Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 1 Efficacy of Topical Rosemary Extract Lotion versus Topical 2% Ketoconazole Lotion in the Treatment of Seborrheic Dermatitis: A Double-Blind Randomized Controlled Clinical Trial Maryam Sadat Sadati1,2, Fateme Alesana1,2, Maryam Hekmat1,2, Mohammad Mahdi Parvizi2,3,4,5 1 Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 2 Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran 3 Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 4 Vice Chancellor of Academic Affairs, Smart University of Medical Sciences, Tehran, Iran 5 Persian Medicine Network, Universal Scientific Education and Research Network, Tehran, Iran Key words: Rosmarinus, Herbal medicine, Seborrheic dermatitis, Skin diseases, Complementary therapies Citation: Sadati MS, Alesana F, Hekmat M, Parvizi MM. Efficacy of topical rosemary extract lotion versus topical 2% ketoconazole lotion in the treatment of seborrheic dermatitis: a double blind randomized controlled clinical trial. Dermatol Pract Concept. 2024;14(4):e2024242. DOI: https://doi.org/10.5826/dpc.1404a242 Accepted: July 2, 2024; Published: October 2024 Copyright: ©2024 Parvizi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: This work was supported by the Vice-chancellor of Research of Shiraz University of Medical Sciences (Grant number: 23446). Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Mohammad Mahdi Parvizi MD, PHD, MPH, Associate professor of Persian Medicine, Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Zand Avenue, Shahid Faghihi Hospital, Shiraz, Iran. E-mail: mmparvizi@gmail.com Introduction: Seborrheic dermatitis manifests as greasy itchy lesions commonly affecting sebum-rich areas like the scalp and face. Its prevalence is 11.6% in the general population, with various internal and environmental factors contributing to its development. Objectives: This study aimed to compare the efficacy of rosemary extract lotion in the treatment of seborrheic dermatitis in comparison with topical 2% ketoconazole lotion. Methods: This double-blind randomized controlled clinical trial included 42 patients with scalp seb- orrheic dermatitis, divided into rosemary lotion and ketoconazole lotion groups. Both lotions were applied twice daily for two months. The severity of scalp dandruff was assessed using the Adherent Scalp Flaking Score (ASFS). The itchiness of the scalp and quality of life were assessed using itchy quant and the Dermatology Life Quality Index (DLQI), respectively. Stata software version 14.2 was applied for statistical analysis. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 Introduction Seborrheic dermatitis is a type of chronic inflammatory skin disorder characterized by the emergence of erythematous scaly lesions on the skin [1]. This condition can affect the scalp and other seborrheic areas of the body, including the face, eyebrows, behind the ears, upper chest regions, flexor areas of the body, and generally areas with higher sebum production [2]. The primary cause of seborrheic dermatitis is not fully understood [3]. A variety of internal and environmental fac- tors can serve as potential triggers for this condition. It is thought that the growth and colonization of Malassezia spe- cies, which are drawn to the lipids found in sebum- producing areas, triggers an immune response and the appearance of symptoms related to this condition [4]. Compounds in the skin’s lipid composition and individual sensitivity are also believed to be involved in this disease [5]. The simultaneous presence of these factors can contribute to the pathogenesis of the disease. The treatment of seborrheic dermatitis focuses on alle- viating symptoms, improving associated signs, and reducing the likelihood of disease recurrence. As mentioned earlier, the primary pathogen responsible for seborrheic dermatitis is Malassezia, so the most commonly used drugs are topical antifungal and anti-inflammatory agents [6]. Several drugs and treatments have been introduced to reduce skin lesions in seborrheic dermatitis. Topical ketoconazole, tacrolimus, and corticosteroids are among the most commonly used drugs, although some side effects have been reported [7]. Research- ers are striving to find systemic or more localized treatments. In terms of treatment, three main categories—keratolytics, anti-inflammatories, and antifungals—are beneficial for managing this condition. Keratolytic drugs prevent the for- mation of scales and at the same time help the penetration of other topical drugs [8]. Topical steroids and calcineurin inhibitors have been found to effectively manage inflam- mation, whereas antifungal medicines exert