Phytophototoxin Poisoning

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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.

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]

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:

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]

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]

Prognosis

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

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.

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] :

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]

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

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.

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.

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]

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:

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

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.

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.

Medication Summary

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

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

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

Class Summary

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

Hydrocortisone topical (Cortaid, Cortizone)

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.

Prednisone (Deltasone, Meticorten, Orasone)

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.

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.

Indomethacin (Indocin)

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

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.

Author

Toluwumi Jegede, MD, Resident Physician, Department of Emergency Medicine, State University of New York Downstate Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Antonia Quinn, DO, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Assistant Residency Director, Attending Physician, Department of Emergency Medicine, Kings County Hospital Center, SUNY Downstate Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

Disclosure: Nothing to disclose.

Chief Editor

Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

Disclosure: Nothing to disclose.

Additional Contributors

Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT, Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center

Disclosure: Nothing to disclose.

Acknowledgements

Michael Hodgman, MD Assistant Clinical Professor of Medicine, Department of Emergency Medicine, Bassett Healthcare

Michael Hodgman, MD is a member of the following medical societies: American College of Medical Toxicology, American College of Physicians, Medical Society of the State of New York, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Thomas Joseph Lydon, MD, PhD Consulting Staff, Section of Emergency Medicine, Dartmouth-Hitchcock Medical Center

Disclosure: Nothing to disclose.

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM Professor of Emergency Medicine, Education Officer, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine; Medical Director, Fast Track, Department of Emergency Medicine

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

William H Shoff, MD, DTM&H Director, PENN Travel Medicine; Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine

