10.5826/dpc.1401a83
Introduction: Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of amphotericin B, its potential for PV treatment warrants investigation. 
Objectives: This study aimed to compare the efficacy of topical liposomal amphotericin B and clotrimazole cream in treating PV.
Methods: A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years, who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all patients through positive microscopic results. The amphotericin group received topical gel containing liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole 1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment.
Results: Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant difference between the groups in terms of the degree of cure (P=0.75).  Adjustments for age, sex, lesion extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete cure rate (P&gt;0.05).
Conclusions: The topical application of liposomal amphotericin B 0.4% is equally effective as topical clotrimazole 1% in treating pityriasis versicolor. These findings suggest that liposomal amphotericin B could be considered as a viable alternative treatment for PV. Further research is warranted to explore its long-term consequences and safety profile.
text/xml
2160-9381
3736
en
Maryam Sadat Sadati
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
topical treatment
Comparison of the Efficacies of Topical Liposomal Amphotericin B and Topical Clotrimazole in the Treatment of Pityriasis Versicolor
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2024-01-31
2023-08-01
2024-01-31
2024-02-21
e2024083
Dermatol Pract Concept
Introduction: Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of amphotericin B, its potential for PV treatment warrants investigation. 
Objectives: This study aimed to compare the efficacy of topical liposomal amphotericin B and clotrimazole cream in treating PV.
Methods: A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years, who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all patients through positive microscopic results. The amphotericin group received topical gel containing liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole 1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment.
Results: Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant difference between the groups in terms of the degree of cure (P=0.75).  Adjustments for age, sex, lesion extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete cure rate (P&gt;0.05).
Conclusions: The topical application of liposomal amphotericin B 0.4% is equally effective as topical clotrimazole 1% in treating pityriasis versicolor. These findings suggest that liposomal amphotericin B could be considered as a viable alternative treatment for PV. Further research is warranted to explore its long-term consequences and safety profile.
Maryam Sadat Sadati
2024/01/31
10.5826/dpc.1401a83
e2024083
Molecular Dermatology Research Center, Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran.
2160-9381
topical treatment
en
e2024083
Leeming J P, Notman F H. Improved methods for isolation and enumeration of Malassezia furfur from human skin. J Clin Microbiol. 1987;25(10):2017-2019. DOI:10.1128/jcm.25.10.2017-2019.1987. PMID: 3667925. PMCID: PMC269393.
Comparison of the Efficacies of Topical Liposomal Amphotericin B and Topical Clotrimazole in the Treatment of Pityriasis Versicolor
https://dpcj.org/index.php/dpc/article/download/3736/2415
  Comparison of the Efficacies of Topical Liposomal
     Amphotericin B and Topical Clotrimazole
      in the Treatment of Pityriasis Versicolor
           Mehdi Ghahartars1, Hossein Hosseini2, Malek Khedri3, Maryam Sadat Sadati1


1 Molecular Dermatology Research Center, Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran
2 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
3 Molecular Dermatology Research Center, Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran



Key words: amphotericin B, clotrimazole, pityriasis versicolor, topical treatment
Citation: Ghahartars M, Hosseini H, Khedri M, Sadati MS. Comparison of the Efficacies of Topical Liposomal Amphotericin B
and Topical Clotrimazole in the Treatment of Pityriasis Versicolor. Dermatol Pract Concept. 2024;14(1):e2024083.
DOI: https://doi.org/10.5826/dpc.1401a83
Accepted: September 21, 2023; Published: January 2024
Copyright: ©2024 Ghahartars 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 Research Council of Shiraz University of Medical Sciences under Grant 22355.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Maryam Sadat Sadati, Molecular Dermatology Research Center, Dermatology Department, Faghihi Hospital,
Zand Street, Shiraz University of Medical Sciences, Shiraz, 7134846114, Iran. ORCID: 0000-0002-8411-0228 Tel: 007132319049
Email: msadati63@yahoo.com




