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Delayed Hypersensitivity Reaction to Acellular Dermal Matrix in Breast Reconstruction Patients
Ingrid Ganske, MD, MPA1, Marguerite Hoyler, BA2, Sharon Fox, MD, PhD3, Donald J. Morris, MD4, Samuel J. Lin, MD4, Sumner A. Slavin, MD4.
1Harvard Combined Plastic Surgery Residency Program, Boston, MA, USA, 2Harvard Medical School, Boston, MA, USA, 3Beth Israel Deaconess Medical Center Pathology Residency, Boston, MA, USA, 4Beth Israel Deaconess Medical Center Division of Plastic and Reconstructive Surgery, Boston, MA, USA.

Introduction: Acellular dermal matrix (ADM) is a valuable tool in reconstructive breast surgery, in part because it is considered to be a non-reactive and non-immunogenic entity. However, a growing body of breast reconstruction literature has described local erythema overlying ADM grafts that is frequently attributed to cellulitis but is largely unresponsive to antibiotic therapy. This phenomenon, the “red breast syndrome,” is poorly understood. We hypothesize that it may represent a delayed type hypersensitivity reaction to ADM products, and that affected patients may benefit from treatment with corticosteroids or similar medications.
Methods: We reviewed the records of four implant-based breast reconstruction patients, previously known to the authors. We analyzed these cases in the context of current scholarship regarding the “red breast syndrome” and the possible antigenicity of biologic mesh implants.
Results: We identified four implant-based breast reconstruction patients who developed erythema overlying their allogeneic or xenogeneic ADM grafts, and whose symptoms responded to corticosteroids or immunosuppressant medications. All patients were initially treated with serial high-dose antibiotics, but had local erythema that either persisted or recurred. Two patients had transient leukocytosis. Ultimately, clinical suspicion for infection diminished. One patient underwent punch biopsy of the erythematous skin and was diagnosed with a delayed type hypersensitivity reaction; she subsequently opted for take-down of her reconstruction. Two other patients had similar clinical presentations, but their symptoms responded to oral corticosteroids such that removal of the biologic mesh or implants was not indicated. One of these patients had a recrudescence of her erythema eight weeks after initial treatment and responded to a second course of corticosteroids. A fourth patient had inferior pole erythema that resolved only after she began adjuvant chemotherapy. Currently, all patients have had full remission of symptoms for at least two years.
Discussion: These cases, along with two others seen at our institution, suggest that localized erythema following ADM-based breast reconstruction may be a delayed-type hypersensitivity (DTH) reaction to a component of the ADM graft. ADM manufacturers acknowledge the possibility of hypersensitivity reactions in written instructions to clinicians, and the medical literature describes several epitopes in biologic meshes that may cause a host immune response. All patients had symptoms consistent with this diagnosis, and one patient received a histologic diagnosis of a DTH reaction. Patients’ transient or partial improvement on antibiotics might be attributed to the anti-inflammatory properties of many anti-microbials, but their failure to fully respond to repeated and varied antibiotics suggests that breast cellulitis was not the underlying etiology. Most notably, resolution of symptoms following treatment with corticosteroids and chemotherapy suggests an inflammatory, as opposed to infectious, etiology.
Conclusion: More research is needed to clarify the etiology and optimal management of the “red breast syndrome,” but these cases present compelling evidence that some patients may have inflammatory reactions to ADM grafts. Accordingly, after carefully ruling out infection, patients with erythema overlying an ADM implant may benefit from corticosteroids or other anti-inflammatory medications. Importantly, this may enable salvage of an ADM graft or an entire reconstructed breast.


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