Therapeutic Evaluation of 2 % Tea Lotion in Comparison with 5 % Zinc Sulfate Solution in the Treatment of Acne Rosacea

Background: There are many effective topical and systemic therapies for acne rosacea. Topical zinc sulfate and tea lotion have been used in treatment of acne vulgaris. Objectives: To evaluate effectiveness of 2% tea lotion in comparison with 5% zinc sulfate solution in the treatment of acne rosacea. Patients and Methods: This single, blinded, comparative therapeutic clinical trial was carried out in the Department of Dermatology—Baghdad Teaching Hospital from June 2006-December 2007. Twenty two patients with acne rosacea were divided into two groups and were instructed to apply the following lotions for two months, Group A used 2% tea lotion twice daily while Group B used 5% zinc sulfate solution twice daily. Patient with severe acne rosacea were excluded from the study. Clinical improvement was evaluated every 2 weeks by determination of the disease severity score (Sharquie’s score) before and after treatment. Results: Eighteen patients with acne rosacea completed the study with their ages ranging from 26 70 (40.5 ± 10.9) years. For Group A and Group B were 39.7 ± 8.2, 41.2 ± 13.1 years respectively, with eight patients in Group A, ten patients in Group B. Five percent zinc sulfate solution was statistically significant in reducing the disease severity score in acne rosacea, while 2% tea lotion was beneficial but did not reach statistically significant level as zinc sulfate solution. Conclusion: Five percent zinc sulfate solution was a good alternative remedy to be used in patients with acnerosacea.


Introduction
Although acne rosacea is a common skin problem but unfortunately its etiopathogenesis still not well established as many factors have been suggested including genetic predisposition, gastrointestinal factor, infections such as Demodex folliculorum [1]; normal skin flora [2]; HIV infection (AIDS) [3], drugs as steroids, food, alcohol [4], sunlight and psychological factor.
Most recently a role of Helicobacter pylori (H.pylori) of the compylobacter group which infects the gastric mucosa has been proposed.It is suggested that there is an etiological relationship between acne rosacea and H. pylori [5].H. pylori have been extensively investigated and do not appear to be central to the etiology of acne rosacea [4].
Zinc is one of essential trace elements [7] that forms an integral part of several enzymes and cofactors which is an essential element in cell growth [8].
After application for 72 hours, percutaneous absorption of zinc sulfate results in increase in zinc concentration in whole skin and epidermis.The more zinc applied to the skin, the greater the increase in epidermal zinc level.Topical zinc ions traverse skin and can be found in dermis and blood.A recent study demonstrated that zinc concentration in skin could be increased eightfold by topical application of zinc sulfate but a concentration of 3% was optimal.Zinc oxide is extremely insoluble and would not be expected to be similarly active [9].
Zinc sulfate has been introduced into dermatology as effective therapy for many specific dermatoses: Two percent zinc sulfate solution was found to be effective as an intralesional therapy for cutaneous leishmaniasis and verruca vulgaris with cure rate 94.7%, 98.2% subsequently [10,11].Also, topical solution [10%] was effectively used for plane warts [12].Recently zinc sulfate solution has shown to be effective in treatment of superficial fungal infection in 10% and 15% concentrations [13,14].Oral zinc sulfate has been successfully tried in the treatment of cutaneous leishmaniasis, acne rosacea and viral warts [15,16].
Tea contains many chemicals like tanin, the phenolic group of tannin (mainly catechine) that are responsible for its antibacterial effect, and it has been shown to be effective topically in the treatment of acne vulgaris and impetigo contagiosum as through its antibacterial activity [17,18].Epigallcatechinsgallate of tea was reported to modulate the production and biological action of androgens and hormones.Modulation of androgenic activity may be useful for treatment of various hormones related abnormality such as baldness, acne and androgen dependent alopecia [19].
So, the objective of the present work is to evaluate effectiveness of 2% tea lotion in comparison with 5% zinc sulfate solution in the treatment of acnerosacea.

