Treatment of a refractory allergic reaction to a red tattoo on the lips with methotrexate and Q-switched Nd-Yag laser

Systemic contact dermatitis to a surgical implant presenting as red decorative tattoo reaction

Despite popularity of tattoos, complications may occur. In particular, red tattoo reactions due to allergic reactions are the most frequent chronic tattoo reactions. However, little is known about its histopathology and underlying pathomechanisms. The aim of this article is to analyze the histopathology of red tattoo reactions for diagnostic purposes and to acquire more insight into pathogenesis. A retrospective cross-sectional study was conducted by reviewing the histopathology of 74 skin biopsies of patients with allergic red tattoo reactions. Histopathological findings, such as inflammation patterns, inflammatory cells and pigment depth and color, were semi-quantified with an in-house validated scoring system by 2 independent senior investigators. Histiocytes and lymphocytes were both present in >93%. Histiocytes were the predominant inflammatory cells in 74.3%, but well-defined granulomas were mostly absent (78.0%). Eosinophils were uncommon (8.1%) The predominantly histiocytic reaction combined with interface dermatitis was the main inflammation pattern (37.9%). Most biopsies showed more than one reaction pattern. Interface involvement was observed in 64.8%, despite the intended depth of standard tattoo procedures, in which pigment is placed deeper, in the upper- and mid-dermis. Statistical analyses showed a significant association between inflammation severity and pigment depth (P = 0.024). In 6 cases (8.1%) pigments could not be retrieved histologically. In this cohort we demonstrated that cutaneous reactions to red tattoo ink are frequently characterized by the combination of dermal predominantly histiocytic infiltrates and epidermal interface dermatitis. Allergic reactions to red tattoo pigments probably represent a combination of a subtype IVa and IVc allergic reaction. Clinicians should be aware of the specific histopathology of these reactions and therefore the importance of taking a diagnostic skin biopsy.

As tattooing practices increase, delayed-type inflammatory reactions represent an uncommon adverse event to tattoo pigments. Different reaction patterns, such as eczematous, lichenoid, granulomatous and pseudolymphomatous reactions, have been previously reported, especially in association with metals contained in red tattoo pigments. We report a lichenoid papular reaction to an organic red tattoo ink, characterized by an intense mononuclear infiltrate dominated by CD8(+) T cells and CD56(+) lymphocytes and distributed in the superficial dermis around the red pigment and in the epidermis. Cytofluorimetric analysis of the lesional skin infiltrate confirmed the high frequency of cytotoxic CD8(+ )T cells and CD56(+)CD16(-) lymphocytes, most of which release type 1 cytokines. Chemical analysis of the red tattoo pigment confirmed its organic nature and the presence of intermediate reactive compounds. The lichenoid tissue reaction to red organic tattoo pigment showed the prototypical features of a cytotoxic inflammatory response to foreign substances (xenobiotics). The chemically unstable and reactive nature of modern tattoo pigments has to be taken into account by the clinician as well by the tattoo recipients.

