Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review
Abstract
:1. Introduction
2. Results
- Idiopathic hyperhidrosis
- Chromhidrosis
- Bromhidrosis
- Epidermolysis bullosa simplex, Weber–Cockayne type
- Darier disease
- Pachyonychia congenita
- Alopecia areata
- Androgenetic alopecia
2.1. Sweat Gland Disorders
2.1.1. Idiopathic Hyperhidrosis
2.1.2. Chromhidrosis
2.1.3. Bromhidrosis
2.2. Facial Erythema and Flushing
2.3. Raynaud Phenomenon
2.4. Pompholyx
2.5. Eccrine Nevus
2.6. Postherpetic Neuralgia
2.7. Oily Skin
2.8. Notalgia Paresthetica
2.9. Hailey–Hailey Disease
2.10. Genodermatoses
2.10.1. Epidermolysis Bullosa Simplex, Weber–Cockayne Type
2.10.2. Darier Disease
2.10.3. Pachyonychia Congenita
2.11. Hidradenitis Suppurativa
2.12. Aquagenic Keratoderma
2.13. Alopecia
2.13.1. Alopecia Areata
2.13.2. Androgenetic Alopecia
2.14. Psoriasis
3. Discussion
4. Materials and Methods
4.1. Literature Searches and Selection
4.2. Data Extraction
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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First Author [Ref.], year | Type of Study | n (site) | BoNT-A Doses | Retreatment | Follow-Up | Results |
---|---|---|---|---|---|---|
Wu [54], 2019 | Prospective | 19 (axilla) | NA | NA | 3 months | mean degree of malodor and mean sweat production in the BoNT-A-treated axilla were significantly lower than those in the control axilla at 3 months after therapy. |
Wang [55], 2018 | Prospective | 62 adolescents (axilla) | 50 U BoNT-a/axilla | Yes | The average follow-up was 2.64 years | 82% of patients (51/62) ranked the BoNT-A treatment to be very good or good. |
He [53], 2017 | Prospective | 53 (secondary bromhidrosis, axillae) | 50 U BoNT-a/axilla | NA | 12months | 48 patients ranked the satisfaction with BoNT-A treatment as “very good” or “good” |
Lee [56], 2004 | Cae report | 1 (genitalia) | 40 different sites (2.5 mU/0.1 mL per site) | NA | 9 months | odorless and anhydrous response in the genital region, |
First Author [Ref.], year | Type of Study | n | BoNT Doses | Follow-Up | Results |
---|---|---|---|---|---|
Al-Niaimi F 2020 [67] | Prospective | 20 | In a 5 ml dilution of 500 units using typically 20–50 units per cheek or onabotulinum (BotoxTM, Allergan, Irvine, CA, USA) at 2.5 mL dilution in 100 units with doses ranging from 10 to 20 units per cheek. | 3,9 months | All patients experienced improvement of erythema (documented by a 3D Antera camera) |
Friedman 2019 [68] | Retrospective | 16 | 100 U of abobotulinumtoxin after Tixel treament | 1,3,6 months | flushing and erythema improvement (photographic assessment) |
Park, 2015 [65] | Case report | 2 | 3 U in chin and the eyebrow area were injected; after 1 week, 5 U in each cheek and 2 U in chin and the eyebrow area were additionally injected (patient 1) 40, 15 U in the first treatment and 5 U in the second treatment for each cheek (patient 2) | 1 week to 3 months | Good improvement (photographic assessment) |
Bloom, 2015 [69] | Prospective | 25 | 15, 45 U of intradermal injections of abobotulinum toxin A into the nasal tip, nasal bridge, and nasal alae | 3 months | The treatment resulted in statistically significant improvement in erythema grade at 1, 2, and 3 months after treatment when compared with baseline (3-grade scale of erythema severity on photographic assessment) |
Geddoa, 2013 [64] | Pilot prospective | 22 | 2 U per injection point with maximum dose of 100 U (neck and/or chest) | 4 weeks | Twenty patients (90.9%) reported immediate improvement, and the remaining 2 patients had a second treatment session to achieve similar responses; at 4 weeks follow-up significant improvement in quality of life was measured with DLQI score |
Odo, 2011 [63] | RCT | 60 | 500 U abobotulinum toxin A, 6.2 U injection at each selected point in the skin (40 injection points of face, chest, neck, scalp); for the control group, saline solution was used at the same volume of 0.04 mL per injection point | 6 months | The symptoms were less severe than before treatment; in the control group, there was no significant difference in mean intensity of sweating or in the mean number of hot flashes |
