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In Reply:

Department of Surgery, Brigham and Women's Hospital, Boston, MA

Kelly K. Hunt, Henry M. Kuerer

Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

We appreciate Dr Vargas’ insightful comments. Methylene blue dye may prove to be an effective alternative to isosulfan blue dye for lymphatic mapping in breast cancer; certainly its cost savings would be an additional benefit.

However, injection of methylene blue dye has been associated with severe adverse as well as allergic reactions. As acknowledged by Dr Vargas, localized reactions due to extravasation of this dye include necrosis of cutaneous and subcutaneous tissues and necrotic abscesses.^1-3 Systemic reactions have been reported after intravenous, intra-amniotic, and intrathecal injection. Intravenous injection of methylene blue dye during urologic procedures can result in the development of burning pain and blue macules that may not resolve for several days.⁴ Intravenous injection of methylene blue dye may cause a bluish skin discoloration, which, similar to the use of isosulfan blue dye, can be mistaken for cyanosis.⁵ When injected into amniotic fluid, methylene blue dye may be systemically absorbed also resulting in a bluish skin discoloration and has been associated with development of fetal congenital anomalies.^6-8 Intrathecal injection of methylene blue dye is known to cause spinal cord necrosis.⁹

Most recently, methylene blue dye used to evaluate Fallopian tube patency resulted in generalized blue urticaria requiring steroid therapy.¹⁰ Finally, an immediate life-threatening reaction has also been reported with methylene blue dye when injection into the lumen of the uterus intraoperatively was associated with flash pulmonary edema requiring intubation and admission to the intensive care unit.¹¹

Its clinical utility, availability, and low cost notwithstanding, methylene blue dye must be regarded as a powerful drug with the potential of causing significant and even life-threatening adverse reactions. At this point, the true incidence of allergic reactions associated with the use of methylene blue dye in breast cancer lymphatic mapping is unknown, as this agent is currently used by only a small fraction of surgeons performing this procedure. Thus, the safety profile of this agent must be prospectively investigated in a much larger patient population before methylene blue dye can be readily accepted as a superior and safer alternative to isosulfan blue dye in lymphatic mapping for breast cancer.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Perry PM, Meinhard E: Necrotic subcutaneous abscesses following injections of methylene blue. Br J Clin Pract 28 : 289 -291, 1974[Medline]

2. Ruhlen JL: Tissue necrosis: Cutaneous and subcutaneous damage following extravasation of methylene blue. J Kans Med Soc 83 : 236 -251, 1982[Medline]

3. Stradling B, Aranha G, Gabram S: Adverse skin lesions after methylene blue injections for sentinel lymph node localization. Am J Surg 184 : 350 -352, 2002[CrossRef][Medline]

4. Rainier SS, Quevedo EM, Johnston RV: Dye rashes. Cutis 63 : 103 -106, 1999[Medline]

5. Blass N, Fung D: Dyed but not dead—Methylene blue overdose. Anesthesiology 45 : 458 -459, 1976[CrossRef][Medline]

6. Porat R, Gilbert S, Magilner D: Methylene blue-induced phototoxicity: An unrecognized complication. Pediatrics 97 : 717 -721, 1996[Abstract/Free Full Text]

7. Nicolini U, Monni G: Intestinal obstruction in babies exposed in utero to methylene blue. Lancet 336 : 1258 -1259, 1990

8. van der Pol JG, Wolf H, Boer K, et al: Jejunal atresia related to the use of methylene blue in genetic amniocentesis in twins. Br J Obstet Gynaecol 99 : 141 -143, 1992[Medline]

9. Sharr MM, Weller RO, Brice JG: Spinal cord necrosis after intrathecal injection of methylene blue. J Neurol Neurosurg Psychiatry 41 : 384 -386, 1978[Abstract]

10. Rzymski P, Wozniak J, Opala T, et al: Anaphylactic reaction to methylene blue dye after laparoscopic chromopertubation. Int J Gynaecol Obstet 81 : 71 -72, 2003[CrossRef][Medline]

11. Trikha A, Mohan V, Kashyap L, et al: Pulmonary edema following intrauterine methylene blue injection. Acta Anaesthesiol Scand 40 : 382 -384, 1996[Medline]

Related Correspondence

• Blue Dye of Choice for Lymphatic Mapping
  Hernan I. Vargas
  JCO 2005 23: 3648 [Full Text]

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