To the Editor: INTRODUCTION Tattoo has numerous potential medical complications well described in the literature. Among these complications, sensitivity reactions to tattoo ink have higher frequency. Clinically, these reactions can present with pruritus, focal edema, papules, nodules, plaques. Usually these lesions confined to the site of causative tattoo pigment. Less commonly generalized reactions have also been reported.1,2 Furthermore anaphylactic reaction has been described in association with colored tattoo pigments.3 Histologically these hypersensitivity conditions could present with allergic, foreign body sarcoidal granulomatous reactions. Particularly mercuric sulfide (cinnabar) containing red tattoos are the most common causes of these delayed allergic reactions.1,4 In addition, cadmium has been reported responsible for photosensitivity reactions in red tattoos.5 CASE REPORT A 41-year-old man presented to our outpatient clinics with papular and nodular overgrowth arising within his tattoo performed 1 month ago situated over his right biceps and on right forearm. As shown in Figures 1–3, on examination there was dome-shaped red papules and nodules with variety of size in the shape of red figures; other colors were unaffected. There was no history of contact allergy and atopic diathesis. Lesions were not photosensitive. Routine blood tests, urinalysis, antinuclear antibodies, inflammatory markers, complements were in reference range. There was no evidence of peripheral lymphadenopathy. Chest x-ray was normal. Biopsy was taken for histopathology from one of the nodules. Histopathological examination showed heavy dermal inflammation with numerous pigment containing histiocytic macrophages and exogenous red pigment deposition in intercellular area, foreign body granulomas containing foreign body giant cells and few mononuclear cells as it is seen in Figure 4. An infectious etiology was not identified. We were unable to identify the trade name of the red pigment used. Patient did not accept any surgical therapies and he has still been on follow-up with topical steroid therapy.FIGURE 1.: Indurated red nodules confined to red portion of the tattoo.FIGURE 2.: Closer view of red nodules.FIGURE 3.: Multiple red papules with diameter of several millimeters.FIGURE 4.: Infiltraton of pigment containing inflammatory cells and deposition of exogenous pigment. (H&E, original magnification, X100).CONCLUSION Tattoo-associated infectious, allergic, and/or granulomatous complications were seen with ratio of 2.1%.1 Nodular, lichenoid,6 pseudolymphomatous,7 granulomatous.8,9 Histological tattoo reaction patterns were well recognized in red tattoos. Granulomatous reactions could occur, either as a foreign body–type reaction to pigment with numerous pigment containing giant cells or as a hypersensitivity reaction with few giant cells. Sarcoidal reactions within a tattoo with systemic disease or without were less common.10 They might present as the first sign of systemic disease11; however, the patient presented did not show any findings of systemic sarcoidosis. Organic pigments containing red tattoo reactions were also strongly associated with UV exposure.12 Our patient's reaction was not photoaggravated. In summary, our report aimed to emphasize tattoo-associated granulomatous tissue reactions. Careful clinicopathologic evaluation is advised to avoid misdiagnosis of systemic sarcoidosis or any other systemic granulomatous diseases.

The aim of this study was to assess the feasibility of Raman spectroscopy as a screening technique for chemical characterisation of tattoo pigments in pathologic reacting tattoos and tattoo ink stock products to depict unsafe pigments and metabolites of pigments. Twelve dermatome shave biopsies from allergic reactions in red tattoos were analysed with Raman spectroscopy (A 785-nm 300 mW diode laser). These were referenced to samples of 10 different standard tattoo ink stock products, three of these identified as the culprit inks used by the tattooist and thus by history the source of the allergy. Three primary aromatic amine (PAA) laboratory standards (aniline, o-anisidine and 3,3'-dichlorobenzidine) were also studied. Application of Raman spectroscopy to the shave biopsies was technically feasible. In addition, all ten inks and the three PAA standards could be discriminated. 10/12 shave biopsies provided clear fingerprint Raman signals which differed significantly from background skin, and Raman spectra from 8/12 biopsies perfectly matched spectra from the three culprit ink products. The spectrum of one red ink (a low cost product named 'Tattoo', claimed to originate from Taiwan, no other info on label) was identified in 5/12 biopsies. Strong indications of the inks 'Bright Red' and 'Crimson Red' were seen in three biopsies. The three PAA's could not be unambiguously identified. This study, although on a small-scale, demonstrated Raman spectroscopy to be feasible for chemical analysis of red pigments in allergic reactions. Raman spectroscopy has a major potential for fingerprint screening of problematic tattoo pigments in situ in skin, ex vivo in skin biopsies and in tattoo ink stock products, thus, to eliminate unsafe ink products from markets.