their therapeu- tic effects by lowering the colonization of Malassezia [9]. Each of these drugs has its own specific side effects. Topical corticosteroids can lead to atrophy, telangiectasia, and acne [10], while calcineurin inhibitors may cause itching, burning, and erythema [11]. Additionally, some species of Malassezia show resistance to antifungal drugs. A meta-analysis conducted by Jain and colleagues aimed to explore recent findings regarding the antifungal proper- ties of plant oils against pathogens involved in dandruff. The study highlighted the global significance of herbal oils such as tea tree oil, lemon oil, and rosemary oil in dermatology. These oils have a lot of aromatic secondary metabolites, like terpenes and phenolic parts, which make them very good at killing microbes and stopping biofilm from forming. The study suggested that these oils have a high potential for de- velopment as anti-dandruff formulations, but further studies are needed to prove their efficacy in treating dandruff [12]. Aytollahi and colleagues conducted a review study that underscored the growing scientific focus on herbal extracts due to their enhanced efficacy and reduced adverse effects within the pharmaceutical and cosmetic sectors. The study mentioned various herbal shampoos with anti-dandruff properties that are effective and safe without the side ef- fects of chemical agents. The researchers concluded that herbal extracts are gaining attention, and clinical evidence regarding their therapeutic effects in seborrheic dermatitis is prompting further studies [13]. Rosemary is among the plants that have gained attention in recent years. This plant is a therapeutic herb that orig- inates in the Mediterranean region and is grown globally. Moreover, the use of this herbal remedy is common among the Iranian population, which could be related to the advice of the Persian medical sages in the treatment of some dis- eases, especially dermatologic conditions [14-17]. Because it has verbenone and other chemicals like camphor, cineole, β-myrcene, carnosic rosmarinic acid, volatile oil, phenolics, and α-pinene, rosemary oil can kill germs and viruses, reduce inflammation, protect nerves, and lower blood sugar. More- over, evidence has revealed that rosemary can enhance blood circulation in the scalp. Therefore, many pharmaceutical Results: The reduction in ASFS score was statistically significant in patients in the ketoconazole group in comparison with the patients in the rosemary group (P = 0.011). However, the reduction in itching score was statistically significant more in the rosemary group at the end of the first and second months in comparison with the ketoconazole group (P < 0.001). The statistical analysis demonstrated no sig- nificant difference in the reduction of DLQI scores between the rosemary and ketoconazole groups at the end of one and two months after stating the treatment in both crude and adjustment with base-line score analysis. Conclusion: Both rosemary and ketoconazole lotions were effective in treating scalp seborrheic der- matitis and in decreasing patients’ DLQI score. Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 3 and cosmetic products have used rosemary in various ways [18-21]. Muyima and colleagues also demonstrated that the oil extracts of three plants, including rosemary, have antifungal effects on various fungal species. They suggested that with extraction of their essential oils, they could be used as an alternative to chemical compounds [22]. Objectives To our knowledge, there were limited number of studies on the effects of rosemary on dandruff and the successful role of rosemary in treating some inflammatory skin condi- tions. Therefore, we aimed to assess the efficacy of a rose- mary lotion in the treatment of dandruff in comparison with ketoconazole. Methods Study Design, Population, Sampling, and Sample Size Calculation This study was a double-blind randomized controlled clin- ical trial on patients suffering from seborrheic dermatitis of the scalp between 2021 and 2022. In this regard, pa- tients were included in the study based on the consecutive sampling method. The sample size was calculated based on similar previous studies and using Stata software version 14.2 with the “sampsi “module. With a type I error (alpha) of 0.05 and a study power of 80%, the minimum sample size was calculated to be 21 patients in each study group. The study protocol was registered on the Iranian Registry of Clinical Trials (IRCT) website with a trial registration number of IRCT20221001056063N1 (link: https://irct .behdasht.gov.ir/trial/66140; https://irct.behdasht.gov.ir/ trial/66140). Inclusion