Beta-blockers are safe and cost-effective agents in treating multiple dermatological conditions. |
They are considered as good alternative therapeutic agents by dermatologists, they can be used as a mono-therapy, or as an adjuvant therapy combined with other current disease-specific therapeutic modalities. |
Their role has been reviewed for several dermatological disorders in 2017 and 2018, furthermore, new dermatological conditions have been reviewed in this article such as acne vulgaris, atopic dermatitis, telangiectasia, ulcers, and keloids. |
Although studies showed promising outcomes, further research is needed to provide more information in order to provide sufficient evidence. |
Introduction
Methods/Literature Search
Results
Eligible Studies
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Oral propranolol/1–3 mg/kg/day/BID—TID | Léaute-Labrèze et al. 2016 [51]/Systematic review including 83 articles with 3766 propranolol-treated patients | 1a | NM | Well tolerated | Sleep disturbances, peripheral coldness, and agitation |
Oral propranolol/1 then 2–3 mg/kg/day for 6 m | Léauté-Labrèze et al. 2017 [52]/Systematic review including RCT, a large cohort study, and a meta-analysis of 1264 cases | 1a | NM | 96–98% complete regression 60% nearly complete regression | Reversible and mostly benign | |
Oral propranolol/1–4 mg/kg/day | Novoa et al. 2019 [18]/Systematic review including 28 RCTs (1728 participants) assessed 12 interventions | 1a | – | Increased IH clearance | No increase in harm | |
Oral propranolol/3 mg/kg/day | Mellerio [53]/Review including 5 RCTs with of 379 children | 1a- | – | Increased IH clearance | No serious AEs | |
Oral propranolol/2–3 mg/kg/day | Al-Haddad et al. 2019 [54]/Review including 7 RCTs | 1a | Periocular | Hemangioma shrinkage | Mild GI symptoms, sleep disturbances, cool or sweaty extremities | |
Oral propranolol/2-3 mg/kg/day | Oberlin et al. 2017 [55]/Review | 2a | – | Propranolol is effective and safe | Not reported | |
Oral propranolol with lasers | Chen et al. 2020 [19]/Systematic review and meta-analysis/14 literature including 2658 patients | 1a | Head, face, trunk, limps and premium | Combined therapy was significantly more effective than monotherapy | No statistically significant differences of AEs | |
Rosacea | Carvedilol 3.125–6.25 mg BID or TID/propranolol 10–40 BID or TID/nadolol 40 mg BID or TID | Logger et al. 2020 [24]/Systematic review/9 studies including 64 patients | 1a | Face | Less erythema and flushing | Bradycardia and hypotension were the most commonly described AEs |
Melanoma | Beta-adrenergic blockers | Williams et al. 2020 [9]/Review | 1b | – | Beta-blocker does not seem to be associated with the development of melanoma | Not reported |
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Oral propranolol/2 mg/kg/day/TID | Kim et al. 2017 [56]/RCT/34 patients | 1b | Scalp, chest, face, abdomen, back, and extremities | Propranolol efficacy was not inferior to steroids | No difference in safety outcomes |
Oral propranolol/2 mg/kg/day | Hu et al. 2016 [57]/RCT/76 patients | 1b | Faciocervical, trunk, and extremities | Increased IH clearance | Safe for IH in pediatric population | |
Oral propranolol/2 mg/kg/day | Zaher et al. 2016 [58]/RCT/30 patients | 1a | – | Propranolol superior to captopril | Not observed | |
Oral propranolol/3 mg/kg/day/BID | Baselga et al. 2018 [59]/Clinical trial/45 patients | 1b | Periorbital, nasal, labial, laryngotracheal, limb joints, glabella, philtrum, chin, and cheek | Treatment was effective in most patients with high-risk IH | Bradycardia | |
Oral propranolol/2 mg/kg/day/TID | Kagami et al. 2018 [60]/Clinical trial/32 patients | 1b | Face, chest, neck, back, scrotum, and extremities | Propranolol was effective and safe | Not observed | |
Oral propranolol/3 mg/kg/day | Kaneko T et al. 2017 [61]/Clinical trial/32 patients | 1b | Face and other body parts | Propranolol was effective and safe | No serious AEs | |
Propranolol 2 mg/kg/day and oral atenolol 1 mg/kg/day | Ashraf R et al. 2019 [62]/RCT/40 patients | 1b | – | Propranolol and atenolol were comparable in efficacy | No serious AEs | |
Propranolol 1–4 mg/kg/day and oral atenolol 1 mg/kg/day | Bayart et al. 2017 [12]/Clinical trial/50 patients | 1b | Diaper, eye lid, nose, face, extremity, scalp, and trunk | Atenolol is at least as effective as propranolol | Atenolol poses less risk of bronchospasm |
