):624-6.
  27. Scott D. Psyllium-induced asthma. Occupational exposure in a nurse. Postgrad Med 1987;82(8):160-1.
  28. Seggev JS, Ohta K, Tipton WR. IgE mediated anaphylaxis due to a psyllium-containing drug. Ann Allergy 1984;53(4):325-6.
  29. Terho ja Martti Torkko EO. Occupational asthma from psyllium laxatives. [Finnish] Duodecim 1980;96(18):1213-6.
  30. Machado L, Zetterstrom O, Fagerberg E. Occupational allergy in nurses to a bulk laxative. Allergy 1979;34(1):51-5.
  31. Busse WW, Schoenwetter WF. Asthma from psyllium in laxative manufacture. Ann Intern Med 1975;83(3):361-2.
  32. Malo JL, Cartier A, L'Archeveque J, Ghezzo H, Lagier F, Trudeau C, Dolovich J. Prevalence of occupational asthma and immunologic sensitization to psyllium among health personnel in chronic care hospitals. Am Rev Respir Dis 1990;142(6 Pt 1):1359-66.
  33. Nelson WL. Allergic events among health care workers exposed to psyllium laxatives in the workplace. J Occup Med 1987;29(6):497-9.
  34. Quirce S, Sastre J. Occupational asthma [Review]. Allergy 1998;53:633-41.
  35. Ford MA, Cristea G Jr, Robbins WD, Gentes GR, Harper SJ, Rindone JP. Delayed psyllium allergy in three nurses. Hosp Pharm 1992;27(12):1061-2.
  36. Cartier A, Malo JL, Dolovich J. Occupational asthma in nurses handling psyllium. Clin Allergy 1987;17(1):1-6.
  37. Vaswani SK, Hamilton RG, Valentine MD, Adkinson NF Jr. Psyllium laxative-induced anaphylaxis, asthma, and rhinitis. Allergy 1996;51(4):266-8.
  38. Machado L, Stalenheim G. Respiratory symptoms in ispaghula-allergic nurses after oral challenge with ispaghula suspension. Allergy 1984;39(1):65-8.
  39. Gauss WF, Alarie JP, Karol MH. Workplace allergenicity of a psyllium-containing bulk laxative. Allergy 1985;40(1):73-6.
  40. Machado L, Olsson G, Stalenheim G, Zetterstrom O. Dust exposure challenge test as a measure of potential allergenicity and occupational disease risk in handling of Ispaghula products. Allergy 1983;38(2):141-4.
  41. Schoenwetter WF, Steinberg P. Psyllium hypersensitivity, nurses, and geriatric units. Ann Intern Med 1985;103(4):642.
  42. McConnochie K, Edwards JH, Fifield R. Ispaghula sensitization in workers manufacturing a bulk laxative. Clin Exp Allergy 1990;20(2):199-202.
  43. Bardy JD, Malo JL, Seguin P, Ghezzo H, Desjardins J, Dolovich J, Cartier A. Occupational asthma and IgE sensitization in a pharmaceutical company processing psyllium. Am Rev Respir Dis 1987;135(5):1033-8.
  44. Marks GB, Salome CM, Woolcock AJ. Asthma and allergy associated with occupational exposure to ispaghula and senna products in a pharmaceutical work force. Am Rev Respir Dis 1991;144(5):1065-9.
  45. Ferrer Marín-Blázquez M, Gázquez Abad I, Herrera Puente P, offujano Pita FJ. Occupational asthma. [Spanish] Aten Primaria 1995;15(1):33-5.
  46. Lemiere C, Cartier A, Malo JL, Lehrer SB. Persistent specific bronchial reactivity to occupational agents in workers with normal nonspecific bronchial reactivity. Am J Respir Crit Care Med 2000;162(3 Pt 1):976-80.
  47. Stack PE, Thomas E. Pharmacobezoar: an evolving new entity. Dig Dis 1995;13(6):356-64.

 

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.