The Oncologist, Vol. 11, No. 10, 1118-1120, November 2006; doi:10.1634/theoncologist.11-10-1118
© 2006 AlphaMed Press
Radiation Recall Dermatitis with Cefotetan: A Case Study
Ayodele Ayoolaa,b,
Young Joo Leeb
a Department of Medicine, Franklin Square Hospital Center, Baltimore, Maryland, USA;
b Department of Medicine, Hematology & Oncology Section, Harbor Hospital Center, Baltimore, Maryland, USA
Key Words. Dermatitis • Radiation-induced • Rash • Cefotetan disodium
Correspondence: Ayodele Ayoola, M.D., Department of Medicine, Franklin Square Hospital Center, 9000 Franklin Square Drive, Baltimore, Maryland 21237, USA. Telephone: 443-983-7101; Fax: 410-833-4022; e-mail: ayodeleayoola{at}hotmail.com
Received June 5, 2006;
accepted for publication September 13, 2006.
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ABSTRACT
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Radiation recall dermatitis (RRD) is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration. This phenomenon may occur from days to years following exposure to ionizing radiation. The case of a 54-year-old Caucasian woman who was initially treated with external-beam radiation to the right thoracic region following the diagnosis of a poorly differentiated squamous cell carcinoma of the right lung is reported. She received four cycles of consolidated chemotherapy with docetaxel and carboplatin. Four months later, she was admitted to the hospital for acute cholecystitis and was placed on cefotetan. She developed a tender, erythematous rash on the posterior region of her right thorax 48 hours later. The drug was withdrawn, supportive care was instituted, and the patient subsequently improved. RRD should be suspected in patients who develop an erythematous rash in a previously irradiated region. To our knowledge this entity has not been associated with cefotetan previously.
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INTRODUCTION
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Radiation recall dermatitis (RRD) is defined as an inflammatory skin reaction in a previously irradiated body part subsequent to drug administration. This may occur from days to years after exposure to ionizing radiation [1]. This entity is associated with chemotherapy and was originally described with the use of actinomycin [2]. Other antineoplastic drugs have been implicated in the development of RRD. These include the plant alkaloids, docetaxel [3–5], anthracyclines, bleomycin, and alkylating agents including carboplatin [3]. Antiestrogen drugs [6], simvastatin [7], interferon-
2b [8], anti-tuberculous drugs [9], and ultraviolet radiation [10] have also been implicated. While mainly associated with the skin, radiation recall reactions can affect other sites, such as the bowel, esophagus [11], lungs [3], and vaginal mucosa [12].
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CASE REPORT
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A 54-year-old woman was diagnosed with stage III poorly differentiated squamous cell carcinoma of the right lung. She was treated with external-beam radiation to the right thorax and mediastinum. She received 3,960 cGy at 180 cGy per fraction through anterior and posterior opposed fields. This was followed with an additional 2,520 cGy through off cord oblique fields to bring the total dose to 6,480 cGy. Mixed6/15MV photons were used. The skin doses at depths of 2 mm and 5 mm were 4,824 cGy and 5,605 cGy, respectively. The patient also received weekly chemotherapy with docetaxel and carboplatin at 20 mg/m2 and an area under the concentration–time curve of 2, respectively, and completed 4 months prior to this hospitalization.
This patient was admitted to the hospital with acute cholecystitis. At the time of admission her medications included zolpidem, acetaminophen, and albuterol.
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HOSPITAL COURSE
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Upon admission, she received famotidine, hydromorphone, and cefotetan. The patient also received platelet transfusion, steroids, i.v. immunoglobulin, and HLA-matched platelets in succession for the thrombocytopenia. On the third day of her hospital stay, she developed severe pain in the right scapular region, which she graded as 10/10 and burning in nature. It was sudden in onset and constant with no radiation. The pain was aggravated even with the light touch of a hospital garment. On examination, the right scapular region was erythematous, minimally edematous, nonfluctuant, desquamated, and severely tender (Fig. 1
). The pain was not alleviated despite escalating doses of morphine. Subsequently, RRD was suspected, and the cefotetan was felt to be the causative agent and was subsequently discontinued. The tenderness, redness, and swelling began to resolve within 2 days and the patient was completely free of pain 4 days after the discontinuation of the antibiotics.
