• Clinical Update

    Watch for Tattoo-Related Uveitis: An Emerging Concern

    Written By: Annie Stuart, Contributing Writer, interviewing James P. Dunn, MD, Gary N. Holland, MD, and Kisha Piggott, MD, PhD

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    A patient comes to you with nonspecific signs and symp­toms of uveitis. You consider the potential causes and connections. Would tattoos be on your list?

    In the last few years, a flurry of case studies and letters to the editor have pointed to an association between tattoos and uveitis—in which tattoo inflammation and ocular inflammation occur concurrently with no obvious systemic etiology. But the link is un­clear. Is the tattoo triggering uveitis? Is there an underlying inflammation that is manifesting in both the eye and tattoo?

    Although tattoo-related uveitis is uncommon, its possibility should be considered in patients with tattoos, said Gary N. Holland, MD, at the University of California, Los Angeles. For one thing, there may be more cases than you think. According to a 2015 Harris poll, 29% of U.S. adults have a tattoo.1 Moreover, tattoo-related uveitis is not something you want to overlook. “It is likely to result in chronic inflammation that may need immunosuppression to prevent blinding complications,” said Dr. Holland.

    Presentation and Risks

    Patients may present with either anterior uveitis or panuveitis, and the manifes­tations may run the gamut, said James P. Dunn, MD, at Wills Eye Hospital in Philadelphia.

    Signs and symptoms. Typical signs and symptoms of severe anterior tattoo-related uveitis at onset include blurring of vision, pain, sensitivity to light, and redness, said Dr. Holland. “It is likely to show up as a sticky kind of uveitis with lots of posterior synechiae,” added Dr. Dunn. “Most of the cases are bilateral or, if not, at least asynchronous anterior uveitis—more commonly nongranulomatous than granuloma­tous. Sometimes there is a lag period between the two eyes.”

    Ophthalmic complications. These patients are at risk for severe vision-limiting complications, said Dr. Holland, including cystoid macular edema, pupillary membranes, pupillary seclusion with iris bombe, and uveitic glaucoma.2

    Some patients end up needing glaucoma surgery, added Kisha Piggott, MD, PhD, who recently published a case study about such a patient.3 “In our patient’s case, however, we were able to control eye pressure with top­ical glaucoma medications,” said Dr. Piggott, at the Washington University School of Medicine in St. Louis.

    Other complications. Infection is another risk related to tattoos, said Dr. Holland. “Just as patients can get non­tuberculous mycobacterial infections from contaminated equipment used in LASIK, they may also get infection of the tattoo from contaminated ink or other tattoo parlor equipment.”

    What’s the Link?

    The association between tattoos and uveitis is not entirely clear, said Dr. Dunn. Depending upon the extent of the disease, different processes may be involved. “Some people just get tattoo granulomas and uveitis—perhaps a type of delayed hypersensitivity,” he said. “For unknown reasons, others get more severe, systemic disease, where other factors such as genetics may have come into play.”

    Inflammatory response. The assumption has been that something in the tattoo itself is triggering the pro­cess, said Dr. Dunn. “However, it may be the other way around. An inflamma­tory process may actually be affecting the tattoos.” He points to a report of a French patient who developed tattoo granulomas and uveitis following initiation of immunotherapy.4 “This suggests that the tattoos may be a site of the inflammation, but not the pri­mary cause.”

    Like sarcoidosis, but not? The in­flammatory response in these cases can resemble sarcoidosis, said Dr. Holland, who calls it “sarcoidosis-like.”

    “Because it is so rare, tattoo-related uveitis has been difficult to study, andinsufficient longitudinal patient follow-up exists,” said Dr. Piggott. “Do patients with an otherwise negative systemic workup represent a subset of yet-to-be-diagnosed sarcoid patients, or a distinct patient population?”

    An allergic reaction? “If this were a true allergy, we would expect more dif­fuse inflammation of the entire tattoo,” said Dr. Piggott. “But most cases have segmental inflammation or nodularity of the tattoo in different areas, which is more consistent with delayed hypersen­sitivity than an allergic response.”

    Delayed hypersensitivity reaction. Typically, uveitis symptoms make an appearance at a minimum of six months after tattoo placement, said Dr. Piggott. Her patient experienced a two-year delay and was referred to her with a history of inflammation in the eye, correlating temporally with tattoo inflammation, induration, and slight redness of the tattooed skin.

