To the Editor: Pyogenic granulomas (PGs) are benign vascular proliferations arising on the skin or mucous membranes, including commonly the nail unit (NU) at periungual or subungual sites.1 PG may resolve spontaneously, although most require treatment. Evidence suggests that surgical excision of PG is the most effective treatment; however, excisions involving the nail may lead to permanent onychodystrophy through matrix disruption.2 Additionally, surgery may be impractical for multiple drug-induced lesions and not all dermatologists feel comfortable performing nail procedures.2,3 Current literature lacks best practice guidelines regarding the treatment of NU PG. Therefore, we conducted a systematic review summarizing the efficacies of current NU PG treatment options, while developing an index of all reported therapies.
PubMed, Embase, Scopus, and Web of Science databases were searched for articles reporting treatment of periungual or subungual PG. Of the 284 articles screened, 76 were included (Fig 1). The 2009 Oxford Levels of Evidence Criteria was referenced to determine the quality of evidence of included studies.
Fig 1.
Flow diagram based on PRISMA 2020.
These manuscripts identified 341 patients with NU PG (Table I). Treatment modalities differed significantly depending on PG cause (drug-induced [n = 166], abnormal nail or trauma [n = 102]) (P <.0001). Stratified by treatment modality, the most frequently reported therapies included topical β-blockers (TBBs) (n = 87, 26.7%) and surgical interventions (n = 31, 9.5%). Response to treatment differed significantly depending on PG location, with PG on fingers resulting in more complete/partial resolution than PG on toes (P = .0267). Statistically significant comparisons of complete/partial resolution among most utilized and reported initial treatments included surgical/removal vs TBB (P <.00011), surgical/removal vs laser (P <.00011), and curettage vs TBB (P = .00301). When comparing TBB to corticosteroids as primary therapies, TBB resulted in significantly less recurrence of PG (P = .0045). PG response to treatment (complete [n = 201] vs partial [n = 69] vs none [n = 47]) differed significantly among all primary treatments (P <.0001). Of those requiring a second therapy, 82.1% PG completely resolved, 16.4% partially resolved, and 1.5% did not respond to treatment (P = .0012). Notably, resolution did not differ significantly among PG treated with TBB or lasers after one treatment (P = .4510). Of the PG treated with TBB, 86.7% (n = 65) completely/partially resolved within 1 to 4 weeks.
Table I.
Patient demographics and clinical characteristics, primary treatment index, and treatment response.
| Patient demographics and clinical characteristics | n | % |
|---|---|---|
| Sex (n = 341) | ||
| Male | 129 | 37.9 |
| Female | 132 | 38.7 |
| Not reported | 81 | 23.8 |
| Patient (n = 341) | ||
| Adult (≥18 y) | 252 | 73.9 |
| Pediatric (<18 y) | 22 | 6.5 |
| Not reported | 74 | 21.7 |
| PG digit location (n = 282∗) | ||
| Hand RI | 20 | 7.1 |
| Hand RII | 14 | 5.0 |
| Hand RIII | 22 | 7.8 |
| Hand RIV | 20 | 7.1 |
| Hand RV | 3 | 1.1 |
| Hand LI | 18 | 6.4 |
| Hand LII | 10 | 3.5 |
| Hand LIII | 18 | 6.4 |
| Hand LIV | 12 | 4.3 |
| Hand LV | 2 | 0.7 |
| Feet RI | 50 | 17.7 |
| Feet RII | 6 | 2.1 |
| Feet RIII | 9 | 3.2 |
| Feet RIV | 6 | 2.1 |
| Feet RV | 4 | 1.4 |
| Feet LI | 46 | 16.3 |
| Feet LII | 9 | 3.2 |
| Feet LIII | 5 | 1.8 |
| Feet LIV | 5 | 1.8 |
| Feet LV | 3 | 1.1 |
| PG nail unit location (n = 341) | ||
| Periungual | 265 | 77.7 |
| Subungual | 29 | 8.5 |
| Digit | 21 | 6.2 |
| Nail | 13 | 3.8 |
| Subungual + periungual | 6 | 1.8 |
| Not reported | 7 | 2.1 |
| PG periungual location (n = 265) | ||
| Lateral nailfold | 122 | 46.0 |
| Proximal nailfold | 53 | 20.0 |
| Lateral + proximal nailfold | 4 | 1.5 |
| Distal nailfold | 1 | 0.4 |
| Not reported | 86 | 32.5 |
