Phytophotodermatitis, also known as berloque dermatitis or margarita photodermatitis, is a

cutaneous Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different d ...

phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to

ultraviolet Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation ...

light (from the sun, for instance). Symptoms include

erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

blisters A blister is a small pocket of body fluid ( lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing ( friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

(

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

and/or bullae), and delayed

hyperpigmentation Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.James, William; Be ...

. Heat and moisture tend to exacerbate the reaction. A reaction may be elicited in any person who has been exposed to adequate amounts of both a

photosensitizer Photosensitizers produce a physicochemical change in a neighboring molecule by either donating an electron to the substrate or by abstracting a hydrogen atom from the substrate. At the end of this process, the photosensitizer eventually returns t ...

and ultraviolet 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

furanocoumarin 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 Rutace ...

s, which are activated by long-wavelength ultraviolet (UVA) light. The most toxic of these organic compounds are the linear furanocoumarins, so called since they exhibit a linear chemical structure.

Bergapten 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 ...

and xanthotoxin (also known as

methoxsalen 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. Met ...

), two linear furanocoumarins derived from

psoralen Psoralen (also called psoralene) 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 ...

, are invariably found in plants associated with phytophotodermatitis.

Symptoms and signs

A reaction typically begins within 24 hours of exposure and peaks at 48–72 hours after exposure. Initially, the skin turns red and starts to itch and burn. Large

blister A blister is a small pocket of body fluid ( lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing ( friction), burning, freezing, chemical exposure or infection. Most blisters are filled ...

s (or bullae) form within 48 hours. The blisters may leave black, brown, or purplish scars that can last for several years. This

of the skin is caused by the production of

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

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. Phytophotodermatitis can affect people of any age. In children, it has sometimes been mistaken for

child abuse Child abuse (also called child endangerment or child maltreatment) is physical, sexual, and/or psychological maltreatment or neglect of a child or children, especially by a parent or a caregiver. Child abuse may include any act or failure to a ...

Phototoxic species

Plants associated with phytophotodermatitis mainly come from four plant families: the carrot family (

Apiaceae 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 plan ...

), the citrus family (

Rutaceae The Rutaceae is a family, commonly known as the rueRUTACEAE
in BoDD – Botanical Der ...

), the mulberry family (

Moraceae The Moraceae — often called the mulberry family or fig family — are a family of flowering plants comprising about 38 genera and over 1100 species. Most are widespread in tropical and subtropical regions, less so in temperate climates; however ...

), and the legume family (

Fabaceae The Fabaceae or Leguminosae,International Code of Nomenc ...

Apiaceae

The carrot family

(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. False bishop's weed (''

Ammi majus ''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 ...

''), the world's major source of the linear furanocoumarin xanthotoxin, has been used since antiquity to treat

vitiligo Vitiligo is a disorder that causes the skin to lose its color. Specific causes are unknown but studies suggest a link to immune system changes. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmen ...

but accidental or inappropriate use of this plant can lead to phytophotodermatitis. Despite this danger, ''A. majus'' continues to be cultivated for its

s, 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 Celery (''Apium graveolens'') is a marshland plant in the family Apiaceae that has been cultivated as a vegetable since antiquity. Celery has a long fibrous stalk tapering into leaves. Depending on location and cultivar, either its stalks, ...

, parsnip, and

parsley Parsley, or garden parsley (''Petroselinum crispum'') is a species of flowering plant in the family Apiaceae that is native to the central and eastern Mediterranean region (Sardinia, Lebanon, Israel, Cyprus, Turkey, southern Italy, Greece, ...

have been reported to cause phytophotodermatitis among agricultural workers, grocery workers, and other occupational food handlers. Cited in McGovern and Barkley 2000, section&nbs
Phytophotodermatitis
Cited in McGovern and Barkley 2000, section&nbs

A number of phototoxic plant species in the carrot family have become

invasive species An invasive species otherwise known as an alien is an introduced organism that becomes overpopulated and harms its new environment. Although most introduced species are neutral or beneficial with respect to other species, invasive species adv ...

