10.5826/dpc.1302a89
Introduction: Several dermatological diseases lead to inflammatory conditions of the scalp. Most of these afflictions are recalcitrant and require long term maintenance treatment.
Objectives: We present a case series where topical tacrolimus was used in a solution vehicle for these conditions.
Methods: A total of 22 patients (aged 24-90 years) with confirmed diagnosis of lichen planus pilaris (LPP),discoid lupus (DL),frontal fibrosing alopecia (FFA),erosive pustulosis of the scalp (EPS) or folliculitis decalvans (FD) were evaluated and treated with tacrolimus solution (0.1%) applied twice daily for 1 month, then once daily for another month and alternate days for 4 months. Efficacy was evaluated by an investigator global assessment,clinical and dermoscopic evaluation at weeks 4,8 and 24.The safety assessment included monitoring of all adverse events.
Results: The study included 13 patients with LPP, 2 with DL, 2 with FD, 2 with EPS and 3 with AFF.After 1 month, 14 patients (63.6%) had a good response and 7 (31.8%) had excellent response.After 2 months, 16 patients (72.7%) had excellent response, and this response was persistent after 6 months of treatment.
Conclusions: Tacrolimus in solution,even if not yet commercially available,was an effective and well tolerated alternative for the maintenance treatment of inflammatory conditions of the scalp.
text/xml
2160-9381
2664
en
Caterina Mariarosaria Giorgio
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
Folliculitis Decalvans
Tacrolimus in Solution as an Option to Inflammatory Conditions of the Scalp
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-06-21
2023-04-29
2023-05-31
e2023089
Dermatol Pract Concept
Introduction: Several dermatological diseases lead to inflammatory conditions of the scalp. Most of these afflictions are recalcitrant and require long term maintenance treatment.
Objectives: We present a case series where topical tacrolimus was used in a solution vehicle for these conditions.
Methods: A total of 22 patients (aged 24-90 years) with confirmed diagnosis of lichen planus pilaris (LPP),discoid lupus (DL),frontal fibrosing alopecia (FFA),erosive pustulosis of the scalp (EPS) or folliculitis decalvans (FD) were evaluated and treated with tacrolimus solution (0.1%) applied twice daily for 1 month, then once daily for another month and alternate days for 4 months. Efficacy was evaluated by an investigator global assessment,clinical and dermoscopic evaluation at weeks 4,8 and 24.The safety assessment included monitoring of all adverse events.
Results: The study included 13 patients with LPP, 2 with DL, 2 with FD, 2 with EPS and 3 with AFF.After 1 month, 14 patients (63.6%) had a good response and 7 (31.8%) had excellent response.After 2 months, 16 patients (72.7%) had excellent response, and this response was persistent after 6 months of treatment.
Conclusions: Tacrolimus in solution,even if not yet commercially available,was an effective and well tolerated alternative for the maintenance treatment of inflammatory conditions of the scalp.
Caterina Mariarosaria Giorgio
2023/04/29
10.5826/dpc.1302a89
e2023089
Dermatology Unit, University of Campania L.Vanvitelli, Naples, Italy 
2160-9381
Folliculitis Decalvans
en
e2023089
Bastida, J., Valerón-Almazán, P., Santana-Molina, N., Medina-Gil, C., & Carretero-Hernández, G. (2012). Treatment of folliculitis decalvans with tacrolimus ointment. International Journal of Dermatology, 51(2), 216–220.
Tacrolimus in Solution as an Option to Inflammatory Conditions of the Scalp
https://dpcj.org/index.php/dpc/article/download/2664/2086
                 Tacrolimus in Solution as an Option
               to Inflammatory Conditions of the Scalp
               Camila Scharf1, Gaetano Licata2, Giulia Briatico1, Sebastiano Pellerone1,
                       Giuseppe Argenziano1, Caterina Mariarosaria Giorgio1


1 Dermatology Unit, University of Campania L.Vanvitelli, Naples, Italy
2 Dermatology Unit, San Antonio Abate Hospital, Trapani, Italy



