Am J Clin Dermatol (2014) 15:525–536 DOI 10.1007/s40257-014-0100-x

REVIEW ARTICLE

Complications of Decorative Tattoos: Recognition and Management Carolina Simunovic • Michi M. Shinohara

Published online: 11 November 2014 Ó Springer International Publishing Switzerland 2014

Abstract Tattooing is an ancient practice that enjoys continued popularity. Although a modern, professionally performed tattoo is generally safe, complications can occur. A skin biopsy of all tattoo reactions is recommended as some tattoo reactions have systemic implications. Tattoo-related infections are seen days to decades after tattooing, and range from acute pyogenic infections to cutaneous tuberculosis. In particular, non-tuberculous mycobacterial infections happen in tattoos with increasing frequency and are introduced at the time of tattooing through contaminated ink or water used to dilute inks. Despite a transition in tattoo pigments from metal salts to industrial azo dyes, hypersensitivity reactions also persist, and include eczematous, granulomatous, lichenoid, and pseudoepitheliomatous patterns (among others). Granulomatous tattoo reactions can be a clue to cutaneous or systemic sarcoidosis, particularly in the setting of interferon use. Pseudoepitheliomatous tattoo reactions have substantial overlap with squamous cell carcinoma and keratoacanthoma, making diagnosis and management difficult. Other malignancies and their benign mimics can occur in tattoos, raising questions about the safety of tattoo ink and its role in carcinogenesis.

C. Simunovic
M. M. Shinohara (&) Division of Dermatology, University of Washington, 1959 NE Pacific Street BB-1353, Box 356524, Seattle, WA 98195-6524, USA e-mail: [email protected]

Key Points Tattoos can be complicated by a variety of inflammatory, infectious, or neoplastic conditions; despite the increasing use of azo dyes in tattoo inks, reactions continue to occur. A skin biopsy of all suspected tattoo reactions is recommended as these can be a harbinger of systemic disease or atypical infections. Although professional tattooing is typically done under aseptic conditions, non-tuberculous mycobacterial infections continue to occur and should be suspected in any tattoo reaction.

1 Introduction Permanent tattooing is the process of body modification by deposition of a pigment into the dermis, and is a practice that has spanned thousands of years and across cultures. ¨ tzi the The earliest tattoos may have been therapeutic; O iceman, who was found in the Italian Alps and dates back to approximately 3300 BC, has over 50 charcoal tattoos that overlie arthritic joints [1]. Tattoo in modern times is usually decorative and remains a popular practice, with as many as one in five adults reporting one or more tattoos in a 2012 Harris Poll [2]. As more people get tattoos, the number of complications from tattooing, which may be as high as 2 %, is likely to increase [3].

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2 Tattooing: Materials and Equipment

2.1 Tattoo Ink

The process of modern professional permanent tattooing entails the repeated injection of ink into the dermis, typically with the use of an electrically powered tattoo machine that punctures the skin at a rate of 50–3,000 times per minute. Components of a tattoo machine include a sterile needle that draws ink through capillary action, an electric motor, and a foot pedal [4]. Disposable materials include single-use sterile needles and ink cups, which are filled from a larger container for single-client use. Tattoo needles are repeatedly dipped into the single-use ink cups. In professional tattoo parlors, materials that contact clients and potentially can become contaminated are usually single-use or sterilized by autoclave before every use. Professional tattooists may also use plastic covers to protect their equipment and surfaces from contamination. The overall setup mimics that of a minor in-office medical procedure, with most tattoo artists abiding by aseptic techniques to prevent blood-borne infection (Fig. 1). Tattooing in informal settings, such as in prisons, homes, or as part of cultural rituals, may be devoid of aseptic techniques and sterile instruments. For example, traditional pe’a tattoos of Samoan culture are created using soot and tools that are handmade from tusks, turtle shell, wood, and bone, and then driven into the skin with a mallet. In prisons, tattoo machines are made using basic motor components or improvised needles. The covert nature of prison tattoos precludes proper sterile technique, and needles and ink are often shared among several users [5].