As tattooing becomes more and more popular, growing numbers of skin reactions caused by tattoos are also becoming frequently encountered by medical professionals. We present a generic case of a tattoo-induced allergic reaction and explore its’ immunological mechanism. This paper also highlights components of tattoo inks, their allergenic potential, and possible options for treatment. There can be different types of allergens in tattoo inks. Some are biodegradable, while others are not. Examples of biodegradable components include natural dyes and preservatives. Allergic reactions caused by such agents may resolve with simple therapy since after a short period they will be cleared from the skin. On the other hand, synthetic molecules and other non-degradable dyes will need invasive therapy, such as surgery, dermatome shaving and most commonly used - laser removal therapy. Most notable in this regard is red ink with the highest incidence. There are no current regulations on tattoo inks, which puts tattoo enthusiasts at a higher risk of developing allergic reactions. There are certain preventive measures, such as patch and dot tests. Because the specificity of these tests is mediocre, despite negative results, an allergic reaction may develop weeks or months later. There are no strict treatment guidelines and each case must be assessed individually. Our patient was a young woman, who developed a local allergic reaction due to the red pigment used in her tattoo. Initial treatment, in this case, was anti-inflammatory to reduce inflammation. The only way to get full resolution in such cases is to remove the allergen (red pigment) from the dermis. The patient was prescribed topical treatment with corticosteroids. Once irritation subsided tattoo removal therapy with Q-switched Nd 532 nm laser was initiated. The inflammation returned after the first session, for which local anti-inflammatory medications were started. Due to the ineffectiveness of laser removal and local treatments systemic therapy with corticosteroids was prescribed with gradually decreasing the dosage and controlling the disease. After two months of this treatment, the patient's condition improved. She is still undergoing therapy with systemic corticosteroids.

Clinicians in the fields of general medicine, dermatology, and plastic surgery are in their work now and then confronted with tattoo complications. Recognizing the rather few important diagnostic groups and urgencies, the medical 'decision tree' of treatment becomes quite simple. Acute conditions are dominated by bacterial infections needing antibiotic treatment. Systemic infection is a matter of urgency and requires intravenous treatment in a hospital without delay to prevent septic shock. Inflammatory reactions are a real challenge. Chronic allergic reactions in red tattoos are mostly nonresponsive to topical corticoid and best treated with dermatome shaving with complete removal of the hapten concentrated in the outer dermis. Laser treatment of allergic reactions can boost the allergy with worsening and a potential risk of anaphylaxis and is thus not recommended in tattoo allergy. Chronic papulonodular reactions in black tattoos with pigment agglomeration can respond to local corticoid or be treated with dermatome shaving or lasers depending on availability. It is important to recognize sarcoidosis, which is strongly associated with reactions in black tattoos. Tattoo complications also include many rare but specific entities, which require individual treatment depending on the case and the disease mechanism. Removal of tattoos in individuals regretting their tattoo is performed using Q-switched nanosecond lasers and the recently introduced picosecond lasers. In view of the various tattoo pigments with different absorption spectra and the limited number of laser wavelengths, it is difficult to predict treatment outcome, and it is recommended to pretreat small test spots. Black and red colors are removed best, while other colors are difficult. Removal of large tattoos, especially when multicolored, is hardly achievable and not recommended. Clients often have unrealistic expectations, and informed consent and dialogue between the client and the laser surgeon before and during a treatment course is important since the client shall know the risk that removal can be unsuccessful, with complications and even disfiguring leading to regret at the end.

Use of the alexandrite laser (755 nm, 100 nsec) for tattoo pigment removal in an animal model

BackgroundRed tattoos are prone to allergic reactions. The identity of the allergen(s) is mostly unknown.ObjectivesChemical analysis of human skin biopsies from chronic allergic reactions in red tattoos to identify culprit pigment(s) and metals.Material and methodsOne hundred four dermatome biopsies were analyzed by matrix‐assisted laser desorption/ionization tandem mass spectrometry (MALDI‐MS/MS) for identification of commonly used organic pigments. Metal concentrations were assessed by inductively coupled plasma (ICP)‐MS and x‐ray fluorescence (XRF). Fourteen patients had cross‐reactions in other red tattoos.ResultsIn total, the identified pigments were mainly azo Pigment Red (P.R.) 22 (35%), P.R. 210 (24%), P.R. 170 (12%), P.R. 5 (0.9%), P.R. 112 (0.9%), and Pigment Orange (P.O.) 13 (11%). P.R. 122 (0.9%) and Pigment Violet (P.V.) 23 (8%) were also common. P.R. 22, P.R. 170, and P.R. 210 also dominated in patients with cross‐reactions. In 22% of the biopsies, no red pigment was detected. Element analysis indicated the presence of the sensitizers nickel and chromium.ConclusionsP.R. 22, P.R. 170, and P.R. 210 were identified as the prevailing pigments behind chronic allergic reactions in red tattoos. The epitope causing the reaction might be a pigment‐degradation product. Metal contamination may derive from different sources, and its role in red tattoo allergy cannot be ascertained.

