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Figure. Clinical images of patients 4 (A and B) and 10 (C and D) showing pyogenic granuloma lesions. A and C, Before treatment with photodynamic therapy (PDT) with 5-aminolevulinic acid intralesional injection (5-ALA ILI). B and D, Two weeks after 2 sessions of PDT with 5-ALA ILI.

Figure. Clinical images of patients 4 (A and B) and 10 (C and D) showing pyogenic granuloma lesions. A and C, Before treatment with photodynamic therapy (PDT) with 5-aminolevulinic acid intralesional injection (5-ALA ILI). B and D, Two weeks after 2 sessions of PDT with 5-ALA ILI.

Table. Summary of PDT With 5-ALA Intralesional Injection for 14 Patients With Pyogenic Granuloma
Table. Summary of PDT With 5-ALA Intralesional Injection for 14 Patients With Pyogenic Granuloma
1.
Ohlerth S, Laluhov á D, Buchholz J, Roos M, Walt H, Kaser-Hotz B. Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.  Lasers Surg Med. 2006;38(3):229-234PubMedArticle
2.
Li W, Yamada I, Masumoto K, Ueda Y, Hashimoto K. Photodynamic therapy with intradermal administration of 5-aminolevulinic acid for port-wine stains.  J Dermatolog Treat. 2010;21(4):232-239PubMed
3.
Park MY, Kim YC. Classic Kaposi sarcoma treated with intralesional 5-aminolevulinic acid injection photodynamic therapy.  Arch Dermatol. 2009;145(10):1200-1202PubMedArticle
4.
Chang CJ, Sun CH, Liaw LH, Berns MW, Nelson JS. In vitro and in vivo photosensitizing capabilities of 5-ALA versus photofrin in vascular endothelial cells.  Lasers Surg Med. 1999;24(3):178-186PubMedArticle
5.
Rodriguez L, de Bruijn HS, Di Venosa G,  et al.  Porphyrin synthesis from aminolevulinic acid esters in endothelial cells and its role in photodynamic therapy.  J Photochem Photobiol B. 2009;96(3):249-254PubMedArticle
Research Letter
Jan 2012

Photodynamic Therapy With 5-Aminolevulinic Acid Intralesional Injection for Pyogenic Granuloma

Author Affiliations

Author Affiliations: Departments of Dermatology, Ajou University School of Medicine, Suwon (Drs Lee and Y. C. Kim), Kwandong University College of Medicine, Goyang (Dr E. H. Kim), and Kyungpook National University School of Medicine, Daegu (Dr Jang), South Korea.

Arch Dermatol. 2012;148(1):126-128. doi:10.1001/archderm.148.1.126

Various treatment techniques have been used to remove pyogenic granuloma (PG). However, surgical excision leaves scars, and other approaches such as curettage or shave excision with electrocautery appear less effective in clearing the lesion. The principal mechanisms associated with tumor destruction through photodynamic therapy (PDT) are direct destruction of tumor cells and indirect destruction of tumor-associated vasculature. Photodynamic therapy –mediated vascular effects range from transient vascular spasm, vascular stasis, and thrombus formation to permanent vessel occlusion and can include enhanced vascular leakiness.1 Recently, PDT has been effectively used to treat vascular lesions such as port-wine stains and Kaposi's sarcoma.2,3 However, to our knowledge, treatment of PG with PDT has not yet been reported. In this study, we investigate the effectiveness and safety of PDT with intralesional injection (ILI) of photosensitizer in the treatment of PG.

Methods

A total of 14 patients with clinically or histologically confirmed PG were included in this study. There were 9 women and 5 men. The mean (SD) age of the patients was 37.7 (18.4) years (age range, 11-74 years). This study was approved by the institutional review board (IRB) of Ajou University Medical Center (IRB No., AJIRB-MED-MDB-10-174).

A skin biopsy was performed before treatment in 4 cases using a 2-mm punch at the margin of the lesion. Approximately 0.3 mL/cm3 of 5-aminolevulinic acid, 20%, solution (Levulan; DUSA Pharmaceuticals; hereinafter “5-ALA ”) was applied by ILI, using a 26-gauge needle, followed by occlusion with polyurethane film. After 3 hours of light-impenetrable occlusion, the lesions were illuminated with red light (600-720 nm) using a noncoherent light source (Waldmann PDT 1200L; Waldmann-Medizin-Technik) at a light dose of 100 J/cm2 and a fluence of 100 mW/cm2.

Treatment efficacy evaluation was conducted 2 weeks after the final PDT treatment. Two dermatologists individually assessed the patients' treatment responses. Clinical responses of the lesions were visually assessed at the end of treatment; no response was defined as a reduction in lesional volume of less than 30%; mild response, as 30% to 59%; moderate response, as 60% to 90%; and marked response, as more than 90%. One year after the last treatment, 1 of the dermatologists who participated in the initial assessment telephoned the patients who showed marked response to ask whether there had been recurrence.