Tattoo inks are suspensions of metal salts and organic compounds in a liquid carrier, such as water, alcohol, or glycerin. The composition of tattoo inks has evolved in recent decades, with tattoo inks comprised predominantly of metal salts such as mercuric sulfide (cinnabar) being essentially phased out due to adverse reactions and the desire for brighter colors. Azo pigments are industrialgrade pigments intended for use in printers or automobile paint, and have replaced the metal salts due to their vibrant colors and longevity [6]. The safety of pigments used in modern tattoos is largely unknown and unstudied. As these pigments are manufactured primarily for industrial practices, they can contain impurities such as carcinogenic aromatic amines that are byproducts of their synthesis [7]. Black inks are primarily based on carbon soot and may contain hazardous polycyclic aromatic hydrocarbons which, when exposed to ultraviolet A, can generate singlet oxygen, resulting in cytotoxic effects [7–9]. Møller and Wallin [10] hypothesize that various azo pigments should be considered genotoxic or carcinogenic. In addition to the pigments themselves, propriety ingredients, diluents, and preservatives such as thiomersal may be used to stabilize the inks [6]. These are sometimes identifiable through the material safety data sheets produced by tattoo-ink manufacturers, although often no list of ingredients is provided [11–13].

3 Regulation of Tattooing

Fig. 1 Typical set up for a professional tattoo: gloves, disposable needles, and plastic sheath covering the parts of the tattoo machine likely to contact the client

Oversight of the practice of tattoo and licensing of tattoo artists and facilities in the US is left to the states and counties, rather than the federal government. These regulations generally address age limitations, set basic parameters for tattooing facilities and the licensing of tattoo professionals, and define the jurisdiction of regulation for medical versus decorative or cosmetic tattooing. Since these regulations are created at the local and state level, there is significant variability both in scope and enforcement across the US. The FDA has the authority to regulate ink and pigments as cosmetics and color additives; however, it is not currently doing so [6]. Until recently, the FDA’s actions had been limited to education and research on the topic, but in July of 2014 it issued its first nationwide voluntary recall of tattoo inks and needles due to confirmed bacterial contamination [14, 15]. By comparison, Germany has adopted regulations in regard to the metal content in tattoo inks, has banned certain substances from being used in tattoo inks, and routinely tests inks for heavy metals, preservatives, and microbial contamination [16].

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Given a relative lack of current regulation, the responsibility for the prevention of adverse effects from tattooing is largely left to tattoo artists and their clients. Tattoo artists often have anecdotal experience with different inks, and may be aware of potential problems, especially reactions associated with red pigments. Persons who intend on obtaining a tattoo should ensure that they visit a licensed tattoo artist in a professional tattoo parlor. They should request that the inks used are those produced by reputable manufacturers and that they are intended for use in permanent tattoos.

4 Cosmetic Tattoos Cosmetic tattooing, also known as permanent makeup, can be used to mimic the appearance of temporary makeup as well as to camouflage dermatologic conditions such as vitiligo or alopecia [17]. The process of micropigmentation is used to achieve these cosmetic results by injecting several colors into the dermis in order to obtain natural-appearing tones. This is typically done using a handheld tattoo pen that is smaller than the traditional decorative tattoo machine. A variety of professionals and non-professionals, including physicians, nurses, cosmetologists, estheticians, and makeup artists perform micropigmentation in physician offices and tattoo parlors. Laser treatment of cosmetic tattoos can be challenging as the pigments used often contain iron oxides and titanium dioxide that can oxidize to a brown-black color with Q-switched laser irradiation [18].

5 Applications of Tattoos in Medicine Tattooing has both practical and aesthetic applications in medicine. In radiation oncology, permanent tattooing is utilized as a marker for properly aligning the field of radiation for therapy. Similarly, endoscopic tattooing is utilized to mark areas of interest to be followed clinically or concerning regions of the gastrointestinal tract prior to surgical intervention. Corneal tattooing is used to manage corneal pathologies and restore eye color, and threedimensional tattooing of the areola and nipple are often the final stage of reconstructive breast surgery. Tattooing for medical alert purposes is also gaining popularity among patients with chronic diseases, such as diabetes or those with severe allergies [19].