Oh, 2011 [70] | RCT | 15 | BoNT-B doses NA; one side of the face was treated with BoNT-B, the other side with saline | 8 weeks | Ineffective; mexameter demonstrated significant improvement of erythema at 8 weeks after injections on both sides; the BoNT-B injection side did not show a significant decrease in objective erythema, compared with the control side; subjective satisfaction did not differ between the treated side and the control side |
Alexandroff, 2006 [61] | Case report | 2 | 10 U spaced/hemifacial 1 cm between injections | 6 weeks | No improvement was noted 6 weeks after treatment |
Kranendonk 2005 [62] | Case report | 1 | 2 U in midcheek region | Not reported | Paralysis of the zygomaticus major; no improvement after 1 week |
Yuraitis, 2004 [60] | Case report | 1 | A total of 10 U were distributed at 1-cm increments to each cheek in the areas of the most prominent erythema | 2 weeks | Marked improvement and high satisfaction |
First Author [Ref.], year | Type of Study | n | BoNT-A Doses/Hand | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
Quintana Castanedo [84], 2020 | Prospective | 8 | _ | _ | No | Reduction in pain and in the frequency of RP episodes (7 patients) any changes (1 patient) |
Winter [83], 2020 | Case series | 4 | 40–300 | 3–21 | Yes (50%) | Improved up to one year after treatment. |
Dhaliwal [89], 2019 | Prospective | 40 | 100 across both hands reconstituted with 2 mL of normal saline by a single surgeon | 6–12 | no | Improved (Colour change and pain, swelling reduction) |
Berk-Krauss [82], 2018 | Case report | 1 | 20 | 1, 3, 6 weeks | no | Improved pain Ulceration healed |
Medina [79], 2018 | Retrospective | 15 | 100 botulinum toxin units type A in 5 mL of saline serum to 0.9% (dilution: 20 IU/mL). | 1 week 1, 3, 6, 12 months | no | Improved pain Ulceration healed (70%) |
Dhaliwal [81], 2018 | Case reports | 3 | 10 | 6 weeks | no | Improved (pain, colour changes and cold intolerance) Thermographic imaging assessed |
Bello [86], 2017 | RCT doubleblind; placebo | 40 | 50 units in 2.5 mL | 1, 4 months | no | Improved (pain) No changes in blod flow. Moor LDI2-IR scanner assessed) |
Motegi [94], 2017 | Randomized trial single-blind no placebo | 45 | 250, 1000 or 2000 (U) of BoNT-B | 16 weeks | No | Improved (pain, DU) |
Motegi [90], 2016 | Prospective, case series | 10 | 10 U/finger | 16 weeks | No | Improved (pain, DU, skin temperature) |
Zhao [80], 2015 | Case series | 2 | 200–280 | 1 week, 5 months | No | Improved (pain, colour change, skin temperature) |
Uppal [92], 2014 | Prospective | 20 | 100 U | 6 months | No | Improved (pain with VAS, DU) |
Jenkins [85], 2013 | RCT pilot; doubleblind; placebo | 8 | 40 U | – | No | Increase in digital pulp temperature |
Todberg [95], 2018 | Case report | 1 | 100 U | – | No | Patient reported improvement in pain and DU |
Neumeister [96], 2010 Neumeister [78], 2009 | Retrospective case series | 33 | 50 U | 1–6 years | Yes (21%) | 100% of DU healed, relief in 85% of patients |
Fregene [87], 2009 | Retrospective case series | 26 | 20, 100 U | 18 months | Yes (20%) | 48% of DU healed, 35% pain reduction (VAS) |
Kossintseva [93], 2008 | Case report | 1 | 100 U | 12 months | No | Pain decreased, DU not reported |
Van Beek [77], 2007 | Retrospective case series | 11 | 50, 200 U | 9.6 months | Yes (45%) | 100% decrease in pain (VAS), 82% of DU healed |
Sycha [76], 2004 | Pilot to RCT, case report | 2 | 12, 300 U | – | No | 37% pain reduced in 1 patient (VAS), other unknown |
First Author [Ref.], year | Type of Study | n | BoNT-A Doses/Hand | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
Ismail [102], 2020 | Prospective non-randomized side-by-side comparative study | 40 | 100 | 1, 4, 6 months | No | Improvement |
Kontochristopoulos [101], 2007 | Case reports | 2 | 4.0 mL saline in 100 U BoNT-A; 100 U/hand | 8 weeks | No | Improvement |
Swartling [96], 2002 | Prospective | 10 | 1.0 mL saline in 100 U BoNT-A; mean of 162 U/hand | 28–59 days | No | 7 of 10 patients reported a good result; improving in VAS for itching and disease activity score |
