10.5826/dpc.1301a12
Introduction: Isotretinoin (ISO)-associated cheilitis is the most common side effect and the most common reason for discontinuation of ongoing therapy. So, various lip balms are also routinely recommended for all patients.
Objectives: We aimed to investigate the effectiveness of local intradermal injections (mesotherapy) of dexpanthenol into the lips to prevent ISO-associated cheilitis.
Methods:  This pilot study was conducted on patients over the age of 18 using ISO (about 0.5 mg/kg/day). All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm. In the mesotherapy group (n=28), 0.1 ml of dexpanthenol was injected into each lip tubercle (4 points total) to the submucosal level. The patients in the control group (n=26) used only the ointment. “ISO cheilitis grading scale (ICGS)” was used in the evaluation of ISO-associated cheilitis. The patients were followed for 2 months.
Results:  Although there was an increase in ICGS scores in the mesotherapy group compared to the baseline, no statistically significant change was observed after treatment (p=0.545). However, in the control group, there was a statistically significant increase in ICGS scores in the 1st and 2nd months compared to the baseline (p&lt;0.001). Lip balms were needed significantly less frequently in the mesotherapy group compared to the control, both in the 1st and 2nd months (p=0.006, p=0.045; respectively).
Conclusions: Lip mesotherapy with dexpanthenol will be a useful option for preventing ISO-associated cheilitis because of its easy application, cost-effectiveness, low complication risk, and high patient satisfaction.
text/xml
2160-9381
2371
en
Ümran Öner
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
mucocutaneous side effect
Lip Mesotherapy With Dexpanthenol As A Novel Approach To Prevent Isotretinoin-Associated Cheilitis
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-01-31
2022-02-06
2023-01-31
2023-02-27
e2023012
Dermatol Pract Concept
Introduction: Isotretinoin (ISO)-associated cheilitis is the most common side effect and the most common reason for discontinuation of ongoing therapy. So, various lip balms are also routinely recommended for all patients.
Objectives: We aimed to investigate the effectiveness of local intradermal injections (mesotherapy) of dexpanthenol into the lips to prevent ISO-associated cheilitis.
Methods:  This pilot study was conducted on patients over the age of 18 using ISO (about 0.5 mg/kg/day). All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm. In the mesotherapy group (n=28), 0.1 ml of dexpanthenol was injected into each lip tubercle (4 points total) to the submucosal level. The patients in the control group (n=26) used only the ointment. “ISO cheilitis grading scale (ICGS)” was used in the evaluation of ISO-associated cheilitis. The patients were followed for 2 months.
Results:  Although there was an increase in ICGS scores in the mesotherapy group compared to the baseline, no statistically significant change was observed after treatment (p=0.545). However, in the control group, there was a statistically significant increase in ICGS scores in the 1st and 2nd months compared to the baseline (p&lt;0.001). Lip balms were needed significantly less frequently in the mesotherapy group compared to the control, both in the 1st and 2nd months (p=0.006, p=0.045; respectively).
Conclusions: Lip mesotherapy with dexpanthenol will be a useful option for preventing ISO-associated cheilitis because of its easy application, cost-effectiveness, low complication risk, and high patient satisfaction.
Ümran Öner
2023/01/31
10.5826/dpc.1301a12
e2023012
Department of Dermatology and Venereology, Kastamonu University School of Medicine, Kastamonu, Turkey
2160-9381
mucocutaneous side effect
en
e2023012
Wolf H, Kieser M. Hamamelis in children with skin disorders and skin injuries: results of an observational study. Eur J Pediatr. 2007; 166: 943-948. doi: 10.1007/s00431-006-0363-1.
Lip Mesotherapy With Dexpanthenol As A Novel Approach To Prevent Isotretinoin-Associated Cheilitis
https://dpcj.org/index.php/dpc/article/download/2371/1968
     Lip Mesotherapy with Dexpanthenol as a Novel
       Approach to Prevent Isotretinoin-Associated
                        Cheilitis
                                                 Çağrı Turan1, Ümran Öner2


1 Department of Dermatology and Venereology, Medical Park Ankara Hospital, Ankara, Turkey
2 Department of Dermatology and Venereology, Kastamonu University School of Medicine, Kastamonu, Turkey