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DISCUSSION
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The incidence of RRD is unknown; however, a few retrospective studies have reported a range of 13%–49% [13, 14]. RRD is reported to occur on first exposure to a specific trigger drug [1], but may follow presensitizing episodes in which a drug is administered several times before eliciting RRD [4, 15, 16].
This recall phenomenon can occur from months to years following the conclusion of radiation therapy. The longest interval was reported with doxorubicin-induced stomatitis, which occurred 15 years after radiotherapy treatment of a palatal sarcoma [17]. RRD occurred in our patient 4 months after the completion of radiotherapy. The relationship between the period of time from radiation to medication exposure and the severity of dermatitis is unclear. It is postulated that the recall seems to be most severe when the duration between the radiotherapy and drug exposure is short [2]. It is also unclear whether the agents carboplatin and docetaxel, which did not cause recall phenomenon in this patient, added to or augmented the reaction by the antibiotic months later.
There does not appear to be a minimum dose, nor an established radiotherapy dose relationship in order for RRD to occur [1]. Several authors have suggested radiation doses associated with RRD in the range of 1,000–8,100 cGy [18, 19]. The patient reported here received a tumor dose of 6,480 cGy, and because of the skin-sparing effects, the skin dose of the affected tissue was calculated to be lower—an effect that is related to linear accelerator energy. Typically, cases described in the literature report radiation dosing to the tumor, and not to the skin. Yeo et al. [4] observed that the recall reaction was highest where skin doses were in the range of 1,680–1,870 cGy. Drugs administered by the i.v. route usually produce RRD more rapidly than oral agents. The time to resolution of this dermatitis also differs by the route of administration, with the i.v. route resolving within weeks, while the oral route may last for several months [6]. The discrepancy may be a result of the different pharmacokinetics of the medications administered by different routes.
Garza et al. [20] reported a case of photosensitive recall with the use of cefazolin, while Krishnan et al. [21] reported cases following the use of ciprofloxacin, tobramycin, and piperacillin. To the best of our knowledge, there has been no reported case of RRD in association with cefotetan in the literature. Chemotherapeutic agents are well described as causing RRD, but antibiotics are increasingly associated with this phenomenon. Because of the temporal relationship between the administration of the antibiotic and the onset of the skin reaction, together with the resolution following discontinuation, cefotetan was felt to be the responsible agent. The fact that the skin inflammation was localized to the radiation field would make other diagnoses unlikely.
The pathogenesis of this phenomenon is unclear. The fact that noncytotoxic drugs are associated with RRD led Camidgeetal. [22] to speculate that it may represent an idiosyncratic drug hypersensitivity reaction. It has also been suggested that the "trauma" of previous irradiation sensitizes an area of the skin into manifesting immune reactions with little or no overt systemic activation, in a way similar to the Koebner phenomenon [22].
Discontinuation of the offending drug has been the mainstay of therapy. Oral dexamethasone and dipheny-hydramine [15], or topical hydrocortisone [16], have been used with success, leading to resolution within 7–10 days. Other case reports noted resolution in the same time frame without the use of antihistamines or steroids [4, 7, 14, 23]. In our patient, complete resolution occurred within 7 days.
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CONCLUSION
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RRD should be suspected in a patient who develops an erythematous rash in a previously irradiated region following the use of cefotetan. Prompt recognition and withdrawal are essential for resolution with minimal morbidity.
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DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
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Y.J.L. has acted as a consultant for Genentech and Eli-Lilly.
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ACKNOWLEDGMENT
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I wish to express my gratitude to Dr. Anna Maria Izquierdo for her encouragement and constructive criticisms of this work. Editing of the manuscript by my program director, Dr. Frederick Williams, is very much appreciated.
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Abstract
Introduction
