Dermatological and Ophthalmological Inflammatory, Infectious, and Tumoral Tattoo-Related Reactions: A Systematic Review



 

Juliana Muñoz-Ortiz, MD1,2; Mariana Teresa Gómez-López, MD2,3; Paula Echeverry-Hernández, MD2; Mario Federico Ramos-Santodomingo, Medical Student2; Alejandra de-la-Torre, MD, PhD2

Perm J 2021;25:20.225

https://doi.org/10.7812/TPP/20.225
E-pub: 05/26/2021

Purpose: The purpose of this work was to review the scientific evidence about dermatological and ophthalmological inflammatory, infectious, and tumoral tattoo-related reactions published in the literature.

Methods: We conducted a literature search from January 1, 2000 to July 15, 2020 in MEDLINE, COCHRANE, EMBASE, and LILACS. Limits regarding the language and period of publication were used. A data collection form was designed in Excel. Four reviewers independently extracted relevant details about the design and the results of each study.

Results: One hundred four studies were included, most of them were conducted in Europe and North America. The remaining studies were conducted in Asia, South America, Africa, and Oceania. We included 52 case reports, 21 cross-sectional studies, 20 case series, 10 case-control studies, and 1 cohort study. Eighty-six studies described skin tattoos, of which 7 were publications of eyebrow tattoos and 6 of eyelid tattoos, and 5 articles included cases of subconjunctival tissue tattoos (eyeball). Fifty-seven studies described local reactions related to tattoos and 47 studies reported systemic reactions or reactions in different locations from the tattoo site. The types of reactions described in the studies were: infections in 45 studies, inflammatory reactions in 53 studies, neoplasia in 4 studies, and hypertrichosis in 2 studies.

Conclusion: This literature review evidenced a close relationship between the application of tattoos on dermatological and ophthalmological tissues, and the possible immunological complications, neoplasms, and infectious complications. Dermatologists and ophthalmologists should be aware of the consequences caused by even small amounts of ink applied on skin and eyes, generating the need for strict regulations for its use.

INTRODUCTION

In the last 20 years, body art, mainly tattoos and piercings, has gained great popularity in Western countries, where the overall prevalence of tattooing in the general population is approximately 10%-20%. Dermal tattoos are types of permanent body modification, where needles, with a 50-3,000 rpm speed, are used to deposit ink in the dermis, providing different color to the tissue to create a design.1 Their use dates back to ancient times around 3250 BC.2

Traditionally, tattooing has been more frequent in men; however, female incidence has quadrupled in the last 20 years, reaching similar statistics in both sexes. An explanation for this phenomenon is the increasing use of tattoos for cosmetic purposes, (permanent makeup) generally but not exclusively, on women.3 In the same way, an increasing trend has been observed in the use of inks at the level of tissues other than the skin, such as the oral mucosa and eyeball, where ink is applied through the injection of pigments directly under the bulbar conjunctiva.4

The inks anteriorly used in tattoos were suspensions of insoluble pigments composed of organic and inorganic elements dispersed in water or glycerin, together with other additives such as dispersants and preservatives.5-7 Currently, inks contain mainly organic components, initially designed as automotive paint components or inks for printing,5,6 and metals such as manganese, lead, vanadium, cadmium, and antimony diluted in water, alcohol, or glycerin.8 Other types of decorating tattoos are the temporary ones, usually made with henna, an organic compound (2-hydroxy-1,4-naphthoquinone). This type of tattoo remains visible for 2-4 weeks and in some cases is related to allergic reactions.9

Ink tattoo’s toxicology depends on the color. Color inks are composed mainly of organic elements, azo or polycyclic pigments, containing impurities such as aromatic amines, which have been described as carcinogenic compounds.10,11 Due to its chemical composition, cutaneous complications occur more frequently related to colored tattoos (83.3%).12 Black ink, the most frequently used (50%), presents carcinogenic components such as carbon black, a substance that induces the inflammatory response with mutagenic effects due to the formation of reactive oxygen species, polycyclic aromatic hydrocarbons, and phenols.5-8,13 Red ink, second in use (14%), is most frequently related to allergic reactions, possibly linked with the photosensitization of cadmium.6,14 White ink is composed mainly of titanium dioxide, a large molecule related to a low number of allergic reactions. This could be explained by the inversely proportional relationship between the particle size and its biological activity; thus, as the size of a particle increases, its biological activity decreases.15,16

Regarding the complications of dermal tattoos, it is known that up to 67.5% of people report cutaneous complications, 6.6% report systemic complications, and 6% report persistent skin problems.14 In the case of ocular complications, these may be due to systemic effects of dermal tattoos17 or the direct application of the ink in the subconjunctival tissue.18

This growing tendency of dermal and eye tattoos and their complications has allowed governments such as the United States of America to carry out modifications in 2017 public health law so that the implementation of eye tattoos indicated in different ophthalmological pathologies can only be done by medical practitioners or other qualified persons.19

METHODS

Protocol

The review protocol was developed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines.20

Purpose

The purpose of this work was to review the scientific evidence about dermatological and ophthalmological inflammatory, infectious, and tumoral tattoo-related reactions, published in the literature.

Study Design

The study design used was a systematic review of the literature.

Eligibility Criteria

We included all observational studies, comprising analytic (comparative cross-sectional studies, case-control studies, and cohort studies) and descriptive studies (case reports, case series, and prevalence studies) published in the last 20 years. Publications were included if they had available full text, presented original data, and described an inflammatory, infectious, and/or tumoral tattoo-related reaction. Articles were excluded from the analysis if the diagnosis of the tattoo-related reaction was not demonstrated, if the publication language was different from English, Spanish, or French, and if the publication was a poster or congress abstract.

