Chemical Irritant Contact Dermatitis
The many thousands of plant species and their numerous chemical products make the study of CICD from plants appear daunting. The vast majority of CICD reactions, however, are caused by one of seven basic irritant groups: calcium oxalate, protoanemonin, isothiocyanates, diterpene esters, bromelain, and alkaloids. These are dissolved or suspended in the latex sap of the plant or housed in specific organelles such as stems, leaves, and bulbs ( Table 3 ).
Found in many genera of plants, calcium oxalate is a water-insoluble salt that forms bundles of needlelike crystals called raphides. Contact with moisture causes plant cells to eject the raphides, which can then come into contact with skin or mucosal surfaces. Irritancy is mechanical in part and due to the anatomically sharp structure of the crystals themselves. The crystals are believed to be more irritant when longer than 180 µm. The raphides of calcium oxalate have been classified historically as a chemical irritant mainly because they allow the penetration of other plant chemical toxins (including proteases, saponins, and other chemicals) that may not normally breach the skin on contact. They also enhance the penetration of known skin irritants, including many alkaloids from daffodil bulbs, bromelain in pineapples, and saponins in Dieffenbachia.
The most frequently cited example of calcium oxalate-induced CICD is that of Dieffenbachia spp, commonly used as decorative plants.[1,2,9] CICD caused by flower bulbs is usually less severe but much more common and economically more significant. Bulbs, including those of tulips, daffodils, and hyacinths, may contain a high concentration of calcium oxalate. Bulb dermatitis is most prominently an occupational hazard of florists, gardeners, bulb planters, and the individuals who cut the flowers. The reactions are localized to those areas in greatest contact with the bulbs, typically the fingertips, hands, and forearms. However, if dust containing calcium oxalate crystals from the bulbs penetrates clothing, the eruption can become more generalized and extensive.
Dieffenbachia. Innocuous-appearing houseplants may result in severe ICD, and some should therefore be treated as poisonous, especially in regard to children and pets. Members of the Araceae family, Dieffenbachia plants are popular as decorative plants in homes and offices. The leaves and the fruit of the plant are notorious for causing severe local effects. Contact can result in ejection of the raphides, penetration into the skin, and induction of histamine release from mast cells. Saponins, cyanogenic glycosides, proteolytic enzymes, and alkaloids likely contribute to the vesicant properties of the plant. The resultant dermatitis can be marked by pruritus and erythema along with vesicular and bullous eruptions that may include the palmar surfaces of the hands. If the plant is eaten, stomatitis, hoarseness, and aphonia can ensue, along with edema and erosions following the path of the plant along the gastrointestinal tract; thus, the plant is also known as "dumb cane." Ingestion of another group of common houseplants in the Araceae family, Philodendron spp, may also result in similar symptoms due to the presence of calcium oxalate. including proteases, saponins, and other chemicals.
It is also noteworthy that splashes of plant tissue juice or the transfer of raphides from the hands to the eyes cause immediate severe pain, lacrimation, and blepharospasm as large numbers of calcium oxalate crystals penetrate the cornea.
Tulips and "Tulip Fingers". The sap of the tulip (family Liliaceae) contains the well-characterized allergen tulipalin A. The individual tulip bulbs contain a tough outer tectum that can fragment and impale the skin, resulting in mechanical irritant injury. Tulip bulbs also have some calcium oxalate raphides. The combined effect of irritant and allergic contact dermatitis from tulips results in "tulip fingers." Contact can be extensive for those who handle the bulbs for peeling, those who sort the bulbs and prepare them for shipping, or those who cut or pick the flowers.
The clinical presentation of tulip fingers may range from fissured and hyperkeratotic fingertips, pulpitis, paronychia, and nail changes, to an extensive eczema, sometimes with pustules on the fingers or even the entire hand. Additionally, the eczema may secondarily spread to the face, the neck, the arms, or the anogenital region.
Daffodils and "Daffodil Itch". Contact with the stems and bulbs of daffodils (Narcissus spp) causes the dermatosis known as daffodil itch or lily rash. This is probably the most common contact dermatitis reaction among florists. It is endemic among those who cut, bunch, and pack daffodils. The mucus from the hollow stems and the sap from the bulbs contain abundant calcium oxalate raphides. Contact with the mucus or sap can result in daffodil itch, the most severe presentation being among individuals who pick the flowers. Features of the rash are generally mild and include xerosis, scaling, fissures, and erythema affecting areas that have been in direct contact with the mucus or sap of the plant, most frequently the fingertips, hands, and forearms. Additionally, transfer of the raphides (such as when the hands touch the face) can result in more extensive dermatitis.
