Clinical and Pathological Features of Persistent Decorative Tattoo Reactions.

Persistent, non-infectious medical complications arising from decorative tattoos have increased considerably. They are difficult to characterize clinically, and histopathology shows a wide variety of overlapping patterns, with lichenoid and granulomatous dermatitis being the most common findings. Both clinical and pathological findings are difficult to ascribe to particular ink colour. The findings in 30 biopsies from 28 patients with persistent reactions in decorative tattoos are reported, including immunohistochemical findings. Copyright:

Introduction

In Western countries, about 10-20% of the population have at least one decorative tattoo and this percentage increases in youngsters.[12] Although tattoos-derived complications are rather common, persistent reactions are far less frequent and involve only 6-10% of tattoos.[23]

Hypersensitivity reactions, usually reported in association to red ink, are the most common type, while black is considered responsible for most non-allergic reactions.[1234] Histopathologically, lichenoid and granulomatous reactions or non-specific inflammation have been described as the most frequent patterns, but the clinical and pathological correlation is not easily assessed.[256]

We have reviewed the clinical, pathological and immunohistochemical features in 30 samples from 28 patients who were submitted to skin biopsy for non-infectious, persistent tattoo-related complications.

Material and Methods

We have retrieved 30 biopsies from 28 patients with persistent hypersensitivity reactions in decorative skin tattoos, defined according to previous papers[3] as non-infectious, chronic and persistent (over a week) lesions, usually restricted to a specific colour, which develop from immediately to years after tattooing.

Immunohistochemistry was performed with antibodies against CD3, CD4, CD8, CD20, CD68 (PGM-1), CD123 and CD138 (All prediluted FLEX Ready to use, Agilent-Dako, Santa Clara, USA), with automatised equipment (Omnis, Agilent-Dako, Santa Clara, USA) and staining was revealed with EnVision.

Results

The total number of patients comprised 20 females and 8 males, with ages ranging from 18 to 67 years [Table 1].

Table 1

Summary of clinical findings, treatment and evolution of lesions

Case nº	Age/Sex	Location	Time since tattooing (months)	Color involved	Clinical description	Evolution
1	F/24	Left shoulder	24	Red	Pruritic, erythematous papular lesions	Improvement with local steroids treatment but lesions relapse after withdrawal. Follow-up lost after 1 year
2	F/31	Left arm	6	Red	Pruritic, erythematous papular lesions	Temporary improvement with local tacrolimus and steroids, but lesions relapse. Follow-up lost after 2 years
3	M/39	Right arm	Unknown	Black	Indurated plaque	Improvement with local steroids treatment. Follow-up lost after 5 months.
4	F/22	Unknown	3	Red	Pruritic, erythematous and poorly defined areas. Partial tattoo regression	Improvement after local steroids infiltration. Tattoo removal.
5	F/25	Unknown	3	Red	Non-descript inflammation	Lost follow-up before treatment
6	F/25	Left forearm	0.5	Red	Desquamative, papular lesions and erythematous plaques	Cultures positive for Staphylococcus aureus. Slight improvement with antibiotics. Lost follow-up
7	F/27	Right ankle	13	Red	Pruritus	Improvement after local steroids infiltration but lesions relapse. Lost follow-up
8	F/27	Ankle	36	Black	Indurated plaque	Slight improvement with topical steroids after 5 months.
9	F/38	Wrist	7	Red	Pruritic indurated plaque	No treatment. No follow-up.
10	F/18	Right foot	Unknown	Red	Pruritic, desquamative and indurated lesions	Unknown
11	M/55	Unknown	Unknown	Red	Papular lesions	Unknown
12	F/20	neck	6	Red	Hyperkeratotic and nodular areas	Improvement after local steroids infiltration. Lost follow-up
13	M/35	Left forearm	Unknown	Black	Unknown	No treatment. Died of uterine cervix cancer
14	V/19		Unknown	Unknown	Unknown	Unknown
15	V/36	Left temporal	Unknown	Black	Black papular lesion. Aneurism	Removal.
16	M/31	Leg (side??)	6	Red	Pruritic, raised lesions.	Local corticosteroid injection. Residual Scar.
17	V/67	Left cheek	Unknown	Blue	Bluish discoloration.	No treatment.
18	M/31	Right leg	120	Red	Bleeding lesion on top of tattoo.	Removal
19	V/34	Right leg	72	Yelow/black	Pruritus.	Lost follow-up
20	V/26	Left wrist	Unknown	Yellow	Inflammatory and exudative lesion	Improvement with local steroids
21	V/57	External malleolus	12	Black	Non-descript inflammation.	Removal
22	M/37	Righ Shoulder	48	Black	Indurated and papular lesions in the last 2 months	Local steroids. Follow-up lost
23	M/47	Eyebrows	Around 20 years	Yellow/black	Pain and itching in eyebrows	Unknown
24	F/25	Right forearm	1	Red	Multiple pruritic and desquamative papular lesions	Improve with topical steroids. Follow-up lost after 13 months
25	F/29	Left forearm	3	Brown	Pruritic plaques	Cured with local steroids
26	F/28	Anterior neck	5	Yellow	Indurated areas	Spontaneous involution after 6 months
27	F/35	Right ankle	24	Blue	Pruritic and painful elevated lesions	Removal
28	F/56	Left forearm	60	Black	Pruritic elevated lesions	Improvement with local steroids

