Plants and Plant Products 41 Christophe J

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Chapter 41 Plants and Plant Products 41 Christophe J. Le Coz, Georges Ducombs

Contents 41.3.14.1 Araliaceae (Ginseng, Aralia, Ivy Family) . . . 785 41.1 Introduction ...... 751 41.3.14.2 Papaveraceae (Poppy Family) ...... 786 41.3.14.3 Guttiferae (St John’s Wort 41.2 Clinical Pictures ...... 752 or Mangosteen Family) ...... 786 41.2.1 Immediate-Type Reactions ...... 752 41.3.14.4 Hydrangeaceae ...... 786 41.2.1.1 Contact Urticaria ...... 752 41.3.14.5 Iridaceae (Iris Family) ...... 786 41.2.1.2 Protein Contact Dermatitis ...... 753 41.3.14.6 Solanaceae (Nightshade Family) ...... 786 41.2.2 Irritant Contact Dermatitis ...... 754 41.4 Diagnosis of Plant Dermatitis ...... 787 41.2.2.1 Mechanical Irritation ...... 754 41.4.1 Raw Plants ...... 787 41.2.2.2 Chemical Irritation ...... 755 41.4.1.1 Plant Identification ...... 787 41.2.3 Allergic Contact Dermatitis ...... 755 41.4.1.2 Prick Tests ...... 787 41.2.3.1 Acute ACD: Acute Eczema ...... 755 41.4.1.3 Patch Tests ...... 787 41.2.3.2 Chronic ACD and the Example of “Tulip Fingers” ...... 755 41.4.2 Plant Extracts ...... 788 41.2.3.3 Erythema Multiforme-like 41.4.3 Allergen Identification ...... 788 and Atypical Dermatitis ...... 757 41.4.4 Commercial Allergens ...... 788 41.2.3.4 Airborne Contact Dermatitis ...... 758 41.4.5 Photopatch Testing ...... 788 41.2.4 Photodermatitis (Phytophotodermatitis) . . 758 41.4.6 Results and Relevance ...... 789 41.2.4.1 Phytophototoxicity ...... 758 41.4.7 Multiple Plant Reactions 41.2.4.2 Phytophotoallergic Contact Dermatitis . . . 761 and Cross-sensitivity ...... 790 41.3 Inducers of Dermatitis ...... 761 41.5 Prevention and Treatment ...... 790 41.3.1 Alliaceae (Onion Family) ...... 761 41.5.1 Removal of the Allergens and Irritants . . . . 790 41.3.2 Alstroemeriaceae (Alstroemer Family) 41.5.2 Barrier Creams ...... 790 and Liliaceae (Lily Family) ...... 762 41.5.3 Gloves ...... 790 41.3.3 Amaryllidaceae (Daffodil Family) ...... 764 41.5.4 Acute Dermatitis ...... 790 41.3.3.1 Anacardiaceae, Ginkgoaceae, and Proteaceae 764 41.5.5 Chronic Dermatitis ...... 790 41.3.4 Compositae (Asteraceae) and Liverworts . . 769 41.5.6 Hyposensitization ...... 791 41.3.4.1 Asteraceae/Compositae (Daisy Family) . . . 769 41.6 Example of Botanical Nomenclature . . . . . 791 41.3.4.2 Liverworts (Jubulaceae) ...... 772 References ...... 791 41.3.4.3 Sesquiterpene Lactone Allergens ...... 772 41.3.5 Cruciferae (Cabbage or Mustard Family, Brassicaceae) ...... 774 41.3.6 Euphorbiaceae (Spurge Family) ...... 775 41.3.7 Lichens ...... 776 41.3.8 Primulaceae (Primrose Family) ...... 778 41.1 Introduction 41.3.9 Ranunculaceae (Buttercup Family) ...... 779 41.3.10 Umbelliferae/Apiaceae (Carrot Family), Contact dermatitis from plants or plant products, Rutaceae (Rue Family) and Moraceae phytodermatitis (Mulberry Family) ...... 780 , is frequently observed in clinical 41.3.11 Woods ...... 781 practice. It is likely that the most frequent reactions 41.3.11.1 American and Australian Woods ...... 782 of this type, which occur due to occasional and irri- 41.3.11.2 Asian Woods ...... 783 tant contacts such as those encountered during lei- 41.3.11.3 African Woods ...... 783 sure activities,are not seen by dermatologists.Practi- 41.3.11.4 European Woods ...... 784 tioners usually see more severe dermatitis cases, with 41.3.12 Mushrooms ...... 785 irritant or allergic mechanisms, of immediate or de- 41.3.13 Ferns ...... 785 layed type, and sometimes photoworsened or even 41.3.14 Miscellaneous Plants ...... 785 photoinduced dermatitis. 41_751_800 05.11.2005 11:33 Uhr Seite 752

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The exact incidence of dermatitis from plants and tanical Dermatology Database, owner Richard J. plant products is not known, but this problem is not Schmitt, see http : //bodd.cf.ac.uk/index.html) for its rare. Many patients likely self-medicate following interesting content [10]. self-diagnosis or diagnosis by a pharmacist,or attend their family doctor who prescribes palliative treatment without necessarily ascertaining the cause of 41.2 Clinical Pictures the skin reaction. In other instances, cases do reach the dermatologist. For example, among 1752 patients 41.2.1 Immediate-Type Reactions considered to have occupational dermatitis, Fregert found that 8% of women and 6% of men were react- The types of reaction reviewed in this section belong ing to plant-derived products [1]. We can therefore to the class of immediate responses that have immu- estimate that, among patients attending dermatolog- nological or nonimmunological mechanisms. ic clinics for dermatitis, an average of 5–10% suffer from dermatitis caused by plants or plant products.It is, however, evident that geographical variations in 41.2.1.1 Contact Urticaria flora considerably influence the epidemiology of plant dermatitis. Contact urticaria appears within minutes following In Europe, many phytodermatitis cases are occu- contact with the plant. It has been described for vari- pationally acquired. Florists, gardeners, horticultur- ous species [11, 12]. ists, foresters, woodworkers, farmers, cookers and people in contact with food preparation are at risk, as Nonimmunological Contact Urticaria described by Paulsen [2–4]. Hobby gardeners, housewives and those who handle or come into contact Probably the best known urticant plants are the net- with plant materials non-occupationally are also at tles belonging to family Urticaceae, like Urtica dioica risk. Indeed, any persons enjoying leisure pursuits in L., U. urens L., and U. pilulifera L. The stinging hairs the garden or countryside (children playing, camp- are disposed on the ventral faces of the leaves, per- ers, walkers and so on) are likely to come into contact mitting skin penetration of histamine, acetylcholine with plant material with the potential to cause con- and 5-hydroxytryptamine after only a very slight tact dermatitis. touch. Nettles are used for rheumatic disorders in For plants and plant products, reactions of mixed folk medicine [7, 13]. aetiology are frequent, like allergic reactions super- Among other nonprotein substances, plant-de- imposed on irritant reactions due to Asteraceae, or rived pharmacological elicitors of urticaria are nu- mechanical plus chemical irritations evoked by merous, and include Myroxylon pereirae (balsam of stinging nettles. It is frequently hard to distinguish Peru) and the cinnamic acid derivatives contained between allergic and irritant mechanisms in clinical therein (Fig. 1), thapsigargin from Thapsia garganica examination and during patch test procedure, and L. (family Apiaceae) [11, 14, 15], and capsaicin from the reader will have to bear this in mind constantly. different species of capsicum, such as paprika and We will limit this chapter to plant contact, and will cayenne (Capsicum spp., family Solanaceae). The not consider the effect of systemic administration of mechanism by which nonimmunologic urticant plants of plant extracts. agents elicit their effect (at least for those agents list- It is clearly impossible to provide an exhaustive ed above) appears to involve the release of histamine catalog of cutaneous side-effects of plants in this from mast cells. chapter (which owes much to the previous edition by Georges Ducombs and Richard J. Schmitt), and the reader will sometimes be invited to examine the Core Message 41 question in more detail using other sources. Some books are prominent in botanical dermatology, like í Contact urticaria from nonprotein those written by Mitchell and Rook [5], Lovell [6], chemicals is most often due to a Sell [7], or Benezra, Ducombs, Sell and Foussereau non-immunological mechanism. [8]. Others focus on, are devoted to, or are restricted to geographical areas [9]. Many (but not all) important medical articles and reviews are indexed in Immunological (IgE-mediated) Contact Urticaria international databases like the United States National Library of Medicine (see http://www.nlm.nih.gov/). Fruits and vegetables may induce allergic contact ur- We also warmly recommend the website BoDD (Bo- ticaria, mainly in people with previous dermatitis, 41_751_800 05.11.2005 11:33 Uhr Seite 753

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Fig. 1. Cinnamic acid, CAS 621–82–9, cinnamic aldehyde, CAS 104–55–2, thapsigargin, CAS 67526–95–8 and capsaicin CAS 404–86–4

like atopic dermatitis (see Sect. 41.2.1.2, Protein Con- exposure to dust derived from cinchona bark (Cin- tact Dermatitis). For example, sensitization from chona spp., family Rubiaceae) [18]. birch pollen (Betula alba L., family Betulaceae) may Allergic urticaria may spread from the initial site be complicated by immediate symptoms occurring of contact, become generalized or be associated with after ingestion (mouth swelling) or skin contact systemic symptoms of anaphylaxis. (contact urticaria) due to apples, hazelnuts, almonds, plums, apricot, peach, cherries, or celery and carrot. This is due to strong homologies with the birch pol- Core Message len allergens Bet v 1 and/or Bet v 2. A case report of occupational contact urticaria í Immunologic-type contact urticaria and type I sensitization attributable to a gerbera is due to specific IgE synthesis, mainly (probably Gerbera jamesonii Bolus, family Astera- to proteins, and can be severe, with ceae) has been reported. Conjunctivitis and respira- generalized or systemic symptoms. tory symptoms are possible [16]. Airborne contact urticaria can be associated with rhinitis, conjunctivitis or asthma. This has been largely reported as an occupational problem in health workers with hypersensitivity to latex proteins 41.2.1.2 Protein Contact Dermatitis from rubber gloves made with natural latex (usually derived from Hevea brasiliensis Muell.Arg., family Protein contact dermatitis is mostly seen in persons Euphorbiaceae). Airborne transmission of the latex (with atopy in 50% of cases) who handle foods, meat allergens is enhanced by their adsorption onto the or vegetables, and has been described with frequent cornstarch (derived from Zea mays L., family Grami- foods like onion, lettuce, potato, carrot or more rare- neae) used as glove powder [17].Airborne contact ur- ly with asparagus (personal observation). It general- ticaria reported in a warehouseman resulted from ly consists of a chronic dermatitis, mainly located on 41_751_800 05.11.2005 11:33 Uhr Seite 754

754 Christophe J. Le Coz, Georges Ducombs

hands and forearms, with acute urticaria appearing within minutes of contact with food proteins, which rapidly disappears. It is followed by worsening of the dermatitis within hours or days [19–23]. Protein contact dermatitis can be of irritant (nonspecific) or allergic (IgE-mediated) type. In such cases, atopy with immediate-type sensitizations to pollens is frequent.

Core Message

í Protein contact dermatitis due to plant or plant products consists of contact urticaria followed by worsening of a previous dermatitis, mainly occurring in food handlers.

41.2.2 Irritant Contact Dermatitis

41.2.2.1 Mechanical Irritation

A number of plants can provoke “macrotraumatic” Fig. 2. Granulomatous lesions on a child’s arm from cactus injury by mechanical means due to their armament (courtesy of F.Vakilzadeh) of prickles, spines or thorns. Others, because of the knife-like morphologies of their leaf edges, may lac- erate the skin. Although typically a trivial and self- limiting event, such mechanical damage may lead to the development of sores, secondary infections such as pyodermitis or tetanus, and granulomatous lesions that may develop insidiously some time after the initial trauma, after it has been forgotten. In arid regions of the Americas for example, cacti (family Cactaceae) are responsible for injuries that may become granulomatous, after dermal embedding of plant material [24, 25] (Fig. 2). Certain plants are injurious because their bristles or barbs (named trichomes or glochids, respectively) can cause “microtrauma.”These structures can pene- trate the outer layer of the skin and cause papular dermatitis, prurigo and even symptoms of urticaria. In 1956, Shanon and Sagher [26] described “Sabra dermatitis,” due to occupational contact with the prickly pear, also named the Indian or Barbary fig Fig. 3. Indian or Barbary fig (Opuntia ficus-indica Miller, fam- 41 (Opuntia ficus-indica Miller, family Cactaceae) ily Cactaceae) (Fig. 3). Dermatitis is caused by penetration of glochids from the spine cushions of the plants and their fruits through the skin, and it simulates chronic ecze- plants that contain crystals such as blue agave (Agave ma or scabies. tequilana Weber) [28]. Penetration of the skin by Microtrauma (and chemical irritant action) from such raphides may be accompanied by intracutane- calcium oxalate needle crystals (named raphides) al- ous injection of plant sap. This can result in an irri- so causes a characteristic dermatitis resembling that tant or allergic skin reaction to one or more of the from glass fiber [27]. Irritant contact dermatitis oc- sap constituents. Thus, preparation of the tubers of curs almost systematically in people who handle various aroids (plants of Araceae family) for food use 41_751_800 05.11.2005 11:33 Uhr Seite 755

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(for example the malanga or cocoyam, Xanthosoma a patient (as with burns) and are limited to sites of sagittifolium L.) carries with it the risk of dermatitis contact, such as the hands, forearms, mucous mem- from the calcium oxalate needle crystals and the sap- branes, perioral regions, buttocks, and so on. They onins it contains [29]. Similarly, calcium oxalate ra- consist of simple dryness of the skin, cracking and phides in dumbcanes (Dieffenbachia spp., family Ar- hyperkeratosis, inflammatory reactions with edema, aceae), which are commonly grown as decorative erythema, papules, and vesicles. Pain rather than house plants, are responsible for an edematous urti- itching is also a feature. Strong irritant plants like caria-like dermatitis, and/or an edematous and bul- spurges (Euphorbia spp., family Euphorbiaceae) may lous stomatitis in people who have handled damaged induce blisters, ulceration, or necrosis by the way of plant material or accidentally chewed the leaves. The their acrid milky juice. Ranunculaceae, such as Ra- reaction in the mouth renders the victim speechless nunculus bulbosus L. or R. repens L., are sometimes (hence the common name of the plant, dumbcanes) used in traditional medicine, have been reported to and may even be life-threatening if the airway be- be strong irritants, inducing bullous or even necro- comes obstructed. The severity of the reaction has tizing dermatitis by the way of ranunculin [7, 13, 31]. been ascribed to the presence of a protease named dumbcain in the plant sap, which contributes to the irritant reaction [30]. Core Message

í Chemical irritation from plants Core Message (such as Euphorbiaceae) may induce severe chemical burns. í Trauma due to plants may be due several mechanisms. Prickles, spines or thorns provoke macrotraumas, and leaves may act like knifes. Microtrauma may be due to dermo-epidermic penetration of trichomes 41.2.3 Allergic Contact Dermatitis (bristles), glochids (barbs), or raphides (calcium oxalate needle crystals). Allergic contact dermatitis (ACD) from plants can present in many forms, depending upon both the allergen and the method of exposure.Typical forms are represented by acute ACD, fingertips or periungueal chronic ACD, airborne ACD, contact urticaria, and 41.2.2.2 Chemical Irritation erythema multiforme-like eruptions.

