More than skin deep

By Emily Margosian, Assistant Editor, July 1, 2024

Humans have been tattooing since the Stone Age. The oldest discovery to date of tattooed human skin is on the body of Ötzi the Iceman, dating back to between 3370 and 3100 BC.

In modern times, this age-old practice has rapidly grown in popularity. The Pew Research Center estimates that in 2023, more than a third of Americans had at least one tattoo. As tattoos become increasingly common, a rise in the number of tattoo-associated skin disorders can be expected.

“With 38% of women and 27% of men in the U.S. having at least one tattoo, it is very important for dermatologists to be aware of how to treat complications, especially as some can be life-threatening, and others can have significant impact on a patient’s quality of life,” said Marie Leger, MD, PhD, FAAD, a dermatologist in private practice in New York and voluntary faculty at Mount Sinai School of Medicine. “I have many patients who travel long distances to see me because the perception is that many U.S. dermatologists don’t know how to treat tattoo reactions — the literature shows that people are more likely to consult with their tattoo artist than a dermatologist when they have an issue with their tattoo.”

This month, dermatologists discuss tattoo tips for patients and physicians, and unravel the current tattoo regulatory status.

What’s in tattoo ink?

A seemingly simple question with a not so simple answer. “We know a lot and we know very little,” said Walter Liszewski, MD, FAAD, assistant professor of dermatology and preventative medicine at Northwestern Feinberg School of Medicine. “We are reliant on what manufacturers tell us. Some companies are very detailed, but for others, it is a mystery which preservatives, solvents, and pigments are used.”

On a basic level, tattoo ink can be broken down into two components: the vehicle and the pigment. Water, witch hazel, or alcohol are the most common vehicle choices. However, it is the pigment that most often poses a mystery — and a problem. Every company has different proprietary mixes, and many unknowns exist about how tattoo inks interact with the skin and within the body.

“An ink may contain one pigment, or it may contain multiple. For example, a red tattoo ink may contain two red pigments, a black pigment, and a white pigment. That’s what makes it somewhat challenging. Multiple pigments are oftentimes used to formulate tattoo inks,” said Dr. Liszewski.

“Many tattoo inks now contain mixtures of metal salts and organic pigments (azo dyes), similar to those used in car paint. These azo dyes are especially common in intensely pigmented colors. There are even fluorescent dyes being used in some tattoo inks.”

Tattoo ink pigments have also evolved over the years. In the past, metal salts, lead, cobalt, and carbon were used in inks. However, today many modern tattoo inks (particularly intense reds and yellows) contain plastic-based pigments that are also used industrially in printing, textiles, and car paint. “Historically, tattoo pigments paralleled those used in paints, with blue inks containing cobalt, chromium, and copper salts, green inks containing chromium or copper, yellow ink containing cadmium salts, and red inks containing mercury, cadmium, or iron oxides,” said Michi Shinohara, MD, FAAD, vice chair of dermatology and director of dermatopathology at University of Washington. “In modern days, though, the composition of inks is much more variable. Many tattoo inks now contain mixtures of metal salts and organic pigments (azo dyes), similar to those used in car paint. These azo dyes are especially common in intensely pigmented colors. There are even fluorescent dyes being used in some tattoo inks.”

“We don’t use the older metallic pigments anymore. There are only so many pigments that are easy to synthesize, inexpensive, and effective. Many pigments may be used for both industrial uses and in tattoo inks as well,” agreed Dr. Liszewski. “Dermatologists should be aware that in textbooks they often describe using metallic pigments like mercury or cadmium. Those haven’t been used for 40 or 50 years, and it’s factually inaccurate.”

Who regulates tattoo ink?

Currently, the FDA classifies tattoo pigments as cosmetics (as opposed to a drug or medical device), even though they are inserted into the body. Therefore, there is currently no federal regulation of pigment production. “The FDA does not have authority to regulate tattoo inks as they do not have a medical purpose. However, if there are bad batches of ink that result in harm, the FDA has authority to investigate these cases,” said Dr. Liszewski.

The practice of tattooing itself (licensing of tattoo artists) is regulated by local state health boards, according to Dr. Shinohara.

