Radiation recall reaction induced by levofloxacin

Journal of Drugs in Dermatology, Jan, 2008 by Sunghun Cho, Jennifer J. Breedlove, Sean T. Gunning

Abstract

We present a case of a 55-year-old female with breast cancer who developed radiation recall dermatitis (RRD) 3 years later after administration of levofloxacin. A vast majority of cases occur after administration of chemotherapeutic medications; however, a review of literature implicates increasing numbers of nonchemotherapeutic agents and supplements in RRD. Although the pathophysiology of RRD has yet to be elucidated, the implication of more nonchemotherapeutic agents may favor a drug hypersensitivity etiology. To our knowledge, this is the first report of RRD secondary to levofloxacin.

Introduction

Radiation recall dermatitis (RRD) is a rare inflammatory reaction that occurs in a previously irradiated area precipitated by certain drugs. Its clinical presentation may vary from mild erythema to necrosis and ulceration. D'Angio first described this phenomenon in relation to actinomycin D therapy over 40 years ago at the Children's Medical Center in Boston. (1) The vast majority of subsequent reported cases have been associated with the administration of chemotherapeutic medications to include actinomycin D, bleomycin, cytarabine, doxorubicin, daunorubicin, idarubicin, etoposide, hydroxyurea, lomustine, methotrexate, paclitaxel, and vinblastine. (2) Newer reports have implicated capecitabine (3) docetaxel, (4) pemetrexed, (5) and gemcitabine in which localized myositis was seen concomitantly. (6) Only a few reports have associated the radiation recall reaction with nonchemotherapeutic agents to include hypericin (St. John's wort), (7) interferon alfa-2b, (8) simvastatin, (9) anti-tuberculoid drugs, (10) phentermine, (11) tamoxifen, (12) cefazolin, (13) and cefotetan. (14) A recent report has described RRD occurring on the buttock of a woman 3 days following gatifloxacin therapy for an upper respiratory infection. (15) In addition, a radiation recall-like phenomenon has been reported 1 month after a severe sunburn in a woman on ciprofloxacin, piperacillin, tobramycin therapy for pseudomonal pneumonia. (16) We report the first example of a radiation recall reaction secondary to levofloxacin in a patient with breast cancer.

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Case Report

A 55-year-old Caucasian female presented with a 2.7-cm invasive ductal grade 2 carcinoma of the upper outer quadrant of the right breast in April of 1998. The tumor was positive for estrogen and progesterone receptors. The patient underwent a modified radical mastectomy with axillary node dissection. Metastatic carcinoma was found in 1 out of 14 nodes of the breast specimen. The patient underwent immediate reconstruction with a transverse rectus adominus myocutaneous (TRAM) flap. She received 4 cycles of adjuvant chemotherapy including cyclophosphamide and adriamycin with subsequent daily tamoxifen maintenance therapy. After completion of chemotherapy, the patient underwent subsequent radiation therapy to the right breast field. She received a dose of 50 Gy in 25 fractions over a 5-week period and developed brisk erythema and moist desquamation in the entire treated field, which responded to local treatment.

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In February of 1999, the patient underwent right nipple/areolar reconstruction with the use of amoxicillin preoperatively and developed a diffuse morbiliform exanthem postoperatively. The amoxicillin was discontinued with resolution of the exanthem.

In July 2001, the patient underwent TRAM revision with opposing breast reduction. Postoperatively, the patient was placed on levofloxacin 500 mg twice daily for 2 days; additional medications included her maintenance tamoxifen and multivitamins. Two days postrevision, the patient developed an asymptomatic nonindurated, nonscaling erythematous confluent papular exanthem localized to the previous radiation port (Figure 1 and 2). The patient was afebrile with screening laboratories complete blood cell (CBC) count, left frontotransverse (LFT), and basic metabolic panel all within normal limits. Patient denied any additional ultraviolet (UV) exposure within this time frame.

Dermatology was consulted and a clinical diagnosis of a radiation recall reaction was made. Levofloxacin was discontinued and triamcinolone cream was applied to the affected area twice daily. The exanthem resolved in approximately 2 weeks. No drug rechallenge was attempted.

Discussion

Many reports in the literature detail exanthems occurring in areas of either previous radiation exposure (UV and external beam) after the administration of a drug. Some of these reactions may represent specific drug eruptions such as toxic epidermal necrolysis; (17) however, most present as nonspecific inflammation. Different and confusing terms for these reactions have been coined including "UV recall," "sunburn reactivation," "reactivation of solar erythema," "radiosensitization/enhancement reactions," and "radiation recall." A simplification of the terminology relating to ionizing external beam radiation was suggested by Camidge and Price in their review article of RRD. (18) They suggested 2 broad categories to describe these types of reactions: radiosensitization/enhancement and recall. Radiosensitization reactions are defined as occurring within 7 days of radiation exposure. Radiosensitization is thought to be due to the effect of medications that either enhance the initial radiation tissue damage or hinder repair of tissues after exposure. It has not been explicitly stated whether the same time scales apply to UV irradiation. A "UV recall" phenomenon, the most common enhancement reaction seen by a dermatologist, can occur if methotrexate is given within 1 to 5 days following a sunburn.