Many plants contain irritant substances (Table 1) which vary from weakly irritant compounds, requir- 41.2.3.1 Acute ACD: Acute Eczema ing repeated exposure or a damaged skin barrier to exert their effects, to some of the most irritant com- The normal presentation is that of a typical ACD, in- pounds known to Man, which can elicit inflamma- volving exposed parts such as the hands, forearms, tion in microgram quantities, like these contained in eyelids, and sometimes the genitals if the allergen is Euphorbiaceae. Such potent skin irritants are also conveyed by the hands or clothing. Lesions onset at mucous membrane irritants, and can cause violent the site of contact are frequently diffuse, spreading purgation after ingestion, and intense ocular irrita- on unexposed areas.The initial maculopapular or ve- tion that may lead to blindness when there is contact sicular eruption may provoke blisters or develop into with the eyes. The mechanical role of calcium oxalate a full-blown erythroderma as, for example, with needles has been described above: they moreover en- Frullania (Jubulaceae family) dermatitis. hance the action of toxic chemicals such as the prot- eloytic enzyme bromelain (of pineapple), or the toxic glucosides contained herein, the so-called saponins. 41.2.3.2 Chronic ACD and the Example Acute irritant dermatitis can arise after some min- of “Tulip Fingers” utes or hours. Chronic dermatitis develops after repeated contact with the irritant agent or on the back- A number of examples of usually occupationally ac- ground of previous contact with weakened skin. The quired finger dermatitis have been described, with clinical presentation of irritant contact dermatitis is some typical features. This takes the form of finger- various, but lesions are generally monomorphous in tip dermatitis, painful rather than pruritic, fissured 41_751_800 05.11.2005 11:33 Uhr Seite 756

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Table 1. Main plants responsible for chemical irritant contact dermatitis

Family Botanical name English name French name German name Offending chemicals

Agavaceae Agave americana Linné. Agave Agave d’Amérique Amerikanische Calcium oxalate Agave Sapogenins

Amaryllidaceae Narcissus pseudo- Daffodil Jonquille Gelbe Narzisse Calcium oxalate narcissus Narcissus poeticus L. Poet’s narcissus Narcisse des poètes Dichternarzisse Calcium oxalate

Araceae Dieffenbachia picta Schott Dumb cane Dieffenbachia Dieffenbachie Calcium oxalate Philodendron spp. Philodendron Philodendron Baumlieb

Bromeliaceae Ananas cosmosus Pineapple Ananas Ananas Calcium oxalate Bromel(a)in

Brassicaceae Armoracia rusticana Horse radish Raifort Meerrettich Isothiocyanates Brassica oleracea var. Broccoli Brocoli Brokkoli italica Brassica nigra L. True mustard Moutarde noire Schwarzer Senf Raphanus sativus L. var. Small radish Radis Radieschen sativus Sinapis alba L. White mustard Moutarde blanche Weisser Senf

Euphorbiaceae Euphorbia spp. Spurge Euphorbe Wolfsmilch Latex: Euphorbia pulcherrima Poinsettia Poinsettia Weinachtsstern esters of phorbol Willdenow Codiaeum variegatum Croton Croton Wunderstrauch esters of ingenol Hippomane mancinella Manchineel tree Mancellinier Manzanillbaum Ricinus communis L. Castor bean Ricin Rizinus, Wunderbaum

Liliaceae Hyacinthus orientalis L. Hyacinth Jacinthe Gartenhyazinthe Calcium oxalate

Polygonaceae Rheum rhaponticum L. Rhubarb Rhubarbe Rhabarber Calcium oxalate

Ranunculaceae Anemone pavonina Lam. Anemone Anémone Anemone Protoanemonin Ranunculus acer L. Meadow Bouton d’or Butterblume butter-cup Aquilegia vulgaris L. Columbine Ancolie des jardins Gemeine Akelei Caltha palustris L. Yellow marsh Souci d’eau Sumpfdotterblume marigold

Solanaceae Capsicum frutescens L. Chillies Piment de Cayenne, Cayennepfeffer Capsaici langue d’oiseau Capsicum annuum L. Sweet pepper, Poivron, piment Tachepfeffer, capsicum doux and piment Paprika fort 41

and hyperkeratotic, of which the best-known exam- aceae) (Fig. 4a, b), garlic (Allium sativum L., family ple is “tulip fingers,”seen in tulip pickers (Tulipa spp. Alliaceae), and so on. The most frequently involved and cultivars, family Liliaceae). Lesions frequently fingers are those that are in direct and prolonged spread on periungueal sites, inducing onychosis. contact with the bulb. For garlic dermatitis in cooks, Similar reactions may arise in persons handling daf- the nondominant hand is generally involved, since it fodil and narcissus bulbs (Narcissus spp. and culti- is the one used to maintain the bulb.Although nomi- vars, family Amaryllidaceae), Alstroemeria flowers nally an immunological delayed-type reaction, tulip (Alstroemeria spp. and cultivars, family Alstroemeri- fingers and related eruptions such as “daffodil itch” 41_751_800 05.11.2005 11:33 Uhr Seite 757

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Fig. 4a, b. a Alstroemeria spp. family Alstroemeriaceae. b Allergic contact dermatitis in a nursery gardener from Alstroe- meria (courtesy of P.J. Frosch)

or “lily rash” in daffodil bulb or flower handlers [32] the literature. An occupationally acquired airborne may arise in part from mechanical and/or chemical erythema multiforme-like eruption was due to py- irritation. rethrum (Tanacetum spp., family Compositae) used as a pesticide [39]. 41.2.3.3 Erythema Multiforme-like and Atypical Dermatitis

Bonnevie first described an erythema multiforme- like rash that developed after contact with leaves of Primula obconica Hance (family Primulaceae) [33]. The clinical picture resembles that of a drug eruption, with confluent pseudo-cockades arising on the contact area. Histopathological features are those of allergic contact dermatitis with severe edema and keratinocyte necrosis. Several authors have reported similar features following contact with poison ivy [34] or tropical woods such as Rio rosewood (Dalber- gia nigra Allemão; pao ferro, Machaerium scleroxylon Tul., family Leguminosae) [35–38] (Fig. 5). Fur- Fig. 5. Erythema-multiforme-like reaction in a carpenter ther nonoccupational cases have been reported in caused by wood dust (pao ferro) (courtesy of P.J. Frosch) 41_751_800 05.11.2005 11:33 Uhr Seite 758

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Erythema multiforme-like dermatitis can be the titis in florists exposed to chrysanthemums (Den- expression of an active sensitization for several days dranthema cultivars, family Compositae) [43] or to following initial contact [40]. Alstroemeria L. [44]. It was also noted that simply Intense blistering can evoke pemphigoid, as was walking in a forest may bring on an attack of eczema observed in the wife of a woodworker who had been in patients who are sensitized to liverworts of the ge- helping her husband work with bois d’Olon, a kind of nus Frullania (Frullania dilatata Dum., family Jubu- satinwood (Fagara heitzii Aubrév.and Pellegrin,fam- laceae for example), suggesting that either particles ily Rutaceae) [41]. of liverwort or vaporized allergens are the causative agents [45]. Other reports describe airborne contact dermatitis from lichen particles [46, 47] or pine dust 41.2.3.4 Airborne Contact Dermatitis (unidentified species of the family Pinaceae) [48]. The last cases exhibited positive patch test reactions Hjorth et al [42] described an airborne ACD of plant to colophony. origin,due to air-conveyed oleoresins of Compositae, In North America and elsewhere it is recognized mimicking and often misdiagnosed as a photoder- that the smoke from burning poison ivy (Toxicoden- matitis. However, some features may differentiate it dron spp.) and related plants in the Anacardiaceae from photodermatitis,since airborne contact derma- family may sensitize if the allergenic oleoresin is va- titis involves the upper eyelids, the triangle of skin porized rather than pyrolyzed [49].Airborne contact behind the earlobe, the backs of facial folds without dermatitis to feverfew or congress grass (Parthenium respect for the triangle under the chin (Fig. 6). Al- hysterophorus L., Asteraceae family) is a major der- though pollens were usually incriminated as the matological problem, particularly in northern India. causative agents of airborne phytodermatitis, it is The classical form involves exposed areas, but sebor- likely that finely pulverized materials derived from rheic-like dermatitis, widespread dermatitis, photo- dead plants are the more likely etiological agents in sensitive lichenoid reactions and prurigo nodularis- the case of ragweeds (Ambrosia spp.) and related like eruptions have been reported [9, 50]. Patients members of the Compositae family. Vaporized aller- suffer seasonal relapses but sensitivity is lifelong,and gens may be responsible for airborne contact derma- sometimes complicated by the development of photosensitivity [50, 51].

41.2.4 Photodermatitis (Phytophotodermatitis)

41.2.4.1 Phytophototoxicity

Oppenheim first described dermatitis bullosa striata pratensis, or “meadow dermatitis,” in 1926 [52, 53]. The condition only develops under particular circumstances. The individual, having been out in the sun for some time with areas of bare skin and having been sunbathing on damp grassy vegetation, notices the appearance, over several hours, of a pruritic erythematous and bullous rash in a distribution pattern mimicking the shape of the grass or the veins of leaves (Fig. 7). Damp vegetation may be replaced by 41 atmospheric humidity or perspiration. The linear, figurate, and vesiculobullous nature of the lesions on sun-exposed skin leads one to suspect the phototoxic nature of the dermatitis. Dermatitis generally peaks around 72 h, and healing is accompanied by postinflammatory hyperpigmentation. Currently, Oppenheim dermatitis occurs frequently after gar- Fig. 6. Airborne contact dermatitis from Compositae in a dening, and the so-called strimmer rash appears to farmer. Note the marked infiltration on the forehead and the be a variant of this condition, having a diffuse rather sharp upper border from wearing a hat (courtesy of N. Hjorth) than striated or figurate presentation; a “strimmer” 41_751_800 05.11.2005 11:33 Uhr Seite 759

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Meadow dermatitis and associated conditions are commonly ascribed to contact with members of the Asteraceae/Umbelliferae plant family that grow in grassy meadows. In Europe in late summer these plants are in fact a common cause of bullous dermatitis, which may present in a wide variety of circumstances. Such dermatitis is caused by furocoumarins (also known as furanocoumarins or psoralens) (Fig. 8), which are present in the implicated plants and cause exaggeration of the burning potential of sunlight or artificial ultraviolet light, generally UVA. Numerous plants contain psoralens, although they have a limited distribution in the plant kingdom, the most important sources being the families Apia- ceae/Umbelliferae, Fabaceae/Leguminosae, Mora- ceae, and Rutaceae [5, 8, 59]. Coumarin derivatives such as isopimpinellin and limettin also possess photosensitizing properties, and large amounts have been isolated from citrus peels [60]. Another category of photosensitizers are the furo- quinolines, among them dictamnine, which is isolated from the roots of Rutaceae such as Dictamnus albus L., Skimmia repens Nakai, Aegle marmelos Cor- rea, Zanthoxylum alatum Roxb., and Ruta graveolens Fig. 7. Phototoxic dermatitis from furocoumarin-containing L. [61–63] (Fig. 9). Important examples of phototoxic plants (courtesy of P.J. Frosch) plants are reported in Table 2. Phototoxic contact dermatitis may present as the so-called berloque dermatitis, induced by perfumes (string trimmer) is an ingenious hand-held device or perfumed cosmetics containing high amounts of for cutting vegetation with a mechanically whirled psoralens, in particular oil of bergamot. Berloque string (nylon filament) [54, 55]. Oppenheim derma- dermatitis normally begins in the neck or décolleté, titis can easily be reproduced in individuals exposed with erythema at the site where perfume runs down to the same conditions [56], rapidly suggesting a the skin and is irradiated by the sun. Again, this is nonallergic mechanism. Some peculiar situations normally followed by postinflammatory hyperpig- have been reported, such as the epidemic of Oppen- mentation, which may last months or years. This der- heim dermatitis in 58 soldiers on an exercise in open matitis is currently rare due to the avoidance of fra- country [57], or the phytophototoxicity with exten- grances containing psoralens, but it can be observed sive linear and blistering skin lesions on the back of with artisan or traditional fragrances [64]. an 8-year-old girl that was mistaken for signs of whipping by her father [58].

Fig. 8. Structures of psoralens.Psoralen (ficusin) CAS 66–97–7,5-methoxypsoralen (bergapten) CAS 484–20–8,and 8-methoxypsoralen (xanthotoxin or methoxalen) CAS 298–81–7 41_751_800 05.11.2005 11:33 Uhr Seite 760

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Table 2. Main phototoxic plants

Family Botanical name English name French name German name

Apiaceae or Umbelliferae Ammi majus L. Bullwort, Bishop’s weed Ammi élevé Grosse Knorpelmöhre Angelica archangelica L. Garden angelica Angélique Engelwurz, Garten Angelik Angelica sylvestris L. Wild angelica Angélique des Wilde Engelwurz bois Anthriscus sylvestris Cow Chérophylle Hoffmann parsley sauvage, cerfeuil Wiesen-Kerbel sauvage Apium graveolens L. Wild celery Céleri sauvage, Echte Sellerie, Epf ache puante Apium graveolens Celery Céleri à côtes Stielsellerie var. dulce Persoon Daucus carrota L. Common garden carrot Carotte Karotte, Möhre ssp sativus Hayek Foeniculum vulgare Fennel Fenouil Gemeiner Fenchel Miller Heracleum lanatum Cow parsnip, Grande berce Herkulesstaude, Michaux. masterwort laineuse Bärenklau Heracleum mantegaz- Giant hogweed, Berce du Kaukasicher zianum Somm and Lev. parsnip tree Caucase Bärenklau Heracleum sphondylium Hogweed Grance berce Wiesen-Bärenklau L. Heracleum stevenii Palm of Tromsø – – Manden Pastinaca sativa L. Parsnip, madnep Panais, Pastinak, queenweed pastenade Hammelmöhre Petroselinum crispum Parsley Persil Petersilie

Fabaceae or Leguminosae Psoralea corylifolia L. Babchi, bakuci Psoralier Harzklee Myroxylon peirerae Balsam tree Baume du Pérou Balsam Baum Klotzsch.

Moraceae Ficus carica L. Fig tree Figuier Feigenbaum Rutaceae Citrus aurantifolia Lime Citron vert Limone Swingle Citrus aurantium L. Bitter orange Bigaradier, Bittere Orange, orange amère Pomeranze, Citrus bergamia Risso Bergamot orange Bergamote Bergamottzitronen, and Poit. Bergamotte Citrus limetta Riss. Sweet lemon Citron doux Süsse Zitrone Citrus limon (L.) Burm. Lemon Citron Zitrone Citrus paradisi Macfad. Grapefruit Pamplemousse Pumpelmuss Citrus sinensis Osbeck Sweet orange Orange douce Apfelzine 41 Cneoridium dumosum Bushrue, berryrue – – Dictamnus albus L. Gasplant, fraxinella, Fraxinelle, Weisser Diptam burning bush buisson ardent

Pelea anisata H. Mann Mokihana fruits Mokihana Mokihana Ruta chalepensis L. Fringed rue Rue à feuilles Aleppo-Raute étroites, rue d’Alep Ruta graveolens L. Rue, Herb of grace Rue fétide, rue Weinraute, des jardins Garten-Raute 41_751_800 05.11.2005 11:33 Uhr Seite 761

Plants and Plant Products Chapter 41 761

Fig. 9. Structures of limettin CAS 487–06–9, isopimpinellin CAS 482–27–9, and dictamnine, CAS 482–27–9