and Exclusion Criteria Patients with seborrheic dermatitis who visited the Derma- tology Clinic of Shahid Faghihi Hospital, Shiraz, Iran were included in the study. The diagnosis was based on the clini- cal presentation of the patients. Patients between 18 and 60 years old with clinically diagnosed scalp seborrheic derma- titis with an Adherent Scalp Flaking Score (ASFS) above 10 and a Dermatology Life Quality Index (DLQI) score above 2 were included in this study. Patients with seborrheic der- matitis in areas other than the scalp, those who had used antibiotics or immune-modulating drugs in the month before the study, those who had used any topical medication in the two weeks before entering the study or systemic medication in the month before entering the study that could affect seb- orrheic dermatitis, and individuals with scalp diseases such as lichen plano pilaris (LPP) were excluded. Patients were prohibited from using soaps or shampoos effective for seb- orrheic dermatitis on the scalp during the study. Randomization and Blinding The patients were divided into two groups using Random Allocation Software version 1.0.0. In this regard, the pa- tients were randomly divided into rosemary lotion and keto- conazole lotion groups using block randomization, with six blocks of four (group A and group B). In addition, dark enve- lopes were used to conceal the random allocation sequence. Moreover, this study was designed as a double-blind clin- ical trial. In order to blind the patients, the clinical trial team, and the outcome assessor of the outcomes, the patients re- ceived the lotions of rosemary and ketoconazole in the same packaging, appearance, volume, and odor. Intervention In this study, we enrolled 21 patients in each group (Group A and Group B). In this regard, rosemary lotion 5% manu- factured by Barij Essence Company, Kashan, Iran, was given to the patients in Group A, and ketoconazole lotion 2% to the patients in Group B. Furthermore, we advised the pa- tients to apply the lotion twice a day to areas with lesions on their scalp for two months. Assessments and necessary evaluations were performed at the beginning of treatment and then one and two months later. A dermatologist who was unaware of the patients’ medication regimens examined and evaluated patients during visits and follow-up. Data Collection and Outcomes Measure In the first visit, we obtained the patients’ medical history and demographic information. We also performed a physical examination, photographed the skin lesions, and assessed the extent of the disease. Then, at each patient visit, the severity of scalp dandruff was assessed using the Adherent Scalp Flaking Score (ASFS) [4]. According to the ASFS scor- ing system, the scalp is divided into eight areas, and each area is scored from 0 to 10 based on the severity of scalp dandruff. It is important to note that flakes detached from the scalp and scattered in the hair are not included in the scoring (Figure 1). Additionally, the level of itching was assessed using the Itchy Quant scale, a numerical rating scale ranging from 0 to 10 [5]. Moreover, the patients’ quality of life was evaluated at each visit using the Persian version of the DLQI, which has been validated for reliability and validity [23]. Adverse drug reactions, such as skin dryness, itching, burning, con- tact dermatitis, peeling, redness, and so on, were also exam- ined at each visit. 4 Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 Outcomes Measures ASFS Score In both groups, the ASFS scores before intervention did not show a statistically significant difference. Both the keto- conazole and rosemary groups demonstrated a reduction in the ASFS score over time. However, the crude and base-line score adjustment analysis showed that the reduction in ASFS score was statistically significant in patients on ketoconazole in comparison with the patients in the rosemary group (P = 0.011), as shown in Table 2. Itchy Quant Scores The initial mean Itchy Quant scores in the rosemary and ke- toconazole groups were 5.19±1.69 and 5.23±1.48, respec- tively, showing no considerable difference between them. After treatment, there was a statistically significant reduc- tion in Itchy Quant scores in both groups. The reduction was more statistically significant in the rosemary group at the end of the first and second months than the ketoconazole group in both crude and base-line score adjustment analyses, as shown in Table 2. DLQI Scale The average DLQI index in the rosemary and ketoconazole groups before treatment was 9.86 ± 4.03 and 9.38 ± 4.18, respectively, showing no considerable difference. After re- ceiving treatment, the