Wollina [100], 2002 | Prospective; side-by-side monotherapy with topical steroid vs. adjuvant BoNT-A injection | 6 | 2.0 mL saline in 100 U BoNT-A | 8 weeks | No | Six of 6 hands treated with topical steroids in combination with BoNT-A showed improvement; BoNT-A showed a more rapid release from itching than steroids alone |
First Author [Ref.], year | Type of Study | n | BoNT-A Doses | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
Sonntag [106], 2005 | Case report | 200 mU Dysport | 36 | Yes | Improvement | |
Honeyman [105], 2008 | Case report | 1 | BoNT-A, dilution in 4 mL of saline, 5 U per injection; total amount not specified | 1 year | Not reported | Improvement |
Lera [103], 2015 | Case report | 1 | 100 U BoNT-A in 2.5 mL of saline, 2 U per injection | 9 months | Yes | Improvement |
Nygaard [107], 2015 | Case report | 1 | 100 U BoNT-A (dilution not specified) | 1 year | Not reported | Improvement |
First Author [Ref.] | Type of Study | n | BoNT-A Doses | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
Ding [113], 2017 | Prospective | 58 | 50 to 100 | 2 weeks 1, 3, 6 months | No | 75% of patients improved (Variable VAS, NPS reduction) |
Jain [112], 2017 | Case report | 2 | 500 units Dysport diluted with 5 mL of normal saline, making a concentration of 100 units/mL | 1, 2, 4, 8, 12, 16 weeks | No | VAS for pain decreased from 9, 10 to 1 |
Moon [118], 2016 | Case report | 2 | 50 U BoNT-A and bupivacaine 0.1% injected under ultrasound guide in brachial plexus | 5 months | No | VAS for pain decreased from 8 to 2, 3 |
Li [110], 2015 | Case report (ophthalmic) | 1 | 100 U of BoNT-A in the orbital region (subcutaneous) | 6 months | No | VAS for pain decreased from 8–9 to 2–3 |
Apalla [115], 2013 | Randomized, double-blind, placebo-controlled trial | 29 (4 postherpetic) | 20, 190 U of BoNT-A intradermally | 16 weeks | No | VAS decreasing |
Emad [114], 2011 | interventional study | 15U per 10 cm2 (The amount of toxin was different for every patient: not reported) intradermally | 2, 4 weeks | No | VAS decreasing | |
Xiao [109], 2010 | Randomized, double-blind, placebo-controlled trial | 60 | 5 U/mL of BoNT-A vs. 0.5% of lidocaine vs. 0.9% of saline | 3 months | No | Decrease in VAS score and improving in sleep hours superior to control group |
Sotiriou [108], 2009 | Case reports | 3 | 100 U of BoNT-A in 4 mL of saline; subcutaneous in chessboard pattern | 12 weeks | No | Decrease in VAS score |
Liu [116], 2006 | Case report | 1 | 100 U of BoNT-A injected in a fanning pattern | 9 months | No | VAS pain reduction from 10 to 1 |
First Author [Ref.], year | Type of Study | n | BoNT-A Doses | Retreatment | Follow-Up | Results |
---|---|---|---|---|---|---|
Maari [126], 2014 | RCT vs. placebo double-blind | 20 | max 200 U | No | 12 weeks, then placebo arm shifted to BoNT-A; total 24 weeks | No significant difference for pruritus (VAS) and hyperpigmentation |
Pèrez-Pèrez [57], 2014 | Retrospective, case series | 5 | 48–56 U | No | 18 months | 2 worsening pruritus, little improvement in other 3 but for only 1 month |
Wallengren [125], 2010 | Prospective | 6 | 18–100 U | No | 18 months | 5/6 patients a mean reduction of VAS by 28% at week 6; at 18 months 1 patient had a VAS of 45%, another one was still free from itch |
Weinfeld [124], 2007 | Case report | 2 | 16–24 U | Yes, 18 months later with 48 U (only 1 patient) | 18 months | Improvement (patient self-assessment) |
First Author [Ref.], year | n | Sites | BoNT-A Doses | Follow-Up | Results |
---|---|---|---|---|---|
Lapiere [131], 2000 | 1 | Axillae | 25 U, 50 U of per axilla after 6 months | 4 months at time of publication | Complete remission |
Kang [129], 2002 | 1 | Groin, axillae | 100 U for each inguinal fold | 6 months | Improvement |
Lopez-Ferrer [134], 2012 | 3 | Axillae groin breast, axilla, axillae and groin | 80 U/axilla 200 U total | 5 months | All patients improved but needed at least one retreatment after 1–3 months |
Charlton [135], 2017 | 1 | Axillae and groin | 50 U for axillae 50 U for groin Once a year | 2 years | This therapy has restricted his disease activity to 1–2 episodes per year |
