Oxytetracycline

Abstract

The long-established notion that rosacea is worsened by light is of particular concern in the phototherapy of diseases such as psoriasis, eczema, or vitiligo, which often can be coexistent with rosacea. A literature search was conducted and much evidence was found to challenge this belief that light adversely affects rosacea. In fact, more patients actually improved with sunlight in a more recent published survey. Several other studies have also shown that rosacea patients were similar to control subjects in sun exposure, solar skin damage, and sun sensitivity. Additionally, all clinical trials to date have failed to find a difference between rosacea patients and control subjects when challenged with ultraviolet light. Thus, phototherapy with rosacea may be safer than is commonly believed.

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Introduction

Rosacea has traditionally been thought to be exacerbated by sunlight. This presents a problem in rosacea patients who also have a photo-responsive condition such as psoriasis, eczema, or vitiligo. Precautions may be instituted in those who undergo phototherapy to avoid exacerbation of the rosacea while treating the co-existing disease. Some clinicians may even elect to avoid phototherapy altogether in this patient population. This article is an update on the evidence regarding the effect of light on rosacea.

Methods

Searches for relevant articles were conducted in electronic databases including PubMed 1951 to 2004, MEDLINE (National Library of Medicine) 1966 to 2004, OLDMEDLINE (National Library of Medicine) 1951 to 1965, and the Cochrane Controlled Trials Register. The search terms combined rosacea with terms reflecting the effect of ultraviolet light on it (light, sunlight, phototherapy, ultraviolet, UVB, UVA, PUVA, psoralen, pathogenesis, etiology, heat). The abstracts were evaluated and the full articles of possibly relevant studies and case reports were read. Additional papers were obtained from the references cited in pertinent articles.

Results

Early anecdotal reports such as those by Haxthausen in 1930 noted that some rosacea patients associated a worsening of their condition with exposure to sunlight. (1) A formal study was not instituted, though, until Sobye conducted a survey followed by a clinical trial in 1950. (2) In his survey, Sobye found that 66.4% of rosacea patients were first seen in the months of March, April, and May, with the rest being distributed evenly throughout the rest of the year. This seasonal variation with presentations mostly in the spring suggested the possibility that light affects rosacea. Sobye tested this hypothesis with a clinical trial, exposing 10 rosacea patients' abdominal skin to light from a quartz lamp (light wavelength not specified) for 5 minutes. All patients were found to have a "normal" reaction, although no comparison group was indicated and no statistical analysis was offered. Sobye concluded that their observation that most rosacea patients present during March, April, and May could be due to light or some other unknown variable.

Brodthagen attempted to correlate minimal erythema dose with alleged sensitivity to sunlight in rosacea patients in 1955. (3) A mercury arc lamp with spectral lines of 297-302-312 nm was used to irradiate the forearm of 57 rosacea patients, and the minimal erythema dose was compared to the patients' report of whether their rosacea was provoked by sunlight. This study failed to show any relationship between light sensitivity (by minimal erythema dose testing) and the provocation of rosacea by sunlight (in a survey), although a statistical analysis was not provided. No attempt was made to compare minimal erythema dose of the rosacea patients to a control population.

In 1968, Marks attempted to assess the role of sunlight on rosacea by comparing the amount of sunlight exposure between 74 rosacea patients and 74 control subjects through a survey. (4) Twenty-six rosacea patients (35%) reported that the sun made their condition worse. However, they reported no apparent difference between the two groups in sun sensitivity or sun exposure (no statistical analysis was given). Eighteen rosacea patients were then tested with monochromatic light at 300 nm on the back to define the minimal erythema dose. All the results were reportedly within the range typical for normal subjects in their experience.

Goetz and Cronen also tested patients with ultraviolet light in 1980. (5) When comparing 20 patients with rosacea versus 14 control subjects by irradiation from an artificial ultraviolet light source, they found no statistically significant difference in reaction to ultraviolet light.