Key words: cheilitis, dexpanthenol, isotretinoin, mesotherapy, mucocutaneous side effect
Citation: Turan Ç, Öner Ü. Lip mesotherapy with dexpanthenol as a novel approach to prevent isotretinoin-associated cheilitis. Dermatol
Pract Concept. 2023;13(1):e2023012. DOI: https://doi.org/10.5826/dpc.1301a12
Accepted: September 22, 2022; Published: January 2023
Copyright: ©2023 Turan 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: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication
Corresponding Author: Ümran Öner, MD, Kuzeykent Mah. Cankat Sok. No: 4 Kastamonu, Turkey. Tel: +905422357700
Email: umran.yildiz9@gmail.com




  ABSTRACT             Introduction: Isotretinoin (ISO)-associated cheilitis is the most common side effect and the most
                       common reason for discontinuation of ongoing therapy. So, various lip balms are also routinely
                       ­recommended for all patients.
                       Objectives: We aimed to investigate the effectiveness of local intradermal injections (mesotherapy) of
                       dexpanthenol into the lips to prevent ISO-associated cheilitis.
                       Methods: This pilot study was conducted on patients over the age of 18 using ISO (about 0.5 mg/kg/
                       day). All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm.
                       In the mesotherapy group (n=28), 0.1 ml of dexpanthenol was injected into each lip tubercle (4 points
                       total) to the submucosal level. The patients in the control group (n=26) used only the ointment. “ISO
                       cheilitis grading scale (ICGS)” was used in the evaluation of ISO-associated cheilitis. The patients were
                       followed for 2 months.
                       Results: Although there was an increase in ICGS scores in the mesotherapy group compared to the
                       baseline, no statistically significant change was observed after treatment (p=0.545). However, in the
                       control group, there was a statistically significant increase in ICGS scores in the 1st and 2nd months
                       compared to the baseline (p<0.001). Lip balms were needed significantly less frequently in the mesother-
                       apy group compared to the control, both in the 1st and 2nd months (p=0.006, p=0.045; respectively).
                       Conclusions: Lip mesotherapy with dexpanthenol will be a useful option for preventing ISO-associated
                       cheilitis because of its easy application, cost-effectiveness, low complication risk, and high patient
                       ­satisfaction.