41.2.4.2 Phytophotoallergic Contact 41.3 Inducers of Dermatitis Dermatitis It is not possible to consider the whole panorama of Plant or plant-product-induced photoallergic der- plants liable to elicit contact dermatitis here, but the matitis occurs only very rarely.Perhaps the only well- plants most often incriminated are described below. authenticated cases are a reaction to Parthenium hys- Occupational contacts [12, 72] are usually the most terophorus L. (family Asteraceae) [65] and a photoal- frequent inducers of plant contact dermatitis. lergy to psoralens [66]. However, experimentally induced photoallergies to psoralens and to other cou- 41.3.1 Alliaceae (Onion Family) marins known to occur naturally have been described [67]. It is difficult to differentiate between a photoworsened allergic contact dermatitis and a true Members of the family Alliaceae are widely grown photoallergy. Photoworsening of an allergic contact and used for culinary purposes. In addition, garlic Allium sativum dermatitis is the more likely diagnosis than true pho- ( L.) has both a contemporary and a toallergy when plant material is implicated as the folkloric history of use as a medicinal agent. Whilst Allium cepa cause of a photosensitivity reaction of the skin [46, the lachrymatory properties of onions ( 47] in lichen pickers with a history of photosensitiv- L.) are widely appreciated, they are rarely discussed ity. in the medical literature. Most commonly reported is A rather different relationship between contact al- occupational dermatitis from garlic and to a lesser lergy and photosensitivity is seen in chronic actinic extent from onion; this includes both immediate and dermatitis (persistent light reaction, photosensitive delayed reactions [19, 73–78]. A typical presentation eczema, or actinic reticuloid). In such patients, gen- is a circumscribed irritable hyperkeratotic eczema erally men over 50 years, dermatitis occurs in photo- on the fingers of one or both hands; sometimes the exposed areas during the sunny season, which then thumb,index and middle fingers of the nondominant worsens with a chronic course, including itching, li- (usually left) hand which may be used to grasp the chenified, and extensive lesions or even erythroder- garlic bulb whilst the knife is held in the right hand ma. Patients have a marked broad spectrum photo- [79]. Less distinct patterns of eczema are likely more sensitivity to UVB, UVA or even visible radiations. It frequent than the presentation described above, but is frequent to observe contact sensitivity (but not remarkable situations can occur, such as haemor- photoallergic reactions) to oleoresins from members rhagic and blistering contact dermatitis [80], cheiro- of the plant family Asteraceae and sesquiterpene lac- pompholyx associated with the ingestion of garlic tones contained herein, or photosensitivity to photo- extract [81], dermatitis of the elbow flexures, lower allergens such as musk ambrette or sunscreens, but back and periorbital regions with cheilitis [82], or the disease expresses itself even in the absence of ex- airborne dermatitis due to garlic powder, which was posure to the plant material. It appears that an initial also reported as a cause of immediate-type reactions contact sensitization progresses to a generalized such as conjunctivitis, rhinitis and asthma [83]. Allium photosensitivity state with a relationship between Garlic and other species have often been plants of the family Compositae, the sesquiterpene reported to have both irritant and allergenic proper- lactones they contain, and chronic actinic dermatitis ties, due to phytochemicals not present in undam- [68–71]. aged plant material, but released as a response to damage. They are derived from a variety of sulfur- containing amino acids present in the intact plants.A 41_751_800 05.11.2005 11:33 Uhr Seite 762

762 Christophe J. Le Coz, Georges Ducombs

Fig. 10. Structures of thipropanal S-oxide CAS 32157–29–2, allicin CAS 539–86–6, diallyl disulfide CAS 2179–57–9, and allypropyl disulfide CAS 2179–59–1

minor structural difference between the principal obtained from a glucoside precursor known as tulip- precursor compounds, namely S-(1-propenyl)-L-cys- oside A. This one can be present as 1-tuliposide A [91] teine sulfoxide and S-(2-propenyl)-L-cysteine sulfox- or more frequently identified as 6-tuliposide A ide or alliin for garlic, results in an enzymatic trans- [92–94]. formation by the thermolabile alliinase: the lachry- Tulips contain a second glucoside, 6-tuliposide B matory thiopropanal-S-oxide from onion, but allicin [89], which is classically considered to be a nonsensi- and diallyldisulfide from garlic, as illustrated in tizer and has antibiotic properties, protecting the Fig. 10 [84]. Diallyldisulfide, allylpropyldisulfide, and plant against bacteria [95]. Patients sensitive to tulips allicin have been identified as the principal low mo- reportedly do not react to either tuliposide B or tu- lecular weight allergens of garlic [85]. Commercial lipalin B. However, it was demonstrated that tulipalin diallyldisulfide seems to be a suitable preparation for B (β-hydroxy-α-methylene-γ-butyrolactone) is a the investigation of garlic dermatitis, although 1% sensitizer in guinea pigs, and that cross-reactivity pet. may carry a lower risk of irritancy or can be neg- between tulipalins A and B does occur [96]. Other tu- ative. Irritant reactions with plants are expected with liposides have been detected in Alstroemeria species, fresh garlic concentrations higher than 10% but con- for example tuliposide D [94]. There is evidence that centrations up to 50% for garlic and onion in arach- the tuliposides themselves can elicit allergic contact nid oil were considered to be safe [78]. It is likely that dermatitis [88, 92], but this may be the outcome of each different extraction procedure affects the man- some spontaneous degradation to tulipalin A on the ner in which the irritants/allergens are released, skin [97]. making it virtually impossible to produce a standard Garden tulips are available both as “species tulips” extract. So, patch tests with plant extracts or plant and as cultivars of hybrid origin. Dermatitis among material used as is must be interpreted with some bulb handlers and florists is a frequent but unpleas- caution [86]. Delayed-type cross-reactions between ant occupational hazard. Bulb collectors, sorters and garlic and onion, although occasionally described, packers develop a characteristic dermatitis called are unlikely. “tulip fingers,” a painful dry fissured hyperkeratotic eczema, at first underneath the true margin of the nails, spreading to the periungueal regions, fingers 41.3.2 Alstroemeriaceae (Alstroemer and hands [98]. Sometimes the dermatitis spreads to 41 Family) and Liliaceae (Lily Family) the face, forearms, and genital region. It seems certain that both irritant and allergic contact dermatitis These two families are considered together because occurs.“Tulip fingers” is common in the Netherlands members of the genera Alstroemeria L.(Peruvian lily, and other parts of Europe. The allergen is found Inca lily) and Bomarea Mirb. (family Alstroemeria- mainly in the epidermis of the bulb, but dermatitis ceae), and the genus Tulipa L. (family Liliaceae) pro- may also occur in those who handle the cut flowers duce the same allergen, tulipalin A (Fig. 11). The sub- [99]. stance is released when the plant material (flowers, Alstroemeria hybrids have been popular in the stems and leaves) is damaged [87–90]. Tulipalin A, cut-flower trade since the 1980s due to their long last- otherwise known as α-methylene-γ-butyrolactone, is ing and colored flowers (Fig. 4a, b). Horticulturists 41_751_800 05.11.2005 11:33 Uhr Seite 763

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Fig. 11. Structures of 1- and 6-tuliposides A (glycosidic precur- 547–65–9 and tulipalin B (β-hydroxy-α-methylene-γ-butyro- sors of tulipalin A) CAS 19870–30–5 and CAS 19870–31–6 re- lactone) CAS 38965–80–9 spectively, tulipalin A (α-methylene-γ-butyrolactone) CAS

and florists are at high risk of both irritant and aller- recommended, since the so-called short ether ex- gic contact dermatitis, and the rate of sensitization tracts of Alstroemeria are too rich in tulipalin A and for tulipalin A can exceed 50% in workers of Alstroe- carry the risk of active sensitization [91]: a filtered meria cultivation [100]. Handling of cut flowers pro- 96% ethanol extract of the reference bulb of Tulipa vokes a dermatitis affecting mainly the fingertips, cv Apeldoorn or an 80% acetone extract of the bulbs which is similar to “tulip fingers” [101–103]. Depig- diluted with 70% ethanol immediately prior to use mentation may follow the resolution of Alstroemeria [98], a tuliposide-rich methanolic extract incorpo- dermatitis or a positive patch test to plant [104]. Con- rated into petrolatum [91], a 50-µl application of 6- tact urticaria and rhinoconjunctivitis, with positive tuliposide A at 0.01% or an α-methylene-γ-butyro- prick tests, were described for Alstroemeria [105]. lactone at 0.001% in ethanol [92]. Currently, the In the preparation of plant material for patch test- 0.01% concentration in petrolatum seems to be effec- ing, it should be remembered that the various culti- tive and safe for detecting sensitive people [91, 107]. vars of Alstroemeria and Tulipa do not necessarily contain similar levels of tuliposide A or associated Core Message contact allergens. For example, the cultivar Rose Copeland is a notorious sensitizer [106], whereas Tu- lipa fosteriana Hoog cv Red Emperor has been found í Tulipalin A (α-methylene-γ-butyrolactone) to contain very much less tuliposide than other culti- is the main contact allergen in Alstroeme- vars [98]. Nonsystematic concomitant patch test re- ria and Tulipa species. It frequently induces actions between tulips and Alstroemeria [101, 104] a fingertip allergy known as “tulip fingers,” may be due to differences in amount of allergens.Dif- mostly in people who have occupational ferent ways of performing patch testing have been contact with flowers and bulbs. 41_751_800 05.11.2005 11:33 Uhr Seite 764

764 Christophe J. Le Coz, Georges Ducombs

Common hyacinth (Hyacinthus orientalis L.) have neck, face, and the genitals [8]. It is likely that the “lily been described above as inducers of irritant contact rash” is mainly caused by an irritant mechanism dermatitis, due to calcium oxalate present in their [108], but that an allergic reaction is possible [110]. bulbs. It is noteworthy that bulbs evoke pruritus in Among many irritant alkaloids, two allergenic ones almost all workers who manipulate them, but derma- were identified from N. pseudonarcissus L., namely titis is less frequent [108]. We observed an unusual masonin and homolycorine (Fig. 12) [32]. Patch tests exposure in two schoolteachers who decided to de- may be performed with leaves, stems and flowers, or scribe the structure of bulbs and explained in detail with ethanol, acetone or water [8]. the way to cultivate hyacinth bulbs to their pupils (personal observations). Hyacinths likely contain as- yet unidentified allergens [106]. 41.3.3.1 Anacardiaceae, Ginkgoaceae, and Proteaceae

41.3.3 Amaryllidaceae (Daffodil Family) These plant families are considered together because they contain similar contact allergens and hence The Amaryllidaceae family comprises some 1100 spe- cause similar dermatitis. Nevertheless, the clinical cies of plant in 85 genera, many of which are cultivat- picture may vary depending upon the precise mode ed for their showy flowers. Amongst these, daffodils of contact. (Narcissus spp. and cultivars) are the most common, this term indicating several species such as trumpet Anacardiaceae (Cashew Family) narcissi (Narcissus pseudo-narcissus L.), narcissi (other species, e.g., N. poeticus) and jonquils (Narcis- The Anacardiaceae family includes 60 genera com- sus jonquilla L.), which constitute a significant der- prising some 600 species of trees and shrubs, distrib- matological hazard because of their irritant and al- uted throughout the tropics, and also found in warm lergenic properties. An important bulb and cut flow- temperate regions of Europe, eastern Asia, and the er industry exists in the Netherlands and the Isles of Americas. They are considered to cause more derma- Scilly in the United Kingdom, and with it the occupa- titis than all other plant families combined [5]. Some tional disease known as “daffodil itch” or “lily rash” tropical species are of economic importance, such as [98, 106], sometimes clinically close to “tulip fingers.” Mangifera indica L., which provides mango fruits, The rash has long been ascribed in part to the cal- Anacardium occidentale L., which yields cashew cium oxalate needle crystals present in both the dry nuts, cashew nut shell oil, which is used in the manu- outer scales of the bulbs and in the sap exuding from facture of brake linings, Semecarpus anacardium L.f., cut flower stems [98]. Observation in the field related which is known as the Indian marking nut tree that the method of picking and then gathering the flowers provides black juice used as an indelible ink when la- to the development of the daffodil pickers’rash,at the beling clothing, the Japanese lacquer tree Toxicoden- points of contact of plant sap with the skin like the dron vernicifluum F. Barkley, or several other species finger webs, the dorsum of the hand and the anterior used for dying or tanning. The main dermatological- aspect of the wrist [109]. Dermatitis may involve the ly important plants are reported in Table 3.

Fig. 12. Structures of masonin CAS 568–40–1 and homolycorine, CAS 477–20–3 41_751_800 05.11.2005 11:33 Uhr Seite 765

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Table 3. Dermatologically important Anacardiaceae plants

Botanical name Synonyms English name French name German name

Anacardium occidentale L. Cashew nut tree Anacardier, Kaschu, Elefantenlaus noix de cajou, Baum, westindischer pomme cajou Nierenbaum Comocladia dodonaea Comocladia ilicifolia Christmas bush, Bois de houx Urban Sw., Ilex dodonaea L. poison ash Gluta laccifera Ding Hou Melanorrhoea laccifera Camboge lacquer Arbre à laque Pierre du Cambodge Gluta renghas L. East coast rengas, ape-nut Gluta usitata Ding Hou Melanorrhoea usitata Burmese lacquer tree, Arbre à laque Wallich. theetsee de Birmanie Holigarna ferruginea March. Lithraea caustica Hook. Lithraea venenosa Litre, aroeira and Arn. Miers. Mangifera indica L. Mango tree Manguier Mangobaum Metopium toxiferum Rhus metopium L. Poisonwood, coral Krug and Urban sumac, Florida poison tree, Honduras walnut Semecarpus anacardium L. Anacardium orientale Indian marking nut Anacarde Tintenbaum Auct. tree, bhilawa tree d’Orient Smodingium argutum African poison ivy, Smodingie, Afrikanischer Giftefeu E. Mey. um-tovane, tovana, lierre toxique rainbow leaf d’Afrique Toxicodendron Rhus diversiloba Torr. Western poison oak, Sumac irrégu- Sumach, verschieden- diversilobum Greene & Gray. R. toxicoden- Pacific poison oak lièrement lobé, lappiger Sumach dron L. ssp. diversiloba sumac de l’ouest Engl. Toxicodendron radicans L. Rhus villosum Sessé & Western poison oak ssp. barkleyi Gillis Moçiño Toxicodendron radicans L. T. divaricatum Greene, Western poison oak ssp. divaricatum Gillis Rhus divaricata Greene Toxicodendron radicans L. T. eximium Greene, Western poison oak ssp. eximium Gillis Rhus eximia Stanley Toxicodendron radicans L. Rhus toxicodendron L. Taiwan tsuta-urushi ssp. hispidum Gillis var. hispida Engl., R. intermedia Hayata Toxicodendron radicans L. T. negundo Greene, Taiwan tsuta-urushi Herbe à puce ssp. negundo Gillis T. arborigunum Greene grimpante Toxicodendron radicans L. T. orientale Greene, Tsuta-urushi ssp. orientale Gillis Rhus orientalis Schneider Toxicodendron radicans L. R. toxicodendron L. var. Tsuta-urushi ssp. pubens Gillis pubens Engelm. Toxicodendron radicans L. T. radicans Kuntze, Poison ivy, three-leaved Sumac radicant, Sumach, Kletter-Gift- ssp. radicans Gillis Rhus radicans L., ivy, eastern poison ivy, lierre toxique, sumach, Rankender Rhus toxicodendron L. poison vine, black vine, herbe à puce Sumach, Giftefeu markweed de l’est T. radicans L. ssp. T. verrucosum Greene, Poison ivy, three-leaved verrucosum Gillis Rhus verrucosa Scheele ivy, poison vine, black vine, markweed 41_751_800 05.11.2005 11:33 Uhr Seite 766

766 Christophe J. Le Coz, Georges Ducombs

Table 3. Continued

Botanical name Synonyms English name French name German name

Toxicodendron rydbergii T. radicans Kuntze var. Rydberg’s poison ivy, Herbe à puce Greene poison ivy rydbergii Erskine, Rhus western poison ivy de Rydberg rydbergii Small, R. toxicodendron L. var. rydbergii Garnett Toxicodendron striatum Rhus striata Ruiz and Manzanillo, hinchador Kuntze Pavón, R. juglandifolia Willd. Toxicodendron Rhus succedanea L. Japanese wax tree succedaneum Kuntze Toxicodendron T. quercifolium Greene, Eastern poison oak, Sumac véné- Echter Gifstsumac toxicarium Gillis T. toxicodendron L. oak leaf ivy neux à feuilles Britten, Rhus querci- de chêne folia Steudel, R. toxicodendron L. var. quercifolium Michx., R. toxicarium Salisb. Toxicodendron vernici- Rhus verniciflua Stokes, Japanese lacquer tree, Sumac à laque, Lacksumach fluum F.Barkley R. vernicifera DC. varnish tree vernis vrai Toxicodendron vernix Rhus vernix L., Poison sumac, poison Sumac à vernis, Giftsumach Kuntze R. venenata DC. dogwood, swamp bois chandelle sumac, poison elder

