Received: 2 May 2021 | Revised: 5 June 2021 | Accepted: 14 May 2021

DOI: 10.1111/jocd.14306

ORIGINAL CONTRIBUTIONS

Botulinum toxin type-­A versus 5-­fluorouracil in the treatment

of plaque psoriasis: Comparative study

Fathia M. Khattab MD | Mai A. Samir MD

Department of Dermatology, Venereology

and Andrology, Faculty of Medicine,
Zagazig University, Zagazig, Egypt
Correspondence
Fathia M. Khattab, Department of
Dermatology, Venereology and Andrology,
Faculty of Medicine, Zagazig University,
Egypt
Email: fathiakhattab@yahoo.com
Funding information
No Funding sources
Abstract
Background: Long-­term remission and total clearance in Psoriasis can only be achieved
in a few patients.
Aim: To compare the efficacy and safety of intradermal Botulinum toxin (BTX) in the
treatment of plaque psoriasis.
Subjects and methods: A comparative study conducted in thirty-­five patients with
chronic plaque psoriasis was treated by split-­body therapy. The patients were either
treated with intradermal BTX or with intralesional 5-­fluorouracil (5-­FU) to each of 2
bilaterally symmetrical psoriatic plaque lesions. The outcomes were assessed using
the following criteria: the sum of erythema, scaling, and induration scores and the
clearing percentage of the target plaque lesion assessed by 2 blinded observers.
Results: At the end of the study, the response rate was 85% on the BTX treatment
side and 90% on the 5-­FU side. There was no significant difference between both
sides regarding a clinical response or side effects. The recurrence rate was 15% on
both sides.
Conclusions: Botulinum toxin was a novel, safe, single injection, and effective therapy
for plaque-­t ype psoriasis. More studies are required to further prove the efficacy of
BTX in the treatment of plaque psoriasis.

KEYWORDS
5-­fluorouracil, Botulinum toxin, psoriasis

1 | I NTRO D U C TI O N improvement of plaque psoriasis after injuries that compromised

Psoriasis is a chronic, inflammatory systemic disease that is charac-
terized by erythematous, scaly patches, or plaques over the skin that
occurs due to the hyperproliferation of epidermal keratinocytes.1,2
The 5-­FU is an antimetabolite that inhibits deoxyribonucleic acid
synthesis, as well as ribonucleic acid processing and therefore, de-
creases epidermal proliferation.3,4 It has been widely used topically,
intravenously,5 and intralesionally in various concentrations (0.5%,
6
1%, and 5%) in various dermatological and non-­dermatological
7,8
diseases.
The role of neurocutaneous pathways in the pathogene-
sis of psoriasis has been suggested based on some reports of
some branches of the peripheral nervous system.9,10 BTX injec-
tions have been reported for the treatment of numerous derma-
tological conditions, such as Keloids, hidradenitis suppurativa, and
folds dermatitis.11
The advantage of intralesional is that it allows higher drug con-
centration in the lesion for a longer duration in comparison with top-
ical treatment while avoiding the systemic adverse effects of these
toxic drugs.12
To study the efficacy and safety of BTX and intralesional
5-­
fluorouracil in patients with mild-­
to-­
moderate chronic plaque
psoriasis and to access clinical improvement based on clinical
photographs.

3128 | © 2021 Wiley Periodicals LLC wileyonlinelibrary.com/journal/jocd J Cosmet Dermatol. 2021;20:3128–3132.

