Comment on “Elevation of transaminases after MMP® session with methotrexate for alopecia areata treatment - how much do we know about the risks of systemic absorption of the technique?”

1) Although evidence derived from case reports is considered low, nevertheless it is important to raise questions in different scenarios. 2) Changes in liver enzyme levels are common in clinical practice and can be caused by many factors including physical activity, use of drugs (e.g., acetaminophen) or alcohol, and viral infections. 3) MMP is a drug delivery technique that uses microneedles and dermo pigmentation equipment. Tattoos are unequivocal evidence of injection and absorption. The main advantages of this technique are the uniform drug distribution in the dermis, without bolus formation (Fig. 1), and increased substance dispersion due to shear stress and turbulent whirling caused by Newton’s law of attrition. 4) Drug absorption delivered through MMP occurs predominantly through the lymphatic channels of the skin and not the subjacent blood vessels. 5) MMP is the only drug delivery technique with published protocols that allow the quantification of the drug density injected in the dermis, offering safety parameters to the dermatologist.


Dear Editor,
We read with interest Nogueira's et al. recent case report. 1 This is an important contribution to the limited evidence about the safety of drug delivery techniques.
As an experienced and enthusiastic user of the MMP ® technique, I have a few considerations: 1) Although evidence derived from case reports is considered low, nevertheless it is important to raise questions in different scenarios.2) Changes in liver enzyme levels are common in clinical practice and can be caused by many factors including physical activity, use of drugs (e.g., acetaminophen) or alcohol, and viral infections. 2 3) MMP ® is a drug delivery technique that uses microneedles and dermo pigmentation equipment.Tattoos are unequivocal evidence of injection and absorption.The main advantages of this technique are the uniform drug distribution in the dermis, without bolus formation (Fig. 1), and increased substance dispersion due to shear stress and turbulent whirling 3 caused by Newton's law of attrition.4) Drug absorption delivered through MMP ® occurs predominantly through the lymphatic channels of the skin 4 and not the subjacent blood vessels.5) MMP ® is the only drug delivery technique with published protocols that allow the quantification of the drug density injected in the dermis, 5 offering safety parameters to the dermatologist.6) Since the procedure was done in an ophiasis region (423 cm 2 ), using a saline solution (estimated density 1.000.000g/mL) and the medication contained 25 mg/mL of the active ingredient, based on published protocols we calculate that 390.907 g (0.390907 mg) of ଝ Study conducted at the DermoCentro Clinic, São José dos Campos, SP, Brazil.

Figure 1
Drug delivery with MMP ® technique.This is a cross section of the reticular dermis demonstrating ink between the collagen fibers, without bolus formation the methotrexate solution was injected in the dermis 5 (Video 1), which corresponds to 9.8 mg of methotrexate.
Considering the aforementioned facts, and the lack of other reports of possible drug toxicity related to methotrexate MMP ® drug delivery, we must consider an alternative hypothesis for the findings described by Nogueira et al. 1 It is possible that this patient's mild transient increase in transaminases may have occurred by chance or have been caused by other factors unrelated to methotrexate MMP ® drug delivery?

Financial support
TRADERM, a company that commercializes tattoo supplies.

Dear Editor,
We agree with the consideration that, regarding the cause of the increase in transaminase levels in the described patient, there are no means of affirming with certainty the association with the MMP ® technique. 1We reinforce, however, that she had already shown an elevation of transaminase levels with the previous use of the medication when administered orally.We attributed it to the technique used after excluding other possible causes such as infections, alcohol consumption, physical activity, or use of any other medication, in addition to the transitoriness of transaminitis in relation to the procedure.
Study conducted at the Service of Dermatology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
The technique involves the penetration of needles into the dermis, 2,3 where vascularization is prominent in the scalp, with biological plausibility in affirming the possibility of absorption of the drug used.Additionally the patient is likely to be susceptible to methotrexate-related adverse effects, despite the small, absorbed dose.
We reaffirm the importance of reporting unexpected adverse effects related to the recent use of percutaneous treatment techniques, aiming at patient safety through adequate monitoring.

Financial support
None declared.