Hyposensitization to poison ivy after working in a cashew nut shell oil processing factory

19 adults were patch tested to urushiol, the allergen in poison ivy/oak, to determine their sensitivity to this allergen after working in a cashew nut shell oil (CNSO) processing plant. The cashew nut tree and poison ivy/oak are in the same botanical family. Anacardiaceae, and they share similar chemicals which cause allergic contact dermatitis. 13 of the 19 workers had a preemployment history of poison ivy sensitivity, with 10 developing CNSO dermatitis. After working in this factory for several months, 9 of the 13 noticed a decreased sensitivity or no sensitivity to poison ivy/oak. When tested to urushiol extract, only 3 reacted positively, 2 minimally. These results imply that hyposensitization to poison ivy/oak occurred in these employees after development of hardening to cashew nut shell oil.     

A potent contact allergen of Phacelia (Hydrophyllaceae)

The major contact allergen of Phacelia crenulata (Hydrophyllaceae) has been identified as geranylhydroquinone. A maximization test of geranylhydroquinone showed this to be a potent sensitizer comparable in degree to poison oak/ivy urushiol. Comparative patch testing on humans with urushiol established that the Phacelia allergen does not cross-react with poison oak or ivy.     

Oral hyposensitization to poison ivy and poison oak

We evaluated the safety and efficacy of a 1:1 mixture of pentadecylcatechol (PDC) and heptadecylcatechol (HDC) diacetate in reducing hypersensitivity to poison ivy and poison oak. The study was double-blind, parallel, randomized, and placebo controlled. The 44 subjects receiving the active drug ingested a cumulative dose of 306.5 mg over a five-week period. Subsequently, 14 patients were continued on a maintenance phase, ingesting an additional 960 mg of drug. The PDC-HDC diacetate was well tolerated, with no significant side effects. Evaluation of efficacy compared poststudy and prestudy reactions to patch tests using urushiol in doses of 0.025, 0.05, 0.125, 0.25, and 0.5 micrograms applied to the forearm. The results indicated that the induction phase as well as the maintenance phase did not induce a statistically significant hyposensitivity to urushiol, and we were thus unable to decrease sensitivity to poison ivy and poison oak in humans using orally ingested PDC-HDC diacetate.     

Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol

Previous studies have established that epicutaneous application of 5-methyl-3-n-pentadecylcatechol (5-Me-PDC), a synthetic analog of a poison ivy urushiol component, leads to immune tolerance to 3-n-pentadecylcatechol (PDC) in mice. The induction of tolerance by 5-Me-PDC may be mediated by a protein conjugate formed via selective reaction of thiol nucleophiles present on the carrier macromolecule with the corresponding o-quinone derived from the parent catechol. In order to examine further the tolerogenic properties of 5-Me-PDC, we have extended our studies to the guinea pig, the generally accepted experimental species for the study of contact allergy. The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog. Furthermore, we were able to show that the treated animals remained tolerant for at least 6 weeks, a period of time comparable to that observed following the intravenous administration of the O,O-bis-acetyl derivative of PDC. The data point to the possibility of developing a therapeutically effective topical tolerogen for poison ivy contact dermatitis.     

Studies on poison ivy

The isolation and purification of poison ivy urushiol is described. The preparation of urushiol-ski protein and urushiol human serum albumin is also described. Lymphocytes from eleven donor naturally sensitized to poison ivy and from four non-sensitive individuals have been cultured for 5 days in the presence of urushiol-carrier conjugates. Lymphocytes from seven of the eleven sensitive donors responded with a stimulation index greater than 3.0 to urushiol-albumin conjugate. When urushiol-skin protein conjugate was used as a stimulant, lymphocytes from only three of the eleven sensitive donors responded. The results suggest that urushiol-protein conjugates can stimulate sensitive lymphocytes in vitro, although a response is not observed in every individual naturally sensitized to poison ivy.     

Leaves of three, let them be: if it were only that easy!

