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.

Anti-SAE autoantibody in dermatomyositis: original comparative study and review of the literature.

OBJECTIVE: Among specific autoantibodies in DM, the anti-small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE-positive DM. METHODS: Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE-negative DM and a review of the literature. RESULTS: Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE-negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P < 0.0001) and less dyspnoea (P = 0.003). CONCLUSION: Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT04637672.

Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours.

Melanoma is a highly metastatic tumour originating from neural crest-derived melanocytes. The aim of this study was to analyse the expression of neuron navigator 3 (NAV3) in relation to membrane type-1 matrix metalloproteinase MMP14, a major regulator of invasion, in 40 primary melanomas, 15 benign naevi and 2 melanoma cell lines. NAV3 copy number changes were found in 18/27 (67%) primary melanomas, so that deletions dominated (16/27 of samples, 59%). NAV3 protein was found to be localized at the leading edge of migrating melanoma cells in vitro. Silencing of NAV3 reduced both melanoma cell migration in 2-dimensional conditions, as well as sprouting in 3-dimensional collagen I. NAV3 protein expression correlated with MMP14 in 26/37 (70%) primary melanomas. NAV3 and MMP14 were co-expressed in all tumours with Breslow thickness < 1 mm, in 11/23 of mid-thickness tumours (1-5 mm), but in only 1/6 samples of thick (> 5 mm) melanomas. Altogether, NAV3 number changes are frequent in melanomas, and NAV3 and MMP14, while expressed in all thin melanomas, are often downregulated in thicker tumours, suggesting that the lack of both NAV3 and MMP14 favours melanoma progression.

Hypersensitivity to permanent tattoos: Literature summary and comprehensive review of patch tested tattoo patients 1997-2022.

We outline constituents of tattoo and permanent make-up ink with regard to inflammatory tattoo reactions and population-based confounders. The comprehensive review of patch-tested tattoo patients between 1997 and 2022 shows that tattoo allergy cannot be reliably diagnosed via patch testing with today's knowledge. Weak penetration and slow haptenization of pigments, unavailability of pigments as test allergens and a lack of knowledge concerning relevant epitopes hamper the diagnosis of tattoo allergy. Patch testing p-phenylenediamine and disperse (textile) dyes is not able to close this gap. Sensitization to metals was associated with all types of tattoo complications, although often not clinically relevant for the tattoo reaction. Binders and industrial biocides are frequently missing on ink declarations and should be patch tested. The pigment carbon black (C.I. 77266) is no skin sensitizer. Patch tests with culprit inks were usually positive with cheap ink products for non-professional use or with professionally used inks in patients with eczematous reactions characterized by papules and infiltration. Tape stripping before patch testing and patch test readings on Day 8 or 10 may improve the diagnostic quality. The meaningfulness of the categorical EU-wide ban of Pigment Green 7 and Pigment Blue 15:3 is not substantiated by the presented data.

Chemical characterization of inks in skin reactions to tattoo.

Skin reactions are well described complications of tattooing, usually provoked by red inks. Chemical characterizations of these inks are usually based on limited subjects and techniques. This study aimed to determine the organic and inorganic composition of inks using X-ray fluorescence spectroscopy (XRF), X-ray absorption spectroscopy (XANES) and Raman spectroscopy, in a cohort of patients with cutaneous hypersensitivity reactions to tattoo. A retrospective multicenter study was performed, including 15 patients diagnosed with skin reactions to tattoos. Almost half of these patients developed skin reactions on black inks. XRF identified known allergenic metals - titanium, chromium, manganese, nickel and copper - in almost all cases. XANES spectroscopy distinguished zinc and iron present in ink from these elements in endogenous biomolecules. Raman spectroscopy showed the presence of both reported (azo pigments, quinacridone) and unreported (carbon black, phtalocyanine) putative organic sensitizer compounds, and also defined the phase in which Ti was engaged. To the best of the authors' knowledge, this paper reports the largest cohort of skin hypersensitivity reactions analyzed by multiple complementary techniques. With almost half the patients presenting skin reaction on black tattoo, the study suggests that black modern inks should also be considered to provoke skin reactions, probably because of the common association of carbon black with potential allergenic metals within these inks. Analysis of more skin reactions to tattoos is needed to identify the relevant chemical compounds and help render tattoo ink composition safer.

Tattoo Ink Market in France: A Field Study among 598 Professional Tattooists.