6 Infectious Complications of Tattoos As a process that violates the skin barrier, tattooing places the recipient at risk for contracting transmissible diseases.

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Although most modern reputable tattoo artists practice aseptic techniques, infections can still occur due to improper preparation of the tattoo site, improperly sterilized equipment, contamination of ink and ink products, or by inadequate care or personal hygiene following tattooing. 6.1 Acute Pyogenic Infections While there are no data regarding the incidence, acute pyogenic infections caused by Staphylococcus aureus or Streptococcus pyogenes, such as impetigo, folliculitis, furunculosis, abscesses, or cellulitis, likely occur with relative frequency. Signs of pyogenic skin infection manifest within days to a few weeks from the time of tattooing [20]. Management relies on bacterial culture with sensitivities, and treatment requires topical and/or oral antibiotics targeting the likely pathogens, just as in non-tattooassociated soft-tissue infections. The use of aseptic techniques and universal precautions is key to preventing pyogenic infections; a fairly recent outbreak of 44 cases of methicillin-resistant Staphylococcus aureus (MRSA) in Kentucky, Ohio, and Vermont associated with unlicensed tattooists using unsterile techniques and/or equipment highlights this point [21]. 6.2 Atypical Mycobacterial Infections The last decade has seen a surge of infections caused by rapidly growing mycobacterial species associated with tattoos, most often due to Mycobacterium chelonae and Mycobacterium abscessus. These non-tuberculous mycobacterial (NTM) infections typically manifest within 1 month of tattooing, and present with erythematous papules, nodules, pustules, ulcers, abscesses or plaques typically confined to the areas of tattoo ink (Fig. 2). No cases of dissemination have occurred. NTM species are ubiquitous in water, and the process of diluting black ink with tap or distilled water has been implicated as a source of contamination [22]. Dilution of tattoo ink with distilled water is still commonly practiced; there is a common misconception that distilled water and reverse osmosis water are equivalent to sterile water [22]. Not only is there potential for the introduction of microbes into the ink by this process, but the dilution of ink also decreases the antimicrobial effectiveness of preservatives that may be present. Outbreaks across the US have demonstrated that contamination can also occur in the inkmanufacturing process as opened and previously unopened bottles of ink grew Mycobacterium chelonae when sampled [23–27]. Work-up for patients with suspected NTM tattoo infections should include skin biopsy for histology as well as tissue culture or polymerase chain reaction for

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manifestations of secondary syphilis [30, 31]. There have been no reported cases of syphilis transmission by tattoo in the last several decades; however, a case of secondary syphilis lesions occurring within a tattoo has been reported [32]. 6.5 Fungal Infections

Fig. 2 Non-tuberculous mycobacterium infection in a tattoo. The patient had a tattoo placed 2 months prior to the development of pustules and itching within the tattoo. Culture of a skin biopsy grew Mycobacterium abscessus

mycobacteria. Special stains for mycobacteria are helpful when positive but are not sufficient to rule out infection [23–25]. Although treatment would ideally be delayed until speciation and susceptibility data return from culture, empiric treatment with dual antibiotic therapy including a macrolide and fluoroquinolone is often initiated when NTM infection is suspected. Although spontaneous regression may occur [27], an infectious disease consultation should be considered as NTM species causing tattoo infections can be highly resistant to conventional antibiotics [26]. Treatment may need to be continued for months and should be directed by the patient’s response to therapy. 6.3 Mycobacterium tuberculosis and Mycobacterium leprae Infections Transmission of cutaneous tuberculosis and leprosy in tattoos was reported with some frequency in the 19th and 20th centuries [29]. In the last decade, a single case of lupus vulgaris in a tattoo was reported in a patient who had a tattoo placed in a commercial tattoo parlor in Singapore [28]. Cases of inoculation leprosy manifesting decades later have also been reported in a large case-series of over 30 women in an endemic area of India [29]. These infections should be considered when patients present with skin reactions decades out from tattoo placement or in patients who have had tattoos placed in prison or cultural settings devoid of a sterile technique. 6.4 Syphilis Of historical note is the transmission of syphilis by tattooing. This was first documented in Western medical literature in the mid to late 19th century, and occurred as a result of contamination with the saliva of syphilitic tattooists, resulting in chancres in tattoos as well as