Information Sources

We used a combination of exploded controlled vocabulary (Medical Subject Headings - MeSH, Emtree, “Descriptores en Ciencias de la Salud”/Health Sciences Descriptors - DeCS) and free-text terms (considering spelling variants, plurals, synonyms, acronyms, and abbreviations) with field labels, truncation, proximity operators, and Boolean operators.

The literature search was conducted in the following electronic databases up to July 15, 2020: MEDLINE, COCHRANE, EMBASE, and LILACS. The limits used included: human subjects, Spanish, French, and English language, year of publication from January 1, 2000 to July 15, 2020, and observational or analytical studies (Annex 1a).

Study Selection

The electronic search was made by 2 reviewers (Juliana Muñoz-Ortiz and Mariana Teresa Gómez-López). Duplicates were eliminated through a Zotero function. We performed an independent review of article titles and abstracts extracting data according to the predefined eligibility criteria. We proceeded to read the full text of the studies selected in the previous step. To solve any discrepancies, a senior researcher acted as a third reviewer (Alejandra de-la-Torre).

Data Collection Process

A data collection form was designed in Excel. Four reviewers (Juliana Muñoz-Ortiz, Mariana Teresa Gómez-López, Paula Echeverry-Hernández, Mario Federico Ramos-Santodomingo) independently extracted relevant details about the design and the results of each study. Later, a consensus was reached to organize the results regarding the literature search results, the characteristics of the studies, inflammatory reactions secondary to dermal tattoos, neoplasms secondary to dermal tattoos, other secondary reactions to dermal tattoos, and ophthalmological inflammatory and infectious reactions secondary to eyebrow, eyelid, and ocular tattoos.

RESULTS

Literature Search Results

Our search strategy extracted 556 published articles (116 from MEDLINE, 437 from EMBASE, 2 from COCHRANE, and 1 from LILACS). After the title, abstract, and full-text screening were performed, 104 articles were assessed for data extraction (Figure 1). We obtained the necessary information to address the topics of interest in the present review.

tpj20225f1 copy

Figure 1. PRISMA flow diagram for included studies.

Studies Characteristics

Forty-five studies were conducted in Europe, 22 in North America, 19 in Asia, 9 in South America, 5 in Africa, and 4 in Oceania. All of them were published between 2000 and 2020. Regarding the study design, we included 52 case reports, 21 cross-sectional studies, 20 case series, 10 case-control studies, and 1 cohort study.

The location of the tattoo in the 104 included studies was distributed as follows: 86 studies of skin tattoos of which 7 were publications of eyebrow tattoos and 6 of eyelid tattoos, and 5 articles included cases of subconjunctival tissue tattoos (eyeball). Fifty-seven studies described local reactions related to tattoos and 47 studies reported systemic-reactions or different location reactions from the tattoo site. The type of reactions described in the studies were: infections in 45 studies, inflammatory reactions in 53 studies, neoplasia in 4 studies, and hypertrichosis in 2 studies.

Eight studies describe dermal tattoos related to local infectious complications and 37 to dermal tattoos related to systemic infectious complications. Detailed information can be found in Tables 1 and 2. Twenty-eight studies describe dermal tattoos related to local inflammatory complications and 7 to dermal tattoos related to systemic inflammatory complications. Detailed information can be found in Tables 3 and 4. Four studies describe dermal tattoos related to neoplasm. Detailed information can be found in Table 5. Two studies describe other secondary reactions to dermal tattoos. Detailed information can be found in Table 6. Finally, 18 studies describe ophthalmological inflammatory and infectious processes secondary to eyebrow, eyelid, and ocular tattoos. Detailed information can be found in Table 7.

Table 1. Dermal tattoos, local infectious complications

N Author Year Location Study design Diagnosis
1 Chatterjee et al63 2017 Asia Case report Viral verruca (HPV)
2 Velez et al57 2018 North America Case report Cutaneous Mycobacterium massiliense infection
3 Kirchhof et al64 2019 North America Case report Viral verruca (HPV)
4 Bechara et al58 2010 South America Case report Cutaneous Mycobacterium abscessus sensu stricto infection
5 Wu et al59 2017 Asia Case series Cutaneous Mycobacterium abscessus infection
6 Sergeant et al60 2013 Europe Case series Cutaneous Mycobacterium chelonae infection
7 Falsey et al61 2013 North America Case series Cutaneous nontuberculous Mycobacteria (Mycobacterium chelonae and Mycobacterium abscessus)
8 Drage et al62 2010 North America Case series Cutaneous Mycobacterium chelonae infection

HPV = human papilloma virus.