DLQI scale in both groups signifi- cantly decreased. As shown in Table 3, the statistical analysis demonstrated no significant difference in the reduction of DLQI scores between the rosemary and ketoconazole groups at the end of one and two months after stating the treatment in both crude and adjustment with base-line score analysis. Adverse Effects Evaluation In the rosemary group, two patients withdrew from the study due to scalp burning and itching. Additionally, two in- dividuals in this group expressed discomfort with the scent of the lotion, but they continued participating in the study, considering its effectiveness. In the ketoconazole group, one patient reported itching but continued to participate in the study. Discussion The present study aimed to investigate the efficacy of a rosemary extract lotion in the treatment of seborrheic der- matitis and compare it with 2% ketoconazole lotion in a double-blind randomized controlled trial. The results of our study revealed that both ketoconazole and rosemary topical Ethical Statements The Research Ethics Committee of Shiraz University of Med- ical Sciences (Ethics Code: IR.SUMS.MED.REC.1401.090) approved the study’s protocol. Furthermore, the research- ers presented the aim of the study to the participants before enrolling them in the study. In addition, all of the patients signed a written informed consent form to participate in the study. The patients were free to withdraw from the study at any time during the study. Statistical Analysis We used Stata software version 14.2 for data analysis. De- scriptive statistics, including mean and standard deviation for quantitative data and frequency and percentage for cate- gorical data, were used. For comparisons between the demo- graphic characteristics of the two groups, the independent t-test was employed for parametric variables, and the chi- square test was used for categorical variables. Moreover, we used the ANOVA/ANCOVA test to compare the outcomes of the study. In this regard, the crude analysis of one and two months after beginning the treatments as well as base- line adjusted analyses were applied. To estimate the effect size, the mean difference (MD) and standard mean difference (SMD), including Cohen’s d, were calculated. A significance level (p-value) was considered equal to or less than 0.05. Results Demographic Data and Patient Information before Treat- ment in Both Groups: The present study enrolled 42 patients, with 21 partic- ipants in each study group. At the end of the study, 39 pa- tients, including 19 patients in the rosemary lotion group and 20 patients in the ketoconazole group, completed the study and were analyzed, as shown in the CONSORT diagram of the study (Figure 2). As shown in Table 1, the patients in both groups were approximately similar in the variables of age, sex, and marital status. Figure 1. Adherent Scalp Flaking Score (ASFS) grading system. Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 5 seborrheic dermatitis significantly decreased in both groups of the study, similarly. Recently, the literature has demonstrated that a remark- able number of patients with chronic and acute conditions preferred to use complementary and alternative medicine, lotion were effective in the treatment of scalp seborrheic der- matitis. However, the ketoconazole lotion was more effective in reducing the ASFS score, although rosemary lotion re- duced the itching score more of the patients with seborrheic dermatitis. In addition, the DLQI score of the patients with Figure 2. CONSORT Flow Diagram of the Study. Table 1. Demographic Characteristics of the Patients who Participated in the Study. Variables Rosemary Lotion (N=21) Ketoconazole Lotion (N=21) p-value Age mean± SD 34.67± 8.88 33.90± 6.60 0.754 Sex N(%) 0.346 Male 11 (52.38) 14 (66.67) Female 10 (47.62) 7 (33.33) Marital Status N(%) 0.513 Single 6 (28.57) 8 (38.10) Married 15 (71.43) 13 (61.90) 6 Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 Ta b le 2 . E ffi ca cy o f R os em ar y L ot io n vs K et oc on az ol e L ot io n in t he T re at m en t of D an dr uf f in S eb or rh ei c D er m at it is : E va lu at io n of t he A SF S an d It ch in g Sc or e Pr e- a nd P os t- In te rv en ti on a cc or di ng t o D if fe re nt M od el s. O u tc o m e M o d el Ti m e p o in t R o se m ar y Lo ti o n (N = 19 ) K et o co n az o le Lo ti o n (N = 20 ) M ea n D if fe re n ce (9 5% C I) C o h en ’s d ( 95 % C I) Pa rt ia l Et a2 p -v al u e$ A d ju st ed R 2 A SF S C ru de Pr e 25 .8 0 ± 7. 50 23 .4 3 ± 5. 48 2. 38 ( -1 .7 2 to 6 .4 8) 1s t m on th 5. 05 ± 2 .1 4 3. 23 ± 2 .0 9 1. 81 ( 0. 44 t o 3. 19 ) 0. 85 ( 0. 19 t o 1. 