Botanical Dermatology

The family Anacardiaceae (the cashew family) includes the genus Toxicodendron (poison ivy, poison oak, poison sumac, etc.) and other genera with cross-reactive allergenic plants (Mangifera, Anacardium, Semecarpus, and Gluta). The Poison Ivy group of plants was initially placed in the very large genus Rhus by Linnaeus. However, the name Toxicodendron ('Poison tree') was colloquially used for poison ivy for millennia. There are many good reasons to separate Rhus from Toxicodendron. Not only are members of Rhus not allergenic, they also possess very different field identification features from Toxicodendrons.⁶⁶ Since three classic treatises successfully argued for the placement of poison ivy, poison oak, and poison sumac in the genus Toxicodendron in 1937,⁶⁷ 1963,¹⁰ and in 1971,¹¹ a major shift toward the use of Toxicodendron has occurred in scientific publications.^{66, 68, 69} However, this acceptance has not occurred in the dermatology literature, and reasons for this are obscure.

Identification of toxicodendrons ⁶⁶

One of the best articles in the dermatology literature teaching the identification of these notorious plants was published in 1986 by Guin and Beaman.⁶⁶ These authors point out that their article serves as the basis for the successful identification of these plants, but that to become truly proficient, one must identify and observe several plants in a location where they can be observed throughout the year.

As noted in the list of Anacardiaceae above, there are two species each of poison ivy and poison oak and one species of poison sumac listed that are common to the United States. Some of these have multiple subspecies. Poison oak and poison ivy are weeds that grow along roads, trails, or streams; they possess three leaflets (sometimes five) per leaf (compound leaves). Poison sumac contains 7-13 leaflets per leaf. Young leaves are frequently red in color, and the mature fruit (drupes) are tan or cream colored and have no hairs. Many botanists say that poison ivy and poison oak are so closely related that they cannot reliably distinguish these plants in the field. Classically, poison ivy leaves have pointed tips and are ovate (widest point below the center). Poison oak leaves usually have rounded ends. Western poison oak has oval leaves, while Eastern poison oak has variable leaf appearances that can mimic white oak leaves.

Toxicodendron leaves have three or more leaflets (ternate). (The old saying about Poison Ivy "Leaves of three; leave them be" refers to each leaf having three leaflets.) Flowers and fruit (which do not grow until a plant is at least three years old) arise in an axillary position, that is, in the angle between the leaf and the twig from which the leaf is borne.

Figure 31: Plant characteristics of Toxicodendron radicans

All toxicodendrons grow as male and female plants. While flowers fall off the male plants, the flowers on female plants are pollinated and later bear fruit. The leaf stalk is enlarged at its origin from the supporting twig and has a groove on its distal surface. Therefore, even in the winter, when the leaf has fallen off, a 'U' or 'V'-shaped scar remains. In contrast, the flower and fruiting structures of true Rhus arise at the end of the branch (not in an axillary position).

The fruit of toxicodendrons are green while growing and off-white when mature. When the outer exocarp peels away, a chalk-white mesocarp can be seen. Longitudinal black lines from the toxic oleoresin in the mesocarp often embellish the surface. Toxic Anacardiaceae sap is self-melanizing; sites of prior plant injury demonstrate areas resembling black enamel paint. This phenomenon results from enzymatic oxidation of sap constituents. The black-spot test, popularized by Guin,⁷⁰ is an additional helpful aid to identification of toxic Anacardiaceae:

"Gather two or three leaves, including the leaf stalk to the point it connects to a supporting twig. Place these in a folded sheet of white paper. Use a stone or other disposable object to thoroughly crush the plant contents, especially the leaf stalks, between the folds of paper. Dispose of the plant contents. Sap from poison oak, poison ivy, and poison sumac turns dark brown within 10 minutes and black by 24 hours. Other Anacardiaceae will also demonstrate a positive result."

T. rydbergii (Northern and Western poison ivy) grows as a small shrub without aerial rootlets and does not climb trees. Branches sometimes grow upright, like tines of a fork, but often these short plants have thick, drooping leaves. Plants only 8-10 inches tall may produce fruit. In the Pacific Northwest, it hybridizes with western poison oak. T. rydbergii, like T. radicans will grow in a variety of soils but prefers moist, fertile soil that is well-drained.

 

Figure 32: Toxicodendron rydbergii, Northern and Western poison ivy

T. radicans ssp. radicans (Eastern poison ivy) grows along the Eastern seaboard, climbs trees and other tall objects, and possesses aerial rootlets. T. radicans ssp. negundo grows in the midwestern United States. Its leaves resemble those of the box elder (Acer negundo, Family Aceraceae, the maple family). Four other subspecies of T. radicans inhabit much smaller geographic areas of the United States.

T. toxicarium (Eastern poison oak) like T. rydbergii, is a small subshrub that never climbs trees, does not produce aerial rootlets, and can produce fruit when only 12 inches tall. While leaflets may resemble white oak leaves, this feature is variable and unreliable. Major features separating this from poison ivy include rounded lobes on leaves, absence of aerial rootlets (v. T. radicans), and preference for nutritionally poor soil. It is found in sandy soil in the midst of oak and pine trees in ridge and valley areas of the southeastern United States.

T. diversilobum (Western poison oak), found along the entire west coast of the United States grows in almost any type of soil. It develops aerial rootlets and climbs, but it mostly exists as a shrub (low, woody plant with several branches arising from the base). In fact, it is the most abundant shrub in California! The leaflets have rounded lobes and may resemble live oak (Quercus agrifolia, Family Fagaceae). It possesses the largest fruits of all native toxicodendrons (7.5mm); these may hang like ripe cherries.

T. vernix (poison sumac) grows as a shrub or small tree in isolated areas east of the Mississippi river in the standing water of swamps or peat bogs, although it has been found on dry land. It does not form colonies and dies in the presence of minimal disturbance (it is not a weed). Compound leaves of 7-13 leaflets per stem, usually in odd numbers, angle up from the stem like rabbit ears. Each leaflet is oval, smooth-edged, and about 10 cm long. Because of its isolation, few people are affected by it. Staghorn sumac (Rhus typhina) has red flowers and red fruit that grow from the ends of the branches, while poison sumac has white flowers and white fruit that grow from an axillary position (between the compound leaf and branch). Staghorn and smooth sumac plants have notched leaves.