Humans of all races and skin color are susceptible and uniquely sensitive to poison ivy, oak, and sumac. Contact with the plant oil, urushiol, found not only in the leaves but in the stems and roots, results in an allergic contact dermatitis in 50% to 60% of people. Clinical manifestations, differential diagnosis, complications, and treatments are discussed, with a special emphasis on the pediatric population.     

Suppression of urushiol-induced delayed-type hypersensitivity responses in mice with serum IgG immunoglobulin from human hyposensitized donors

Serum IgG immunoglobulin fractions from human subjects hyposensitized to poison ivy/oak by oral administration of urushiol suppressed the induction of delayed-type hypersensitivity (DTH) responses in mice to this hapten. This suppressive activity was hapten specific because it did not modify DTH responses to dinitrofluorobenzene (DNFB). Absorption of human serum with lymph node cells from urushiolsensitized but not DNFB-sensitized mice removed the suppressive activity, suggesting that anti-idiotypic antibodies reacting with T-cell receptors are involved.     

Quantitation and cloning of human urushiol specific peripheral blood T-cells: isolation of urushiol triggered suppressor T-cells

A limiting dilution assay was developed to quantitate urushiol (the antigen of poison ivy; Toxicodendron radicans) specific T cells from peripheral blood of a patient with a history of rhus (poison ivy) dermatitis. It was found that maximal sensitivity with minimal nonspecific proliferation could be produced with the use of 5 U/ml of recombinant IL2 added to the assay on day 6. This donor was found to have a frequency of urushiol specific peripheral blood T cells of (1/2935). Five interleukin 2 (IL2) dependent urushiol specific T-cell clones were generated from the peripheral blood of this patient. These T-cell clones had a CD8+ (T8+) phenotype and proliferated specifically to both extracts of Toxicodendron radicans (poison ivy) leaves and pure urushiol. Pentadecylcatechol was an inferior antigen, only stimulating proliferation of one clone. The ability of all clones to proliferate to pure urushiol, despite their having been induced with leaf extract, suggests that urushiol, or closely related catechols, represent the only allergenic constituents of Toxicodendron radicans. Lymphokine production in response to antigen varied between (0.6-5.0) units/ml of interleukin 2 (IL2) and (1.0-120) units/ml of gamma interferon. Although none of the clones showed significant cytotoxicity against NK targets, three of five lines showed considerable cytotoxicity against concanavalin A treated (lectin approximated) targets. However, cytotoxicity for rhus conjugated autologous targets was not detected. It was found that several of these CD8+ clones could suppress IgG production in the presence of rhus antigen. The isolation of these T-cells from peripheral blood several months after rhus dermatitis suggests that these clones may have a role in down regulating delayed hypersensitivity to urushiol.     

Regulation of the contact sensitivity response to urushiol with anti-urushiol monoclonal antibody ALG 991

The objective of the studies was to demonstrate that the contact sensitivity (CS) response to poison ivy/oak could be downregulated following treatment with a monoclonal antibody (mAb) reacting with the allergen urushiol. Conjugation of urushiol and its synthetic analogue 3-n-pentadecylcatechol (PDC) to N-acetylcysteine yielded hydrosoluble derivatives which induced humoral immune responses in BALB/c mice. Hybridomas secreting monoclonal antibodies (mAbs) reacting with urushiol and PDC were generated by fusion of B lymphocytes from immunized mice with mouse myeloma P3NS0 cells. The specificity of mAb ALG 991 (IgM isotype) was defined by inhibition of antibody binding by PDC analogues. This demonstrated that mAb ALG 991 reacted with the catechol moiety of urushiol, the region of the allergen being critically important in the induction of contact dermatitis. The CS response to urushiol in BALB/c mice was suppressed by stimulation with mAb ALG 991 and the role of sensitized T cells, including suppressor T cells, has been considered. Suppression of CS was most effective with low doses (1 microg) of mAb incorporated into a vaccine with Freund's adjuvant. This treatment suppressed CS responses in BALB/c mice already sensitized to urushiol.     

