Phytophotodermatitis

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Phytophotodermatitis
Other namesberloque dermatitis, margarita photodermatitis, lime disease, lime phytodermatitis
Phytophotodermatitis from exposure to lime juice.jpg
Phytophotodermatitis caused by lime juice
Specialty Dermatology   OOjs UI icon edit-ltr-progressive.svg
Causes photosensitizer and UV-A light
Differential diagnosis skin burn; allergic contact dermatitis

Phytophotodermatitis, also known as berloque dermatitis, [1] [2] [3] margarita photodermatitis, [4] [5] lime disease [6] or lime phytodermatitis [6] is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent (such as lime juice) followed by exposure to ultraviolet A (UV-A) light (from the sun, for instance). Symptoms include erythema, edema, blisters (vesicles and/or bullae), and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.

Contents

A reaction may be elicited in any person who has been exposed to adequate amounts of both a photosensitizer and UV-A light. Phytophotodermatitis is not an immunologic response; no prior exposure to the photosensitizing agent is required.

The photosensitizing substances found in phototoxic plants belong to a class of chemical compounds called the furanocoumarins, which are activated by long-wavelength ultraviolet (UV-A) light. The most toxic of these organic compounds are the linear furanocoumarins, so called since they exhibit a linear chemical structure. Bergapten and xanthotoxin (also known as methoxsalen), two linear furanocoumarins derived from psoralen, are invariably found in plants associated with phytophotodermatitis. [2]

Symptoms and signs

A severe case of phytophotodermatitis in an 11-year-old boy. Phytophotodermatitis-Severe-Case.jpg
A severe case of phytophotodermatitis in an 11-year-old boy.

A reaction typically begins within 24 hours of exposure and peaks at 48–72 hours after exposure. [7] Initially, the skin turns red and starts to itch and burn. Large blisters (or bullae) form within 48 hours. [8] The blisters may leave black, brown, or purplish scars that can last for several years. This hyperpigmentation of the skin is caused by the production of melanin triggered by the furanocoumarins.

Although media reports have suggested that eye exposure to the agent can lead to temporary or permanent blindness, the risk of permanent blindness is not supported by existing research. [9]

Phytophotodermatitis can affect people of any age. In children, it has sometimes been mistaken for child abuse. [10]

Phototoxic species

Plants associated with phytophotodermatitis mainly come from four plant families: [2] [11] the carrot family (Apiaceae), the citrus family (Rutaceae), the mulberry family (Moraceae), and the legume family (Fabaceae).

Apiaceae

The carrot family Apiaceae (or Umbelliferae) is the main family of plants associated with phytophotodermatitis. Of all the plant species that have been reported to induce phytophotodermatitis, approximately half belong to the family Apiaceae. [12]

False bishop's weed ( Ammi majus ), the world's major source of the linear furanocoumarin xanthotoxin, has been used since antiquity to treat vitiligo [2] but accidental or inappropriate use of this plant can lead to phytophotodermatitis. [13] Despite this danger, A. majus continues to be cultivated for its furanocoumarins, [14] which are still used for the treatment of skin disease.

Numerous species in the family Apiaceae are cultivated as food products, some of which exhibit phototoxic effects. In particular, celery, parsnip, and parsley have been reported to cause phytophotodermatitis among agricultural workers, grocery workers, and other occupational food handlers. [15] [16] [17] [18] [19] [20] [2] [ excessive citations ]

A number of phototoxic plant species in the carrot family have become invasive species, including wild parsnip ( Pastinaca sativa) [21] [22] and the tall hogweeds of the genus Heracleum , [23] [24] namely, Persian hogweed ( Heracleum persicum ), Sosnowsky's hogweed ( Heracleum sosnowskyi ), and giant hogweed ( Heracleum mantegazzianum ). In particular, the public health risks of giant hogweed are well known. [25]

Other plant species in the family Apiaceae that are associated with phytophotodermatitis include blister bush ( Notobubon galbanum ), cow parsley ( Anthriscus sylvestris ), wild carrot ( Daucus carota ), various species of the genus Angelica (e.g., Korean angelica Angelica gigas ), and most (if not all) species of the genus Heracleum (esp. the tall invasive hogweeds and the cow parsnips, Heracleum sphondylium and Heracleum maximum ).

