Phytophototoxin Poisoning

Practice Essentials

Phytophotodermatitis (PPD) is a phototoxic inflammatory dermal reaction mimicking a burn injury. It is induced by exposure to certain light-sensitizing plant products, most often furocoumarins, followed by exposure to long-wave ultraviolet light (UV-A 320-380 nm).^[1] Both components (plant and light) are required; neither agent alone can cause phytophotodermatitis.

The phototoxic inflammatory eruption usually appears 24 hours after exposure and peaks within 48-72 hours. Initial burning erythema is followed by blistering, epidermal necrosis (shown in the photo below), and desquamation. The acute process may be followed by postinflammatory irregular hyperpigmentation that can last weeks to months.

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Close-up view of vesicular linear streaks with morphology suggestive of scattered foci of epidermal necrosis.

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Pathophysiology

Phototoxic dermatitis is 1 of the 4 mechanisms of cutaneous inflammation produced by plant exposure. Plants may also cause irritant contact dermatitis, urticarial dermatitis, or allergic contact dermatitis.^[2]

Phytophotodermatitis (PPD) can occur through ingestion of the plant or, more commonly, through topical contact. Furocoumarins (bergaptol, xanthotal, 5-methoxypsoralens, 8 methoxypsoralens, angelican) are the major photoreactive essential plant oils involved in PPD. Plants are thought to produce furocoumarins for disease resistance.

Melough and collegues measured the total furocoumarin concentration in various foods and beverages and showed that grapefruit juice (95341 ng/g), fresh parsley (23215 ng/g), grapefruits (21858 ng/g), lime juice (14580 ng/g), limes (9151 ng/g), and lemon juice (1561 ng/g) had the greatest concentration of furocoumarins. Additional foods with high furocoumarin concentration included celeriac (also known as turnip-rooted celery, celery root, or knob celery) (396 ng/g), parsnips (335 ng/g), and carrots (68 ng/g).^[3]

Exposure to certain wavelengths of ultraviolet A (UV-A 320-380 nm) light enable furocoumarins to absorb energy, thereby altering reactivity of the molecular structure and causing it to attain a high-energy state.^[4] In the presence of oxygen, activated molecules form photoaddition products with DNA pyrimidine bases via DNA interstrand crosslinking at cytosine and thymidine with the furan ring of the psoralen and result in epidermal cell nucleic acid damage (type I reaction). In the absence of oxygen, activated furocoumarins can also produce oxygen, superoxide, and hydroxy radicals, which cause cellular membrane damage (type II reaction).

Both mechanisms result in arachidonic acid pathway activation, cellular dysfunction, and tissue destruction. When acute, the process is phototoxic.

The chronic presentation of phytophotodermatitis involves a photoallergic response; light-activated plant products act as haptens and produce a cell-mediated hypersensitivity response. Psoralens may not be primarily involved in this chronic mechanism of injury.^{[5, 6]}

Phytophototoxicity is amplified by humidity and perspiration.

Postinflammatory irregular hyperpigmentation may develop and can last weeks to months. Affected areas may remain hypersensitive to ultraviolet light for many years. In some individuals, these pigmentary changes may be the only portion of the process that is noticed, as the initial inflammatory reaction may be minimal. Irregular hyperpigmentation occurs via 2 mechanisms. Melanin is displaced from the epidermis into the dermis and ingested by melanophages. A larger number of melanocytes and melanosomes are distributed in the epidermis. Hyperpigmentation may be a protective mechanism to avoid additional solar injury.^[4]

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Etiology

Phytophotodermatitis (PPD) is induced by exposure to certain plants with subsequent exposure to sunlight. PPD can occur through ingestion of the plant or, more commonly, through topical contact.

Members of the following plant families are noted to cause a phytophotodermatitis reaction:

• Umbelliferae
• Leguminosae
• Apiaceae
• Rutaceae
• Moraceae
• Rosaceae
• Asteraceae
• Brassicaceae
• Clusiaceae
• Convolvulaceae
• Anacardiaceae
• Fabaceae
• Ranunculaceae

Common plants implicated in these families include celery, giant hogweed, angelica, parsnip, fennel, dill, anise, parsley, lime, lemon, rue, fig, mustard, scurf pea, and chrysanthemums.^{[7, 4, 8, 9, 10, 11, 12, 13, 14, 15]}  Photos of a couple of the common plants are shown below.