Fungal infections arising in tattoos are rare. There has been one reported case of zygomycosis occurring in a tattoo in an otherwise healthy male who developed a deep necrotic ulcer in a tattoo several years after having the tattoo placed [33]. Similarly, a case of Aspergillus fumigatus was reported in a home-made tattoo [34]. Dermatophyte infections can occur in tattoos due to exposure to an infected person or animal, and should be suspected if an inflammatory tattoo reaction worsens while using topical corticosteroids [35, 36]. 6.6 Leishmaniasis There are rare reports of leishmaniasis arising in tattoos, with all reported cases occurring in the setting of HIV infection and visceral leishmaniasis [37, 38]. 6.7 Viral Infections 6.7.1 Viral Hepatitis/HIV The nature of tattooing places patients at risk for contracting blood-borne pathogens such as hepatitis B and C viruses as well as HIV [39]. Abiding by aseptic techniques mitigates the risk, but tattoos performed in informal settings by amateur tattoo artists remain high risk. Two possible cases of HIV transmission attributed to tattooing have been reported, both occurring in men who received tattoos while in prison [40]. In an analysis by Carney et al. on the risk factors for hepatitis C virus (HCV) infection, having a tattoo remained an independent risk factor, even after adjusting for practices such as injection drug use and blood transfusions prior to 1992 [41]; however, analysis of the current literature suggests that there may no longer be an increased risk of acquisition of HCV when tattoos are performed in a professional tattoo parlor [42]. Those pursuing a tattoo should be advised to get the tattoo at a reputable professional tattoo parlor; however, they can generally be reassured that the risk of acquiring a blood-borne infection such as HCV from a professional tattoo is low. 6.7.2 Herpes Simplex Virus While direct inoculation of the herpes simplex virus (HSV) is possible in the setting of tattooing, only one case of HSV

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type 1 has been reported in the literature thus far [43], with a low incidence likely attributable to the widespread use of aseptic techniques.

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years. Destructive treatment modalities such as curettage, cryotherapy, cantharidin, and topical keratolytics can be used.

6.7.3 Human Papilloma Virus 7 Inflammatory Reactions in Tattoo There are several reports of verruca appearing at tattoo sites, with an onset of months to years after tattooing [44– 48]. In some cases the lesions were restricted to one tattoo color, while in others they were visible across various colors of multicolored tattoos. One particular case was triggered after an intense sunburn, and it was postulated that local UV-induced immunosuppression triggered reactivation of the human papilloma virus [49]; prevention may thus reasonably involve protecting newly tattooed skin from UV exposure. Treatment modalities include those commonly used for the destruction of warts, such as cryotherapy, curettage, and topical immunomodulators such as imiquimod. 6.7.4 Molluscum contagiosum Molluscum contagiosum virus (MCV) is a common disease of childhood transmitted by skin-to-skin contact or by contact with fomites. When molluscum occurs in healthy adolescents and adults it can represent a sexually transmitted disease. MCV occurs within tattoos weeks to months after tattooing [15–17] (Fig. 3). Widespread MCV can occur in the setting of immunodeficiency, thus it may be prudent to screen for HIV infection in an adult who presents with MCV in a tattoo. Complete regression of MCV can occur without treatment, but can take months to

All manner of inflammatory reaction patterns can occur in tattoos, including eczematous, lichenoid, granulomatous, scleroderma or morphea-like, sarcoidal, pseudoepitheliomatous, pseudolymphomatous, and photoallergic. Some inflammatory reactions may represent delayed-type hypersensitivity reactions to the pigments or components of the ink solution; identification of a culprit allergen via patch testing is rarely successful due to the difficulty in obtaining accurate ingredient lists of tattoo inks and comparable allergens for testing. In addition, alteration of tattoo pigments via UV decomposition or haptenization further complicate the matter. Despite a transition away from mercury to azo dye containing tattoo inks, red ink still remains the most common color involved in tattoo reactions (Fig. 4) [53]. 7.1 Granulomatous Reactions Granulomatous tattoo reactions can be subclassified by histologic pattern, with foreign body and sarcoidal types representing the majority of cases. Granuloma annulareand necrobiosis lipoidica-like reactions can also occur but are rare [54–56]. Tuberculoid granulomas, discussed elsewhere, occur in inoculation tuberculosis and leprosy from tattoos. Tuberculoid granulomas have also been reported in response to ferric oxide and chromium salts in cosmetic tattoos [57, 58]. 7.1.1 Foreign-Body Granulomatous Reactions Foreign-body granulomas are relatively common in tattoos and are characterized by pigment-laden foreign-body-type

