Toxicodendron Toxicity

Article Author:
Trevor Lofgran
Article Editor:
Gauri Mahabal
Updated:
4/19/2020 4:49:48 PM
PubMed Link:
Toxicodendron Toxicity

Introduction

Toxicodendron is a genus of plants, shrubs, vines, and trees within the Anacardiaceae family. Common names of plants within the family include poison oak, poison ivy, poison sumac, and the Chinese lacquer tree. Many of these names come from similar appearances to other leaves that are non-toxic. The genus as a whole is widespread throughout North American except for Hawaii and Alaska and can have regional variations in appearance. Many of these plants prefer lower elevations and are typically found below 1500 meters. An often-repeated adage regarding their identification is “leaves of three, leave it be” but should be the sole method used. Poison ivy is pervasive throughout North American and has been known to hybridize where their geographic distribution overlaps. Eastern poison ivy (Toxicodendron radicans) is commonly found in the eastern half of North America and typically appears as a vine with almond-shaped leaves in groups of three. Leaves change from green to red in the fall. Western or Rydberg’s poison ivy (Toxicodendron rydbergii) is commonly found as a shrub with small yellow berries. It is distributed throughout much of North America, with the general exception of the Southeastern United States. All parts of both plants contain urushiol, which causes characteristic dermatitis associated with exposure. While the genus and its many subspecies have a strong predilection for North America, they can both be found in China, Mexico, Africa, Australia, and New Zealand, to name a few other places. Poison oak has two common variations. Western poison oak (Toxicodendron diversilobum) is a deciduous shrub with scalloped or lobed leaves, generally appearing in groups of three that resemble true oak leaves. It is found primarily west of the Rocky Mountains, as the name suggests. Eastern or Atlantic poison oak (Toxicodendron pubescens or quercifolium) is frequently confused with Eastern poison ivy as it has three grouped leaves that are structurally similar in appearance. A unique feature useful in identification is the presence of clustered small green fuzzy berries on the plant. Distribution is more common in the Southeastern United States but can extend as far north as New Jersey. The leaves of both western and Atlantic poison oak change colors in the fall time and drop off in the Western species. Poison sumac (Toxicodendron vernix) is a deciduous tree or tall shrub found in moist, swampy areas of the eastern United States. It has red stems with a pinnate or feather-like leaf arrangement comprised of 7 to 13 oblong or oval-shaped leaves. The plant also produces green clustering flowers and small globular fruit. The leaves and fruit of the plant are the primary sources of urushiol. The Chinese lacquer tree (Toxicodendron vernicifluum) is a common deciduous tree in many Asian countries and gets its name for the use of its urushiol containing sap in lacquer production. Leaves are large and grouped in leaflets of 7 to 19 with flowers that bloom in the summer. All parts of Toxicodendron plants contain urushiol, which is found in sap channeled within the plant. When exposed to air, urushiol turns black and hardens to prevent moisture loss and can be useful in identifying plants in the fall. Urushiol is the primary allergenic cause of contact dermatitis and is typically encountered by brushing up against damaged stems or leaves. Exposure to the plants results in rapid absorption of the urushiol on contact due to its lipophilic nature. Names for the toxicity are variable and include names such as Rhus dermatitis, urushiol-induced contact dermatitis, and Toxicodendron dermatitis.

Etiology

Toxicodendron dermatitis is the most common cause of allergic contact dermatitis in North America and is caused by skin exposure to urushiol, producing a type IV hypersensitivity reaction.[1] The chemical structure of urushiol is variable and primarily comprised of catechol with a long hydrocarbon chain.[2][3] Evidence suggests longer saturated hydrocarbon side chains, the addition of aliphatic side chains and phenolic groups are associated with increasing clinical severity.[4][5] It is estimated that 50 to 75% of adults are allergic to urushiol.[6] 

Epidemiology

A large portion of the population is sensitized to urushiol. Acute allergic dermatitis affects virtually all ages, ethnicities, and skin types, with an estimated 25 to 40 million cases requiring treatment yearly.[7][8] Occupational exposure is common in forest service workers and comprises a large portion of these cases with exposure to extremities being more common.[8][9][10] 

Pathophysiology

Acute allergic dermatitis is caused by contact with bruised or broken parts of plants within the aforementioned Toxicodendron species. Urushiol is the primary inciting compound causing the release of local cytokines and inflammatory mediators that initiate the process of sensitization. The compound is rapidly absorbed due to its lipophilic nature and picked up by Langerhans cells in the epidermis, making additional efforts to wash or remove the compound ineffective after absorption.[4] Initial exposure results in pruritus and erythema, followed by a papulovesicular eruption, edema, and oozing within 10 to 14 days. Symptoms of re-exposure are more acute and appear in 24 to 72 hours.[11] Aerosolized urushiol from forest fires or the burning of plant debris has been known to cause airway inflammation or generalized dermatitis in severe cases.