Patients and Methods
This single-blinded, comparative, therapeutic clinical study was conducted at the Department of Dermatology and Venereology-Baghdad Teaching Hospital between June 2006 to December 2007.
A total number of 22 patients (15 Females and 7 males) with female to male ratio 2.1:1 (probably because female seeking medical advice more than male for cosmetic reason) were enrolled in this study.Their ages ranged from 26 -70 years with a mean ± SD of 40.5 ± 10.9 years.
History was taken from each patient including: age, gender, social status, job, history of the disease itself, the age of onset, duration, complaint of the patient, family history of the same disease or any other skin diseases, drug history (topical and systemic), presence of other skin diseases, other systemic diseases such as hypertension, diabetes mellitus or others, involvement of other systems such as eye involvement, gastrointestinal problems.Exacerbating factors (sun exposure, heat and psychological factors etc.), and habits (smoking, alcohol).
The nature and target of this study were explained for each patient and formal consent was taken for each patient before starting the therapy, after full explanation about the nature of the disease, course, the procedure of treatment, follow up, prognosis and the need for pre and post treatment photographs by Sony-Digital, high sensitivity, 16.1 megapixels, 5 × optical zoom camera in the same place with fixed illumination and distance.Also, ethical approval was given by the scientific committee of the Scientific Council of Dermatology and Venereology-Iraqi Board for Medical Specializations.
Patients were instructed to stop any other medications at least one month before starting the therapy.Physical Examination of the patients and assessment of their disease was done according to the disease severity score (Sharquie's score) [16] which includes: severity of erythema, number of papules and pustules, telangectasia, and presence or absence of rhinophyma.The severity of erythema was determined according to a color chart (Fig- ure 1, Table 1).
Patients with stage I and II rosacea, including those with eye involvement, were included in this trial.Patients with stage III rosacea and those with severe steroid-induced rosacea were excluded.Patients were divided into two groups: 1) Group A: Ten patients (7 Females and 3 males) were treated with 2% tea lotion.Their ages ranged from 33 -53 years with a mean ± SD of 39.7 ± 8.2 years.Each patient instructed to use the lotion topically twice daily for 2 months and clinical evaluation was done every 2 weeks.The assessment carried out by observing the severity of erythema and counting the number of the papules, pustules and telangiectasia and recording any side effects.Ophthalmological examination was done for all the patients by referring them to the ophthalmology clinic.
2) Group B: Twelve patients (8 Females and 4males) were used 5% zinc sulfate solution in a similar way of Group A. Their ages ranged from 26 -70 years with a mean ± SD of 41.2 ± 13.1 years.These cases were followed up for 2 months by observing the severity of erythema and counting the number of the papules, pustules, telangiectasia and mentioned any adverse effects.Ophthalmological examination was done for all the patients by referring them to the ophthalmology clinic.
The response of the patients to treatment was classified as: 1) Good response when the reduction in the mean score is more than 50%, 2) Moderate response; when the reduction in the mean score is running from 10% -50%.
3) No response; when the reduction of the mean score is less than 10%.
Done by computer using EPI version 6. Calculation of mean and SD done for disease severity score.Comparison before and after treatment in each group was done by using paired t-test, and p-value less than 0.05 was considered as level of significance.
In this method, the tea leaves (apple brand mark) was added to boiled water (35 gm of tea was mixed with 100 ml boiling hot distilled water), and then flame reduced to minimum and kept on low flame for 30 minutes (Iraqi method of decoction), then we let the tea extract to cool down, then we took 100 ml of tea extract and 100 ml of distilled water and we weigh them.The excess weight in the extracted tea is the amount of pure tea in tea lotion, for example if the difference is one gram between tea lotion and distilled water then the percent is 1%, if the excess is two grams the concentration of tea will be 2% [17].
The 1% tea extract was boiled again until two thirds of water was evaporated, to reach 3% tea extract concentration The 2% tea lotion (100 ml) was prepared by adding 75 ml tea extract and 25 ml of ethanol (95% purity) which is used as preservative.

Results
Eighteen patients were completed the course of treatment in this work.Eight patients in Group A, 5 (62.5%) females and 3 (37.5%)males, 10 patients in Group B, 8 (80%) females and 2 (20%) males, 4 (18.1%)patients did not complete the treatment and considered defaulter for unknown reason(2 from Group A and 2 from Group B).
The duration of the disease ranged between 1 month and 20 years.Positive family history was found in 3 (13.6%)patients.
Eye involvement occurred in 4 (18%) patients: in the form of blepharitis in 3 patients, and conjunctivitis in one patient.
Gastrointestinal problems were found in one (4.5%)patient in the form of gastritis.