Fig. 3 Molluscum contagiosum virus infection limited to tattooed skin

Fig. 4 Tattoo reaction isolated to red-inked areas. Image courtesy of David Friedman, MD

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giant cells. Foreign body granulomas may be admixed with other reaction patterns, including lesions suspicious for sarcoidosis. Work-up for sarcoidosis should be pursued, especially if the patient presents with systemic symptoms. Treatment of foreign-body granulomas is directed at reducing the inflammatory response or removal of the inciting trigger. There are rare reports of spontaneous resolution of granulomatous tattoo reactions, twice reported to resolve shortly following biopsy [59, 60]. First-line approach is a trial of superpotent topical steroids or intralesional corticosteroids. Surgical excision or treatment with laser therapy have also been reported to be successful; however, the risk of a generalized/systemic reaction with the use of laser surgery should be considered and discussed with the patient prior to treatment. 7.1.2 Sarcoidosis Sarcoidosis is an autoimmune condition of unknown etiology defined by non-caseating epithelioid granulomas in the skin and/or internal organs. There are regular reports of sarcoidal granulomas occurring in scars (‘scar sarcoid’), as well as secondary to foreign material, including decorative and cosmetic tattoos. The association of sarcoidosis with tattoos is unique in that sarcoidal granulomas arising in tattoos may be the initial presentation of systemic disease. Sarcoidal tattoo reactions are typically papules, nodules, or plaques, with or without scale, which may be pruritic or tender, and usually limited to the tattooed skin (Fig. 5). The onset of skin lesions has been reported from weeks to years (even decades) after tattoo placement [61]. The reaction may be restricted to specific colors or involve several colors of multicolored tattoos. Despite the fact that red is the most commonly involved color in tattoo reactions in general, there does not appear to be a color predilection

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in tattoo sarcoidosis as red, black, blue, and green colored areas of tattoos have all been affected [61]. All patients presenting with cutaneous sarcoidosis warrant a thorough work-up for systemic involvement which includes a thorough history and physical as well as appropriate imaging and diagnostic testing [62]. Skin biopsies of suspicious lesions should be performed and sent for histology, tissue stains for microorganisms, as well as microbial culture. As many as 25 % of sarcoidosis biopsies may contain polarizable foreign-body material, and the presence of polarizable foreign material does not exclude the diagnosis of sarcoidosis [63–65]. The management of tattoo sarcoidosis depends on the extent of systemic involvement and is the same as management of non-tattoo-associated sarcoidosis. Limited cutaneous sarcoidosis can be treated with superpotent topical steroids or intralesional corticosteroid injections. Widespread cutaneous disease or systemic disease may warrant a multidisciplinary approach and systemic treatment with antimalarial agents, oral corticosteroids, methotrexate, or biologic therapy. Surgical excision of cutaneous sarcoidosis lesions should generally be avoided or attempted only after failure of other therapies, given the predilection of sarcoidal granulomas for scars. Special mention should be made of patients treated with interferon who develop sarcoidosis in previously asymptomatic tattoos. More than 50 documented cases of interferon-induced sarcoidosis have been reported, of which more than 30 have had cutaneous involvement, implying that skin involvement is overrepresented in sarcoidosis secondary to interferon. At least four sarcoidal tattoo reactions in this setting have been reported [66–71]. These are typically patients undergoing interferon-based therapy for chronic HCV, although a sarcoidal tattoo reaction with systemic involvement has also been reported in patients treated with interferon-b for multiple sclerosis, and interferon-a for melanoma [67, 71, 72]. The disease course of sarcoidosis occurring in the setting of interferon is thought to be relatively benign, with most patients experiencing spontaneous resolution soon after discontinuing interferon therapy. Hurst and Mauro recommend that interferon-a therapy for HCV be continued during skin flares of sarcoidosis, and they caution against the use of systemic steroids in this setting given the risk of increasing viral load [73]. Patients with pre-existing sarcoidosis should be monitored closely during and after interferon therapy, and generally counseled to avoid tattooing for cosmetic or decorative purposes. 7.2 Pseudolymphoma