51 ) 0. 16 0. 01 1 0. 13 6 2n d m on th 2. 63 ± 1 .1 6 1. 6 ± 1. 72 1. 03 ( 0. 25 t o 1. 81 ) 0. 85 ( 0. 19 t o 1. 49 ) 0. 16 0. 01 1 0. 14 0 A dj us te da Pr e 25 .8 0 ± 7. 50 23 .4 3 ± 5. 48 2. 38 ( -1 .7 2 to 6 .4 8) 1s t m on th 4. 85 ± 1 .7 6 3. 42 ± 1 .7 2 1. 42 ( 0. 28 t o 2. 55 ) 0. 82 ( 0. 16 t o 1. 47 ) 0. 09 0. 01 6 0. 42 7 2n d m on th 2. 57 ± 1 .1 1 1. 66 ± 1 .1 1 09 1 (0 .1 8 to 1 .6 3) 0. 10 ( -0 .5 4 to 0 .7 2) 0. 12 0. 01 6 0. 26 7 It ch in g sc or e C ru de Pr e 5. 19 ± 1 .6 9 5. 23 ± 1 .4 8 -0 .0 5 (- 1. 04 t o 0. 94 ) 1s t m on th 0. 90 ± 0 .4 8 1. 48 ± 0 .4 7 -0 .5 8 (- .8 9 to - 0. 27 ) -1 .2 1 (- 1. 89 t o -0 .5 2) 0. 27 <0 .0 01 0. 25 3 2n d m on th 0. 47 ± 0 .5 1 0. 9 ± 0. 55 -0 .4 2 (- 0. 77 t o -0 .0 8) -0 .7 9 (- 1. 45 t o 0. 14 ) 0. 14 0. 01 7 0. 12 0 A dj us te da Pr e 5. 19 ± 1 .6 9 5. 23 ± 1 .4 8 -0 .0 5 (- 1. 04 t o 0. 94 ) 1s t m on th 0. 92 ± 0 .4 2 1. 45 ± 0 .4 1 -0 .5 3 (- 0. 80 t o -0 .2 6) -1 .2 8 (- 1. 96 t -o 0 .5 8) 0. 23 <0 .0 01 0. 44 4 2n d m on th 0. 49 ± 0 .5 0 0. 88 ± 0 .5 0 -0 .3 8 (- 0. 76 t o -0 .0 6) -0 .7 7 (- 1. 41 - to 0 .1 9) 0. 12 0. 02 2 0. 21 8 *C al cu la te d ba se d on o ne -w ay A N O V A /A N C O V A ; * *S ig ni fi ca nt ( P≤ 0. 05 ); a . A dj us te d fo r ba se lin e pr e- tr ea tm en t sc or e (c al cu la te d ba se d on O ne w ay A N O V A / A N C O V A m od el ). Ta b le 3 . E ffi ca cy o f R os em ar y L ot io n vs K et oc on az ol e L ot io n in t he T re at m en t of D an dr uf f in S eb or rh ei c D er m at it is : E va lu at io n of t he D er m at ol og y L if e Q ua lit y In de x Pr e- a nd P os t- In te rv en ti on a cc or di ng t o D if fe re nt M od el s. o u tc o m e M o d el Ti m e p o in t R o se m ar y Lo ti o n (N = 19 ) K et o co n az o le Lo ti o n (N = 20 ) M ea n D if fe re n ce (9 5% C I) C o h en ’s d ( 95 % C I) Pa rt ia l Et a2 p -v al u e$ A d ju st ed R 2 D L Q I C ru de Pr e 9. 86 ± 4 .0 3 9. 38 ± 4 .1 8 0. 47 ( -2 .0 9 to 3 .0 4) 1s t m on th 2 ± 1. 01 2. 14 ± 0 .9 8 -0 .1 4 (- 0. 79 t o 0. 50 ) -0 .1 4 (- 0. 77 t o 0. 49 ) 0. 01 0. 65 7 -0 .0 21 2n d m on th 1. 15 ± 0 .7 6 0. 95 ± 0 .7 6 0. 21 ( -0 .2 9 to 0 .7 0) 0. 27 ( -0 .3 6 to 0 .9 0) 0. 02 0. 40 0 -0 .0 07 A dj us te da Pr e 9. 86 ± 4 .0 3 9. 38 ± 4 .1 8 0. 47 ( -2 .0 9 to 3 .0 4) 1s t m on th 1. 99 ± 0 .6 2 2. 15 ± 0 .6 0 -0 .1 6 (- 0. 56 t o 0. 24 ) -0 .2 6 (- 0. 89 t o 0. 37 ) 0. 01 0. 41 9 0. 61 2 2n d m on th 1. 17 ± 0 .6 3 0. 94 ± 0 .6 3 0. 22 ( -0 .1 8 to 0 .6 4) 0. 36 ( -0 .2 8 to 0 .9 9) 0. 02 0. 26 9 0. 31 1 *C al cu la te d ba se d on o ne -w ay A N O V A /A N C O V A ; * *S ig ni fi ca nt ( P≤ 0. 05 ); a . A dj us te d fo r ba se lin e pr e- tr ea tm en t sc or e (c al cu la te d ba se d on O ne w ay A N O V A / A N C O V A m od el ). Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 7 particularly herbal remedies [24-26]. In this regard, some ev- idence supports the efficacy of herbal remedies in the treat- ment or improvement of several dermatological conditions [27-29]. Considering the concerns associated with the use of conventional drugs for seborrheic dermatitis, such as non-compliance with medication instructions, drug resis- tance, and side effects, various studies have been conducted on the use of medicinal plants. Coronata serratula, Cirsium eriophorum, Myrtus communis, Apium graveolens, Quas- sia amara, and Ananas comosus are some plants that have been shown to help reduce the itching and flaking that come with the disease and to stop the growth of Malassezia fungi in the lab. After four weeks of treatment with the prepared cream containing these ingredients, a significant reduction in the seborrheic dermatitis score was recorded [30]. These compounds of medicinal plants have led to a more diverse range of treatments for seborrheic dermatitis. For example, a shampoo based on Rosa centifolia petal extract was found to have anti-inflammatory, antioxidant, and sebum secretion prevention properties. Similar effects were reported for tea tree oil-based shampoos [31]. Recent studies have highlighted the anti-microbial, an- tioxidant, and anti-inflammatory properties of rosemary, making it suitable for various dermatological conditions. Panahi and colleagues conducted a study to investigate the clinical efficacy of rosemary oil in treating androgenetic alo- pecia and compared its effects with 2% minoxidil over a pe- riod of six months in 100 patients. Both groups experienced a significant increase in hair count at the 6-month endpoint compared to the baseline [32]. The study conducted by Lah- raseb and colleagues also showed that the simultaneous use of rosemary topically can enhance the efficacy of minoxidil in the treatment of