Table 2. Dermal tattoos, systemic infectious complications

N Author Year Location Study design Diagnosis
1 Suan et al25 2019 Africa Case-control Hepatitis C infection
2 Ngo et al26 2007 Asia Case-control Hepatitis C infection
3 Shahriari-Fard et al27 2018 Asia Case-control Hepatitis C infection
4 Kermani et al28 2018 Asia Case-control Hepatitis C infection
5 Goldman et al29 2009 North America Case-control Hepatitis C infection
6 Carney et al30 2013 North America Case-control Hepatitis C infection
7 Brandão et al31 2002 South America Case-control Hepatitis C infection
8 Tse et al85 2009 Europe Case report Bacterial endocarditis
9 Viswanathan et al50 2011 Europe Case report Hepatitis B infection
10 Hendren et al86 2017 Europe Case report Vibrio vulnificus septic shock
11 Akkus et al87 2014 North America Case report Bacterial endocarditis
12 Porter et al88 2005 Oceania Case series Necrotizing fasciitis and cellulitis
13 McLean et al89 2011 Oceania Case series Cellulitis and septic shock
14 Gasmi et al55 2019 Africa Cross-sectional Hepatitis D infection
15 Khan et al51 2011 Asia Cross-sectional Hepatitis B infection
16 Kim et al32 2012 Asia Case-control Hepatitis C infection
17 Seong et al33 2013 Asia Cohort Hepatitis C infection
18 Toresen et al34 2014 Europe Cross-sectional Hepatitis C infection
19 Avramovic et al35 2020 Europe Cross-sectional Hepatitis C infection
20 Cheung et al36 2000 North America Cross-sectional Hepatitis C infection
21 Belaunzaran-Zamudio et al48 2017 North America Cross-sectional Hepatitis B and C infection
22 Vickery et al37 2009 Oceania Case-control Hepatitis C infection
23 Nakhla et al38 2015 Africa Cross-sectional Hepatitis C infection
24 Komas NP et al52 2018 Africa Cross-sectional Hepatitis B infection
25 Zhang et al53 2013 Asia Cross-sectional Hepatitis B infection
26 Ba-Essa et al49 2016 Asia Cross-sectional Hepatitis C infection
27 Ansari-Moghaddam et al54 2016 Asia Cross-sectional Hepatitis B infection
28 Moradi et al39 2018 Asia Cross-sectional Hepatitis C infection
29 Hodžić et al40 2017 Europe Cross-sectional Hepatitis C infection
30 Belaunzarán-Zamudio et al41 2017 North America Cross-sectional Hepatitis C infection
31 Poulin et al42 2018 North America Cross-sectional Hepatitis C infection
32 Peña-Orellana et al43 2011 South America Cross-sectional Hepatitis C infection
33 Paraboni et al44 2012 South America Cross-sectional Hepatitis C infection
34 Silverman-Retana et al45 2017 South America Cross-sectional Hepatitis C infection
35 Teles et al46 2018 South America Cross-sectional Hepatitis C infection
36 Chalmers et al90 2010 North America Case report Xanthogranulomatous pyelonephritis by methicillin-resistant Staphylococcus aureus
37 Mitrovic et al47 2018 Europe Case-control Hepatitis C infection

Table 3. Dermal tattoos, local inflammatory complications

N Author Year Location Study design Diagnosis
1 Chung et al91 2001 Asia Case series Allergic contact dermatitis following application of temporary tattoos
2 Lamchahab et al92 2011 Africa Case report Allergic contact dermatitis following application of temporary tattoos
3 Le Coz et al93 2000 Europe Case series Allergic contact dermatitis following application of temporary tattoos
4 Martin et al94 2005 Europe Case report Allergic contact dermatitis following application of temporary tattoos
5 Ballard S95 2006 Europe Case report Allergic contact dermatitis following application of temporary tattoos
6 Jones et al66 2008 Europe Case report Granulomatous reaction to a cosmetic lip tattoo
7 Jovanovic et al96 2009 Europe Case report Allergic contact dermatitis following application of temporary tattoos
8 Gunasti et al97 2010 Europe Case report Allergic contact dermatitis following application of temporary tattoos
9 Tammaro et al98 2011 Europe Case report Allergic contact dermatitis following application of gold in a tattoo
10 Pasolini et al99 2011 Europe Case report Pseudolymphoma mimicking malignant skin lymphoma
11 Vílchez-Márquez et al67 2012 Europe Case report Granulomatous reaction
12 Prcic et al100 2012 Europe Case series Allergic contact dermatitis following application of temporary tattoos
13 Wood et al68 2014 Europe Case report Necrobiotic granulomatous inflammation
14 Levancini et al101 2015 Europe Case report Allergic contact dermatitis following application of temporary tattoos
15 Ruiz-Villaverde et al69 2018 Europe Case series Granulomatous reaction
16 Saulite et al102 2018 Europe Case report Pseudolymphomatous reaction
17 Balfour et al103 2003 North America Case report Pseudoepitheliomatous hyperplasia
18 Cui et al104 2007 North America Case report Pseudoepitheliomatous hyperplasia
19 Goodie et al105 2016 North America Case report Allergic contact dermatitis following application of temporary tattoos
20 Saunders et al106 2004 Oceania Case report Allergic contact dermatitis following sensitization from a temporary skin tattoo
21 Souza et al107 2014 South America Case report Cutaneous lymphoid hyperplasia
22 Wenzel et al108 2010 Europe Case series Delayed skin allergic reaction
23 de Roeck et al109 2013 Europe Case series Florid pseudoepitheliomatous hyperplasia mimicking a well-differentiated squamous cell carcinoma
24 Körner et al110 2013 Europe Case series Acute contact dermatitis (15.3%), lupus-like patterns (15.3%), foreign body dermatitis (38.4%), deposition of pigment without inflammation or simple scarring (15.3%), and tumors (15.2%), 1 of which was a malignant melanoma
25 Braswell et al111 2019 North America Case series Of 56 patients with lichenoid granulomatous dermatitis (7.1%) were related to skin tattoos
26 Serup et al112 2017 Europe Cross-sectional Of 405 patients with a complete study of tattoo complications 184 (37%) presented allergic reactions, with plaque elevation in 32.2%, excessive hyperkeratosis in 3.7%, and ulceration in 1.4%; 66 (13%) presented papulo-nodular reactions; 53 (11%) had bacterial infections; 46 (9%) were psycho-social complications; 144 (30%) belonged to several specific diagnostic entities, including photosensitivity, pain syndrome, and lymphopathy
27 Nikkels et al113 2001 Europe Case series Allergic contact dermatitis following application of temporary tattoos
28 Wollina et al70 2008 Europe Case report Granulomatous tattoo reaction and erythema nodosum