Key words: Tacrolimus, Lichen Planus Pilaris, Discoid Lupus, Frontal Fibrosing Alopecia, Folliculitis Decalvans
Citation: Scharf C, Licata G, Briatico G, Pellerone S, Argenziano G, Giorgio C. Tacrolimus in Solution as an Option to Inflammatory
Conditions of the Scalp. Dermatol Pract Concept. 2023;13(2):e2023089. DOI: https://doi.org/10.5826/dpc.1302a89
Accepted: September 22, 2022; Published: April 2023
Copyright: ©2023 Scharf 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: Camila Scharf, MD, University of Campania L. Vanvitelli, Naples, Italy. E-mail: kmischarf@gmail.com




  ABSTRACT             Introduction: Several dermatological diseases lead to inflammatory conditions of the scalp. Most of
                       these afflictions are recalcitrant and require long term maintenance treatment.
                       Objectives: We present a case series where topical tacrolimus was used in a solution vehicle for these
                       conditions.
                       Methods: A total of 22 patients (aged 24-90 years) with confirmed diagnosis of lichen planus pilaris
                       (LPP), discoid lupus (DL), frontal fibrosing alopecia (FFA), erosive pustulosis of the scalp (EPS) or
                       folliculitis decalvans (FD) were evaluated and treated with tacrolimus solution (0.1%) applied twice
                       daily for 1 month, then once daily for another month and alternate days for 4 months. Efficacy was
                       evaluated by an investigator global assessment, clinical and dermoscopic evaluation at weeks 4, 8
                       and 24. The safety assessment included monitoring of all adverse events.
                       Results: The study included 13 patients with LPP, 2 with DL, 2 with FD, 2 with EPS and 3 with AFF.
                       After 1 month, 14 patients (63.6%) had a good response and 7 (31.8%) had excellent response. After
                       2 months, 16 patients (72.7%) had excellent response, and this response was persistent after 6 months
                       of treatment.
                       Conclusions: Tacrolimus in solution, even if not yet commercially available, was an effective and well
                       tolerated alternative for the maintenance treatment of inflammatory conditions of the scalp.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023089                                                                        1
Introduction                                                       males), with confirmed histologic diagnosis of LPP, DL, FFA,
                                                                   FD or EPF. Histological diagnosis had been recorded on pa-
Several dermatological diseases may lead to inflammatory           tients charts, after a 4 mm punch biopsy and analyzed by
conditions of the scalp. Hyperkeratosis, pruritus, alopecia,       an experienced dermatopathologist. Patients were informed
and inflammatory signs (such as erythema and purulence)            of the potential benefits and risks of topical application of
are common symptoms of scalp disorders and therefore a             tacrolimus and had agreed to apply as indicated and signed
significant overlap in clinical symptomatology can be seen.        the informed consent. Patients who did not complete the
Most of these afflictions are recalcitrant conditions, and cor-    24-week follow-up were excluded from the study.
ticosteroids have been widely used, in spite of its well-known        Assessment included the patients age, gender, clinical and
side effects of atrophy and rebound [1,2].                         dermoscopical images, past therapies and adverse events. All
    Treatment of these conditions varies accordingly to the        patients after enrolment were subsequently followed-up and
disease itself, as the pathogenic principles are also different,   assessed by the same 3 dermatologists at 4-week intervals
however, the large amount of hair follicles and intense pro-       until 24 weeks, and related data and information regarding
duction of sebum in the region presents a challenge for topi-      improvement were recorded. An Investigator Global Assess-
cal therapies. The most common conditions are lichen planus        ment (IGA) score of poor, good or excellent response was
pilaris (LPP), discoid lupus (DL), frontal fibrosing alopecia      stablished in every visit.
(FFA), Erosive pustulosis of the scalp (EPS) and folliculitis         The response rate was graded as excellent (>75% of hair
decalvans (FD).                                                    regrowth or absence of inflammatory signs), good (>50 to
    Among the drugs that can be used as an alternative to          75% of hair regrowth or improve of inflammatory signs),
corticosteroids, tacrolimus is a valid option. Tacrolimus is a     poor (>0 to 25%), and no response. The effective rate =
metabolite of the fungus Streptomyces tsukubaensis, devel-         (good + excellent cases number)/total cases number) was
oped as an anti-T-cell immunosuppressor. It acts by inhibit-       calculated. Additionally, local adverse reactions, including
ing the production of interleukins, such as IL-2, IL-3, IL-4,      erythema, atrophy, telangiectasia, pigment changes, and fol-
TNFα, and GM-CSF, being more effective and with slightly           liculitis were observed throughout the study period.
fewer secondary effects than cyclosporine [1]. It is available        Tacrolimus solution 0.1% (Tacrolimus Monohydrate
commercially for oral, intravenous and topical use, being the      0.5-mg/mL in SyrSpend™ SF solution, pH 4, Fagron) was
latter commercialized as creams, ointment or ophthalmo-            prepared by the same pharmacist, as it is not commercially
logic drops.                                                       available, and was applied twice daily for one month, then
    Topical immunomodulators (such as tacrolimus and               once daily for another month and alternate days for 4
pimecrolimus) have been originally developed for the treat-        months. Safety parameters included symptoms and objective
ment of atopic dermatitis but their safety profiles and ex-        findings. Patients were required not to apply other medica-
cellent efficacy as anti-inflammatory agents make them             tions during the study period.
attractive candidates to treat many other skin disorders. In
this context, these drugs have been extensively studied in
dermatology for not only atopic dermatitis but also allergic
                                                                   Results
contact dermatitis, erosive mucosal lichen planus, seborrheic      Baseline demographics of the 22 patients enrolled were re-
dermatitis, and pyoderma gangrenosum [2].                          corded, including 13 women and 9 men, with ages ranging
                                                                   from 24 to 90 years. Of these 22, 13 patients had a diagnosis
Objectives                                                         of LPP, 2 of DL, 2 of FD, 2 of EPS and 3 of FFA, all with
                                                                   previous punch biopsies that confirmed histologically the di-
In this article, we discuss the use of tacrolimus in solution,     agnosis. The average course of disease was of 8 ± 3 months.
which even if not commercially available can be prepared in           The overall effective rate, defined as some degree of hair
a compounding pharmacy, as an alternative for different in-        regrowth and cessation of inflammation (good or excellent
flammatory conditions of the scalp that typically require ste-     response), was of 95,4% and 86% after 1 and 6 months
roids for long-term treatment. We present a case series where      respectively.
it has been used as an alternative for maintenance treatment.         Table 1 presents the results for each condition.
                                                                      Mild redness and scratch occurred in one patient. No se-
                                                                   rious local adverse reactions were detected. One patient with
Methods
                                                                   LPP did not respond to the therapy and two patients with
This study was conducted at a referral Dermatology Unit            LPP lost response after 6 months of therapy.
in Italy, under open-label conditions. Were enrolled patients         Figures 1-4 show clinical and tricoscopic results before
aged 24–90 years, from both genders (13 females and 9              and after treatment.