KHATTAB and SAMIR
2 | S U B J EC T A N D M E TH O DS
A comparative study was conducted from February 2020 to
August 2020. A group of thirty-­f ive patients above 18 years of
age with chronic plaque psoriasis were divided by split-­
b ody
therapy where one side treated with intradermal BTX and intral-
esional 5-­FU on the other side. They gave written informed con-
sent for the treatment. A written informed consent approved by
the Committee of Human Rights in Research at Zagazig University
was obtained from every participant before the study. The study
had been approved by the Institutional Review Board (IRB) (IRB#:
4799/1-­8–­2019).
Inclusion criteria were patients with mild to moderate, bilaterally
symmetric, and chronic plaque psoriasis. A history of plaque psoria-
sis for a minimum of 2 years with a history of resistance to at least 2
topical treatments (eg, corticosteroids or calcipotriene analogs) with
men or women between 18 and 60 years old.
Exclusion Criteria were Chronic plaque psoriasis involving 60%
of the body surface, pustular or generalized erythrodermic psoriasis,
exposure to sunlight, use of medications that affect or treat psoriasis
during the study, patients with neuromuscular disease, or patients
with the intake of aminoglycoside-­t ype antibiotics and Lactating or
pregnant female.
A complete history was taken; clinical examination and biopsy
were done wherever it was necessary.
The patients were divided into the side was treated with a sin-
gle intradermal botulinum toxin injection and other was treated
with four injections were given at weekly intervals of intralesional
5-­fluorouracil.
2.1 | Botulinum toxin injection side
Botox injections are intradermal at a dose of 100 U, diluted with 5-­ml
sterile physiological sodium chloride solution. Each patient received
individual injections of 2.4 U (Refinex; Made in China) using a grid
with points set at a distance of 2.8 cm apart. Total dosages ranged
from 50 to 100 U, depending on the extent and severity of the af-
fected area. All psoriasis plaques were measured and photographed.
2.2 | 5-­fluorouracil injection side
Another plaque on the other side was treated with intralesional
5-­FU (50 mg/ml) at a dosage of 0.1 ml/cm2. Patients have taken their
sessions weekly for 4 weeks.
2.3 | The outcome was assessed based on
Clinical assessment was done using the total sign score (TSS), also
known as psoriasis severity index, which is the summation of ery-
thema, induration, and scale points and ranges between 0 and 12,
| 3129
where each point was given a grade (0 none, 1 mild, 2 moderate,
3 severe, and 4 very severe).13 The response to treatment was
graded as follow.
No response if 0–­10% improvement
Mild response if 10–­30% improvement
Moderate response if 30–­70% improvement
Excellent response if 70–­90% improvement
Clearance if 90–­100% improvement
It was evaluated at baseline and then every 4 weeks for 16 weeks
and the last follow-­up was at 8, 16, or 24 weeks.
2.3.1 | Psoriasis disability index
The patients' quality of life was assessed using the psoriasis disability
index (PDI).14 The PDI is a 15-­item scale that specifically addresses
self-­reported disability in areas of daily activities, employment, per-
sonal relationships, leisure, and treatment effects. The items are
concerned with the practical effects of psoriasis in everyday's life.
The scores are calculated based on the series of 4 answers.
Not at all—­scores 0
A little—­scores 1
A lot—­scores 2
Very much—­scores 3
If the question remains unanswered score is 0. The PDI is cal-
culated by summing the score of each of the 15 questions resulting
in a maximum of 45 and a minimum of 0. The higher the score, the
more quality of life is impaired. Clinical improvement was assessed
based on photographic documentation done at baseline and then
after 24 weeks.
The recurrence area was rated on a 10-­point scale at 2 months
after treatment in contrast to the baseline lesion: grade 0 (no recur-
rence), grade 1 (1–­10%), grade 2 (11–­20%), grade 3 (21–­30%), grade
4 (31–­4 0%), grade 5 (41–­50%), grade 6 (51–­60%), grade 7 (61–­70%),
grade 8 (71–­8 0%), and grade 9 (81–­100%).13
2.4 | Statistical analysis
The student's unpaired t test was used to test the significant differ-
ence in the outcome between the two groups. Mean and the stand-
ard deviation was used for continuous variable and the p-­value of
<0.05 was considered significant.
3 | R E S U LT S
Thirty-­five patients diagnosed with chronic plaque psoriasis with
two identical lesions on each side and were treated with botulinum
toxin injection and intralesional 5-­fluorouracil. The baseline data of
all these patients are given in Table 1.
3130 | KHATTAB and SAMIR

TA B L E 1 Demographic data at baseline

Patients data (n = 35)

Age (in years) 42.65 ± 2.07

(mean ± SD)
Male: female ratio 19:13
Duration of psoriasis 13 ± 1.68
(in years; mean ± SD)

Abbbreviation: n, total number of patients in each group.

TA B L E 2 PASI score at baseline, at 8 and 16 weeks and% of improvement in PASI score at 16 weeks

PASI score (mean ±SD)

% Of improvement in PASI
Drugs At baseline At 8 weeks At 16 weeks score p-­value

BTX side 19.88 ± 2.65 9.94 ± 1.90 3.28 ± 1.47 85% <0.0001
5 FU side 19.54 ± 3.15 10.01 ± 0.83 3.06 ± 1.05 90% <0.0001

F I G U R E 1 Clearance of the psoriatic

(A) (B)
plaque over the left elbow after
intralesional botox (A) Clinical photograph
before treatment (total sign score=8);
(B) clinical photograph 2 months after
treatment showing a significant decrease
in total sign score which became 0