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Oral propranolol/2 mg/kg/day | Li et al. 2019 [15]/Retrospective study/235 patients | 2b | Head, neck, trunk, and extremities | Propranolol was not associated with a higher incidence of AE | Propranolol was not associated with a higher incidence of AE |
Oral propranolol/2 -3 mg/kg/day | Lahrichi et al. 2018 [63]/Prospective study/121 patients | 2b | Face and neck | Treatment proved to be safe and effective | Not reported | |
Oral propranolol/2 mg/kg/day | Tan et al. 2021 [64]/Retrospective review/88 patients | 2b | Head, neck, trunk, groin, and upper limps | Treatment proved to be safe and effective | Low incidence of AEs | |
Oral propranolol/2 mg/kg/day | Frost et al. 2021 [14]/Prospective pilot study/55 patients | 2b | – | No significant difference was found in sleep quality | Not reported | |
Oral propranolol/2 mg/kg/day/TID | Turhan et al. 2016 [65]/Retrospective study/34 patients | 2b | Face, head, neck, trunk, extremities | Propranolol was a well-tolerated, efficacious, and safe drug | Not observed | |
Oral propranolol | Tognetti et al. 2020 [66]/Prospective study/94 patients | 2b | Head, neck, trunk, extremities, perineal | HRVD allows a real time monitoring of vascular changes in IH treated with oral propranolol | Not reported | |
Oral propranolol/2-3 mg/kg/day/BID or TID | Schwartz et al. 2017 [67]/Literature review | 2a | Subglottic | Propranolol was effective | Not reported | |
Propranolol combined with topical timolol | Mannschreck et al. 2019 [68]/Retrospective review/559 patients | 2b | – | Minimize potential AE of systemic treatment | Not reported | |
Oral propranolol and topical timolol/2 mg/kg/day/BID timolol maleate 0.5% gel/TID | Ge et al. 2016 [69]/Retrospective study/89 patients | 2b | Head and face | Clinical response in 100% of the patients | Few minor AEs were noted: cold extremities agitation during the night and diarrhea | |
Atenolol 0.3–1 mg/kg/day/NM | Gumina et al. 2019 [13]/Case series/4 patients | 4 | Face and neck | Atenolol does not cause sleep disturbance | Sleep disturbance with propranolol | |
LUMBAR syndrome | Oral propranolol/2 mg/kg/day | Yu et al. 2017 [70]/Case report/1 patient | 4 | Lower extremity, perineum, and gluteal region | Increase IH clearance | No reported AEs |
PHACE syndrome | Oral propranolol/0.3 mg/kg/day or more | Olsen et al. 2019 [11]/Retrospective cohort study/76 patients | 2b | – | No serious AEs during treatment with propranolol | No serious AEs |
Rosacea | Carvedilol 12.5 mg daily | Seo et al. 2020 [71]/Retrospective review/24 patients | 2b | Face | Less erythema and flushing | Mild dizziness and GI discomfort |
Melanoma | β-adrenergic blockers | Katsarelias et al. 2020 [27]/Retrospective registry study/12,738 patients | 2b | – | No conclusion on survival in melanoma patients | Not reported |
β-adrenergic blockers | De Giorgi et al. 2017 [72]/Prospective review/121 patients | 2b | – | Beta-blockers reduced the risk of recurrence and mortality | Not reported | |
Oral propranolol/80 mg OD | De Giorgi et al. 2018 [25]/Prospective cohort study/53 patients | 2b | – | Beta-blockers protect patients from melanoma recurrence | No AEs in the PROP group | |
Keloid | Carvedilol, bisoprolol and atenolol | Enoshiri et al. 2017 [30]/Case–control/60 patients | 3b | – | Effective for preventing and treating keloids | Not reported |
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Topical timolol maleate 0.5%/BID | Novoa et al. 2019 [18]/Cochrane systematic review/1728 patients | 1a | – | Decreased redness | No increase in harm |
Topical timolol maleate 0.5%/BID | Mellerio et al. 2019 [53]/Abridged review | 3a | – | Decreased redness | Not reported | |
Topical timolol | Al-Haddad et al. 2019 [54]/Review/– | 1a | Periorbital | Improvement, esp. superficial IH | Mild GI symptoms, sleep disturbances, cool, or sweaty extremities | |
Topical timolol/BID | Khan et al. 2017 [74]/Systematic review and meta-analysis/31 studies of 691 patients | 1a | – | Improvement of small IH, 91% resolution rate | No significant AE noted | |
Topical timolol 0.5% gel forming solution | Randall Bly 2017 [17]/Review/- | 2a | Head and neck | Timolol 0.5% gel forming solution is preferred over other topical beta-blockers | Safe treatment | |