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Queen Anne's lace, a member of the Umbelliferae family of plants, is well known to produce a furocoumarin-induced phototoxic eruption.

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Ficus. The common fig contains furocoumarins and should be considered amidst the list of potential offending agents that cause phytophotodermatitis.

Oil of bergamot, extracted from the rind of fresh bergamot oranges (Citrus bergamia), is commonly used to scent commercial perfumes and colognes. Perfume-induced berloque dermatitis is a specific form of a phytophotodermatitis reaction; areas of skin reaction correspond to areas exposed to perfume.

A case of phytophotodermatitis caused by carrot extract-containing sunscreen has been reported.^[16]

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Epidemiology

Incidence varies per population and exposure. Individuals who handle produce or receive significant sunlight exposure (eg, field workers, farmers, gardeners, grocery workers, bartenders, vegetarians, persons who use tanning salons) are at an increased risk. Cases of phytophotodermatitis (PPD) more commonly occur in late spring and summer, when furocoumarins are found in increased concentration in plants and when individuals experience increased UV exposure.^[17]

No difference exists between United States and international occurrence. 

No racial predisposition is demonstrated. Cases are more frequently reported in fair-skinned individuals. Both sexes are at risk. PPD may be seen in all age groups.^[17]

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Prognosis

Significant long-term skin changes (hyperpigmentation, scarring) can occur with chronic exposure. Secondary wound infection may occur.

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Patient Education

Patients should be educated regarding plants that produce phytophototoxicity in order to avoid skin exposure. Patients may be counseled to wear gloves and skin coverings when their work necessitates ongoing exposure to these plant oils and to the sun. Patients should be educated regarding use of appropriate sunscreens when sun-exposed.

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History

The history is essential in making the diagnosis of phytophotodermatitis (PPD). All of the following patient items may provide essential information to the health care provider^{[7, 18, 19, 20, 21, 22, 23, 24, 25, 26, 14, 27, 28]} :

• Employment history
• Eating and drinking habits
• Recreational activities
• Tanning habits, including the use of herbal tanning lotions and citrus hair lighteners
• Prescription and over-the-counter medications
• Travel experience  

A phototoxic reaction can result from contact with a specific plant via skin exposure, or less commonly, ingestion, followed by exposure to sunlight. The rash often occurs in linear and odd patterns, including "handprints." The photos below show a reaction after exposure to a plant and sunlight. The second image is a close-up view of the rash. 

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A 37-year-old white woman presented to the clinic complaining of a rash on the medial part of her right thigh and left arm that was acquired after cle....

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Closer clinical view of bizarre angulated vesicular streaks, which occurred after contact with a plant and ultraviolet light exposure.

Onset of PPD is usually within 24-48 hours after sunlight exposure. Initial manifestations are often described as burning pain and erythema. These are followed by blistering, which occurs within 48 hours.

Pruritus is uncommon. The absence of pruritus helps distinguish PPD from allergic phytodermatitis (eg, toxicodendron dermatitis).

The irregular "burns" and handmark patterns produced, often without a clear-cut history, have been mistaken for child abuse. A good history is essential in differentiating the two in children.^{[29, 30, 31, 32]}

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Physical Examination

A usually sharp demarcation between normal covered skin and abnormal exposed skin is observed. The color of lesions may vary depending on the individual's underlying skin tone and the degree of exposure.

The initial manifestaiton is nonpruritic erythema of exposed areas. For example, a "burst" of skin lesions may been seen after contact with squirted lime juice or with sprayed plant materials onto an individual's uncovered arms or legs while utilizing a "weed whacker". Photos below show a rash caused by lime juice and subsequent sunlight exposure. The second photo was taken at follow-up visit.