As regards the TSS, At the end of the study, the response rate
was 85% on the BTX side, while it was 90% on the 5-­FU side. The
grade of improvement evaluated by TSS on both sides is shown in
Table 2. There was no statistically significant difference between
both sides regarding the grade of improvement (Figure 1 and 2).
There was no statistically significant correlation between the
grade of improvement on both sides in all patients (age, sex, dura-
tion of psoriasis, family history of psoriasis, pruritis, and smoking),
which was evaluated and tested at the baseline, every 4 weeks for
16 weeks. (Table 2). On follow-­up, patients on the BTX side showed
sustained results as compared to that of patients on the 5-­FU side.
Recurrence in BTX side was on 3 patients (one with grade 7 and
two with grade 4), while in 5-­FU was in two patients with grade 9.
Psoriasis disability index score was used and was assessed at the
baseline and then at the end of 16 weeks and the time of follow-­up.
At the end of treatment that is after 16 weeks, the PDI became
16.90 ± 3.87 on the BTX side was statistically insignificant (p = 0.24)
as compared to patients in 5-­FU which were 18.63 ± 2.98 (Table 3).
PDI score showed consistency at the time of follow-­up in BTX side
patients as compared to another side.
No clinically significant systemic side effects or treatment-­
related adverse medical events were observed in our study. Most
patients suffered from pain on the injection site, two patients
complain of necrosis and one with hyperpigmentation on the
5-­FU side.
4 | DISCUSSION
Psoriasis is defined as a chronic inflammatory disorder that is ge-
netically determined and leads to hyperproliferation of the skin. It
is a disfiguring condition in which there is an alteration in growth
KHATTAB and SAMIR
F I G U R E 2 Clearance of the psoriatic
(A)
plaque over the right leg after intralesional
5-­fluorouracil (A) Clinical photograph
before treatment (total sign score =7);
(B) clinical photograph 2 months after
treatment showing significant decrease
in total sign score which became 0
TA B L E 3 Psoriasis disability index (PDI) at baseline and at
16 weeks
PDI (Mean ±SD)
Sides Baseline At 16 weeks
BTX side 36.26 ± 3.69 16.90 ± 3.87
5 FU side 37.81 ± 3.34 18.63 ± 2.98
Note: Patients were categorized into 6 groups based on the extent of
individual improvement at week 12. Patients were classified as worse,
no change (0%–­<25% improvement), mild improvement (25%–­<50%
improvement), moderate improvement (50%–­<75% improvement),
near clearance (75%–­<90% improvement), or clearance (Š90%
improvement).
and differentiation of the epidermis, the treatment of that remains
15
challenging.
The nervous system's function in psoriasis was hypothesized
after several studies revealed a high concentration of nerve fibers
in psoriatic skin and an increased level of sensory nerve-­derived
16
CGRP and SPP. BTX inhibits the nerve-­derived release of CGRP
and SP, which may clarify the subjective clinical finding of condition
improvement in inverse psoriasis after Zanchi et al administered
17
BTX-­A .
In our study, the dosage of BTX used for the patient's injections of
2.4 U (Refinex; Made in China) using a grid with points set at a distance
of 2.8 cm apart. Total dosages ranged from 50 to 100 U, depending
on the extent and severity of the affected area and patients achieved
an 85% response rate was; Ten (28.5%) patients showed clearance,
Twelve (34%) patients showed excellent improvement, seven (20%) of
them with moderate improvement, five (14%) with mild improvement
and one patient with no response (3.5%). The psoriasis disability index
showed a reduction from 36.26 to 16.90 (mean).
| 3131
(B)
BTX-­A intradermal injections have shown to increase acanthosis
against placebo and reduce a cutaneous lymphocytic infiltrate, ac-
cording to different studies.15
The positive response of 15 patients with reverse psoriasis was
reported by a patient's self-­evaluation (VAS scale for itching and
pain) and photographic assessment of erythema.16,17 This can be due
to BTX-­ability A's to inhibit neuropeptide release.18,19
5 FU is an antimetabolite that inhibits thymidylate synthase en-
zyme leading to inhibition of DNA synthesis as well as RNA process-
ing and, therefore, decreases epidermal proliferation as in the case
of psoriasis.6
The 5-­FU (50 mg/ml) at a dosage of 0.1 ml/cm2. Patients have
taken their sessions weekly for 4 weeks. The affected area and
patients achieved a 90% response rate; six (17%) patients showed
clearance, 14 (40%) achieved excellent improvement, 6 (17%) with a
moderate improvement, 7 (20%) mild improvement, while two (6%)
patient did not respond to treatment. The psoriasis disability index
showed a reduction from 37 to 18 (mean). Side effects observed in
our study in the group with 5-­FU. Most patients suffered by painful
injections, two patients complain of necrosis, and one with hyper-
pigmentation on the 5-­FU side.
Our results are consistent with Pearlman et al.7 and Mahajan
and Singla, 20 who found 82% and 87.5%, respectively. Taheri et al21
achieved 70–­90% improvement in 61% of patients and greater than
90% improvement in 33.3% of patients and another one showed im-
provement in 60% of psoriatic plaque.6
5 | CO N C LU S I O N
This study demonstrated that intralesional BTX and 5-­FU is a prom-
ising treatment for localized plaque psoriasis with no significant
3132 | KHATTAB and SAMIR
difference. This improvement in psoriasis lesions with BTX as single
application with a high safety profile proposes a novel target in pso-
riasis treatment.
C O N FL I C T O F I N T E R E S T
No conflict of interest.
ORCID
Fathia M. Khattab https://orcid.org/0000-0002-2600-4021
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How to cite this article: Khattab FM, Samir MA. Botulinum
toxin type-­A versus 5-­fluorouracil in the treatment of plaque
psoriasis: Comparative study. J Cosmet Dermatol.
2021;20:3128–­3132. https://doi.org/10.1111/jocd.14306