It is believed that, along with the calcium oxalate raphides, alkaloids in the sap and mucus of the daffodil may contribute to the rash (see the discussion of alkaloids, below). Unlike cases of tulip fingers, which can have a large allergic component, most cases of daffodil itch are primarily an ICD. The rash, unlike that in tulip fingers, is often self-limiting because of the mildness of the dermatitis and the brevity of the daffodil picking season. After going to great lengths to observe the work habits of daffodil pickers and handlers, Julian and Bowers documented the variations in the presentation of daffodil itch.
Hyacinths. Hyacinths (Hyacinthus spp) can elicit a CICD that closely resembles daffodil itch and occurs via a similar mechanism. The outer tectum of the hyacinth bulb can be broken into particles that cause mechanical trauma to the skin. Additionally, up to 6% of the hyacinth bulb is composed of calcium oxalate crystals. Handling the bulbs causes the tecta to break into small sharp particles, simultaneously releasing calcium oxalate crystals. These particles can readily become airborne, making contact with body regions other than the hands.
Agave. Agave spp are laden with calcium oxalate raphides and saponins. A single droplet (0.03 mL) of juice extracted from the leaves of the agave plant is reported to contain hundreds of calcium oxalate raphides, each as long as 500 µm. These crystals and saponins are the presumptive source of the marked pruritus and stinging associated with exposure to the agave plant. The plant is indigenous to North America, and the fruit of some species (including Agave tequilana) is used in the production of tequila. On agave plantations and in tequila distilleries, CICD related to agave is more routinely seen.
Other Plants. Raphides are present in various amounts in other genera of plants. Some cacti, such as Cephalocereus senilis, contain up to 85% calcium oxalate by dry weight. CICD from plants in the Asteraceae family (which includes daisies and carnations) has been reported, and calcium oxalate is a putative culprit.
Protoanemonin is a chemical irritant found almost exclusively among various members of the Ranunculaceae (buttercup) family. Upon maceration or bruising of plant tissue, ranunculin (a glycoside) is hydrolyzed into protoanemonin, which is a volatile unsaturated lactone of ?-hydroxyvinylacrylic acid. While the mechanism of protoanemonin irritancy is not completely understood, protoanemonin has been shown to combine with sulfhydryl groups in the skin and disrupt disulfide bonds, resulting in subepidermal dysjunction and bulla formation.
Crushing of the plant leaves results in the production and release of protoanemonin, which can subsequently cause an irritating odor, conjunctival irritation, and irritation of the nasal airway. Transient contact of freshly crushed leaves with the skin results in warmth, burning, and irritation; sustained contact results in erythema, edema, vesiculation, blistering, ulceration, and residual hyperpigmentation. Linear streaks are a hallmark of exposure to protoanemonin from field buttercups (Ranunculus spp), potentially contributing to a misdiagnosis of phytophotodermatitis.[2,9] Only freshly macerated leaves are involved in irritant reactions because protoanemonin rapidly and spontaneously polymerizes into anemonin, which is not a skin irritant.
Specifically among Ranunculus spp, Ranunculus illyricus is a ubiquitous weed commonly used in South America and the Middle East for medicinal purposes. CICD reactions have been well documented in the literature.[29,30]
Apart from Ranunculus, irritant members of the family Ranunculaceae include several genera of decorative flowering plants, including Anemone, Clematis, and Helleborus. A notable genus is Pulsatilla, which includes the European pasqueflower (Pulsatilla vulgaris) and the American prairie crocus (Pulsatilla patens), a common species on the dry prairies of Minnesota. The leaves, in particular, induce bullous irritant reactions. Also noteworthy within the family is Ceratocephalus falcatus, a ubiquitous weed in the Middle East, known for causing second-degree burns.[27,31] This weed, like many members of the Ranunculaceae family, is often used as an herbal medicine.
Mustard Oils (Isothiocyanates)
Isothiocyanates are the principal irritant constituents of the mustard oils found in many members of Brassicaceae (previously Cruciferae), the mustard family. Mustard oils are not found in intact plants but are instead generated upon injury to the plants. Glucosides (glucosinolates), which serve as precursors to isothiocyanates are found in all parts of the plants but especially in the seeds. The oil-generating reaction is catalyzed by an enzyme, myrosinase, which is released upon damage to the plant. The product in the reaction is isothiocyanate.[26,32]
Isothiocyanates react readily with the amino-groups of proteins on human skin and mucosal surfaces. Interestingly, the spicy taste of plants in the Brassicaceae family is due to the irritant isothiocyanates. The skin's reaction is generally an immediate and short-lived burning, erythema, and urticaria, which is especially prominent among food handlers and those who cook. The eyes are particularly sensitive; thus, mustard oil was used as a component of tear gas in warfare.