2                                                                      Original Article | Dermatol Pract Concept. 2023;13(2):e2023089
                                                            Table 1. Results
                                                                                IGA                      IGA                     IGA
         AGE                GENDER                 DIAGNOSIS                  1 Month                 2 Months                6 Months
          62            Female                  LPP                              2                        3                       3
          24            Male                    LPP                              3                        2                       1
          52            Male                    LPP                              2                        2                       1
          75            Female                  LPP                              2                        2                       2
          72            Female                  LPP                              2                        3                       3
          73            Female                  LPP                              2                        2                       3
          63            Female                  LPP                              2                        3                       3
          36            Male                    LPP                              2                        3                       2
          61            Male                    LPP                              0                        0                       0
          40            Female                  LPP                              3                        3                       3
          70            Female                  LPP                              2                        3                       3
          54            Female                  LPP                              2                        3                       3
          51            Female                  LPP                              3                        3                       2
          90            Male                    EPS                              3                        2                       2
          84            Male                    EPS                              2                        3                       3
          77            Female                  DL                               2                        3                       2
          74            Male                    DL                               3                        3                       3
          40            Male                    FD                               3                        3                       3
          53            Male                    FD                               2                        3                       3
          62            Female                  FFA                              2                        3                       3
          64            Female                  FFA                              2                        2                       2
          47            Female                  FFA                              3                        3                       3

IGA: Investigators Global Assessment (1: poor / 2: good / 3: excellent); LPP: Lichen Planus Pilaris, FD: Folliculitis Decalvans; EPS: Erosive
Pustulosis of the Scalp; DL: Dyscoid Lupus; FFA: Fibrosing Frontal Alopecia




          Figure 1. (A) Clinical presentation at first visit of a 68-year-old female with dyscoid lupus. An erythematous and desquama-
          tive plaque of the vertex. (B) Trichoscopy (20x) showing squamation, prominent arborizing blood vessels and brown scattered
          pigmentation. (C) Clinical presentation after 1 month of treatment. (D) Trichoscopy showing no more signs of inflammation.