Although these and many other species in the ural regions, mouth, and anal itching may occur after family Anacardiaceae are dermatologically hazard- ingestion of cashew nuts in people previously sensi- ous [111–120], perhaps the most important genus is tized to poison ivy [130]. The “black spot poison ivy Toxicodendron. This genus includes the poison ivy dermatitis” is a rarer condition, consisting of black complex (Toxicodendron radicans Kuntze and sub- enamel spots, due to colored and dried plant sap, sec- species such as T. radicans Kuntze var. rydbergii Ers- ondarily surrounding patch dermatitis, mainly of al- kine), the poison oak complex with Toxicodendron lergic origin [131]. diversilobum Greene (in western North America) Early literature refers to poison ivy and its rela- and Toxicodendron toxicarium Gillis (in eastern tives as species of Rhus. On the basis of morphologi- North America), and the poison sumac (Toxicoden- cal grounds and phytochemical distinction, it ap- dron striatum Kuntze, T. vernix Kuntze) of North pears that Toxicodendron is more suited, and that the America and elsewhere [121–125]. Over half of the genus Rhus must be distinguished from the genus population of the United States is sensitive to poison Toxicodendron [10, 132], although other authors ivy and its relatives [126] while,because the plants are argue for using the term Rhus [7]. There is conse- not a part of the natural flora, poison ivy dermatitis quently a frequent nomenclatural confusion in the is generally unknown in Europe [127]. Clinical as- dermatological literature, especially with the numer- pects vary with exposure. Dermatitis initially ap- ous synonyms. Individual subspecies of Toxicoden- pears on the fingers, forearms, arms, legs, and some- dron rarely appear in the dermatological literature, times genitalia [8, 126]. Lesions consist of papules, largely because case reports of poison ivy dermatitis 41 vesicles, and/or blisters. Erythema multiforme-like hardly warrant publication, partly because of the dif- eruption is sometimes observed. Systemic contact ficulty in precisely identifying the subspecies of the dermatitis may occur after accidental, medicinal or plants. The distributions of the various Toxicoden- alimentary ingestion of plant materials. It may dron species and subspecies have been described for present as eczema, as a generalized maculopapular the United States [132–134]. The “black spot test” con- eruption or as erythroderma occurring generally sists of carefully crushing sap from the leaves of the within 48 h following administration. When general- plant onto white paper: the test is positive with Toxi- ized rash occurs, leukocytosis and neutrophilia are codendron, the stain darkening on exposure to the air frequent, and liver dysfunction is possible [128, 129]. [135]. The same phenomenon occurs with wood sap The same features with eczematous eruption of flex- (Fig. 13). Poison ivy, poison oak, and poison sumac 41_751_800 05.11.2005 11:33 Uhr Seite 767

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are native to North America but can be exported. The dermatitis can present after an individual has been in contact with the plant whilst visiting an endemic area. As the plant has the potential to grow in Europe too (Fig. 14a), it is possible for an individual to be sensitized and subsequently to develop the rash without leaving their country [136], particularly in the case of workers at botanical gardens (personal observations). Cross-reactivity between Anacardiaceae has been reported for a long time. Similarities between urushiols from poison ivy and cashew nut shell oil are well known. In South America, species of Lithraea, and especially L. caustica Hook. and Arn. [10], are a frequent cause of a poison ivy-like dermatitis. In 17 Fig. 13. Stain darkening of sap of Toxicodendron species is the Lithraea-sensitized subjects, reactions to poison oak basis of the “black spot test”, here demonstrated with sap of urushiol were constant, and reactions to extracts pre- here demonstrated with sap of a recently cut down Japanese pared from Lithraea molleoides Engl. and Lithraea lacquer tree (Toxicodendron ver nicifluum F.Barkley) brasiliensis Marchand occurred in 13/17.The responses to poison oak urushiol were stronger and occurred at lower concentrations than those to Lithraea extracts [137]. Similar studies of cross-reactivity between Lithraea and other members of the Anacar- diaceae were reported [138, 139]. Concomitant reactions have been observed, but without systematic cross-reactivity, as in a patient sensitized to poison ivy or poison oak (Toxicodendron spp.) whilst in the United States and who subsequently showed appar- ent cross-reactions to Rhus copallina L., R. semialata Murray (syn. R. javanica L.), and R. trichocarpa Miq. [127].

Ginkgoaceae (Maidenhair Family) a Ginkgo biloba L.,the ginkgo tree,is the solitary representative of the family Ginkgoaceae and is regarded as one of the world’s oldest surviving tree species. Contact dermatitis from the ginkgo tree is not due to its leaves but to its malodorous fruits [140], in fact to the ovules exclusively borne by female trees (Fig. 14b). Contact occurs through inadvertent contamination of the skin with the fruit pulp [141], col- lecting and using the nut within the fruit in an Asian cooking style [141, 142], or in children through playing marbles with the fallen fruits. The lesions consist of erythematous papules and vesicles, with severe swelling in severe cases. They usually affect the face, the forearms and the thighs, and sometimes the genitalia [142, 143]. Stomatitis, cheilitis, and proctitis fol- b lowing ingestion of ginkgo fruit were described [144]. Cross-reactions between ginkgo fruit pulp, poison Fig. 14a, b. a Toxicodendron radicans growing in the botanical garden of Strasbourg, France. b Female Ginkgo tree (Ginkgo ivy, or ginkgo and cashew nut have been discussed biloba L.) bearing ovules (Jardin botanique, Strasbourg, [145]. They were, however, not supported by a recent France) study of the ginkgolic acids found in Ginkgo fruits 41_751_800 05.11.2005 11:33 Uhr Seite 768

768 Christophe J. Le Coz, Georges Ducombs

and urushiol from Toxicodendron [146]. Patch testing flowers of Kahili or Bank’s Grevillea (Grevillea bank- can be performed with fruit pulp in 1% acetone [144]. sii R. Br.) was described in Hawaii [152].

Proteaceae Allergens The Proteaceae family comprises 1050 species in 62 The allergenic agents in all these members of the An- genera found in tropical areas. In Australia, members acardiaceae, Ginkgoaceae and Proteaceae are deriva- of the family Proteaceae are the cause of a poison ivy- tives of catechol, phenol, resorcinol or salicylic acid like dermatitis. The best known are probably the so- with a side chain (-R) (Fig. 15). This side chain is Grevillea robusta called silky oak or silver oak ( mostly a C15 (sometimes a C17) alkyl (saturated) or Cunn.) and related Grevillea species and cultivars. alkenyl (one, two or three double bonds C=C) chain Contact with the wild and cultivated tree [147–149], [4, 8]. The alk(en)yl catechols are also known as uru- as well as with objects made from the wood [150], shiol, a generic name that in fact refers to the blend of have been recorded as being allergenic. “Grevillea several close molecules (urushiols) naturally con-

poisoning” was described as a severe contact derma- tained in the plant. An urushiol with a C15 side chain titis on exposed areas in people cutting trees or is named pentadecylcatechol (a term sometimes em- maintaining electric power lines in the Los Angeles ployed in medical literature for poison ivy urushiol),

area [151]. Allergic dermatitis following contact with and an urushiol with a C17 side chain is a heptadecyl-

Fig. 15. Structures of urushiol and related allergens from Anacardiaceae (T. radicans Kuntze, A. occidentale L.), Proteaceae (G. robusta L.), and Ginkgoaceae (G. biloba L.) families 41_751_800 05.11.2005 11:33 Uhr Seite 769

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41.3.4.1 Asteraceae/Compositae (Daisy Family)

The family Asteraceae/Compositae comprises some 13,000 to 20,000 species in over 900 genera. Repre- sentatives are found throughout the world, and examples may be found living in almost every situa- tion, the majority being herbaceous plants. The family provides a number of food plants, for example let- Fig. 16. Structure of geranylhydroquinone CAS 10457–66–6, tuce, endive, chicory, dandelion, salsify, scorzonera, from Phacelia crenulata Tor rey and artichoke. Many more are grown for their decorative flowers, such as chrysanthemums, dahlias, and heleniums. Others are widespread and common weeds [157]. Additionally, some species such as arni- catechol (mostly encountered in poison oak uru- ca, chamomile or feverfew are used medicinally, by shiol). Phenol, resorcinol, and salicylic acid com- skin application or systemic administration. It is pounds substituted with an alk(en)yl chain have tra- therefore difficult to avoid contact with these plants. ditionally been called cardanol, grevillol and gink- Plants of dermatological interest are indicated in golic acid, respectively. Because the allergenic natural Table 4. plant material is a mixture of closely related com- Allergic contact dermatitis from Asteraceae has pounds, and because of the close similarity between several clinical presentations (Fig. 6). Accidentally individual compounds from a variety of botanical exposed subjects can develop an acute and single epi- sources, there is the possibility of cross-sensitization sode of dermatitis. Chronic exposure, of occupation- between different species throughout the world [153]. al origin for example, can induce acute dermatitis The risk of cross-sensitization extends to families that can often relapse, or a primary chronic and sec- other than those described in this section. The genus ondarily lichenified dermatitis. When the lesions are Philodendron (family Araceae) yields sensitizing al- localized to the elbow or knee flexures, they can sim- kyl resorcinols [154]. The genera Phacelia and Wi- ulate atopic dermatitis.The eczema,which may be lo- gandia belonging to the Hydrophyllaceae family calized initially on the face, hands, and genitals, can yield alkenyl hydroquinones. Prenylated quinones become generalized as an erythroderma and can and prenylated phenols were identified in W. caraca- even be, in rare instances, fatal [158]. sana Kunth [155], and geranylhydroquinone in P. cre- Exposure to the sesquiterpene lactones by the way nulata Torrey (Fig. 16); this molecule does not cross- of airborne plant material produces an airborne con- react with poison oak or ivy [156]. tact dermatitis (sometimes mistaken for a photodermatitis). In the United States, this is known as “rag- Core Message weed dermatitis” because it is largely caused by ragweeds, which are species of Ambrosia [159, 160] or “weed dermatitis” in regions where other composite í Plants of the family Anacardiaceae weeds predominate [161], such as Ambrosia, Artemi- are frequent cause of contact dermatitis. sia, Helenium,and Iva [162–171] species. For example, The skin reaction occurs following sensiti- cases of severe airborne ACD from triangle-leaf bur- zation to various alkyl or alkenyl catechols sage (Ambrosia deltoidea) were reported in the USA, (urushiol), phenols, resorcinols or salicylic with positive reactions to ether extracts of the plant acid derivatives. These compounds are also [172]. primary irritants. In Australia, the same condition is described as “bush dermatitis” due to species such as Arctotheca, Cassinia, Conyza, Cynara,and Dittrichia [167, 173–176]. In India, another variant has been called “parthenium dermatitis”[9, 177,178] after the offend- 41.3.4 Compositae (Asteraceae) Parthenium hysterophorus and Liverworts ing plant ( L.). The environmental conditions favoring ragweed dermatitis and its variants in hot and arid climates The two families are considered together because are not normally encountered in the temperate re- they contain sesquiterpene lactones as allergens. gions of Europe. Nevertheless, there are also Europe- 41_751_800 05.11.2005 11:33 Uhr Seite 770

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Table 4. Dermatologically important Apiaceae/Umbelliferae plants Asteraceae/Compositae Correct name Synonyms English name French name German name

Achillea millefolium L. Achillea lanulosa Nuttall Yarrow, nosebleed, Achilée mille- Gemeine Schafgarbe milfoil, thousand leaf feuille, herbe à la coupure Ambrosia acanthicarpa Franseria acanthicarpa Bur-ragweed, sandbur Franserie Falsche Ambrosie Hook. Cov. lampourde Ambrosia artemisiifolia Ambrosia elatior L. Short ragweed, Ambroisie à Beifussblättrige Am- L. common ragweed feuille d’armoise, brosie, hohes Tauben- ambroisie élevée kraut, Wermutblätt- rige Ambrosie Ambrosia psilostachya Western ragweed, Herbe à poux Ausdauernde DeCambolle perennial ragweed, vivace Ambrosie common ragweed Ambrosia trifida L. Ambrosia aptera DC. Giant ragweed, Dreispaltige Ambrosie tall ragweed Anthemis arvensis L. Field chamomile, corn Fausse camomile, Acker Hundskamille ssp. arvensis chamomile (scentless) camomille sauvage, anthémis des champs Anthemis cotula L. Maruta cotula DC. Stinking chamomile, Anthémis cotule, Stinkende corn chamomile anthémis fétide Hundskamille (scented) Arctotheca calendula Arctotis calendulacea L., Capeweed Artothèque souci Dune Calendula Levyns Cryptostemma calendulacea R. Br. Arnica montana L. Arnica, mountain Arnica, tabac desBerg-Wohlverleih, tobacco, wolf’s bane Vosges, quinqui- Arnika na des pauvres Artemisia ludoviciana Artemisia ludoviciana Dark-leafed mugwort, Armoise argentée Edelraute Nutt. Nutt., prairie sage Artemisia purshiana Artemisia vulgaris L. Common mugwort Armoise vulgaire, Gewöhnlicher Beifuss, herbe aux cent Fliegenkraut goûts Cassinia aculeata R. Br. Common cassinia, dogwood, cauliflower bush Chamaemelum nobile Anthemis nobilis L. Roman chamomile, Camomille Römische Kamille All. dog fennel romaine Cichorium endivia L. Common endive Endive, chicorée Winter Endivie spp. endivia L. des jardins Cichorium intybus L. Chicory, wild chicory Chicorée sauvage, Wilde Zichorie, barbe de capucin gemeine Wegwarte, Sonnenwedel Conyza bonariensis Erigeron bonariensis L. Fleabane Érigéron crépuSüdamerikanisches Cronq. Conyza ambigua DC., Berufskraut Conyza crispa Rupr. Cynara cardunculus L. Cynara cardunculus L. Cardoon Cardon, carde Kardone, Gemüse- 41 ssp. cardunculus; Cynara Artischocke cardunculus L. ssp. flavescens Cynara scolymus L. Cynara cardunculus L. Globe artichoke Artichaut Artischoke, ssp. scolymus; Cynara Alcachofra cardunculus L. ssp. flavescens Dahlia variabilis Desf. Dahlia x hortensis Dahlia Dahlia Dahlia Dendranthema Chrysanthemum x Autumn flowering Chrysanthème Chrysanthemen, hortorum W.Miller, chrysanthemum de Chine, Allerseelen-Aster Chrysanthemum mori- chrysanthème folium Ramat. d’automne 41_751_800 05.11.2005 11:33 Uhr Seite 771

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Table 4. Continued Correct name Synonyms English name French name German name