Results

Eleven patients showed marked improvement (79%); 1 patient showed a moderate response (7%); and 2 patients did not respond to therapy (14%) (Figure) (Table). In the cases showing a marked response, the mean (SD) number of treatment sessions was 1.18 (0.41). One patient who had a PG lesion on her lip was treated with a single session of PDT with 5-ALA ILI and showed a moderate response. Because she complained of perilesional swelling after injection, 7 further sessions of PDT were conducted with topical application of 5-ALA, but there was no further improvement. Two patients with a large PG lesion (diameter >1 cm) who received PDT with 5-ALA ILI once or twice did not show any response. Adverse events were reported in 3 patients, all of whom complained of perilesional swelling after ILI of 5-ALA. However, all patients except the patient who had PG on the lip tolerated the treatment well. All patients who showed marked response had no recurrence for 1 year.

Comment

Photodynamic therapy can directly cause tumor cell destruction by toxic action via apoptosis, necrosis, or by inducing cellular hypoxia as a result of microcirculatory shutdown. Microcirculatory shutdown may be induced by toxic action on the endothelial and vascular smooth-muscle cells. A previous report demonstrated that PDT has the ability to destroy vascular endothelial cells both in vitro and in vivo.4 In addition, Rodriguez et al5 showed that endothelial cells may generate protoporphyrin IX from photosensitizer. These studies suggest that PDT might be used for the treatment of hypervascular dermal lesions.

Previous reports have proposed that ILI of photosensitizer may be a safe, effective method of application of photosensitizer with thick lesions. Li et al2 suggest that intradermal injection of 5-ALA is a safe administration route for destroying vascular structures after PDT, and it might be applicable to the clinical treatment of port-wine stains. Our research group3 has previously observed marked clinicopathologic remission of Kaposi's sarcoma after PDT treatment with 5-ALA ILI, with no substantial adverse effects.

In the present study, 3 cases exhibited moderate or no response. The PG that showed moderate response was located on the lip. Although PDT with 5-ALA ILI provided a moderate response, the patient complained of perilesional swelling after the injection. Therefore, we could not continue treatment with ILI; instead, we delivered PDT 7 times after topical application of 5-ALA; however, there was no further improvement. This suggests that ILI of 5-ALA is more effective than topical application of 5-ALA in treatment of PG. Only the large lesions, more than 1 cm on the longest axis, showed no response. Therefore, the location and size of the lesions should be considered in PDT of PG.

A skin biopsy was performed in 4 cases before PDT. However, the difference of large diameter of the lesions was minimal between before and after the skin biopsy.

The limitations of our study include the small sample size and short follow-up. Clinically, ILI PDT for PGs is time-consuming, expensive, and not approved by the US Food and Drug Administration. Also, it can induce a hypersensitivity reaction after ILI of photosensitizer and is less effective in large lesions.

In conclusion, PDT with 5-ALA ILI may be considered as an effective alternative treatment technique for the treatment of PGs, especially in patients with small lesions who refuse surgical excision.

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Article Information

Correspondence: Dr Y. C, Kim, Department of Dermatology, Ajou University School of Medicine, San 5 Woncheon-dong, Yeongtong-gu, Suwon 443-721, South Korea (maychan@ajou.ac.kr).

Accepted for Publication: September 2, 2011.

Author Contributions: All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Lee, E. H. Kim, Jang, and Y. C. Kim. Acquisition of data: Lee, E. H. Kim, and Jang. Analysis and interpretation of data: Lee, E. H. Kim, Jang, and Y. C. Kim. Drafting of the manuscript: Lee, E. H. Kim, Jang, and Y. C. Kim. Critical revision of the manuscript for important intellectual content: E. H. Kim, Jang, and Y. C. Kim. Statistical analysis: Lee, E. H. Kim, and Jang. Study supervision: E. H. Kim, Jang, and Y. C. Kim.

Financial Disclosure: None reported.

Funding/Support: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by grant 2010-0022412 from the Ministry of Education, Science, and Technology (Dr Y. C. Kim).

References
1.
Ohlerth S, Laluhov á D, Buchholz J, Roos M, Walt H, Kaser-Hotz B. Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.  Lasers Surg Med. 2006;38(3):229-234PubMedArticle
2.
Li W, Yamada I, Masumoto K, Ueda Y, Hashimoto K. Photodynamic therapy with intradermal administration of 5-aminolevulinic acid for port-wine stains.  J Dermatolog Treat. 2010;21(4):232-239PubMed
3.
Park MY, Kim YC. Classic Kaposi sarcoma treated with intralesional 5-aminolevulinic acid injection photodynamic therapy.  Arch Dermatol. 2009;145(10):1200-1202PubMedArticle
4.
Chang CJ, Sun CH, Liaw LH, Berns MW, Nelson JS. In vitro and in vivo photosensitizing capabilities of 5-ALA versus photofrin in vascular endothelial cells.  Lasers Surg Med. 1999;24(3):178-186PubMedArticle
5.
Rodriguez L, de Bruijn HS, Di Venosa G,  et al.  Porphyrin synthesis from aminolevulinic acid esters in endothelial cells and its role in photodynamic therapy.  J Photochem Photobiol B. 2009;96(3):249-254PubMedArticle
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