Group A (Tea lotion):
1) Evaluation of patient's response to treatment.Three (37.5%) patients showed no response while two (25%) patients showed moderate response and three (37.5%)patients had good response.
2) The assessment of mean ± SD of disease severity score (Sharquie's score) before and after treatment was as follow: The score was ranged before treatment between 4 -9 with a mean ± SD of 6.1 ± 1.8 that reduced to 4.2 ± 2.6 after treatment.This reduction was statistically not significant (P = 0.1) (Table 2).
No important side effects were reported apart from burning sensation in one (12.5%)patient and itching in another one (12.5%)patient in the early course of treatments which were reduced with subsequent treatment.
2) The assessment of mean ± SD of disease severity score (Sharquie'sscore) before and after treatment was as follow: The score was ranged before treatment between 5 -11 with a mean ± SD of 7.4 ± 1.9 that reduced to 2.9 ± 1.9 after treatment.This reduction was statistically significant (p = 0.00003) (Table 2, Figure 2).
The papules and pustules showed a significant decrease in their numbers one month after starting treatment with zinc sulfate.Erythema was also reduced, but it needed longer time to show a significant response (becomes statistically significant after the second month of treatment).There was no significant effect of zinc sulfate on telangiectasia.
No important side effects were reported apart from burning sensation in 2 (20%) patients and itching in 1 (10%) patient in the early course of treatments which were reduced with subsequent treatment and not needed for cessation of therapy.

Discussion
The etiology of acne rosacea is still not well known and it seems that rosacea may have a multifactorial etiology [1][2][3][4][5].Many medications have been used to control the activity of the disease including topical and systemic therapies, and these drugs might have side effects and cannot be tolerated by the patients for long term therapy [4,5].Therefore, the present work aims to find simple and cost effective therapy to control the disease.
The present study confirmed that 5% zinc solution was effective in the clearance of the rash of rosacea while 2% tea lotion was much inferior in its effectiveness when compared with 5% zinc sulfate solution.These findings had been similarly noticed in the treatment of acne vulgaris but 2% tea lotion was more effective than 5% zinc solution [20].
Five percent topical zinc sulfate solution has been shown also effective in treatment of acne vulgaris [20].
The mechanisms of action of tea lotion in rosacea is not fully understood, but it may be due to antibacterial activity against normal skin flora which might behave abnormally in rosacea patients due to higher facial skin temperature [5], skin protection effect against UVB-induced inflammatory responses [25,26], antioxidant, antiinflammatory effects [25,26] and immune modulating action [27].
The 2% tea lotion showed no side effects.To increase the effectiveness of 2% tea lotion we recommend further studies using 5% tea lotion as topical therapy with higher number of patients.
The effect of zinc sulfate solution on the papules and pustules became statistically significant one month after starting therapy.
These results are comparable to systemic azithromycin and metronidazole that are used to treat rosacea and results in significant improvement of the papules and pustules that continue 4 weeks after treatment [28].While 0.1% tacrolimus ointment showed no significant effect on papulopustular rosacea [29].
Regarding erythema, there was gradual reduction which becomes statistically significant after the second month of treatment with zinc sulfate solution which is comparable to other therapies [28,29].
Zinc sulfate solution had no significant effect on telangiectasia and this is like other modalities mentioned in literature [30].
The present study confirmed the findings in Iraqi study, which showed that oral zinc sulfate was an effective in controlling rosacea lesions [30].
Results of previous studies showed that oral zinc sulfate was effective in controlling rosacea lesions, and side effects were mild and transient [30].In this study it was found that zinc sulfate solution was simple, effective and with no important side effects, this makes zinc sulfate (especially the solution) superior to other drugs in the treatment of acnerosacea.
Treatment with topical zinc sulfate solution had no important side effects and could be used as topical therapy in mild cases and could be combined with oral therapy like oral zinc sulfate [30], azithromycin and others.

Conclusion
In conclusion, 5% zinc solution and 2% tea lotion were effective in the management of mild to moderate acne rosacea and could be used alone or combined with oral therapy.

Disclosure
This study was an independent study and not funded by any drug companies.

Figure 1 .
Figure 1.A color chart for the severity of erythema.

Figure 2 .
Figure 2. (a) Thirty five years old female with acne rosacea; (b) 35 years old female with acne rosacea after 2 months treatment with zinc sulfate solution.