Dittrichia graveolens Inula graveolens Desf, Stinkwort Inule fétide Duftender Alant Greuter Erigeron graveolens L. Gaillardia pulchella Gaillardia picta Sweet Showy gaillardia Gaillarde Kurzlebige Foug. Foug. pulchella Kokardenblume Helenium autumnale L. Sneezeweed, Hélénie Sonnenbrot swamp sunflower, automnale false sunflower Helenium amarum Helenium tenuifolium Sneezeweed, – – H. Rock Nutt., Gaillardia amara bitterweed Raf. Helianthus annuus L. Sunflower Tournesol, soleil Einjährige Sonnen- blume Inula helenium L. Elecampane, Aunée officinale, Echter Alant, Muxiang horseheal, scabwort grande aunée, inule aulnée Iva angustifolia Nutt. Narrow-leaf marshelder Iva xanthifolia Nutt. Marshelder Lactuca sativa L. Lettuce Laitue Lattich Leucanthemum vulgare Tanacetum leucanthemum Marguerite, ox-eye Marguerite Gemeine Wucher- Lam. Schultz-Bip, Chrysan- daisy blume, Wissen- themum leucanthemum L. Margerite Matricaria chamomilla Matricaria chamomilla German chamomile, Matricaire, Echte Kamille, L. var recutita Grieson L., Matricaria recutita wild chamomile camomille deutsche Kamille L., Chamomilla recutita allemande Rauschert Parthenium argentatum Guayule Guayule Guayule A. Gray Parthenium hystero- Congress grass, Absinthe bâtard Parthenium phorus L. Santa Maria, whitetop hysterophorus Petasites albus Gaertner White butterbur Pétasite blanc Weisse Pestwurz Saussurea lappa C.B. Saussurea costus Lipsch. Costus Costus Costus Clarke Silybum marianum Blessed milk-thistle, Chardon de Mariendistel Gaertn. holy thistle Marie Tagetes minuta L. Tagetes glandulifera Small-flowered Tagète des Tagetes Schrank marigold, stinking décombres roger Tanacetum cinerariifo- Chrysanthemum cinera- Pyrethrum, Pyrèthre Dalmatinische lium Schultz-Bip. riifolium Vis., Pyrethrum Dalmatian Insektenblume cinerariifolium Trevir. py rethrum Tanacetum parthenium Chrysanthemum parthe- Feverfew Grande Mutterkraut, Schultz-Bip. nium Bernh., Matricaria camomille Falsche Kamille parthenium L. Tanacetum vulgare L. Chrysanthemum tanace- Tansy, bitter buttons Tanaisie,tanacée, Gemeiner Rainfarn, tum Karsch., C. vulgare herbe aux vers Wurmkraut Bernh. Taraxacum officinale Leontodon taraxacum Dandelion, blowball Pissenlit, laitue Gebräulicher Löwen- Weber L., Taraxacum dens- de chien, dent zahn, Kuhlblume leonis Desf., T. taraxa- de lion cum Karst Xanthium spinosum L. Spiny cocklebur Lampourde Dornige Spitzklette épineuse, petite bardane Xanthium strumarium L. Noogoora burr Lampourde ordi- Gemeine Spitzklette, naire, herbe aux Kropfspitzklette écrouelles X. italicum Moretti X. californicum Greene, Californian burr Lampourde Italienische Xanthium strumarium d’Italie Spitzklette L. ssp italicum D. Löve 41_751_800 05.11.2005 11:33 Uhr Seite 772

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an variants of ragweed dermatitis which have been United States (Oregon), and in the Bordeaux and described in rather specialized circumstances, with Strasbourg regions of France. They are a cause of oc- feverfew (Tanacetum parthenium Schultz-Bip.) [179, cupational contact dermatitis in forest workers and 180], chicory (Cichorium intybus L.) and lettuce (Lac- woodcutters [201, 202], and domestic allergy in peo- tuca sativa L.) [181–183], liverworts of the genus Frul- ple who use lobe-leaved trees as firewood. Frullania lania [45], and the chrysanthemums of florists [43]. dilatata Dum., F. tamarisci Dum. and F. tamarisci Contact dermatitis from ragweed particularly affects Dum. ssp. nisquallensis Hatt. are the most aggressive male subjects and spares women and children [158] species. Instances of cross-sensitivity reactions but Compositae-induced dermatitis generally ap- between Frullania species and members of the Com- pears to be rare in childhood [184]. positae family are accounted for by the occurrence of Many cases have been described with sensitiza- structurally similar sesquiterpene lactones in the tion to Asteraceae [8, 5] like with yarrow (Achillea plants concerned, such as costunolide [8, 203]. More millefolium L.) [162], chamomile (Anthemis spp L.) specifically, Frullania dilatata Dum. and tamarisci [166], arnica (Arnica montana L.) [168], small-flow- Dum. are sources of (+)- and (–)-frullanolide, re- ered marigold (Tagetes minuta L.) [185], pyrethrum spectively [204, 205]. There is a risk of active sensiti- (Tanacetum cinerariifolium Schultz-Bip) [186], dan- zation by patch testing [201], sometimes occult, as re- delion (Taraxacum officinale Wiggers) [187], elecam- vealed by a new patch test session (personal observa- pane (Inula helenium L.) [188, 189], sunflower (Heli- tions). anthus annuus L.) [190], guayule (Parthenium argentatum Gray) [191],or Noogoora Burr (Xanthium strumarium L.) [192]. Cultivated plants, such as dahlia or Core Message chrysanthemum cultivars, are an important source of occupational contact allergy [193–197]. Botanical and í The liverwort Frullania spp. induces vernacular names of dermatologically important As- contact allergy in foresters and people teraceae are reported in Table 4. who are in contact with raw woods Phototoxicity may theoretically occur following (firewood). contact with α-terthienyl, a natural phototoxic thiophene compound of many Asteraceae species [198], but no authentic clinical cases appear to have been described in the literature. Contact urticaria has been described with this 41.3.4.3 Sesquiterpene Lactone Allergens family [12, 199]. The main allergens of Asteraceae are sesquiterpene lactones, and different ones may occur in a single Core Message species. They are characterized by the presence of a γ-butyrolactone ring bearing an exocyclic α-methyl- í The large Asteraceae/Compositae family ene group (Fig. 17). Hundreds of molecules have been is a frequent inducer of allergic contact (and continue to be) identified to date [206]. They dermatitis, due to the sesquiterpene are also present in related plant families such as Mag- lactones contained in the plants. noliaceae, Winteraceae, Jubulaceae and Lauraceae [207]. The range of structures encountered among sesquiterpene lactones known to be allergenic is very wide, and each individual species contains a more or 41.3.4.2 Liverworts (Jubulaceae) less complex mixture of these compounds. So, cross- 41 sensitivity between various species in the Asteraceae Liverworts, together with mosses and hornworts, is common but neither complete nor predictable comprise a group of small,nonvascular plants known [169, 196, 208]. This unpredictability may be exempli- as bryophytes [200]. Typically they grow as epiphytes fied by the fact that individual cultivars of the au- in damp locations, although they can withstand peri- tumn-flowering chrysanthemums (Dendranthema ods of desiccation. Of the liverworts, only a few spe- cultivars) do not necessarily cross-react [43, 195, cies of Frullania have been described as causes of al- 209], whilst cross-reactions between members of the lergic contact dermatitis. These are found on trees in Compositae and liverworts of the genus Frullania several regions of the world, notably in British Co- (family Jubulaceae), laurel (Laurus nobilis L., family lumbia in Canada, the Pacific North-West of the Lauraceae) and various members of the family Mag- 41_751_800 05.11.2005 11:33 Uhr Seite 773

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Fig. 17. Structures of some allergenic sesquiterpene lactones. 40776–40–7, L-frullanolide CAS 27579–97–1, parthenin CAS Alantolactone CAS 546–43–0, costunolide CAS 553–21–9, dehy- 508–59–8 and its diastereoisomer hymenin, parthenolide CAS drocostus lactone CAS 477–43–0, D-frullanolide CAS 20554–84–1, and laurenobiolide

noliaceae, such as Michelia lanuginosa have been re- In order to facilitate the diagnosis of sesquiter- ported [5, 45, 210–214]. Data have been reviewed in pene lactone-induced allergic contact dermatitis, a the literature [215]. Cross-reactivity between sesqui- mixture of three representative lactones from various terpene lactones largely depends on their stereo- structural classes (alantolactone, costunolide, and chemistry. Parthenin and hymenin are examples of dehydrocostus lactone) has been made available for diastereoisomers found in the same plant (Partheni- testing. This mixture, called Sesquiterpene lactone um hysterophorus L.) but not produced in the same mix, has been widely tested but detects only about region, since parthenin is found in India, but hyme- 30% of cases of sensitization [217–220]; this poor nin is found in South America. There is no cross-re- sensitivity is partially explained by phytogeographic activity between the disatereoisomers parthenin and variations [221]. Compositae mix is an alternative hymenin [216]. preparation comprising a mixture of plant extracts A vast number of species in the Compositae fami- (arnica, yarrow, tansy, German chamomile, and ly have been described either as causes of contact feverfew), which seems to detect a higher proportion dermatitis or as elicitors of positive patch test reac- of cases [218]. Other blends have been proposed,such tions. Many more may be regarded as potential con- as a blend of Achillea millefolium L., Chamaemelum tact allergens on the basis of their reported content of nobile All. (syn. Anthemis nobilis L.), Helianthus an- sesquiterpene lactones bearing an α-methylene-γ- nuus L., Tagetes minuta L., and Tanacetum vulgare L. butyrolactone ring. [222], or a mixture of short ether extracts of arnica, 41_751_800 05.11.2005 11:33 Uhr Seite 774

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German chamomile, feverfew, tansy, and yarrow pungens) and Capparaceae (Capparidaceae) families, [223]. Dandelion and feverfew extracts, together or Cruciferae characteristically contain glucosidic com- individually [224, 225], also appear to be more useful pounds (glucosinolates) which, in many species, re- than sesquiterpene lactone mix alone. lease mustard oils (isothiocyanates, Fig. 18) when the plant material is damaged.These mustard oils impart pungency to the Cruciferae that contributes to the Core Message value of many in food or as irritants in traditional counterirritant remedies and rubefacient ointments. í Sesquiterpene lactones are potent contact The most commonly used compound is the oil from allergens in Asteraceae/Compositae and black mustard seed (Brassica nigra Koch), which liverworts. The numerous molecules gener- principally contains allyl isothiocyanate. This isothi- ally do not cross-react. ocyanate is produced from its glucosinolate precursor sinigrin [226] by the action of an enzyme named myrosinase, activated when the plant material is damaged. Notwithstanding the irritant properties of mus- 41.3.5 Cruciferae (Cabbage or Mustard tard oils and pharmaceutical preparations made Family, Brassicaceae) from them, Coulter [227] observed no irritant reactions following rough handling of Cruciferae. Clini- The Brassicaceae family contains about 3200 species cally,these plants are more commonly found to be re- in 375 genera, covering a large number of food plants sponsible for allergic contact dermatitis in food han- such as cabbages (Brassica oleracea L.) with several dlers [7]. Radishes induced finger dermatitis in a varieties, for example, curly kale (B. oleracea var. fim- waitress who chopped them (Raphanus sativus L.) briata Miller), cauliflower (B. oleracea var. botrytis [228]. Cabbages (Raphanus sativus var. capitata L.), Brussels sprouts (B. oleracea var. gemmifera DC.), Alef.) provoked occupational contact dermatitis kohl rabi (B. oleracea var. gongyloides L.), broccoli (B. [229], and cabbage juice produced positive patch test oleracea var. botrytis ssvar. Cymosa Lam), turnips reactions in 5/53 patients with hand dermatitis sus- (Brassica campestris L. var rapifera Metz), radishes, pected to have been caused by vegetables [75]. rutabagas, mustard, and cress. To avoid irritant reactions, patch test concentra- Together with the smaller Cleomaceae (which tions with isothiocyanates should be prepared in the comprises the increasingly popular garden flower range 0.1–0.05% pet. [5, 230]. Positive patch test reac- cleome or Spider flower, Cleome spinosa Jacq., syn. C. tions to all four of these isothiocyanates have been

Fig. 18. Structures of methyl isothiocyanate CAS 556–61–6, phenyl isothiocyanate CAS 103–72–0, benzyl isothiocyanate CAS 622–78–6 and ally isothiocyanate CAS 57–06–7, and its precursor sinigrin CAS 3952–98–5 41_751_800 05.11.2005 11:34 Uhr Seite 775

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reported in various circumstances, but cross-reac- a bank as an inducement to open a savings account tions,if they exist,are not systematic [228,231].Meth- [240], examined the irritant properties of a number yl isothiocyanate [232] should be tested if plants be- of tigliane, ingenane and daphnane polyol esters in longing to the Capparaceae family are suspected as humans [241], or described a case of an 8-year-old being the cause of dermatitis. girl who developed irritation and swelling of the face and eyelids as a result of a fight in which a boy beat her with snow-on-the-mountain (Euphorbia margin- Core Message ata Pursh) [242]. We have observed irritant dermatitis in a botanist who had botanized and made con- í Brassicaceae are irritant and allergenic, tact with euphorbia (Fig. 19). due to the isothiocyanates they release It is frequently difficult to ascertain whether Eu- when the plant is damaged. phorbiaceae are responsible for irritant or allergic contact dermatitis. Allergy rather than irritation is documented for two common ornamental Euphorbi- aceae, namely croton (Codiaeum variegatum Blume var. pictum Muell. Arg.), and poinsettia (Euphorbia 41.3.6 Euphorbiaceae (Spurge Family) pulcherrima Willd.), although the allergens have not yet been characterized [243–247]. Out of 305 cases of The Euphorbiaceae family comprises some 5000 spe- contact dermatitis presented at the dermatology cies in about 300 genera which, with the exception of clinic on the Hawaiian island of Kauai, 61 were attrib- the polar regions, are found throughout the world. utable to contact with plants. Among the most fre- The largest and most widely distributed genus is quently blamed, Mango (Mangifera indica L., family Euphorbia. In Europe, euphorbias are small weeds Anacardiaceae) caused allergic contact dermatitis, known as spurges; tropical species are shrubs or and mokihana (Pelea anisata H. Mann, family Ruta- trees, often resembling cacti in arid parts of Africa. ceae) induced irritant photodermatitis, but the They contain a latex which, in many species, is a skin mechanism of the reactions to the euphorbias, aller- irritant. The irritant compounds are diterpene esters gic or irritant, was not stated [248]. It should be re- belonging to three general classes: the tiglianes, inge- membered that the irritant properties of these plants nanes, and daphnanes. These irritant diterpenes are are sometimes utilized in popular remedies,for treat- also found in other genera of the Euphorbiaceae and, ing warts and basal cell carcinomas [249]. The poten- interestingly, in the unrelated family Thymelaeaceae tial for using euphorbias to produce dermatitis arte- (daphne family). Reviews deal with the distributions facta should also be recognized. of these compounds within the two families, their ir- Among the irritants isolated from Euphorbiaceae ritant properties and their tumor-promoting and (Fig. 20), 12-Deoxyphorbol-13-phenylacetate is an ex- other biologically hazardous properties [233–235]. ample of a tigliane polyol ester, found in the common Irritant contact dermatitis from Euphorbiaceae sun spurge (Euphorbia helioscopia L.) [250]. Resin- and Thymelaeaceae is rarely seen by European prac- iferatoxin, a daphnane polyol ester that is one of the titioners, but it is likely that accidental skin contact most irritant compounds known to Man, is found in occurs quite frequently. As the irritant reaction re- officinal spurge (Euphorbia resinifera Berg) [251, solves spontaneously within 1–2 days, it is unlikely to be seen in a dermatology clinic. Thus, whilst there is extensive anecdotal literature supported by numerous scientific studies of the irritant compounds, clinical studies and case reports are rare: 60 cases of irritant contact dermatitis from the infamous manchineel tree (Hippomane mancinella L.) of tropical America [236], irritant contact dermatitis from the African milk bush (Synadenium grantii Hook.f.) in a gardener [237], an irritant patch test reaction to the petty spurge (Euphorbia peplus L.), a garden weed presented by the patient as a house plant [238], perioral dermatitis from a pencil tree (Euphorbia tirucal- li L.) [239]. Several authors described the irritant properties of the friendship cactus (Euphorbia hermentiana Lemaire) following the use of this plant by Fig. 19. Bullous irritant hand dermatitis due to Euphorbia spp. 41_751_800 05.11.2005 11:34 Uhr Seite 776

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Fig. 20. Structures of the irritant phorbol CAS 17673–25–5 and representative irritants from the Euphorbiaceae and Thymelaea- ceae: resiniferatoxin CAS 57444–62–9, 12-deoxyphorbol-13-phenylacetate, and 3-O-hexadecanoylingenol

252]. The ingenane polyol ester 3-O-hexadecanoyl in- 41.3.7 Lichens genol is found in the caper spurge (Euphorbia lathy- ris L.) [170]. Readers interested in a comprehensive Lichens are not really plants, and consist of a symbi- survey of the occurrence of such compounds in the otic association of a fungus (mycosymbiont, King- Euphorbiaceae and Thymelaeaceae are referred to dom Fungi) and an alga (phytosymbiont, Kingdom works by Evans [253] and Schmidt [10, 254, 255]. Protoctista), the first one providing morphology and sexual reproduction via spores, the second one pro- 41 Core Message ducing organic materials by the way of photosynthe- sis [256]. Lichens grow on walls, roofs, trees, and rocks. í Euphorbiaceae are very strong irritant and Several species are sensitizing, and those most of- sometimes allergenic plants. ten found to be the causes of allergic contact dermatitis are species of Cladonia, Evernia,and Parmelia, although reactions have been described with other species such as Hypogymnia, Platismatia, Physconia, Usnea,and Alectoria (Bryoria) [201]. Frequent sensitizing compounds from lichens are described in 41_751_800 05.11.2005 11:34 Uhr Seite 777