  ABSTRACT             Introduction: Pityriasis versicolor (PV) often exhibits recurrence even despite treatment, and a
                       ­standardized therapy with a complete cure rate remains elusive. Given the fungicidal property of
                        ­amphotericin B, its potential for PV treatment warrants investigation.
                       Objectives: This study aimed to compare the efficacy of topical liposomal amphotericin B and
                       ­clotrimazole cream in treating PV.
                       Methods: A randomized controlled trial was conducted with 44 PV patients, aged 15 to 70 years,
                       who were equally assigned to either the amphotericin or clotrimazole group. The trial was registered
                       at the Iranian Registry of Clinical Trials on March 7th, 2022. PV diagnosis was confirmed in all
                       ­patients through positive microscopic results. The amphotericin group received topical gel containing
                        liposomal amphotericin B 0.4%, while the other group received topical cream containing clotrimazole
                        1%. Both treatments were applied twice daily to the affected skin lesions for 14 days. The primary
                        outcomes assessed were mycologic cure, clinical cure, and complete cure at day 14 post-treatment.
                       Results: Both drugs demonstrated successful treatment outcomes, with comparable rates of mycologic
                       cure (77.3%), clinical cure (63.6%), and complete combined cure (63.6%). There was no significant
                       difference between the groups in terms of the degree of cure (P=0.75). Adjustments for age, sex, lesion
                       extent, and lesion site yielded insignificant risk ratio and risk difference estimates for the complete
                       cure rate (P>0.05).



Original Article | Dermatol Pract Concept. 2024;14(1):e2024083                                                                   1
                       Conclusions: The topical application of liposomal amphotericin B 0.4% is equally effective as topical
                       clotrimazole 1% in treating pityriasis versicolor. These findings suggest that liposomal amphotericin B
                       could be considered as a viable alternative treatment for PV. Further research is warranted to explore
                       its long-term consequences and safety profile.




Introduction                                                       with clotrimazole cream in the treatment of tinea versicolor,
                                                                   with a focus on determining the most effective therapeutic
Pityriasis versicolor (PV), also known as tinea versicolor, is     approach for PV management.
a prevalent superficial fungal infection of the skin that is be-
nign and noncontagious [1]. The treatment of PV can be ef-
fectively achieved through the use of topical and/or systemic      Methods
agents [1,2]. Topical medications are generally considered
                                                                   Study Design and Ethical Considerations
the first-line therapy for PV [1]. Among the various topical
                                                                   This study was conducted as a single-blind clinical trial
antifungal agents available, several azole compounds that
                                                                   from March 7 to July 22, 2022. The trial utilized systematic
disrupt ergosterol biosynthesis have been extensively stud-
                                                                   random sampling, and the blinding method is described in
ied for their efficacy in treating PV [3]. These studies have
                                                                   detail below. Ethical approval for the study was obtained
primarily focused on comparing the effectiveness of newer
                                                                   from the Ethics Committee of Shiraz University of Medical
topical and oral antifungal agents with well-established clo-
                                                                   Sciences in February 2021 (Ethical Committee Approval ID:
trimazole, which has been widely recognized for its thera-
                                                                   IR.SUMS.MED.REC. 1399.543). The study was registered
peutic benefits [1].
                                                                   in the Iranian Registry of Clinical Trials on March 7, 2022,
    However, there is a noticeable dearth of research explor-
                                                                   with trial registration number IRCT20220221054082N1.
ing the use of amphotericin B in the treatment of PV, despite
                                                                   Written informed consent was obtained from all participants
its lipophilic properties and ability to bind to ergosterol, a
                                                                   after explaining the study purpose, research procedures, and
crucial sterol in the fungal cell wall. This binding action
                                                                   the protection of patients privacy. The publication of skin
leads to the leakage of intracellular components, while also
                                                                   images included in the manuscript was done only with the
stimulating free radical production and enhancing the body’s
                                                                   patients’ written informed consent. The study adhered to
phagocytic system for fungi elimination [3,4]. As a fungicidal
                                                                   the applicable CONSORT guidelines and was conducted in
agent, amphotericin B is effective against a broad range of
                                                                   accordance with the principles stated in the Declaration of
organisms, such as yeast, protozoa (leishmania), flat worms,
                                                                   Helsinki.
molds, and algae [5-7]. However, considering the unique
characteristics and pharmacologic features of amphoteri-
cin B, its potential as a therapeutic option for treating PV       Participant Selection
warrants investigation. Therefore, we hypothesized that li-        Patients with pityriasis versicolor who visited Shahid
posomal amphotericin B could exhibit favorable therapeutic         Faghihi, Dermatology Clinic, Shiraz, Iran, were included in
effects and demonstrate comparable efficacy to clotrimazole.       the study. The diagnosis of PV was based on clinical grounds
Additionally, we sought to explore whether factors such as         and Wood’s light examination. Microscopic confirmation
patients’ age, gender, and site of lesion would influence treat-   of the skin infection was performed using two consecutive
ment success.                                                      potassium hydroxide (KOH) smear examinations, with
                                                                   a 2-day interval between each examination. The study in-