Dupont, in a letter in 1986, investigated the relationship between solar skin damage and rosacea. (6) One hundred forty-four rosacea patients were interviewed and given a questionnaire and compared with 144 controls. Patients were also inspected for signs of solar skin damage. No significant difference was found between the two groups in sun exposure or the extent of solar skin damage; however, the statistical analysis was not offered.

The association between actinic damage and rosacea was again investigated in 1988 by Engel et al. (7) A group of 20,637 subjects received a dermatologic examination and the presence of actinic damage and rosacea was documented. In a selected group of 9,293 subjects, a statistically significant increase in actinic damage (including actinic keratoses, fine telangiectasia, and senile elastosis) was not found in men with rosacea, but was found in women with rosacea. However, no mention was made of how these men and women were selected from the total 20,637 subjects that were examined. A statistical analysis also was not done on women and men combined.

In a 1989 case report, McFadden et al gave a description of one patient with a facial rash clinically and histologically consistent with rosacea that developed at the end of a 3.5-week course of PUVA therapy. (8) The condition resolved after PUVA was discontinued and oxytetracycline 250 mg twice daily was given for 3 months.

Berg and Liden published a survey in 1989 of 809 randomly selected office employees and, within this group, compared those with rosacea and those without rosacea. (9) They found no statistical difference in sun-bathing habits between the two groups. Those with skin type IV seemed to be less prone to develop rosacea, but there was no statistically significant difference in prevalence of rosacea between skin types I-III. Unexpectedly, they also found that of the individuals in the study with rosacea, more felt that they improved with sunlight (26%) than worsened with sunlight (17%). Also contrary to prior studies, the group found that those with rosacea reported a statistically significant worsening of their condition more frequently in the winter than in the summer.

Murphy et al published an abstract in 1997 detailing their experiments with monochromatic ultraviolet irradiation in the UVA (320-400 nm) and UVB (290-320 nm) ranges. (10) On comparing 21 rosacea patients with 56 control subjects, they found that the mean minimal erythema dose at 300 nm, 320 nm, and 370 nm on the back was the same between the two groups. Another arm of the study compared the minimal erythema dose on the face with that on the back of rosacea patients. They found that a majority of rosacea patients had a greater minimal erythema dose (ie, less prone to a phototoxic reaction) on the face than on the back. However, no statistical analysis was done and no comparison was made with controls. Furthermore, no evidence could be found in the literature to ascertain whether an individual from the general population would also be less prone to burning on the face than on the back after a single dose of ultraviolet radiation.

Discussion

In this review of the studies performed on the effects of light on rosacea, it is apparent that much of the traditional teaching is based on anecdotal evidence from nearly a century ago or earlier. However, the belief that sunlight exacerbates rosacea has been questioned by much of the data since 1950. In fact, a more recent survey has shown that more patients found their rosacea to be improved rather than worsened with sunlight. (9) Other previous surveys may have missed this as they focused on identifying the exacerbating factors of rosacea and asking patients only if their rosacea was worsened by sunlight, but not if it was improved with sunlight. (1,2)

If light is indeed an etiology in the pathogenesis of rosacea, one might expect that patients with the condition have spent more time in the sun, especially prior to the development of rosacea. Several surveys have examined this possibility, but only in one survey reviewed was an association found between actinic damage and rosacea. (7) However, this association was found only in one subgroup of the survey (white women only). There was no association found with white men, and the paper did not comment on whether an analysis was done including all surveyed individuals. All the other surveys reviewed have found no difference between rosacea patients and control subjects in sun exposure, solar skin damage, and sun sensitivity. (4,6,9) Moreover, if sensitivity to sun was a factor in the development of rosacea, one would expect its prevalence to be greatest in patients with skin type I and progressively less in darker skin types. Only one survey examined this and, although rosacea was less prevalent in skin type IV, there was no statistical difference in the prevalence of rosacea between skin types I-III. (9) This is further evidence against the idea that sunlight initiates or adversely affects rosacea.

