Efficacy of available treatments for periungual and subungual pyogenic granulomas: A systematic review

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.1Alessandrini A. Bruni F. Starace M. Piraccini B.M. Periungual pyogenic granuloma: the importance of the medical history.Skin Appendage Disord. 2016; 1: 175-178Crossref PubMed Google Scholar 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.2Lee J. Sinno H. Tahiri Y. Gilardino M.S. Treatment options for cutaneous pyogenic granulomas: a review.J Plast Reconstr Aesthet Surg. 2011; 64: 1216-1220Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Additionally, surgery may be impractical for multiple drug-induced lesions and not all dermatologists feel comfortable performing nail procedures.2Lee J. Sinno H. Tahiri Y. Gilardino M.S. Treatment options for cutaneous pyogenic granulomas: a review.J Plast Reconstr Aesthet Surg. 2011; 64: 1216-1220Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar,3Hare A.Q. Rich P. Clinical and educational gaps in diagnosis of nail disorders.Dermatol Clin. 2016; 34: 269-273Abstract Full Text Full Text PDF PubMed Google Scholar 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. 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 4 mm to 10 mm)4513.2Large (>10 mm)185.3Not reported25574.8Treatment vs spontaneous resolution of PG (n = 341)Treatment32795.9Spontaneous resolution144.1Resolution post-first treatment (n = 327)Complete resolution20161.5Partial resolution6921.1No response4714.4Not reported103.1Resolution post-second treatment (n = 86)Complete resolution5564.0Partial resolution1112.8No response11.2Not reported1922.1Time to complete/partial resolution, overall (n = 270)1-2 mo228.1>2 mo41.5Not reported10137.4Time to complete/partial resolution, treated with TBB (n = 75)1-2 mo810.7>2 mo00.0Not reported11.3If resolution post-first treatment, did PG recur (n = 270)Yes248.9No14152.2Not reported10538.9Index of primary reported treatment modalities (n = 327)Topical β-blocker‡Topical β-blockers: 0.5% timolol maleate ophthalmic solution, topical 1% propranolol cream, 1 mg/g timolol maleate gel, 0.25% betaxolol ophthalmic solution.8726.7Surgical intervention§Surgical intervention: excision, biopsy, “gutter method,” nail avulsion, nail debridement, matricectomy, incision and drainage.319.5Antibiotic + corticosteroid257.6Surgical intervention + cautery257.6Laser װLaser: pulsed-dye laser (PDL) and Nd-YAG with differing numbers of impulses, energy densities, wavelengths, pulse durations, and treatment intervals.247.3Phenolization195.8Phenolization + cautery + antiseptic185.5Surgical intervention + curettage92.8Curettage82.4Curettage + corticosteroid + antibiotic72.1Corticosteroid61.8Discontinued medication + corticosteroid61.8Antibiotic51.5Table salt51.5Discontinued medication41.2Cauterization + antibiotic41.2Cauterization41.2Phototherapy41.2Topical β-blocker + corticosteroid41.2Discontinued medication + corticosteroid + antibiotic30.9Surgical intervention + corticosteroid + antibiotic30.9Cauterization + corticosteroid + antibiotic30.9Placebo30.9Discontinued medication + antibiotic20.6Curettage + antibiotic20.6Cryotherapy20.6Surgical intervention + antibiotic20.6Surgical intervention + curettage + antibiotic + corticosteroid20.6Surgical intervention + phenolization10.3Cryotherapy + antibiotic10.3Topical α-blocker10.3Antibiotic + antifungal + medication dose decrease10.3Medication dose decrease + corticosteroid + antibiotic + shave biopsy10.3Curettage + topical β-blocker10.3Medication dose decrease + antibiotic + corticosteroid10.3Curettage+ cautery10.3Antibiotic + antifungal10.3Boric acid10.3Direct comparisons of individual first treatmentsTreatmentComplete responsePartial responseP valueTopical β-blocker (n = 75)34 (45.3%)41 (54.7%)<.0001¶χ2 P value,Surgical/removal (n = 29)29 (100.0%)0 (0.0%)Topical β-blocker (n = 75)34 (45.3%)41 (54.7%).4510¶χ2 P value,Laser (n = 24)13 (54.2%)11 (45.8%)Surgical/removal (n = 29)29 (100.0%)0 (0.0%)<.0001¶χ2 P value,Laser (n = 24)13 (54.2%)11 (45.8%)Topical β-blocker (n = 75)34 (45.3%)41 (54.7%).0030¶χ2 P value,Curettage (n = 8)8 (100.0%)0 (0.0%)First treatment (n = 317#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.)TreatmentComplete response (n = 201)Partial response (n = 69)No response (n = 47)P valueTopical β-blocker34 (16.9%)41 (59.4%)12 (25.5%)<.0001¶χ2 P value,Surgical/removal29 (14.4%)0 (0.0%)0 (0.0%)Other16 (8.0%)3 (4.3%)14 (29.8%)Laser13 (6.5%)11 (15.9%)0 (0.0%)Curettage8 (4.0%)0 (0.0%)0 (0.0%)Corticosteroid5 (2.5%)0 (0.0%)1 (2.1%)Medication discontinued2 (1.0%)1 (1.4%)0 (0.0%)Antibiotic1 (0.5%)1 (1.4%)1 (2.1%)Combination therapy93 (46.5%)12 (17.4%)19 (40.4%)Second treatment (n = 67n is not equivalent to total number of patients who received a second treatment (n = 86) because the outcome of 19 patients was not reported.)TreatmentComplete response (n = 55)Partial response (n = 11)No response (n = 1)P valueTopical β-blocker21 (38.2%)1 (9.1%)0 (0.0%).0012¶χ2 P value,Laser10 (18.2%)1 (9.1%)0 (0.0%)Other9 (16.3%)0 (0.0%)1 (100.0%)Medication discontinued8 (14.5%)1 (9.1%)0 (0.0%)Surgical/removal4 (7.3%)1 (9.1%)0 (0.0%)Corticosteroid1 (1.8%)1 (9.1%)0 (0.0%)Curettage1 (1.8%)1 (9.1%)0 (0.0%)Combination therapy1 (1.8%)5 (45.5%)0 (0.0%)Cause of PG vs treatment response (n = 268)Cause of PGComplete responsePartial responseNo responseP valueDrug-induced (n = 166)89 (53.6%)48 (28.9%)29 (17.5%)<.0001¶χ2 P value,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.װ Laser: pulsed-dye laser (PDL) and Nd-YAG with differing numbers of impulses, energy densities, wavelengths, pulse durations, and treatment intervals.¶ χ2 P 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. Open table in a new tab PG, Pyogenic granuloma; TBB, topical β-blockers. NU PG treatment is generally tailored to the cause, ie, drug-induced, mechanical trauma, and peripheral nerve injury.4Piraccini B.M. Bellavista S. Misciali C. Tosti A. de Berker D. Richert B. Periungual and subungual pyogenic granuloma.Br J Dermatol. 2010; 163: 941-953Crossref PubMed Scopus (100) Google Scholar 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.5Sollena P. Mannino M. Tassone F. Calegari M.A. D'Argento E. Peris K. Efficacy of topical beta-blockers in the management of EGFR-inhibitor induced paronychia and pyogenic granuloma-like lesions: case series and review of the literature.Drugs Context. 2019; 8212613Crossref PubMed Scopus (14) Google Scholar 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. None disclosed.