While tattoo inks sold and manufactured in the United States are largely unregulated, that may change. In 2022, Congress passed the Modernization of Cosmetics Regulation Act, which expanded FDA authority in regulating tattoo inks. The law allows mandatory recall of adulterated or misbranded inks, requires adverse event reporting by industry, and requires manufacturing facility registration.

Last year, the FDA solicited comments on a draft document outlining practices to minimize microbial contamination of tattoo inks, indicating that it intends to establish manufacturing practice regulations for the manufacturing of tattoo inks. “This is particularly important — a survey of U.S. tattoo inks in 2018 showed that almost 50% of them were contaminated with microorganisms,” said Dr. Leger.

In late 2023, the AADA responded to the FDA Center for Food Safety and Nutrition’s request for input on its draft ‘Insanitary Conditions in the Preparation, Packing, and Holding of Tattoo Inks and the Risk of Microbial Contamination’ guidance. The AADA supports the FDA’s efforts to protect the public from contaminated tattoo ink and encourages manufacturers and distributors to mitigate situations where a tattoo ink product may become contaminated with microorganisms.

The AADA also urged the FDA to consider additional safety requirements for tattoo manufacturers and distributors to ensure the safe use of tattoo pigments and the devices used to inject these pigments into the skin, and encouraged policymakers to require tattoo artists to keep a detailed record of the materials they use, including recording the color, manufacturer, distributor, and lot number of pigments used in each tattoo. Not only will this help track the tattoo ink used, but it will also help with reporting adverse health reactions to pigments that should be reported to the local health department and the FDA.

“In an ideal world, regulation of tattoo inks would identify the most meaningful clinical risks and protect consumers from them, but this isn’t always the case. For example, in Europe, two pigments were recently banned that eliminated the ability for artists to use most green and blue inks. These bans were not based on real-world epidemiological or toxicology data, and it has been difficult for chemists and dermatologists to have a say in this regulatory process,” said Dr. Leger.

“The European Union has taken a different approach where they are closely regulating the contents and concentrations of pigments and chemicals in inks. However, the EU has made many of these regulations without consulting tattoo ink manufacturers or tattoo artists,” said Dr. Liszewski. “As such, many of the EU regulations are technically impossible to enforce and they have negatively impacted the ability of tattoo ink manufacturers to bring new inks to market.”

Cutaneous complications of tattoos

Infection

Among tattoo-related complications, infection can be a common adverse event depending on a patient’s after-care, the cleanliness of the equipment used to administer the tattoo, or even contaminated ink.

Infection onset can occur immediately after getting the tattoo, or days or months after. “Bacterial infections occur relatively quickly — days to weeks after obtaining a tattoo — and because of this, dermatologists are unfortunately not seeing these as often as primary care physicians, even though we are so well equipped to diagnose and treat these kinds of infections,” said Dr. Leger. “Post-tattoo infections can be due to Staphylococcus, Corynebacterium, Pseudomonas, Streptococcus, Mycobacteria, HPV, HSV, and other organisms.”

Signs of infection can include darkening, redness over time, intensifying pain, an itchy or painful rash over the tattooed area, fever, chills, pus, or open sores. Along with localized bacterial infections (including atypical mycobacterial infections), there have been reports of people being infected with syphilis and hepatitis B and C due to non-sterile tattooing practices.

Allergic reaction to tattoo ink

Patients may also experience allergic reactions to the ink used in their tattoos. Symptoms can include redness, swelling, itch, small bumps, raised or scaly patches, deep lumps, blisters, flaking or crusted skin, or watery fluid seeping from the tattooed area. “These reactions are often associated with intractable pruritus,” said Dr. Leger. Signs of a serious reaction can include trouble breathing, racing heart, tightness in chest, dizziness, stomachache, intense swelling, serious pain, flushing, or hives.

Onset can occur immediately after getting the tattoo, weeks or years later, or potentially decades later. An allergic reaction long after getting a tattoo may be linked to subsequent medical treatments that trigger the body’s immune response (e.g., antiretroviral treatment, joint replacement surgery, etc.).