Fig. 5 Sarcoidosis occurring in a tattoo. Scaly, indurated papules limited to the tattooed skin. The patient also had sarcoidal lesions elsewhere on the skin

Pseudolymphomatous tattoo reactions are benign cutaneous lymphoid hyperplasias that can mimic B- or T-cell

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theoretical risk of triggering a systemic hypersensitivity response and treatment should proceed with caution.

lymphomas both clinically and histologically. These have been reported to occur frequently, but not exclusively, in red-inked areas of tattoos, and are thought to be a consequence of chronic antigen stimulation [74–81]. Pseudolymphomatous tattoo reactions present as asymptomatic or pruritic papules, plaques, or nodules, arising months to years after tattooing [76, 82]. While pseudolymphomatous infiltrates may have a predilection for tattooed skin, they are not necessarily always confined to the tattoo [75]. Evaluation includes biopsy for histology, special stains to rule out infectious processes (particularly if there are neutrophils or granulomas present) and, in some circumstances, tissue culture. Histologic features of pseudo-lymphomatous reactions can include nodular dermal lymphocytic infiltrates or dense, band-like lichenoid infiltrates. Immunohistochemical workup can show B- or T-cell predominant or mixed lymphocytic infiltrates, and gene rearrangement studies to assess for B- and/or T-cell clonality will show polyclonal lymphocyte populations [83]. Although the vast majority of these types of infiltrates in tattoos are benign, a case of a cutaneous B-cell lymphoma arising in a long-standing pseudolymphomatous tattoo reaction has been reported, which highlights the potential for malignant transformation as well as the need for ongoing monitoring of these patients [84]. CD30? lymphoproliferative disorders, including lymphomatoid papulosis or mimics, can also occur within tattoos [113] (Fig. 6). Cutaneous pseudolymphomas may regress spontaneously. Treatment options include superpotent topical steroids or intralesional corticosteroids; surgical excision can be considered if these conservative measures fail. Hydroxychloroquine has also been successfully used [25]. Laser surgery with the Q-switched Nd:YAG has also been reported as an effective treatment for pseudolymphomatous tattoo reactions [76, 85, 86], although there is at least a

Cutaneous lupus erythematosus-like reactions can occur in tattoos and may be a variant of lichenoid tattoo reactions [75, 91], although patients should be evaluated for other signs of cutaneous or systemic lupus. Sclerodermatous or morphea-like reactions in tattoos also occur and may represent end-stage dermal sclerosis and/or fibrosis in the setting of untreated long-standing hypersensitivity reactions to tattoo ink, or could represent isomorphic phenomenon in a patient otherwise prone to connective tissue disease (Fig. 7).

Fig. 6 Lymphomatoid papulosis within a tattoo. The patient had a crop of infiltrated papules and papulonodules limited to the tattooed skin; biopsy showed a CD30? lymphoproliferative disorder that was consistent with lymphomatoid papulosis, and the lesions spontaneously resolved without treatment

Fig. 7 Morphea-like tattoo reaction occurring after a red-inked tattoo was placed. This patient subsequently developed linear morphea on the contralateral leg. Image courtesy of John Olerud, MD

7.3 Lichenoid Lichenoid-type tattoo reactions are frequently reported hypersensitivity reactions. They present clinically as pruritic papules or plaques within recently tattooed skin. Histologically, interface changes with vacuolar degeneration of the basal layer and dyskeratotic keratinocytes are seen. There is likely a preponderance of lichenoid reactions occurring in red-colored tattoos as these are more frequently reported, but lichenoid reactions are also seen in multicolored tattoos as well as in black tattoos [87, 88]. Lichenoid tattoo reactions can also generalize [89]. Components of the red pigment, including nickel, mercury, and cadmium, have been implicated but identifying the culprit ingredient through patch testing or metals analysis has proven difficult [90]. Patients with pre-existing lichenoid dermatoses should be counseled against obtaining tattoos as it may trigger an isomorphic response.