Figure 34: Toxicodendron vernix, Poison Sumac	T.vernix (fall)	T.vernix (fall)
	Figure 35: Rhus slabra, "smooth" Sumac

Guin and Beaman point out excellent tips for winter identification of toxicodendrons. Remember, the non-leaf portions of the plant can induce dermatitis, even in the winter.⁷¹ Beware clusters of off-white fruit on female plants, aerial rootlets, and 'U' or 'V'-shaped leaf scars. The "winter" shape of poison ivy on fence posts resembles 'Medusa heads' that are said to be identifiable while driving down the highway! Strongly suspect any vine climbing by aerial rootlets connected at the bottom to a tree or log. In snow, T. rydbergii grows so low to the ground, that the upward, tine-like branches may be the only clue to its identification.

Poison ivy and poison oak plants are difficult to eradicate once they have developed root growth, which requires only one year. They are quite resistant to herbicides after roots have developed from seedlings. One can pull poison ivy off tree trunks, sever the plant at the base, and bury the plant parts. Burning them can result in severe airborne allergic contract dermatitis.¹⁵

Allergens in Poison Ivy, Poison Oak, and Poison Sumac 

The allergenic substance, urushiol, derives its name from the Japanese word for the sap found in the stems, canals, and roots of the Japanese lacquer tree, kiurushi (T. verniciflua).⁶⁹ It is a thick grayish fluid that turns black in air and dries to form a lustrous translucent varnish. It contains a mixture of catechols (1,2-dihydroxybenzenes) and resorcinols (1,3-dihydroxybenzenes)

Urushiol avidly binds to skin, but it is readily degraded in the presence of water. Therefore, one should soak with cool water in the field as soon as contact with Anacardiaceae is suspected.⁷³ Beware, exuberant bathing may increase the area of exposure in very sensitive individuals.⁷³

Figure 36: Skeletal structures of dihydric benzenes (benzene rings with two hydroxyl groups). 'R' indicates the site of attachment for a side chain. Members of Anacardiaceae contain sensitizing resorcinols and catechols, but they contain no hydroquinones. 72

Saturation of the side chain decreases allergenicity, while lengthening of side chains increases irritancy and allergenicity. The immunologic specificity of the alkyl side chains is a rare instance where a molecular component without the capability of ionic interaction, hydrogen bonding, or covalent linkage can sensitize. The reactivity most likely results from van der Waals forces. Location of the side chain at position 3 of the catechol ring increases antigenicity, while location at position 6 induces tolerance. Anacardiaceae contain pyrocatechols with C13, C15, or C17 side chains containing zero to three double bonds. Poison ivy contains mainly C15 side chains, poison oak C17 side chains, and poison sumac, C13 and C15

Cashew nut shell oil contains cardol, a resorcinol with a similar side chain to poison oak and poison ivy allergens. Members of Ginkgoaceae and Proteaceae contain sensitizing resorcinols.⁷²

Catechol or an alkyl side chain alone is immunologically inert. However, their combination produces potent sensitizers. While virtually all self-described poison ivy allergic individuals react to C-15 catechols with two double bonds (Figure 10 - see urushiol with R₃ side chain) only 37% responded to a C-15 catechol with an unsaturated side chain (pentadecylcatechol - PDC).

Figure 37: Structure of urushiol, a sensitizing phenol

Therefore, PDC, which is easily synthesized, is not an appropriate patch test allergen for Anacardiaceae sensitivity! Interestingly, the diolefin (containing two double bonds) is the major component in poison ivy and poison oak urushiol, and the unsaturated version is a minor component. Alkylcatechols with more than eight carbons have very low water solubility and are more potent sensitizers and irritants than their shorter relatives. Even so, within one hour of cutaneous application, pyrocatechols have distributed throughout the body. Excision of skin at the site of application after one hour decreases, but does not eliminate, initial sensitization.

Other allergenic Anacardiaceae

The cashew nut tree (Anacardium occidentale) is a Brazil native that was introduced into the West Indies centuries ago ⁷⁴ and was taken to Asia by the Portuguese where it has also naturalized.⁷⁵ It now grows worldwide in the tropics. Even Florida is not a warm enough climate to sustain it. It produces nuts that contain an oily, brown juice between the two layers of its shell. The concentration of phenols in the nutshell and bark is so high, that contact with them causes an immediate vesicant reaction. Africans used this in ritual scarification and keloid formation while others used the nut shell oil for wart removal. In fact, dermatitis can be caused by contact with any part of the tree, except the roasted nut.⁷⁴

The cashew nut shell (pericarp) is three-layered. The outer, leathery exocarp and thin, hard, inner endocarp envelop a honeycombed mesocarp filled with an oily fluid. The cashew nut shell liquid (CNSL) is used to produce friction dusts in brake linings and clutch facings, and to make epoxy resins, paints, varnishes, and foundry core oil. This juice contains two active allergens: cardol, that is mainly an irritant, and anacardic acids.⁷⁶ The nuts are processed by heating them in a bath. The epicarp bursts, the CNSL is released (simultaneously decarboxylating the anacardic acids into less allergenic cardanols), and the nuts are centrifuged in sawdust to remove residual phenols. The endocarp is then removed to yield an edible and hypoallergenic nut.⁷⁴

Figure 38: Anacardium occidentale, cashew nut

Mango (Mangifera indica) is the most popular fruit tree in tropical and subtropical America.⁷⁴ Some 35 species of mango grow in Southeast Asia.⁷⁵ Unlike the cashew nut tree, it does grow in the continental United States in southern portions of Florida, Texas, and California. The leaves, bark, stems, and skin of the mango contain urushiol and other long-chain phenols such as cardol. Peeling the fruit before eating it prevents allergic contact dermatitis that occurs most commonly on the hands and periorally when eating unpeeled fruit. Hawaiian natives rarely react to mango. Likewise, Latin Americans who frequently mush up the fruit, make a hole through the rind, and suck out the fruit, rarely, if ever, report dermatitis.⁷⁷ It is thought that early and oral exposure to mango results in immunologic tolerance. One paper reported a 40 year-old woman with widespread vitiligo that repigmented after she developed allergic contact dermatitis after picking mangoes and pruning her mango tree.⁷⁸