Rutaceae

The citrus family Rutaceae is the second most widely distributed family of plants associated with phytophotodermatitis.

Effect of common rue on skin Effet de la rue officinale.jpg
Effect of common rue on skin

Numerous citrus fruits in the family Rutaceae exhibit phototoxic effects. Of these, perhaps the best known is lime. [26] [27] [28] [29] Phytophotodermatitis associated with limes is sometimes colloquially referred to as "lime disease," [30] [31] not to be confused with Lyme disease.

In the family Rutaceae, the most severe reactions are caused by the essential oil of the bergamot orange (Citrus bergamia). [2] [32] Bergamot essential oil has a higher concentration of bergapten (3000–3600 mg/kg) than any other citrus-based essential oil, even lime oil, which contains 1700–3300 mg/kg of bergapten. [33]

Other plant species in the family Rutaceae that are associated with phytophotodermatitis include burning bush ( Dictamnus albus ), [34] common rue ( Ruta graveolens ), [35] [36] [37] [38] and other plants in the genus Ruta .

Moraceae

The mulberry family Moraceae is often associated with phytophotodermatitis. Multiple species in the genus Ficus are known to exhibit phototoxic effects. Of these, the common fig (Ficus carica) is well known and thoroughly documented.

Like Ammi majus in the family Apiaceae, the common fig has been used since antiquity to treat vitiligo [39] but the milky sap of fig leaves can cause phytophotodermatitis if used accidentally or inappropriately. [40] [41] [42] [43] [44] [45] A literature search revealed 19 cases of fig leaf-induced phytophotodermatitis reported between 1984 and 2012. [45] In Brazil, several hospitals reported more than 50 cases of fig leaf-induced burn in one summer. [44] In most cases, patients reportedly used the leaves of the fig plant for folk remedies, tanning, or gardening.

Other plant species in the family Moraceae that are associated with phytophotodermatitis include Ficus pumila [46] [47] and Brosimum gaudichaudii . [48] Like Ficus carica, the South American species Brosimum gaudichaudii has been shown to contain both psoralen and bergapten.

Prevention

The first and best line of defense against phytophotodermatitis is to avoid contact with phototoxic substances in the first place:

A second line of defense is to avoid sunlight, so as not to activate a phototoxic substance:

Phytophotodermatitis is triggered by long wavelength ultraviolet light (called UVA) in the range of 320–380 nanometers, [7] so the best sun-protective clothing and sunscreen products will block these wavelengths of UVA radiation.

In 2011, the U.S. Food and Drug Administration (FDA) established a "broad spectrum" test for determining a sunscreen product's UVA protection. [51] Sunscreen products that pass the test are allowed to be labeled as "Broad Spectrum" sunscreens, which protect against both UVA and UVB rays.

There is no equivalent test or FDA-approved labeling for sun-protective clothing. Some clothing is labeled with an Ultraviolet Protection Factor (UPF) but test results from Consumer Reports [52] suggest that UPF is an unreliable indicator of UV protection.

Treatment

Many different topical and oral medications may be used to treat the inflammatory reaction of phytophotodermatitis. A dermatologist may also prescribe a whitening cream to help treat the hyperpigmentation and return the skin pigmentation back to normal. If the patient does not receive treatment, the affected sites may develop permanent hyperpigmentation or hypopigmentation. [7]

History

The photosensitizing effects of plants have been known since antiquity. In Egypt around 2000 B.C., the juice of Ammi majus "was rubbed on patches of vitiligo after which patients were encouraged to lie in the sun." [2] In A.D. 50, the Greek physician Dioscorides observed that pigment would return to patches of vitiligo if "cataplasmed with the leaves or the boughes of the Black Figge," [39] an apparent reference to Ficus carica, the common fig. These ancient practices acknowledged the hyperpigmentation effects now known to accompany phytophotodermatitis.

One of the earliest reports of plant-based dermatitis was given by Chaumton in 1815, who noted that the outer rind and root of cow parsnip (a common name for any Heracleum species of plant) contained an acrid sap sufficiently strong to inflame and ulcerate the skin. [53] Similarly in 1887 Sornevin reported that Heracleum sphondylium caused dermatitis. However, neither of these early reports recognized the crucial role of ultraviolet radiation.

