Paclitaxel-induced Neutrophilic Adverse Reaction and Acral Erythema

Abstract

Paclitaxel, a microtubule-stabilizing anti-neoplastic agent that belongs to the family of taxanes, is used in the treatment of advanced and/or refractory lung, breast, head, neck and other epithelial cancers. Site-specific reactions, such as inflammation at injection sites or cellulitis after extravasation ( 1 ), have been reported. Adverse cutaneous reactions associated with paclitaxel treatment include bullous fixed drug eruption (2), erythema multiforme (3), pustular eruption (4), scleroderma-like cutaneous lesions (5), onycholysis (6), and acral erythema (one case) (7). Of note, acral erythema (erythrodysesthesia) has been reported with multi-drug chemotherapy protocols that included paclitaxel (8,9). We report here the first case of paclitaxel-induced neutrophilic adverse reaction with concomitant acral erythema, and highlight the mechanisms that may be involved. CASE REPORTA 77-year-old Caucasian woman undergoing chemotherapy for breast cancer presented with mildly sensitive skin lesions on the dorsal hands and painful lesions on the lower extremities. She had been treated with weekly intravenous paclitaxel for 3 months, and the skin lesions were noticed after the second cycle of the drug, flared after each subsequent dose of the medication. There was no history of fever or other systemic symptoms, and no prior trauma to the extremities. The treatment protocol involved premedication with diphenhydramine and ranitidine 3 h prior to receiving paclitaxel. Other medications during this period were alendronate sodium, levothyroxine, vitamin D and aspirin. The patient had been taking these medications for several years prior to paclitaxel exposure and continued taking them after the skin lesions resolved. Physical examination revealed erythematous, mildly edematous, tender papules and plaques on the dorsal hands ( Fig. la), palms, dorsal feet and soles, as well as multiple, tender, erythematous, dusky red or violaceous papules and plaques symmetrically on the lower extremities (Fig. lb).Biopsy specimens from the left leg demonstrated hyperkeratosis, acanthosis, spongiosis, dyskeratosis with occasional satellite cell necrosis, and a moderately dense predominantly neutrophilic infiltrate (Fig. 2). Stains for microorganisms (Gram and Giemsa) were negative. Complete blood cell count and differential, urinalysis, electrolytes, liver function tests, serum protein electrophoresis, hepatitis sérologies and autoantibody profile (antinuclear, SSA, SSB and anti-neutrophic cytoplasmic antibodies) were within normal limits. Treatment with clobetasol 0.05% cream was not helpful. The lesions on the legs resolved spontaneously over the course of several weeks after the last cycle of paclitaxel.

Hand–foot syndrome caused by docetaxel with no recurrence after switch to paclitaxel, a different taxane

“…8 To date, only two cases of HFS due to paclitaxel have been described. 11 Our experience confirms the hypothesis that HFS development may be molecule-associated; in fact, changing the therapy from docetaxel to a different taxane (paclitaxel) did not lead to disease recurrence. A possible explanation of this phenomenon may be the greater intracellular retention of docetaxel as compared with paclitaxel with consequent major skin toxicity.…”

Management of Paclitaxel-Induced Hand-Foot Syndrome

“…The patient refused further chemotherapy. The 3 rd case report of acral erythema associated with paclitaxel was reported by Cruz et al in 2010 [6]. The symptoms started after the 2nd week of drug administration, after which paclitaxel was discontinued.…”

“…Examples of such events include mucositis, onycholysis, radiation recall dermatitis, erythema multiforme, pustular eruptions, and scleroderma-like changes [6,9]. One uncommon cutaneous manifestation of paclitaxel is HFS of which only 5 cases have been reported in the literature.…”

“…Like many other antineoplastic drugs, they have various toxicities that include myelosupression, neuropathies, and mucocutaneous manifestations [2]. Although docetaxel, a widely used taxane chemotherapeutic agent, has been linked to palmoplantar dysesthesia in clinical trials, clinical practice, and many case reports [3,4,5], such an association has not been as frequently established with paclitaxel, except in 3 reported cases and in 1 prospective study [2,3,6,7]. When HFS is diagnosed, physicians usually discontinue the offending agent, and the syndrome starts to resolve slowly, with residual skin pigmentation in some cases [2,8,9,10,11].…”

Preparation of anti-HER2 monoclonal antibody-paclitaxel immunoconjugate and its biological evaluation

“…Paclitaxel (TAX) is an outstanding anti-cancer drug for the treatment of ovarian cancer, and plays important roles in interrupting the cell cycle and promoting apoptosis of ovarian cancer cells. Notwithstanding its wide spectrum of antitumor activity, TAX is non-specific and acts on almost all the intracellular microtubule systems in body, which limits its therapeutic application owing to many severe adverse effects it causes, such as bone marrow suppression, cardiac toxicity, allergic reaction, and so on [10][11][12] . For this reason, increasing the specificity and reducing the adverse effects of TAX have become a matter of urgency in the filed of anti-cancer drug research.…”