    If this is a delayed hypersensitivity reaction, she said, it remains unclear whether it’s due to a dye contaminant or to the heavy metals or other organic compounds that constitute the ink. In some individuals, said Dr. Holland, only one color in the tattoo will be associated with inflammation. “The cause is difficult to determine since the tattoo ink composition is largely unregulated,” said Dr. Piggott.

    Pinning It Down

    The first step toward diagnosis is to get a complete history. Asking about tattoos is now a standard part of Dr. Dunn’s review of systems. “You can’t al­ways see the tattoos, and patients often won’t think to bring up induration of the tattoos,” he said. “But if you don’t ask about it, you may not consider it.”

    Questions to ask. It may be difficult for the patient to make the connection between skin and eye involvement, added Dr. Piggott. “Get more informa­tion and think broadly when obtaining the patient history. Include open-ended questions during the review of systems, allowing the patient to describe any atypical occurrences in the past few months or years.”

    If a patient has unexplained uveitis, said Dr. Holland, ask the patient, “Do you have any tattoos? Are any of your tattoos swollen or itchy?” That might unearth valuable clues, but it doesn’t obviate the need to evaluate the patient for other more common causes, includ­ing sarcoidosis.

    How will you know that the con­nection between skin and eye inflam­mation is not just coincidental? Dr. Holland said, “There is typically a temporal association: The uveitis and tattoo swelling will have started within a similar time period.”

    To rule out other potential causes, ask about any history of tuberculosis or sexually transmitted diseases, said Dr. Piggott. “The goal is to determine whether this is an infectious or inflam­matory cause. When inflammation is present, the knee-jerk response may be to treat with local or systemic anti-inflammatory medications, but we know that there are many infectious causes of inflammation.”

    Dermatological exam. If you’re unsure about the diagnosis, but suspect that uveitis might be linked to tattoos, said Dr. Dunn, consider referring the patient to a dermatologist for a full-body exam.

    Potential tests. There is no stan­dard workup, but testing is usually directed at possible causes of granulo­matous disease. Some doctors will test for angiotensin-converting enzyme or C-reactive protein and use results as a marker of general inflammatory burden, said Dr. Dunn. Some may also conduct thyroid studies because of potential links to thyroid disease and other autoimmune diseases, he noted.

    Although punch biopsies are rarely done, Dr. Piggott did order one of her patient’s tattoo. “It was helpful in making the diagnosis after ruling out other common causes.” Dr. Dunn does not routinely refer patients for punch biopsies. However, he said, if the extent of skin disease indicates a greater likelihood of systemic disease, a punch biopsy might help confirm diagnosis.

    Special Types of Tattoos

    Whether a tattoo is on the eyelids or on the arm or chest, the sarcoid-like inflammation and uveitis is similar, said Dr. Holland. Tattoos don’t need to be adjacent to the eye to cause tattoo-related uveitis. But proximity to the eye may introduce other problems.

    Eyeliner tattoos. Eyeliner tattoos may cause cilia loss, eyelid scarring, and infection.1 “Induration of the eyelids can affect the tear film and perhaps lead to eyelid margin infections and similar problems,” said Dr. Holland.

    Episcleral tattoos. People have even put tattoos under the conjunctiva. Some of these episcleral tattoos have resulted in severe infections of the globe, said Dr. Holland. Moreover, these types of tattoos may also cause ocular complications that require surgery for globe repair following inadver­tent penetration with the needle used to administer the dye, said Dr. Piggott. Other complications may include headaches, severe photophobia, persistent foreign body sensation, and migration of ink staining.2

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    1 L Cheng-Wei et al. Exp Ther Med. 2017;14(1):283-285.

    2 Brodie J et al. BMC Ophthalmol. 2015;15:95.

    Treatment-Resistant Problem

    In some cases, patients will need what amounts to lifetime therapy for tattoo-related uveitis, but spontaneous remis­sion is possible, said Dr. Dunn.

    The goal is to figure out the underly­ing cause of the uveitis, said Dr. Piggott. The ocular inflammation can be treated with topical or periocular steroids, for example, but many patients require systemic treatment.

    Work with a dermatologist. Al­though dermatologists are likely to be familiar with skin reactions from tattoos, some may not be aware that they can cause eye complications as well, said Dr. Holland. “It’s important to work as a team to control both skin and eye reactions.”

