Successful Treatment of Granuloma Annulare Using Ablative Fractional Carbon Dioxide Laser-Assisted Photodynamic Therapy

Dear Editor:

Granuloma annulare (GA) is a benign granulomatous inflammatory skin disease. While some cases of GA resolve spontaneously, management of GA may include topical or intralesional steroids¹. Photodynamic therapy (PDT) has been reported as an alternative treatment for localized recalcitrant GA². Herein, we report the successful treatment of localized recalcitrant GA through ablative fractional carbon dioxide laser (eCO₂)-assisted PDT using methyl aminolevulinate (MAL).

A 59-year-old otherwise healthy man presented with a one-year history of persistent mildly pruritic, erythematous annular, and arcuate plaques on the bilateral dorsa of the hands (Fig. 1A) in the absence of trauma history. Histopathologic analysis revealed a palisading granuloma and necrobiosis with mucin deposition and a few multinucleated giant cells (Fig. 2). Treatment with systemic corticosteroids, antimalarial drugs, and a topical class I steroid for 6 months did not improve his lesions. As a result, eCO₂ laser (wavelength: 10,600 nm; Lutronic Inc.) followed by PDT using MAL (Metvix) was conducted every 4 weeks.

Fig. 1. (A) Physical examination reveals erythematous annular and arcuate plaques on the bilateral dorsa of hands. (B) Follow-up examination after seven sessions of fractional carbon dioxide laser-assisted photodynamic therapy shows almost complete resolution of the lesions.

Fig. 2. (A) Histopathologic examination demonstrates palisading granuloma with necrobiosis and mucin deposition (H&E, ×100). (B) A few multinucleated giant cells are identified (H&E, ×400).

A single-pass eCO₂ laser (pulse energy of 37 mJ, spot density of 100 spots/cm², power of 30 W, and beam size of 120 µm) was used each time for pre-treatment to enhance the delivery of MAL. Topical MAL was then applied to the affected areas and incubated for 60 minutes. Subsequently, the lesions were irradiated with red light using a Waldmann PDT 1,200 L lamp (wavelength: 570~730 nm; Herbert Waldmann GmbH & Co. KG) at a starting light dose of 10 J/cm² which was gradually increased by 10 J/cm² every 4 weeks and a light intensity of 50 mW/cm².

While treatment response was not observed at low light doses, a significant effect was evident at a light dose of 50 J/cm². After seven sessions, the lesions were almost completely resolved, with a cumulative dose of 220 J/cm² including starting dose (Fig. 1B) without any side effects. Maintenance treatment was not initiated. Follow-up examination revealed no recurrences.

PDT has been described as an alternative treatment for GA¹,². While the exact pathogenesis of GA remains unknown, Th1 helper cell-mediated granulomatous inflammatory processes were implicated³. Moreover, several studies revealed that protoporphyrin IX (PpIX) inhibited T cell proliferation when activated by light at an appropriate wavelength through reactive oxygen species-induced apoptosis²,⁴.

To obtain a good therapeutic response, it is important to enhance the penetration of the photosensitizer and increase PpIX-induced cytotoxicity. The use of eCO₂ laser prior to PDT can reduce the incubation time of the photosensitizer by creating vertical holes for increased absorption⁵.

This study highlights the utility of eCO₂ laser-assisted PDT as an effective treatment option for recalcitrant GA. To the best of our knowledge, this is the first case of combining PDT with eCO₂ laser in GA treatment, suggesting that it probably be effective at a light dose greater than 50 J/cm². It is necessary to set up the optimal light dose for increasing the effectiveness and reducing the number of PDT procedures.