"Berloque dermatitis" [3] (from the French word "berloque" meaning trinket or charm) is a term coined by Rosenthal in 1925 to describe the pendant-like streaks of pigmentation observed on the neck, face, and arms of patients. [54] [2] He was unaware that, in 1916, Freund had correctly observed that these pigmentation effects were due to sun exposure after the use of Eau de Cologne, a perfume infused with bergamot oil. [55] It is now known that bergamot oil contains a significant amount of bergapten, [2] a linear furanocoumarin that gets its name from the bergamot orange.

In 1937, dermatitis from Heracleum mantegazzianum was reported by Miescher and Burckhardt who suspected the possibility of light sensitization. [56] A few years later, Kuske confirmed this hypothesis. [57] [58] In 1942, Klaber introduced the term "phytophotodermatitis" to emphasize that both plants and light were required to affect a reaction. [59] [29]

Darrell Wilkinson, a British dermatologist, gave an accurate description of the clinical entity in the 1950s. [60] [61] In 1961, Efremov reported 357 cases of phytophotodermatitis from Heracleum dulce (sweet cow parsnip). He "noted the requirement for sunlight in evoking the dermatitis since inunction of the juice of the plant without exposure to sunlight was harmless." [62] Between 1962 and 1976, numerous reports of phytophotodermatitis from giant hogweed ( Heracleum mantegazzianum ) were reported. By 1980, the photosensitizing effects of various plant species had become well known (as evidenced by the comprehensive work of Mitchell and Rook [63] ).

See also

Related Research Articles

<span class="mw-page-title-main">Apiaceae</span> Family of flowering plants

Apiaceae or Umbelliferae is a family of mostly aromatic flowering plants named after the type genus Apium and commonly known as the celery, carrot or parsley family, or simply as umbellifers. It is the 16th-largest family of flowering plants, with more than 3,800 species in about 446 genera, including such well-known and economically important plants as ajwain, angelica, anise, asafoetida, caraway, carrot, celery, chervil, coriander, cumin, dill, fennel, lovage, cow parsley, parsley, parsnip and sea holly, as well as silphium, a plant whose exact identity is unclear and which may be extinct.

<span class="mw-page-title-main">Lime (fruit)</span> Citrus fruit

A lime is a citrus fruit, which is typically round, green in color, 3–6 centimetres (1.2–2.4 in) in diameter, and contains acidic juice vesicles.

<i>Heracleum</i> (plant) Genus of flowering plants in the celery family

Heracleum is a genus of biennial and perennial herbs in the carrot family Apiaceae. They are found throughout the temperate northern hemisphere and in high mountains as far south as Ethiopia. Common names for the genus or its species include hogweed and cow parsnip.

<i>Heracleum maximum</i> Species of flowering plant

Heracleum maximum, commonly known as cow parsnip, is the only member of the genus Heracleum native to North America. It is also known as American cow-parsnip, Satan celery, Indian celery, Indian rhubarb, poison turnip or pushki.

<i>Heracleum mantegazzianum</i> Species of flowering plant

Heracleum mantegazzianum, commonly known as giant hogweed, is a monocarpic perennial herbaceous plant in the carrot family Apiaceae. H. mantegazzianum is also known as cartwheel-flower, giant cow parsley, giant cow parsnip, or hogsbane. In New Zealand, it is also sometimes called wild parsnip or wild rhubarb.

<span class="mw-page-title-main">Photodermatitis</span> Skin condition

Photodermatitis, sometimes referred to as sun poisoning or photoallergy, is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure. The second and subsequent exposures produce photoallergic skin conditions which are often eczematous. It is distinct from sunburn.

<span class="mw-page-title-main">Bergamot orange</span> Citrus fruit

Citrus bergamia, the bergamot orange, is a fragrant citrus fruit the size of an orange, with a yellow or green colour similar to a lime, depending on ripeness.

<span class="mw-page-title-main">Phototoxicity</span> Chemically-induced skin irritation following exposure to light

Phototoxicity, also called photoirritation, is a chemically induced skin irritation, requiring light, that does not involve the immune system. It is a type of photosensitivity.