Mustard oils are well known for their pungent odor and for centuries have been used for cooking and for their medicinal properties. The isothiocyanate components of mustard oils have recently gained attention because of their potential for inhibiting carcinogenesis.
Along with mustards, members of the Brassicaceae family include cabbage, cauliflower, and radish. Horseradish (Armoracia rusticana) and wasabi (Japanese horseradish, Wasabia japonica) contain extremely reactive isothiocyanates and are accordingly especially potent irritants.
Plants from other families that produce similar oils include mignonettes (Resedaceae), papaya (Caricaceae), spurges (Euphorbiaceae), nasturtiums (Tropaeolaceae), pokeweed (Phytolaccaceae), plantains (Plantaginacaeae), and capers (Capparaceae). Numerous accounts appear in the literature regarding the glucosides and isothiocyanates of Capparaceae and their erythema-inducing and vesicant properties on the skin.
Phorbol, daphnane, and diterpene are chemical irritants collectively known as diterpene esters. They are among the most irritant of plant-derived chemicals. Most commonly associated with these irritant esters are the spurges (family Euphorbiaceae), a very large, ubiquitous, and varied family that encompasses more than 8,000 species in 300 genera. One commonality that is largely preserved within this diverse family is the corrosive irritant latex produced by almost all of its member plants. The primary active agents in the latex (or sap) are believed to be diterpene esters. In fact, almost 90% of the species of Euphorbiaceae screened for inflammatory capability have been show to have activity in this regard.[36,37] Besides their corrosive properties, diterpene esters are also believed to play a role in tumorigenesis, specifically by activation of intracellular protein kinase C.
Because of the irritant esters within their latex, euphorbs are among the most aggressively irritant plants. The skin and eyes are particularly susceptible, and presentations include pain, erythema, edema, blistering, conjunctivitis, and even blindness.[2,39] If the leaves or fruits of euphorbs are consumed, bloody diarrhea and vomiting may ensue. These gastrointestinal manifestations are believed to be the basis of the common name given to euphorbs: "spurge."
Plants of the genus Euphorbia bear special mention because every species is believed to have irritant properties in some form. Poinsettias (Euphorbiapulcherrima) are a prominent member of this group, given their popularity as decorative plants. They contain minimally irritant latex and generally cause a mild CICD reaction. Other common members of Euphorbia include the spotted spurge (Euphorbia maculata), the petty spurge (Euphorbia peplus), and snow-on-the-mountain (Euphorbia marginata), all of which are weeds that can cause irritation when pulled or handled with bare hands.[32,33]
Perhaps the most notorious and formidable member of the Euphorbiaceae family is the manchineel tree, or beach tree (Hippomane mancinella). The tree is commonly found coastally in Central America, the Caribbean, and the southern regions of Florida. The tree produces a sweet-smelling fruit that can cause severe oral pain, mucosal edema, and blistering if consumed, as well as vomiting and hemorrhagic diarrhea if swallowed. Any part of the tree can cause cutaneous irritation from direct contact; the hands, face, and genitalia are common sites of irritation. Even the dried wood of the tree is toxic and cannot be cut or burned without risk of irritation. More widespread but also coastally located, the pencilbush (Euphorbia tricualli) produces copious amounts of milky latex that can cause severe dermatitis and even temporary blindness.
Most euphorbs in the United States are shrubs such as Texas croton (Croton texensis), a species that produces immediate skin blisters from phorbol esters in the leaves, stems, and seeds. About 45 species of croton are found in the United States. They may occasionally be seen as decorative garden plants, but most species can be found proliferating across prairie land because cattle do not willingly eat them.[32,41]
An economically important euphorb is the castor bean plant (Ricinus communis), from which castor oil is extracted. The oil is used in the production of soap, detergents, paints, dyes, and lubricants. Of note, the seeds of the plant are poisonous because they contain ricin, a chemical that inhibits protein synthesis and that has the potential for use in biological warfare. Castor oil is itself a contact irritant because it is extracted from the beans of the plant, which contain a sap laden with diterpene esters.
Closely related to the euphorbs are plants in the family Thymelaeaceae, which includes species of daphne, including Daphne odora (winter daphne) and Daphne mezereum (February daphne). They produce daphnane, an ester considered to be among the most irritant of all plant chemicals. Most daphnes are evergreen shrubs that bear creamy sweet-smelling flower clusters that are lethal to eat and produce a CICD similar to that caused by the euphorbs.