Persistent reactions were limited to one tattoo and involved only one color, except for two cases affecting two colours. They were related with red colour in 15 patients, followed by black in 8, yellow in 3 and blue in 2. In two cases, lesions were both in yellow and black colours while for the remaining two, the involved colour was not recorded.

They were more commonly papules or plaques (16 cases), followed by erythematous and desquamative lesions (7 cases), while others were labeled as nondescript inflammation [Figure 1]. Only one lesion was ulcerated. Pruritus and pain were specifically reported in eight and two cases, respectively, but more commonly patients complained of vague discomfort. The partial disappearance of the tattoo was noted in two cases. Latency from tattooing was recorded in 19 cases and it ranged from 2 weeks to 10 years. Eleven cases were treated with local steroidal injection, in one associated with topical tacrolimus, with only partial response to relapse weeks or months later, except for one patient with complete remission. Tattoo removal or ablative laser surgery was recommended in most cases, but it was recorded to be made in only two patients. Spontaneous regression was described in only one patient, after 6 months of symptoms. Follow-up was incomplete, and it was lost in all unresolved cases after 5 to 12 months.

Figure 1

Several examples of papulo-nodular lesions involving decorative tattoos. They are limited to one color (red or black) and only B shows superficial scaling

Biopsies showed variable, usually diffuse and very dense, mixed inflammatory dermal infiltrate, which extended to the reticular dermis in 28 cases but involved the subcutaneous fat tissue in only four, one reaching the underlying muscle. Distribution in the deep reticular dermis was usually perivascular, in contrast with the more diffuse distribution in the papillary dermis. Lymphocytes and macrophages were the predominant cells, and although other cell types were also present, they were never predominant. Plasma cells, noted in 12 cases (7/14 with red color, 2/7 with black, 2/3 with blue and 1/3 with yellow), were particularly abundant in a case of morphea-type sclerosis, but they were scarce in all the remaining cases. Eosinophils were present in only six cases (three with red colour).

In three cases the infiltrate was considered a pseudolymphoma, given its density and diffuse deep involvement.

Interface dermatitis, present in 17 cases [Figure 2], was not associated with any particular color. It was graded as severe in only five (three red and two black). Necrotic keratinocytes were present in 15 cases, but they were abundant in only one patient (with two biopsies) which showed also severe interface dermatitis.

Figure 2

Non-necrotizing granulomas (a and b) were common but only rarely the predominant inflammatory pattern. In two cases, collagen necrobiosis was extensive and transepidermal elimination was noted in one case (c and d)

Granulomas were noted in 11 cases (4/14 with red colour, 3/3 with yellow, 2/7 with black, 1/3 blue and 1/2 yellow-black), but they were the main form of inflammation in only five cases, associated in two cases with yellow ink and with red, black and yellow in one case each [Figure 3]. A purely sarcoid-like granulomatous reaction pattern was not found. Two patients presented extensive dermal necrobiosis as the main histopathologic pattern [Figure 3] with marked collagen degeneration but without mucin deposition, one showing epidermal perforation. Finally, one patient presented with a scleroderma-like reaction.

