Radiation recall dermatitis: case report and review of the literature.

"Radiation recall"-also called "radiation recall dermatitis"-has been defined as the "recalling" by skin of previous radiation exposure in response to the administration of certain response-inducing drugs. Although the phenomenon is relatively well known in the medical world, an exact cause has not been documented. Here, we report a rare occurrence of the radiation recall phenomenon in a breast cancer patient after palliative radiotherapy for bone, brain, and orbital metastases.


HISTORY
A 55-year-old woman was diagnosed with breast adenocarcinoma in August 2006.In late September, she complained of back pain and slight numbness.A bone scan revealed a mild increase in activity in the thoracic spine and the proximal fourth and anterior sixth ribs.Magnetic resonance imaging (MRI) of the spine confirmed metastatic involvement in the tenth thoracic vertebra.The patient received radiotherapy with 20 Gy in 5 fractions in October 2006.She tolerated the treatment very well with complete pain relief.
The woman returned to her medical oncologist for systemic therapy.A combination of paclitaxel (175 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) was commenced in November 2006.After receiving a single dose, the patient complained of double vision.A computed tomography examination confirmed left orbital metastases (Figure 1) and multiple intraparenchymal brain metastases in the left frontal lobe and left cerebellum.The woman was treated with wholebrain radiotherapy (WBRT), including the left orbit, which received a dose of 20 Gy in 5 fractions.The initial chemotherapy treatment took place 13 days Ten days after completion of the WBRT, the patient received her second dose of paclitaxel and gemcitabine.Within 2 days, the patient detected discoloured and inflamed skin limited to the region that had previously been irradiated.She also experienced swelling in the left ear, muffled hearing, and discomfort in the eyes as a result of the reaction.Surprisingly, increased pigmentation also occurred in the area of the thoracic bone metastases treated with palliative radiotherapy approximately 7 weeks earlier.Silver sulphadiazine cream and hydrocortisone eardrops were prescribed to treat external symptoms.All chemotherapy was put on hold.
Approximately 4 weeks after development of the skin reaction, the patient developed new cervical nodes compatible with clinical progression of her breast cancer.Once the external skin reaction had improved significantly, with only mild discolouration remaining, chemotherapy was resumed.At this time, nearly 6 weeks had passed since the appearance of the radiation recall dermatitis (RRD).A chemotherapy regimen of cyclophosphamide (600 mg/m 2 ), epirubicin (100 mg/m 2 ), and 5-fluorouracil (600 mg/m 2 ) replaced the paclitaxel and gemcitabine.Dexamethasone (Decadron: Merck, Whitehouse Station, NJ, U.S.A) was administered at 20 mg before the first chemotherapy treatment and at 10 mg before each subsequent treatment.No adverse reactions have occurred since.At follow-up, the patient's double vision had improved, and a computed tomography scan revealed a stable appearance in the orbital metastases.New MRI examination of the brain, orbits, and spine revealed no demyelination corresponding to the areas affected by the RRD reaction.

DISCUSSION
"Radiation recall"-also called RRD-is defined as the "recalling" by skin of previous radiation exposure in response to the administration of certain responseinducing drugs 1 .In the medical world, the RRD phenomenon has been termed anything from "moderately rare" to "moderately common."No exact cause or incidence has been documented 2 .
D'Angio and colleagues originally documented RRD in 1959 3 ; the trigger for the abnormal reaction was dactinomycin 1 .Cytotoxics are common instigators 1 .Some medications have been documented to be more commonly involved with RRD: docetaxel, doxorubicin, gemcitabine, and paclitaxel (Tables I  and II).Although the association is only a loose one, Camidge and Price proposed that more-severe skin reactions are more common when the period between radiation and the recall-triggering drug is smaller 1 .According to Putnik et al. 60 , the median time between the conclusion of radiation treatment and the materialization of RRD is 39 days.In the present case, materialization of the RRD occurred within 2 days.
Although the precise mechanism of action for RRD is not known, several mechanisms that may, or may not, lead to the development of radiation recall have been proposed.These mechanisms include changes in vascularization, DNA repair, radiation-impaired epithelial function of stem cells, and increased sensitivity to drugs 1 .Corticosteroids have been suggested to have some protective effects 61 .We found that steroids are commonly used in the treatment of external symptoms and with the intention of preventing recurrent reactions during subsequent chemotherapy administration 23,25,26,30,32,33,39,40,43,45,46,50,53,55,59,60 .
Although RRD is a rare phenomenon, it poses a significant barrier to treatment for patients.The condition creates a paradox: patients and clinicians alike wish to proceed with the most desirable treatment in the given circumstances, but are unable to do so because of the rare skin reaction.The present report serves as a reminder to palliative health care professionals of the possible danger of a recall reaction if an insufficient period has passed between radiotherapy and commencement of a potential recallinducing drug.

FIGURE 1 Retrobulbar metastasis, axial, and coronal computed tomography images with contrast. (A) Axial view of the inferior orbits demonstrates enhancing abnormal soft tissue posterior and lateral to the left globe (arrow). (B) Axial view of the upper orbits demonstrates enhancing abnormal soft tissue in the medial left orbit inseparable from the medial rectus muscle (arrow). (C) Coronal view demonstrates abnormal soft tissue in the medial left orbit inseparable from the medial rectus (arrow) and in the lateral inferior left orbit inseparable from the inferior rectus and in contact with the optic nerve (arrowhead).
report and review of the literature A.E. Hird BSc(C),* J. Wilson MD, † S. Symons MD, ‡ E. Sinclair MRTT,* M. Davis RN,* and E. Chow MBBS* before the commencement of the WBRT.No adverse reactions were observed immediately after the radiation treatment.