A study of cross-reactions between mango contact allergens and urushiol

The allergens causing mango dermatitis have long been suspected to be alk(en)yl catechols and/or alk(en)yl resorcinols on the basis of observed cross-sensitivity reactions to mango in patients known to be sensitive to poison ivy and oak (Toxicodendron spp.). Earlier, we reported the 3 resorcinol derivatives: heptadecadienylresorcinol (I), heptadecenylresorcinol (II) and pentadecylresorcinol (III); collectively named 'mangol', as mango allergens. In this study, we extracted the 1st 2 components (I and II) from the Philippine mango, adjusted them to 0.05% concentration in petrolatum and patch tested the components on 2 subjects with mango dermatitis. Both subjects reacted to I. 1 subject also elicited a weaker positive reaction to II. To investigate the cross-reaction between mangol and urushiol, we also patch tested the same subjects with urushiol. The subject sensitive to II reacted to urushiol. 6 subjects with a history of lacquer contact dermatitis and positive reactions to urushiol were similarly patch tested. 5 persons reacted to I. 2 subjects also exhibited a slower but positive reaction to II. This is the 1st report in which heptadec(adi)enyl resorcinols known to be present in mango have been shown to elicit positive patch test reactions in mango-sensitive patients.     

Exploring the mango-poison ivy connection: the riddle of discriminative plant dermatitis

A relationship between sensitivity to poison oak or poison ivy and mango dermatitis has been suggested by previous publications. The observation that acute allergic contact dermatitis can arise on first exposure to mango in patients who have been sensitized beforehand by contact with other urushiol-containing plants has been documented previously. We report 17 American patients employed in mango picking at a summer camp in Israel, who developed a rash of varying severity. All patients were either in contact with poison ivy/oak in the past or lived in areas where these plants are endemic. None recalled previous contact with mango. In contrast, none of their Israeli companions who had never been exposed to poison ivy/oak developed mango dermatitis. These observations suggest that individuals with known history of poison ivy/oak allergy, or those residing in area where these plants are common, may develop allergic contact dermatitis from mango on first exposure. We hypothesize that previous oral exposure to urushiol in the local Israeli population might establish immune tolerance to these plants.     

Assessment of the ability of the topical skin protectant (TSP) to protect against contact dermatitis to urushiol (Rhus) antigen.

BACKGROUND: Military personnel have a need for effective protection against cutaneous exposure to chemical warfare agents (CWA). Topical Skin Protectant (TSP) is being developed to supplement chemical warfare protective garments. TSP protects against CWA exposure in animals, but does it work for humans? Because humans should not be tested with live CWA, urushiol (poison ivy) extract was used as a surrogate substance in place of CWA for human efficacy testing of TSP. OBJECTIVE: Determine whether TSP protects human skin against experimentally-induced urushiol dermatitis. METHODS: Open urushiol patch testing of 50 rhus-sensitive subjects comparing the 96-hour dermatitis severity scores between TSP protected and TSP unprotected sites. There were 4 paired sites (i.e., protected versus unprotected) per subject. Test sites were scored using a 9-point dermatitis scale of 0.0 to 4.0 (using 0.5 increments). RESULTS: Analysis of variance of the dermatitis scores from 192 paired sites on 48 evaluable subjects showed that TSP protected sites had mean dermatitis scores about 2 points lower than TSP unprotected sites (P <.001). CONCLUSION: Although this study does not provide direct scientific evidence that TSP protects humans against the percutaneous absorption of CWA, it does provide circumstantial evidence that this is the case. The fact that TSP is so highly effective against a lipophilic substance like urushiol and that most common vesicant CWAs are lipophilic and are weaponized in oleaginous vehicles, makes the effectiveness of TSP in preventing absorption and dermatitis from CWA seem likely.     