Objectives                                                         cluded patients aged between 15 to 70 years whose disease
                                                                   extent was less than 10%. Exclusion criteria for the study
In a clinical context, finding a medication with improved ef-      were as follows: patient dissatisfaction to participate, his-
ficacy and minimal side effects for the treatment of PV is of      tory of receiving topical or systemic antifungal agents in the
significant value. This is particularly crucial due to the com-    past month, immunosuppressed conditions, sensitivity to an-
mon recurrence of the disease, which can adversely affect a        tifungal drugs, negative result in either of the KOH smear
patient’s quality of life. The primary outcomes assessed in        examinations, non-adherence to medications, and pregnancy
this study were mycologic cure and clinical cure at the end        or breastfeeding. Initially, 80 patients were recruited, but
of the treatment course. Accordingly, the aim of this study is     some patients declined to participate in the second sampling
to compare the efficacy of topical liposomal amphotericin B        for KOH smear examination. Ultimately, 44 patients were



2                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024083
        Figure 1. Changes in Sample Size at Different Stages.




randomly allocated to two groups: the Amphotericin group         formulations of the antifungal agents (gel versus cream), the
(A group) and the Clotrimazole group (B group). Figure 1         study was not blinded to the patients. Thus, blinding was
illustrates the patient allocation process.                      maintained for the researchers. The patients’ data was coded
                                                                 with the letter A indicating the amphotericin group and the
Intervention                                                     letter B representing clotrimazole, followed by a consecutive
The diagnosis of PV was initially made based on clinical         numerical assignment (A/B1, A/B2, etc.) to conceal the pa-
grounds and Wood’s light examination. Mycologic confirma-        tients categorization and the intervention drug used.
tion was then performed through microscopic examination
of scales soaked in 10% potassium hydroxide (KOH) during         Data Collection and Clinical Assessment
the first visit. For the subsequent KOH examination, patients    During the first visit, a dermatologist obtained the patient
were instructed not to bathe or use any antifungal agent for     medical history, performed a physical examination, evalu-
2 days before the second sampling. Patients with two posi-       ated the eligibility criteria, photographed the skin lesions,
tive KOH smear results were randomly assigned to either the      and assessed the extent of the disease. The dermatologist
intervention group or the control group using a permuted         also recorded information related to the skin lesions, such as
block technique. To maintain blinding, the intervention med-     color, size, site of involvement, time of onset, and any previ-
ications were prepared by a researcher who was not involved      ous treatments received. Demographic information, includ-
in the study and were directly delivered to the patients. The    ing age, sex, height, weight, and personal contact number,
intervention group applied liposomal amphotericin B topi-        was collected using a new medical record for each patient.
cal gel (Sina Ampholish 0.4%, Exir Nano Sina Company),           Microscopic examination of specimens in KOH were per-
while the control group applied clotrimazole topical cream       formed twice by another researcher, and the results were
(Clotrimazole-Najo 1% cream, Najo Company) on their              reported to the dermatologist. Patient who met the eligi-
skin lesions twice a day for 14 days. Due to the different       bility criteria were randomized to receive the intervention