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Fig. 21. Structure of some sensitizing lichen compounds. (+)-Usnic acid CAS 125–46–2, evernic acid, CAS 537–09–7,perlatolic acid, atranorin CAS 479–20–9, chloroatranorin, atranol CAS 526–37–4 and chloroatranol CAS 57074–21–2

Fig. 21. Dermatitis usually affects forestry workers titis has also been suggested to contribute to the clin- and lichen pickers, and appears on the hands, fore- ical features seen in patients with lichen allergy [46]. arms, face and other exposed areas [257,258]. Allergy Immediate-type allergies with asthma and urticaria to lichens may also be observed following exposure were described following inhalation of, or direct con- to perfumes containing oak moss (which is not a tact with, algae from lichens [268]. moss!), which is extracted from Evernia prunastri Lichens can be tested “as is,”but irritant reactions (L.) Ach. and related species [259, 260]. E. prunastri may occur. Oak moss is present in the fragrance mix contains atranorin and chloroatranorin, depsides of the European standard series, as a mixture of that lead to the formation of atranol and chloroatra- mainly Evernia prunastri Ach. (oak moss stricto sen- nol during preparation of oak moss absolute. With su) and Pseudevernia furfuracea Zopf. (syn. Parmelia methyl-β-orcinol carboxylate, they are potent aller- furfuracea Ach., tree moss).As tree moss, growing on gens identified in oak moss absolute [261–263]. both lobe-leaved trees and conifers, is frequently au- A history of abnormal photosensitivity is asso- tomatically picked with bark, it may contain deriva- ciated with lichen sensitivity, and has been discussed tives of colophony. Such resinic acids are responsible below. Irradiation of patch tests to lichens and their for some positive reactions to fragrance mix in co- extracts may elicit enhanced responses [264–267].An lophony-sensitive patients [269]. Lichen-derived airborne contact dermatitis simulating photoderma- compounds such as atranorin, usnic acid and evernic 41_751_800 05.11.2005 11:34 Uhr Seite 778

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acid can be tested at 0.1% or 1% pet. Whether cross- sensitization occurs between structurally related lichen compounds is not clear.Because of the common occurrence of some of the lichen compounds in a number of species, concomitant sensitization is possible [257, 258].

Core Message

í Lichens are responsible for some cases of contact allergy from plants or from plant extracts in perfumes.

41.3.8 Primulaceae (Primrose Family)

This family of cosmopolitan distribution comprises 1000 species in 20 genera (among them Cyclamen spp), but only Primula (Primula obconica Hance) presents a common dermatological hazard. P. obconica is popularly grown in Europe as a house and greenhouse plant for its showy and long-lasting flowers, and the first report of contact allergy in 1888 by White has since been followed by many other reports [5, 270, 271]. Dermatitis (Fig. 22) generally affects the eyelids, face, neck, fingers, hands, and forearms, but P. obconica can also cause conjunctivitis and erythema-multiforme-like eruption [272]. The most impor- Primula Fig.22. Unusually severe exudative edematous primula derma- tant allergen of is a quinone named primin titis on the face (courtesy of N. Hjorth) [273], formed by oxidation of its biosynthetic precursor miconidin (which is also allergenic [274]) in min- ute glandular hairs (trichomes) present at the surface of the plant (Fig. 23). Dermatitis may be due to direct primin-free Primula have recently been developed, contact with plants, dust particles or to primin re- among them the “Touch Me” cultivar [281]. leased directly from intact P. obconica plants [275]. Because the content of primin in the leaves varies This explains flares of dermatitis in highly sensitized with the season, method of cultivation and cultivar patients after entering a room containing P. obconi- identity [282, 283], the outcome of using fresh plant ca. The presence of other allergens has been suggest- material as such for patch testing varies from the oc- ed [271, 276], for example the quinhydrone formed currence of false negatives during the winter months from primin and miconidin [183], the flavone prime- [284] to active sensitization between the months of tin present in Primula mistassinica Michaux, and April to August, when primin levels are at their high- skin oxidized into a quinone derivative [277]. These est [283, 285]. It was previously recommended that an 41 could explain allergic contact dermatitis with posi- ether extract of the leaves harvested in spring (60 g tive allergic patch test reactions to fragments of the fresh weight dipped in 100 ml ether before concen- plant but negative to primin ([278], personal obser- trating to 50 ml at room temperature) should be used vation, Fig. 24). Other species of Primula are report- [286]. Patch testing with commercially available syn- ed to be allergenic, such as P. auricula and P. denticu- thetic primin carries a real risk of active sensitization lata [279,280].For a number of years,P.obconica was if concentrations greater than the usual (0.01%) are the most common cause of plant-induced contact used. dermatitis in Europe, but has become less of a problem in recent years, as its reputation has stimulated a widespread avoidance response. It is noteworthy that 41_751_800 05.11.2005 11:34 Uhr Seite 779

Plants and Plant Products Chapter 41 779

Fig. 23. Chemical structures of primin CAS 15121–94–5, miconidin CAS 34272–58–7 and primetin CAS 548–58–3

Systemic symptoms may occur after accidental ingestion of fresh plants by humans or animals, with systemic, digestive, renal, cardiorespiratory, neuro- logic and possibly life-threatening symptoms. Protoanemonin is the irritant agent in Ranuncula- ceae. It is released from its precursor ranunculin by an enzymatic cleavage when the plant material is damaged [292–295]. Protoanemonin rapidly loses its irritant properties by dimerization into anemonin (Fig. 25). Dried plants are therefore inoffensive. The following genera are representative members of the Ranunculaceae that have to be regarded as possible causes of irritant contact dermatitis:

í Anemone Anemone Primula obconica spp. with wood anemone ( Fig. 24. Positive patch test reactions to nemorosa Hance, performed in a horticulturist negative to primin L.) í Actaea spp. with baneberry or herb Christo- pher (Actaea spicata L.), and white baneberry (Actaea alba Miller) í Caltha spp. with marsh marigold or kingcup Core Message (Caltha palustris L.) í Clematis spp. with Traveller’s Joy, called “Old í Primulaceae are a source of contact Man’s Beard” because of long and feathery sensitization, mainly in florists who achenes or “herbe aux gueux” because middle handle Primula obconica Hance. age mendicants scrubbed their face with sap to provoke dermatitis and pity (Clematis vitalba L.) í Pulsatilla spp. such as prairie crocus (Pulsatil- la patens Miller, syn. Anemone patens L.), 41.3.9 Ranunculaceae (Buttercup Family) Pasque flower (Pulsatilla vulgaris Mill., syn. Anemone pulsatilla L.) The family contains 1900 species in 50 genera. Most- í Ranunculus such as common meadow butter- ly herbaceous with rhizomes, Ranunculaceae chiefly cup (Ranunculus acris L., syn. Ranunculus ac- grow in northern temperate regions. Many members er Auct.), corn buttercup (Ranunculus arvensis of the family are very caustic, and can cause skin or L.), bulbous buttercup (Ranunculus bulbosus mucous membrane irritation [10, 29, 31]. This has led L.) or creeping buttercup (Ranunculus repens to the use of poultices of the plants as counterirri- L.) tants in traditional medicine for the treatment of í Helleborus spp. with Christmas rose rheumatic joints, and severe adverse cutaneous reac- (Helleborus niger L.). tions, with skin necrosis, may occur [287–291]. 41_751_800 05.11.2005 11:34 Uhr Seite 780

780 Christophe J. Le Coz, Georges Ducombs

Fig. 25. Structure of ranunculin CAS 644–69–9, precursor of the strong irritant protoanemonin CAS 108–28–1, loses irritancy after dimerization into anemonin CAS 508–44–1

Core Message roads, railways, and streams [55]. Because several members of these families are important sources of food, phototoxic reactions may occasionally be ob- í Ranunculaceae are very strong irritants, served following occupational or household contact containing protoanemonin. They can and sun exposure, on areas such as hands, the upper induce severe skin damage, as systemic limbs and around the mouth. intoxication after ingestion. The Apiaceae/Umbelliferae family contains 2850 species in 275 genera with a cosmopolitan distribution, chiefly in north temperate regions. Some are food plants such as celery (Apium graveolens L. var. dulce Pers.) [299–301], parsnip (Pastinaca sativa Peucedanum sativum 41.3.10 Umbelliferae/Apiaceae (Carrot L.syn. Benth. and Hook.) [302, Angelica Family), Rutaceae (Rue Family) 303], carrot (Daucus carota L.) [8], angelica ( archangelica Anthriscus cerefoli- and Moraceae (Mulberry Family) L.) [8, 304], chervil ( um Hoffm.), or parsley (Petroselinum crispum A.W. Hill, syns. Apium crispum Miller, Petroselinum sat- Members of these families have been considered to- ivum Hoffm.) [305]. Others are medicinal, wild or gether because of their capacity to induce photoder- cultivated plants such as Bishop’s weed (Ammi majus matitis,of phototoxic origin.The phototoxicity is due L.) [306], Palm of Tromsø (Heracleum stevenii Man- to furocoumarins contained in them. The synonym den syn.Heracleum laciniatum Hornem.) [307],giant psoralen is derived from the Latin name of the In- hogweed (Heracleum mantegazzianum Somm. and dian plant babchi or bakuchi (Psoralea corylifolia L., Lev) [55, 297], and hogweed (Heracleum sphondylium Leguminosae family), a plant that was used for treat- L.) [308]. Several dermatologically significant plants 41 ment of vitiligo [296]. The most classical feature is are reported in Table 2. Oppenheim dermatitis and its variants,discussed be- Allergic contact dermatitis from Apiceae/Umbel- low. Children using the stems of hogweeds (Heracle- liferae is possible, and has been described for carrot, um mantegazzianum Somm. and Lev. and H. sphon- celery and parsley. Falcarinol, also contained in dylium L.) as toy telescopes or peashooters in late members of Araliaceae (see later section),is probably summer typically develop bullous and erythematous the delayed-type allergen present [309, 310]. lesions around the eyes and mouth [297, 298]. Other The Rutaceae family comprises citrus fruits. Many exposed areas of skin may be affected if contact with of them have induced phototoxicity, such as lime [59, the sap occurs during horseplay amongst these 60, 311], bergamot [312, 313], and orange [314, 315]. Fu- plants, which are weeds of uncultivated land along ranocoumarins are isolated mainly from citrus rind. 41_751_800 05.11.2005 11:34 Uhr Seite 781

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Pulp also contains photosensitizers, but to a lesser for practical reasons. Most dermatoses from contact degree, with an average ratio of 1 : 20 to 1 : 100 [60]. with woods are occupational and are observed in Garden rue (Ruta graveolens L.) grows in gardens carpenters, joiners, cabinet-makers and in associated and may elicit phototoxic reactions after being tradespersons [5, 8, 12, 72, 332], as forest workers are picked [316, 317], as may other rue species such as Ru- generally affected by liverwort and lichens growing ta chalepensis L. (syn. Ruta bracteosa DC.) [318]. Per- on trees.Less commonly,dermatitis is due to finished fumes with psoralens from bergamot oil (Citrus ber- wood products, such as violin chin-rests [333], neck- gamia Risso and Poit.) can induce phototoxicity pre- laces [334], bracelets [335], and knife handles [336]. senting as “berloque dermatitis.” Gas plant (Dictam- Woodworkers are highly exposed to sawdust, and nus albus L., syn. Dictamnus fraxinella Pers.) [59, 62, contact initially occurs on exposed areas (hands and 302, 319], mokihana (Pelea anisata H. Mann) [320, forearms, face and neck, Fig. 26). Standard clothing is 321], blister bush (Phebalium anceps DC), and West- not good protection.Airborne sawdust,however,may ern Australian blister bush (Phebalium argenteum drift inside loosely fitting protective clothing, and Smith) also contain psoralens [322], which largely ac- adhere to sweaty areas of skin like the axillae, waist- count for the (sometimes very severe) bullous der- band, groin and ankles. Such areas can be prone to ir- matitis [60]. ritant and/or allergic contact dermatitis. The Moraceae family contains edible fig (Ficus The additional hazards of asthma and sinus eth- carica L.) [323–326], breadfruit (Artocarpus altilis), moidal adenocarcinoma from inhaling the sawdust other Ficus spp (naturally growing or as indoor of certain woods, and the higher risks of Hodgkin’s plants in temperate countries), and the tropical wood disease associated with woodworking as well as of iroko or African teak (Chlorophora excelsa Benth. systemic symptoms if the wood contains pharmaco- and Hook. f.), which contains chlorophorin. logically active constituents have been reviewed [337, Although allergic reactions to psoralens do not 338]. Reviews on wood-induced dermatitis are rec- seem to have been described, photoallergic reactions ommended for detailed information [8, 72, 337–342], can occur [66, 67]. However, a number of psoralen- like the website (http : //biodiversity.bio.uno.edu/del- containing plants may also sensitize as a result of ta/wood) [343] to which readers can refer for further other compounds that they contain. For example, cit- information. rus oils are generally weakly allergenic but they are The most highly sensitizing woods are of tropical also irritant and some are phototoxic [327]. Similarly, origin, as they commonly contain quinones as sensi- carrots (Daucus carota L., family Umbelliferae) have sensitized workers in the canning industry [328–330], but there is no convincing evidence that they may elicit phototoxic reactions, although weak phototoxicity has been observed experimentally [331]. Thus, if an allergic reaction is suspected, it is important to realize that irritancy and photoaggrava- tion may occur during patch testing.

Core Message

í The Apiaceae/Umbelliferae family is mainly responsible for phototoxic contact dermatitis (Oppenheim dermatitis and variants) like Rutaceae (citrus family) and Moraceae (fig family) because of the furocoumarins contained in them.