Original Article | Dermatol Pract Concept. 2023;13(1):e2023012                                                                            1
Introduction                                                       (dexpanthenol) in the prevention of ISO-associated cheili-
                                                                   tis on patient satisfaction, need for moisturizer, and clinical
Acne vulgaris is the most common disease in dermatology            outcomes.
practice, which can occur at any age, especially in adolescents.
Systemic isotretinoin (ISO, 13-cis-retinoic acid) is frequently
                                                                   Methods
prescribed for approximately 6-12 months in patients with
moderate to severe acne vulgaris, based on a total cumula-         This study was approved by the Local Ethics Committee
tive dose of 120-150 mg/kg. [1,2] Despite its high efficacy,       (Decision No: 2021/12-186). The study was performed as
it has mucocutaneous side effects such as xerosis and chei-        per the latest version of the Helsinki Declaration and the
litis, which significantly affect the comfort of the patients’     Guidelines for Good Clinical Practice.
life, as well as systemic side effects such as muscle-bone pain,      In the study protocol, the aim was not to investigate the
headache, teratogenicity, lipid metabolism, and liver func-        superiority of mesotherapy over lip balm, but to evaluate
tion impairment [1]. Side effects other than teratogenicity        the benefits of combining it with conventional topical care.
are thought to be dose-dependent [2]. Although long treat-         This pilot study was conducted on patients who received
ment duration and side effects are challenging for patients,       ISO for the first time in Dermatology outpatient clinics be-
it is a safe treatment [3]. Severe side effects may lead to dose   tween January 2021 and March 2021. Only patients over
reduction or termination of treatment. Therefore, it is crucial    18 years using about 0.5 mg/kg/day ISO were enrolled in the
to control side effects in successful patient management.          study. Written informed consent was obtained from all par-
    ISO-associated cheilitis is the most common side effect        ticipants. Exclusion criteria from the study were the follow-
caused by treatment-related reduction in sebum produc-             ing: the presence of atopy, change of dose during follow-up,
tion, thinning of the stratum corneum, and changes in the          presence of any rheumatological disease, additional drug
skin barrier [2-4]. The frequency of cheilitis was found to        use, lip-licking/biting habit, acne excorie, immunodeficiency,
be 77.5% at low doses (0.26-0.50 mg/kg/day) and 96.4%              local infection, using any steroid cream on the lips and dex-
at high doses (0.76-1 mg/kg/day) [2]. It has been reported         panthenol allergy.
that the most common cause of patients’ ongoing-treatment             In our practice, we recommend dexpanthenol mesother-
refusal is cheilitis [2]. So, various lip balms/moisturizers       apy to the lips in addition to lip balm to all eligible patients
are also routinely recommended for all patients prescribed         using ISO with a proactive approach to reduce the risk of
ISO. The disadvantages of lip moisturizers are their cost,         cheilitis or dry lips. We have got quite positive feedback from
frequent use, and unsatisfactory results. Although vitamin         this procedure, which has a low side effect profile. In this
E and omega-3 supplements have been reported to reduce             study, we retrospectively evaluated patients with and with-
ISO-associated mucocutaneous side effects, they have not           out dexpanthenol mesotherapy to the lips. We convention-
been exactly adopted in practice yet [5,6].                        ally recommend a lip balm to every patient using ISO, even
    Dexpanthenol (D-pantothenyl alcohol, provitamin B5) is         if lip mesotherapy has been applied. All patients included in
frequently used as a topical and localized intradermal micro-      the study were prescribed only hamamelis virginiana distil-
injection (mesotherapy) in dermato-cosmetology and various         late in ointment form (Hametan® 25% ointment) as a lip
diseases. Dexpanthenol moisturizes the skin thanks to its hy-      balm. None of the patients used any additional product to
groscopic properties and repairs the skin barrier by hydrating     moisturize their lips.
the stratum corneum and reducing transepidermal water loss            Firstly, 5% lidocaine pomade was applied to the lips of
[7]. It has been commonly used as an over-the-counter topical      patients who approved the procedure. After waiting approx-
drug for more than 70 years in diseases such as nappy rash,        imately 10-15 minutes, 0.1 ml of dexpanthenol ­(Bepanthen®
contact dermatitis, seborrheic dermatitis, cracked nipples, es-    500 mg/2 ml Ampoule with the solution for injection) was
pecially atopic dermatitis, and dry skin [7]. It supports skin     injected into each lip tubercle (4 points in total) to the
regeneration and wound healing by increasing epidermal dif-        submucosal level (approximately 3-4 mm depth) using
ferentiation [8]. Also, it reduces inflammation after irritation   a 30 gauge-13 mm needle. During the follow-up with the
with its anti-inflammatory properties [9,10]. Allergic reac-       ­p­atients, data such as the pain level of the procedure (Visual
tion due to dexpanthenol is rare, and it is a safe agent [11].     Analog Scale (VAS, 0-10 points)), possible side effects such
Dexpanthenol may be useful in the prevention and treatment         as edema and ecchymosis, subjective satisfaction levels, and
of ISO-associated cheilitis due to these properties.               effect duration of the treatment were recorded. “ISO cheilitis
                                                                   grading scale (ICGS)” developed by Ornelas et al. was used
                                                                   in the evaluation of ISO-associated cheilitis [5] (Table 1).
Objectives
                                                                      All procedures were conducted using Statistical Package
We aimed to investigate the effect of the combination              for Social Sciences software (SPSS Inc., Chicago, IL, USA,
of conventional topical lip balm and lip mesotherapy               v21.0). After checking the normality distribution of scale

2                                                                      Original Article | Dermatol Pract Concept. 2023;13(1):e2023012
                                        Table 1. Isotretinoin Cheilitis Grading Scale.
          Erythema                 Scale/Crust           Fissure                               Commissures
 0     No involvement          No involvement        No fissures        No involvement
 1     Mild erythema           Mild scale/crust      One fissure        Mild involvement: erythematous or scaly
 2     Moderate                Moderate scale/       Two to four        Moderate involvement: erythematous and scaly, lichenified,
       erythema                crust                 fissures           mild fissuring
 3     Severe erythema         Severe scale/crust    Greater than       Severe involvement: more extensive erythema, scale, and
                                                     four fissures      lichenification or any of those with severe fissuring