BACKGROUND: Tattoo ink safety is one of the main concerns surrounding tattooing practices. In order to better assess the risks and increase the safety of tattoo inks, it is important to know about the habits of tattooists in real life. OBJECTIVE: We investigated the most popular inks in the French market and how professional tattooists used them in their daily practice. METHODS: We performed an observational, self-reported, online survey concerning the French tattoo artists. All active professional tattooists in France were invited to take part in a six-question Internet survey regarding their tattoo inks usage habits. RESULTS: 598 tattooists reported 36 different brands of black inks and 30 of colored inks. However, 6 brands of black inks were used by 14.2-44% of the tattooists and, for colored inks, 5 manufacturers were favored by 11.2 up to 55.7% of the tattooists. The majority of tattooists (68.9%) mixed two different colors or more to obtain a new shade while 21.7% would try to find the adequate shade within the assortment provided by a manufacturer. 54.4% had between 10 and 40 references, 31.9% had less than 10 references, 11.5% had 40-100 references, and 2.2% had >100 references. CONCLUSIONS: The market of tattoo inks in France is dominated only by a fistful of brands. Controls by official authorities should target those popular brands, even though all brands should respect the law. Toxicological studies should always precise the provenance market and which brands are tested, so we can assess their impact in real life. Tattooists should also try to lower the number of ready-made colors they require.

Tribal makeup painting mimicking achromic lupus in a Teke tribal chef: icono-diagnosis is a dangerous art.

A close-up photograph of a Teke community Chief (Congo, circa 1880-1890) seemed to be of diagnostic interest, as areas of achromic maculae were visible on the hands: the most relevant diagnoses were a Koebner phenomenon on a background of vitiligo, or a diagnosis of lupus. However, examination of the entire photograph showed that the 'maculae' were in fact tribal makeup, showing the methodological limits of icono-diagnosis.

Nickel and tattoos: Where are we?

Tattoos are not mentioned as a source of exposure to nickel. Traces of nickel are, however, almost inevitably found in tattoo inks as impurities and sometimes in tattooed skin. Whether nickel in tattoos has any health consequence is debated. We performed a narrative review of what is currently known about this topic. Today, nickel is frequently detected in inks, but at highly variable levels. It appears to be at higher concentrations in green, blue, and sometimes brown and violet inks. Only nickel allergy in tattooed individuals and nickel-associated tattoo ink allergy are addressed in the literature. Reports of tattoo ink allergy related to nickel are rare and heterogenous. Authors often neglect possible implications of other metals or dyes. A positive patch test is not enough to confirm the role of nickel in a reaction observed after tattooing. We found no report of any systemic complication attributed to nickel from tattoos. The Council of Europe ResAP(2008)1 bans the presence of nickel at high levels in tattoo inks, which is a safety net for individuals with nickel allergy. Large epidemiologic case-control studies with systematic biopsies on normal and inflamed tattoos and patch testing would help to understand the role of nickel in tattoo ink allergies.

Calcium-Sensing Receptor Autoantibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1: Epitopes, Specificity, Functional Affinity, IgG Subclass, and Effects on Receptor Activity.

A major manifestation of autoimmune polyendocrine syndrome type 1 (APS1) is hypoparathyroidism, which is suggested to result from aberrant immune responses against the parathyroid glands. The calcium-sensing receptor (CaSR), which plays a pivotal role in maintaining calcium homeostasis by sensing blood calcium levels and regulating release of parathyroid hormone (PTH), is an autoantibody target in APS1. In this study, the aim was to characterize the binding sites, specificity, functional affinity, IgG subclass, and functional effects of CaSR autoantibodies using phage-display technology, ELISA, and bioassays. The results indicated that CaSR autoantibody binding sites were at aa 41-69, 114-126, 171-195, and 260-340 in the extracellular domain of the receptor. Autoantibodies against CaSR epitopes 41-69, 171-195, and 260-340 were exclusively of the IgG1 subclass. Autoantibody responses against CaSR epitope 114-126 were predominantly of the IgG1 with a minority of the IgG3 subclass. Only autoantibodies recognizing CaSR epitopes 114-126 and 171-195 affected receptor activity; inositol-phosphate accumulation was increased significantly in HEK293-CaSR cells, and PTH secretion from PTH-C1 cells was reduced significantly when either were incubated with purified Ab and Ca2+ compared with Ca2+ alone. In conclusion, although the majority of APS1 patients do not have CaSR-stimulating autoantibodies, the hypoparathyroid state in a small minority of patients is the result of functional suppression of the parathyroid glands.