alopecia areata [33]. This finding of our study regarding the reduction in the ASAF score in patients with seborrheic dermatitis was consistent with a study by Mangion and colleagues, who re- ported that azoles could significantly reduce the ASFS score after treatment [34]. Another study, by Ashtiani and col- leagues, showed a reduction in flaking and itching as well as a decrease in the ASFS score in the group using ketoconazole. Another group of patients used Cepigene® shampoo, which includes rosemary plant in the composition of this shampoo; the ASFS score in this group decreased after the use of this substance [35]. Another remarkable finding in our study was the re- duction in the level of scalp itching in both groups receiv- ing ketoconazole and rosemary, and this reduction was significantly more prominent in the patients in the rose- mary group. A comprehensive review by Francisco and col- leagues supports this result, indicating that patients using rosemary-containing compounds reported less itching after treatment [36]. This result was in line with the findings of a study by Bidhendi and colleagues [37], who showed that participants who used a polyherbal extract lotion, includ- ing the extract of rosemary, experienced less scalp itching than those in the azole group. The study by Ashtiani and colleagues also showed that Cepigene® shampoo, compared to ketoconazole, had a greater ability to reduce the itch and scale of the disease [35]. Additionally, in this study, the DLQI score showed an increase in patient quality of life after each visit for both the rosemary and ketoconazole treatment groups. A review of the effects of herbal oils on seborrheic dermatitis found that rosemary-containing oils led to better treatment outcomes, decreased disease recurrence, and higher patient satisfaction [12], which supported the results of our study. The scientific research suggests that rosemary extract’s essential oils are rich in aromatic secondary metabolites, such as terpenes and phenolic components, which possess antimicrobial properties. Furthermore, empirical data have indicated that rosemary essential oil has the potential to be utilized in the development of anti-dandruff products [12 38-42]. Additionally, rosmarinic acid has been identified as the primary component of rosemary plant, according to multiple studies. This component has the potential to con- tribute to the reported antibacterial and anti-inflammatory activities [21 43 44]. There were some limitations in this study. First, the wide ranges of the confidence interval values of the effect sizes reported in Tables 2 and 3 indicated that the results of this study were inconclusive, which could be due to the low sam- ple size of this study. Therefore, further studies with a larger sample size are strongly recommended. Moreover, the pres- ent study was only focused on the clinical aspect of treat- ing seborrheic dermatitis with a lotion made from rosemary extract in comparison with ketoconazole lotion. Therefore, the phytochemical component analyses of this herbal remedy were not conducted in this study, and it is recommended to do so in future studies. Finally, in this case, we did not follow up with the patients for a longer time to evaluate the reoc- currence of the disease. Therefore, we recommend further studies to examine patients for the reoccurrence of sebor- rheic dermatitis and its symptoms over a longer period of time, especially after discontinuing the medication. Conclusion According to the results of our study, both 5% rosemary ex- tract lotion and 2% ketoconazole lotion demonstrated effi- cacy in reducing the ASFS scale, with the role of rosemary being more pronounced. Both treatments reduced the itching scale (itchy quant) and improved the quality of life for pa- tients. No significant difference was observed between the 8 Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 Drug Metab. 2018;19(5):414-23. DOI:  10.2174/13892002186 66170810170124. 16. Hosseinkhani A, Ziaian B, Hessami K, Kashkooe A, Pasalar M. An Evidence-Based Review of Antitussive Herbs Containing Essential Oils in Traditional Persian Medicine. Curr Drug Dis- cov Technol. 2021;18(2):179-85. DOI: 10.2174/156800962066 6200421091245. 17. Memariani Z, Moeini R, Hamedi SS, Gorji N, Mozaffarpur SA. Medicinal plants with antithrombotic property in Per- sian medicine: a mechanistic review. J Thromb Thrombolysis. 2018;45:158-79. DOI: 10.1007/s11239-017-1580-3. 18. Ait‐Ouazzou A, Lorβn S, Bakkali M, et al. Chemical com- position and antimicrobial activity of essential oils of Thymus algeriensis, Eucalyptus globulus and Rosmarinus offi- cinalis from Morocco. J Sci Food Agric. 