Citric Acid Treatment of Refractory Chronic Postmastectomy Raw Area During Chemotherapy: A Novel Approach

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Wounds or raw areas that occur at a sutured site are a major postoperative complication. Superficial tissue ischemia and wound tension contribute to tissue loss, wound gap, and surgical site infection. The management of suture wounds focuses on control of any nidus of infection as well as local debridement to prepare the wound bed for secondary suturing or reconstruction as needed. Malnutrition, anemia, uncontrolled comorbidities (eg, diabetes, malignancy, leprosy), and certain drugs (immunosuppressive agents and antiproliferative chemotherapeutic agents) hamper the process of wound healing and appropriate wound bed preparation. Sutured wounds need a prolonged duration of dressings and systemic management. The need for repeated hospital visits adds to the cost of care.

The current study reports the use of a simple, yet effective, novel treatment option for refractory chronic postoperative raw area in a surgical case of breast carcinoma.

A 60-year-old female with left breast carcinoma (T3N1M0) underwent an uneventful modified radical mastectomy. On the 5th POD, minimal superficial marginal necrosis at the suture line was noticed, which progressed in size to 2 cm on each side of the suture line and 10 cm in length (ie, overall area of 4 cm × 10 cm) over the next 2 days. Because the necrosis was superficial and dry, nonsurgical management was attempted. By the 12th POD, the superficial scabs had peeled off, leaving a patch of deeper necrosis on only the lateral aspect of the wound (Figure 1A). A frank wound gap was noted on the 15th POD. The wound was locally debrided. The pus culture was sterile; thus, it was decided to continue with daily dressing changes until the wound improved.

The medical oncologist had cleared the patient to start adjuvant chemotherapy. However, the patient was lost to follow-up and returned 3 days before her 3rd chemotherapy cycle. The first 2 chemotherapy cycles were very well tolerated. At the time of presentation prior to the 3rd chemotherapy cycle, the locoregional examination was normal except for the raw area measuring 10 cm × 4 cm on the left chest wall (Figure 1B). The patient said that the wound size had remained the same over the past 2 months despite daily dressing changes. Re-culture of pus from the wound was sterile. The wound was thoroughly cleaned (Figure 1C). The plastic surgeon had advised excision of the raw area with reconstruction using a latissimus dorsi myocutaneous flap, after the upcoming chemotherapy cycle. To avoid a large gap in the patient’s chemotherapy cycles, the authors of the current manuscript planned the intervention 2 weeks after her current cycle.

Based on the authors’ past experiences, daily application of citric acid was advised to promote a favorable wound bed during this waiting period. The benefits, side effects, evidence of prior studies,^1-7 and related ethical constraints were discussed in detail with the patient.

After the patient granted consent and institutional ethical approval was received, the ointment was prepared by triturating 2 g of citric acid in 30 g of 2% lidocaine gel and 70 g of 100% pure petroleum jelly as a base. The wound was cleaned with normal saline, after which citric acid ointment and a dry, light dressing was applied (Figure 1C). The daily application procedure was explained to the patient. In addition, the Bluebelle Wound Healing Questionnaire was explained and a copy provided to the patient in the local language.⁸ The patient was also asked to send her wound photographs to the clinic. The patient provided written informed consent to publish her case details and associated images.

The wound remained largely unchanged during the first week of ointment use. The appearance of the wound on day 3 is shown in Figure 2A and on day 5 is shown in Figure 2B. To the surprise of the authors of the current manuscript, the wound started contracting significantly through day 9, 12, 21, and 23 (Figure 2C-F, respectively). The wound had completely healed by day 30 of citric acid application (Figure 2G). There was no residual edema. During this period, the patient received 3rd and 4th chemotherapy cycles that were well tolerated.