Figure 3

Interface dermatitis with some lichenoid features was the most common histopathological finding (a). Immunohistochemistry demonstrated the presence of T-cells (b) as the main component, with different proportions of CD4 (c) and CD8 cells (d)

Immunohistochemistry demonstrated that T lymphocytes were predominant in all cases, with a diffuse or perivascular distribution. The proportion of CD4 and CD8 cells was usually similar, although in four cases the CD8 expression was more intense than CD4. B-cells were very scarce or completely absent, except for one case with a prominent granulomatous reaction.

The presence of plasmacytoid dendritic cells, stained with CD123, was almost negligible, and only in cases of granulomatous reaction, some isolated cells or small groups were noted. CD68 positive histiocytes were also present in most cases, diffusely intermingled with T lymphocytes, and they were more abundant in granulomatous reactions or cases showing a necrobiotic pattern.

Comments

Persistent reactions to decorative tattoos are a large and heterogeneous group of complications characterised by a variable latency period from tattooing to the beginning of clinical manifestations.[347] In our series, intervals ranged from 2 weeks to 10 years and once established, they were persistent without significant clinical fluctuations. The reason for latency is unknown, but it could be related to the local transformation of ink components or haptenisation, forming neoantigens recognised by immune cells which trigger a cytotoxic response.[37] The exact composition of tattoo stains is not well-known, and spectrophotometry has demonstrated traces of metals in proportions that exceed the usually considered safe limits.[178] Although red is the colour more commonly involved, other dyes may also be implicated, and they represented 50% of our cases.

Clinical-pathological classification is difficult since clinical manifestations are often nonspecific and histologic patterns tend to overlap. It has been proposed[23] that plaque, hyperkeratotic and ulcer-necrotic patterns would be indicative of an allergic reaction, more commonly associated with red colour, in contrast with papular-nodular lesions, usually due to underlying pigment overload in black tattoos. Yet, in our cases, most lesions corresponded to multiple papules in one colour area, sometimes confluent or plaque-forming, not associated with any particular color.

Although sometimes asymptomatic, tattoo reactions are usually referred to as pruritic or even painful. Nevertheless, in our series, pruritus was a complaint found in eight patients and pain in only two, probably indicating the wide spectrum of clinical manifestations and differences in intensity. According to previous reports, all our cases were confined to the tattooed areas of a certain colour, except for two cases, who presented lesions in yellow and black areas, pigments blending during the tattooing process being the most probable explanation. All lesions were limited to one tattoo suggesting a local reaction, inconsistent with the allergic nature usually proposed as their etiology.

We have found interface lichenoid dermatitis as the most usual inflammatory reaction pattern, a common but not constant feature in previous papers.[4579] It has been described as indistinguishable from lichen planus but in our cases, the inflammation extends much deeper, involving the reticular dermis, is more polymorphic and shows perivascular arrangement at least focally, features not present in conventional lichen planus. The interpretation of this interface reaction is not clear: Initially considered allergic,[49] the presence of apoptotic keratinocytes and CD8 predominant response could suggest a cytotoxic mechanism.[7] Only a subset of patients develops adverse reactions involving the same color in other tattoos, which could be expectable if the allergy was the mechanism involved. Moreover, eosinophils are not conspicuous in most cases[47] which is unexpected in allergic cutaneous reactions.

Necrobiotic granulomatosis is rarely reported as a tattoo complication and is most commonly associated with red colour.[410] was prominent in only two patients, one with transepidermal collagen elimination. None showed mucin deposition and were closer to necrobiotic granuloma (NG) than granuloma annulare, (GA). Several similar, but mucin deposits have not always been confirmed, and one case showed simultaneous features of GA and NL.[10] Possibly, this unusual form of tattoo-related reaction could show features intermediate between GA and NL and collagen damage would be related to persistent inflammatory reaction or directly inflicted by tattoo ink sub-products. None of our patients or previously reported cases developed lesions of GA elsewhere.

Pseudoepitheliomatous hyperplasia and keratoacanthomas have rarely been reported as tattoo complications.[25] Five of our cases showed epidermal hyperplasia but not enough to raise the differential diagnosis with epidermal carcinoma. Epidermal atrophy was rarely present and, similar to hyperplasia, seemed to be merely a consequence of dermal inflammation.

In summary, we report a series of patients with late adverse reactions to decorative tattoos. Clinically, lesions were non-specific and interface dermatitis with focal cytotoxic features is the predominant histopathological feature.

Ethics committee approval

Ethics Committee approval reference 2020/302.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.