Original Article | Dermatol Pract Concept. 2024;14(1):e2024083                                                                3
medication. After 2 weeks, the patients returned to the clinic       variables were reported as standardized mean difference
without bathing, and another dermatologist assessed the              (SMD) ± standard deviations (SD) or medians with inter-
clinical improvement of their lesions compared to the ini-           quartile ranges, depending on their distribution. For descrip-
tial visit.                                                          tive analysis, we used T-test, ANOVA test, Mann-Whitney
                                                                     test, paired T-test, and independent tests. Using a binominal
Outcome Measures                                                     regression model, we assumed a log link function to produce
The primary time point for measurement was 2 weeks after             risk ratios, when exponentiated, can be directly interpreted
the start of treatment or when patients completed a 14-day           as risk ratios. To obtain risk difference, the method assumes
course of treatment. The proportion of participants with my-         an identity link function to obtain regression coefficients
cological cure was determined based on a negative result in          that are risk differences. A P value of less than 0.05 was
the KOH smear examination at 14 days post-­treatment [1,8].          considered statistically significant.
Another primary outcome was clinical cure after 2 weeks of
treatment, which was subjectively assessed by a dermatol-
                                                                     Results
ogist based on the improvement of skin lesions (absence of
scaling and skin lesion removal) compared to the initial visit.      A total of 44 patients participated in the study, comprising
Clinical cure also included participant-reported cure based          24 female (54.5%) and 20 male (45.5%). The mean age of
on cessation of symptoms, such as scaling, itching and dis-          participants in amphotericin and clotrimazole was 31.18±
appearance of the lesion. Complete cure was defined as both          14.94 and 36.77± 14.74 years, respectively. There were no
100% clinical cure and laboratory cure. Incomplete cure was          significant differences between the groups in terms of sex
referred to either clinical cure without laboratory cure or          (P = 0.22) and age (P = 0.21). The most common form of fun-
laboratory cure without full clinical cure. The adverse effects      gal cutaneous infection in both study groups was observed on
assessment included harms reported in the study at any time          the head, neck, extremities, or trunk with regionally isolated
during treatment.                                                    lesions, without a significant difference (P = 0.24) (Table 1).
                                                                     Patients were also categorized based on the extent of skin
Statistical Analysis                                                 involvement into <1%, 1-3%, and >3% groups (Table 1).
According to the study conducted by Kausar et al [9] and             More than 80% of patients treated with amphotericin had
using Cochrane formula, we reached a P value of 28% and              1-3% involvement, while 50% of patients treated with clo-
P = 0.2 (D = 0.2P). The standard error obtained was 0.05.            trimazole had >3% involvement. The study groups differed
Finally, a sample size of 22 patients was obtained for each          significantly in terms of lesion extent (P = 0.02). The average
group. Data were analyzed using SPSS v.21 software. De-              duration of the disease was 4.27± 3.87 months for the am-
scriptive statistics were used to summarize the demographic          photericin group and 6.77 ±6.80 months for the clotrimazole
and clinical characteristics of the participants. Continuous         group, without a significant difference (P = 0.14). The most


                     Table 1. Baseline Demographic Information of the Study Population
                           and Distribution of Patients across Variable Categories.
        Variable                 Category                 Amphotericin Group                Clotrimazole Group            P-value
 Gender                 Female                                    10 (45.45%)                   14 (63.64%)                0.226
                        Male                                      12 (54.55%)                    8 (36.36%)
 Age                    Mean (years)                              31.18± 14.94                  36.77± 14.74               0.218
 Lesion extent          Less than 1%                                0 (0%)                       1 (4.55%)                 0.027
                        1-3%                                      18 (81.83%)                   10 (45.45%)
                        More than 3%                              4 (18.18%)                    11 (50.00%)
 Disease duration       Mean (months)                              4.27± 3.87                    6.77 ±6.80                0.141
 Lesion color           Brown                                     14 (81.82%)                   18 (63.64%)                 0.16
                        White                                     7 (31.82%)                     2 (9.09%)
                        Red                                         0 (0%)                       1 (4.55%)
                        Reddish brown                              1 (4.55%)                     1 (4.55%)
 Site of lesion         Head, neck, or extremities                12 (54.55%)                    7 (31.82%)                0.244
                        Trunk                                     8 (36.36%)                    10 (45.45%)
                        Multiple sites                             2 (9.09%)                     5 (22.73%)



4                                                                        Original Article | Dermatol Pract Concept. 2024;14(1):e2024083
      Table 2. Distribution of Patients across Mycologic, Clinical Cure, and Degree of Cure Modules.
                                                 Amphotericin             Clotrimazole
      Cure definition          Category            group                     group             P-value             RR (95% CI)
    Microscopic cure         Effective            17 (77.3%)               17 (77.3%)               1            1 (0.73 to 1.38)
                             Ineffective           5 (22.7%)                5 (22.7%)
    Clinical cure            < 50%                 3 (13.6%)                2 (9.1%)            0.752               Reference
                             50-99%                5 (22.7%)                7 (31.8%)                           0.69 (0.26 to 1.85)
                             100%                 14 (63.6%)               13 (59.1%)                           0.86 (0.39 to 1.93)
    Degree of cure           Complete             14 (63.6%)               13 (59.1%)           0.757           1.08 (0.67 to 1.72)
                             Partial               8 (36.4%)                9 (40.9%)

CI = confidence interval.