2011;91(14):2643-51. DOI: 10.1002/jsfa.4505. 19. Ayala‐Zavala JF, Gonzβlez‐Aguilar GA, Del‐Toro‐Sβnchez L. Enhancing safety and aroma appealing of fresh‐cut fruits and vegetables using the antimicrobial and aromatic power of es- sential oils. J Food Sci. 2009;74(7):R84-R91. DOI: 10.1111 /j.1750-3841.2009.01294.x. 20. Bernardes WA, Lucarini R, Tozatti MG, et al. Antibacterial activ- ity of the essential oil from Rosmarinus offi cinalis and its major components against oral pathogens. Z Naturforsch C J Biosci. 2010;65(9-10):588-93. DOI: 10.1515/znc-2010-9-1009. 21. Hashem MM, Attia D, Hashem YA, Hendy MS, AbdelBasset S, Adel F, Salama MM. Rosemary and neem: an insight into their combined anti-dandruff and anti-hair loss efficacy. Sci Rep. 2024;14(1):7780. DOI: 10.1038/s41598-024-57838-w. 22. Muyima NO, Nkata L. Inhibition of the growth of dermatophyte fungi and yeast associated with dandruff and related scalp in- flammatory conditions by the essential oils of Artemisia afra, Pteronia incana, Lavandula officinalis and Rosmarinus offici- nalis. Journal of Essential Oil Bearing Plants. 2005;8(3):224-32. DOI:10.1080/0972060X.2005.10643451. 23. Tamer F, Yuksel ME, Sarifakioglu E, Karabag Y. Staphylococ- cus aureus is the most common bacterial agent of the skin flora of patients with seborrheic dermatitis. Dermatol Pract Concept. 2018;8(2):80. DOI: 10.5826/dpc.0802a04. 24. Parvizi MM, Fatehi N, Jaladat AM, Gholampour Z, Shahriarirad R, Erfani A. Epidemiological factors in patients with dermatologic conditions referring to the clinic of traditional Persian Medicine: A cross-sectional study. Int J Clin Pract 2021;75(11):e14788. DOI: 10.1111/ijcp.14788. 25. Parvizi MM, Forouhari S, Shahriarirad R, Shahriarirad S, Bradley RD, Roosta L. Prevalence and associated factors of com- plementary and integrative medicine use in patients afflicted with COVID-19. BMC Complement Med Ther. 2022;22(1):251. DOI: 10.1186/s12906-022-03722-x. 26. Dastgheib L, Farahangiz S, Adelpour Z, Salehi A. The Preva- lence of Complementary and Alternative Medicine Use among Dermatologic Outpatients in Shiraz, Iran. Iran J Med Sci. 2016; 41(3 Suppl):S70. 27. Niazi M, Mehrabani M, Namazi MR, et al. Efficacy of a top- ical formulation of henna (Lawsonia inermis L.) in contact dermatitis in patients using prosthesis: A double-blind random- ized placebo-controlled clinical trial. Complement Ther Med. 2020;49:102316 DOI: 10.1016/j.ctim.2020.102316. 28. Mojahedi M, Alizadeh M, Kebria AS, Parvizi MM. Successful maintenance treatment of a patient with chronic dermatitis with two groups. Considering the results of this study, rosemary may be a suitable treatment option for patients with scalp seborrheic dermatitis, particularly in cases of non-response to azoles, side effects, or severe itching. However, further ex- tensive studies are recommended to provide more reliable results for the treatment of these patients. References 1. Borda LJ, Perper M, Keri JE. Treatment of seborrheic dermati- tis: a comprehensive review.  J Dermatolog Treat. 2019;30(2): 158-169. DOI:10.1080/09546634.2018.1473554 2. Akbaş A, Kılınç F, Şener S, Hayran Y. Vitamin D levels in pa- tients with seborrheic dermatitis. Rev Assoc Med Bras (1992). 2023;69:e20230022. DOI: 10.1590/1806-9282.20230022 3. Dessinioti C, Katsambas A. Seborrheic dermatitis: etiology, risk factors, and treatments: facts and controversies. Clin Dermatol. 2013;31(4):343-51. DOI: 10.1016/j.clindermatol.2013.01.001 4. Bakardzhiev I, Argirov A. New insights into the etiopathogen- esis of seborrheic dermatitis. Clin Res Dermatol Open Access. 2017;4(1):1-5. DOI:10.15226/2378-1726/4/1/00152 5. Zani M, Soares R, Arruda A, de Arruda L, Paulino L. Ketoconazole does not decrease fungal amount in patients with seborrhoeic dermatitis. Br J Dermatol. 2016;175(2):417-21. DOI: 10.1111/bjd.14501 6. Araya M, Kulthanan K, Jiamton S. Clinical characteristics and quality of life of seborrheic dermatitis patients in a tropical country. Indian J Dermatol. 2015;60(5):519. DOI: 10.4103 /0019-5154.164410 7. Dall’Oglio F, Nasca MR, Gerbino C, Micali G. An overview of the diagnosis and management of seborrheic dermatitis. Clin Cosmet Investig Dermatol. 2022:1537-48.  DOI: 10.2147/CCID.S284671 8. Gupta AK, Madzia S, Batra R. Etiology and management of seborrheic dermatitis. Dermatology. 2004:208(2):89-93. DOI: 10.1159/000076478. 9. Faergemann J, Borgers M, Degreef H. A new ketoconazole topi- cal gel formulation in seborrhoeic dermatitis: an updated review of the mechanism. Expert Opin Pharmacother. 2007;8(9): 1365-71. DOI: 10.1517/14656566.8.9.1365. 