When Scientists Get It Wrong

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For the most part, scientific research and analysis is an exhaustive, almost pedantic process that attempts to investigate factors that may or may not influence a particular outcome. This usually involves careful consideration of previous studies and their findings. The next step is usually establishing a set of research questions and hypotheses, followed by a careful design of experimental methods, which are then rigorously analysis and reported.

In addition, scientific research proposes that methodologies of any investigation are presented accurately enough so that replication of the experiment by other researchers wishing to test the reported outcomes is possible.

The following journal article released by the American Academy of Dermatology, Inc. is an example of researchers assuming cause and effect without testing of any kind or consideration of possible alternative causes.

It does not propose possible investigations that need to be carried out in order to test their hypothesis nor does it propose a clinical study or in fact any further study at all. It does propose however that because of their observations of only 2 cases, which may have been exposed to the essential oil of Bergamot that resulted in adverse skin reactions, that ... a necessity for strict governmental surveillance and scrutiny of these increasingly popular preparations is implemented.

This is preposterous and totally against every scientific rule of investigation. Read this article and judge for yourself.

Accidental bullous phototoxic reactions to bergamot aromatherapy oil

Steven Kaddu, MD, Helmut Kerl, MD, and Peter Wolf, MD Graz, Austria

Brief reports J AM ACAD DERMATOL SEPTEMBER 2001

Abstract

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that has a pleasant, refreshing scent; until a few years ago it had been widely used as an ingredient in cosmetics but was restricted or banned in most countries because of certain adverse effects. More recently, oil of bergamot preparations have been gaining renewed popularity in aromatherapy. Oil of bergamot possesses photosensitive and melanogenic properties because of the presence of furocoumarins, primarily bergapten (5-methoxypsoralen [5-MOP). However, 5-MOP is also potentially phototoxic and photomutagenic. Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil. We describe two patients with localized and disseminated bullous phototoxic skin reactions developing within 48 to 72 hours after exposure to bergamot aromatherapy oil and subsequent ultraviolet exposure. One patient (case 2) had no history of direct contact with aromatherapy oil but developed bullous skin lesions after exposure to aerosolized (evaporated) aromatherapy oil in a sauna and subsequent UVA radiation in a tanning salon. This report highlights the potential health hazard related to the increasing use of psoralen-containing aromatherapy oils.

Comment: In the paragraph above the publishers clearly state that the 2nd case actually had no direct contact with the supposed aerosolized aromatherapy oil. They also report (source not given) that the oil of bergamot has gained popularity and despite its increase in use, only 2 cases of phototoxic reactions have been reported. This should raise the question of what, other than bergamot oil, may be the cause of the phototoxic reaction in the 2 cases, shouldn?t it?

Introduction

Oil of bergamot is an extract from the rind of bergamot orange (Citrus aurantium ssp bergamia) that is grown mainly in southwestern Italy. Because oil of bergamot has a pleasant, refreshing scent and easily blends into perfume formulations, it had long been used as an ingredient in cosmetics until a few years ago when its use in perfumery was restricted or banned in most countries because of the report of adverse effects, primarily phototoxicity and Berloque dermatitis.1 More recently, oil of bergamot is gaining renewed popularity in aromatherapy.2 The photosensitizing and melanogenic properties of oil of bergamot are due to the presence of furocoumarins, mainly bergapten (5-methoxypsoralen [5-MOP).3-5 Apart from potential phototoxic effects, 5-MOP has also been shown to be photomutagenic and photocarcinogenic.6-8 Consequently in Europe, 5-MOP?containing cosmetics have been banned or restricted to certain concentrations. However, currently there are no official limits to 5-MOP concentrations in aromatherapy oils and no strict legal requirement for placing warning labels on these products in some countries.

Comment: While 5-MOP in isolation may have been shown to be potentially photomutagenic and photocarcinogenic, the pure essential oil of Bergamot (used as a 100% pure essential oil, not testing isolated, extracted ingredients) has not been shown to be photocarinogenic.

It must be said, that many substances including Bergamot oil do cause photosensitivity, for example Hypericum oil may also cause photosensitivity.

In this report, we describe two patients in whom bullous phototoxic reactions developed after unintended contact to bergamot aromatherapy oil and subsequent UVA exposure in sunlight in one patient and in a tanning salon in the other.

