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Painless skin erythema in a patient with a chemoport: Anthracycline therapy extravasation presenting with skin necrosis

N Suvorava MDa, C Pena MDa, J Riaz MDb, F Hardwicke MDc

Correspondence to Natallia Suvorava MD. 
Email: Natallia.suvorava@ttuhsc.edu

+ Author Affiliation - Author Affiliation
a residents in Internal Medicine at TTUHSC in Lubbock, TX
b a fellow in medical oncology at TTUHSC in Lubbock, TX
c a faculty member in the Division of Hematology and Oncology at TTUHSC in Lubbock, TX

SWRCCC 2014;2(7):29-32  
doi:10.12746/swrccc2014.0207.088

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Case

A 67-year-old Hispanic woman was admitted to the hospital with newly diagnosed diffuse large B cell lymphoma. The patient underwent right internal jugular port placement and was started on R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone). Her nurse reported that the port was flushing nicely but not drawing blood. She was asked to start chemotherapy as long as the port was flushing. The patient was discharged home next day after finishing her first cycle of chemotherapy. On the day of discharge patient had some redness around the port site possibly secondary to the surgical incision but didn’t complain of any pain or discomfort in that area.

She presented to the ER three days after discharge with redness, swelling, and desquamation of the skin on her right chest and breast along with pain (Figure 1). A CT of the chest showed marked inflammation of the right chest wall and probable mastitis and abscess formation in the right breast. There were no inflammatory changes around the port. She was diagnosed with chemical burn secondary to extravasation of chemotherapy (doxorubicin hydrochloride) and was taken to the OR for extensive debridement, right mastectomy, and port removal (Figure 2). Post operatively she received wound care and antibiotics and was discharged to a LTAC with a wound-vac and plans for a possible skin graft at a later date. She was readmitted twice within the next two months for the surgical site abscess and persistent infection with Pseudomonas aeruginosa.


fig1

Figure1


fig2

Figure2:


Discussion

Extravasation is leakage of any liquid (fluid or drug) into the perivascular or subcutaneous space. It is one of the most dreaded complications of chemotherapy due to the potential for severe tissue destruction, long term complications, and morbidity.1 Extra- vasation injuries accounts for 0.5% - 6% of adverse effects related to chemotherapy2 with an annual incidence is of 0.1% - 0.7%.3 In 2012 the European Society for Medical Oncology released clinical guidelines for management of chemotherapy extravasation using a simplified scheme for management, prevention, and classification. Chemotherapy medications can be classified according to their ability to cause local damage after extravasation as blistering agents, as non-blistering agents, and as irritants (Table 1).Vesicants are defined as chemicals causing blister formation of the skin and/or mucous membranes; irritants are drugs, not associated with blistering, that cause local inflammation or irritation. There are two mechanisms proposed for vesicant tissue damage. One involves damage to DNA with polymerase activation and depletion of NAD+ that lead to inhibition of glycolysis and cleavage of the fibrils which connect the basal epidermal cells to the basement membrane by the cellular proteases. The other mechanism involves direct damage to the tissues due to local depletion of glutathione and subsequent damage from free radicals.4

Blistering

Irritants

Non-Blistering

DNA-Binding Compounds

Alkylating agents

• Ifosfamide

Arsenic trioxide

Alkylating agents

• Mechloretamine

Anthracyclines

• Liposomal class

Asparaginase

Anthracyclines

• Doxorubicin
• Danorubicin

Topoisomerase II inh.

Bleomycin

Dactinomycin

5-FU

Fludarabine

Non-DNA-Binding

Platin salts

Interferons

Vinka Alkaloids

Topoisomerase I inh.

Monoclonal antibodies

Taxanes

 

Cyclophosphamide


The risks for chemotherapy extravasation can be either patient or infusion related.1,2,5,6 For example, a small, frail vein with an unfavorable cannulation site which is running a bolus injection in a morbidly obese patient will have a high risk for extravasation. In the event of an extravasation, the general consensus for treatment is a step by step approach to diminish acute injury and to prevent further morbidity. No randomized trials on the treatment of extravasation have been carried due to ethical reasons. But regardless of the chemotherapy drug, early initiation of treatment is considered mandatory, and infusion personnel need training to manage these adverse events.1,2,6,7

First, it is important to stop the infusion and try to aspirate as much drug as possible. It is mandatory to identify the leaked agent. Second, remove the cannula but avoid exerting any manual pressure over the extravasated area.6 After the chemotherapeutic agent is identified and classified as either non-blistering or blistering/irritant, the next steps are clear. If it is a non-vesicant (non-blistering agent) local management, such as dry cold compresses, should be adequate. But if the extravasated agent is identified as a vesicant, the management will be drug specific and more difficult(Figure 3).1,2,6,8 Finally, the use of corticosteroids is uncertain. A single-arm clinical study in 53 patients with extravasations due to different drugs showed that multiple subcutaneous injections of hydrocortisone followed by topical betamethasone prevented tissue necrosis or sloughing necessitating surgical treatment. However, in a retrospective series of 175 cases of extravasation, up to 46% patients receiving intralesion corticosteroids needed surgical debridement. In contrast only 13% of those without corticosteroid treatment needed surgery, suggesting a deleterious effect of these agents. Therefore, subcutaneous corticosteroids are not recommended.6

References

  1. Harrold K, Gould D, Drey N. The efficacy of saline washout technique in the management of exfoliant and vesicant chemotherapy extravasation: a historical case series report. Eur J Cancer Care (Engl) 2013; 22(2):169-78.
  2. Goolsby TV, Lombardo FA. Extravasation of chemotherapeutic agents: prevention and treatment. Semin Oncol 2006; 33(1):139-43.
  3. Hahn JC, Shafritz AB. Chemotherapy extravasation injuries. J Hand Surg Am 2012; 37(2):360-2.
  4. Barbee MS, Owonikoko TK, Harvey RD. Taxanes: vesicants, irritants, or just irritating? Ther Adv Med Oncol 2014; 6: 16–20, DOI: 10.1177/ 1758834013510546.
  5. Langer SW. Extravasation of chemotherapy. Curr Onc Rep 2010 Jul; 12(4):242-6.
  6. Perez Fidalgo J A, Garcia Fabregat L, Cervantes A, et al. Management of chemotherapy extravasation: ESMO-EONS clinical practice guidelines. Ann Oncol 2012; 23 Suppl 7:vii167-73.
  7. Perez-Fidalgo JA, Cervante A. Reply to “comment on: management of chemotherapy extravasation: ESMO-EONS clinical practice guidelines”. Ann Oncol 2013; 24(4):1129-30.
  8. Schulmeister L, Pollack CV Jr. Images in emergency medicine. Swollen hand. Anthracycline chemotherapy extravasation. Ann Emerg Med. 2011; 57(4): 417,422.

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Received: 05/21/2014
Accepted: 06/25/2014
Reviewers: Kenneth Nugent MD
Published electronically: 07/15/2014
Conflict of Interest Disclosures: none

 

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