Histopathology

Sensitization and reexposure are mediated by a type IV cell-mediated hypersensitivity reaction.[12][13][14] Langerhans cells, or antigen-presenting cells (APCs), and other acute inflammatory mediators are activated initiating a local response. APCs break down urushiol into antigens, which either combine with major histocompatibility complex II (MHC II) or are exposed on the surface of APCs. Transit of Langerhans cells to lymph nodes results in the presentation of the MHC II/antigen complex or free surface antigens to T cell receptors on CD8+ T cells via MHC II or through MHC I on CD4+ T cells respectively. Clonal expansion then occurs, and subsequent exposure and recognition of antigens by T cells result in repeat allergic dermatitis. While it is estimated that 50 to 75% of adults are allergic to urushiol, variations can occur where no T cells able to recognize the presenting antigens are present, and no immunologic response occurs.[6] Activation of T cells on initial exposure results in the production of CD4 and CD8 T cells sensitive to urushiol, which then activate a more robust immune response on repeat exposure to the offending agent. Keratinocytes and monocytes also appear to place a role in the release of local cytokines and pro-inflammatory mediators.[14][15][16] Many of these pathways are the target of corticosteroid treatment.

History and Physical

A thorough history should include any potential occupational and environmental exposure within the past 2 to 3 weeks as initial sensitization may be unknown. Clinicians should be aware of local geographic distributions of the Toxicodendron species. Patients often initially present with complaints of intense pruritis and the beginning stages of a papular or vesicular rash in a linear pattern. Distribution may be scattered as patients often do not recognize exposure until they have contacted other body areas. Black spots may be noted on affected skin or clothing and should be avoided, and it is the result of oxidized urushiol exposed to air.[17][18][19][20] Secondary exposure can occur when the skin is exposed to oxidized urushiol or animal fur that came in contact with the Toxicodendron species.

Evaluation

The diagnosis is primarily determined by a thorough history and physical, and no additional testing is required. Allergy patch testing is widely available and may be useful in identifying patients with severe urushiol sensitivity, but is not necessary. It can also increase the risk of sensitization in unsensitized subjects. Dermoscopy, if available, is another alternative for evaluation of black spot dermatitis caused by Toxicodendron species and would show jagged red-rimmed dark brown lesions.[18]

Treatment / Management

Toxicodendron dermatitis is typically self-limited and resolves within a couple of weeks.[1] Initial management consists of immediate irrigation with soap and decontamination of clothing upon exposure.[4] Specific instruction should be given to clean under fingernails as they are commonly missed.[21] Mild detergents are a reasonable choice when compared to expensive alternatives.[22] Additional anecdotal options include cool, moist compresses, oatmeal baths, calamine lotion, and topical astringents.[7][23] A small study comparing topical commercially available cream containing polyethylene granules, sodium lauroyl sarcosinate, nonoxynol-9, C12-15 pareth-9, disodium EDTA, quaternium-15, carbomer (2%), triethanolamine, and water, to placebo, showed improvement in symptoms if applied early. There is a small amount of literature suggesting the use of prophylactic homeopathic oral preparations of poison ivy may be somewhat protective, but randomized controlled trials (RCTs) are lacking.[24] 

Topical and oral antihistamines are another group of commonly taken medications to decrease pruritus and are typically ineffective outside of their sedative effects as the biochemical process is not due to histamine release. Management should be centered on moderate to high dose topical or systemic corticosteroids that are beneficial early in the disease course, particularly before the appearance of papules or vesicles.[25][26][27] A tapered dose of prednisone for severe cases can begin at 1 mg/kg/day (0.5 mg/kg/day in pediatric patients) for a max dose of 60mg/day and tapered weekly over three weeks to prevent rebound dermatitis.[28][29] Alternatives for patients who are not candidates for systemic corticosteroids include the application of moderate strength topical corticosteroids with an occlusive dressing for 24 hours that is then repeated 48 hours after initial application.[30] 

Initial studies assessing the use of topical immunosuppressants for atopic dermatitis were mixed.[31][32] Newer evidence shows some benefit with the use of tacrolimus and pimecrolimus compared to topical corticosteroids (TCS); however, a meta-analysis of RCTs showed increased adverse events in comparison to TCS.[33] Both appear to be well tolerated and may play a role in patients who require long-term treatment. While there is considerable interest in the development of a vaccine-like compound, current research is ongoing, with the initial phases of clinical trials sound promising.[34] Although patients typically appear relatively late in the clinical course, care should be taken to actively treat any signs of secondary skin infection with appropriate antibiotics. Excoriations and decreased skin integrity are common etiologies of secondary infections, with the most common pathogen being Staphylococcus aureus. Evidence also supports the possibility of polymicrobial infections.[35] Hyperpigmentation is a possible complication of contact dermatitis in patients with darker skin types and typically resolves within a couple of months.[1]

