Medical Journal of Zambia, Vol. 38, No. 1 (2011)

CASE REPORT Radiation Recall; A Paediatric Case Report From University Teaching Hospital, Lusaka

Caroline Allfrey¹, Cansu Mamurekli¹, Anjali Menon¹, Pauline Sambo², Kennedy Lishimpi³

¹Foundation Year 2 Doctors, United Kingdom ² University Teaching Hospital, Lusaka, Zambia ³ Disease Hospital, Lusaka, Zambia

ABSTRACT cause it (see table 1), the most common being the cytotoxic (, , , and ), the Radiation Recall Dermatitis (RRD) is an acute 1 inflammatory reaction that develops within an area (. ), and . Due to of previous irradiation, occurring after limited evidence and lack of knowledge regarding administering a chemotherapeutic agent. We present aetiology it is not possible to determine which the case of a 3-year-old Zambian girl with a patients will react to which drugs. 'There are no nephroblastoma who developed radiation recall identifiable characteristics of drugs, that cause after the administration of dactinomycin, radiation recall, and thus it must be kept in mind with the use of any drug after radiotherapy including new doxorubicin and . Our case attempts to 4 highlight the importance of this rare condition. drug classes' Given that radiotherapy and have such a close relationship in a multitude of we Table 1 feel it increasingly important to further understand this phenomenon and specifically its associations Drugs Causing Radiation Recall Dermatitis Drug with certain drugs and susceptible individuals. To 5-fluoro uracil the best of our knowledge this is the first Bleomycin Hydroxyurea documented paediatric case of radiation recall from Interferon-á-2b Zambia. Cyclophosphamid e BACKGROUND Dactinomycin Daunarubicin Me thotrexate Doxorubicin Radiation recall dermatitis was first described in Edatrexate Paclitaxel 3 1958 when it was observed with dactinomycin . As Tamoxifen most information comes from case reports pertaining to adults, it is not possible to determine the true incidence or prevalence The three manifestations of radiation recall are: The most frequent site of RRD is the skin but other 1. A mild reaction consisting of erythema, reported involved organs include mucous oedema and dry desquamation membranes, lungs, oesophagus, gastrointestinal 2. A moderate reaction with moist 1 desquamation, vesiculation, blister tract, central nervous system, bladder, and heart . A formation and erosion number of different drugs have been identified to 3. Severe necrotic ulcerative reactions that 1 Corresponding Author could result in skin hypopigmentation Anjali Menon Foundation Year 2 Doctors, United Kingdom Key Words: Radiation Recall Dermatitis, Doxorubicin, Email: [email protected] Dactinomycin

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It has been proposed that the more-severe skin On day eight there was a significant turning point; an reactions, occur more frequently when the period erythematous patch of dry desquamation on the right between radiation and the recall-triggering drug is side of the back was noted correlating with the site of shorter 2. Our patient presented thirty days post radiation. The patient was treated symptomatically radiation and eight days post chemotherapy. with oral steroids and antihistamines. After However radiation recall dermatitis may present consulting the radio-oncologist, a working with a latency period of months to years 3. diagnosis of radiation recall was reached. This was largely due to the specific location (within the irradiated area), timing (after chemotherapy) and CASE PRESENTATION presentation (absence of any other cause or pre- existing skin pathology) of the dermatitis in this A three year old Zambian girl with no significant case. The patch of dry desquamation failed to past medical history and from an affluent respond to treatment and rapidly transformed into an background, presented in April 2011 to the area of ulcerative necrotic tissue. paediatric department at the University Teaching Hospital, Lusaka. She had a ten day history of a right Over the course of the next few weeks, her clinical sided abdominal mass, on a background of reduced state decompensated. She developed overwhelming appetite and non specific weight loss. Ultrasound sepsis secondary to induced by confirmed the presence of a capsulated abdominal chemotherapy and radiotherapy. It was thought by mass and a prompt subsequent intravenous the medical team that the area of was a pyelogram indicated a large right-sided hyperdense possible contributing factor to her sepsis. lesion, approximately 12.5 x 10cm with some mass effect. Unfortunately due to a combination of immunosuppression, sepsis and hepatorenal failure She went on to have an Magnetic Resonance the patient died six months after her initial Imaging (MRI), to establish the aetiology of the presentation. mass. A subsequent Vanillyl Mandelic Acid (VMA) test diagnosed a nephroblastoma, which was later DIFFERENTIAL DIAGNOSIS confirmed histologically. The nephroblastoma chemotherapy protocol was swiftly commenced, ten Radiation recall dermatitis could show clinical days after initial presentation. This consisted of: findings similar to those of acute radiation induced dactinomycin, vincristine and doxyrubicin. She dermatitis 1. tolerated this well and after six cycles a repeat MRI concluded that the mass had reduced in size. A Areas of skin irritation or infection can also become successful right nephrectomy was undertaken six further inflamed during the administration of a weeks after initial presentation. chemotherapeutic agent thereby making it difficult to differentiate between radiation recall dermatitis There were no post operative complications and and acute radiation induced dermatitis, which is three weeks later she was re-commenced on 1 related directly to radiotherapy . chemotherapy solely in the form of vincristine. After a total of ten cycles of chemotherapy, radiotherapy In our case, the initial medical report indicates that was commenced and finished three weeks later. The the patient had no skin abnormalities prior to subsequent second phase of chemotherapy began commencing radiotherapy. She presented with with the re-administration of all three original features of a mild radiation enhancement reaction, cytotoxic agents. crucially eight days post adjuvant chemotherapy. Both the location of the dermatitis and the natural Three days later she presented with fever, reduced history of when it occurred is in keeping with a appetite and drowsiness. Broad spectrum antibiotics diagnosis of radiation recall. were administered as a precautionary measure. Despite this, her clinical state was such that Camidge and Price have further defined the clinical chemotherapy was able to continue. entity and have made a clear separation between

