Background

Berloque dermatitis is a phototoxic reaction induced by exposure to long-wave ultraviolet (UV) A (UV-A) radiation in the presence of bergapten (5-methoxypsoralen [5-MOP]), a furanocoumarin (furocoumarin) found in bergamot oil. Bergapten is the photoactive component of bergamot oil, which comes from the rind of the bergamot lime (Citrus bergamia) and has been a popular ingredient in perfumes and fragrances. The combined exposure to UVA and to bergapten induces an intensification of melanogenesis and hyperpigmentation (see the image below).

Hyperpigmented streaks on dorsa of hands of patient with bergapten phototoxicity

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Berloque dermatitis obtains its name from the French word berloque (German Berlock), meaning trinket or charm. Rosenthal coined the term in 1925 to describe pendantlike streaks of pigmentation on the neck, face, arms, or trunk. He suspected that they were due to fluid droplets, unaware that Freund in 1916 had described hyperpigmented macules due to sun exposure after the application of eau de cologne.

The phototoxic ingredient causing the pigmentation proved to be bergapten. Several cases were reported in the 1950s and 1960s following wider use of perfumes containing oil of bergamot and increased enthusiasm for sunbathing. Since the introduction of artificial oil of bergamot and the reduced use of the natural product in perfumes, berloque dermatitis has become rare.

Avoidance of the offending compound is the primary goal of treatment. If hyperpigmentation persists, hydroquinone is used. Laser therapy may be recommended for postinflammatroy hyperpigmentation, including berloque dermatitis.^[1]

Next: Pathophysiology

Pathophysiology

Phototoxicity or photoirritation is a chemically induced nonimmunologic acute skin irritation induced by exposure to light (usually within the UV-A spectrum, 320-400 nm).^[2] The skin response resembles exaggerated sunburn and requires no prior sensitization; it can be caused by a single simultaneous exposure to the chemical and the light source. The photoactive chemical may enter the skin via topical administration or via ingestion, inhalation, or parenteral administration. The reaction can be evoked in all subjects as long as the concentration of the chemical and the dose of light are sufficient.

In the case of berloque dermatitis, the phototoxic reaction is induced by the effect of long-wave UV-A radiation on bergapten (5-MOP; see the image below), which is known to be the only photoactive component of bergamot oil. The combination of bergapten and UV-A induces an intensification of melanogenesis and a corresponding increase in the number of functional melanocytes, which are more dendritic and dopa-positive. The distribution of melanosomes in keratinocyte changes from the aggregate to the nonaggregate form.

Molecular structure of 5-methoxypsoralen (5-MOP; bergapten)

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Next: Pathophysiology

Etiology

Bergapten (5-MOP) has been a popular ingredient in perfumes and fragrances. Aside from their obvious presence in cosmetics and toiletries (eg, toilet water, aftershave lotions, colognes, sunscreen lotions, and moisturizers), perfumes and fragrances also are found in soap, household cleaners, detergents, air fresheners, and a myriad of other everyday items.

Besides the bergamot lime, various other fruits and plants contain bergapten as a naturally occurring component (see Table 1 below). Examples include the common fig (Ficus carica), celery (Apium graveolens), lemon oil, the Tromso palm (Heracleum laciniatum),^[3] Queen Anne's lace (Ammi majus), and giant hogweed (Heracleum mantegazzianum).^[4] All these are capable of inducing bergapten phototoxicity, though they are not used in perfumes or fragrances and therefore are considered to be causes of phytophotodermatitis rather than berloque dermatitis.

Table 1. Plants Containing Bergapten (Open Table in a new window)

Family	Genus	Species	Common Name(s)
Umbelliferae (Apiaceae)	Ammi	majus	Queen Anne's lace
	Heracleum	laciniatum	Tromso palm
	Heracleum	sphondylium	Common hogweed, cow parsnip
	Heracleum	mantegazzianum	Giant hogweed
	Heracleum	hypoleucum
	Cymopterus	watsonii	Spring parsley
	Pastinaca	sativa	Parsnip
	Pastinaca	opaca
	Pastinaca	urens
	Apium	graviolens	Celery
Rutaceae	Citrus	bergamia	Bergamot lime
	Dictamnus	albus	Fraxinella, burning bush, gas plant
Moraceae	Ficus	carica	Fig

Next: Pathophysiology

Epidemiology

US and international statistics

The exact incidence of berloque dermatitis is unknown. In the United States, the use of bergapten-free fragrance formulations has rendered berloque dermatitis exceedingly rare. The US Hazardous Substances Act issued regulations stating that in products containing oil of bergamot, the concentration of the oil must not exceed 2%, or 62 ppm bergapten. Even lower concentrations have since been recommended (< 0.3% bergamot oil, 0.001% bergapten).

The use of bergapten-free bergamot oil has come to be almost universal in the United States; however, in some countries where bergamot oil continues to be used, berloque dermatitis remains a problem. Even in the United States, some cases still occur. In one report, a patient developed severe berloque dermatitis as a consequence of using a suntan booth immediately after applying some 40-year-old Shalimar perfume, which contained bergamot oil.