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7.5 Reactivation/Exacerbation of Underlying Dermatoses 7.5.1 Psoriasis The isomorphic phenomenon was originally described in a patient with pre-existing psoriasis who developed psoriatic plaques within a new tattoo [92, 93], and undoubtedly occurs with relative frequency in clinical practice. Patients with psoriasis should be counseled in regard to the risks of developing psoriatic lesions from tattooing. 7.5.2 Atopic Dermatitis Although not readily reported in the literature, eczematous tattoo reactions can be exacerbated in the setting of severe flares of atopic dermatitis (Fig. 8). Patients with a history of atopy should be counseled in regard to potential tattoo reactions, particularly contact allergy and photosensitivity reactions. 7.5.3 Pyoderma Gangrenosum Pyoderma gangrenosum (PG) is a rare complication of tattooing and has been reported in two patients, one of whom had an underlying hematologic malignancy [94, 95]. Patients with known pre-existing PG should be strongly cautioned against tattooing, particularly on the lower extremities. PG-like ulcers arising in tattoos should be biopsied and cultured to rule out infectious etiologies. 7.5.4 Lichen Sclerosus Lichen sclerosus has been reported to occur in tattoos, presumably as an isomorphic response [96].

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8 Neoplasms in Tattoos Kluger and Koljonen [97] reviewed approximately 50 cases of skin cancers, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and 20 cases of keratoacanthoma (KA) in association with tattoos over the last 4 decades. The authors highlighted a correlation between the color of the tattoo ink and type of neoplasm; BCC and MM occurred more commonly on black, dark blue, or dark-colored tattoos, while SCCs, KAs, and benign pseudoepitheliomatous (pseudocarcinomatous) hyperplasia (PEH) are reported more frequently in red tattoos. It is unclear as to whether the finding of neoplasms within tattoos is purely coincidental, especially given the increased prevalence of tattoos, or if there are potential carcinogenic properties of tattoo inks [98]. Attempts have been made at addressing the question of whether tattoo inks could contain carcinogens; carbonaceous soot is the main component of black ink, and has been demonstrated to contain significant levels of polycyclic aromatic hydrocarbons [8]. Furthermore, the behavior of tattoo ink is likely not completely inert; for example, some of the yellow azo dyes release photodecomposition products upon UV exposure [99]. 8.1 Pseudoepitheliomatous (Pseudocarcinomatous) Hyperplasia PEH is a benign reactive tissue pattern seen in association with various infectious and neoplastic processes and, by definition, has histologic features that make it difficult to differentiate from KA or verrucous carcinoma [100, 104], a scenario made even more challenging as KAs themselves can occur in tattoos (see Sect. 8.2). The clinical presentation of PEH in tattoos can be varied, from large verrucous plaques, cutaneous nodules, to ulcerated lesions [100–103]. As these lesions are difficult to distinguish from cutaneous neoplasms, both clinically and histologically, a full-thickness, preferably excisional, biopsy and regular follow-up for recurrence should be performed [101]. 8.2 Keratoacanthoma and Squamous Cell Carcinoma

Fig. 8 Atopic dermatitis preferentially affecting a tattoo. The patient had a long-standing history of atopic dermatitis; during this flare, the tattoo developed discrete erythema and scale that improved with topical and systemic corticosteroids

Squamous proliferations occurring in tattoos are frequently inflammatory in nature; however, there is substantial overlap, clinically and histologically, between pseudocarcinomatous proliferations, SCC, and KA. KA in particular has been reported in tattoos with some frequency [105] (Fig. 9). As KAs often develop soon after tattooing (within 1–2 months), they may simply be a consequence of local skin trauma, although the preponderance of KA occurring in areas of red ink raises the possibility of a hypersensitivity reaction or carcinogenic property to components of red ink

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Fig. 9 Keratoacanthoma in a tattoo