William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

References

  1. Matthews MR, VanderVelde JC, Caruso DM, Foster KN. Lemons in the Arizona Sunshine: The Effects of Furocoumarins Leading to Phytophotodermatitis and Burn-like Injuries. Wounds. 2017 Dec. 29 (12):E118-E124. [View Abstract]
  2. Pragya Nair. Dermatitis, Contact. Amber Atwater. StatPearls. Treasure Island (FL): StatPearls Publishing LLC; 2018 Jan.
  3. Melough MM, Lee SG, Cho E, Kim K, Provatas AA, Perkins C, et al. Identification and Quantitation of Furocoumarins in Popularly Consumed Foods in the U.S. Using QuEChERS Extraction Coupled with UPLC-MS/MS Analysis. J Agric Food Chem. 2017 Jun 21. 65 (24):5049-5055. [View Abstract]
  4. Bensasson RV, Land EJ, Salet C. Triplet excited state of furocoumarins: reaction with nucleic acid bases and amino acids. Photochem Photobiol. 1978 Mar. 27(3):273-80. [View Abstract]
  5. Pathak MA, Kramer DM. Photosensitization of skin in vivo by furocoumarins (psoralens). Biochim Biophys Acta. 1969 Nov 19. 195(1):197-206. [View Abstract]
  6. Solis RR, Dotson DA, Trizna Z. Phytophotodermatitis: a sometimes difficult diagnosis. Arch Fam Med. 2000 Nov-Dec. 9(10):1195-6. [View Abstract]
  7. Bassioukas K, Stergiopoulou C, Hatzis J. Erythrodermic phytophotodermatitis after application of aqueous fig-leaf extract as an artificial suntan promoter and sunbathing. Contact Dermatitis. 2004 Aug. 51(2):94-5. [View Abstract]
  8. Ivie GW, Holt DL, Ivey MC, et al. Natural toxicants in human foods: psoralens in raw and cooked parsnip root. Science. 1981 Aug 21. 213(4510):909-10. [View Abstract]
  9. Juckett G. Plant dermatitis. Possible culprits go far beyond poison ivy. Postgrad Med. 1996 Sep. 100(3):159-63, 167-71. [View Abstract]
  10. Massmanian A. Contact dermatitis due to Euphorbia pulcherrima Willd, simulating a phototoxic reaction. Contact Dermatitis. 1998 Feb. 38(2):113-4. [View Abstract]
  11. Moloney FJ, Parnell J, Buckley CC. Iatrogenic phytophotodermatitis resulting from herbal treatment of an allergic contact dermatitis. Clin Exp Dermatol. 2006 Jan. 31(1):39-41. [View Abstract]
  12. Sharma A, Goel HC. Some naturally occurring phytophototoxins for mosquito control. Indian J Exp Biol. 1994 Oct. 32(10):745-51. [View Abstract]
  13. Tunget CL, Turchen SG, Manoguerra AS, et al. Sunlight and the plant: a toxic combination: severe phytophotodermatitis from Cneoridium dumosum. Cutis. 1994 Dec. 54(6):400-2. [View Abstract]
  14. White W. Club Med dermatitis. N Engl J Med. 1986 Jan 30. 314(5):319-20. [View Abstract]
  15. Son JH, Jin H, You HS, Shim WH, Kim JM, Kim GW, et al. Five Cases of Phytophotodermatitis Caused by Fig Leaves and Relevant Literature Review. Ann Dermatol. 2017 Feb. 29 (1):86-90. [View Abstract]
  16. Bosanac SS, Clark AK, Sivamani RK. Phytophotodermatitis related to carrot extract-containing sunscreen. Dermatol Online J. 2018 Jan 15. 24 (1):[View Abstract]
  17. Raam R, DeClerck B, Jhun P, Herbert M. Phytophotodermatitis: The Other "Lime" Disease. Ann Emerg Med. 2016 Apr. 67 (4):554-6. [View Abstract]
  18. Bollero D, Stella M, Rivolin A, Cassano P, Risso D, Vanzetti M. Fig leaf tanning lotion and sun-related burns: case reports. Burns. 2001 Nov. 27(7):777-9. [View Abstract]
  19. Burnett JW, Nguyen TV. Phytophotodermatitis: differentiation from jellyfish stings. Australas J Dermatol. 1989. 30(2):101-2. [View Abstract]
  20. Centers for Disease Control and Prevention. Phytophotodermatitis among grocery workers--Ohio. MMWR Morb Mortal Wkly Rep. 1985 Jan 11. 34(1):11-3. [View Abstract]
  21. Chiarugi A, Nardini P, Borgognoni L, Brandani P, Crocetti E, Carli P. Clinico-pathological characteristics of familial melanoma in a Mediterranean population. Melanoma Res. 2008 Oct. 18(5):367-9. [View Abstract]
  22. Goskowicz MO, Friedlander SF, Eichenfield LF. Endemic "lime" disease: phytophotodermatitis in San Diego County. Pediatrics. 1994 May. 93(5):828-30. [View Abstract]
  23. Kerr AC, Muller F, Ferguson J, Dawe RS. Occupational carprofen photoallergic contact dermatitis. Br J Dermatol. 2008 Dec. 159(6):1303-8. [View Abstract]
  24. Ljunggren B. Severe phototoxic burn following celery ingestion. Arch Dermatol. 1990 Oct. 126(10):1334-6. [View Abstract]
  25. Mark KA, Brancaccio RR, Soter NA, Cohen DE. Allergic contact and photoallergic contact dermatitis to plant and pesticide allergens. Arch Dermatol. 1999 Jan. 135(1):67-70. [View Abstract]
  26. Maso MJ, Ruszkowski AM, Bauerle J, et al. Celery phytophotodermatitis in a chef. Arch Dermatol. 1991 Jun. 127(6):912-3. [View Abstract]
  27. Ozkol HU, Akdeniz N, Ozkol H, Bilgili SG, Calka O. Development of phytophotodermatitis in two cases related to Plantago lanceolata. Cutan Ocul Toxicol. 2012 Mar. 31(1):58-60. [View Abstract]
  28. Zhang R, Zhu W. Phytophotodermatitis due to chinese herbal medicine decoction. Indian J Dermatol. 2011 May. 56(3):329-31. [View Abstract]
  29. Carlsen K, Weismann K. Phytophotodermatitis in 19 children admitted to hospital and their differential diagnoses: Child abuse and herpes simplex virus infection. J Am Acad Dermatol. 2007 Nov. 57(5 Suppl):S88-91. [View Abstract]
  30. Coffman K, Boyce WT, Hansen RC. Phytophotodermatitis simulating child abuse. Am J Dis Child. 1985 Mar. 139(3):239-40. [View Abstract]
  31. Mehta AJ, Statham BN. Phytophotodermatitis mimicking non-accidental injury or self-harm. Eur J Pediatr. 2007 Jul. 166(7):751-2. [View Abstract]
  32. Mill J, Wallis B, Cuttle L, Mott J, Oakley A, Kimble R. Phytophotodermatitis: case reports of children presenting with blistering after preparing lime juice. Burns. 2008 Aug. 34(5):731-3. [View Abstract]
  33. Machado M, Vidal RL, Cardoso P, Coelho S. Phytophotodermatitis: a diagnosis to consider. BMJ Case Rep. 2015 Dec 23. 2015:[View Abstract]
  34. De Almeida Jr HL, Magalhaes Jorge V. The many faces of phytophotodermatitis. Dermatol Online J. 2008. 12:
  35. Hu Y, Wang D, Shen Y, Tang H. Photopatch Testing in Chinese Patients Over 10 Years. Dermatitis. 2016 May-Jun. 27 (3):137-42. [View Abstract]
  36. Rhodes LE. Topical and systemic approaches for protection against solar radiation-induced skin damage. Clin Dermatol. 1998 Jan-Feb. 16(1):75-82. [View Abstract]
  37. Sasseville D. Phytodermatitis. J Cutan Med Surg. 1999 Jul. 3(5):263-79. [View Abstract]

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

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

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

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 clearing some weeds in her yard. A phototoxic combination of sunlight and a psoralen-containing plant produced this bizarre linear vesicular eruption.

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

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 significant sun exposure. The combination of lime juice and sun exposure led to a drip-pattern blister formation on the dorsal forearm consistent with phytophotodermatitis. This picture clearly delineates the potential severity of phytophotodermatitis with extensive blister formation.

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

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 clearing some weeds in her yard. A phototoxic combination of sunlight and a psoralen-containing plant produced this bizarre linear vesicular eruption.

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

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 significant sun exposure. The combination of lime juice and sun exposure led to a drip-pattern blister formation on the dorsal forearm consistent with phytophotodermatitis. This picture clearly delineates the potential severity of phytophotodermatitis with extensive blister formation.

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

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

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

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