Various factors deter the cellular and molecular pathways of tissue repair. Due to these factors, the wound healing trajectory shifts to the right, resulting in a chronic wound.⁹ Typically, the chronic wound is characterized by senescent cells, which are nonresponsive to tissue signals of wound healing. This shift to the right manifests locally as a disproportionate influx of inflammatory cells and improper migration of fibroblasts and endothelial cells. There is a resultant delay in the appearance of collagen or extracellular matrix, rate of open wound closure, and recovery of tissue breaking strength.⁹

Common conditions that mediate this delay are coexisting comorbidities (eg, diabetes, chronic kidney disease, malnutrition), tissue hypoxia, and wound infection.^9-11 Drugs such as steroids and antineoplastic agents are well known to hamper the wound healing process by affecting DNA, RNA, and protein synthesis and cellular division.^9,12 Despite advances in chemotherapy principles, these antineoplastic agents still affect the cellular and molecular pathways common to both tumor growth and wound healing.⁹

Various experimental and clinical studies report variable results concerning the effect of antineoplastic drugs on wound healing.^12,13 Cytotoxicity of antineoplastic agents affects all the phases of wound healing.^12,13 Microcirculation and neovascularization are hampered in all phases. Leucopenia, complement depletion, and malnutrition associated with chemotherapy affect the inflammatory phase and increase the risk of wound infection.^12,13 Chemotherapy hampers the key steps of the proliferative phase (fibroblast production and collagen synthesis). Altered collagen metabolism also affects the maturation phase.¹³ Common antineoplastic drugs such as doxorubicin and 5-fluorouracil, and even new-generation angiogenesis inhibitors, hamper effective wound healing.^9,11,13 Conventionally, chemotherapy is deferred in the presence of active wound inflammation and infection. Acute wounds take more time to heal in the presence of chemotherapy and may progress to chronic refractory wounds.¹²

The experiences of Nagoba and colleagues^1-7 with chronic wounds prompted the use of citric acid on the refractory wound in the current case, despite local care and a good diet (ie, adequate intake of fruits and vegetables along with oral multivitamin supplementation). Citric acid modulates the wound pH by creating an acidic milieu and inhibits bacterial growth and multiplication. Citric acid also promotes hydration of the wound bed, which facilitates removal of slough.^5,6 Citric acid improves microcirculation, accelerates fibroblast growth, and promotes healthy angiogenesis and epithelialization.^5,6 Citric acid has demonstrated favorable antimicrobial action in a hard-to-heal diabetic foot ulcer with multidrug-resistant methicillin-resistant Staphylococcus aureus.⁷ A petroleum base maintains adequate moisture and barrier function, which is necessary according to the TIME (tissue, infection/inflammation, moisture, and edge of wound) concept.^3,14

Because this is a case study, the research lacks the randomization and other benefits of a randomized controlled trial. Literature on the use of citric acid is mostly limited to case reports and low volume series. A randomized controlled trial with a larger sample size is needed to further evaluate the efficacy of citric acid treatment. High-quality evidence will improve the acceptability of this simple treatment approach among clinicians and patients.

The citric acid treatment approach used in the current case was proposed with the sole intention of preparing an appropriate wound bed before flap reconstruction. Surprisingly, the wound contracted and epithelialized on its own without any need for reconstructive surgery. Even though the patient in the current report had a low level of education, she was able to advocate to receive wound care and to apply the citric acid at home by herself. Thus, unnecessary expenses related to hospitalization and specialist care were avoided. Moreover, there was no break in the patient’s chemotherapy regimen. These findings indicate that citric acid can be a cost-effective, safe, efficient, and novel option to promote faster granulation and epithelialization of chronic wounds in immunosuppressed patients on antineoplastic drugs and that it may avoid the need for major reconstructive surgery.

Authors: Basavraj S. Nagoba, PhD¹; Abhijit S. Rayate, MS¹; Hardi B. Mavani, MS²; and Basawraj S. Warad, MS¹

Affiliations: ¹MIMSR Medical College, Latur, Maharashtra, India; ²SAL Institute of Medical Sciences, Ahmedabad, Gujarat, India

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Basavraj S. Nagoba, PhD; Assistant Dean, Professor of Microbiology, MIMSR Medical College, Vishwanathpuram, Ambajogai Road, Latur 413 531, Maharashtra, India; dr_bsnagoba@yahoo.com

Manuscript Accepted: July 1, 2024