Table 4. Dermal tattoos, systemic inflammatory complications

N Author Year Location Study design Diagnosis
1 Zaharopoulos114 2003 Europe Case report Dermatopathic lymphadenopathy
2 Pinal-Fernandez et al115 2014 Europe Case report “Sparing phenomenon” of a purpuric rash
3 Pandya et al116 2017 Europe Case report Systemic sarcoidosis with uveitis manifestation
4 Tiew71 2019 Europe Case report Panuveitis
5 Kluger74 2017 Europe Cross-sectional Of 31 patients with cutaneous tattoo reactions, 52% presented with an allergic tattoo reaction. Reactions included lichenoid, granulomatous, pseudolymphomatous, or less specific with a dermal lymphohistiocytic or plasmocytic infiltrate reactions. Other diagnoses included tattoo blow-out (13%), melanoma within a tattoo, naevi within a tattoo (10% each), lichen planus (6%), granulomatous reaction with uveitis, sarcoidosis, and dermatofibroma (3% each)
6 Ostheimer et al18 2014 North America Case series Cutaneous granulomatous reaction and uveitis
7 Moschos et al117 2004 Europe Case report Severe posterior uveitis related to retinal vasculitis and cystoid macular edema

Table 5. Dermal tattoos related to neoplasia

N Author Year Location Study design Diagnosis
1 Kluger et al118 2008 Europe Case report Keratoacanthoma
2 Kluger et al73 2008 Europe Case series Basal cell carcinomas and ulcerated nodular melanoma (superficial spreading type)
3 Sherif et al119 2017 Europe Case report Squamous cell carcinoma
4 Maxim et al120 2017 North America Case report Multiple squamous cell carcinomas

Table 6. Other secondary reactions to dermal tattoos

N Author Year Location Study design Diagnosis
1 Habr et al75 2015 Asia Case report Hypertrichosis
2 Nazik et al76 2018 Asia Case series Hypertrichosis

Table 7. Ophthalmological inflammatory and infectious processes secondary to eyebrow, eyelid, and ocular tattoos

N Author Year Location Study design Tissue Reaction location Type of reaction Diagnosis
1 Kojima et al121 2005 Asia Case report Eyelids Local Inflammation/infection Meibomian gland loss and mucocutaneous junction changes leading to post-LASIK infectious keratitis and consequent lamellar keratoplasty
2 Moshirfar et al122 2009 Europe Case report Eyelids Local Inflammation Perilimbal pigmentation involving the conjunctiva and the superficial cornea
3 Tourlaki et al123 2010 Europe Case report Eyelids Local Inflammation Granulomatous tattoo reaction induced by intense pulse light treatment
4 Bee et al72 2014 Europe Case report Eyelids Local Inflammation Granulomatous reaction
5 De et al124 2008 North America Case report Eyelids Local Inflammation Full-thickness penetration of the lid margin, resulting in a line of pigment along the superior bulbar conjunctiva with a related inflammatory reaction
6 Vagefi et al125 2006 North America Case series Eyelids Local Inflammation Granulomatous reaction
7 Tukenmez et al126 2016 Asia Case report Eyebrows Systemic Inflammation Sarcoidosis
8 Martín et al127 2007 Europe Case report Eyebrows Systemic Inflammation Sarcoidosis
9 López Villaescusa et al128 2013 Europe Case report Eyebrows Local Inflammation Granulomatous reaction
10 Wollina129 2011 Europe Case series Eyebrows Local Inflammation/infection Granulomatous reaction/infection by Mycobacterium haemophilum
11 Antonovich et al130 2005 North America Case report Eyebrows Systemic Inflammation Sarcoidosis
12 Naeini et al131 2017 Asia Case report Eyebrows Systemic Inflammation Cutaneous and pulmonary sarcoidosis
13 Ebrahimiadib et al132 2020 Asia Case report Eyebrows Systemic Inflammation Intermediate uveitis as the first manifestations of systemic sarcoidosis
14 Brodie et al133 2015 Europe Case report Eye Local Inflammation Conjunctivitis
15 Tubek et al134 2019 Europe Case report Eye Local Inflammation Eyelid edema and black deposits of tattoo ink under the bulbar conjunctiva, dye deposits in the anterior chamber, covering corneal endothelium, iris, and anterior lens capsule. Secondary uveitis and glaucoma were diagnosed
16 Rodríguez-Avila et al135 2019 North America Case report Eye Local Inflammation In the anterior chamber, pigment granules and filaments were suspended on the aqueous humor, and the lens capsule was also stained red. Ultrasonography showed high-density nonmobile echoes in the conjunctiva; anterior chamber and vitreous cavity revealed high-density mobile echoes corresponding to pigment particles. Conjunctival tattoo with inadvertent globe penetration was the clinical diagnosis
17 Cruz et al82 2017 South America Case report Eye Local Inflammation Deposits over the conjunctiva, corneal endothelium, anterior chamber angle, iris, and anterior capsular lens due to the tattooing pigment. Besides, severe anterior uveitis triggered by the pigments, and, later, secondary glaucoma was diagnosed
18 Cruz et al80 2017 South America Case report Eye Local Inflammation Conjunctivitis and anterior uveitis

Given the heterogeneity of the study designs found in the systematic review, the analysis plan included a narrative synthesis of the results; we did not consider performing a metanalysis or other type of integrative analysis. We made a structured summary and discussion of the studies’ characteristics and findings.