Figure 39: Mangifera indica, Mango

The Brazilian Pepper Tree (Schinus terebinthifolius), also known as Florida holly, is probably the most common cause of allergic contact dermatitis in southern Florida. Since its introduction into Florida, it has escaped widely from cultivation and become resistant to efforts at eradication. The tree bark latex and crushed berries possess a variety of potentially sensitizing phenols.⁷⁴ In a humorous sidelight, an entrepreneur marketed whole, dried berries of the tree as flavoring. This unfortunately led to a number of cases of diarrhea and perianal dermatitis and was even referred to as the 'pink peppercorn caper' on the front page of the Wall Street Journal.⁷⁹ The Food and Drug Administration eventually seized the spice as a "poisonous and injurious substance...injurious to health."⁷⁴

Figure 40: Schinus terebinthifolius, Florida holly

The mango, cashew, and Florida Holly are incredibly common throughout Latin America. However, dermatitis to these is rare in contrast to the frequent reactions developed by residents of the United States. The main allergens in toxicodendrons are catechols while the cross-reacting allergens in the listed trees are phenols and resorcinol. The catechols have been demonstrated to possess greater allergenicity than the phenols and resorcinol. One author has speculated that early exposure to catechols in North America may prepare residents for cross-reactions to other Anacardiaceae. Early, oral exposure to the less allergenic phenols and resorcinols may induce a state of tolerance.⁷⁷

The poisonwood tree (Metopium toxiferum) grows in subtropical Florida, the Caribbean, and Central America. It contains C-15 catechols similar to those in poison ivy. Contact with any external part of the tree can cause dermatitis. The bare wood and pollen are allergen free.⁷⁴

The genus Gluta (Latin for 'glue') includes about 30 trees commonly found in Southeast Asia; local botanists have referred to this genus as Melanorrhoea. The trees, referred to popularly as 'rengas,' release a black sap on their surfaces when damaged. Slashing tree bark with a knife reveals a bright pink or reddish-brown inner bark with black lines and white sapwood deep to that.⁷⁵ Tree trunks and limbs will often have black stains caused by leaking sap. As can be imagined, the timber from these trees is dangerous to handle. However, if it is dried for several years, the wood loses its allergenicity.⁷⁵ Furniture made from these trees can cause dermatitis years after production.

In 1963, the first cases of African poison ivy were reported as caused by Smodingium argutum (Anacardiaceae) known locally as 'tovana' and 'rainbow leaf'.⁷⁹ This plant is found only in South Africa and is the only member of its genus. Like 'classic' poison ivy, it possesses self-melanizing sap, dentate trifoliate leaves, and diolefin C-17 catechols.⁸⁰

The 15-20 meter tall Japanese lacquer tree (Toxicodendron verniciflua) provides a thick, self-melanizing, viscous bark sap used for varnishing furniture, floors, canes, wooden toilet seats, and ornaments. Lacquering a single piece of wood may require several years and 300-400 coats! Because polymerized urushiol remains in the lacquer, it has been known to maintain its allergenicity for thousands of years! Its urushiol contains a pentadecylcatechol with side chain double bonds at positions 8, 11, and 13 instead of positions 8, 11, and 14 as in poison ivy. Patients allergic to poison ivy usually react to Japanese lacquer tree allergens. Like poison sumac, it has leaves composed of 7-13 oblong or oval leaflets.^15,75 T. verniciflua has been recognized as a cause of dermatitis for more than 1000 years. The raw lacquer contains 60-65% urushiol and its oligomer. Interestingly, lacquer craftsmen become hardened to the lacquer by chewing raw lacquer. In a survey of 232 lacquer craftsmen, 189 had developed dermatitis from the lacquer (81%)! Fully 83% (158/189) of these reactions resolved with continued lacquer exposure! A sequential patch test study of students learning the art of applying lacquer demonstrated that most students develop an allergic contact reaction early. Most of these students then lose their reactivity and become 'hardened' (hyposensitized).⁸¹

Figure 41: T. verniciflua, Japanese lacquer tree

The black juice of the Indian marking tree nut (Semecarpus anacardium), also known as the bhilawa tree, is mixed with alum to mark laundry in India and Malaya. The Indian laundry workers (dhobies) often develop 'dhobie mark dermatitis,' and 15-20% English soldiers stationed in India during World War II were affected after wearing marked garments. The juice contains a pentadecylcatechol that cross-reacts with poison ivy urushiol.

Ginkgoaceae

Ginkgolic acid in the fruit of the Ginkgo tree (Ginkgo biloba L.), the only living member of the family Ginkgoaceae, cross-reacts with poison ivy and poison oak. Fossils of this genus have been dated to be 200 million years old. ^{9, 82} The popularity of these trees, also known as the maidenhair tree, has spread into many urban and suburban areas having become popular in Massachusetts, Michigan, Washington, DC, Canada (along the St. Lawrence River), and France (in Paris and Strasbourg).⁸³ These beautiful trees grow to be 40 meters tall and are resistant to high levels of air pollution. ^{82, 83} The male trees are much preferred to the female trees. Only female trees produce seeds; the plant does not flower and therefore, it produces no fruit. The yellowish seed capsule disintegrates forming, among other chemicals, butyric acid producing the characteristic odor of rancid butter. ^{9, 82} When the outer coat is removed, the ginkgo seed kernel is a delicacy served with bird's-nest soup.⁸² Allergic reactions may occur to both the pulp and the seed kernel. According to one report, the allergic reaction only occurs when the seed is opened and people are exposed to the pulp. Handling the intact seed supposedly does not cause dermatitis in sensitized individuals.⁸³ Additionally, the seed pulp can cause a strong irritant reaction. ^{82, 83} The unique leaf morphology, resembling a fan, makes them easy to recognize. ^{9, 15, 82}

Figure 42: Ginkgo bilboa, Ginkgo tree	G. bilboa, leaf

Figure 43: G.bilboa, nuts

The C15 side chain of ginkgolic acid resembles that of poison ivy and poison oak urushiols. The main sensitizing allergen, anacardic acid, has a hydroxyl group in position 1, and a carboxyl group on position 2 of a benzene ring. It has the same or similar side chains to urushiol catechols. In one study, eight patients sensitive to poison ivy were not allergic to anacardic acid. There is no evidence to support chemical transformation of anacardic acid into any of the catechols in urushiol, or vice versa. Therefore, true polysensitization likely occurs in individuals allergic to Ginkgo trees and poison ivy.^{15, 84}