Hidradenitis Suppurativa Influences Tattooing Practice in Women.

BACKGROUND: The reasons or the motivations that compel people to get a tattoo or a body piercing (BP) are plentiful and personal. Patients with chronic cutaneous or systemic conditions may be interested in getting tattooed or pierced. OBJECTIVE: To determine the frequency of body art practices in hidradenitis suppurativa (HS) and to evaluate the possible impact of HS in the decision-making process. METHODS: An anonymous specific paper-based questionnaire was prospectively offered to patients (≥18 years) consecutively managed for HS from September 2016 to March 2017 in a French specialized center. RESULTS: In total, 209 patients participated in the study, of whom 77 (37%) and 50 (24%) had tattoos and BP, respectively. These proportions were higher than those reported in the French population. HS prevented the decision to get a BP or a tattoo in 2 and 5%, respectively (fear of infection or healing difficulties). Fifteen patients (7%) got tattooed to hide a surgical HS scar (n = 5, 2%), to regain control over the pain or their bodies (n = 9, 4%), or to turn others' eyes away from HS lesions or scars (n = 1, 0.5%). HS severity influenced a proportion of patients who intended to get a new tattoo. CONCLUSION: HS is associated with a significant increase in body art practices.

Body Piercing: A National Survey in France.

BACKGROUND: There are no recent data available in France regarding body piercing (BP). OBJECTIVE: We examined the demographics, motivations, quality of life, cutaneous conditions, and cutaneous side effects after BP within the French population. METHODS: A representative sample of 5,000 individuals (aged 15 and over) from the general population responded to a survey online between April and August 2017. Data regarding demographics, BP characteristics (location, age at first piercing, hesitation, regrets, motivations, cutaneous side effects), tobacco, skin conditions (acne, contact eczema, atopic eczema, rosacea, psoriasis, vitiligo), and tattoos were collected. Respondents also filled an SF-12 quality of life questionnaire. RESULTS: Overall, 12% of the respondents reported at least one BP (women: 19.4%, men: 8.4%, p < 0.01). The prevalence was highest among those aged between 25 and 34 years (25.8%). Individuals with BP were more likely to smoke (p < 0.01). The most common body parts for piercings were the external part of the ear (42%), the navel (24%), the tongue (15%), and the nose (11%). Gender differences included localization (belly button and nose for women, eyebrows for men) and motivations (embellishment of the body for women, individuality and sexuality for men). A total of 33.6% of the study participants reported having skin problems after BP, primarily infection (44%). Individuals with BPs were more likely to report having contact eczema, atopic dermatitis, and acne. BP was associated with a lower mental quality of life score. CONCLUSION: This is the largest epidemiological study on BP in France to date. It allows us to draw a precise current snapshot of French indi viduals with BP.

Anticommensal Responses Are Associated with Regulatory T Cell Defect in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Patients.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autoimmune disease caused by mutations in the AIRE gene. Although mainly an endocrine disease, a substantial fraction of patients have gastrointestinal manifestations. In this study, we have examined the role of anticommensal responses and their regulation. APECED patients had increased levels of Abs against Saccharomyces cerevisiae (p < 0.0001) and against several species of commensal gut bacteria, but not against species predominantly associated with other locations. The anticommensal Ab levels did not correlate with gastrointestinal autoantibodies, neutralizing anti-IL-17 or -IL-22 Abs, or gastrointestinal symptoms, although scarcity of the available clinical data suggests that further study is required. However, the anti-S. cerevisiae Ab levels showed a significant inverse correlation with FOXP3 expression levels in regulatory T cells (Treg), previously shown to be dysfunctional in APECED. The correlation was strongest in the activated CD45RO(+) population (ρ = -0.706; p < 0.01). APECED patients also had decreased numbers of FOXP3(+) cells in gut biopsies. These results show that APECED patients develop early and sustained responses to gut microbial Ags in a pattern reminiscent of Crohn's disease. This abnormal immune recognition of gut commensals is linked to a systemic Treg defect, which is also reflected as a local decrease of gut-associated Treg. To our knowledge, these data are the first to show dysregulated responses to non-self commensal Ags in APECED and indicate that AIRE contributes to the regulation of gut homeostasis, at least indirectly. The data also raise the possibility of persistent microbial stimulation as a contributing factor in the pathogenesis of APECED.