Bromelain is a plant-derived collection of enzymes originally extracted from the pineapple plant (Ananas comosus of the family Bromeliaceae). The enzymes include proteases, phosphatases, and peroxidase. Because of its enzymatic activity, bromelain has been used by the food and beverage industries for the tenderizing and processing of meat and for the clarification of beer during brewing.
The proteolytic activity of bromelain is purported to be the source of cutaneous irritation. It is thought that calcium oxalate raphides in the pineapple plant cause microabrasions, allowing bromelain to exert its proteolytic effect on dermal blood vessels. It is therefore not surprising that pineapple workers often develop fissures and fingerprint loss on their hands.
Capsaicin and Other Alkaloids
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is an alkaloid derived from members of the Solanaceae family, including chili peppers (Capsicum spp) (Figure 9). In humans, capsaicin binds to vanilloid receptors on sensory neurons, which can also be stimulated by heat and pain. The neuronal activation results in the sensation of heat. As only nerves are affected, capsaicin elicits a dose-related cutaneous burning and erythema without any overt blistering. Other local effects include smooth-muscle stimulation, glandular secretion, and vasodilation. By these same actions, capsaicin contributes to the pungency of chili peppers.
Irritation from chili peppers has been reported in the literature as "Hunan hand syndrome" or "chili burns." It is reported to frequently present among those who handle chili peppers, including cooks and workers who handle large batches for processing.
The alkaloids as a chemical group are very diverse and include many of the commonly known bioactive compounds derived from plants, such as ephedrine, morphine, and quinolones. Colchicine, for example, is a cytotoxic alkaloid used in the treatment of various malignancies and is derived from the autumn crocus (Colchicum autumnale). Nicotine is presumed to be the active irritating component of the tobacco plant, which has been reported to cause cutaneous irritation among workers on tobacco plantations.
Not all alkaloids are innately cutaneous irritants, but they can often irritate the skin upon breaching the skin barrier. For example, at least 15 alkaloids have been isolated from daffodils, some of which (including homolycorin, lycorin, and masonin) are believed to contribute to the ICD caused by the plant's calcium oxalate raphides.[4,23]
Other Plants and Chemical Irritants
Garlic. Garlic, onions, and chives are all members of the Allium genus within the Alliaceae family. With regard to garlic, allergic cutaneous reactions are more typical. However, clinical presentations have also been reported that more closely resemble an irritant picture, suggesting that garlic may cause a mixed allergic and irritant dermatitis. Workers in the food industry, such as cooks, are most frequently affected. Generally, the dermatitis involves the fingertips of the first three fingers of the nondominant hand, which hold the garlic in place for chopping.
The possible chemical irritants in garlic have not been well characterized, but it is believed that many of the bulbs of plants in this genus may contain the previously discussed irritant isothiocyanates.
Garlic has been used as an herbal remedy, and irritation from the topical application of crushed garlic to intact skin has been well documented (Figure 10). Cases of individuals with erosions, ruptured hemorrhagic bullae, and second-degree burns have been documented.[29,47,48]
Patient with severe irritant contact dermatitis that occurred after the application of raw garlic as home therapy for a tinea corporis lesion on the lateral thigh. (Photograph courtesy of Dr. Blancha Ochoa)
Juglone. Juglone is an aromatic naphthoquinone found in the leaves, roots, and bark of many members of the Juglandaceae family, particularly walnut trees (Juglans spp). It has been documented to cause an ICD as well as hyperpigmentation of the skin. The hyperpigmentation is not postinflammatory but rather occurs via chromophore groups, similar in mechanism to henna. The pigmenting properties of juglone has resulted in the juice of fresh walnut husks being used in dyes and tanning products.
Woods and Trees. ICD from woods is more common than allergic contact dermatitis from woods, and almost any wood has the potential to be a mechanical irritant when its dust comes in contact with the skin. Trees are constituents of many of the culprit plant families previously discussed, and their irritant chemicals include various alkaloids and diterpene esters. These irritating compounds occur in many woods commonly found throughout the United States. Pine and spruce trees are well-documented sources of ICD among woodcutters, carpenters, and builders.
Acids. Acids (citric, acetic, formic, malic, salicylic, and oxalic) make up a group of chemical irritants that deserve brief mention.[1,52] The cutaneous irritant properties of salicylic acid (from the salix tree, Salix spp) are used in the treatment of many dermatologic conditions such as acne. The vegetable rhubarb comes from the stalk of the rhubarb plant (Rheum rhabarbarum of the family Polygonaceae). Whereas the stalk is commonly consumed, the leaves contain oxalic acid and are toxic when consumed.
Dermatitis. 2009;20(2):63-78. © 2009 American Contact Dermatitis Society
Cite this: Irritant Contact Dermatitis from Plants - Medscape - Mar 01, 2009.