The increasing popularity of tattooing has paralleled an increase in associated cutaneous reactions. Red ink is notorious for eliciting cutaneous reactions. A common reaction is pseudoepitheliomatous hyperplasia (PEH), which is a benign condition closely simulating squamous cell carcinoma (SCC). Differentiating PEH from SCC is challenging for pathologists and clinicians alike. The exact pathogenesis of these lesions secondary to red ink is not known, and there are no sources outlining diagnostic and treatment options and their efficacy. We present four study cases with different pathologies associated to red ink tattoos including lichenoid reaction, granulomatous reaction, PEH, and an SCC. Additionally, an extensive review of 63 articles was performed to investigate pathogenesis, diagnostic approaches, and treatment options. Hypotheses surrounding pathogenesis include but are not limited to the carcinogenic components of pigments, their reaction with UV and the traumatic process of tattooing. Pathogenesis seems to be multifactorial. Full-thickness biopsies with follow-up is the recommended diagnostic approach. There is no evidence of a single universally successful treatment for PEH. Low-dose steroids are usually tried following a step up in lack of clinical response. For SCC lesions, full surgical excision is widely used. A focus on clinicians’ awareness of adverse reactions is key for prevention. Regulation of the unmonitored tattoo industry remains an ongoing problem.
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