“An allergic reaction to a tattoo ink usually occurs months to years after the tattoo is placed. An allergic reaction that presents following the tattoo, or in the first days to weeks, is usually an allergy due to antibiotics that may have been applied, or to ingredients in the aftercare lotion like fragrances or preservatives,” said Dr. Liszewski. “That will manifest with edema, itching, and sometimes vesicle formation. Delayed-type allergies to pigments tend to appear months to years later. That’s because fresh, whole pigments are usually not allergenic, but as they slowly degrade into smaller pieces, those pieces become allergenic.”

Treatment for allergic reactions to tattoos involves several options. “Classically, these have been treated with topical and intralesional steroids, and/or removal of the tattoo with an ablative laser or dermatome shaving, which is done more often in Europe than here,” said Dr. Leger. “This is an important technique that more U.S. dermatologists should learn — the cosmetic and clinical outcomes are much better than surgically removing the tattoo.”

“While you can just cut the tattoo out, in Europe the preferred treatment is oftentimes to do a broad shave which removes all the pigment,” agreed Dr. Liszewski. “You can also do laser tattoo removal. However, the problem with that is that it will further degrade the pigment, and you run the risk of causing a severe whole body allergic reaction.”

“Historically, red inks have been the most allergenic. I always tell patients, if in doubt, always pick black. Black is just carbon. It’s very inert.”

Systemic treatments may also offer a less-invasive treatment for patients experiencing tattoo allergies. “Medications like methotrexate and mycophenolate mofetil have been used. Dupilumab has also been reported to be successful in treating tattoo allergies resistant to other approaches,” said Dr. Leger. “We recently published a case series of ruxolitinib working well for tattoo allergies, which is exciting because it’s not associated with the atrophy or hypopigmentation that steroids often cause.”

Certain ink colors have been associated with more reactivity, although the reasons why remain unclear. “Red tattoo ink is the most common cause of tattoo allergies, thought to be because of the azo pigment use,” said Dr. Leger.

“Historically, red inks have been the most allergenic,” agreed Dr. Liszewski. “I always tell patients, if in doubt, always pick black. Black is just carbon. It’s very inert.”

As it’s theorized that the source of tattoo allergies is not an ingredient found in the ink bottle itself, but rather a breakdown product of the ink, patch testing to a particular pigment does not typically yield useful results.

“Patch testing is not currently helpful for tattoo allergies,” affirmed Dr. Liszewski. “This is for two reasons. Immune responses to tattoos occur in the dermis, while patch testing stimulates immune cells in the epidermis. There is likely a difference in the immune response between the two. Second, fresh tattoo ink is inert and rarely allergenic. However, as tattoo ink degrades over months to years, the broken-down components become allergenic. This process is somewhat random, so we cannot identify which broken-down products of an ink are allergenic. Beyond this, no one even knows which pigments are in their skin. Not all tattoo manufacturers disclose their pigments, and for a color, there may be 10 or more different pigments used. Even then, tattoo artists do not keep logs of which inks they used for clients.”

Allergic reaction to tattoo aftercare products

While patients may experience an allergic reaction to their tattoo itself, a more likely culprit is often the products used on the skin during the healing process, experts say.

“The tattoo aftercare space is full of ‘natural’ products. However, using these on a disrupted skin barrier can provoke irritant and contact dermatitis,” said Dr. Leger. “The best product to use on healing tattoos is most likely petrolatum — which is unlikely to cause allergies, inexpensive, and widely available,” said Dr. Leger.

“There is a huge industry of tattoo aftercare products. Many different companies have started to create treatment lines for wound care for fresh tattoos,” said Dr. Liszewski. “The problem is, a lot of these use a lot of essential oils and fragrances, which is probably the worst thing you can put on a fresh wound. I’m someone who specializes in patch testing, so I have a lot of concerns about these because they’re incredibly irritating, and potentially very allergenic. Ask your patients about their aftercare products because a lot of them are nasty stuff.”