                       Table 3. Impact of Age, Gender, Lesion Site, and Size on Drug Efficacy
                              for Complete Cure (Log-Binomial Logistic Regression).
                       Complete cure                             Risk ratio (95% CI)      P-value        Risk difference (95% CI)
    Interventions (crude)                                        1.07 (0.67 to 1.72)       0.757            0.04 (-0.24 to 0.33)
    Interventions (adjusted by age)                              1.05 (0.65 to 1.69)       0.833            0.04 (-0.24 to 0.34)
    Interventions (adjusted by gender)                           1.30 (0.87 to 1.93)       0.199            0.13 (-0.13 to 0.40)
    Interventions (adjusted by the size of the lesion)b          1.08 (0.68 to 1.74)       0.729          -0.001 (-0.30 to 0.29)
    Interventions (adjusted by the site of the lesion)c          1.02 (0.65 to 1.68)       0.922            0.04 (-0.24 to 0.34)
a
Men in comparison with women; b>3% in comparison with ≤3%; cin comparison with head, neck, or extremities.
CI = confidence interval.



common lesion color was brownish discoloration, observed                risk difference for complete cure without any adjustments
in 81.82% and 63.64% of the patients in each group, re-                 were estimated at 1.07 (95% CI: 0.67 to 1.72) and 0.04
spectively. There was no significant difference in lesion color         (-0.24 to 0.33), respectively. In other words, the likelihood of
between the groups (P = 0.16). One patient in the topical               complete cure in the amphotericin group increased by only
amphotericin B group experienced (irritation and dryness),              0.07 compared to the clotrimazole group, which was not sta-
which was tolerable, and the intervention was continued. No             tistically significant (P = 0.75). Binomial logistic regression
adverse effects were reported by the patients who received              was used to compute adjusted estimates of the risk ratio and
clotrimazole.                                                           risk difference. Adjustments for age, sex, lesion extent, and
      The results of the primary outcome measures are sum-              lesion site resulted in negligible relative and absolute changes
marized in Table 2 using the chi-square test. Both liposomal            in the clinical outcome. Therefore, regardless of their age,
amphotericin B and clotrimazole successfully treated most               sex, lesion size, and site, patients in both groups showed
patients (77.3%) based on microscopic examination. There                almost equal response to amphotericin B and clotrimazole.
was no significant difference in microscopic cure between               None of these factors had a statistically significant effect on
the two antifungal agents (P= 1, RR=1, 95%CI: 0.73-1.38).               the efficacy of the drugs (P > 0.05).
Regarding clinical cure, 14 (63.6%) and 13 (59.1%) of the
patients who received amphotericin B and clotrimazole, re-
                                                                        Conclusions
spectively, achieved full recovery. The analysis also showed
similar clinical effectiveness of both medications (P > 0.05).          PV is commonly treated with ketoconazole, a topical anti-
When assessing mycologic and clinical treatments combined,              fungal agent [10,11]. Previous studies have shown that ke-
14 (63.6%) and 13 (59.1%) of patients in amphotericin and               toconazole cream is equally effective as 1% clotrimazole
clotrimazole groups, respectively, showed complete cure.                and 1% terbinafine cream [12,13]. Although clotrimazole is
No significant difference was found between the groups                  widely used and proven effective [3], there is ongoing re-
regarding the degree of cure (P = 0.75, RR=1.08, 95%                    search to identify alternative effective agents for PV treat-
CI: 0.67-1.72).                                                         ment, beyond the commonly used azoles.
      Table 3 presents the estimation of the interventions effect          Several studies have explored the efficacy of different
on complete cure as a clinical outcome. The risk ratio and              treatment options for PV. For example, the effectiveness



