The enhanced use of exogenous substances for cosmetic and reconstructive procedures is paralleled by an increase in reports of cutaneous adverse reactions to several of these agents. Recognition of the histological features of these reactions is of importance to both dermatologists and dermatopathologists but is not always easy for several reasons. First, cost-related issues are resulting in an increasing number of these procedures being performed overseas. Thus, patients are often unsure about the exact product used. Compounding this is the fact that practitioners who perform these procedures are not forthright in divulging this information, given that improper substances may be admixed in the filler injected. Furthermore, cutaneous reactions may occur at sites distant from injected sites, secondary to migration of the filler substance and a lapse of months to years may occur prior to the development of a cutaneous reaction. Thus, a causal relationship between the procedure and the reaction is often not made. We present an overview of the histological features of adverse reactions to currently available soft tissue fillers, both in the United States and overseas, in an attempt to enhance awareness of the diversity of these reactions.

The patient, a 70-year-old woman with type 2 diabetes mellitus and rheumatoid factor2positive (130 KIU/liter) erosive nodular rheumatoid arthritis, presented with a 4-week history of painful superficial erosions and ulcers involving the lower lip (A), left submammary crease (B), and left inguinal area extending to the proximal thigh (C). Her medications included methotrexate (MTX) 20 mg/week (total duration of treatment 6 months; dosage increased from 15 mg/week 3 months prior), hydroxychloroquine 400 mg/day, folic acid 10 mg/week, and aspirin 80 mg/day. There was no history of exposure to antibiotics, diuretics, or other nonsteroidal antiinflammatory drugs (NSAIDs). Laboratory studies revealed the following: creatinine 91 mmoles/liter (pre-MTX 55 mmoles/liter), albumin 34 gm/liter, white blood cell count 4.70 3 10 9 /liter, hemoglobin 82 gm/liter (pre-MTX 130 gm/liter), mean corpuscular volume 98.5 fL, platelet count 427 3 10 9 /liter, alanine aminotransferase 17 units/liter, aspartate aminotransferase 19 units/liter, serum MTX ,0.06 mmoles/liter, and vitamin B 12 74 pmoles/liter. MTX-induced cutaneous erosion/ulceration was suspected, and this drug was stopped. Leucovorin and B 12 treatment were prescribed. Pathologic examination of the skin showed hyperplastic epidermal changes with mild dermal chronic inflammation, fibrosis, and vascular telangiectasia. One week after MTX discontinuation the skin lesions had resolved (D2F). MTX-induced erosions in patients without a history of psoriasis are rare (1). Reported predisposing factors include initiation/increase or restarting MTX treatment, renal impairment, NSAID intake, age .55 years, folate deficiency, low serum albumin level, and drug interactions (e.g. with trimethoprim/sulfamethoxazole) (2). Psoriatic plaque erosions as a side effect of low-dose MTX are an indicator of impending life-threatening pancytopenia; thus, rapid discontinuation of this drug is critical (3).1. Kurian A, Haber R. Methotrexate-induced cutaneous ulcers in a nonpsoriatic patient: case report and review of the literature. J Cutan Med Surg 2011;15: 275-9. 2. Shiver MB, Hall LA, Conner KB, Brown GE, Cheung WL, Wirges ML. Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity. Dermatol Online J 2014;20(7). 3. Jariwala P, Kumar V, Kothari K, Thakkar S, Umrigar DD. Acute methotrexate toxicity: a fatal condition in two cases of psoriasis.

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