Berloque Dermatitis
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Berloque dermatitis obtains its name from the German word berlock or the French berloque, meaning trinket or charm. Rosenthal [1] coined the term in 1925 to describe pendantlike streaks of pigmentation on the neck, face, arms, or trunk. He suspected they were due to fluid droplets, unaware that Freund [2] 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, a component of oil of bergamot, derived from the rind of Citrus bergamia, the bergamot lime. Several cases were reported in the 1950s and 1960s following increased use of perfumes containing oil of bergamot and the passion 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. Note the image below.
Phototoxicity or photoirritation is a chemically induced nonimmunologic acute skin irritation requiring light (usually within the UVA spectrum, ie, 320-400 nm). The skin response resembles exaggerated sunburn and does not require prior sensitization; it can be caused by a single simultaneous exposure to the chemical and 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. For a discussion of phototoxicty, there are several recent reviews. [3]
In the case of berloque dermatitis, the phototoxic reaction is induced by the effect of long-wave ultraviolet (UVA) radiation on bergapten, or 5-methoxypsoralens, a furocoumarin now known to be the only photoactive component of bergamot oil (see the image below). The bergapten-UVA radiation combination 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 nonaggregate form.
The exact incidence of berloque dermatitis is unknown. In the Untied States, berloque dermatitis now is exceedingly rare due to the use of bergapten-free fragrance formulations. The US Hazardous Substances Act issued regulations stating that products containing oil of bergamot must not exceed 62 ppm bergapten, 2% bergamot oil. Following work performed by Marzulli and Maibach [4] and reported in 1970, even lower concentrations than this have been recommended (< 0.3% bergamot oil, equivalent to 0.001% bergapten), and bergapten-free bergamot oil is used almost always now in the Untied States. However, in some countries where bergamot oil continues to be used, berloque dermatitis remains a problem. Even in the Untied States, milder forms still are being observed. Recently, a patient was reported to have severe berloque dermatitis due to using a suntan booth immediately after applying some 40-year-old Shalimar perfume, which contained bergamot oil.
Apart from the bergamot lime, bergapten also is a component in other substances, inducing bergapten phototoxicity without the typical pendantlike appearance of berloque dermatitis. For instance, in Norway, bergapten phototoxicity has been reported due to Heracleum laciniatum and in Denmark due to Heracleum mantegazzianum (giant hogweed). [5, 6]
Precise information about racial predilection is not available.
Berloque dermatitis usually occurs in females who wear fragrances containing oil of bergamot, but males who wear fragrances or fragrance-containing products, such as aftershave lotion, also may develop berloque dermatitis.
Berloque dermatitis usually occurs in women, although it can occur in persons of any age who apply fragrances containing oil of bergamot.
Rosenthal O. Berloque dermatitis: Berliner Dermatologische Gesellschaft. Dermatologische Zeitschrift. 1925. 42:295.
Freund E. Uber bisher noch nicht bershriebene Kunstlicke hauverfarbungen. Dermatol Wochenschr. 1916. 63:931-3.
Elkeeb D, Elkeeb L, Maibach H. Photosensitivity: a current biological overview. Cutan Ocul Toxicol. 2012 Feb 17. [Medline].
Marzulli FN, Maibach HI. Perfume phototoxicity. J Soc Cosmetic Chem. 1970. 21:695-715.
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. [Medline].
Camm E, Buck HW, Mitchell JC. Phytophotodermatitis from Heracleum mantegazzianum. Contact Dermatitis. 1976 Apr. 2(2):68-72. [Medline].
Matsumoto N, Akimoto A, Kawashima H, Kim S. Comparative study of skin phototoxicity with three drugs by an in vivo mouse model. J Toxicol Sci. Jan 2010. 35:97-100. [Medline].
Zhai H, Wilhelm K, Maibach HI. Photoirritation (phototoxicity/phototoxic dermatitis). Dermatotoxicology. 7th ed. Washington, DC: Taylor & Francis; 2008. 209-14, 537-46.
Holtz R. REACH and In Vitro Alternatives: Phototoxicity Testing. Cosmet Toilet. 2008 May. 123:61-3.
Onoue S, Seto Y, Gandy G, Yamada S. Drug-induced phototoxicity; an early in vitro identification of phototoxic potential of new drug entities in drug discovery and development. Curr Drug Saf. 2009 May. 4(2):123-36. [Medline].
Onoue S, Seto Y, Oishi A, Yamada S. Novel methodology for predicting photogenotoxic risk of pharmaceutical substances based on reactive oxygen species (ROS) and DNA-binding assay. J Pharm Sci. 2009 Oct. 98(10):3647-58. [Medline].
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Spielmann H, Lovell WW, Hoelzle E, Johnson BE, Maurer T, Miranda MA, et al. In vitro phototoxicity testing. The report and recommendations of ECVAM workshop 2. Altern Lab Anim. 1994. 22:314-48.
Spielmann H, Muller 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. 28:777-814.
Spielmann H, Balls M, Brand M, Doring B, Holzhutter HG, Kalweit S, et al. EEC COLIPA project on in-vitro phototoxicity testing – first results obtained with BALB/C 3T3 cell phototoxicity assay. Toxicol In Vitro. 1994. 8:793-6.
Jones PA, King AV. High throughput screening (HTS) for phototoxicity hazard using the in vitro 3T3 neutral red uptake assay. Toxicol In Vitro. 2003 Oct-Dec. 17(5-6):703-8. [Medline].
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Kejlová K, Jírová D, Bendová H, Kandárová H, Weidenhoffer Z, Kolárová H, et al. Phototoxicity of bergamot oil assessed by in vitro techniques in combination with human patch tests. Toxicol In Vitro. 2007 Oct. 21(7):1298-303. [Medline].
Hans RK, Agrawal N, Verma K, Misra RB, Ray RS, Farooq M. Assessment of the phototoxic potential of cosmetic products. Food Chem Toxicol. 2008 May. 46(5):1653-8. [Medline].
Kligman AM, Willis I. A new formula for depigmenting human skin. Arch Dermatol. 1975 Jan. 111(1):40-8. [Medline].
Baran R, Maibach HI. Textbook of Cosmetic Dermatology. 4th ed. Boca Raton, Fla: CRC Press; 2010.
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.
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.
David F Butler, MD 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, Association of Military Dermatologists, American Academy of Dermatology, American Society for MOHS Surgery, Phi Beta Kappa
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.
William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, 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, Society for Investigative Dermatology
Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.
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.
Berloque Dermatitis
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