Proteaceae

Grevillea includes 250 species of plants in the family Proteaceae ranging from low shrublets to forest trees. They contain a pentadecylresorcinol (no double bonds) that may cross-react with poison ivy. Because it has an unsaturated side chain, it is of lower allergenicity than the diolefins in poison ivy and poison oak. It grows naturally in eastern Australia. The flower of the Hawaiian kahili tree (Grevillea banksii) is a significant cause of allergic contact dermatitis in the Islands. ¹⁵

Clinical aspects of Anacardiaceae-induced dermatitis

Because these plants do not contain resin canals that drain to the surface, uninjured plants do not release urushiol that can induce a dermatitis.⁷¹ Brushing against uninjured leaves is innocuous.⁷¹ Only injured plants release urushiol.⁸⁵ When urushiol is exposed to air, it forms black deposits on the leaves, stems, or trunk. While this is not a specific finding for members of the genus Toxicodendron, it should alert one to stay away from these plants as potential causes of severe contact dermatitis. Patch tests to the fluid content of vesicles and bullae are routinely negative. ^{71, 85}

After a contact with urushiol, a sensitized person develops an erythematous, pruritic eruption within an average of two days. However, dermatitis may occur up to 3 weeks after first contact, or within hours of secondary contact. Streaks of erythema and juicy papules, followed by vesicles and bullae, develop later. Uncommonly, other clinical reaction patterns resembling erythema multiforme, measles, scarlatina, urticaria, and nephritis appear.⁸⁵ These have been ascribed to deposition of immune complexes.⁷¹ Without treatment, the dermatitis lasts about 3 weeks. Permanent post-inflammatory pigmentation may occur in dark-skinned individuals.

Figure 44: Poison ivy dermatitis	Figure 45: Impetiginized Poison Ivy

Figure 46: Poison ivy dermatitis from wiping with leaves.

 

Figure 47: Cashew oil Allergic Contact Dermatitis	Figure 48: "Toilet seat" allergic contact dermatitis to Japanese lacquer

Figure 49: Allergic Contact Dermaitis to Mango

Under controlled testing conditions, over 70% of the United States population reacts to the urushiol in poison ivy and poison oak. Probably no more the 50% will react to these plants in the field. ^{69, 71} Interestingly, only 15% of atopic persons were sensitive, and blacks are less reactive than whites.⁶⁹ Studies suggest that sensitivity to urushiol runs in families.⁶⁹ Members of Anacardiaceae probably account for more cases of allergic contact dermatitis than all other plant families combined. ^{71, 85}

Urushiol on skin may cause a clinical entity recognized as black-spot poison-ivy dermatitis.⁸⁶ The sap of virtually any member of the family Anacardiaceae turns brown within 10 minutes and blackens within 24 hours on exposure to air. The catechols bind covalently to proteins and cannot be removed by thorough washing. This indelible nature was exploited to mark clothing or lacquer furniture. The histologic picture is one of an acute, primary irritant contact dermatitis superimposed on an acute allergic contact dermatitis. The oleoresin acts both as an irritant and as an allergen. This form of dermatitis is uncommonly seen, because most people wash off the resin as soon as it is noted.⁸⁷

Treatment and Prevention of Anacardiaceae-induced allergic contact dermatitis

As soon as exposure to poison ivy or related plants is recognized, the entire body should be thoroughly washed with soap and water. Fisher has shown that urushiol can be removed in significant amounts only if washed off very early. After 10 minutes, only 50% can be removed; after 15 minutes, only 25%; after 30 minutes, only 10%; and after 60 minutes, none of it can be removed.⁷³ Strong soap and scrubbing need not be used since these irritate the skin and remove the urushiol no better than mild soap and gentle washing.⁷³

In 1958, Kligman discovered, to his dismay, that no topical product used to treat poison-ivy dermatitis "influenced the course of acute poison ivy dermatitis when compared with standard, bland dermatologic treatment."⁸⁸ The intervening years brought high-potency fluorinated topical steroids. The most potent of these only have an impact if applied during the earliest stages of the outbreak when vesicles and blisters are not yet present.⁶⁹ Weepy lesions are best treated with wet-to-dry soaks. Burow's solution works well to cool and dry lesions when applied as a wet dressing that is allowed to dry. Systemic steroids are extremely effective when indicated. These are best given in a dose of 1-2 mg/kg/day slowly tapered over two to three weeks.⁷¹ I have seen too many patients referred to me for a 'recurrence' of their poison ivy dermatitis after completing a short, six-day course of oral corticosteroids. Oral antihistamines may decrease pruritus, but topical antihistamines should be avoided because of the high risk of inducing allergy when applied to dermatitis skin.⁷¹

Hyposensitization programs have basically been failures. While sometimes eliciting small reductions in allergenicity in individual patients, they more generally result in pruritus ani, generalized pruritus, urticaria, and other rashes. The hyposensitized patients often comment that the "treatment is worse than the disease." ^{69, 89} The FDA has not approved any hyposensitization products for poison ivy.⁷³ Natural desensitization probably occurs through early, oral ingestion of allergens. It appears that hyposensitization after becoming sensitized to the potent allergens in Poison Ivy and Poison Oak is difficult if not impossible.

