Activation of melanocytes in idiopathic guttate hypomelanosis after 5-fluorouracil infusion using a tattoo machine: Preliminary analysis of a randomized, split-body, single blinded, placebo controlled clinical trial
Authors: Samir Arbache, Dirlene Roth, Denise Steiner, Juliano Breunig, Nilceo Schwery Michalany, Samia Trigo Arbache, Luciana Gasques de Souza, Sergio Henrique Hirata
Journal: Journal of the American Academy of Dermatology (2017)

To the Editor: This letter presents a preliminary analysis of the first 8 patients who have completed a randomized clinical trial for idiopathic guttate hypomelanosis (IGH) treatment that was approved by the respective ethics committee and registered in the ClinicalTrials.gov database under identifier NCT02904564. The rationale for this study was the preliminary histologic analysis of IGH spots in which we observed varying degrees of papillary dermis fibrosis.1Falabella R. Escobar C. Giraldo N. et al.On the pathogenesis of idiopathic guttate hypomelanosis.J Am Acad Dermatol. 1987; 16: 35-44Abstract Full Text PDF PubMed Scopus (60) Google Scholar Fulton et al2Fulton J.E.J. Rahimi A.D. Mansoor S. et al.The treatment of hypopigmentation after skin resurfacing.Dermatol Surg. 2004; 30: 95-101PubMed Google Scholar described the repigmentation of hypopigmented scars arising from different etiologies after mechanical removal of dermal fibrosis. The formulated hypothesis was that IGH repigmentation could occur if the underlying dermal fibrosis were removed. Instead of mechanically removing this fibrosis, as described by Fulton et al,2Fulton J.E.J. Rahimi A.D. Mansoor S. et al.The treatment of hypopigmentation after skin resurfacing.Dermatol Surg. 2004; 30: 95-101PubMed Google Scholar we attempted to remove or reduce it by delivering medication with antifibrotic properties. Because of its low cost, injectable 5-fluorouracil (5-FU) was the drug of choice, which has been used for scar treatment since 1990.3Fitzpatrick R.E. Treatment of inflamed hypertrofic scars using 5-FU.Dermatol Surg. 1999; 25: 224-232Crossref PubMed Scopus (291) Google Scholar We named the drug delivery technique used in this clinical trial MMP (the Portuguese acronym for microinfusão de medicamentos na pele [ie, microinfusion of drugs into the skin]).4Arbache S. Godoy C.E. Microinfusion of drugs into the skin with tattoo equipment.Surg Cosmet Dermatol. 2013; 5: 70-74Google Scholar This technique drew inspiration from the ancient art of tattooing. In MMP, the tattoo machine's needles convey the medication contained in the sterile needle cartridge into the skin (Fig 1, B and C)—ie, the microneedling and injection processes occur simultaneously (Fig 1, A). Needling depth is gradually adjusted until mild pinpoint bleeding is achieved (Fig 1, D), which is an indication that the dermis has been reached. The intervention was done using a Cheyenne tattoo machine by MT.DERM (Berlin, Germany), the only equipment of the sort approved by the Brazilian Health Agency (ANVISA) for medical use. Two dermatologists, blinded to the randomization, determined the limb present the best therapeutic outcome by clinical analysis (Fig 2, A-D). Statistical analysis was performed using Antera 3D5Matias A.R. Ferreira M. Costa P. Neto P. Skin colour, skin redness and melanin biometric measurements: comparison study between Antera® 3D, Mexameter® and Colorimeter®.Skin Res Technol. 2015; 21: 346-362Crossref PubMed Scopus (87) Google Scholar (Miravex, Dublin, Ireland; Fig 2, E and F), a device with image analytics software capable of quantifying melanin in each IGH macule (Fig 2, G). Fig 2, H presents the repigmentation percentages of both limbs for all patients. The data show that IGH repigmentation after 5-FU MMP treatment was statistically higher when compared with placebo MMP (75.3% 5-FU repigmentation vs. 33.8% placebo, P < .001). Two patients submitted to biopsy 40 days after the procedure presented numerous melanocytes in the 5-FU–treated areas, thereby eliminating the possibility of postinflammatory hyperpigmentation. One patient with Fitzpatrick skin phototype III developed hyperpigmentation areas on both treated limbs 30 days after the intervention, which spontaneously reversed within 2 months. Partial repigmentation of placebo-treated lesions may have been caused by collagen remodeling induced by simple microneedling of the papillary dermis. We believe that 5-FU MMP treatment may be beneficial in treating IGH. Even though no adverse effects were observed in MMP-treated patients, the safety and efficacy of this 5-FU drug delivery method needs to be proven by means of additional studies. Tattooing is an ancient technique under public domain done mainly by tattoo artists, we have chosen to copyright the acronym MMP in Brazil and the United States and grant free use exclusively to dermatologists who are members of the Brazilian Society of Dermatology and equivalent entities around the world. Dr Arbache's commercial involvement in this investigation was required in order to obtain approval of the equipment for medical use under Brazilian health legislation (as enforced by Agência Nacional de Vigilância Sanitária) and to render this investigation acceptable for the relevant ethics committee. We hereby inform that the clinical results described and documented herein can be achieved using any available tattoo machine. Dr Arbache is a member of a staff that trains Brazilian dermatologists in the use of this technique. Comment on "Activation of melanocytes in idiopathic guttate hypomelanosis after 5-fluorouracil infusion using a tattoo machine: Preliminary analysis of a randomized, split-body, single blinded, placebo controlled clinical trial"Journal of the American Academy of DermatologyVol. 79Issue 4PreviewTo the Editor: I read with interest Arbache et al's preliminary results of repigmentation of idiopathic guttate hypomelanosis in 8 patients by 5-fluorouracil tattooing in a randomized, saline-controlled, split-body trial.1 As an enthusiast of the innovative technique of using professional tattoo machines as drug-delivery devices,2,3 some comments are made necessary for better interpretation and reproduction of the trial. Full-Text PDF