, including wild parsnip ('' Pastinaca sativa'') and the tall hogweeds of the genus '' Heracleum'', 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. Other plant species in the family Apiaceae that are associated with phytophotodermatitis include blister bush ('' Notobubon galbanum''), cow parsley (''

Anthriscus sylvestris ''Anthriscus sylvestris'', known as cow parsley, wild chervil, wild beaked parsley, Queen Anne's lace or keck, is a herbaceous biennial or short-lived perennial plant in the family Apiaceae (Umbelliferae), genus '' Anthriscus''. It is also some ...

''), wild carrot (''

Daucus carota ''Daucus carota'', whose common names include wild carrot, European wild carrot, bird's nest, bishop's lace, and Queen Anne's lace (North America), is a flowering plant in the family Apiaceae. It is native to temperate regions of the Old Wo ...

''), various species of the genus '' Angelica'' (e.g., Korean angelica ''

Angelica gigas ''Angelica gigas'', also called Korean angelica, giant angelica, purple parsnip, and dangquai, is a monocarpic biennial or short lived perennial plant from Korea and China. It inhabits forests, grasslands and banks of streams. The roots are used ...

''), and most (if not all) species of the genus '' Heracleum'' (esp. the tall invasive hogweeds and the cow parsnips, ''

Heracleum sphondylium ''Heracleum sphondylium'', commonly known as hogweed, common hogweed or cow parsnip, is a herbaceous perennial or biennial plant, in the umbelliferous family Apiaceae that includes fennel, cow parsley, ground elder and giant hogweed. It is nat ...

'' and '' Heracleum maximum'').

Rutaceae

The citrus family

Rutaceae The Rutaceae is a family, commonly known as the rueRUTACEAE
in BoDD – Botanical Der ...

is the second most widely distributed family of plants associated with phytophotodermatitis. Effet de la rue officinale

Numerous

citrus ''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is native to ...

fruits in the family Rutaceae exhibit phototoxic effects. Of these, perhaps the best known is lime. Phytophotodermatitis associated with limes is sometimes colloquially referred to as "lime disease," not to be confused with

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...

. In the family Rutaceae, the most severe reactions are caused by the

essential oil An essential oil is a concentrated hydrophobic liquid containing volatile (easily evaporated at normal temperatures) chemical compounds from plants. Essential oils are also known as volatile oils, ethereal oils, aetheroleum, or simply as the o ...

of the

bergamot orange ''Citrus bergamia'', the bergamot orange (pronounced ), is a fragrant citrus fruit the size of an orange, with a yellow or green color similar to a lime, depending on ripeness. Genetic research into the ancestral origins of extant citrus cult ...

(''Citrus bergamia''). Cited i
CIR 2013
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. Other plant species in the family Rutaceae that are associated with phytophotodermatitis include burning bush ('' Dictamnus albus''), common rue ('' Ruta graveolens''), and other plants in the genus ''

Ruta ''Ruta'' (commonly known as rue) is a genus of strongly scented evergreen subshrubs, 20–60 cm tall, in the family Rutaceae, native to the Mediterranean region, Macaronesia and southwest Asia. About ten species are accepted in the genus ...

''.

Moraceae

The mulberry family

is often associated with phytophotodermatitis. Multiple species in the genus ''

Ficus ''Ficus'' ( or ) is a genus of about 850 species of woody trees, shrubs, vines, epiphytes and hemiepiphytes in the family Moraceae. Collectively known as fig trees or figs, they are native throughout the tropics with a few species extendi ...

'' are known to exhibit phototoxic effects. Of these, 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 and western Asia, it has been cultivated since ancient times and is now widely grown throughout the worl ...

(''Ficus carica'') is well known and thoroughly documented. Like ''

'' in the family

, the common fig has been used since antiquity to treat

but the milky sap of fig leaves can cause phytophotodermatitis if used accidentally or inappropriately. A literature search revealed 19 cases of fig leaf-induced phytophotodermatitis reported between 1984 and 2012. In Brazil, several hospitals reported more than 50 cases of fig leaf-induced burn in one summer. 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'' Cited in Mitchell and Rook 1979. and ''

Brosimum gaudichaudii ''Brosimum'' is a genus of plants in the family Moraceae, native to tropical regions of the Americas. The breadnut ('' B. alicastrum'') was used by the Maya civilization for its edible nut. The dense vividly colored scarlet wood of '' B. par ...