41.3.11 Woods

Although woods are not derived from a botanically Fig. 26. Positive patch test reaction to woodfloor (wood dust homogeneous source, we will consider them together diluted in petrolatum) in a “do it yourself” carpenter 41_751_800 05.11.2005 11:34 Uhr Seite 782

782 Christophe J. Le Coz, Georges Ducombs

tizers. Because of the wide occurrence of quinones, inadvertently or deliberately. For example, the single reactivity to several woods may be expected. For ex- milowood (Thespesia populnea Sol. ex Corrêa) is also ample, 2,6-dimethoxy-1,4-benzoquinone is found in named Álamo, álamo blanco, algodón de monte, many woods, such as African or American mahogany beach maho, bosch-katoen, catalpa, clamor, clemón, (Khaya spp., Meliaceae family), Bubinga (Guibourtia cork-tree, cremón, emajagüilla, frescura, grós ha- spp., family Caesalpinaceae), Capomo (Brosimum ali- haut, haiti-haiti, jaqueca, John-Bull-tree, macoi, ma- castrum Schwartz, family Moraceae), Bowdichia spp. hault de Londres, maho, mahot bord-de-mer, maja- (Bowdichia nitida Benth.) and Diplotropis spp. (Di- gua de Florida, majagüilla, otaheita, palo de jaqueca, plotropis purpurea), Doussié (Afzelia spp.), Afrormo- palu santu, portiatree, santa maría, seaside mahoe, sia or Kokrodua (Pericopsis elata van Meeuwen), Spanish cork, and tuliptree. It is imperative, for seri- Makoré (Tieghemella africana Pierre, T. heckelii ous diagnosis and exploration, that a solid sample of Pierre ex A. Chev.), Sipo (Entandrophragma spp., a wood believed to be the cause of contact dermatitis family Meliaceae) and Wengé (Millettia spp. laurentii (or any other pathological lesion) is sent to a wood De Wild, Milettia stuhlmanii Taub. family Papiliona- anatomist for identification [337]. Its origin and any ceae) [342]. available trade names should also be made known to In studies with guinea pigs, cross-reactivity the wood anatomist. between primin, deoxylapachol, various dalbergiones, mansonones and other quinones have been observed [337], but cross-sensitivity between primin 41.3.11.1 American and Australian Woods and various wood quinones does not seem to occur in humans [344]. In addition to quinonoid allergens, A variety of American and Australian woods deserve a number of other types of low molecular weight al- a mention in this context [10, 72, 342–346]. lergens have been identified from woods, reflecting Australian blackwood (Acacia melanoxylon R. Br., the variety of botanical sources from which exploit- Mimosaceae family), is a very important wood in able woods are obtained. Structures of some of the Australia, inducing occupational contact dermatitis best known wood allergens are given in the following due to 2,6-dimethoxy-1,4-benzoquinone, acamelin, figures. and melacacidin. Woods provide some rather significant problems The Australian silky oak (Grevillea robusta A. with their identification. Most are transported under Cunn., Proteaceae family) has been discussed above. a trivial rather than botanical name, and it is not un- Brazilian rosewood or palissander (Dalbergia ni- usual for these trivial names to be misapplied either gra All., Papillionaceae family) such as East India

Fig. 27. Allergens from American and Australian woods: (R)- 490–91–5, 2,6-dimethoxy-1,4-benzoquinone CAS 530–55–2, γ- 3,4-dimethoxydalbergion CAS 3755–64–4, oxyayanin A CAS thujaplicin CAS 672–76–4, and 7-hydroxy-4-isopropyltropo- and oxyayanin B CAS, bowdichione, thymoquinone CAS lone 41_751_800 05.11.2005 11:34 Uhr Seite 783

Plants and Plant Products Chapter 41 783

rosewood (Dalbergia latifolia Roxb.), cocolobo (Dal- 41.3.11.2 Asian Woods bergia retusa Hemsl., Dalbergia granadilla,and Dal- bergia hypoleuca) or grenadil (Dalbergia melanoxylon Several Asian woods are reported to be sources of al- Guill. and Perr.) are used for high-class furniture lergens [10, 72, 343, 346]. such as wooden jewels and musical instruments. Dal- Teak (Tectona grandis L., Verbenaceae family) is bergiones such as (R)-3,4-dimethoxydalbergione, R S S largely used for various indoor and outdoor applica- ( )- and ( )-4-methoxydalbergione, ( )-4-methoxy- tions (such as in doors and windows) due to its high dalbergione, (S)-4,4´-dimethoxydalbergione and S durability. The sensitizers are naphthoquinones ( )-4´-hydroxy-4-methoxydalbergione are the sensi- named deoxylapachol and lapachol, which have sim- tizers (Fig. 27). Apuleia leiocarpa ilar reactivities [72, 346] (Fig. 28). Grapia is a Brazilian wood ( East-Indian rosewood is similar to Brazilian rose- Macbr., Caesalpinioidae family) that can induce con- wood in terms of use and allergens. tact dermatitis and mucous membrane symptoms. Macassar (Diospyros celebica Bakh., family Ebena- Main allergens are likely ayanin, oxyayanin-A and ceae) is related to coromandel and ebony. oxyayanin-B, the latter also being an allergen in mo- vingui (Distemonanthus benthamianus Baill., family Caesalpinioidae). 41.3.11.3 African Woods Incense cedar (Calocedrus decurrens Florin, Cu- pressaceae family) used for pencils, chests or toys is a The following African woods are the most relevant to cause of contact dermatitis due to the allergen thy- this discussion [10, 72, 343, 347]. moquinone. African ebony (Diospyros crassifolia Hiern., family Pao ferro,“Santos-palissander”or caviuna vermel- Diospyros melanoxylon Machaerium scleroxylon Ebenaceae), coromandel ( ha ( Tul., Papilionaceae fam- Roxb.) are wood species with black heartwood used ily) is frequently used as a substitute of rosewood. R for precious works. The sensitizers are dalbergiones, including ( )-3,4- African mahogany (Khaya grandiflora DC.), dimethoxydalbergione,which is very potent allergen. Khaya mahogany (Kahya ivorensis A. Chev.), Krala Polynesian rosewood or milowood (Thespesia po- Khaya anthotheca pulnea ( C. DC.) and Senegal mahogany Sol., Malvaceae family) is a wood used for (Khaya senegalensis A. Juss., Meliaceae family) are small articles and wood jewels. It contains manso- sensitizers by the way of allergens such as anthothe- nones such as mansonone X. Bowdichia nitida col (Fig. 29). Sucupira ( Spruce, Fabaceae fam- African red padauk wood (Pterocarpus soyauxii ily) is a Brazil wood,used for flooring,responsible for Taub., Papillonaceae family), is a hardwood tree used allergic contact dermatitis in joiners and flooring to manufacture veneer, furniture and musical instru- workers. Among the allergens present, 2,6-dimeth- p ments. oxy- -benzoquinone and Bowdichione are the best Ayan (Distemonanthus benthamianus Baillon, known. Thuja plicata Caesalpinaceae family) is used for flooring or win- Western cedar ( Donn., family Cu- dows. Its allergens are oxyayanin A and B. pressaceae) is used as a hardwood in construction Iroko, African teak or kambala (Chlorophora ex- work or on boats. Its main contact allergen is thymo- celsa γ Benth and Hook. f., Moraceae family) has good quinone. It also contains -thujaplicin and 7-hy- strength and durability and is used for indoor and droxy-4-isopropyl-tropolone.

Fig. 28. Structure of deoxylapachol CAS 3568–90–9, and lapachol CAS 84–79–7 41_751_800 05.11.2005 11:34 Uhr Seite 784

784 Christophe J. Le Coz, Georges Ducombs

Fig. 29. Structures of some allergens in African woods: anthothecol CAS 10410–83–0, chlorophorin CAS 537–41–7, mansonone A CAS 7715–94–8, and mansonone X

outdoor constructional work. Chlorophorin is its 41.3.11.4 European Woods main allergen. Mansonia altissima Mansonia or bete ( A. Chev, Woods derived from trees growing in temperate re- Sterculiaceae family) is used as a substitute for wal- gions in Europe are also sensitizers [72, 346, 348, 349]. nut. It has several sensitizers called sesquiterpenoid Dermatitis has been reported in association with al- ortho mansonones, with the -quinone mansonone A der (Alnus sp., Betulaceae family), ash (Fraxinus sp., being the main allergen. Oleaceae family), beech (Fagus sp., Fagaceae family), birch (Betula sp. Betulaceae family) and poplar (Pop- ulus sp., Salicaceae family) woods. The most extensively grown and exploited trees in temperate regions are the pines (Pinus spp.), spruces

Fig. 30. Examples of oxidation products of colophony, responsible for sensitization 41_751_800 05.11.2005 11:34 Uhr Seite 785

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(Picea spp.), firs (Abies spp.), and related conifers black mushrooms (Lentinula edodes Pegler) [355]. (family Pinaceae). These are rarely implicated as Other mushrooms have been reported as being aller- causes of allergic contact dermatitis. It is worth not- genic, such as yellow boletus (Boletus luteus L., syn. ing that patients with dermatitis from pine or spruce Suillus luteus Gray), cep or Polish mushroom (Bole- have positive reactions to colophony. Pines are sourc- tus edulis Bull.Fr), meadow mushroom (Agaricus es of turpentine oil and of colophony, both of which campestris L.), cultivated mushroom (white type: are well-known sensitizers. In both of these wood- Agaricus hortensis Imai; brown type: Agaricus bispor- derived products, the actual sensitizers are the hy- us Pilát), orange agaric (Lactarius deliciosus Gray), droperoxidic autoxidation products that are formed pine yellow clavaria or fairy clubs (Clavaria flava Fr., in contact with the air, rather than the major constit- syn. Ramaria flava Quélet), oyster (Pleurotus ostrea- uents from which they are derived. tus Kummer, and yamabushitake or monkey’s head The major resinic acids in colophony are abietic mushroom (Hericicum erinaceum Pers.) [356–359]. and dehydroabietic acids. Abietic acid was formerly claimed to be the cause of colophony (rosin) dermatitis. However, it appears to be neither a sensitizer 41.3.13 Ferns nor an elicitor of colophony dermatitis if rigorously purified, whereas numerous oxidation products such Ferns and related plants [360] have rarely been im- as 15-hydroperoxyabietic acid or products from sec- plicated in plant dermatitis. Leatherleaf or Baker fern ondary oxidation are the allergens responsible (Arachnoides adiantiformis Tindale, Aspidiaceae or (Fig. 30) [350–352]. Dryopteridaceae family) provoked allergic contact In turpentine oil, hydroperoxides of 3-carene, and dermatitis in a flower shop worker [361]. not ∆3-carene itself, are sensitizers [353, 354]. 41.3.14 Miscellaneous Plants Core Message Many plants have been described as inducing derma- í Woods induce contact dermatitis, mainly titis. Case reports are sometime scarce or even in woodworkers. Irritation is frequent, and unique. Many are reported in dermato-botanical contact allergy can be severe due to potent books, but it is interesting to cite some recent reports allergens like quinones. of dermatitis due to plants belonging to families not mentioned above.

41.3.14.1 Araliaceae 41.3.12 Mushrooms (Ginseng, Aralia, Ivy Family)

Several cases of occupational allergic contact derma- Common ivy (Hedera helix L.) is a very common titis have been described from mushrooms, which plant in Europe that may induce contact irritation mainly induce immediate-type symptoms. The best and more rarely sensitization. It contains three pow- known manifestation is likely shiitake dermatitis, erful irritants and weak sensitizers, namely didehy- due to contact or ingestion of raw or half-cooked drofalcarinol and falcarinol (Fig. 31) that have mod-

Fig. 31. Falcarinol, CAS 21852–80–2, and didehydrofalcarinol, CAS 110927–49–6 41_751_800 05.11.2005 11:34 Uhr Seite 786

786 Christophe J. Le Coz, Georges Ducombs

erate sensitizing potentials [310,362,363].These aller- sponsible for cutaneous side-effects such as contact gens or related molecules are also present in other dermatitis and photosensitivity [368–371]. members of this family, such as ginseng (Panax gin- Tamanu oil (Calophyllum inophyllum), extracted seng C. Meyer), Schefflera arboricola Hayata [310] or from the fruits or seeds of Calophyllum tacamahaca kakuremino (Dendropanax trifidus Makino) [364]. L. and used as a cosmetic or traditional medicine in- Falcarinone, an oxidation product of falcarinol, is gredient, has been reported to be a cause of allergic commonly found in the Apiaceae/Umbelliferae fami- contact dermatitis, with photoworsening of patch ly [310], and falcarinol is likely a delayed-type aller- tests [372]. gen of Apiaceae/Umbelliferae,as in carrot,celery,and parsley [309, 310]. 41.3.14.4 Hydrangeaceae

41.3.14.2 Papaveraceae (Poppy Family) Dermatitis due to Hydrangea macrophylla Thunb (Hydrangeaceae family) appears as a chronic, fissur- Greater celandine, sometimes named “wart plant” ing and scaling dermatitis of hand and finger.Irritant (Chelidonium majus L., Papaveraceae family), is well dermatitis is possible, but allergy is not rare and is known in traditional topical treatments of warts, epi- due to hydrangenol (Fig. 33). Occupational exposure thelial tumors, and hyperkeratotic lesions [365]. Its is mainly found in nursery workers, florists or gar- orange-colored juice has irritant properties and has deners. Patch tests with leaves and stems are strongly been reported to be a probable allergenic [366]. positive, as hydrangenol 0.1% pet., which gives Systemic (liver) toxicity is possible after ingestion strongly positive reactions [373]. [367]. 41.3.14.5 Iridaceae (Iris Family) 41.3.14.3 Guttiferae (St John’s Wort or Mangosteen Family) Contact dermatitis to iris (safflower) (Iris germanica var florentina Dykes) was reported, with positive re- This family comprises herbs, lianes, shrubs, and trees actions to petals [374], but not to leaves in one obser- that have a colored resinous juice. They are used for vation [375]. timbers, drugs, dyes, gums, pigments, and resins. St John’s wort (Hypericum perforatum L.) has been used for centuries for wounds, burns or dermatitis 41.3.14.6 Solanaceae (Nightshade Family) [365]. It has recently been used systemically for de- pression. It contains hyperforin, which has antibacte- The family contains more than 2000 species in 90 rial or claimed antidepressant properties, and the genera, providing numerous food plants such as to- phototoxic substance hypericin (Fig. 32), which is re- matoes (Lycopersicon lycopersicum), potatoes (Sola- num tuberosum L.), paprika and pepper (Capsicum), and tobacco (Nicotiana tabacum). Occupational hand contact dermatitis is frequent in pickers or harvesters [376], mainly irritant, but sometimes allergic. Leaves of eggplants or brinjal (Solanum melongena L.) were tested positive when

Fig. 32. Hypericin, CAS 548–04–9, extracted from Hypericum Fig. 33. Hydrangenol, CAS 480–87–7 the allergen of hydrangea perforatum L. 41_751_800 05.11.2005 11:34 Uhr Seite 787

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chopped in petrolatum [377]. Fruits (aubergine) and pollens may induce immediate symptoms.

41.4 Diagnosis of Plant Dermatitis

Finding the source of a plant-induced contact dermatitis is often difficult.A provisional diagnosis may be made by asking patients about their occupation, hobbies and recent excursions during which plant contact may have occurred. It is often necessary to enlist the help of a botanist to identify plants brought in by patients. If the results of an investigation of a plant-induced dermatitis are to be published, it is es- Fig. 34. Positive prick tests to rose (petal, stem, leave and sential to identify the plant precisely. Whilst photo- thorn) in a florist with immediate symptoms following contact graphs of plants are helpful, they are usually less with roses helpful than accurate drawings showing features that enable similar species to be distinguished one from another. There is no substitute for a botanist who is familiar with the taxonomic literature on the plant 41.4.1.3 Patch Tests concerned, but just as there are specialities in the medical profession, no one botanist is an expert on It is often possible to carry out tests with plant mate- all plants. rial “as is,” and a diagnosis of plant dermatitis can usually be established with a few grams of fresh plant material. The practitioner has to patch test several 41.4.1 Raw Plants plant pieces such as roots, stems, leaves, and reproductive organs (flowers and/or fruits). It is some- 41.4.1.1 Plant Identification times useful to patch test crushed leaves or slices of stem [378]. The practitioner has to consider not only the plant It is important to use, whenever possible, the actu- species itself, but also its generic and familial iden- al plant material that is believed to be responsible for tity. The genetic information that groups plants into the current dermatitis.This is because distinct chem- species, genera and families actually determines to a ical races may exist in outwardly identical plants, large extent the nature of the plant’s secondary me- where one specimen contains the allergen whilst the tabolites. Thus, sesquiterpene lactones are a common second does not. As noted above, cultivars of plants feature of members of the family Compositae, whilst such as tulips and chrysanthemums exhibit varying mono- and dihydroxyalk(en)ylbenzenes are com- propensities to induce and elicit allergic contact monly found in members of the family Anacardia- dermatitis. If an inappropriate sample of plant mate- ceae. Once a plant has been implicated and identi- rial is tested,the risk of a missed diagnosis clearly ex- fied, reference to the literature should reveal whether ists. or not it has been recorded as an allergenic plant. Woods should not be tested as is, because of the risk of irritation and active sensitization. Wood dust can be tested diluted in white petrolatum, 10–20% 41.4.1.2 Prick Tests (weight/weight). Extracts obtained with solvents such as acetone or ethanol can be used. Controls are Pricks can be performed through the crude material useful when they are negative because of the high in- as is,or by the “prick by prick”method (prick into the cidence of irritancy [38, 339, 345], but they raise ethi- plant, and then into the skin). Plant materials can be cal considerations. When purified isolates from crushed and diluted with saline (for example, 1 : 9 woods are available for patch testing, these may be parts) in order to obtain a solution that can be easily prepared according to the recommendations of Hau- pricked (Fig. 34, rose). sen [340]. Here too, the risk of active sensitization is real ([345]; A. Goossens, personal communication). Care should be taken with plants known to contain either irritant compounds (such as Euphorbia spp.) or highly allergenic compounds (such as Pri- 41_751_800 05.11.2005 11:34 Uhr Seite 788