Age-, sex-, and race-related demographics

Berloque dermatitis usually occurs in adults, though it can occur in persons of any age who apply fragrances containing oil of bergamot.

Berloque dermatitis most commonly develops in females who wear fragrances containing oil of bergamot, but it may also develop in males who wear fragrances or fragrance-containing products (eg, as aftershave lotion).

No racial predilection has been established.

Clinical Presentation

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Kavli G, Raa J, Johnson BE, Volden G, Haugsbø S. Furocoumarins of Heracleum laciniatum: isolation, phototoxicity, absorption and action spectra studies. Contact Dermatitis. 1983 Jul. 9 (4):257-62. [QxMD MEDLINE Link].
Camm E, Buck HW, Mitchell JC. Phytophotodermatitis from Heracleum mantegazzianum. Contact Dermatitis. 1976 Apr. 2 (2):68-72. [QxMD MEDLINE Link].
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Holtz R. REACH and In Vitro Alternatives: Phototoxicity Testing. Cosmet Toilet. 2008 May. 123:61-3.
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Spielmann H, Balls M, Dupuis J, Pape WJ, Pechovitch G, de Silva O, et al. The International EU/COLIPA In Vitro Phototoxicity Validation Study: Results of Phase II (Blind Trial). Part 1: The 3T3 NRU Phototoxicity Test. Toxicol In Vitro. 1998 Jun 1. 12 (3):305-27. [QxMD MEDLINE Link].
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Spielmann H, Müller L, Averbeck D, Balls M, Brendler-Schwaab S, Castell JV, et al. The second ECVAM workshop on phototoxicity testing. The report and recommendations of ECVAM workshop 42. Altern Lab Anim. 2000 Nov-Dec. 28 (6):777-814. [QxMD MEDLINE Link].
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Media Gallery

Hyperpigmented streaks on dorsa of hands of patient with bergapten phototoxicity
Molecular structure of 5-methoxypsoralen (5-MOP; bergapten)
Bergapten-containing plants

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Table 1. Plants Containing Bergapten

Table 1. Plants Containing Bergapten

Family	Genus	Species	Common Name(s)
Umbelliferae (Apiaceae)	Ammi	majus	Queen Anne's lace
	Heracleum	laciniatum	Tromso palm
	Heracleum	sphondylium	Common hogweed, cow parsnip
	Heracleum	mantegazzianum	Giant hogweed
	Heracleum	hypoleucum
	Cymopterus	watsonii	Spring parsley
	Pastinaca	sativa	Parsnip
	Pastinaca	opaca
	Pastinaca	urens
	Apium	graviolens	Celery
Rutaceae	Citrus	bergamia	Bergamot lime
	Dictamnus	albus	Fraxinella, burning bush, gas plant
Moraceae	Ficus	carica	Fig

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Author

Ali Alikhan, MD Clinical Assistant Professor, Director of Clinical Trials, Residency Program Co-Director, Department of Dermatology, University of Cincinnati College of Medicine

Ali Alikhan, MD is a member of the following medical societies: American Academy of Dermatology, National Psoriasis Foundation, Cincinnati Dermatological Society, National Psoriasis Foundation, Ohio Dermatological Association

Disclosure: Nothing to disclose.

Coauthor(s)

Ai-Lean Chew, MBChB, MRCP Honorary Consultant, St John's Institute of Dermatology, Guy's and St Thomas' Hospital NHS Trust, UK and Locum Consultant, South London Healthcare NHS Trust, UK

Ai-Lean Chew, MBChB, MRCP is a member of the following medical societies: British Medical Association, Royal Society of Medicine, British Association of Dermatologists

Disclosure: Nothing to disclose.

Howard I Maibach, MD Professor and Vice Chairperson, Department of Dermatology, University of California, San Francisco, School of Medicine; Consulting Staff, University of California Hospitals

Howard I Maibach, MD is a member of the following medical societies: American Academy of Dermatology, American College of Forensic Examiners Institute, Pacific Dermatologic Association, American Contact Dermatitis Society, American Federation for Clinical Research, American College of Physicians, American Medical Association, California Medical Association, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Edward F Chan, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine

Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Emeritus Professor, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, American Contact Dermatitis Society, Association of Military Dermatologists, Association of Professors of Dermatology, American Dermatological Association, Women's Dermatologic Society, Medical Dermatology Society, Dermatology Foundation, Society for Investigative Dermatology, Washington DC Dermatological Society, Atlantic Dermatologic Society, Philadelphia Dermatological Society, Pennsylvania Academy of Dermatology, College of Physicians of Philadelphia

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Marjan Garmyn, MD, PhD Professor, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium; Chair and Adjunct Head, Department of Dermatology, University of Leuven, Belgium

Disclosure: Nothing to disclose.