Because so many workers (soldiers, loggers, farmers, fire fighters, construction workers, and utility maintenance workers) are at risk for contact with poison ivy, many have tried to develop effective barrier creams.⁷³ More than 150 different preparations have been tested.⁷³ In 1995, Marks and co-workers published encouraging results with an organoclay compound, 5% quaternium-18 bentonite lotion ('Ivy-Block', Enviroderm Pharmaceuticals, Louisville, KY).⁹⁰ In a study of 144 subjects who were patch-test positive to a mixture of poison ivy and poison oak allergens, lotion application prevented any dermatitis in 68%. The 32% who responded did so later and more mildly than their control sites.⁹⁰ Patients should realize that the allergenic catechols pass through rubber gloves, but not through heavy-duty vinyl gloves.⁷³

COMPOSITAE AND RELATED FAMILIES

The Family Compositae (Asteraceae) is known as the daisy family, chrysanthemum family, or sunflower family. It includes some 25,000 species and includes many troublesome weeds (e.g. dandelions), ornamentals (e.g. sunflowers), herbaceous perennials (e.g. dahlias and chrysanthemums), and vegetables (e.g. lettuce, chicory, and artichokes). ^{91, 92} Tanacetum parthenium (feverfew, Bachelor's buttons, or mutterkraut) and marigolds (Calendula spp.) have found their way into herbal medicine.⁹² At least 180 species of Compositae are important causes of contact dermatitis worldwide.⁹³ Insects pollinate most species, but some species, such as the various types of ragweed, pollinate by the wind.⁹¹

Identification of Compositae

The classic Composite has many tiny flowers (florets) that are clustered to form a flower head (capitulum) at the stem apex.⁹¹ The flower head is then surrounded by bracts (modified leaves) that form an involucre (whorl of bracts beneath or around a flower cluster).^{15, 91}

Figure 50: Typical composite head cut vertically in half

In some genera (Taraxacum, the dandelion), all the florets are similar. In many others, the flower head is divided into an inner 'disc' of short, tubular florets; the outer 'ray' florets are long and strap-like, as in the common daisy.

 

Figure 51: Chrysanthemum sp., White Daisy (composite flower)	Figure 52: Chrysanthemum sp., green bracts beneath flower head

Allergens in Compositae

The major sensitizers, sesquiterpene lactones (SQL) are found in the leaves, stems, flowers, and some pollens.⁹¹ The highest concentrations are found in trichomes on stems, the underside of the leaves, and in the flowering heads. ^{91, 92} A SQL is a 15-carbon molecule composed of a sesquiterpene and a lactone ring.

Figure 53: Diagram of a sesquiterpene (lactone ring)

A sesquiterpene contains three isoprene units (each composed of a five carbon backbone) with a formula C₁₅H₂₄. A lactone is a type of cyclic ester. Over 200 skeletal types and 1350 individual types of SQLs have been described, and each of these may have multiple functional groups attached.⁹¹ Interestingly, the composition of lactones produced by any species varies by location and weather,⁹¹ and closely related species may vary greatly in the chemical composition of their SQLs.⁹⁴ An alpha-methylene group attached to the lactone ring is necessary for sensitization.⁹¹

Cross-reactivity between SQLs does not follow any apparent rules. No single SQL, in fact, not even the commonly used SQL mix of three common SQLs (alantolactone, dehydrocostus lactone, and costunolide), will serve as a reliable screen for SQL allergy. ^{91, 92} Therefore, pieces of the suspect plant should always be used when patch-testing a patient.⁹⁵

Important dermatitis-causing Compositae

Yarrow (Achillea millefolium) is a common lawn weed found all over North America and Eurasia. ⁹¹ It can be easily found along roadsides and in prairies. Yarrow has caused 'strimmer dermatitis'.⁹⁶

Figure 54: Achillea millefolium, Yarrow

Ragweeds (Ambrosia spp.) cause epidemic hay fever only during airborne pollen season, but they cause allergic contact dermatitis throughout their entire growing season.^{97, 98} These aggressive weeds are found not only throughout the United States, Canada, and Mexico, but they have also been found in Australia, Europe, and Japan. ^91,97 An oleoresin borne to the leaf's surface and onto pollens causes an airborne contact dermatitis affecting the face, neck, and arms that often becomes lichenified. Dermatitis seems to occur prototypically in atopic American male farmers, 40-65 years old.⁹¹ In fact, a 20:1 male to female ratio is claimed.⁹⁸ Pollen is a rare cause of type IV hypersensitivity.⁹⁷ Different allergens cause ragweed hay fever and dermatitis.⁹⁸

Figure 55: Ambrosia, Common ragweed

Artemisia spp., known as mugwort, wormwood, motherwort, and prairie sage, are found throughout northern temperate regions of Europe, Africa, Asia, and North America.⁹¹ The genus name comes from Queen Artemis who popularized the plant for the treatment of female disorders. Herbal medicine still uses the plant to treat epilepsy and helminth infections.⁹¹ The sensitizing sesquiterpene lactones are ludovicins A, B, and C.

The florist's chrysanthemum belongs to a hybrid genus known as X Dendrathema.^{15, 99} Many sources incorrectly list these as belonging to the genus Chrysanthemum. Allergic contact dermatitis frequently occurs in amateur florists who spend hours 'disbudding' or 'dead-heading' plants to encourage larger blooms. They represent the most common cause of occupational dermatitis due to Compositae. The major sesquiterpene lactone allergen is arteglasin-A, a guainolide also found in Artemisia spp. Patch testing patients to any random chrysanthemum is unreliable; the specific suspected flower should be used in patch testing. 

Chicory (Cichorium intybus) is a weed that grows throughout the temperate regions of the world. The clear blue-purple flowers resemble dandelions, and they are commonly found along roadsides in dry, calcareous soil. Chicory shoots (chicons) have become popular in foods, and during World War II, chicory roots were used to brew a coffee substitute. The roots may also be roasted to caramelize sugars that are then used with coffee. The leaves are used in salads and called 'endive'. The major allergens, lactucin and lactopicrin, also found in lettuce (Lactuca sativa), are found in sap of the leaves or chicons.^15,91

Sunflowers (Helianthus annuus) probably arose in Mexico, but are now found throughout Eastern Colorado and Kansas and are grown worldwide for seeds and oil. ^{15, 91} They have caused allergic contact dermatitis occupationally in those who harvest or prepare plants for production of sunflower seeds and sunflower oil. The allergens are secreted by trichomes on leaf surfaces. Windblown trichomes from dry plants can cause airborne contact dermatitis. The major allergen is known as 1-0-methyl 1-4,5-dihydroniveusin A.¹⁵ The pollen is said to be a minor allergen.⁹⁷