DISCUSSION

The present study reviewed the literature of the last 20 years regarding the health complications of dermatological and ophthalmological tattoos. In the first place, we found that the literature that addresses this topic is very heterogeneous and geographically diverse. This may show that although it is a practice carried out all over the world, well known and with thousands of years of history, it represents in some cases risk to human health.

On the other hand, it is striking that infectious and inflammatory reactions secondary to tattoos are reported with similar numbers in the literature. We understand that inherently, ink generates a mediated immune reaction; however, infections can be due to controllable factors such as the hygiene of the procedure. As mentioned by Islam et al21 in their review, one-quarter of tattoos are performed in homes or vans by unlicensed practitioners in questionable sanitary conditions. It shows the need for strict hygiene standards and licensing requirements for the prevention of infectious diseases.

Infections Related to Dermal Tattoos

Dermal tattoos imply skin injury, which contributes to the micro-organisms passing through the epidermal barrier. In the process of tattooing, a needle enters the dermis, and there comes into contact with the blood and lymphatic vessels of the skin, which can lead to localized or systemic infections.22 These infections can be caused by the use of contaminated ink, nonsterile thinners, inadequate disinfection of the skin to be tattooed, inadequate sterilization of instruments, use of equipment previously used, or inadequate care during the healing process.22-24

In a study conducted by Nho et al24 about the microbiological contamination of the inks used for tattoos and permanent makeup in the US, it was found that 42 of the 85 inks analyzed were contaminated, 40 of them by bacteria and 9 by fungi. Staphylococcus aureus has been reported as the main etiological agent of skin infections secondary to tattoos. However, agents such as Streptococcus spp and Pseudomonas aeruginosa have also been implicated in this entity.24 These results are related to some of the systemic infections and etiological agents reported in the studies reviewed in the present article, including cellulitis, bacterial endocarditis, xanthogranulomatous pyelonephritis, necrotizing fasciitis, and septic shock. Nevertheless, it is important to mention that, as shown in the present review, the viral agents are the most morbid and frequent systemic infections. The hepatitis C virus is the most frequently reported systemic infection in these patients (25 of the 37 studies mentioning systemic compromise by dermal tattoos24-49), followed by the hepatitis B virus (6 studies)48,50-54 and the hepatitis D virus (1 study)55.

On the other hand, regarding local infections including impetigo, folliculitis, furunculosis, and ecthyma, nontuberculous Mycobacteria has been implicated as an important etiological agent.22,56 As shown in the results of our review, where 8 articles mentioned local involvement by dermal tattoos, 6 corresponded to Mycobacterial infections57-62 and only 2 to human papilloma virus.63,64

Inflammatory Reactions Secondary to Dermal Tattoos

The inks used in dermal tattoos are composed of particles with an approximate size of 6-800 nm. These are molecules of low solubility with resistance to the degradation of enzymes and macrophages, a factor that contributes to the long duration of the pigments in the dermis. Also, they can conform agglomerates thanks to the electrical charge of their surface, generating its subsequent recognition by the immune system as foreign bodies, capable of triggering local or systemic inflammatory responses.16

The pathology reports of biopsies taken from areas with complications secondary to dermal tattoos show a great variety of inflammatory reactions, among them: eosinophilic infiltrates with B and T cells and plasma cells, epidermal hyperplasia with vacuolar alteration of the basal keratinocytes and lymphocytic infiltration, and pigmented macrophages.5 Also, the dyes are encapsulated and can be seen as secondary lysosomes or as particles phagocytosed in the macrophages of the dermis. The deposit of pigments in organs such as the liver, spleen, and kidneys has been described in people with skin tattoos, and although the mechanism is still not well understood, dissemination is considered to be through the bloodstream.65

The granulomatous reactions are mainly related to mercury-containing particles. It is believed that the formation of granulomas corresponds to the stimulation of an antigen on T cells that lead to the release of cytokines such as the monocyte chemotactic protein-1, necessary for the recruitment of monocytes/macrophages.15 In our review, multiple granulomatous skin reactions secondary to dermal tattoos were identified; they were related to systemic granulomatous compromise, uveitis, and lichenoid reactions.17,66-72

Regarding hypersensitivity reactions, dermal pigments can lead to an inflammatory response where there is a release of histamine, prostaglandins, and leukotrienes. This reaction has been seen mainly as a response to the cobalt inks.15 This was the most frequently observed reaction in our review, in the section of articles that showed local inflammatory complications of dermal tattoos, mainly associated with temporary tattoos.

Neoplasms Secondary to Dermal Tattoos

In our literature review, we found reports of cases of dermal tattoos associated with the presence of melanoma, squamous cell carcinoma, keratoacanthoma, and basal cell carcinoma of the skin. The hypothesis that supports this relationship is based on several factors, among which are the trauma of the skin during the performance of the tattoo, the chronic inflammatory reaction that occurs in the dermis in response to the ink pigments, and exposure of the skin tattooed to ultraviolet light.73 However, the low number of cases reported so far, despite a large number of people tattooed, suggests that the association between skin cancer and tattoos is coincidental.73,74

Other Secondary Reactions to Dermal Tattoos

Temporary black henna tattooing is a highly popular practice in some regions. Hypertrichosis secondary to henna pseudotattoo is a rare, newly recognized cutaneous manifestation. In some cases, it resolves spontaneously after 2 months. In our literature search, 2 articles of patients in Asia were identified describing this condition.75,76

Ophthalmological Inflammatory Reactions Secondary to Eyebrow, Eyelid, and Ocular Tattoos

Although our review found a low number of reports of patients with ophthalmological tattoos, this procedure has remarkably high comorbidity, since it is an immunologically privileged organ that reacts with different inflammatory processes in the face of an immunological affront,77 putting vision at risk.