10. Coondoo A, Phiske M, Verma S, Lahiri K. Side-effects of topi- cal steroids: A long overdue revisit. Indian Dermatol Online J. 2014;5(4):416. DOI: 10.4103/2229-5178.142483. 11. Safarini OA, Patel J. Calcineurin inhibitors. 2020. 12. Jain S, Arora P, Nainwal LM. Essential oils as potential source of anti-dandruff agents: a review. Comb Chem High Throughput Screen. 2022;25(9):1411-26. DOI: 10.2174/138620732466621 0712094148. 13. Ayatollahi A, Firooz A, Lotfali E, Mojab F, Fattahi M. Herbal Therapy for the Management of Seborrheic Dermatitis: A Nar- rative Review. Recent Adv Antiinfect Drug Discov. 2021;16(3): 209-26. DOI: 10.2174/2772434416666211029113213. 14. Hadizadeh-Talasaz F, Mardani F, Bahri N, Rakhshandeh H, Khajavian N, Taghieh M. Effect of Rosemary cream on episi- otomy wound healing in primiparous women: A randomized clinical trial. BMC Complement Med Ther. 2022;22(1):226. DOI: 10.1186/s12906-022-03675-1. 15. Shirbeigi L, Dalfardi B, Abolhassanzadeh Z, Nejatbakhsh F. Dementia etiologies and remedies in traditional Persian med- icine; A review of medicinal plants and phytochemistry. Curr Original Article | Dermatol Pract Concept. 2024;14(4):e2024242 9 37. Bidhendi N, Ahmadi Ashtiani H, Ayatollahi A, Yadangi S, Ghorban Dadras O, Firooz A. Comparison of the efficacy and safety of a herbal extract lotion with clotrimazole 1% lotion in the treatment of seborrheic dermatitis: A randomized clinical trial. Dermatology and Cosmetic 2017;7(4):189-99. 38. del Pilar Sβnchez-Camargo A, Herrero M. Rosemary (Rosmarinus officinalis) as a functional ingredient: recent scientific evidence. Curr Opin Food Sci. 2017;14:13-19. DOI:10.1016/j.cofs.2016 .12.003 39. Ojeda-Sana AM, van Baren CM, Elechosa MA, Juβrez MA, Moreno S. New insights into antibacterial and antioxidant activities of rosemary essential oils and their main components. Food control. 2013;31(1):189-95. DOI:10.1016/j.foodcont.2012.09.022 40. Stojiljkovic J, Trajchev M, Nakov D, Petrovska M. Antibacterial activities of rosemary essential oils and their components against pathogenic bacteria. Advances in Cytology & Pathology 2018. 41. Wulandari D, Sopyan I, Ginaris RP, Fathurrohim MF, Maya I. Potential of Essential Oil as Anti-Dandruff in Scalp Treatment Preparations. Fitofarmaka: Jurnal Ilmiah Farmasi 2022;12(2): 156-68. DOI: 10.33751/jf.v12i2.5600. 42. Sumintarti S, Hajrah-Yusuf AS, Ruslin M. Effects of rosemary (Rosmarinus officinalis L.) leaf extract on angular cheilitis in- duced by staphylococcus aureus and candida albicans in male wistar rats. Int J App Pharm. 2018;10(1):178-81. DOI:10.22159 /ijap.2018.v10s1.39. 43. Sharma Y, Velamuri R, Fagan J, Schaefer J. Full-spectrum anal- ysis of bioactive compounds in rosemary (Rosmarinus officina- lis L.) as influenced by different extraction methods. Molecules. 2020;25(20):4599. DOI:10.3390/molecules25204599. 44. Colica C, Di Renzo L, Aiello V, De Lorenzo A, Abenavoli L. Rosmarinic acid as potential anti-inflammatory agent. Rev Recent Clin Trials. 2018;13(4):240-42. DOI: 10.2174/1574887 11304180911095818. leech therapy. J Res Med Sci. 2023;28:60 DOI: 10.4103/jrms .jrms_199_22. 29. Parvizi MM, Heydari M, Namazi MR. Successful treatment of chronic scalp seborrheic dermatitis using traditional Persian medicine: a case report and literature review. Galen Medical Journal 2017;6(2):157-59. DOI: 10.22086/GMJ.V6I2.706 30. Mustarichie R, Rostinawati T, Pitaloka DAE, Saptarini NM, Iskandar Y. Herbal Therapy for the Treatment of Seborrhea Dermatitis. Clin Cosmet Investig Dermatol. 2022:2391-405. DOI: 10.2147/CCID.S376700. 31. Barak-Shinar D, Green LJ. Scalp seborrheic dermatitis and dan- druff therapy using a herbal and zinc pyrithione-based ther- apy of shampoo and scalp lotion. J Clin Aesthet Dermatol. 2018;11(1):26. 32. Panahi Y, Taghizadeh M, Marzony ET, Sahebkar A. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial. Skinmed. 2015;13(1):15-21. 33. Lohrasb MH, Ghodrat M, Meshkibaf MH. Therapeutic Effects of Topical Minoxidil or Rosemary and the Combination of Both on the treatment of Alopecia areata. J. adv. biomed. sci. 2014;4(4):475-84. DOI: 20.1001.1.22285105.2015.4.4.12.0. 34. Mangion SE, Mackenzie L, Roberts MS, Holmes AM. Seborrheic dermatitis: Topical therapeutics and formulation design. Eur J Pharm Biopharm. 2023; 185:148-164. DOI: 10.1016/j.ejpb .2023.01.023. 35. Ashtiani HA, Rastegar H, Aghaei M, Ehsani A, Barikbin B, Salout MH. Clinical efficacy of natural formulated shampoo in subjects with dandruff and seborrheic dermatitis. Am. J. Res. Commun. 2013;1(8):63-80. 36. Gonzβlez-Minero FJ, Bravo-Díaz L, Ayala-Gómez A. Rosmari- nus officinalis L.(Rosemary): An ancient plant with uses in personal healthcare and cosmetics. Cosmetics 2020;7(4):77. DOI: 10.3390/cosmetics7040077.