| Cause of PG (n = 341) | ||
| Antineoplastic | 146 | 42.8 |
| Ingrown nail | 29 | 85.0 |
| Immobilization | 20 | 5.9 |
| Trauma | 19 | 5.6 |
| Retinoid | 15 | 4.4 |
| Antiretroviral | 14 | 4.1 |
| Friction | 13 | 3.8 |
| Retronychia | 7 | 2.1 |
| Foreign body | 6 | 1.8 |
| Other | 6 | 1.8 |
| Onychotillomania | 2 | 0.6 |
| Anti-inflammatory | 1 | 0.3 |
| Not reported | 63 | 18.5 |
| Diagnosis of PG (n = 341) | ||
| Histologically | 61 | 17.9 |
| Clinically† | 96 | 28.2 |
| Not reported | 184 | 54.0 |
| Size of PG (n = 341) | ||
| Small (≤4 mm) | 23 | 6.7 |
| Moderate (>4 mm to 10 mm) | 45 | 13.2 |
| Large (>10 mm) | 18 | 5.3 |
| Not reported | 255 | 74.8 |
| Treatment vs spontaneous resolution of PG (n = 341) | ||
| Treatment | 327 | 95.9 |
| Spontaneous resolution | 14 | 4.1 |
| Resolution post-first treatment (n = 327) | ||
| Complete resolution | 201 | 61.5 |
| Partial resolution | 69 | 21.1 |
| No response | 47 | 14.4 |
| Not reported | 10 | 3.1 |
| Resolution post-second treatment (n = 86) | ||
| Complete resolution | 55 | 64.0 |
| Partial resolution | 11 | 12.8 |
| No response | 1 | 1.2 |
| Not reported | 19 | 22.1 |
| Time to complete/partial resolution, overall (n = 270) | ||
| <1 wk | 1 | 0.4 |
| 1 wk to 1 mo | 142 | 52.6 |
| >1-2 mo | 22 | 8.1 |
| >2 mo | 4 | 1.5 |
| Not reported | 101 | 37.4 |
| Time to complete/partial resolution, treated with TBB (n = 75) | ||
| <1 wk | 1 | 1.3 |
| 1 wk to 1 mo | 65 | 86.7 |
| >1-2 mo | 8 | 10.7 |
| >2 mo | 0 | 0.0 |
| Not reported | 1 | 1.3 |
| If resolution post-first treatment, did PG recur (n = 270) | ||
| Yes | 24 | 8.9 |
| No | 141 | 52.2 |
| Not reported | 105 | 38.9 |
| Index of primary reported treatment modalities (n = 327) | ||
| Topical β-blocker‡ | 87 | 26.7 |
| Surgical intervention§ | 31 | 9.5 |
| Antibiotic + corticosteroid | 25 | 7.6 |
| Surgical intervention + cautery | 25 | 7.6 |
| Laser װ | 24 | 7.3 |
| Phenolization | 19 | 5.8 |
| Phenolization + cautery + antiseptic | 18 | 5.5 |
| Surgical intervention + curettage | 9 | 2.8 |
| Curettage | 8 | 2.4 |
| Curettage + corticosteroid + antibiotic | 7 | 2.1 |
| Corticosteroid | 6 | 1.8 |
| Discontinued medication + corticosteroid | 6 | 1.8 |
| Antibiotic | 5 | 1.5 |
| Table salt | 5 | 1.5 |
| Discontinued medication | 4 | 1.2 |
| Cauterization + antibiotic | 4 | 1.2 |
| Cauterization | 4 | 1.2 |
| Phototherapy | 4 | 1.2 |
| Topical β-blocker + corticosteroid | 4 | 1.2 |
| Discontinued medication + corticosteroid + antibiotic | 3 | 0.9 |
| Surgical intervention + corticosteroid + antibiotic | 3 | 0.9 |
| Cauterization + corticosteroid + antibiotic | 3 | 0.9 |
| Placebo | 3 | 0.9 |
| Discontinued medication + antibiotic | 2 | 0.6 |
| Curettage + antibiotic | 2 | 0.6 |
| Cryotherapy | 2 | 0.6 |
| Surgical intervention + antibiotic | 2 | 0.6 |
| Surgical intervention + curettage + antibiotic + corticosteroid | 2 | 0.6 |
| Surgical intervention + phenolization | 1 | 0.3 |
| Cryotherapy + antibiotic | 1 | 0.3 |
| Topical α-blocker | 1 | 0.3 |
| Antibiotic + antifungal + medication dose decrease | 1 | 0.3 |
| Medication dose decrease + corticosteroid + antibiotic + shave biopsy | 1 | 0.3 |
| Curettage + topical β-blocker | 1 | 0.3 |
| Medication dose decrease + antibiotic + corticosteroid | 1 | 0.3 |
| Curettage+ cautery | 1 | 0.3 |
| Antibiotic + antifungal | 1 | 0.3 |
| Boric acid | 1 | 0.3 |
|
Direct comparisons of individual first treatments | ||||
|---|---|---|---|---|
| Treatment | Complete response | Partial response | P value | |
| Topical β-blocker (n = 75) | 34 (45.3%) | 41 (54.7%) | <.0001¶ | |
| Surgical/removal (n = 29) | 29 (100.0%) | 0 (0.0%) | ||
| Topical β-blocker (n = 75) | 34 (45.3%) | 41 (54.7%) | .4510¶ | |
| Laser (n = 24) | 13 (54.2%) | 11 (45.8%) | ||
| Surgical/removal (n = 29) | 29 (100.0%) | 0 (0.0%) | <.0001¶ | |
| Laser (n = 24) | 13 (54.2%) | 11 (45.8%) | ||
