Lessons learned in a decade: Medical-toxicological view of tattooing.

Tattooing has been part of the human culture for thousands of years, yet only in the past decades has it entered the mainstream of the society. With the rise in popularity, tattoos also gained attention among researchers, with the aim to better understand the health risks posed by their application. 'A medical-toxicological view of tattooing'-a work published in The Lancet almost a decade ago, resulted from the international collaboration of various experts in the field. Since then, much understanding has been achieved regarding adverse effects, treatment of complications, as well as their regulation for improving public health. Yet major knowledge gaps remain. This review article results from the Second International Conference on Tattoo Safety hosted by the German Federal Institute for Risk Assessment (BfR) and provides a glimpse from the medical-toxicological perspective, regulatory strategies and advances in the analysis of tattoo inks.

Tattoo Pigment Identification in Inks and Skin Biopsies of Adverse Reactions by Complementary Elemental and Molecular Bioimaging with Mass Spectral Library Matching.

Tattooing has become increasingly popular throughout society. Despite the recognized issue of adverse reactions in tattoos, regulations remain challenging with limited data available and a missing positive list. The diverse chemical properties of mostly insoluble inorganic and organic pigments pose an outstanding analytical challenge, which typically requires extensive sample preparation. Here, we present a multimodal bioimaging approach combining micro X-ray fluorescence (µXRF) and laser desorption ionization-mass spectrometry (LDI-MS) to detect the elemental and molecular composition in the same sample. The pigment structures directly absorb the laser energy, eliminating the need for matrix application. A computational data processing workflow clusters spatially resolved LDI-MS scans to merge redundant information into consensus spectra, which are then matched against new open mass spectral libraries of tattoo pigments. When applied to 13 tattoo inks and 68 skin samples from skin biopsies in adverse tattoo reactions, characteristic signal patterns of isotopes, ion adducts, and in-source fragments in LDI-MS1 scans yielded confident compound annotations across various pigment classes. Combined with µXRF, pigment annotations were achieved for all skin samples with 14 unique structures and 2 inorganic pigments, emphasizing the applicability to larger studies. The tattoo-specific spectral libraries and further information are available on the tattoo-analysis.github.io website.

Histopathology of Red Tattoo Reactions.

BACKGROUND: Despite popularity of tattoos, complications may occur. In particular, red tattoo reactions due to allergic reactions are the most frequent chronic tattoo reactions. However, little is known about its histopathology and underlying pathomechanisms. OBJECTIVE: The aim of this article is to analyze the histopathology of red tattoo reactions for diagnostic purposes and to acquire more insight into pathogenesis. METHODS: A retrospective cross-sectional study was conducted by reviewing the histopathology of 74 skin biopsies of patients with allergic red tattoo reactions. Histopathological findings, such as inflammation patterns, inflammatory cells and pigment depth and color, were semi-quantified with an in-house validated scoring system by 2 independent senior investigators. RESULTS: Histiocytes and lymphocytes were both present in >93%. Histiocytes were the predominant inflammatory cells in 74.3%, but well-defined granulomas were mostly absent (78.0%). Eosinophils were uncommon (8.1%) The predominantly histiocytic reaction combined with interface dermatitis was the main inflammation pattern (37.9%). Most biopsies showed more than one reaction pattern. Interface involvement was observed in 64.8%, despite the intended depth of standard tattoo procedures, in which pigment is placed deeper, in the upper- and mid-dermis. Statistical analyses showed a significant association between inflammation severity and pigment depth (P = 0.024). In 6 cases (8.1%) pigments could not be retrieved histologically. CONCLUSIONS: In this cohort we demonstrated that cutaneous reactions to red tattoo ink are frequently characterized by the combination of dermal predominantly histiocytic infiltrates and epidermal interface dermatitis. Allergic reactions to red tattoo pigments probably represent a combination of a subtype IVa and IVc allergic reaction. Clinicians should be aware of the specific histopathology of these reactions and therefore the importance of taking a diagnostic skin biopsy.

Assessment of cytotoxicity and sensitization potential of intradermally injected tattoo inks in reconstructed human skin.

BACKGROUND: The number of people within the European population having at least one tattoo has increased notably, and with it the number of tattoo-associated clinical complications. Despite this, safety information and testing regarding tattoo inks remain limited. OBJECTIVE: To assess cytotoxicity and sensitization potential of 16 tattoo inks after intradermal injection into reconstructed human skin (RHS). METHODS: Commercially available tattoo inks were injected intradermally into RHS (reconstructed epidermis on a fibroblast-populated collagen hydrogel) using a permanent makeup device. RHS biopsies, tissue sections, and culture medium were assessed for cytotoxicity (thiazolyl blue tetrazolium bromide assay [MTT assay]), detrimental histological changes (haematoxylin and eosin staining), and the presence of inflammatory and sensitization cytokines (interleukin [IL]-1α, IL-8, IL-18; enzyme-linked immunosorbent assay). RESULTS: Varying degrees of reduced metabolic activity and histopathological cytotoxic effects were observed in RHS after ink injection. Five inks showed significantly reduced metabolic activity and enhanced sensitization potential compared with negative controls. DISCUSSION: Using the RHS model system, four tattoo inks were identified as highly cytotoxic and classified as potential sensitizers, suggesting that allergic contact dermatitis could emerge in individuals carrying these inks. These results indicate that an RHS-based assessment of cytotoxicity and sensitization potential by intradermal tattoo ink injection is a useful analytical tool to determine ink-induced deleterious effects.

Quantification of cutaneous allergic reactions using 3D optical imaging: A feasibility study.