Kothapalli [136], 2018 | NA | Axillae and groin | 50 units per axilla or groin | NA | Improvement |
First Author [Ref.], year | Type of Study | n | BoNT-A Doses | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
O’Reilly [150], 2005 | Case report | 1 | 250 U Dysport/axilla | 10 months | No | Complete remission |
Feito-Rodriguez [151], 2009 | Case report | 1 | 40 U total dose (inguinal folds) | 6 months | Yes | Complete remission |
Khoo [152], 2014 | Case report | 3, but only 1 described | 50 U/axilla | 3 years | Yes (3 other times) | Complete remission |
Shi [153], 2019 | Case report | 1 | 100 units for each area (bilateral axillary, inframammary and groin) | NA | Yes (5 total injections) | Resolution of inflammation and healing of draining sinuses |
Campanati [154], 2019 | Case report | 2 | 50 U per axilla 100 U for each side of groin | 1 year | Yes (for patient 1, after 10 months after the first injection) | Real improvement |
Grimstad [156], 2020 | Randomised, Double-Blind, Placebo-Controlled Pilot Study | 20 | 150 U/armpit, 200 U/groin, and 600 U in the perianal/perigenital areas | 6 months | Yes (3 months after the first injection) | Clear improvement of the quality of life |
First Author [Ref.], year | Type of Study | n | BoNT Doses | Follow-Up | Retreatment | Results |
---|---|---|---|---|---|---|
Freund [168], 2010 | Open-label pilot study | 50 male | 150 U | 60 weeks | Two treatment cycles of 24 weeks each | Treatment response rate was 75 percent |
Singh [169], 2017 | Open-label pilot study | 10 male | 150 U | 6 months | No | Of 10 patients, 8 had good to excellent response on photographic assessment |
Zhang [170], 2019 | Open-label pilot study | 24 male | 50 U | 6 months | No | Variable results |
Shon [172], 2020 | Open-label pilot study | 18 male | 30 U | 6 months | Yes (every 4 weeks for 24 weeks). | Air density was significantly improved after 6 months but not after 3 months. |
Zhou [173], 2020 | Opena label, randomized study (BoNT-A vs. BoNT-A+Finasteride) | 63 male and 1 woman | 100 U | 1 year | Yes (every 3 months) | BTA combined with FNS presents excellent results |
First Author [Ref.], year | Type of Study | n (Type of Psoriasis) | BoNT-A Doses | Retreatment | Follow-Up | Results |
---|---|---|---|---|---|---|
Zanchi [178], 2008 | Observational, no RCT | 15 (inverse psoriasis) | 50-100 U | Not reported | 12 weeks | Improvement in VAS scale score; photographic assessment with improvement of erythema, infiltration (87%) |
Saber [181], 2011 | Case report | 1 (inverse psoriasis and hyperhidrosis) | 100 U per axilla | No | 4 weeks | Greatly improved (photographic documentation) |
Gilbert [182], 2014 | Case report | 1 (plaque psoriasis) | 30 U for a single plaque | No | 8 months | Complete remission but recurrence after 8 months. |
Todberg [186], 2018 | Exploratory, multicenter, randomized double-blinded trial (BoNT-A vs. vehicle). | 8 (plaque psoriasis) | 36 U for a single plaque | No | 8 weeks | No clinical or histological differences from the vehicle |
Aschenbeck [179], 2018 | Open-label pilot study | 8 (plaque psoriasis) | Variable number of units per plaque (average units, 53; range, 25–92) | No | 10 weeks | PASI and BSA reduction |
González [185], 2018 | Descriptive cross-sectional study | 8 (plaque psoriasis) | Variable number of units per plaque (maximum 50 U) | No | 4 weeks | All parameters evaluated (desquamation, erythema and infiltration) for TCS score showed improvement |
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Martina, E.; Diotallevi, F.; Radi, G.; Campanati, A.; Offidani, A. Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review. Toxins 2021, 13, 120. https://doi.org/10.3390/toxins13020120
Martina E, Diotallevi F, Radi G, Campanati A, Offidani A. Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review. Toxins. 2021; 13(2):120. https://doi.org/10.3390/toxins13020120
Chicago/Turabian StyleMartina, Emanuela, Federico Diotallevi, Giulia Radi, Anna Campanati, and Annamaria Offidani. 2021. "Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review" Toxins 13, no. 2: 120. https://doi.org/10.3390/toxins13020120