Tattoo-Associated Uveitis

The word ‘tattoo’ was introduced into the English language in the mid-eighteenth century through the writings of James Cook, a British naval officer who sailed and explored the South Pacific. These travels took Cook and his crew to Polynesia, where skin art was common and referred to by the local inhabitants as ‘tatau’ or ‘tatu’ - meaning ‘to strike.’¹ At least five types of tattoos are recognized by dermatologists, including: 1) traumatic, as can occur following a penetrating injury with asphalt or pencil lead; 2) medical, which are used to direct and dose radiation and other therapeutic interventions; 3) identification, used historically in prisons and labor or concentration camps and increasingly for medical alert in diabetics or those with severe allergies; 4) cosmetic, as applied to mimic temporary eyeliner and/or eyebrow contours, or to camouflage dermatologic conditions such as vitiligo; and 5) decorative – by far the most common and often involving large and multiple areas of skin.^2,3 While various forms of tattooing have been performed for millennia, the practice has become particularly commonplace in recent decades, with 10% to 30% people in developed countries and up to half or more of some regional or sub-populations having at least one decorative or cosmetic tattoo.^4–6 Tattoos are produced by injection of dyes and pigments into the dermis through a needle; while some tattoos are still applied by hand, tattoo machines are now used more commonly by commercial tattoo artists.

The prevalence of localized tattoo-related complications may be as high as 2%,⁷ and include acute and chronic infections, inflammatory reactions, and dermatologic malignancies.^7–10 Among the inflammatory reactions, foreign body and sarcoid-like responses are identified most often histologically, supporting a search for cutaneous or systemic sarcoidosis, particularly pulmonary, in all patients who present with such findings. The occurrence of associated inflammatory reactions can occur weeks to years after tattoo placement and has been suggested to be more common in cases of dark blue or black tattoos as compared to more brightly colored tattoos.^7–10 Even though inciting factors are rarely identified, isolated case reports have suggested a role for interferon,^11,12 BRAF, MEK and immune checkpoint inhibitor therapies,^13–20 tumor necrosis factor (TNF) inhibitors,²¹ highly active anti-retroviral therapy (HAART)-associated immune reconstitution,^22–24 and vaccination^25,26 as triggers for tattoo-related granulomatous reactions.

Since the first report of tattoo-associated uveitis by Lubeck and Epstein 70 years ago,²⁷ there have been more than 40 cases added to the literature.²⁸ The absence of a standard case definition of tattoo-associated uveitis has made epidemiologic and comparative studies more challenging. Cases of tattoo-associated uveitis have been divided broadly into those that occur without tattoo or systemic sarcoid-like involvement (10–20%), those with a sarcoid-like reaction limited to the tattoo (20–30%), and those concurrently diagnosed with distant cutaneous or systemic sarcoidosis, with or without tattoo involvement (50–60%).²⁸ It should be noted, however, that thorough testing for distant cutaneous or systemic sarcoidosis has been described inconsistently in prior reports and so the precise prevalence and extent of non-ocular sarcoidosis in patients with tattoo-associated uveitis remains unknown. Tattoo-associated uveitis is most often non-granulomatous, anterior, and bilateral, although granulomatous features and more extensive panuveitis with or without choroiditis, retinal vasculitis, macular or optic disc edema, and serous retinal detachment can occur.^28–32 Treatment typically consists of short-term regional and systemic corticosteroids, although chronic or recurring inflammation can require the longer-term use of systemic non-corticosteroid immunosuppressive agents.^32–34 Given the high rate of granulomatous skin findings, Kluger has suggested use of the term Tattoo-Associated Granuloma with Uveitis (TAGU) to describe this distinctive clinical condition.²⁸