Skin sensitivity to ultraviolet light has also been studied more rigorously. Five sets of authors have found no difference in the effect of ultraviolet light between the skin of rosacea patients and the skin of control subjects. (2,3-5,10) This result was the same regardless of whether the light used was in the UVA (320-400 nm) or UVB (290-320 nm) spectrum. The site of irradiation on the body also did not change the results, although it is unclear why only one uncontrolled study was done on the face, which is the usual site of rosacea.

These results are of particular interest in phototherapy, where ultraviolet light is used to treat other skin disorders that may be coexistent with rosacea. The case report of rosacea after PUVA therapy was a single isolated incident, and it remains unknown if the temporal association between PUVA therapy and the onset of rosacea was only a coincidence. (8) No reports were found on any adverse effect of UVB on rosacea. In addition, in each of the studies where patients were exposed to ultraviolet light, the authors of the studies either observed that no rosacea-like lesions were induced or no comment was made. This sets rosacea apart from a disorder such as lupus erythematosus, in which cutaneous lesions can be induced by ultraviolet light. (11)

Conclusion

The traditional belief that sunlight exacerbates rosacea must be questioned. Several recent surveys have found no relationship between sun exposure and rosacea and that, in some patients, sunlight may even have a beneficial effect. Furthermore, five different clinical trials to date all have shown no difference in the way ultraviolet light affects rosacea patients and control subjects. These data strongly suggest that ultraviolet exposure per se may not be a problem in rosacea patients after all and that phototherapy in patients with rosacea is safer than commonly believed. However, cautions cannot entirely be discarded when treating these patients. Phototherapy units are known to produce much heat, which in an ingested liquid has been shown to induce flushing in rosacea patients. (12) In addition, no trial has yet been done to directly observe the response on rosacea after ultraviolet light therapy to the face. Further studies such as these are needed in order to ascertain in more detail the effect of light on rosacea.

References

1. Haxthausen H. Changes in the skin vessels from protracted action of climatic factors and their significance in various skin diseases. Brit J Derm. 1930;42:105-125.

2. Sobye P. Aetiology and pathogenesis of rosacea. Acta Derm Venereol. 1950;30:137-153.

3. Brodthagen H. Mepacrine and chloroquine in the treatment of rosacea. Br J Dermatol. 1955;67:421-425.

4. Marks R. Concepts in the pathogenesis of rosacea. Br J Dermatol. 1968;80:170-177.

5. Goetz H, Cronen J. Die UV-lichtempfindlichkeit der Haut bei der Rosacea. Z Hautkr. 1980; 55:232-236.

6. Dupont C. The role of sunshine in rosacea. J Am Acad Dermtol. 1986;15(4 Pt 1):713-714.

7. Engel A, Johnson ML, Haynes SG. Health effects of sunlight exposure in the United States. Results from the first National Health and Nutrition Examination Survey, 1971-1974. Arch Dermatol. 1988;124:72-79.

8. McFadden JP, Powles AV, Walker M. Rosacea induced by PUVA therapy. Br J Dermatol. 1989;121:413.

9. Berg M, Liden S. An epidemiological study of rosacea. Acta Derm Venereol. 1989;69:419-423.

10. Murphy A, Powell FC, Murphy GM. Assessment of ultraviolet thresholds in rosacea. J Invest Dermatol. 1997;108:389.

11. Epstein JH, Tuffanelli DL, Dubois EL. Light sensitivity and lupus erythematosus. Arch Dermatol. 1965;91:483-485.

12. Wilkin JK. Oral thermal-induced flushing in erythematotelangiectatic rosacea. J Invest Dermatol. 1981;76:15-18.

Melvin Lee, (a) John Koo MD (b)

a. Medical Student, Rosalind Franklin University of Medicine and Science, Chicago, IL

b. Professor and Vice Chairman, Department of Dermatology, UCSF Director, UCSF Psoriasis and Skin Treatment Center and Phototherapy Unit, San Francisco, CA

Address for Correspondence

Melvin Lee

4645 Whitewood Ave

Long Beach, CA 90808

Phone: (312) 543-0205

e-mail: melvin.lee@students.rosalindfranklin.edu

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