Total score: ranges from 0 to 12




                Table 2. Comparison of patient characteristics and ISO dose between groups.
                                                                Mesotherapy group               Control group
                                                                     (n=28)                        (n=26)                 p-value
 Age, years                                                          23.8 ± 3.2                    24.0 ± 3.6              0.917
 Sex            Man                                                  9 (32.1%)                    10 (38.5%)              0.627*
                Woman                                                19 (67.9%)                   16 (61.5%)
 Baseline ICGS (ranging 0-12 points)                                  0.6 ± 0.7                    0.6 ± 0.7               0.728
                           2
 Body-mass index (kg/m )                                             22.3 ± 3.4                    22.4 ± 2.9              0.890
 Daily ISO-dose (mg/day)                                             29.6 ± 6.4                    31.9 ± 4.0              0.142
 Daily ISO-dose/kg (mg/kg/day)                                       0.50 ± 0.06                  0.51 ± 0.05              0.141

ICGS: Isotretinoin Cheilitis Grading Scale, ISO: Isotretinoin
Mann Whitney U and Pearson’s chi-square* tests were used.



variables by Shapiro Wilks, Wilcoxon and Friedman’s tests               (p=0.545). However, there was a statistically significant
were used to compare two and more than two dependent                    increase in ICGS scores at the 1st and 2nd months of ISO
groups, respectively. Bonferroni adjustment was applied as              treatment in the control group compared to the baseline
post-hoc (Wilcoxon signed-rank tests) after Friedman’s test             (p<0.001). While there was no difference between the groups
(Bonferroni-adjusted two-sided significance level<0.05).                in terms of ICGS scores at baseline, there was a statistically
Mann-Whitney U test was used for independent groups.                    significant difference at both 1 and 2 months (both, p<0.001)
Pearson’s chi-square test was used to compare independent               (Figure 1). The daily need for lip balm increased significantly
categorical variables.                                                  in both groups compared to the baseline (both, p<0.001).
                                                                        However, in the mesotherapy group, lip balms were needed

Results                                                                 significantly less frequently compared to the control group
                                                                        both in the 1st and 2nd months of ISO treatment (p=0.006,
The study involved 28 patients receiving dexpanthenol me-               p=0.045; respectively). As seen in Table 3, the patients had
sotherapy (mesotherapy group) and 26 patients without                   high satisfaction rates from dexpanthenol mesotherapy, and
the procedure (control group, ointment only). The groups                a statistically significant increase was observed in the sat-
were identical in terms of age and sex distribution (p=0.917,           isfaction rates after the 2nd session (p=0.005). According
p=0.627; respectively). The groups were identical for base-             to 96.4% (n=27) of the patients, the effect of mesotherapy
line ICGS (p=0.728). All patients were using ISO at a dose              appeared in only 1-2 days. After two mesotherapy sessions,
of approximately 0.5 mg/kg, and there was no statistical                it was observed that the patients’ opinions about the effect
difference between the groups in terms of dosage (p=0.141)              duration of the treatment had altered. The effect duration
(Table 2).                                                              was more than four weeks according to 26.1% of the pa-
     The groups were compared with themselves and each                  tients, and 2-4 weeks according to 34.8%-65.2% of them.
other for the ICGS scores and frequencies of daily use of               In the follow-up with the patients, mild angular cheilitis was
lip balm during the 2-month follow-up period (Table 3).                 observed in 3 (10.7%) patients in the mesotherapy group.
In the mesotherapy group, despite the ISO treatment, al-                    The mean score of the procedure-related pain after top-
though there was an increase in ICGS scores compared to                 ical anesthesia was 4.1±1.1. No additional complications
the baseline, no statistically significant change was observed          were observed.

Original Article | Dermatol Pract Concept. 2023;13(1):e2023012                                                                       3
           Table 3. Comparison of several parameters with dependent and independent groups.
                                                                          Baseline         1st month         2nd month         p-value *
 Grade score of ISO-associated cheilitis (ranging 0-12 points)
    Mesotherapy group (n=27)                                              0.6 ± 0.7         1.1 ± 1.3          0.8 ± 0.7         0.545
    Control group (n=26)                                                  0.6 ± 0.7         2.8 ± 0.7          3.4 ± 1.5       <0.001a,b
                                          p-value **                        0.728            <0.001             <0.001
 Frequency of daily use of lip balm (hamamelis ointment)
    Mesotherapy group (n=27)                                              0.9 ± 0.5         4.7 ± 2.3          4.3 ± 2.4       <0.001a,b
    Control group (n=26)                                                  0.8 ± 0.7         6.0 ± 2.5          6.9 ± 4.6       <0.001a,b
                                          p-value **                        0.597             0.006              0.045
 The patients’ opinions in the mesotherapy group regarding the treatment
    Satisfaction level (n=23)             Very satisfied                       -            7 (30.4%)         13 (56.5%)         0.005
                                          Satisfied                            -           14 (60.9%)         10 (43.5%)
                                          Slightly satisfied                   -            2 (8.7%)           0 (0.0%)
                                          Unsatisfied                          -            0 (0.0%)           0 (0.0%)
    Effect duration (n=23)                ≥4 weeks                             -            6 (26.1%)         6 (26.1%)          0.106
                                          2-4 weeks                            -            8 (34.8%)         15 (65.2%)
                                          ≤2 weeks                             -            9 (39.1%)          2 (8.7%)