Figure 56: Helianthus annus, sunflower

Parthenium hysterophorus (congress grass, congress weed, carrot weed, wild feverfew, the 'Scourge of India') caused a fair amount of allergic contact dermatitis in the southern United States in the middle part of this century. With the mechanization of agriculture, it has become less of a problem. In 1956, it accidentally traveled in a consignment of US wheat to Poona, India. ^{15, 91,92,100} In fact, the epithet 'congress weed' is a reference to the US congress (who allocated the shipment for India).⁹⁴ The plant found an inviting ecologic niche without natural enemies, and within seven years it became one of the most common plants in Poona!⁹¹ Since that time, it has spread rapidly along canal banks, roads, and railways to become a major field weed.^15,91,100 Both rural and urban areas alike have been traumatized by its presence.¹⁰⁰ Unlike South American P. hysterophorus, the Indian plant contains large amounts of the sesquiterpene lactones parthenin and ambrosin.^15,91,100

Figure 57: Parthenium hysterophorous, "Scourge of India"

Marigolds (Tagetes spp.) contain a-terthienyl and bithienyl in the roots. Both compounds cause phototoxic reactions in experimental models, but no cases of phytophotodermatitis have been recorded in the wild. Allergic contact dermatitis is rare, and no sesquiterpene lactones have been isolated from marigolds.¹⁵

Figure 58: Tagetes spp., Marigold

The dandelion (Taraxacum officinale) derives its name from the French, 'dent de lion'; the immature seeds or notched leaves resemble lion's teeth.^15,91,101 This troublesome weed flourishes worldwide.⁹¹ The tap root has been used as a coffee substitute, like chicory, and has a strong diuretic effect giving rise to the alternative name, 'piss-a-bed.' ¹⁵ Airborne allergic contact dermatitis (aided by parachute-shaped seeds) is most common after mowing the lawn during long stretches of hot, dry weather when dandelions flourish and grass does not.^15,91,99 The allergen is taraxinic acid (1-0-b-glucopyranoside), a sesquiterpene lactone linked to glucose via an ester linkage.^15,91,99 If the SQL mix is used to test for dandelion dermatitis, the test is usually negative.¹⁰¹

Figure 59: Taraxacum officinale, dandelion

Non-Compositae with sesquiterpene lactones

Frullania spp. (Jubulaceae), known as liverworts because of their superficial resemblance to lobes of a liver, contain sesquiterpene lactones that frequently cause airborne allergic contact dermatitis in forestry workers, especially in western Canada.¹⁰² They grow as epiphytes on the smooth-barked trunks and branches of trees and shrubs and also on cliffs and rocks.⁹¹ They are related to the moss family.^97,102 The allergens are known as frullanolides and cyclocostunolide and locally cause 'woodcutter's eczema'.¹⁰² Most patients react to the alantolactone in the sesquiterpene lactone mix.¹⁰²

Magnolia grandiflora (Magnoliaceae), the magnolia tree, and sweet bay (Laurus nobilis, Lauraceae) contain various SQLs. Parthenolide, a sesquiterpene lactone found in feverfew, has also been isolated from Magnolia grandiflora. Primary sensitization from magnolia is rare.¹⁵ An outbreak of allergic contact dermatitis due to sweet bay occurred in Strasbourg between 1962 and 1973. The essential oil from the leaves of sweet bay were used to make a product called Vegebom^® used to treat insect bites.⁹¹

Clinical Aspects of Compositae Dermatitis

Compositae may cause irritant dermatitis. Thistles (Cirsium spp. and Carduus spp.) possess sharp spines while the bur marigold (Bidens tripartita) have prickly, barbed fruits. An irritant latex is found in dandelions, lettuce, and chicory. There are also rare reports of contact urticaria to Compositae.¹⁵

 

Figure 60: Cirsium spp., Candida Thistle	note the sharp spines characteristic of thistles

The most common clinical form of Compositae dermatitis resembles an airborne allergic contact dermatitis, however, the true mode of sensitization remains a mystery.⁹⁴ It classically involves men older than 40 years with a history of outdoor exposure. Strangely, even when women and children have similar exposure as older men, they are less frequently sensitized. Plant hairs or dust from dried plant material, or pollen carrying SQLs are thought to sensitize individuals, but none of these routes has been proven to be responsible. Pollen has not been shown to be a potent cutaneous sensitizer, and it does not carry SQLs. As for dust that is more plentiful after plants die, more frequent sensitization occurs during the growing season when dust is low.⁹⁴

Typically, a single area of the body is involved for some time. Then, a more widespread eruption occurs that may even involve unexposed sites. The eyelids, nasolabial folds, retroauricular sulci, and antecubital fossae are generally involved, unlike the situation in photosensitive dermatitis. All exposed areas develop a chronic lichenified, eczematous and intensely pruritic eruption, including the face, neck, forearms, and dorsal hands. During the first several years, the dermatitis flares in the summer during the Composite growing season. The dermatitis usually disappears in the winter. However, after several years untreated, a persistent, pruritic, lichenified dermatitis develops.^{15,91,92,94,97,103,104} Flowers and leaves are more potent sensitizers than stems.¹⁰⁵

Parthenium hysterophorus dermatitis in India affects adult males more than adult females or children, even though in India, exposure is similar for all groups.^{15,91,100,106} Early studies estimated a ratio of 20:1 between men and women.^91,94 One author surmises that Indian women have less skin exposed than men.⁹⁴ One Indian study of 45 men and 15 women with SQL allergy found that 41/45 men (91%) and 7/15 women (47%) reacted to plant material from P. hysterophorus.¹⁰⁶ This study demonstrated a surprisingly low rate of cross-reactivity to various Composites. Of the 60 individuals, 47 (78%) reacted to P. hysterophorus, 25 (42%) reacted to a chrysanthemum species, 11 (18%) reacted to Dahlia pinnata, and only 4 (7%) reacted to Tagetes indica (marigold).¹⁰⁶ In this study 35/60 (58%) responded to only one of the four Composites used. The affected skin often becomes lichenified, and patients may even develop leonine facies. It seems to spare vitiliginous areas.¹⁵

In a review of 10 studies of 450 individuals who had relevant positive patch tests to members of Compositae and/or SQLs, several clinical patterns of dermatitis were seen.⁹¹ Only hands were involved in 36%, face alone in 11%, hands and face alone in 20%, generalized dermatitis in 22%, and other patterns in the remaining patients. The large male preponderance of patients seems to be changing as shown by a recent study from Minnesota.⁹³ Menz and Winkelmann found a 1.4:1 male:female ratio in those sensitive to Compositae. The most common sources of sensitization were garden (40%), recreational (17%), and farming (15%).