Original Article | Dermatol Pract Concept. 2024;14(1):e2024083                                                                        5
of oral griseoflovin [14], 1% diclophenac gel [15], a single          To address this gap in the literature, we conducted a
400 mg dose of itraconazole [16], and fluconazole [17] were        study to investigate the therapeutic effects of liposomal am-
found to be lower than that of topical clotrimazole [18].          photericin B in treating PV. Based on its pharmacological
Other antifungal agents, such as mycoderm lotion [19], top-        characteristics and potential advantages, we hypothesized
ical terbinafine [20,21], and sertaconazole cream [22], have       that amphotericin B would demonstrate comparable efficacy
demonstrated even better efficacy compared to topical clotri-      to clotrimazole in terms of clinical and microscopic cure
mazole. In a study by Khosravi et al [19], the therapeutic ef-     rates. Microscopic cure refers to a negative result of KOH
fects of a new antifungal lotion (mycoderm) were compared          smear examination of the lesion after the treatment course.
to clotrimazole lotion in 68 patients. The patients applied the    In our study, topical liposomal amphotericin B achieved mi-
lotions twice a day for two weeks. The cure rates reported         croscopic cure in 77.3% of cases after two weeks of treat-
by patients in the clotrimazole and mycoderm groups were           ment, which was comparable to the therapeutic success rate
71% and 91.9%, respectively, with a statistically significant      as patients treated with topical clotrimazole cream. In terms
difference (P < 0.05). The rate of full clinical cure was ob-      of clinical cure, 14 (63.6%) of the patients who received am-
served in 51.6% and 70.3% of the clotrimazole and myco-            photericin B and 13 (59.1%) of those who received clotri-
derm groups, respectively.                                         mazole were fully treated (P > 0.05). These findings suggest
    Amphotericin B, a polyene antifungal agent, exhibits           that topical liposomal amphotericin B is an effective anti-
broad-spectrum activity against various fungal organisms.          fungal agent for both mycological and clinical treatments of
It binds to ergosterol, disrupting the fungal cell wall and        patients with PV. Figures 2 and 3 depict the before and after
causing leakage of intracellular contents [4]. Addition-           treatment images of a male and a female with PV who were
ally, amphotericin B stimulates the body immune response           treated with amphotericin B.
against fungi by inducing the production of free radicals [3].        In a similar study conducted by Sepaskhah et al in
While amphotericin B is commonly used for systemic fun-            2017 [18], topical tacrolimus was compared to topical
gal infections [4], its topical formulation, specifically lipo-    ­clotrimazole in 50 patients. Clinical and microscopic as-
somal amphotericin B, has been primarily investigated for          sessments were performed at the beginning of the study, as
the treatment of other fungal conditions such as cutaneous         well as at the end of 3rd and 5th weeks of treatment. The
leishmaniosis, cutaneous candidiasis, vaginal mucormycosis,        results showed no significant differences were observed in
and onychomycosis [5-7]. The potential of liposomal am-            laboratory and clinical cure rates between the two groups.
photericin B in the topical treatment of PV remains largely        However, the 5-week treatment with tacrolimus did not
unexplored.                                                        significantly affect the hypopigmentation of the lesions.




               Figure 2. (A) A 37-Year-Old Man from Shiraz with a Whitish Neck Lesion for 5 Months, with <1% Skin
               Involvement. (B) Complete Clinical and Mycological Cure of the Same Patient after 14 Days of Topical
               Amphotericin B Treatment.



6                                                                      Original Article | Dermatol Pract Concept. 2024;14(1):e2024083
              Figure 3. (A) A 17-Year-Old Girl from Shiraz with Lesions on the Lower Abdominal Area for 3 Weeks, with
              <1% Skin Involvement. She Was Advised to Apply Amphotericin Gel Twice Daily for 2 Weeks. (B) Complete
              Cure Observed Two Weeks after Treatment.