''. 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: * Avoid contact with the plant family

citrus fruits ''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is nativ ...

, and other biological agents known to have phototoxic effects. Do not incinerate phototoxic plants and agents since this will serve to disperse the phototoxic substances more widely. * In outdoor situations where contact with phototoxic plants is likely, wear long pants and a long-sleeve shirt. Wear gloves and protective eyewear before handling such plants. * If protective clothing is not available, apply

sunscreen Sunscreen, also known as sunblock or sun cream, is a photoprotective topical product for the skin that mainly absorbs, or to a much lesser extent reflects, some of the sun's ultraviolet (UV) radiation and thus helps protect against sunbur ...

to exposed areas. This will provide some measure of protection if contact is made. * After an outdoor activity, take a shower or a bath as soon as possible. Wash your clothing and then wash your hands after handling the dirty clothes. A second line of defense is to avoid sunlight, so as not to activate a phototoxic substance: * If you come in contact with a phototoxic substance, ''immediately wash the affected area with soap and cold water, and avoid any further exposure to sunlight'' for at least 48 hours. Heat and moisture can worsen the skin reaction, which is why it’s important to wash the affected area with soap and cold water. * Stay indoors, if possible. Be sure to avoid light shining through windows. * If staying indoors is not an option, cover the affected area with sun protective clothing. * In lieu of sun-protective clothing, apply

to the affected areas after washing. Phytophotodermatitis is triggered by long wavelength ultraviolet light (called UVA) in the range of 320–380 nanometers, 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. 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 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 Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medica ...

may also prescribe a whitening cream to help treat the

and return the skin pigmentation back to normal. If the patient does not receive treatment, the affected sites may develop permanent hyperpigmentation or hypopigmentation.

History

The photosensitizing effects of plants have been known since antiquity. In Egypt around 2000 B.C., the juice of ''

'' "was rubbed on patches of

after which patients were encouraged to lie in the sun." In A.D. 50, the Greek physician

Dioscorides Pedanius Dioscorides ( grc-gre, Πεδάνιος Διοσκουρίδης, ; 40–90 AD), “the father of pharmacognosy”, was a Greek physician, pharmacologist, botanist, and author of '' De materia medica'' (, On Medical Material) —a 5-vo ...

observed that pigment would return to patches of vitiligo if "cataplasmed with ye leaves or ye boughes of ye Black Figge," Cited in McGovern and Barkley 2000, section&nbs
Phytophotodermatitis
an apparent reference to ''Ficus carica'', the

. These ancient practices acknowledged the

effects now known to accompany phytophotodermatitis. One of the earliest reports of plant-based

dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved c ...

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. Similarly in 1887 Sornevin reported that ''

'' caused dermatitis. However, neither of these early reports recognized the crucial role of ultraviolet radiation. "Berloque dermatitis" (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. Cited in Alikhan 2016. 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 Eau de Cologne (; German: ''Kölnisch Wasser'' ; meaning "Water from Cologne"), or simply cologne, is a perfume originating from Cologne, Germany. Originally mixed by Johann Maria Farina (Giovanni Maria Farina) in 1709, it has since come to be a ...

, a perfume infused with bergamot oil. Cited in McGovern and Barkley 2000, section&nbs
Phytophotodermatitis
It is now known that bergamot oil contains a significant amount of bergapten, a linear furanocoumarin that gets its name from the

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

Darrell Wilkinson Peter Edward Darrell Sheldon Wilkinson (7 August 1919 – 17 August 2009) was a leading figure in dermatology who was consultant at Aylesbury and High Wycombe, co-edited the first edition of Rook's 1968 '' Textbook of Dermatology'' and found ...

, a British dermatologist, gave an accurate description of the disease in the 1950s. 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." Cited by Mitchell and Rook (1979), p. 693. 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).

References

External links

* {{Radiation-related disorders Skin conditions resulting from physical factors