Differential Diagnosis

Several other conditions may be confused with Toxicodendron toxicity, and a careful history and physical examination are necessary to differentiate between them. Herpes zoster often presents as a vesiculopapular rash but follows a dermatomal pattern that doesn’t cross the midline of the body. It is also often preceded by pain in the affected area and would not have a history of environmental exposure. Phytophotodermatitis is another potential mimicker, as it follows a similar timeline. Differentiating factors include plant exposure on sun-exposed areas of the body and the absence of pruritus. Irritant dermatitis is usually sudden in onset and associated with exposure to metals or other irritating compounds with distinct dermal patterns. Other arthropod bites such as bed bugs (Cimex lectularius) or scabies (Sarcoptes scabiei) may present similarly and be pruritic but lack the appropriate timing and are typically non-vesicular. Scabies has a characteristic burrowing pattern, while bed bug bites tend to have a rapid onset in skin findings. 

Pertinent Studies and Ongoing Trials

Ongoing clinical trials are being performed by the University of Mississippi in conjunction with a biochemical company. Several patents have been issued with regards to vaccine development and initial phase 1 safety studies were completed in 2017.

Staging

Presenting symptoms vary in their onset depending upon initial or repeat exposure and consist of a linear appearing papulovesicular eruption of the dermis with erythema and pruritus.[12][36] As the rash begins to resolve, it is often followed by continued intense pruritis and excoriations. Repeat exposure can last 14 to 21 days, and care should be taken to treat any signs suggestive of secondary infection due to excoriations.[7] There is a small subset of the population who are hypersensitive to urushiol and present with rapid onset of widespread symptoms within a few hours. Hyperpigmentation can be a late finding and does not require treatment despite potentially lasting up to several months.

Toxicodendron dermatitis can be mild, moderate, or severe. Mild cases present mainly with localized or linear erythema and/or edema with minimal symptoms. Moderate to severe cases will have more diffuse involvement associated with severe pain, burning, and/or pruritus.

Prognosis

Prognosis is largely dependent upon the extent and duration of exposure. Outcomes are typically excellent as management is directed primarily at decreasing innate and adaptive responses. In rare cases of complications or severe exposure, management may be prolonged and require hospital admission.

Complications

Uncommon complications include secondary bacterial infection and skin hyperpigmentation. Secondary infections are most commonly due to Staphylococcus aureus or streptococci and should be treated appropriately with additional consideration of concurrent polymicrobial infection.[7] Hyperpigmentation of darker skin types is often self-limited with resolution within months. More severe symptoms are often associated with hypersensitive individuals or cases of aerosolized urushiol exposure. These cases should begin with airway assessment and management of any potential signs of anaphylaxis followed by systemic high dose corticosteroids. In rare circumstances, nephropathy has been reported with Toxicodendron dermatitis.[37]

Deterrence and Patient Education

Patients should be counseled regarding the identification of local Toxicodendron species and avoidance. If occupational exposure is encountered, proper protective equipment should be outlined with specific instructions to use vinyl gloves as urushiol can penetrate rubber or latex gloves.[8] As part of decontamination, all clothing and objects with potential exposure should be cleaned with warm water and detergents. There is evidence to alternatively support the use of bentonite, and other commercially available organoclay barrier creams, prior to exposure.[38][39] Current evidence does not support the use of desensitization programs.[40][41][42]

Pearls and Other Issues

The best prevention of Toxicodendron dermatitis is avoidance, followed by appropriate barriers and decontamination. Regional variations in plant structure often make identification challenging, making misidentification the most common pitfall. Poison ivy comprises a large percentage of exposures throughout North America and is the most commonly misidentified species.[43] Key points in the identification of poison ivy include leaves that are found in groups of three without the presence of thorns or jagged/scalloped edges. Management of exposure should begin by immediately washing affected skin with soap and water and early application of topical corticosteroids. In severe cases or where there is respiratory system involvement, hospital admission may be necessary. Of special note, several other species within the cashew/sumac family or Anacardiaceae have cross-reactivity with urushiol sensitized patients. Some of the more commonly known causes include exposure to the fruit or trees of mangos, cashew nuts, and ginkgo biloba.[44][45]

Enhancing Healthcare Team Outcomes

Communication between physicians and other professionals is essential in the management of these patients as they may present in a variety of clinical settings. Management should be followed primarily by a primary care provider or dermatologist as the mainstay of treatment is corticosteroids, which have many potential side effects. Evidence supporting the use of corticosteroids or other topical immunosuppressive’s is well documented and supported by a meta-analysis of randomized controlled trials (RCT) [Level 1]. Knowledge and understanding of management by nurses and pharmacists is also critical as they tend to be more readily accessible to patients and should be knowledgeable regarding potential complications and management. Outcomes are typically excellent with or without treatment, and patients should be given specific instructions regarding prevention, decontamination, and when to return if symptoms spread or worsen.[Level 4] If there is a concern for systemic or respiratory exposure, then patients should be admitted to the hospital for further observation and management.


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