The hypopigmentation observed in pityriasis versicolor may           clotrimazole reported any side effects. However, it is pos-
be attributed to the inhibitory effect of azelaic acid, pro-         sible for some individuals to experience local side effects
duced by Malassezia species, on tyrosinase, an enzyme in-            such as skin irritation, dryness, and allergic reactions [25].
volved in melanogenesis [23]. Additionally, the production           Serious systemic side effects with topical clotrimazole are
of free radicals by lipoperoxidase can lead to skin damage           extremely rare. Topical amphotericin B is generally consid-
and impaired pigmentation [23]. It is important to note that         ered safe, although there is a potential for dose-dependent
pigmentary changes may take weeks to months to resolve,              adverse reactions, particularly with higher concentrations
even after successful eradication of the fungus [1].                 or prolonged use [26]. One case in our study experienced
    In our study, when considering both mycologic and clin-          tolerable skin sensitivity while receiving topical liposomal
ical treatments combined, 14 (63.6%) and 13 (59.1%) of               amphotericin B. The appropriate concentrations for topical
patients in the amphotericin and clotrimazole groups, re-            amphotericin B range from 0.1% to 0.4%, and treatment
spectively, achieved complete cure. Although there was no            typically lasts 2 to 4 weeks, depending on the formulation
statistically significant difference in the complete cure rates      and severity of the condition [27]. Prolonged use, however,
between the two groups, liposomal amphotericin B showed a            is not recommended. It is worth noting that liposomal for-
slight numerical advantage (RR = 1.07; 95% CI: 0.67-1.72).           mulations of amphotericin B improve drug delivery and
However, this difference was not statistically significant           enhance efficacy and safety [26]. On the other hand, the
(P > 0.7). Azoles are known to possess anti-inflammatory             intravenous use of liposomal amphotericin B is associated
properties and have fungistatic effects [24]. In contrast, topical   with side effects such as hyperpyrexia, hypotension, renal
liposomal amphotericin B has fungicidal properties and may           damage, and hypokalemia [4]. For severe or recurrent cases,
theoretically lead to better treatment outcomes. The lack of         oral medications such as itraconazole and fluconazole are
a significant difference in complete cure rates observed be-         considered second-line treatments [28].       While polyene
tween the two groups may be attributed to the limited sta-           antifungals like amphotericin B provide broad-spectrum
tistical power of the study, raising the possibility that the        coverage against most pathogenic fungi, they are generally
benefits of amphotericin B may have been underestimated.             less effective against dermatophytes [4]. As a result, azoles,
Further studies with larger sample sizes should be conducted         which primarily target superficial infections caused by der-
to confirm these findings. Nevertheless, it is worth noting          matophytes, are recommended as the first-line treatment,
that all patients who achieved full clinical cure were also          while polyene antifungals should be reserved for severe fun-
found to be microscopically free of PV at the end of the             gal infections.
study, irrespective of the treatment received.                          We also hypothesized that the therapeutic efficacy of
    In the present study, we found that topical clotrimazole         our intervention would not be influenced by patients’ demo-
was well-tolerated, and none of the patients treated with            graphic and baseline characteristics. The statistical analysis