BACKGROUND: User-independent quantitative measures of cutaneous allergic reactions can help the physicians manage and evaluate the treatment of cutaneous allergic reactions. In this paper, we present and validate a method to quantify the elevation, volume and area of cutaneous allergic reactions to red tattoos. METHODS: The skin surface of allergic tattoo reactions was imaged using an optical 3D scanner. The in-house developed analysis tool measured the elevation, volume and area of the lesions, compared to a reference surface. This reference surface was created by 3D interpolation of the skin after manual removal of the lesions. The error of the interpolation tool was validated using a digital arm model. The error of our optical scanner was determined using a 3D printed lesion phantom. The clinical feasibility of the method was tested in 83 lesions in 17 patients. RESULTS: The method showed clear potential to assess skin elevation, volume change and area of an allergic reaction. The validation measurements revealed that the error due to interpolation increases for larger interpolation areas and largely determined the error in the clinical measurements. Lesions with a width ≥4 mm and an elevation ≥0.4 mm could be measured with an error below 26%. Patient measurements showed that lesions up to 600 mm2 could be measured accurately, and elevation and volume changes could be assessed at follow-up. CONCLUSION: Quantification of cutaneous allergic reactions to red tattoos using 3D optical scanning is feasible and may objectify skin elevation and improve management of the allergic reaction.

Comparison of the skin sensitization potential of 3 red and 2 black tattoo inks using interleukin-18 as a biomarker in a reconstructed human skin model.

BACKGROUND: During the last decade, the number of people with ≥1 tattoo has increased noticeably within the European population. Despite this, limited safety information is available for tattoo inks. OBJECTIVES: To test the skin sensitization potential of 5 tattoo inks in vitro by using reconstructed human skin (RHS) and the contact sensitization biomarker interleukin (IL)-18. METHODS: Two red and 3 black tattoo inks, 1 additive (Hamamelis virginiana extract) and 1 irritant control (lactic acid) were tested. The culture medium of RHS (reconstructed epidermis on a fibroblast-populated collagen hydrogel) was supplemented with test substances in a dose-dependent manner for 24 hours, after which cytotoxicity (histology; thiazolyl blue tetrazolium bromide assay) and skin sensitization potential (IL-18 secretion; enzyme-linked immunosorbent assay) were assessed. RESULTS: All but 1 ink showed cytotoxicity. Notably, 1 red ink and 1 black ink were able to cause an inflammatory response, indicated by substantial release of IL-18, suggesting that these inks may be contact sensitizers. CONCLUSIONS: The in vitro RHS model showed that 4 tattoo inks were cytotoxic and 2 were able to cause an inflammatory IL-18 response, indicating that an individual may develop allergic contact dermatitis when exposed to these tattoo inks, as they contain contact sensitizers.

[A permanent discoloration of the skin surrounding a tattoo]. / Een persisterende verkleuring rond een tatoeage.

A 64-year-old man visited the dermatology department because of an asymptomatic discoloration of the skin surrounding a tattoo. Based on the clinical presentation we diagnosed a 'blow-out', which is a chronic halo around a recently placed tattoo caused by diffusion of tattoo inks in the lower dermis or subcutis.

Cutaneous Malignancies in Tattoos, a Case Series of Six Patients.

BACKGROUND: A variety of side effects following the tattooing of the skin were reported over the years. Analytical studies showed that some tattoo inks contain harmful compounds. METHODS: We presented six patient cases with cutaneous malignancies in tattooed skin and performed an extensive literature research. RESULTS: Two patients with black ink tattoos that were diagnosed with malignant melanoma raises the number of described cases to 36 patients. One of the patients developed an immunologic reaction limited to the tattoo area after treatment with a targeted immune therapy. In the other patient, the malignancy (malignant melanoma) was fatal. Basal cell carcinoma was seen in four patients with tattoos containing varying ink colors (black, green, red). This increased the number of described patient cases to 18. Although some ink components and their cleavage products have carcinogenic properties, epidemiological evidence for a causative correlation fails. Further epidemiologic studies on tattoos and malignancies, as well as on the appearance of naevi in tattoos, are necessary. Determining the type of mutation might be helpful to separate sun-induced tumors from skin cancers due to other pathogenic mechanisms.

Cutaneous non-allergic complications in tattoos: An overview of the literature.

Tattooing is creating a permanent design by placing exogenous pigment particles and additives into the dermis. An adverse reaction may occur due to the act of tattooing and subsequent application of aftercare products. Numerous articles report the wide spectrum of adverse reactions related to tattooing, ranging from superficial infections and vasculitis to Koebner triggered autoimmune diseases. These reactions have different time of onset of symptoms, appearing immediately after placement of the tattoo until several years later. In this article we will give an overview of cutaneous non-allergic adverse reactions of tattoos.

[Morgellons, a 'socially transmitted' disease]. / Morgellons, een 'sociaal overdraagbare' aandoening.

BACKGROUND: Morgellons disease is a controversial condition characterised by a great variety of skin-related symptoms such as wounds, itch and pain and whereby the patient strongly believes these are caused by threads or fibres penetrating the skin. The subject is often discussed in social media, which leads to increasing numbers of patients who think they have the condition. CASE DESCRIPTION: A 56-year-old woman had been suffering for three years of compulsive behaviour involving her hair and scratching her skin. She was convinced there were threads running under her skin. She had self-diagnosed 'Morgellons disease'. Psychodermatological treatment led to reduced symptoms. CONCLUSION: The majority of medical practitioners believe that Morgellons disease is a type of delusional infestation. Even though there are some medical and non-medical practitioners who take the position that there is an infectious cause, such a cause has never been found.

[A boy with a chronic swelling of the upper lip]. / Een jongen met chronische zwelling van de bovenlip.

A 14-year-old boy developed a chronic painless swelling of the upper lip. Histology of a skin biopsy showed non-necrotizing tuberculoid granulomas. The diagnosis cheilitis granulomatosa was made.