While the tissue of the eyebrows and eyelids is skin, they are part of the annexes of the eyeball and therefore the medical approach is made by an ophthalmologist. The secondary reactions to tattoos of these tissues are mostly granulomatous, as shown in the studies included in the present review, where 8 studies of patients with eyebrow and eyelid tattoos presented granulomatous reactions, including systemic sarcoidosis.

Regarding eye tattoos, they are considered an extreme form of body modification. It is a phenomenon that is becoming more popular throughout the world and consists of the application of some type of pigment directly under the bulbar conjunctiva of the eye with a needle.78

Intraocular pigments, also called episcleral tattoos, were first described in 2007,79 and since then, in the literature, there have been multiple cases of short and long-term complications secondary to this practice, possibly due to the lack of standardization on the type of pigments, the technique, and the appropriate personnel to perform it.

Concerning the composition of the pigments, according to the case reports published, the spectrum of substances used includes aqueous suspensions of vegetable pigments and a mixture of nonionic surfactants,80 sterile water, glycerol isopropanol, and copper phthalocyanine,81 conventional ink used to tattoo the skin, known as “eternal ink” composed of organic pigments, distilled water, witch hazel, and alcohol,82 or titanium dioxide particles.78 The long-term effects of ocular exposure to these pigments are unknown, but pure copper can cause retinal toxicity due to acute calcosis, a potential cause of permanent vision loss.81

The cytological analysis of ocular tissues has revealed the presence of macrophages containing cytoplasmic pigmented material and hemosiderin, as well as cells of acute inflammation in the vitreous.78,81 While in conjunctival samples, pigment particles, polymorphonuclear infiltrate, and connective tissue of the collagenized conjunctiva without epithelium have been observed.82

As for complications, these can be presented hours after the application of the inks. Among the most frequently described in the articles included in the present study are proptosis, deposits of pigment in the conjunctiva, corneal endothelium, iridocorneal angle, iris, and anterior capsule of the lens and vitreous; inflammatory processes such as nodular episcleritis, chemosis, anterior nongranulomatous uveitis, hypopyon, cataract, secondary glaucoma, vitritis, serous retinal detachment associated with vitreoretinal proliferation, and choroidal detachment. These complications can trigger endophthalmitis, blindness, and even require the enucleation of the organ given the severity of the immune response that occurs in these tissues.78,83

Under ideal conditions, this type of cosmetic procedure must be performed by trained personnel, using a surgical microscope and in sterile conditions. However, there is currently not enough literature on long-term eye damage. For these reasons, and because of the current conditions in which this procedure is carried out, regulations for its realization are needed.84

Limitations

There are few studies with solid scientific evidence on the subject, most of them correspond to case series and case reports. Studies with large cohorts of patients and extensive follow-ups should be done to evaluate the presence of short- and long-term complications related to the use of dermal and ocular tattoos.

CONCLUSION

Dermal tattoos are body modifications that represent an affront to humoral and cellular immunity, both locally and systemically. This review presents the literature evidence describing the strict relationship between the application of tattoos on dermatological and ophthalmological tissues and the immunological, neoplastic, and infectious complications. The trend of eye tattoos is generating a public health concern. Because of the lack of standardization and regulation, tattoos put an individual’s health at risk. Dermatologists and ophthalmologists should be aware of the severe damage caused by even small amounts of tattoo ink on the skin and in the eyes, thus requiring strict regulations for its use.

Supplemental Material

aSupplemental Material is available at: www.thepermanentejournal.org/files/2021/20.225supp.pdf

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Funding

No funding was received to carry out this study. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgments

We thank Enago and Universidad del Rosario for the language edition of the manuscript.

Author Affiliations

1Grupo de investigación Escuela Barraquer, Escuela Superior de Oftalmología del Instituto Barraquer de América, Bogotá, Colombia

2Grupo de investigación en neurociencias NeURos, Centro de Neurociencia (NeuroVitae), Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia

3Grupo de investigación Dermatología Clínica e Infecciosa, Programa de Dermatología de la facultad de Medicina, Universidad El Bosque, Bogotá, Colombia

Corresponding Author

Alejandra de-la-Torre (alejadelatorre@yahoo.com)

Author Contributions

Juliana Muñoz-Ortiz participated in management, research ideas, title and abstract reading, data extraction, and synthesis. Mariana Teresa Gómez-López participated in data extraction, manuscript writing, and discussion. Paula Echeverry-Hernández participated in manuscript writing and discussion. Mario Federico Ramos-Santodomingo participated in manuscript writing and discussion. Alejandra de-la-Torre participated in management, research ideas, manuscript writing, and thematic authority. Juliana Muñoz-Ortiz, Mariana Teresa Gómez-López, Paula Echeverry-Hernández, Mario Federico Ramos-Santodomingo

Abbreviations

HPV, human papilloma virus; PRISMA-P, Systematic Reviews and Meta-Analysis Protocols

Availability of Data and Material 

All data generated or analyzed during this study are included in this published article and available from the corresponding author on reasonable request.