CASE REPORTS

Case 1

A 54-year-old woman of Fitzpatrick skin type III presented with painful, red, edematous, sharply demarcated areas with bullae and crusting on the face in a butterfly-like distribution (Fig 1). She gave a history of having unsuspectingly used a bergamot aromatherapy oil preparation 3 days earlier and subsequently stayed outdoors for several hours on a sunny day. She denied a history of using any other creams or taking any medications.

Comment: The patient may not have used a bergamot aromatherapy oil preparation or taken any medication, however, is it not possible that this patient came in contact with an allergen during the 3 days which could have caused the same reaction? Was this investigated?

I am not claiming that it was not the Bergamot oil, however I am suggesting that other possibilities do not appear to have been investigated or considered.

A sample of bergamot aromatherapy oil, which the patient had used, was available for analysis of 5-MOP concentration. High-performance liquid chromatography (HPLC) performed on the aromatherapy oil preparation revealed a very high 5-MOP concentration of 2400 ppm, well above 5-MOP levels officially permitted in cosmetics and tanning agents (0.1 ppm) in Austria.

The patient was treated with a topical steroid cream. Within 7 days, the skin lesions had improved significantly, except for the persistence of mild swelling and blistering on some areas of her face. These lesions also resolved over the next 2 weeks without any complications. The patient was instructed to avoid sun exposure for the next few weeks to prevent post-inflammatory hyperpigmentation. Follow-up examination at 1 year revealed no residual hyperpigmentation on the face in the previously affected areas.

Comment: One has to ask whether the so-called Aromatherapy oil of Bergamot was indeed a 100% pure essential oil of Bergamot, as the label shown in the illustration (not provided here) does not show a manufacturers name or any indication of purity.

Also, I would be interested to read whether the analysis of other brands of Bergamot aromatherapy oil showed similar concentrations of 5-MOP? After all isn?t replication one of the key principles in scientific testing?

At the top of the label in the picture provided, it can be discerned that 100g would appear to be the content of the bottle. Essential oils, however, are liquid and are not sold per gram rather they are sold in milliliters. So the question ?is this a cream?? needs to be asked.

The researchers are not making any comment as to whether this preparation was synthetic/artificial or a 100% pure essential oil. Or whether it contained other ingredients in addition to Bergamot oil.

Furthermore, Bergamot oil is traditionally used in Aromatherapy forits reputed strong antiseptic effect and its affinity for the respiratory, digestive and urinary systems, it has also been used for a variety of infections and inflammations of these areas. One has to ask, why was this patient using it on her face?

Bergamot oil, like most essential oils, should never be used undiluted and especially not on sensitive skin such as facial skin. This would be spelled out on the label, if this product were indeed made by a reputable manufacturer.

Did the patient not read the label? Or was this information not on the label? The researchers do not make any mention of indications, contra-indications or warnings provided on the label of the product.

Case 2

A 41-year-old woman with Fitzpatrick skin type II presented with disseminated, painful, red, edematous, sharply demarcated areas with bullae mainly on the face, neck, arms, palms, and thighs. Smaller erythematous lesions displayed a linear distribution. She gave a history of a visit to a sauna 2 days previously where she was exposed to a bergamot aromatherapy oil preparation. According to the patient, the aromatherapy oil, initially dissolved in water, was poured on a hot stone to vaporize for inhalation. Within a few minutes, the patient was exposed to UVA radiation in an adjacent tanning salon. The skin lesions developed gradually within 48 to 72 hours. The patient denied a history of taking medications before her visit to the tanning salon. She was treated with a topical steroid cream and oral analgesics and was instructed to avoid sun exposure.

Significant improvement was observed within 5 days except for the persistence of swollen and blistered areas of the neck and palms, which also resolved after several days, leaving no residual hyperpigmentation.

Comment: Again one has to wonder as to the purity of the essential oil used, as it is common practice to use fragrant (often synthetic) oils to enhance an atmosphere in spas and other venues of this type. To simply assume that the Bergamot oil was the cause in this and the previous case is a big assumption.

In the 2nd case, considering the small isolated areas that became irritated, one would have to question the implication of Bergamot oil in the first place. If indeed the Bergamot oil, vaporized into the air through exposure to hot rocks was responsible, why were the skin reactions so isolated and small? Would it not be more reasonable to see much larger areas of skin react?