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mula), where the past experiences of other dermatol- known to be present in the plant, or a somewhat la- ogists (reported in the literature, at congresses or via borious extraction, isolation, purification, and char- networks) should be heeded. acterization procedure using, ideally, several kilo- Irritant reactions are frequent with plant materi- grams of fresh plant material. als and have to be considered when doubtful or weakly positive (edema and erythema) reactions are observed. 41.4.4 Commercial Allergens

Core Message Relatively few plant constituents are available commercially for patch testing. Table 5 indicates the main plant allergens available from Chemotechnique, Fir- í Patch tests with plant or wood materials ma, and Hermal. Some of them are natural extracts have to be performed cautiously, heeding that contain the major allergen as well as other im- recommendations, and interpreted careful- purities. Volatile oil constituents, which are found in ly because of the irritant and sensitizing the aromatic oils of plants, are unstable to air oxida- risk. tion and are generally virtually impossible to purify (except through derivatization and resynthesis) if liquid at room temperature. It should be remembered that the air oxidation products themselves may be the sensitizers. Synthetic or purified extracts con- 41.4.2 Plant Extracts tain one or a mixture of molecules. There is an ongoing search to identify mixtures of Plant allergens, which are generally low molecular compounds that can be used to reliably detect partic- weight secondary plant metabolites, are likely to be ular common types of plant- or plant product-in- soluble in acetone, ethanol or ether. Thus, a filtered duced dermatitis. Thus, various authors have recom- acetone or ethanol extract of dried plant material, or mended mixtures to detect colophony allergy,sesqui- a short ether extract of fresh material usually pro- terpene lactone allergy, lichen allergy, and so on. It is duces a solution suitable for patch testing. Producing likely that none of these mixtures will ever be regard- water extracts of fresh plant material is not recom- ed as an absolutely certain means of detecting the mended, although this is often carried out and can group allergy in question. For example, allergy to As- produce active substances. Water extracts seem to teraceae is difficult to screen, as discussed above. The degrade rapidly and lose their sensitizing power Compositae mix gives more frequent patch test reac- within a month [170], due to chemical degradation tions than sesquiterpene lactone mix [379, 380], but and/or to microbial contamination.For example,ace- its sensitivity, ascertained by relevance of positive re- tone extracts of Parthenium hysterophorus have been actions, seems lower than that of SLM [379]. demonstrated to be more sensitive than water extracts, with very good sensitivity to 1% acetone extract [50]. 41.4.5 Photopatch Testing Extracts in organic solvents are generally more stable, but they should not be regarded as having an Airborne contact dermatitis from plants can closely indefinite shelf life. Moreover, with time, evaporation simulate photocontact dermatitis, but plant-induced of the solvent may increase the concentration and the photoallergy is actually very rare. However, patients sensitizing effect of the allergen(s). Incorporating an with photosensitivity have frequent positive reac- evaporated extract into petrolatum represents a stan- tions to plants or plant extracts. Photoworsening of dard means of retaining material for patch testing, patch test reactions may be indicative of an underly- 41 but it is questionable whether this extra manipula- ing acquired photosensitivity, a state that may or may tion of the extract confers any benefit over the appli- not be causally associated with contact with the plant cation of a known volume of the extract onto a stan- material being investigated. dard occlusive patch chamber. Photopatch tests have to be performed in dupli- cate, one series being a dark (non irradiated) control removed after 48 h as in usual patch tests. The series 41.4.3 Allergen Identification that will be irradiated is removed after 24 or 48 h,and irradiated by a UVA source, generally with a dose of Identification of the phytochemical(s) responsible 5 J/cm2. When a total spectrum irradiation is pos- requires either a supply of the purified sensitizers sible, which allows us to test both UVA and UVB sen- 41_751_800 05.11.2005 11:34 Uhr Seite 789

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Table 5. Commercially available plant allergens (C Chemotechnique Diagnostics, Malmö, Sweden, F Firma, Italy, T Trolab Her- mal, Reinbeck, Germany) Allergens Concentration Sources of exposure Providers (%)

Achillea millefolium extract 1 Yarrow C, T Alantolactone 0.1 C, F α-methylene-γ-butyrolactone** 0.01 (C), 0.005 (F) Tulipa, Alstroemeria, Bomarea, C, F Disocorea Hispida, Erythronium, Gagea, Fritillaria Arnica montana extract 0.5 Mountain tobacco C, T Chamomilla romana (Anthemis nobilis) 1 (C), 2.5 (T) Roman chamomile C, T extract Chrysanthemum cinerariifolium extract 1 Pyrethrum C Compositae mix (emulsified with 6 (T), 5 (F) T, F sorbitan sesquioleate) Costunolide Diallyl disulfide 1 (C), 2 (F) Garlic C, F Lichen acid mix (atranorin, usnic acid, 0.3 C evernic acid) Parthenolide 0.1 Tanacetum par thenium (feverfew), Parthe- C nium hysterophorus L. (congress grass) Primin 0.01 Primula obconica,Primulaceae C,F,T Propolis 10 Beekeepers, medications C Sesquiterpene lactone mix 0.1 Asteraceae/Compositae, Jubulaceae C (Alantolactone, costunolide, (Frullania) dehydrocostus lactone, each 0.033%) Tanacetum parthenium extract 1 Feverfew T Tanacetum vulgare extract 1 Tansy T, C Taraxacum officinale extract 2.5 Dandelion C Usnic acid 0.1 (T), 1 (F) Lichens T, F

** Only 0.01% can be considered safe [91])

sitivity, a third series has to be applied. Two series are can be difficult to establish because the patient may removed after 24 h and then the first one is irradiat- have handled several plants over a period of time and ed with UVA,and the second one with a sunlight sys- become sensitized to some or all. The phenomenon tem, delivering 75% of the minimal erythematous of cross-sensitization adds a further dimension to dose (MED). the problem of relevance. False-positive reactions may be due to an irritant reaction, and it is useful to refer to guidelines before 41.4.6 Results and Relevance testing plants. Testing with numerous plants or extracts can cause an angry back or excited skin syn- Contact urticaria appears within minutes of patch drome. Each plant part or plant extract must then be testing and disappears rapidly. Patient interrogatory, tested again separately. Sometimes, positive reac- literature data, and if necessary results from open tions arise from contamination of the plant material tests, prick tests or a search for a specific IgE will lead with pesticides or other agricultural/horticultural to the diagnosis of immunologic or nonimmunolog- chemicals [381], or from fungal contamination. An- ic contact urticaria. other cause of positive reactions is the use of an ex- Contact dermatitis is much more difficult to extract at a concentration that is too high, whereby a plore. The realization of patch tests, their readings subclinical sensitivity may be unmasked. and the validity of patch test results are often hard to Active sensitization to the material should not be determine. The relevance of positive test reactions overlooked, but patch test reactions are generally de- 41_751_800 05.11.2005 11:34 Uhr Seite 790

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layed,occurring after 7–10 days.They are theoretical- working environment.However,the patient may have ly (and practically) possible with many plant materi- to consider a change of workplace (for example, in als, such as plant extracts. the case of Primula dermatitis), and sometimes leave False-negative reactions may arise if an inappro- his or her occupation (as in the case of foresters aller- priate sample of plant material is tested (such as gic to Frullania). patch testing with a leaf when the allergen is contained in the stem), or if the extract contains an in- sufficient concentration of the allergen, perhaps as a 41.5.2 Barrier Creams result of using a stored extract or of seasonal variations of allergen content. Barrier creams,used as recommended,can be helpful in the prevention of irritant dermatitis. The practi- 41.4.7 Multiple Plant Reactions tioner must carefully read their composition in rela- and Cross-sensitivity tion to some allergens such as lanolin, methyldi- bromoglutaronitrile and other allergens. Their use in primary and secondary prevention of In most cases, reactions to several plants in the same allergic contact dermatitis is discussed [382]. patient are not due to cross-sensitization. First, co- sensitization is frequent, particularly in people who are frequently in contact with plants. Many plants 41.5.3 Gloves contain the same hapten, and so a patient sensitized to a particular compound in one plant will react to It has been demonstrated that wearing gloves is a another plant containing the same compound. More- useful approach. over, he or she will react to plants that present a dif- However, tuliposide A (present in Alstroemeria ferent compound, but one that will be still metabo- and Liliaceae) readily penetrates through vinyl lized into the same allergen. Such situations are false gloves [103]. Nitrile gloves may prevent contact with cross-reactions. tuliposide A [103]. A recent study shows that vinyl, In rarer cases, true cross-sensitization arises, polyethylene and latex gloves are likely permeable to when the immune surveillance process misidentifies plant allergens such as α-methylene-γ-butyrolac- a second compound due to its structural similarity to tone, primin and diallyldisulfide. Nitrile gloves could the primary sensitizer. Difficult and long procedures, protect from primin [383]. for example chemical studies of spatial molecular structures, correlated to clinical reactivity patterns, and clinical experimentation such as cross-retests 41.5.4 Acute Dermatitis permit us to assume a true cross-reactivity between different molecules. Clearly, false cross-reactions and cross-reactions Acute dermatitis has to be rapidly treated with po- are almost impossible to detect with certainty in hu- tent topical corticosteroids, such as betamethasone mans because the primary sensitizer cannot easily be esters. They have to be applied once (or twice) a day, determined. Thus, reactions may occur to plants not in adequate quantities (for example, an average of previously encountered by the patient, as well as to 20 g/day of topical 0.05% betamethasone dipropion- isolates that are not actually present in the sensitiz- ate cream for each upper limb), every day until total ing plant. healing. Pulverization, or compresses with saline (around 10 g NaCl per liter of fresh or warm water), are frequently useful. Systemic corticosteroids are 41.5 Prevention and Treatment used by some authors for severe cases. A high daily 41 dose for a short period, until healing (1 mg/kg per 41.5.1 Removal of the Allergens day prednisone) is better than a lower regimen that and Irritants requires a longer duration.

As soon as the plant responsible for contact dermatitis has been identified, steps should be taken to 41.5.5 Chronic Dermatitis avoid further contact.In cases of occupational phytodermatitis, work practices and occupational hygiene Treatment is symptomatic too. We use topical corti- measures should first be reviewed because of the costeroids in the same manner as described below, employer’s legal responsibility to provide a safe sometimes with emollients, until healing. 41_751_800 05.11.2005 11:34 Uhr Seite 791

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Other solutions such as UV therapy are helpful for í Gymnosperms: conifers, cycads, ginkgos, diffuse dermatitis. Photochemotherapy with UVA ephedras, chlamydosperms and 8-MOP, or even systemic immunosuppressive í Angiosperms (Magnoliophyta) group: chemicals such as azathioprine or ciclosporin can be plants with flowers, which are divided into discussed for severe and intractable phytophotoder- two classes: matitis with or without persistent light reactions – Dicotyledon (Magnoliopsidae) class, [384]. subdivided into nine subclasses Preventive measures (wearing gloves, removal of – Monocotyledon (Liliopsidae) class, allergens or irritants) are always indispensable. subdivided into three subclasses Subclasses are subdivided into orders 41.5.6 Hyposensitization Orders are divided into families Each family is made up of genera (singular: genus) Hyposensitization measures have been attempted Each genre is divided into species with limited success when avoidance of contact is im- practical, such as with poison ivy in certain outdoor occupations.After a note by R. Dakin in 1829, the first Ideally, to identify a plant, we need information on its attempts in this direction were attributed to Scham- roots, stems (aerian or underground), leaves (inser- berg in 1919 [385]. Other authors have then carried tion, venation, arrangement, simple or compound or- out oral or parenteral hyposensitization with varied ganization, margins) and its reproductive organs results and sometimes severe side-effects, with re- (flowers, fruits). ports of fatal renal complications [386–388]. Oral de- Following the considerable work of the Swedish sensitization with daily intake of leaf extract in water naturalist Dr. Carl von Linné (1707–1778), each spe- has been reported as being beneficial on skin lesion cies is characterized by two names written in Latin: and patch test results [389]. A similar approach was the first name is the genus, the second the species. attempted in 24 Indian patients positive to P. hyste- These are often related to the name of the author who rophorus, with increasing amounts of plant extracts. first described the species, and are frequently abbre- Of 20 who completed the study, six suffered wors- viated. ened dermatitis and stopped treatment. In the re- The purple foxglove (Digitalis purpurea L.) be- maining 14 patients, a progressive fall in the mean longs to the plant kingdom, the Spermatophyta divi- clinical severity score was noted, but no significant sion, the Angiospermae subdivision, the Dicotyledo- change in the titer of test reactivity. Long-term re- nae class, the Gamopetalae subclass, the Tubiflorales sults are unspecified, with 3/7 patients free of symp- order, the Scrophulariaceae family, the Rhinanthoi- toms after 1 year [51]. Currently, there is no scientific deae family, the genus Digitalis, and the species basis behind this practice, and the risk of toxic side purpurea, as described by Linné [8]. The white dead effects should be considered [388, 390]. Induction of nettle (Lamium album L.) belongs to the Lamiaceae tolerance in naive subjects appears to be a more suc- family, the Lamium genus, and the album species [7]. cessful strategy than desensitization of those already sensitized [391]. So-called hardening is also a procedure that has References been discussed, and it has been described as an ex- ternal topical hyposensitization. It consists of repeat- 1. Fregert S (1975) Occupational dermatitis in a 10-year ma- ed patch test application, until the reactivity progres- terial. Contact Dermatitis 1 : 96–107 sively fades [388]. 2. Paulsen E, Sogaard J, Andersen KE (1997) Occupational dermatitis in Danish gardeners and greenhouse workers. I.Prevalence and possible risk factors.Contact Dermatitis 41.6 Example of Botanical Nomenclature 37 : 263–270 3. Paulsen E (1998) Occupational dermatitis in Danish gardeners and greenhouse workers. II. Etiological factors. The plant kingdom, which comprises around 350,000 Contact Dermatitis 38 : 14–29 species, is divided into five divisions:phycophytes 4. Evans FJ, Schmidt RJ (1980) Plants and plant products (seaweeds or algae), bryophytes (mosses, liver- that induce contact dermatitis. Planta Med 38 : 289–316 worts/hepatics and hornworts), mycophytes (fungi 5. Mitchell J, Rook A (1979) Botanical dermatology. Plants and plant products injurious to the skin. Greengrass,Van- or mycetes), pteridophytes (ferns and related) and couver spermatophytes (seed plants) [7, 8]. Spermatophytes 6. Lovell CR (1993) Plants and the skin. Blackwell Scientific, are divided into two groups: Oxford 41_751_800 05.11.2005 11:34 Uhr Seite 792

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7. Sell Y, Benezra C, Guérin B (2002) Plantes et réactions 29. Morton JF (1972) Cocoyams (Xanthosoma caracu, X. atro- cutanées. John Libbey Eurotext, Paris virens and X. nigrum), ancient root- and leaf-vegetables, 8. Benezra C, Ducombs G, Sell Y, Foussereau J (1985) Plant gaining in economic importance. Proc Fl State Hort Soc contact dermatitis. Decker, Toronto 85 : 85–94 9. Behl PN, Captain RM (1979) Skin-irritant and sensitizing 30. Walter WG, Khanna PN (1972) Chemistry of the aroids. plants found in India. Chand, Ram Nagar, New Delhi I. Dieffenbachia seguine, amoena,and pitta. Econ Bot 26 : 10. Schmidt RJ (2005) The botanical dermatology database: 364–372 homepage. (See http : //bodd.cf.ac.uk/index.html) 31. Metin A, Çalka O, Behçet L, Yildirim E (2001) Phytoder- 11. Bourrain JL (2001) Les agents étiologiques des urticaires matitis from Ranunculus damascenus. Contact Derma- de contact. Ann Derm Venereol (Stockh) 128 : 1363–1366 titis 44:183 12. 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