<span class="mw-page-title-main">Methoxsalen</span> Chemical compound

Methoxsalen sold under the brand name Oxsoralen among others, is a medication used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to ultraviolet (UVA) light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Levels of individual patient PUVA exposure were originally determined using the Fitzpatrick scale. The scale was developed after patients demonstrated symptoms of phototoxicity after oral ingestion of methoxsalen followed by PUVA therapy. Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically.

<span class="mw-page-title-main">Psoralen</span> Chemical compound

Psoralen is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone. Psoralen occurs naturally in the seeds of Psoralea corylifolia, as well as in the common fig, celery, parsley, West Indian satinwood, and in all citrus fruits. It is widely used in PUVA treatment for psoriasis, eczema, vitiligo, and cutaneous T-cell lymphoma; these applications are typically through the use of medications such as Methoxsalen. Many furanocoumarins are extremely toxic to fish, and some are deposited in streams in Indonesia to catch fish.

<i>Heracleum sphondylium</i> Species of flowering plant in the celery family Apiaceae

Heracleum sphondylium, commonly known as hogweed or common hogweed, is a herbaceous perennial plant in the carrot family Apiaceae, which includes fennel, cow parsley, ground elder and giant hogweed. It is native to most of Europe, western Asia and northern Africa, but is introduced in North America and elsewhere. Other common names include cow parsnip or eltrot. The flowers provide a great deal of nectar for pollinators.

<i>Ammi majus</i> Species of plant

Ammi majus, commonly called bishop's flower, false bishop's weed, laceflower, bullwort, etc., is a member of the carrot family Apiaceae. The plant, which has white lace-like flower clusters, has a large distribution through Southern Europe, North Africa and West and Central Asia, though it is hypothesized to be native to the Nile River Valley.

<span class="mw-page-title-main">Furanocoumarin</span> Class of organic chemical compounds

The furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. Most of the plant species found to contain furanocoumarins belong to a handful of plant families. The families Apiaceae and Rutaceae include the largest numbers of plant species that contain furanocoumarins. The families Moraceae and Fabaceae include a few widely distributed plant species that contain furanocoumarins.

Heracleum persicum, commonly known as Persian hogweed or by its native name Golpar is a species of hogweed, a perennial herbaceous plant in the carrot family Apiaceae. It grows wild in humid mountainous regions in Iran and some adjacent areas. Having been introduced in the 1830s, it has spread across Scandinavia. It is now very common in northern Norway, where one of its names is Tromsø palm. The plant has also been spotted in Sweden. In Finland, it has been declared an invasive species.

<span class="mw-page-title-main">Bergapten</span> Chemical compound

Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. In the family Rutaceae, various Citrus species contain significant amounts of bergapten, especially the bergamot orange, the micrantha, and certain varieties of lime and bitter orange.

<span class="mw-page-title-main">Fig</span> Species of flowering plant known as the common fig

The fig is the edible fruit of Ficus carica, a species of small tree in the flowering plant family Moraceae, native to the Mediterranean region, together with western and southern Asia. It has been cultivated since ancient times and is now widely grown throughout the world. Ficus carica is the type species of the genus Ficus, containing over 800 tropical and subtropical plant species.

<i>Heracleum sosnowskyi</i> Species of flowering plant

Heracleum sosnowskyi, or Sosnowsky's hogweed, is a monocarpic perennial herbaceous flowering plant in the carrot family Apiaceae. Its native range includes the central and eastern Caucasus regions of Eurasia and extends into the southern Caucasus region called Transcaucasia. The native ranges of Heracleum sosnowskyi and H. mantegazzianum, a close relative, overlap in the Caucasus region. Sosnowsky's hogweed is now a common weed in the Baltic States, Belarus, Russia, Ukraine, and Poland.

<span class="mw-page-title-main">Angelicin</span> Chemical compound

Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarin.

The micrantha is a wild citrus from the papeda group, native to southern Philippines, particularly islands of Cebu and Bohol. Two varieties are recognized: small-flowered papeda, locally known as biasong, and small-fruited papeda or samuyao.

<span class="mw-page-title-main">Bergamot essential oil</span> Cold-pressed essential oil

Bergamot essential oil is a cold-pressed essential oil produced by cells inside the rind of a bergamot orange fruit. It is a common flavoring and top note in perfumes. The scent of bergamot essential oil is similar to a sweet light orange peel oil with a floral note.

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