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98. Tammaro A, Tuchinda P, Persechino S, Gaspari A. Contact allergic dermatitis to gold in a tattoo: A case report. Int J Immunopathol Pharmacol 2011 Oct-Dec;24(4):1111-3. DOI: https://doi.org/10.1177/039463201102400432, PMID:22230420

99. Pasolini G, Ghidini P, Arisi M, Pedretti A, Ungari M, Pinton PC. Pseudolymphoma tattoo-induced, Dermatol Reports 2011 Oct;3(3):e47. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L364607018 DOI: https://doi.org/10.4081/dr.2011.e47

100. Prcic S, Matic A, Matic M, Petrovic A, Djuran V, Gajinov Z. Henna tattoo contact dermatitis - a report of four cases and brief review of the selected literature. Cent Eur J Med 2012 Feb;7(1):124-8. DOI: https://doi.org/10.2478/s11536-011-0106-1

101. Levancini CF, Sancho MI, Serrano VE, Torres EB. Erythema multiforme-like secondary to paraphenylenediamine due to henna tattoo plus residual hypopigmentation. Indian J Dermatol 2015 May-Jun;60(3):322. DOI: https://doi.org/10.4103/0019-5154.156455, PMID:26120183

102. Saulite I, Pekar-Lukacs A, Kerl K, Cozzio A, Hoetzenecker W, Guenova E Pseudolymphomatous reaction to red tattoo pigment. Case Rep Dermatol 2018 May-Aug;10(2):162-8. DOI: https://doi.org/10.1159/000489875, PMID:30022936

103. Balfour E, Olhoffer I, Leffell D, Handerson T. Massive pseudoepitheliomatous hyperplasia: An unusual reaction to a tattoo. Am J Dermatopathol 2003 Aug;25(4):338-40. DOI: https://doi.org/10.1097/00000372-200308000-00010

104. Cui W, Mcgregor DH, Stark SP, Ulusarac O, Mathur SC. Pseudoepitheliomatous hyperplasia - an unusual reaction following tattoo: Report of a case and review of the literature. Int J Dermatol 2007 Jul;46(7):743-5. DOI: https://doi.org/10.1111/j.1365-4632.2007.03150.x, PMID:17614808

105. Goodie PE, Burkhart CG. Temporary henna tattooing: A case of contact dermatitis. Open Dermatol J 2016 May;10:82-4. DOI: https://doi.org/10.2174/1874372201610010082

106. Saunders H, O'Brien T, Nixon R. Textile dye allergic contact dermatitis following paraphenylenediamine sensitization from a temporary tattoo. Australas J Dermatol 2004 Nov;45(4):229-31. DOI: https://doi.org/10.1111/j.1440-0960.2004.00110.x, PMID:15527435

107. Souza ES, Rocha Bde O, Batista Eda S, Oliveira RF, Farre L, Bittencourt AL. T-cell-predominant lymphoid hyperplasia in a tattoo. An Bras Dermatol 2014 Nov-Dec;89(6):1019-21. DOI: https://doi.org/10.1590/abd1806-4841.20143231, PMID:25387518

108. Wenzel SM, Welzel J, Hafner C, Landthaler M, Bäumler W. Permanent make-up colorants may cause severe skin reactions. Contact Dermatitis 2010 Oct;63(4):223-7. DOI: https://doi.org/10.1111/j.1600-0536.2010.01799.x, PMID:20831688

109. de Roeck A, Joujoux JM, Fournier F, Dandurand M, Meunier L, Stoebner PE. Florid pseudoepitheliomatous hyperplasia related to tattoo: A case report. Int Wound J 2013 Oct;10(5):539-41. DOI: https://doi.org/10.1111/j.1742-481X.2012.01013.x, PMID:22712583

110. Körner R, Pföhler C, Vogt T, Müller CSL. Histopathology of body art revisited - analysis and discussion of 19 cases. JDDG J der Deutschen Dermatol Gesellschaft 2013 Nov;11(11):1073-80. DOI: https://doi.org/10.1111/ddg.12178

111. Braswell DS, Hakeem A, Walker A, Sokumbi O, Kapil J, Motaparthi K. Lichenoid granulomatous dermatitis revisited: A retrospective case series. J Am Acad Dermatol 2019 Nov;81(5):1157-64. DOI: https://doi.org/10.1016/j.jaad.2019.05.100

112. Serup J, Sepehri M, Carlsen KH. Classification of tattoo complications in a hospital material of 493 adverse events. Dermatology 2017 Apr;232(6):668-78. DOI: https://doi.org/10.1159/000452148

113. Nikkels AF, Henry F, Piérard GE. Allergic reactions to decorative skin paintings. J Eur Acad Dermatol Venereol 2001 Mar;15(2):140-2. DOI: https://doi.org/10.1046/j.1468-3083.2001.00227.x, PMID:11495521

114. Zaharopoulos P. Fine-needle aspiration cytology in lesions related to ornamental body procedures (skin tattooing, intraoral piercing) and recreational use of drugs (intranasal route). Diagn Cytopathol 2003 May;28(5):258-63. DOI: https://doi.org/10.1002/dc.10277, PMID:12722121

115. Pinal-Fernandez I, Solans-Laqué R. The 'sparing phenomenon' of purpuric rash over tattooed skin. Dermatology 2014 Feb;228(1):27-30. DOI: https://doi.org/10.1159/000356779, PMID:24356492

116. Pandya VB, Hooper CY, Merani R, McCluskey P. Tattoo-associated uveitis with choroidal granuloma: A rare presentation of systemic sarcoidosis. Retin Cases Brief Rep 2017 Summer;11(3):272-6. DOI: https://doi.org/10.1097/ICB.0000000000000342, PMID:27258541

117. Moschos MM, Guex-Crosier Y. Retinal vasculitis and cystoid macular edema after body tattooing: A case report. Klin Monbl Augenheilkd 2004 May;221(5):424-6. DOI: https://doi.org/10.1055/s-2004-812815, PMID:15162298

118. Kluger N, Minier-Thoumin C, Plantier F. Keratoacanthoma occurring within the red dye of a tattoo. J Cutan Pathol 2008 May;35(5):504-7. DOI: https://doi.org/10.1111/j.1600-0560.2007.00833.x

