Granulomatous reaction after an aesthetic electroporation procedure

ARTICLE

Auteur(s) : Clara De Simone, Teresa Sisto, Selenia Vallone, Angelo Carbone, Maurizio Rotoli, Pierluigi Amerio

Department of Dermatology, Catholic University of the Sacred Heart, Largo Gemelli 8, 00168 Rome Italy

Electroporation produces transient hydrophilic pores across cell membranes through application of short electric field pulses. The pores allow the passage of macromolecules through a combination of diffusion, electrophoresis and electro-osmosis. Skin electroporation with short, high-voltage pulses (0.3-1.0 V) increases permeability of the stratum corneum, enhancing percutaneous drug delivery [1]. We describe a 60-year-old Caucasian woman with a granulomatous reaction arising after transdermal permeation of a gel for facial skin rejuvenation by electroporation. The patient presented with a 20-day history of bilateral erythematous infiltrated plaques in the glabellar, periorbital and perioral areas, associated with intense pain and fever (38.5 °C) (figure 1A). Forty days previously, a carnitine and creatine gel had been permeated on her face via electroporation. The patient had been treated at another hospital with systemic prednisone (60 mg/day), suspended after one week because of severe and treatment-resistant arterial hypertension (200-100 mmHg). When she came to our observation she had mild leukocytosis (16.70 × 10⁹/L) with an elevated neutrophil count (80%). Magnetic resonance study of the face excluded bone inflammation. An erysipelas was hypothesized, but systemic treatment with ceftriaxone, teicoplanin and vancomycin was ineffective. Histological examination of a skin biopsy from the glabellar region showed an inflammatory granulomatous dermal infiltrate with foamy histiocytes, suggestive of foreign body granuloma (figures 1C, D). Cultures for common aerobic and anaerobic germs were negative. Ziehl-Nielsen acid fast staining and PAS staining excluded mycobacterial and fungal infections. Reports of the anti-inflammatory efficacy of tetracyclines in similar cases of granulomatous reactions [2, 3] prompted treatment with doxycycline 100 mg/d, associated with nimesulide, a well known antinflammatory drug, at a dosage 100 mg/d. After a month, the cutaneous lesions were considerably improved and the systemic symptoms (body temperature, leukocytosis) normalized. At a six-month follow-up complete resolution of the skin lesions was observed (figure 1B). Electroporation has a variety of applications in relation to the diverse substances that can be delivered, e.g. dyes, heavy metal ions, gene segments, antibodies, enzymes, and drugs. Dermatological applications comprise transdermal delivery of cytotoxic drugs to treat cutaneous tumours and cosmetics to improve aesthetic appearance [4]. Granulomatous reactions after subcutaneous injection of filler materials, such as hyaluronic acid, polylactic acid, bovine or human-derived collagen, and polymerized silicones have been widely reported [2]. Treatment includes topical, intralesional, and systemic corticosteroids, topical tacrolimus and imiquimod, intralesional 5-fluorouracil, and systemic isotretinoin, cyclosporine, allopurinol, colchicines, and tetracyclines [2]. Surgical intervention is recommended for circumscribed nodular lesions. The most significant side effects of skin electroporation are a painful sensation due to direct electric stimulation of underlying nerves and muscles and transient erythema caused by a temporary increase in blood flow [5]. Foreign body granuloma due to transdermal permeation of drugs or cosmetic gels by electroporation has never been described. We hypothesized that adulterated substances or contaminating agents delivered through electroporation could be responsible for the inflammatory response. Nevertheless its exact mechanism is unclear and no other substances except for creatine and carnitine were reported on the product summary. We used an association of doxycycline and nimesulide at dosage of 100 mg/d each in order to obtain a combined anti-inflammatory effect with lower doses than those usually administered.

The patient’s complete response suggests that the combination may be effective in treating cutaneous foreign body granuloma induced by cosmetic procedures. Since various materials and techniques have come into use for cosmetic or reconstructive purposes, further investigation into the ingredients that may cause adverse reactions is needed. In addition, patients should be adequately informed of the chemicals used and the administration techniques applied and give their written consent to the procedure. Although electroporation for aesthetic purposes is becoming increasingly popular, only experienced physicians should perform these interventions [6].

Acknowledgements

References

2 Lloret P, Espana A, Leache A, et al. Successful treatment of granulomatous reactions secondary to injection of esthetic implants. Dermatol Surg 2005; 31: 486-90.

3 Senent P, Bachelez H, Ollivaud L, et al. Minocycline for the treatment of cutaneous silicone granulomas. Br J Dermatol 1999; 140: 985-7.

4 Ti-Fei Y. Electroporation: an arsenal of application. Cytotechnology 2007; 54: 71-6.

5 Prausnitz MR. The effects of electric current applied to the skin: a review for transdermal drug delivery. Adv Drug Deliv Rev 1996; 18: 395-425.

6 Kerscher M. Aesthetic and cosmetic dermatology. Eur J Dermatol 2009; (in press).