29 Medical Journal of Zambia, Vol. 38, No. 1 (2011) radiation induced dermatitis and radiation recall administration of TAC chemotherapy, the irradiated dermatitis. They suggest designating any reaction skin started to show an erythema with a purplish occurring within seven days after administration of aspect. Since the indication of adjuvant drugs as sensitisation and not as radiation recall chemotherapy was considered to be crucial, she was dermatitis 2. In our case the interval was eight days encouraged to continue without doxorubicin. On post chemotherapy and thirty days post day 22 the second chemotherapy course was radiotherapy. This can, by the above definition, be administered consisting of TC and the skin reaction called radiation recall dermatitis. Although the did not re-occur. Subsequent courses could be interval of eight days can be considered relatively administered without reappearance of the recall 5 short, much longer intervals of up to 25 years have phenomena . been described 6. Despite the fact that the first documented case of TREATMENT radiation recall involved dactinomycin we were unable to find any current evidence to support how There are no proven interventions to relieve strong this link is. The same can be said with regards symptoms or to enhance recuperation. Once the to vincristine. radiation recall dermatitis has occurred almost all reports advice to discontinue the triggering drug 2. It is difficult to appreciate the total contribution that However, a re-challenge does not always result in the radiation recall dermatitis made in the days 2 leading up to this patient's death. It was clear that the occurrence of the skin reactions . severe sepsis was the major contributing factor to mortality. However, we were unable to establish the DISCUSSION exact site of this or a specific causative organism. We believe however that regardless of its direct role Dactinomycin and doxorubicin were the most likely in this patient's mortality, the diagnosis of radiation agents to have caused the radiation recall in our case recall should not be underplayed. 5. From literature that was reviewed we found no other reported cases involving dactinomycin, CONCLUSION doxorubicin and vincristine in the same treatment regime causing radiation recall. Most reports of In Zambia, dactinomycin, doxorubicin and radiation recall are in response to administration of a vincristine are commonly used in the treatment of single chemotherapeutic agent. However, there is no nephroblastoma. It would therefore be pertinent that evidence to suggest that combination chemotherapy physicians treating patients with these drugs need to either increases or decreases the risk of radiation 2 be aware of the potential of radiation recall recall compared with monotherapy . dermatitis so as to aid early diagnosis and initiate appropriate management. The sporadic and Approximately fifteen cases of doxorubicin induced unpredictable nature of this condition makes radiation recall dermatitis have been cited 7. One management challenging. More research in this area such case demonstrates quite clearly the crucial needs to be carried out to better recognise relationship between radiotherapy and the susceptible individuals thereby preventing this administration of the offending chemotherapeutic reaction. agent: INFORMED CONSENT A 44 year old female patient with a large grade three Obtained from parents infiltrating ductal carcinoma and local metastases commenced treatment for breast cancer. Six weeks COMPETING INTEREST after breast conserving surgery she was irradiated None to the left breast, axilla and internal mammary chain. Exactly fourteen days after completion of ACKNOWLEDGEMENTS radiotherapy she started her adjuvant chemotherapy; taxotere, doxorubicin and Many thanks to the patient's family for their (TAC). On day four after patience and support.

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REFERENCES 5. R.L.M. Haas1*, G. de Klerk2; An illustrated case of doxorubicin-induced recall dermatitis 1. Martin D Abeloff, James O Armitage, Michael B and a review of the literature. The Netherlands Kastan, John E Niederhuber, W Gillies journal of medicine. McKenner. Clinical Oncology 2004 3rd Edition. 6. Christian Spirig, Aurelius Omlin, Giannicola 2. Camidge R, Price A. Characterizing the D'Addario, Klaus-Dieter Loske, Philipp phenomenon of radiation recall dermatitis. Esenwein, Jan H Geismar and Thomas Radiother Oncol. 2001;59:237–45. Ruhstaller; Radiation recall dermatitis with soft 3. Muffaddal Morkas, Donald Fleming, Michael tissue necrosis following : a Hahl. Case 2. Radiation recall associated with case report. Journal of Medical Case Reports docetaxel. Journal of Clinical Oncology. 2009, 3:93 doi:10.1186/1752-1947-3-93. 2002.20: 867-869. 7. Ovid online: http://gateway.ovid.com/autologin.cgi 4. Burris H.A., Hurtig J. Radiation recall with anticancer agents. Oncologist. 2010; 15 (11) 1227-1237.

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