Prevalence of SQL allergy

The prevalence of SQL-induced allergic contact dermatitis is not known. However, we have a good idea of SQL allergy based on two large patch test studies ^95,107 of patients with suspected allergic contact dermatitis. In these two studies, 1.7% of 11,431 patients reacted positively, and in one of these studies, 84% of reactions were thought to be relevant.¹⁰⁷ Both studies employed the SQL mix with equimolar amounts of costunolide, dehydrocostus lactone, and alantolactone. Since the SQL mix does not detect all, or necessarily most, SQL allergies, the incidence is greater than 1.7%.

One study found that this mix detected only 35% of patients with known Compositae allergy. ¹⁸⁵ A mixture of short ether extracts from five composites gave a positive response in 3.1% of 3,851 tested individuals,¹⁸⁴ a rate almost double that found with the SQL mix. Based on these data, patients with suspected allergy to Composites should be tested with material from the plant in question.

Photosensitivity and SQL allergy

A key question regarding Compositae dermatitis remains unsolved: What is the relationship between photosensitivity and Compositae dermatitis? First, keep in mind that SQLs are not photosensitizers; they have neither phototoxic nor photoallergic properties.^91,92 Frain-Bell and Johnson reported that 47 of 55 patients (85%) with chronic photosensitivity dermatoses had positive patch tests to Compositae.¹⁰⁸ Other studies have demonstrated that patients allergic to Compositae have abnormal reactions to light testing.⁹² In fact, one report demonstrated that a 61 year-old gardener with a four year history of chronic hand dermatitis, and one year of facial dermatitis, reacted to the SQL mix on patch testing. At that time he had normal monochromator photopatch test results. Only six months later, the patient was again tested and demonstrated very low minimal erythema dose to UVB and minimal phototoxic dose to UVA.¹⁰⁹

Compositae-allergic individuals frequently react to plant allergens in perfumes, woods, Balsam of Peru, colophony, and lichens.^92,108 These allergies, furthermore, often precede the development of chronic actinic dermatitis.¹⁰⁸ While alpha-terthienyl and various polyacetylenes with phototoxic properties have been found in some Compositae, no link has been established between their presence and dermatitis.⁹² Numerous hypotheses have been put forth to explain these findings, but, alas, no good explanation has been found.^91,92

Prevention and Treatment of Compositae Dermatitis

Of course the most effective treatment (if possible) is prevention by avoiding plants containing SQLs. While no widespread studies of oral hyposensitization have been reported, several small studies have reported success: patch test reactions decreased or became negative, and patients clinically improved.^91,92 This result is believable based on the facts that while chrysanthemum allergy is the most common Compositae allergy in Europe, it is extremely rare in Japan where chrysanthemum leaves and flowers are eaten with sushi, salad, and soups.⁹¹ As with Toxicodendron hyposensitization, side effects include pruritus ani, urticaria, dyspepsia, and other skin eruptions.

Potent topical steroids and oral prednisone are relatively ineffective unless employed early and if further exposure to SQLs is prevented.^15,91,92,100 Azathioprine in a dose of 2 mg/kg/d may be helpful, even in protracted cases of dermatitis.^91,92,110 An Indian physician who treats many cases of Parthenium dermatitis uses chloroquine, 200 mg, TID for one week and then tapers it.¹⁰⁰ He also uses 0.05 mg ethinyl estradiol in both adult men and women and tapers it after three weeks. He bases his use of the estrogen on the fact that the only involved women are post-menopausal.

PUVA therapy has reportedly helped Compositae dermatitis. A protocol developed by Storrs and others employs the combination of PUVA and oral prednisone.⁹¹

OTHER PLANT FAMILIES CAUSING ALLERGIC CONTACT DERMATITIS

Alliaceae

The family Alliaceae, genus Allium, includes many species of onion, garlic, and chives. Most are important vegetables, but some are grown as ornamental plants. Most species are bulbous: garlic (A. sativum) has a bulb made of a cluster of small bulbs (cloves or bulblets), onion (A. cepa) has a typical bulb made of overlapping arcs of expanded leaf bases (petioles), while leek (A. porrum) has a 'bulb' that is merely a continuation of the leaf stalk.

Garlic probably originated in south central Asia and has enjoyed a long history of use in cooking and folk medicine: orally for its diuretic and antilipemic effects and topically to treat insect bites, boils, and skin infections.^111,112 Garlic is the most frequent cause of fingertip dermatitis in housewives and caterers.¹¹³ It typically presents on the thumb, index, and middle fingertips of the non-dominant hand.¹⁵ The fingertips typically display hyperkeratosis, desquamation ,and fissuring in an asymmetrical pattern. Fresh garlic is a potent irritant that has caused second and third degree burns when applied to injured skin.¹¹² Therefore, patch testing to whole garlic should never be done. The irritants and allergens are thought to be diallyl disulfide (the most important one), allylpropyl disulfide, and allicin.^111,112

Figure 62: Garlic

Figure 63: Contact Dermatitis secondary to garlic

Cut onions release thiopropanal-s-oxide, an irritant sulfur compound known as 'lacrimatory factor' for its effects on tearing.¹¹⁴ This compound has not been linked to any cutaneous reactions. Allergic contact dermatitis to onion is reported much less often than to garlic.¹⁵ However, patch tests to onion may be positive in garlic-sensitive individuals. One 45 year-old female homemaker developed a chronic fingertip dermatitis exacerbated by cutting onions. Patch testing to dilute onion extracts were positive.¹¹⁴ Onion allergens are unknown but likely include diallyl disulfide.¹⁵

Alstroemeriaceae and Liliaceae

'Tulip fingers' is an allergic contact dermatitis (with a minor irritant component)caused by handling tulip bulbs (Tulipa spp., Liliaceae). Erythematous, scaling plaques mark the fingertips and periungual skin, particularly on the first and second fingers of the dominant hand. Tuliposide A, a glycoside, is found in the white epidermis of tulip bulbs as well as in the stems, flowers, pistils, and leaves. Acidic hydrolysis converts it to tulipalin A (alpha-methylene-gamma-butyrolactone), the allergen. Tuliposide B (and therefore its hydrolytic product, tulipalin B), the beta-hydroxy derivative of tuliposide A, is commonly found in tulips, but is not an allergen.^15,115