Recognizing the Toxicodendrons (poison ivy, poison oak, and poison sumac)

Poison ivy, poison oak, and poison sumac are now classified in the genus Toxicodendron which is readily distinguished from Rhus. In the United States, there are two species of poison oak, Toxicodendron diversilobum (western poison oak) and Toxicodendron toxicarium (eastern poison oak). There are also two species of poison ivy, Toxicodendron rydbergii, a nonclimbing subshrub, and Toxicodendron radicans, which may be either a shrub or a climbing vine. There are nine subspecies of T. radicans, six of which are found in the United States. One species of poison sumac, Toxicodendron vernix, occurs in the United States. Distinguishing features of these plants and characteristics that separate Toxicodendron from Rhus are outlined in the text and illustrated in color plates.     

Quantitative structure-activity relationships for skin sensitization potential of urushiol analogues

The relative alkylation index (RAI), a theoretically derived parameter intended to quantify the relative extent of carrier haptenation resulting from a given dose of a given sensitizer, has previously been successfully applied to the analysis of relative sensitization potential and dose-response data for a variety of contact allergens which are directly electrophilic. Here the RAI concept is applied to analysis of data on compounds related to urushiol (i.e., 3-substituted catechols), the naturally occurring mixture of allergens responsible for contact allergy to poison ivy and poison oak. These allergens are believed to act as pro-electrophiles, being oxidized to electrophilic orthoquinones in vivo. It is found that the various types of urushiol derivatives fit the same sort of RAI-sensitization relationships as expected theoretically and as found previously with direct acting electrophiles. There is evidence that in many cases, the test conditions were such that overload effects, whereby the degree of sensitization induced decreases with increasing carrier haptenation, applied. It is also concluded that the question as to the relative sensitization potencies of the naturally occurring urushiols remains open. The commonly held view that with these materials, sensitization potential increases with increasing unsaturation in the 3-hydrocarbyl chain of the 3-hydrocarbyl catechols, is based on evidence that is capable of alternative interpretation.     

Poison ivy/oak dermatitis. Use of polyamine salts of a linoleic acid dimer for topical prophylaxis

Closed patch tests were used to evaluate the ability of 156 different preparations (based on 22 different chemicals) to prevent poison ivy dermatitis. Several polyamine salts of a linoleic acid dimer were identified that were totally able to prevent the usual dermatitis in approximately 70% of subjects. The effectiveness of the preparations improved when the antigen and the protectant were washed off within eight to 12 hours, instead of remaining on the skin for 48 hours. When washed off, and depending on the protectant, concentration, and vehicle used, several of the preparations were totally able to prevent a dermatitis in a range of 56% to 100% of subjects tested. Further work with these compounds may greatly benefit the many people currently plagued by their allergy to poison ivy and poison oak.     

Regulation of murine contact sensitivity to urushiol components by serum factors

Mice epicutaneously painted with components of poison ivy urushiol oil exhibit contact sensitivity (as detected by ear swelling reactions) that persist for about 25 days. Sera taken from mice at times when the contact sensitization response is waning suppressed the induction of sensitization to 3-n-pentadecylcatechol (PDC), a urushiol component, in recipients. The suppressive serum factor was present in greatest amount 25 days after sensitization, but was no longer detectable 40 days post sensitization. Suppression was antigen-specific, absorbed out with PDC-immune, but not normal lymph node cells, and transferable with a single 0.6 ml dose 7 days prior to sensitization of recipients. Suppression was transferable by the purified IgG fraction of desensitized mice. Results indicate that contact sensitivity to urushiol in mice is regulated by serum factors.     