While there are no official guidelines on tattoo aftercare, Dr. Liszewski recommends patients stick to fragrance-free products. “It’s very controversial because there’s no consensus on what aftercare should be. Some tattooists recommend using a petrolatum base for aftercare. Others tell patients to never use petrolatum. The best thing I recommend is to use fragrance-free products, both in terms of thick emollients, but also in terms of hypoallergenic, fragrance-free soaps to clean the tattoo as it heals.”

Triggered skin disease

Less commonly, tattooing can trigger skin disease to appear within or around a tattoo, as early as three days, or in some cases, years later. This has been referred to as the “Koebner phenomenon,” which indicates the appearance of new skin lesions of a pre-existing dermatosis on areas of cutaneous injury in otherwise healthy skin.

“Koebnerization can occur with tattooing. Conditions like vitiligo, lichen planus, and psoriasis, for example, can be associated with this,” said Dr. Leger. “In one small study, about a third of the test subjects experienced a flare of psoriasis in the tattooed area within the first few weeks after tattooing. However, this isn’t necessarily a reason for patients with these conditions to not get a tattoo if they understand the risk. In the psoriasis study, for example, about 80% of people also reported a positive effect on their body image.”

While patients with existing skin disease can generally get tattooed without issue, they should consult with a physician before undergoing the needle. “Patients with a history of keloid scarring or skin disorders that can occur at the site of skin trauma — such as psoriasis or pyoderma gangrenosum — as well as anyone on immunosuppressive medications should always check with their dermatologist or care team,” recommends Dr. Shinohara.

“Certain conditions contain more risk,” added Dr. Leger. “For example, a history of melanoma, sarcoidosis, immunocompromised status, or inflammatory skin conditions like vitiligo, eczema, and psoriasis. For people with these conditions, I recommend that tattoo artists have their clients see a dermatologist first.”

Rare tattoo-associated reactions

While common complications from tattoos often don’t make it to the dermatologist’s office, physicians should be prepared to address more serious and rare complications, according to Dr. Shinohara. “More uncommon reactions that a dermatologist might be confronted with include lichenoid or granulomatous reactions to tattoo dyes. These types of reactions are often delayed, sometimes for months to years,” she noted. “An important pearl for dermatologists is to remember that sarcoidosis can occur within tattoos as a form of ‘scar sarcoid.’ If a patient presents with pustules or significant inflammation within their tattoo, dermatologists should consider biopsy to rule out atypical infections. These can occur weeks to months after tattooing.”

“Another important complication for dermatologists to recognize are papulonodular reactions, most often seen in black tattoos,” added Dr. Leger. “As dermatologists, we often see these subtle bumps in tattoos, but patients don’t always point them out to us. In a tattoo clinic in Copenhagen, these slightly raised, sometimes subtle bumps in tattoos showed sarcoidal granulomas about one third of the time when biopsied, and these patients often have systemic involvement, including uveitis and pulmonary symptoms, and need a sarcoidosis workup. I have had several patients with systemic sarcoidosis that presented initially as subtle bumps in their tattoos.”

Promoting safe tattooing

As tattooing continues to grow in popularity, dermatologists have an opportunity to improve public health outcomes as experts in skin. “Nearly a third of Americans have tattoos. Given their popularity, we will see many patients with tattoos,” said Dr. Liszewski. “However, many tattooists do not have adequate training on recognizing the medical complications of tattoos. There is an ongoing opportunity for dermatologists to partner with tattooists to provide the highest quality of care possible.”

To avoid potential complications, Dr. Shinohara recommends patients follow several key guidelines. “Patients should make sure that they visit a professional licensed tattoo artist. Although any color of tattoo ink can cause a reaction, black inks seem less associated with reactions,” she said. “Patients should also follow post-tattoo care instructions carefully to avoid infection and let their tattoo artist and/or dermatologist know if they have concerns about their tattoo site.”

“In general, the safest color is black,” affirmed Dr. Liszewski. “Beyond this, make sure you are getting your tattoo in a state or municipality that regulates tattoo artists — not all of them do. Follow the instructions your tattooist gives you, and if you have any signs of infections, be sure to reach out to your tattooist and a board-certified dermatologist.”

Additional DermWorld Resources