It is my opinion that the Bergamot oil used in both these cases was neither pure nor applied in the correct manner and may indeed not even be responsible for the skin reactions experienced by the 2 patients.

DISCUSSION

The use of aromatherapy oil has increased in recent years, primarily because of a growing interest in aromatherapy, a form of alternative medicine involving application of essential oils often in combination with massage to achieve therapeutic effects.9 Despite the growing popularity, to our knowledge there are only two reports documenting accidental phototoxicity to oil of bergamot?containing aromatherapy preparations.4,10

Phototoxic reactions in our two cases developed within 48 to 72 hours after contact with bergamot aromatherapy oil and UV exposure. This time interval is consistent with that of phototoxic reactions arising after local application or ingestion of psoralens.11,12 Conversely, phototoxic reactions from other substances, such as phenothiazines, have a relatively shorter induction time interval. Therefore this report emphasizes the importance of considering the possibility of a phototoxic reaction to bergamot aromatherapy oil in all patients presenting with bullous lesions within a few days after a visit to a sauna and tanning salon or after contact with aromatherapy oil.

The skin lesions of case 1 occurred exclusively on the face, consistent with a local phototoxic reaction to oil of bergamot. However, in case 2 the lesions

were disseminated, some of which displayed a linear distribution. The severity of phototoxic reactions to oil of bergamot have been shown to depend on several

factors, including vehicle used, skin site, interval between application of psoralen and irradiation, hydration of the skin, and the degree of constitutive or sun-induced pigmentation.12 In this case, high hydration of the skin from vaporized water in the sauna may have played a special role by increasing local penetration of psoralens. Localization of the skin lesions at different body sites may have been influenced by mechanical factors. Similar phototoxic lesions displaying a linear arrangement have also been observed in another case of phototoxic reaction to aromatherapy oil.3

Long-term follow-up in our two cases showed no evidence of hyperpigmentation in previously affected areas. This observation implies that in cases of phototoxic reactions to bergamot aromatherapy oil, hyperpigmentation such as that occurring in Berloque dermatitis might be prevented by the use of topical steroid creams and subsequent avoidance of sun exposure.

In this report, we have highlighted yet another adverse reaction related to sunbeds, especially those with adjacent saunas in which bergamot aromatherapy

oil is applied. In addition to the possible link of the use of UVA-tanning devices to melanoma,13 several authors have also reported several acute cutaneous

reactions including burns, erythema, pruritus, polymorphous light eruption, as well as phototoxic and photoallergic reactions.14-18 Accidental phototoxic burns occurring after UVA exposure have been observed after local application of psoralen-containing cosmetics or ingestion of psoralen-containing food and medications.16,19,20 Severe, extensive, life threatening phototoxic reactions, such as the case of a woman who died of a massive phototoxic skin reaction, have been described after ingestion of food and medication containing psoralen and subsequent exposure to artificial UV radiation.16 Despite health education and warnings about possible short- and long-term harmful effects, tanning salons are still popular in Europe.

In conclusion, our two cases provide evidence that commercially available bergamot aromatherapy oil may cause serious bullous phototoxic reactions. In

our opinion, there is a need for the public to be made more aware of these potential dangers and a necessity for strict governmental surveillance and scrutiny of these increasingly popular preparations.

Comment: Sorry, but there is absolutely no evidence what so ever in this report to conclusively show that Bergamot oil was indeed the causative factor to these skin reactions. At best the authors could suggest is that a scientifically sound study be proposed to investigate the possibility that 100% pure Bergamot oil can indeed cause any adverse skin reaction, if used in the manner suggested by trained clinical Aromatherapists/Herbalists.

Some other questions that should have been considered by the authors include:

  • Investigation of presents of pesticide in the preparations used;
  • Investigation of present of herbicides in the preparations used;
  • Investigation of other constituents (not part of 100% pure essential oil of Bergamot) in the product(s) such as synthetic agents and other ingredients;
  • Reporting on the amount used by the woman reported on in Case 1 and whether the oil was applied in a diluted form as would be suggested by the Aromatherapist how sold her the product;
  • Reason for the use of Bergamot oil on the face in Case 1;
  • Sensitivity of both patients to other citrus fruit extracts/allergy to citrus?

These are just some of the questions that need to be asked and carefully researched before any conclusions can be made. It is my opinion that this research is inadequate and of little use as it does not quantify its findings nor provide any clinical testing or provide evidence of Bergamot oil being the causative factor for either of the 2 Cases reported.