FS11.5Toxicodendron dermatitis in the United Kingdom

We describe two cases of Toxicodendron dermatitis, one acquired in the United States but presenting in the United Kingdom, the other a recurrent dermatitis following importation to the UK. Poison ivy, poison oak and poison sumac are native to North America and belong to the genus Toxicodendron. This group of plants is of interest to the dermatologist because they contain a mixture of potent sensitisers which cause a severe allergic contact dermatitis. The dermatitis can present to the dermatologist in Europe after an individual has been in contact with the plant whilst visiting an endemic area. The plants have the potential to grow in the UK and it is therefore possible for an individual to be sensitised and subsequently to develop the rash without leaving the UK. A 35‐year‐old American man who lived in the UK visited his family in Marietta, Georgia USA. Shortly before his return to the UK he cut some plants back in his mother’s garden. Two days following his arrival back in the UK he developed a widespread pruritic and painful vesicobullous eruption. He required admission for intensive potent topical corticosteroid therapy and the eruption settled over the next two weeks. The plant he had been pruning was subsequently identified as poison sumac (Toxicodendron vernix). A 54‐year‐old woman living in Wales was referred to the Contact Dermatitis Investigation Unit because during the summer months for the previous four years she had experienced an intermittent, intensely pruritic, vesicular and in parts linear eruption affecting her face, arms and legs. This responded slowly to potent topical corticosteroids. She is a keen gardener and suspected that it was related to a plant in her garden. She was patch tested to our Standard Series, Plant Series and all the plants in her garden. She showed ++ allergic reactions to sodium metabisulphite, propolis and a strong vesicular reaction to the leaf of one of the plants from her garden Inspection of the plant revealed that it had three leaflets per stem. She had taken a cutting whilst visiting friends in Pennsylvania in 1996 and on returning to the UK had planted it in her garden. It grew but had never flowered or produced seeds. Once the cause of her dermatitis had been confirmed our patient took the necessary protective measures and removed the plant including its roots from her garden. She has not experienced any further problems with her skin. She contacted her friends in the USA who knew precisely where she had picked the plant. A further specimen was taken to the local Conservation Office where it was confirmed to be poisonivy. Poison ivy and poison sumac belong to the genus Toxicodendron which is native to North America and Mexico. They cause an allergic contact dermatitis when there is exposure to a bruised portion of the plant. This leads to the oleoresin, urushiol coming into contact with the skin. 25–60% of North Americans are reported be allergic to poison ivy and its relatives. The importation of plants into the UK is restricted by law. It is clear that this plant grew in its new habitat but did not extend beyond the confines of the garden. With frequent and more extensive air travel it seems reasonable to speculate that similar occurrences have taken place and that plants not endemic to Europe should be considered in those with suspected plant dermatitis.     

Treatment of toxicodendron dermatitis (poison ivy and poison oak)

Toxicodendron dermatitis results from a reaction to an oil soluble oleoresin that is present in many parts of the poison ivy and poison oak plants. Prophylactic measures include avoidance, protective clothing, barrier creams and hyposensitization. Treatments include washing the area immediately with a solvent suitable for lipids and the use of anti-inflammatory agents, especially corticosteroids.     

Immunologic studies of poisonous Anacardiaceae: oral desensitization to poison ivy and oak urushiols in guinea pigs

Poison ivy and oak urushiols or their components were compared with the respective esterified derivatives for efficacy in oral desensitization of Hartley guinea pigs sensitized to urushiols. The esterified derivatives produced a significantly greater degree of hyposensitization than did free urushiol counterparts. Suppression produced by esterified urushiols was of longer duration than that produced by free urushiols. Groups of sensitized guinea pigs were given high (100 mg/kg) or low (10 mg/kg) doses of a mixture of acetylated, saturated urushiol congeners over a 1-, 2-, or 3-week period. High doses produced a greater degree of hyposensitization regardless of the dosage schedule used. Low doses did not produce significant hyposensitization unless given over a shorter (1 week) schedule. Large single booster doses (33 mg/kg/week) of the acetate derivatives produced a rebound in responsiveness when given, 2 weeks following the last dose of the initial series, to animals hyposensitized with 10 mg/kg. No such rebound in sensitivity occurred in animals given a series of high initial doses.