Original Article | Dermatol Pract Concept. 2024;14(1):e2024083                                                                   7
of relative risk and risk difference estimates, adjusted to ac-        3. Gupta A K, Kogan N, Batra R. Pityriasis versicolor: a review of
count for potential confounding effects of age, sex, lesion               pharmacological treatment options. Expert Opin Pharmacother.
                                                                          2005;6(2):165-178 DOI:10.1517/14656566.6.2.165. PMID:
extent, and lesion site, did not yield significant results in our
                                                                          15757415.
study. Thus, it appears that the therapeutic efficacy of these
                                                                       4. Hay R. Antifungal drugs-an introduction. J Dermatolog Treat.
antifungal agents is independent of patients age, gender, and             1990;1(sup2):1-3. DOI:10.3109/09546639009089020.
the location of skin lesions.                                          5. Carlile M J, Watkinson S C, Gooday G W. The Fungi. Elsevier
    There are several limitations to our study that should                Science; 2001;3:179.
be considered. First, there are various diseases that share            6. Pazouki M, Panda T. Understanding the morphology of fungi.
                                                                          Bioprocess Biosyst eng. 2000;22:127-143. DOI:10.1007
similar manifestations to pityriasis versicolor and must be
                                                                          /s004490050022.
differentiated, including seborrheic dermatitis, secondary
                                                                       7. Heitman J, Carter D A, Dyer P S, Soll D R. Sexual reproduction
syphilis, pityriasis rosea, pityriasis alba, vitiligo, erythrasma,        of human fungal pathogens. Cold Spring Harb Perspect Med.
and Malassezia furfur [29]. While we relied on the standard               2014;4(8):a019281. DOI:10.1101/cshperspect.a019281. PMID:
KOH examination for confirmation of mycologic cure, the                   25085958. PMCID: PMC4109574.
lack of color contrast in the KOH mount may have affected              8. Bamford JTM, Flores-Genuino RNS, Ray S, et al. Interventions
                                                                          for the treatment of pityriasis versicolor. Cochrane Database
the visualization and accuracy of the results. The use of ad-
                                                                          Syst Rev. 2018;2018(6):CD011208. DOI: 10.1002/14651858
ditional staining techniques, such as methylene blue stain,
                                                                          .CD011208.pub2. PMCID: PMC6513390.
ink blue stain, or Swartz-Medrik stain, could have improved            9. Ahmed N, Kausar S, Shaikh Z, Malik S. Comparison of oral
the diagnostic accuracy. Another limitation is the absence of             itraconazole versus topical clotrimazole in treatment of pityriasis
long-term follow-up care in our study. Pityriasis versicolor              versicolor. Pak Armed Forces Med J. 2017;67:458-461.
is known for its tendency to recur, and longer-term assess-           10. Shi T-W, Zhang J-A, Tang Y-B, Yu H-X, Li Z-G, Yu J-B. A
                                                                            randomized controlled trial of combination treatment with
ments would have provided valuable insights into the dura-
                                                                            ­ketoconazole 2% cream and adapalene 0.1% gel in pityriasis
bility of treatment outcomes. Additionally, our study design
                                                                             ­versicolor. J Dermatolog Treat. 2015;26(2):143-146. DOI:10.3109
only included patients with limited skin involvement, which                   /09546634.2014.921661. PMID: 24802530.
may limit the generalizability of our findings to cases with          11.     Mellen L A, Vallee J, Feldman S R, Fleischer A B. Treatment
more extensive or severe disease. Further studies involving a                 of pityriasis versicolor in the United States. J Dermatolog
broader range of patients, including those with more severe                   Treat. 2004;15(3):189-192. DOI:10.1080/09546630410032421.
                                                                              PMID: 15204154.
or widespread pityriasis versicolor, are needed to evaluate
                                                                      12.     Balwada R P, Jain V K, Dayal S. A double-blind comparison
the potential dose-dependent adverse reactions associated
                                                                              of 2% ketoconazole and 1% clotrimazole in the treatment
with topical amphotericin B and to assess its efficacy in di-                 of pityriasis versicolor. Indian J Dermatol Venereol Leprol.
verse populations.                                                            1996;62(5):298-300. PMID: 20948094.
    In conclusion, our study demonstrates that the topical            13.     Chopra V, Jain V K. Comparative study of topical terbinafine
application of liposomal amphotericin B 0.4% is compara-                      and topical ketoconazole in pityriasis versicolor. Indian J Der-
                                                                              matol Venereol Leprol. 2000;66(6):299-300. PMID: 20877107.
ble in efficacy to topical clotrimazole 1% for the treatment
                                                                      14.     Mansoori P, Mortazavi M. A comparison between topical
of pityriasis versicolor. These findings suggest that topical
                                                                              ­Griseofulvin and topical Clotrimazole in Tinea Versicolor. T­ ehran
liposomal amphotericin B can serve as a viable alternative                     Univ Medical J. 1998;56(2):35-37.
treatment option for pityriasis versicolor. However, it is im-        15.      Sharquie K E, Al-Hamamy H M, Noaimi A A, Al-Shawi I A.
portant to note that based on our current findings, we do not                  Treatment of pityriasis versicolor using 1% diclofenac gel and
recommend topical liposomal amphotericin B as the primary                      clotrimazole cream (comparative therapeutic study). Journal
                                                                               of the Saudi Society of Dermatology & Dermatologic Surgery.
treatment choice for PV. Further research is needed to bet-
                                                                               2011;15(1):19-23.DOI: 10.1016/j.jssdds.2010.10.004.
ter understand the potential consequences and safety profile
                                                                      16.      Köse O, Taştan H B, Gür A R, Kurumlu Z. Comparison of a single
of using liposomal amphotericin B in the long term, as well                    400 mg dose versus a 7-day 200 mg daily dose of itraconazole in
as its comparative effectiveness and cost-effectiveness com-                   the treatment of tinea versicolor. J Dermatolog Treat. 2002;13(2):
pared to other treatment options.                                              77-79. DOI:10.1080/095466302317584430. PMID: 12060506.
                                                                      17.      Dehghan M, Akbari N, Alborzi N, Sadani S, Keshtkar A A.
                                                                               Single-dose oral fluconazole versus topical clotrimazole in pa-
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Original Article | Dermatol Pract Concept. 2024;14(1):e2024083                                                                           9