119. Sherif S, Blakeway E, Fenn C, German A, Laws P. A case of squamous cell carcinoma developing within a red-ink tattoo. J Cutan Med Surg 2017 Jan;21(1):61-3. DOI: https://doi.org/10.1177/1203475416661311

120. Maxim E, Higgins H, D’Souza L. A case of multiple squamous cell carcinomas arising from red tattoo pigment. Int JWomen's Dermatol 2017 Dec;3(4):228-30. DOI: https://doi.org/10.1016/j.ijwd.2017.07.006

121. Kojima T, Dogru M, Matsumoto Y, Goto E, Tsubota K Tear film and ocular surface abnormalities after eyelid tattooing. Ophthalmic Plast Reconstr Surg 2005 Jan;21(1):69-71. DOI: https://doi.org/10.1097/01.iop.0000153028.08506.47, PMID:15677957

122. Moshirfar M, Espandar L, Kurz C, Mamalis N. Inadvertent pigmentation of the limbus during cosmetic blepharopigmentation. Cornea. julio de 2009 Jul;28(6):712-3. DOI: https://doi.org/10.1097/ico.0b013e318190737b

123. Tourlaki A, Boneschi V, Tosi D, Pigatto P, Brambilla L. Granulomatous tattoo reaction induced by intense pulse light treatment. Photodermatol Photoimmunol Photomed 2010 Oct;26(5):275-6. DOI: https://doi.org/10.1111/j.1600-0781.2010.00537.x, PMID:21175859

124. De M, Marshak H, Uzcategui N, Chang E. Full-thickness eyelid penetration during cosmetic blepharopigmentation causing eye injury. J Cosmet Dermatol 2008 Mar;7(1):35-8. DOI: https://doi.org/10.1111/j.1473-2165.2008.00340.x, PMID:18254809

125. Vagefi MR, Dragan L, Hughes SM, Klippenstein KA, Seiff SR, Woog JJ. Adverse reactions to permanent eyeliner tattoo. Ophthalmic Plast Reconstr Surg 2006 Jan;22(1):48-51. DOI: https://doi.org/10.1097/01.iop.0000196713.94608.29

126. Tukenmez Demirci G, Mansur AT, Yıldız S, Güleç AT. Is it a sarcoidal foreign-body granuloma or a cutaneous sarcoidosis on a permanent eyebrow make-up? J Cosmet Laser Ther 2016 Jan;18(1):50-2. DOI: https://doi.org/10.3109/14764172.2015.1052516, PMID:26073118

127. Martín JM, Revert Á, Monteagudo C, Villalón G, Godoy R, Jordá E. Granulomatous reactions to permanent cosmetic tattoos successfully treated with topical steroids and allopurinol. J Cosmet Dermatol 2007 Dec;6(4):229-31. DOI: https://doi.org/10.1111/j.1473-2165.2007.00338.x

128. López Villaescusa MT, Faura Berruga C, Martínez Martínez MaL, Gómez Sánchez MaE, Pérez García L, Iñiguez De Onzoño Martí L. Foreign body granulomas after eyebrow tattoos. Med Cutanea Ibero-Lat-Am 2013 Jan;41(4):183-5. DOI: https://doi.org/10.4464/MC.2013.41.4.5083

129. Wollina U. Nodular skin reactions in eyebrow permanent makeup: Two case reports and an infection by Mycobacterium haemophilum. J Cosmet Dermatol 2011 Sep;10(3):235-9. DOI: https://doi.org/10.1111/j.1473-2165.2011.00564.x

130. Antonovich DD, Callen JP. Development of sarcoidosis in cosmetic tattoos. Arch Dermatol 2005 Jul;141(7):869-72. DOI: https://doi.org/10.1001/archderm.141.7.869, PMID:16027303

131. Naeini FF, Pourazizi M, Abtahi-Naeini B, Saffaei A, Bagheri F. Looking beyond the cosmetic tattoo lesion near the eyebrow: Screening the lungs. J Postgrad Med 2017 Apr-Jun;63(2):132-4. DOI: https://doi.org/10.4103/0022-3859.201421, PMID:28272073

132. Ebrahimiadib N, Adelpour F, Ghahari M, Mehrpour M. Intermediate uveitis associated with tattooing of eyebrows as a Manifestation of systemic sarcoidosis: Report of two cases. Ocul Immunol Inflamm 2020 Jan;16:1-4. DOI: https://doi.org/10.1080/09273948.2019.1699581 http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L2004090585

133. Brodie J, El Galhud H, Bates A. A case of episcleral tattooing--an emerging body modification trend. BMC Ophthalmol 2015 Aug;15(1):95. DOI: https://doi.org/10.1186/s12886-015-0095-y, PMID:26252991

134. Tubek K, Berus T, Leszek R. The girl with the eyeball tattoo-what the ophthalmologist may expect? Case report and a review of literature. Eur J Ophthalmol 2019 Sep;29(5):NP1-NP4. DOI: https://doi.org/10.1177/1120672118803855

135. Rodríguez-Avila JO, Ríos y Valles-Valles D, Hernández-Ayuso I, Rodríguez-Reyes AA, Morales Cantón V, Cernichiaro-Espinosa LA. Conjunctival tattoo with inadvertent ocular globe penetration and vitreous involvement: Clinico-pathological correlation and scanning electron microscopy X-ray microanalysis. Eur J Ophthalmol 2020 Sep;30:NP18-NP22. DOI: https://doi.org/10.1177/1120672119850076. http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L628000299

Keywords: allergy and immunology, dermatology, inflammation, ophthalmology, tattooing

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