Considering the ever increasing popularity of tattoos, significant reactions remain unusual. Red pigments are the commonest cause of delayed tattoo reactions. Histology typically shows extensive lichenoid basal damage, well away from the dermal pigment. We report two cases of lichenoid reactions to red tattoo pigment and review the literature on the subject.

Methotrexate injection site reactions: Case report and literature review

Aim: Tattoo pigments are deposited in the skin and known to distribute to regional lymph nodes. Tattoo pigments are small particles and may be hypothesized to reach the blood stream and become distributed to peripheral organs. This has not been studied in the past. The aim of the study was to trace tattoo pigments in internal organs in mice extensively tattooed with 2 different tattoo ink products. Material/Methods: Three groups of mice were studied, i.e., 10 tattooed black, 10 tattooed red, and 5 untreated controls. They were tattooed on the entire back with commercial tattoo inks, black and red. Mice were sacrificed after 1 year. Samples were isolated from tattooed skin, lymph nodes, liver, spleen, kidney, and lung. Samples were examined for deposits of tattoo pigments by light microscopy and transmission electron microscopy (TEM). Results: TEM identified intracellular tattoo pigments in the skin and in lymph nodes. TEM in both groups of tattooed mice showed tattoo pigment deposits in the Kupffer cells in the liver, which is a new observation. TEM detected no pigment in other internal organs. Light microscopy showed dense pigment in the skin and in lymph nodes but not in internal organs. Conclusion: The study demonstrated black and red tattoo pigment deposits in the liver; thus, tattoo pigment distributed from the tattooed skin via the blood stream to this important organ of detoxification. The finding adds a new dimension to tattoo pigment distribution in the body, i.e., as observed via the blood in addition to the lymphatic pathway.

Tattooing is a skin trauma and involves a special vulnus punctatum (with inserted tattoo ink, a vulnus venenatum), which should heal with no infection and no local complication. Local treatment in the healing phase ideally builds on the 'moist wound' principle using plastic film, hydrocolloids, silver dressing, and compression. Bacterial infections during healing are treated with oral antibiotics, and a list of first-line antibiotics is proposed. Notice is given to severe infections with affected general condition, and it is emphasized that intravenous antibiotic treatment must be instituted as early as possible to prevent septic shock and death. Hydrophilic antibiotics shall be given in high load and maintenance dose due to increased renal clearance of such antibiotics. Chronic allergic reactions of red tattoos respond little to local corticoids and are best treated with dermatome shaving. Laser removal is contraindicated due to the risk of photochemical activation of the allergy with anaphylaxis or worsening. Chronic reactions in black tattoos can be treated with local corticoids, dermatome shaving, and lasers as well. Systemic corticoid is used in allergic reactions in red tattoos and in cross-allergic reactions of other red tattoos as well as in black tattoo reactions associated with sarcoidosis and with cutaneous 'rush phenomenon' affecting any black tattoo. Systemic corticoid is also indicated in generalized eczema due to nickel allergy or another allergy challenged through tattooing or introduced by tattooing as a primary sensitization. The use of intralesional corticoid, antihistamines, and immunosuppressive medicines is discussed. A warning against the use of lactic acid and other caustic chemicals for tattoo removal is given, since such chemicals and commercial products cannot be dosed properly and very often result in disfiguring scarring.

Eighteen patients who developed cutaneous reactions to red tattoos were studied to identify the chemicals responsible for the reactions to modern red tattoo pigments. Biopsies from the tattoos were examined histologically and the chemical composition of the red pigments was analysed by X-ray microanalysis. A variety of metallic elements including aluminium, iron, calcium, titanium, silicon, mercury and cadmium were detected. Patch tests were performed to the relevant chemicals in nine cases, and only one patient reacted to mercury. This study demonstrates that although reactions to mercury still occur, other red dyes containing a variety of inorganic pigments may provoke a cutaneous inflammatory response.

Q-switched alexandrite laser treatment (755 nm) of professional and amateur tattoos