Data are expressed as mean ± standard deviation.
* Wilcoxon and Friedman’s tests were used for comparisons of two and more than two dependent groups, respectively. Bonferroni
­adjustment was applied as post-hoc (Wilcoxon signed-rank tests) after Friedman’s test (Bonferroni-adjusted significance level<0.05).
 ** Mann Whitney U test was used for independent groups.
 a: p<0.05 for the difference between baseline and 1st month; b: p<0.05 for the difference between baseline and 2nd month; c: p<0.05 for the
difference between 1st month and 2nd month in 2-month patient follow-up




                                  5      CONTROL GROUP (HAMETAN® OINTMENT)

                                         MESOTHERAPY GROUP (BEPATHEN® AMPOULE)


                                  4
                   ICGS (95%CI)




                                  3




                                  2




                                  1




                                  0

                                        BASELINE                1ST MONTH                  2ND MONTH

                   Figure 1. ISO-associated mucositis was significantly lower in the mesotherapy group than in
                   the control group both at 1st month and 2nd months when compared by ICGS scores.
                   ICGS: Isotretinoin cheilitis grading scale, CI: Confidence interval.



4                                                                             Original Article | Dermatol Pract Concept. 2023;13(1):e2023012
Conclusions
Cheilitis is characterized by erythema, dryness, crusting, fis-
sures, and inflammation of the commissures on the lips. It
greatly affects the quality of life of patients due to burning,
itching, and edema [5]. Various sub-clinical types of chei-
litis can be encountered secondary to different etiological
factors such as actinic damage, systemic diseases, immu-
nosuppression, nutritional deficiencies, local irritants and
allergens, infections, and drugs [9,10]. The main cause of
drug-associated cheilitis is systemic retinoids [10]. ISO is an
indispensable and safe agent of dermatology practice with
high cure rates for acne vulgaris [1]. However, it should not
be overlooked that ISO-associated cheilitis is the leading
cause of early termination of treatment, with a rate of 1.4%
[2]. Effectively reducing the risk of cheilitis will increase pa-
tient comfort and treatment sustainability. Although various
supplements such as vitamin E, omega 3, and primrose oil
have been recommended in some studies for mucocutaneous
side effects, there is no established treatment method other
than moisturizers [6,11,12]. In randomized controlled stud-
ies, it was reported that vitamin E supplementation did not
significantly reduce the xerosis associated with ISO [13,14].
Patients may not be willing to use another systemic therapy
while also undergoing long-term ISO therapy. Therefore, we
consider it to be challenging to use oral supplements in prac-
tice. We introduce lip mesotherapy with dexpanthenol as a
novel approach.
    We have experienced highly satisfactory results with lip
mesotherapy with dexpanthenol, which has a high safety
profile and which we frequently prefer in indications such as
hair loss, wound healing, and rejuvenation. To the best of our
knowledge, the effectiveness of dexpanthenol in lip meso-           Figure 2. Patients administered with dexpanthenol mesotherapy to
therapy has not been reported so far. In this study, we found       the lips.
that dexpanthenol mesotherapy combined with topical ther-
apy has excellent efficacy in preventing ISO-associated chei-       minerals, and various bioactive substances into the skin lay-
litis. While there was no difference between the groups in          ers to stimulate fibroblast activity and collagen genesis and
terms of the severity of baseline cheilitis and the frequency of    reverse elastin degeneration and transepidermal water loss
lip balm use before treatment, both parameters were lower           [15,16]. Patients may experience injection-related side ef-
in the mesotherapy group compared to the control group              fects such as pain, erythema, edema, and ecchymosis. Only
in both 1st and 2nd-month examinations. However, even               one of the patients in the study hesitated to continue treat-
if mesotherapy is performed in patients using ISO, topical          ment because of pain. The patients stated that they had no
care should be offered to every patient due to the significant      experience of any bruising or ongoing pain after the proce-
increase in the need to use lip balm. The clinical results re-      dure and that the edema on the lips usually regressed within
corded in the follow-up of the patients in the mesotherapy          1-2 hours. Mild-moderate pain was noted despite topical an-
and control groups after ISO were presented in Figure 2 and         esthesia. We think that this may be reduced further by add-
Figure 3, respectively.                                             ing lidocaine solution to dexpanthenol. Since we observed
    It is assumed that mesotherapy allows slower diffusion,         angular cheilitis in some patients, although the vermilion
higher levels, and longer-lasting effects of drugs in the tis-      was normal, we concluded that 0.05-0.1 ml dexpanthenol
sues around the injection site compared to intramuscular            mesotherapy to the lip commissures, in addition to 4-point
injection or topical applications [15]. This method is a safe       injection, would yield better clinical results. The satisfaction
transdermal drug delivery tool applied by injecting vitamins,       rates of the patients were high, and the significant increase