| Topical β-blocker (n = 75) | 34 (45.3%) | 41 (54.7%) | .0030¶ | |
| Curettage (n = 8) | 8 (100.0%) | 0 (0.0%) | ||
|
First treatment (n = 317#) | ||||
|---|---|---|---|---|
| Treatment | Complete response (n = 201) | Partial response (n = 69) | No response (n = 47) | P value |
| Topical β-blocker | 34 (16.9%) | 41 (59.4%) | 12 (25.5%) | <.0001¶ |
| Surgical/removal | 29 (14.4%) | 0 (0.0%) | 0 (0.0%) | |
| Other | 16 (8.0%) | 3 (4.3%) | 14 (29.8%) | |
| Laser | 13 (6.5%) | 11 (15.9%) | 0 (0.0%) | |
| Curettage | 8 (4.0%) | 0 (0.0%) | 0 (0.0%) | |
| Corticosteroid | 5 (2.5%) | 0 (0.0%) | 1 (2.1%) | |
| Medication discontinued | 2 (1.0%) | 1 (1.4%) | 0 (0.0%) | |
| Antibiotic | 1 (0.5%) | 1 (1.4%) | 1 (2.1%) | |
| Combination therapy | 93 (46.5%) | 12 (17.4%) | 19 (40.4%) | |
|
Second treatment (n = 67∗∗) | ||||
|---|---|---|---|---|
| Treatment | Complete response (n = 55) | Partial response (n = 11) | No response (n = 1) | P value |
| Topical β-blocker | 21 (38.2%) | 1 (9.1%) | 0 (0.0%) | .0012¶ |
| Laser | 10 (18.2%) | 1 (9.1%) | 0 (0.0%) | |
| Other | 9 (16.3%) | 0 (0.0%) | 1 (100.0%) | |
| Medication discontinued | 8 (14.5%) | 1 (9.1%) | 0 (0.0%) | |
| Surgical/removal | 4 (7.3%) | 1 (9.1%) | 0 (0.0%) | |
| Corticosteroid | 1 (1.8%) | 1 (9.1%) | 0 (0.0%) | |
| Curettage | 1 (1.8%) | 1 (9.1%) | 0 (0.0%) | |
| Combination therapy | 1 (1.8%) | 5 (45.5%) | 0 (0.0%) | |
|
Cause of PG vs treatment response (n = 268) | ||||
|---|---|---|---|---|
| Cause of PG | Complete response | Partial response | No response | P value |
| Drug-induced (n = 166) | 89 (53.6%) | 48 (28.9%) | 29 (17.5%) | <.0001¶ |
| Abnormal nail or trauma (n = 102) | 84 (82.4%) | 7 (6.9%) | 11 (10.8%) | |
PG, Pyogenic granuloma; TBB, topical β-blockers.
n varies from total because of patients with multiple PG reported and others with location not reported.
Clinical diagnosis signifies that PG was diagnosed based on the typical characteristic morphology of PG, history of ulceration, bleeding, and/or crusting with no biopsy performed.
Topical β-blockers: 0.5% timolol maleate ophthalmic solution, topical 1% propranolol cream, 1 mg/g timolol maleate gel, 0.25% betaxolol ophthalmic solution.
Surgical intervention: excision, biopsy, “gutter method,” nail avulsion, nail debridement, matricectomy, incision and drainage.
Laser: pulsed-dye laser (PDL) and Nd-YAG with differing numbers of impulses, energy densities, wavelengths, pulse durations, and treatment intervals.
χ2P value,
n is not equivalent to total number of patients who received a first treatment (n = 327) because the outcome of 10 patients was not reported.
n is not equivalent to total number of patients who received a second treatment (n = 86) because the outcome of 19 patients was not reported.
NU PG treatment is generally tailored to the cause, ie, drug-induced, mechanical trauma, and peripheral nerve injury.4 Our findings suggest that TBBs are more commonly used to treat drug-induced PG compared with PG resulting from abnormal nail or trauma. However, the latter were more likely to result in complete resolution than drug-induced PG, 82.4% and 53.6%, respectively (P <.0001). TBBs were the most frequently implemented intervention overall, likely due to the low risk of local and systemic side effects.5 Regardless of PG etiology, the majority of PG treated with TBB partially resolved by the first follow-up and completely resolved at subsequent assessment. Although treatment of PG with TBB has risen in popularity, this study highlights the benefits of several therapeutic options.
Limitations include small sample size and heterogeneity of collected data. Further investigations are needed to standardize guidelines regarding the most efficacious treatment for NU PG.
Conflict of interest
None disclosed.
Footnotes
Funding sources: None.
IRB approval status: Not applicable.
References
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