    Manage patients’ pain. The skin lesions can be extremely irritating; they may cause severe pruritis and a lot of pain, said Dr. Dunn. “The dermatologist may have therapy for the skin lesions that wouldn’t necessarily respond well to systemic corticosteroids.”

    Suppress inflammation. “To prevent uveitic complications, initially suppress the anterior segment inflammation with local corticosteroids, as you would for any noninfectious cause of uveitis,” said Dr. Holland. He added that main­taining suppression with corticosteroid eye drops is not an appropriate long-term strategy.

    Immunomodulatory therapy may be needed. “When we tapered the top­ical corticosteroids in our most recent patient, the inflammation and symp­toms came back,” said Dr. Holland. In many cases, these patients require immunomodulatory therapy such as methotrexate to maintain control of the inflammation.

    “The most striking finding for me has been the severity of the uveitis and how resistant it has been in some patients,” said Dr. Dunn. “We’ve started patients on topical steroids, then moved to steroid injections or systemic steroids. But immunosuppressants are often needed to get it controlled. Even then, uveitis has not always been con­sistently controlled and may recur.”

    As a result, he advised, “If you’re not comfortable managing patients with aggressive immunosuppressant therapy, get them to a uveitis specialist quickly.”

    Further Reading

    Letters

    Kluger N. Tattoo granulomas with uveitis rather than Vogt-Koyanagi-Harada dis­ease after tattooing? Can J Ophthalmol. 2019;54(3):401.

    Gill I et al. Probable Vogt-Koyanagi-Ha­rada disease with granulomatous tat­too-related dermatitis. Can J Ophthalmol. 2018;53(5):e179-e182.

    Maijer KI et al. Granulomatous tattoo re­action with associated uveitis successfully treated with methotrexate. J Eur Acad Der­matol Venereol. 2018;32(9):e338-e339.

    Case reports

    Piggott KD, Rao PK. Blurry vision and a black ink tattoo. JAMA. 2019;321(7):699-700.

    Tiew S. Tattoo-associated panuveitis: A 10-year follow-up. Eur J Ophthalmol. Published online May 10, 2019.

    Reinhard R et al. Recurrent tattoo reactions in a patient treated with BRAF and MEK inhibitors. J Eur Acad Dermatol Venereol. 2017;31:e375-e377.

    Review Article

    Kluger N. Tattoo-associated uveitis with or without systemic sarcoidosis: A compar­ative review of the literature. J Eur Acad Dermatol Venereol. 2018;32(11):1852-1861.

    Is Tattoo Removal Appropriate?

    Some data suggest that excising tattoos may alleviate the uveitis, said Dr. Dunn. “In our experience, however, most of these patients have multiple tattoos, and removing them is simply not prac­tical, especially since it would be chal­lenging to do adequate skin grafting.”

    If a patient wants a tattoo removed, the procedure may be done with laser. However, although the tattoo may no longer be visible on the skin, removal disperses the ink into the body. “If ink is the inciting factor, dispersing it won’t make uveitis better—it might make it worse,” Dr. Holland said. Newer dyes in development may be completely destroyed by laser.

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    1 https://theharrispoll.com/tattoos-can-take-any-number-of-forms-from-animals-to-quotes-to-cryptic-symbols-and-appear-in-all-sorts-of-spots-on-our-bodies-some-visible-in-everyday-life-others-not-so-much-but-one-thi/.

    2 Ostheimer TA et al. Am J Ophthalmol. 2014;158(3):637-643.

    3 Piggott KD, Rao PK. JAMA. 2019;321(7):699-700.

    4 Reinhard R et al. J Eur Acad Dermatol Venereol. 2017;31:e375-e377.

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    Dr. Dunn is director of the uveitis unit at Wills Eye Hospital in Philadelphia. Relevant financial disclosures: None.

    Dr. Holland is director of the Ocular Inflamma­tory Disease Center at the UCLA Stein Eye Insti­tute, at the University of California, Los Angeles. Relevant financial disclosures: None.

    Dr. Piggott is an assistant professor of ophthal­mology at the Washington University School of Medicine in St. Louis. Relevant financial disclo­sures: None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Dunn None.

    Dr. Holland None.

    Dr. Piggott None.

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    Employee E Employed by a commercial company.
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    Equity owner O Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
    Patents/Royalty P Patents and/or royalties for intellectual property.
    Grant support S Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.