Therefore, in my opinion, the authors? conclusions are premature and baseless.

We thank Dr W. Ramer (Gerot Pharmazeutika, Vienna, Austria) for performing HPLC analysis on 5-MOP levels of the oil of bergamot preparation.

REFERENCES USE IN ORIGINAL ARTICLE

1. Zaynoun ST,Aftimos BA,Tenekjian KK,Kurban AK. Berloque dermatitis: a continuing cosmetic problem. Contact Dermatitis 1981;7:111-6.

2. Guenther E. The essential oils. Vol 3. Princeton (NJ): van Nostrand Co; 1958. p. 260.

3. Makki S,Treffel P,Humbert P,Agache P. High-performance liquid chromatographic determination of citropten and bergapten in suction blister fluid after solar product application in humans. J Chromatogr 1991:563:407-13.

4. Clark SM, Wilkinson SM. Phototoxic contact dermatitis from 5-methoxypsoralen in aromatherapy oil. Contact Dermatitis 1998;38:289-90.

5. Levine N, Don S,Owens C, Rogers DT, Kligman AM, Forlot P. The effects of bergapten and sunlight on cutaneous pigmentation. Arch Dermatol 1989;125:1225-30.

6. Ashwood-Smith MJ, Poulton GA, Barker M, Mildenberger M. 5-Methoxypsoralen, an ingredient in several suntan preparations, has lethal mutagenic and clastogenic properties. Nature 1980;285:407-9.

7. Blog FB, Szabo G. The effects of psoralen and UVA (PUVA) on epidermal melanocytes of the tail of C57BL mice. J Invest Dermatol 1979;73:533-7.

8. Young AR,Walker SL, Kinley JS, Plastow SR,Averbeck D, Morliere P, et al. Phototumorigenesis studies of 5-methoxypsoralen in bergamot oil: evaluation and modification of risk of human use in albino mouse skin model. J Photochem Photobiol B 1990;7: 231-50.

9. Price S. Practical aromatherapy: how to use essential oils to restore vitality.Wellingborough (UK): Thorsons; 1983.

10. Tisserand R, Balacs T. Essential oil safety: a guide for health care professionals.New York: Churchill-Livingstone; 1995.

11. Arora SK, Willis I. Factors influencing methoxsalen phototoxicity in vitiliginous skin. Arch Dermatol 1976;112:327-32.

12. Zaynoun ST, Johnson BE,Frain-Bell W. A study of oil of bergamot and its importance as a phototoxic agent. Contact Dermatitis 1977;3:225-39.

13. Lim HW,Cooper K.The health impact of solar radiation and prevention strategies: report of the Environment Council, American Academy of Dermatology. J Am Acad Dermatol 1999; 41:81-99.

14. Devgun MS, Johnson BE, Paterson CR. Tanning, protection against sunburn and vitamin D formation with a UV-A ?sunbed.? Br J Dermatol 1982;107:275-84.

15. Rivers JK, Norris PG, Murphy GM, Chu AC,Midgley G, Morris J, et al. UVA sunbeds: tanning, photoprotection, acute adverse effects and immunological changes. Br J Dermatol 1989;120: 767-77.

16. Ljunggren B. Severe phototoxic burn following celery ingestion. Arch Dermatol 1990;126:1334-6.

17. Bruyneel-Rapp F,Dorsey SB,Guin JD.The tanning salon: an area survey of equipment, procedures, and practices. J Am Acad Dermatol 1988;18:1030-8.

18. Cohen HB, Bergstresser PR. Inadvertent phototoxicity from home tanning equipment. Arch Dermatol 1994;130:804-6.

19. Nettelblad H,Vahlqvist C,Krysander L, Sjoberg F.Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn injury. Burns 1996;22:633-5.

20. Bickers DR, Epstein JH, Fitzpatrick TB, Harber LC, Pathak M, Urbach F. Risks and benefits from high-intensity ultraviolet A sources used for cosmetic purposes. J Am Acad Dermatol 1985;12:380-1.

Danny Siegenthaler is a doctor of traditional Chinese medicine and together with his wife Susan, a medical herbalist and Aromatherapist, they have created Natural Skin Care Products by Wildcrafted Herbal Products to share their 40 years of combined expertise with you.

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