Keratopigmentation, also known as corneal tattooing, has been used for centuries by physicians and ophthalmologists to treat optically symptomatic or cosmetically disfiguring corneal scars and iris irregularities,^35–37 with generally good results.^38,39 While infectious or non-infectious keratitis can occur following such procedures, secondary uveitis appears to be rare.³⁸ In contrast, tattooing of the ocular surface by medically untrained tattoo artists is a relatively recent form of extreme body modification associated with a high rate of globe penetration and related complications, including uveitis, glaucoma, endophthalmitis, and retinal detachment –resulting frequently in loss of vision and, less often, loss of the eye.⁴⁰

This issue of Ocular Immunology & Inflammation (OII) contains detailed descriptions of two patients who developed TAGU following permanent makeup tattooing,⁴¹ and a single case of presumed endophthalmitis associated with retinal necrosis and retinal detachment following inadvertent intraocular injection of tattoo ink during scleral tattooing performed by a tattoo artist.⁴²

Ebrahimiadib et al⁴¹ described two otherwise healthy women seen at a tertiary referral center in Teheran, Iran, who developed skin inflammation associated with anterior and intermediate uveitis four and six months following cosmetic tattooing applied to the eyebrows, respectively. Skin inflammation preceded uveitis by three weeks in each patient. Fluorescein angiography showed retinal vasculitis and, in one subject, cystoid macular edema. Both patients were found to have evidence of previously undiagnosed systemic sarcoidosis with elevated serum angiotensin converting enzyme levels and lung involvement – including mild interstitial involvement in one patient and hilar adenopathy in the second. Biopsy of the inflamed tattoo lesions, which showed redness, scaling, and papule formation, revealed non-caseating granulomas. One patient developed a nodule in an un-tattooed area that was also found to contain non-caseating granulomas on biopsy. Purified protein derivative testing for exposure to Mycobacterium tuberculosis was negative in each patient. Both patients responded well to topical and systemic corticosteroids followed by systemic methotrexate. The authors noted that tattoo-associated uveitis is uncommon and may occur with or without evidence of cutaneous or systemic inflammation. Whether such patients experience reactivation of previously asymptomatic systemic sarcoidosis or develop sarcoidosis de novo following tattoo placement was not known.

Haq et al⁴² reported a 47-year-old man who developed presumed endophthalmitis associated with retinal necrosis and retinal detachment two days after inadvertent intraocular injection of tattoo ink during a decorative scleral tattoo procedure. In addition to the presence of subconjunctival ink, examination of the affected eye showed conjunctival injection, hypopyon formation, dense vitreous opacities, and retinal detachment suggesting scleral penetration. The infection was managed with intravitreal vancomycin and ceftazidime, systemic moxifloxicin and vitrectomy, lensectomy, retinectomy, evacuation of subretinal tattoo ink, and retinal detachment repair with silicone oil placement. Bacterial and fungal cultures obtained on intraocular fluid at the time of surgery were negative, but mass spectrometry analysis demonstrated high levels of copper, which is known to be both retinotoxic and pro-inflammatory. The patient developed acute granulomatous anterior uveitis five weeks after surgery, which was successfully managed with regional and systemic corticosteroids. Vision at last follow-up was a remarkable 20/25.

Together, these cases highlight the emergence of both skin and ocular tattooing as uncommon causes of intraocular inflammation. Patients who develop uveitis should be questioned about their tattoo history and whether or not any such tattoos have become elevated, inflamed, painful, itchy or show color change prior to or concurrent with the onset of their uveitis. For those suspected of having TAGU, a systematic search for distant cutaneous or systemic sarcoidosis should be initiated, including a complete dermatologic examination, full-body computerized tomography (CT) or combined CT/positron emission tomography (CT/PET) to look for foci of inflammation, and biopsy of both the inflamed tattoo and any readily accessible areas identified on imaging. Recent receipt of interferon, TNF inhibitors, cancer therapies, vaccination, and HIV status and treatment should also be queried. Most patients with TAGU respond well to short-term topical, regional, or systemic corticosteroids, with a minority requiring longer-term systemic immunotherapy. Although rare, reports of scleral or subconjunctival tattooing suggest an alarming high rate of globe penetration and associated complications, supporting a role for prompt surgical intervention in eyes with evidence of intraocular dye injection.

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