Original Article | Dermatol Pract Concept. 2023;13(2):e2023089                                                                             3
    Figure 2. (A) Clinical image of a scarring alopecia of the vertex with signs of inflammation, histologically compatible with
    folliculitis decalvans. (B) Trichoscopy showing follicular hyperkeratosis, perifollicular erythema, tufted hairs, and cicatricial
    white patches. (C) Clinical image of a scarring alopecia of the vertex without signs of inflammatory activity. (D) Trichoscopy
    of a scarring alopecia.




      Figure 3. (A) Clinical image of a scarring alopecia of the vertex with signs of desquamation, histologically compatible
      with lichen planus pilaris. (B) Trichoscopy reveals absent follicles, white dots, tubular perifollicular scale and perifollic-
      ular erythema, follicular inflammation and fibrosis. (C) Clinical image of a scarring alopecia of the vertex without signs
      of inflammatory activity. (D) Trichoscopy of a spent scarring alopecia.


4                                                                           Original Article | Dermatol Pract Concept. 2023;13(2):e2023089
    Figure 4. (A) Clinical image of a scarring frontotemporal alopecia histologically compatible with frontal fibrosing alopecia.
    (B) Trichoscopy showing follicular hyperkeratosis, perifollicular erythema, lonely hair and cicatricial white patches. (C) Clinical im-
    age of repilation after 6 months without signs of inflammatory activity. (D) Trichoscopy revealing discreet follicular hyperkeratosis
    and repilation.



Conclusions                                                              inhibitors, hydroxychloroquine, and retinoids [13]. Intrale-
                                                                         sional triamcinolone acetonide has also been described, with
In this case series we discussed the use of tacrolimus in a              different response rates and recurrence levels.
solution for different inflammatory conditions of the scalp.                 FD, even though several publications are available regard-
Even if those conditions differ in pathology and have dif-               ing the treatment, most studies evaluated had small sample
ferent approaches regarding therapy, topical steroids are                size, lacked control groups, and randomization, and in these
usually the first line of therapy for LP, DL, FFA and EPS                studies combination of clindamycin and rifampicin were the
and antibiotics for FD. Sometimes, however, corticosteroids              most commonly referred [14]. Nevertheless, we agree initial
might not be completely effective and these conditions                   treatment with antibiotics is required, most patients recur
when left untreated might evolve into scarring alopecia.                 after the treatment, so maintenance with tacrolimus solution
Literature review did not show any results for the use of                is a viable option. A study that evaluated 4 patients with FD
tacrolimus in solution instead of ointment or cream as an                with tacrolimus in ointment showed that these patients sig-
alternative treatment for inflammatory conditions of the                 nificantly controlled their condition, stopping inflammatory
scalp [10-18].                                                           lesions and progression of the disease, although alopecia and
    The majority of studies available consider the treatment             tufted hairs remained unchanged and the discontinuation of
of LP and DL as the same regarding all anatomic sites, ex-               the therapy produced rapid relapses in all cases [19].
cept for oral mucosa, being the use of topical or systemic                   Calcineurin inhibitors have already been described in the
corticosteroids the first line therapy [10,11]. However, most            literature as a good choice for inflammatory conditions of
patients eventually relapsed, since the corticosteroid treat-            the scalp. Some case reports showed only limited improve-
ment could not be maintained for longer periods.                         ment in LPP (total number of patients: 12; global response
    FFA has been extensively studied in the more recent                  rate: 23.1% (2 of 12); response rate in monotherapy: 11.1%)
years, and current consensus recommends topical treat-                   [15]. Regarding EPS, tacrolimus has recovered skin atrophy
ments including corticosteroids, minoxidil, and calcineurin              both during and after treatment and also led to 40–50% re-
inhibitors and/or systemic treatments including 5α-reductase             growth of hair after 2 months of therapy [16].

Original Article | Dermatol Pract Concept. 2023;13(2):e2023089                                                                                5
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