Topical timolol | Wang et al. 2021 [16]/Meta-analysis including 11 RCTs with 1235 patients | 1a | Multiple areas | Topical beta-blockers are as effective as oral propranolol | Less AEs than oral propranolol |
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Topical timolol and PDL/(5 ml: 25 mg) TID (for 20 min each) | Chen et al. 2021 [75]/RCT/20 patients | 1b | Vulva or scrotum, perianal region, buttocks, lip, and trunk | Effective | No significant AEs |
Pyogenic granuloma | Propranolol 1% cream. Timolol 0.5% cream/BID | El-Taweel et al. 2021 [21]/Interventional study/30 patients | 2b | Hands, neck, and limps | Complete resolution with no recurrence | No local or systemic AE noted |
Acne (scars, erythema) | Timolol maleate 0.5%/OD | Al Mokadem et al. 2020 [23]/Clinical trial/58 patients | 1b | Face | Decrease severity of acne | Mild and tolerable |
Timolol maleate 0.5%/BID | Kimwattananukul et al. 2021 [29]/Clinical trial/25 patients | 1b | Face | Enhanced skin-barrier function and wound healing | Not observed | |
Wounds | Topical timolol | Dabiri et al. 2017 [32]/RCT/9 patients | Timolol resulted in more cosmetically favorable scars | Not observed | ||
Chronic leprosy ulcers | Topical 1% propranolol/BID | Abdelmaksoud et al. 2018 [31]/Clinical trial/3 patients | 1b | Sole of foot | Improvement of leprosy ulcers | No local or systemic AEs |
Chronic recalcitrant wound | Galenic preparation of 1% propranolol-hydrochloride/TID | Vestita et al. 2016 [33]/Clinical trial/1 patient | 1b | Sole of foot | Complete healing of ulcer | No local or systemic AEs |
Fissures and erosions of hand eczema | Timolol 0.5% ophthalmic solution, 2–3 drops OD | Manoj Pawar 2021 [36]/Clinical trial/1 patient | 1b | Palms of hands | Healing of erosions and fissures | Not observed |
Deep fissures of heels | Timolol 0.5% ophthalmic solution, 2–3 drops OD | Manoj Pawar 2021 [37]/Clinical trial/1 patient | 1b | Heels of feet | Healing of fissures with no recurrence | Not observed |
Topical glucocorticoid-induced skin telangiectasia | Timolol maleate 0.5%/eye drops BID | Li et al. 2018 [38]/RCT/30 patients | 1b | Face | Improvement in erythema and telangiectasia | No AEs |
Dermatoses | Treatment/dose/frequency | Study/study design/sample size | Level of evidence* | Affected area | Outcomes | |
---|---|---|---|---|---|---|
Efficacy | Adverse events (AEs) | |||||
Infantile hemangioma | Propranolol 1% cream, timolol 0.5% cream/QID | Ying et al. 2017[76]/Prospective study/21 patients | 2b | Extremities, trunk, hand | Significant clinical improvements in both treatments | No permanent AEs |
Carteolol 2% drops/BID | Gan et al. 2017 [77]/Prospective study/349 children | 2b | Head, neck, trunk, and hand or leg | Effective with proliferative superficial IHs | No AEs noted | |
Topical propranolol 4%/BID | Mashiah et al. 2017 [78]/Retrospective study/63 patients | 2b | Head, neck, trunk, extremities, and genital area | Good to partial response | Minor local AEs | |
Oral Propranolol and topical Timolol/NM | Mannschreck et al. 2019 [68]/Retrospective study/559 patients | 1b | – | Minimized potential AE of systemic treatment | Not reported | |
Pyogenic granuloma | - Topical timolol 0.5% gel/BID - Propanolol 1% cream/OD - Betaxolol 0.25% eye drops/OD | Sollena et al. 2019 [22]/Case series/9 patients | 4 | Feet and hands | Complete resolution to partial improvement | No systemic AEs reported |
Propranolol 4% gel/BID | Mashiah et al. 2019 [20]/Uncontrolled retrospective study/18 patients | 2b | Cheek, neck, arm, labia, chest, forehead, and scalp | Complete to almost complete resolution | local AEs in 1 patient | |
Propranolol ointment 1%/BID | Neri et al. 2018 [79]/Prospective study/22 patients | 2b | Chest, back, face, upper extremities, and scalp | 59% completely regressed, 18.2% remained stable, and 22.7% did not respond | No AEs were observed | |
Acne (scars, erythema) | Timolol maleate 0.5%/One drop | Afra et al. 2021[28]/Case report/1 patient | 4 | Face | Less erythema Less pigmentation | Not observed |
Kaposi sarcoma | 0.1% timolol gel/BID | Abdelmaksoud et al. 2017 [39]/Case series/4 patients | 4 | Leg, foot, arm | Complete resolution of lesions, edema, and pain | No reported adverse events 4 to 5 weeks later |