Medical-Toxicological Knowledge Gaps Pose Challenges Despite Advances in Tattooing

Researchers Giulbudagian et al. recently reviewed the medical and toxicological landscape of tattooing in a review titled, "Lessons learned in a decade: Medical-toxicological view of tattooing," which was published in the Journal of the European Academy of Dermatology and Venereology.¹

They noted that the last time a review of this nature was published was approximately a decade ago in the Lancet in an article titled, "A medical-toxicological view of tattooing," which warrants further examination given the amount of time and research that has taken place in the time since.²

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In Review

Health Risks

The health risks associated with tattoos are multifaceted and encompass various complications, which can be classified into inflammatory, infectious, proliferative, and miscellaneous reactions. Among these, inflammatory allergic reactions are particularly prevalent, often characterized by chronic itch or pain localized to specific tattoo colors, with reddish pigments being the most commonly implicated. These reactions typically manifest as plaque-like elevations, excessive hyperkeratosis, or, in severe cases, ulceration, with symptoms typically emerging around a year post-tattooing.

Papulo-nodular granulomatous reactions represent another significant complication, primarily observed in black tattoos but also reported in blue and red tattoos. These reactions manifest as chronic papules or nodules confined to the tattooed area, often with no signs of infection. Histologically, granulomatous inflammation or sarcoid granulomas may be present, with systemic involvement reported in a notable percentage of cases, including pulmonary sarcoidosis and uveitis. Treatment typically involves local corticosteroids, but in severe cases, systemic immunosuppressants or biologics may be necessary.

Tattooing has also been associated with triggering or exacerbating various skin diseases such as psoriasis, lichen planus, cutaneous lupus erythematosus, and vitiligo, possibly due to the inflammatory response induced by needle trauma.

In addition to these complications, other reactions such as "blowouts," hypertrophic scarring, keloid formation, photosensitivity, and neurosensory pain or itch have been documented. However, despite the extensive trauma involved in tattooing, complications such as keloids are relatively rare.

Tattoo removal procedures, particularly laser-based methods, also carry risks, including hypo- or hyperpigmentation, blistering, scarring, and incomplete tattoo removal. Alternative removal approaches, such as caustic products, may lead to severe ulceration, infection, and scarring.

Recent research has also shed light on potential allergens associated with tattoo reactions, suggesting that the allergenic epitope may arise from chemical breakdown products of tattoo pigments rather than from the pigments themselves. Patch testing for tattoo pigment allergies presents methodological challenges, with tape stripping and prolonged reading periods potentially improving diagnostic accuracy.

Microbiological contamination of tattoo and permanent makeup (PMU) inks, along with the presence of preservatives, has been implicated in allergic reactions following tattoo or PMU application. Studies have detected various preservatives in tattoo and PMU ink formulations, with undisclosed use of preservatives being common. Isothiazolinone derivatives, particularly benzisothiazolinone, were frequently detected.

Risk of Skin Cancer?

Despite an increase in reported cases of skin cancers on tattoos, causality remains undocumented, with only isolated case reports or limited case series available. Keratoacanthomas, rapidly growing tumors with debated malignancy, have been observed shortly after tattooing, particularly in red-colored tattoos. These lesions, sharing features with squamous cell carcinoma, may heal spontaneously.

Studies in mice have shown contrasting results regarding the development of skin cancer in tattooed skin upon UV exposure, with fewer skin cancers observed despite the presence of potentially carcinogenic substances in tattoo inks. However, the transport of tattoo pigments raises concerns about their exposure to regional lymph nodes, where they could trigger immune responses and chronic inflammation, potentially linked to cancer development.

Risk assessment of tattoo inks is challenged by limited exposure data and gaps in toxicological testing methods, particularly for intradermal application routes. While standardized in vitro tests exist for soluble ink ingredients, they may not fully address tattoo-specific adverse effects like contact allergies or photoreactions.

Conclusions

Current toxicological standard models used to assess risks like carcinogenicity and allergic reactions are mainly designed for soluble substances and are not directly suitable for tattoo inks and pigments.

Consequently, there are no established algorithms for evaluating tattoo ink safety, according to authors, who recommend that moving forward, experts develop and implement surveillance strategies to register and mitigate potential risks associated with tattooing.

"Medical-toxicological insights of tattoo complications as well as the preventions of risks remain despite better knowledge today hampered by huge knowledge gaps with respect to clinical, epidemiological, chemical, physical, toxicological and experimental research," according to Giulbudagian et al. "The research field is highly complicated and facetted. Tattoo inks are industrial products with many impurities and contaminants and major variations between brands, batches and particles."

References

1. Giulbudagian M, Battisini B, Bäumler W, et al. Lessons learned in a decade: Medical-toxicological view of tattooing. J Eur Acad Dermatol Venereol. May 6, 2024. doi:10.1111/jdv.20072
2. Laux P, Tralau T, Tentschert J, Blume A, Al Dahouk S, Bäumler W, et al. A medical-toxicological view of tattooing. Lancet. 2016; 387(10016): 395–402.