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A 26-year-old female airline flight attendant exposed to lime while serving drinks en route to the Caribbean. During the Caribbean layover, she had si....

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The 2-month follow-up photo of the patient above demonstrates the potential postinflammatory pigmentation changes and scarring that may occur with sev....

Subsequently, edema develops, leading to vesicles, bullae, or both (usually within 24-72 h). Desquamation is possible.

Finally, dense hyperpigmentation may result from a melanocytic response. This can persist for several months. Finally, the affected area may remain hypersensitive to ultraviolet light for many years

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Laboratory Studies

Phytophotodermatitis (PPD) is a clinical diagnosis. No serum level assay for psoralens is available or appropriate. Clinical presentation is delayed, and systemic clearance of psoralens is complete. Laboratory data (eg, porphyrin levels) may be obtained to exclude other diagnoses.

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Other Tests

With yeast inhibition technique, plant extract is used to evaluate for presence of psoralens.

In individuals in whom the diagnosis is in question, referral to a dermatologist for photopatch testing may be warranted. Testing should include pesticides and plant allergens.

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Procedures

In individuals in whom the diagnosis is in question, referral to a dermatologist for a skin biopsy may be warranted. A skin biopsy may demonstrate epidermal hyperkeratosis, necrotic keratinocytes, "sunburn cells," epidermis spongiosus, and an inflammatory cell infiltrate. An increase in melanocytes is seen.^[34]

A photopatch test may be useful if the clinical picture does not clearly suggest phototoxicity rather than photoallergy.^[35]

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Emergency Department Care

If the patient presents shortly after exposure, the affected area should be washed with soap and water to remove plant sap. Protect the affected area from sunlight by covering and/or applying sunblock until at least 48 hours post exposure.

Treat inflammatory condition based on severity of symptoms, as follows:

• Treat mild reactions with cool wet dressings, topical steroids, and nonsteroidal anti-inflammatory drugs (NSAIDs)
• Severe reactions may require systemic steroids
• Topical application of 4% hydroquinone cream once or twice daily for several weeks may lessen hyperpigmentation; this is best done in conjunction with a dermatologist^{[36, 37]}

Patient reassurance that the problem will resolve once the offending agent has been removed is very helpful. Consultation with a dermatologist may be helpful.

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Prevention

Limit or avoid contact with the specific plant. Limit sun exposure. Regular use of a UV-A-blocking sunscreen may help to prevent phytophotodermatitis.

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Long-Term Monitoring

While phytophototoxicity cases may spontaneously resolve within 3 to 5 days, wound care may be necessary for up to 3 weeks for adequate treatment before clinical wound resolution.^[1]

Long-term exposure and severe reactions may result in hyperpigmentation requiring continued topical steroid treatment. If symptoms persist or worsen instead of improving, other illnesses, such as the primary light disorders, should be considered and further evaluation is warranted by a dermatologist.

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Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Useful measures include anti-inflammatory drugs and depigmenting agents.

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Hydroquinone (Claripel, Eldoquin-Forte, Solaquin-Forte)

• Dosing, Interactions, etc.

Clinical Context:  Suppresses melanocyte metabolic processes, especially enzymatic oxidation of tyrosine to 3,4-dihydroxyphenylamine. Exposure to sun reverses effects and causes repigmentation.

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Class Summary

These agents have been shown to be useful in the treatment of phytophototoxin plant poisoning.

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Hydrocortisone topical (Cortaid, Cortizone)

• Dosing, Interactions, etc.

Clinical Context:  Applied to skin and mucus membranes provides general anti-inflammatory activity via intracellular mechanisms. Absorption from skin and potency depend on modifications to drug structure, vehicle of application, and condition of exposed skin.

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Prednisone (Deltasone, Meticorten, Orasone)

• Dosing, Interactions, etc.

Clinical Context:  Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.

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Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

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Indomethacin (Indocin)

• Dosing, Interactions, etc.

Clinical Context:  Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation; inhibits prostaglandin synthesis.

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Class Summary

Although most NSAIDs are used primarily for their anti-inflammatory effects, they are effective analgesics and are useful for the relief of mild to moderate pain.

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