Original Article | Dermatol Pract Concept. 2023;13(1):e2023012                                                                    5
                                                                     and gene regulation effects of dexpanthenol on dermal fi-
                                                                     broblasts [8,19,20]. We think dexpanthenol injected into
                                                                     the submucosa reduces the severity of cheilitis and the need
                                                                     for moisturizer by increasing hydration and regeneration
                                                                     in ISO-damaged skin, reducing irritation. There are limited
                                                                     studies comparing the efficacy of mesotherapy compared to
                                                                     topical applications of the same agent. While there is no re-
                                                                     search on the efficacy of dexpanthenol, submucosal injection
                                                                     of vitamin C in gingival hyperpigmentation has been found
                                                                     to be superior to the use of its topical form [21].
                                                                         Although the main limitation is a small sample size, sta-
                                                                     tistically significant high efficacy rates were achieved. Tran-
                                                                     sepidermal water loss measurement was not included in the
                                                                     protocol due to technical impossibility. The shortcoming of
                                                                     the study was that we could not compare dexpanthenol me-
                                                                     sotherapy with the topical form of dexpanthenol and pla-
                                                                     cebo. The non-reimbursement of dexpanthenol ointment
                                                                     and the excessive diversity of similar products on the mar-
                                                                     ket necessitated the use of hamamelis virginiana as a con-
                                                                     trol group in our retrospective study. Because hamamelis
                                                                     virginiana (Hametan® ointment), an alternative to dexpan-
                                                                     thenol, is one of the most frequently preferred reimbursed
                                                                     medical products in our country. Indeed, Wolff and Kieser
                                                                     investigated the clinical effects of ointment forms of ham-
                                                                     amelis and dexpanthenol in the treatment of skin/mucous
                                                                     membrane inflammation in children [22]. Accordingly, phy-
                                                                     sicians’ and parents’ efficacy assessments revealed similar or
                                                                     better treatment ratings of hamamelis ointment than dex-
                                                                     panthenol. While it is plausible that water intake reduces
                                                                     the mucocutaneous side effects of ISO, there is no evidence
                                                                     to our knowledge. Therefore, water intake is lacking in the
                                                                     study protocol.
                                                                         In conclusion, the effectiveness of lip mesotherapy with
                                                                     dexpanthenol in the prevention of ISO-associated cheilitis
Figure 3. Control patients applying hamamelis ointment to the lip.   was remarkable. We believe that this method will be a useful
                                                                     adjuvant option for both the prevention and treatment of
in the satisfaction rates after the second session was remark-       ISO-associated cheilitis because of its easy application, low
able. It has been claimed that the most disturbing period in         cost, low complication risk, and high patient satisfaction.
ISO-associated cheilitis is the first month of treatment, after      However, patients’ opinions and approvals on whether they
which patients adapt to xerotic changes [11]. The increase in        want such a needle application should be evaluated. Further
the satisfaction levels of the patients after the second session     placebo-controlled, randomized studies with larger sample
may be related to this adaptation process.                           sizes are needed.
    Dexpanthenol is an important molecule for the physio-
logical function of the epithelium. After absorption through
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Original Article | Dermatol Pract Concept. 2023;13(1):e2023012                                                                                   7