[106]. Treatment of KA and atypical squamous proliferations occurring within tattoos is similar to non-tattooed skin, with surgical management the mainstay of therapy. 8.3 Melanocytic Neoplasms and Malignant Melanoma There have been numerous reported cases of MM arising in tattoos, and the collision of pigmented lesions and tattoos poses diagnostic and management challenges. Clinical and dermatoscopic examination may be altered by the presence of tattoos, and clinical monitoring of melanocytic nevi can be difficult in tattooed skin. Patients with multiple melanocytic lesions, especially those with melanoma risk factors, should be counseled to avoid tattooing over pigmented lesions. particularly with dark pigments that can obscure melanocytic lesions. This counseling should also be undertaken by tattoo artists, who should be instructed on the basics of pigmented skin lesions and to avoid them during tattooing (Fig. 10). Tattoo pigment can also alter the interpretation of sentinel lymph nodes, where pigment-laden macrophages can be clinically mistaken for metastatic melanoma [107– 110]. The decision to perform radical lymph node dissection should be delayed until there is histologic confirmation of metastatic disease; the use of immunohistochemical stains such as Melan-A or S100 can aid in distinguishing melanocytes from tattoo pigment [109–111].

9 Miscellaneous 9.1 Magnetic Resonance Imaging Transient inflammation and pain has been reported in patients with tattoos undergoing MRI [112–114]. The cause is postulated to be the ferromagnetic properties of metals in tattoo pigment that are capable of conducting induced currents and heating adjacent tissues. Larger tattoos, those with loop or ring designs, and tattoos containing darker pigments are at greater risk [113]. The reactions are temporary and require minimal

Fig. 10 Melanocytic nevus and tattoo. This responsible tattoo artist ensured that the melanocytic nevus was not affected by tattoo ink

supportive care with cold compresses. Prophylactic measures such as cold compresses prior to imaging can be used. Tattoos are not a contraindication for MRI. 9.2 Ink Diffusion Blurry halos surrounding new, darkly pigmented tattoos can occur due to the placement of tattoo pigment too deeply in the dermis or subcutis, resulting in diffusion of the ink [20]. Pigment diffusion has also been described in the setting of local injection of anesthesia within and around tattoos prior to laser tattoo removal [115]. This esthetic complication may be improved with the Q-switched Nd:YAG laser [116].

10 Conclusions A wide range of complications can occur in tattoos and, as the number of tattooed people increases, the number of complications presenting to dermatologists is also likely to increase. Most of these tattoo reactions are merely inconveniences; however, there is potential for more serious reactions, and patients should be counseled as such. At a minimum, persons desiring a tattoo should be advised to thoroughly research and visit only licensed tattoo artists at licensed tattoo parlors. Ensuring that the tattoo artist practices basic aseptic techniques, including the use of disposable gloves and single-use sterile needles, is prudent. Patients with pre-existing dermatoses that are prone to the isomorphic phenomenon are at particular risk of tattoo complications, and those with potentially serious dermatoses, such as PG, should be advised to avoid tattooing altogether.

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Although aseptic techniques reduce the likelihood of infection from tattooing, infections do still occur and biopsy for histology, special stains for microorganisms, and culture should be performed when a tattoo infection is suspected, particularly if the patient has already failed to respond to conventional antibiotic therapy. As the composition of tattoo inks shifts towards increasing use of the azo dyes, the incidence and types of reactions occurring in tattoos are also likely to evolve. As tattoo inks are minimally regulated in the US, their safety and purity cannot be guaranteed at the present time. Existing evidence suggests that there is at least the potential for carcinogenic compounds in some ink components, and further research is needed to investigate the safety of tattoo inks. Clinicians encountering adverse cutaneous reactions to tattoos should report these to the FDA by way of the MedWatch reporting system (http://www.fda.gov/ Safety/MedWatch). Acknowledgments Carolina Simunovic, MD, and Michi Shinohara, MD, thank Drs. David Friedman, Stanley Hurst, Roy Colven, and John Olerud for providing clinical photos. Carolina Simunovic and Michi Shinohara report no conflicts of interest or sources of funding.

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