Since its popularization in Holland in 1963, Peruvian lilies (Alstroemeria auriantiaca and A. ligtu, Alstroemeriaceae) have become incredibly popular in floral arrangements.¹¹⁶ Handlers remove individual flowers and thread wire through the stems.¹¹⁷ These workers often develop erythema, fissuring, vesicles, hyperkeratosis, and exfoliation of fingertips, greater on the dominant hand.^116,118 Unfortunately, the allergen passes through vinyl (polyvinyl chloride) gloves. Nitrile (synthetic rubber) gloves, however, are protective.¹¹⁶ Tuliposide A and B are found in virtually all portions of the plant. Attempts are being made to grow non-allergenic cultivars that contain only tuliposide B.¹¹⁹

Lamiaceae¹⁵

The mint family contains many aromatic plants, including herbs used in medicines, perfumes, and cooking. Essential oils of the herbs are considered potential sources of allergic contact dermatitis. (Essential oils are merely volatile plant oils with pleasing fragrances.) Lavender (Lavendula spp.) species provide lavender oil and water. Lavender oil contains geraniol, linalool, and lanalylacetate. Mint plants (Mentha spp.) are cultivated as herbs and ground covers, and they provide oil of peppermint and spearmint. Peppermint oil contains menthol and L-carvone that may be the allergens. Bartenders have acquired allergic contact dermatitis from making mint juleps. Salvia officinalis, sage, is a widely cultivated herb. Tea made from sage has caused stomatitis and cheilitis. One patient allergic to sage was also allergic to Compositae; the authors reporting him suggested that alantolactone may be the allergen in sage. Thyme (Thymus vulgaris) is a garden herb that grows as a low ground cover. Oil of thyme is used as a rubefacient in perfumes and toothpastes which have been known to cause irritant dermatitis. Thyme oil contains thymol and its isomer, carvacrol, which may be merely irritants or also allergens.

Myrtaceae^120,121

Many people are buying 'natural' products that contain melaleuca oil (tea tree oil), an essential oil derived by steam distillation from the crushed leaves of Melaleuca alternifolia (Myrtaceae). Two other species (M. linariifolia and M. leucadendron) also contain the essential oil. Tea trees are hardy, shrubby, paper-bark trees indigenous to swampy coastal areas of New South Wales in Australia. Melaleuca oil does have some proven antibacterial properties and has been hailed as a remedy for lice infestation, furuncles, psoriasis, acne, and fungal infections. One paper in the American literature reports seven individuals with allergic contact dermatitis.¹²¹ All patients were applying pure melaleuca oil to damaged skin for tinea pedis, dog scratches, "pimples of the legs," insect bites, and hand rashes. The most common allergen was d-limonene followed by aromadendrene and a-terpinene.

Figure 64: Melaleuca quinquenervia, Tea tree	M. quinquenervia, bark

M. quinquenervia, leaves

Orchidaceae ^{15, 122, 123}

More than 25,000 species comprise the family Orchidaceae, and the number increases each year with the production of new hybrids. Flowers of the genus Cypripedium are known as 'Lady Slippers.' Though orchids form the largest family of plants, they uncommonly cause allergic contact dermatitis, unlike the second largest plant family, the Compositae. In a survey of 53 employees of orchid farms, none had hand dermatitis. However, employees and managers could recall episodes of hand dermatitis that usually coincided with the introduction of a new chemical for disease control. Many people find raising orchids an enjoyable hobby, and contact is increasing. Vanilla comes from a species of orchid, but since most vanilla is manufactured synthetically, less contact dermatitis due to vanilla has been seen. Quinones, such as 2,6-dimethoxybenzoquinone, are the main cause of contact dermatitis and are thought to be most common in the leaf trichomes or pollen. Quinones have been renamed 'ubiquinones' and include co-enzyme Q which is involved in electron transport

Primulaceae ^{15, 124}

Primula obconica (Primulaceae) contains an allergen, primin, in its microscopic glandular hairs. No other primrose species contains this sensitizer. The concentration of these is greatest on the bracts surrounding the flower heads. To maintain cultivation, the plant requires frequent 'dead-heading,' pulling off the highly allergenic petals and sepals. This results most frequently in a fingertip dermatitis, but a nondescript, patchy dermatitis may also be present. The dermatitis is usually seasonal as plants are purchased in the spring and discarded in the fall or winter. This sensitizer is widely recognized in Europe. A patch test study of 3462 patients in London found that 1% were sensitive to primin.

ALLERGENIC TREES ^{15, 125}

Members of the family Pinaceae, such as Pinus spp. (pine trees) and Picea spp. (spruce trees) are major sources of colophony and turpentine. Allergic contact dermatitis to handling the trees is uncommon. Colophony is a sticky, amber-colored material derived from conifers and is named after the western Turkish town of Colophon. In the United States, we more commonly refer to colophony as wood rosin; it is obtained from the distillates of pine stumps. Contact dermatitis to colophony most commonly occurs from medical adhesives. The major use of colophony is as a paper finish to prevent spreading of ink. The main allergens of colophony are oxidation products of abietic acid, and its isomer, primaric acid.

Turpentine is an oleoresin derived from various conifers. Gum tapped from the trunk is separated by vacuum or steam distillation. Although once used commonly as a paint thinner, brush cleaner, and component of waxes, polishes, and industrial soaps, it has been replaced by other spirits. It is an irritant that also sensitizes. Its volatile fumes cause facial dermatitis and direct contact causes periungual dermatitis. It contains irritants such as alpha-pinene and allergens such as delta-3-carene.

The Leyland cypress, a hybrid member of the family Cupressaceae known as X Cupressocyparis leylandii, has become a popular evergreen conifer for hedging and screening in temperate climates. While its allergens are not known definitively, they cross-react with colophony. Possible allergenic constituents include carvacrol (methylisopropyl phenol), sesquiterpenes, and terpenes. Most patients that react to this tree have likely been sensitized to colophony by some other source.

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