Postradiation breast erythema, skin thickening, and peau d’orange

A 69-year-old woman developed erythema and skin thickening on her breast 1 year after ipsilateral breast cancer therapy, which included lumpectomy, adjuvant chemotherapy (adriamycin, cyclophosphamide, and paclitaxel), and whole breast radiation (42.5 Gy in 16 fractions with boost to 48 Gy). Within a month of presentation, there was erythema across the whole breast, fullness, nipple stretching, skin thickening, and peau d’orange (Fig 1). The deeper tissue was soft and pliable, with no palpable masses. She denied pain, fever, and other constitutional symptoms. A punch biopsy showed dermal thickening and fibrosis and pronounced perivascular inflammation with the infiltration of lymphocytes (Fig 2).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: Which of the following is the most likely diagnosis?A.Acute radiation dermatitisB.Carcinoma en cuirasseC.CellulitisD.Postirradiation fibrosisE.Radiation-induced morphea (RIM) Answers:A.Acute radiation dermatitis – Incorrect. Acute radiation dermatitis may resemble the above lesion, but, unlike RIM, it presents in a more acute time frame and is histologically characterized by edema, vasodilation, thrombi, and erythrocyte extravasation.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google ScholarB.Carcinoma en cuirasse – Incorrect. Though cutaneous metastases of breast cancer most commonly present as solitary to multiple erythematous infiltrating papules and nodules, carcinoma en cuirasse may resemble the above lesion. Carcinoma en cuirasse may be histologically characterized by the infiltration of atypical cells (arranged in dense linear sheets) within the dermis and lymph vessel obstruction.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,2Reich A. Samotij D. Szczęch J. Woźniak Z. Szepietowski J. Carcinoma en cuirasse as an initial manifestation of inflammatory breast cancer.Postepy Dermatol Alergol. 2016; 33: 142-145https://doi.org/10.5114/pdia.2015.48069Crossref PubMed Scopus (10) Google ScholarC.Cellulitis – Incorrect. Cellulitis may resemble the above lesion and may even cause peau d’orange. However, it is typically poorly demarcated and presents with pain (whereas RIM is more often painful in its later stages). Additionally, cellulitis is histologically characterized by the perivascular infiltration of neutrophils, dermal edema, and lymph vessel dilation.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,3Raff A.B. Kroshinsky D. Cellulitis: a review.JAMA. 2016; 316: 325-337https://doi.org/10.1001/jama.2016.8825Crossref PubMed Scopus (201) Google ScholarD.Postirradiation fibrosis – Incorrect. Postirradiation fibrosis may resemble the above lesion, but, when histologically compared to RIM, it lacks significant inflammatory infiltration and has fibrosis in deeper skin layers (ie, subcutaneous/fascial).1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google ScholarE.RIM – Correct. This clinical picture is most consistent with RIM, which is generally an erythematous, edematous plaque that progresses to induration, violaceous discoloration, peau d’orange, and pain in its later stages. The early stages are histologically characterized by slight dermal collagen thickening and the perivascular/periadnexal infiltration of lymphocytes, and the later stages by prominent dermal fibrosis and a loss of periadnexal adipose tissue and lymphocyte infiltration.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar Question 2: How would you manage this condition?A.Topical calcipotrieneB.Topical corticosteroidsC.Topical tacrolimusD.Topical therapy plus systemic methotrexateE.Watch and wait Answers:A.Topical calcipotriene – Incorrect. Many treatments have shown some efficacy in RIM, including topicals (eg, steroids, calcipotriene, tacrolimus), systemic medications (eg, prednisone, methotrexate), and phototherapy (eg, narrow-band ultraviolet B).1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar However, those receiving systemic methotrexate or phototherapy may respond better than those receiving only topical therapy.4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google ScholarB.Topical corticosteroids – Incorrect. Many treatments have shown some efficacy in RIM, including topicals (eg, steroids, calcipotriene, tacrolimus), systemic medications (eg, prednisone, methotrexate), and phototherapy (eg, narrow-band ultraviolet B).1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar However, those receiving systemic methotrexate or phototherapy may respond better than those receiving only topical therapy.4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google ScholarC.Topical tacrolimus – Incorrect. Many treatments have shown some efficacy in RIM, including topicals (eg, steroids, calcipotriene, tacrolimus), systemic medications (eg, prednisone, methotrexate), and phototherapy (eg, narrow-band ultraviolet B).1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Indeed, for limited plaque morphea, tacrolimus has been recommended as a first-line topical option.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar However, those receiving systemic methotrexate or phototherapy may respond better than those receiving only topical therapy.4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google ScholarD.Topical therapy plus systemic methotrexate – Correct. Many treatments have shown some efficacy in RIM, including topicals (eg, steroids, calcipotriene, tacrolimus), systemic medications (eg, prednisone, methotrexate), and phototherapy (eg, narrow-band ultraviolet B).1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar However, those receiving systemic methotrexate or phototherapy may respond better than those receiving only topical therapy.4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google ScholarE.Watch and wait – Incorrect. Although RIM does regress spontaneously in some cases, this is likely not common, and earlier treatment is associated with better outcomes.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,4Fruchter R. Kurtzman D.J.B. Mazori D.R. et al.Characteristics and treatment of postirradiation morphea: a retrospective multicenter analysis.J Am Acad Dermatol. 2017; 76: 19-21https://doi.org/10.1016/j.jaad.2016.08.059Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Question 3: Which is NOT likely to affect a person’s risk for developing this condition?A.History of autoimmune disordersB.Patient sexC.Obesity or larger breast sizeD.SmokingE.Type and dose of radiation Answers:A.History of autoimmune disorders – Incorrect. This is a proposed risk factor for RIM.5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarB.Patient sex – Incorrect. Being female is a strong risk factor for RIM, which most often occurs following radiation for breast cancer.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarC.Obesity or larger breast size – Incorrect. These are proposed risk factors for RIM.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarD.Smoking – Incorrect. This is a proposed risk factor for RIM.5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google ScholarE.Type and dose of radiation – Correct. This is not a known risk factor for RIM.1Spalek M. Jonska-Gmyrek J. Galecki J. Radiation-induced morphea—a literature review.J Eur Acad Dermatol Venereol. 2015; 29: 197-202https://doi.org/10.1111/jdv.12704Crossref PubMed Scopus (40) Google Scholar,5Mittal A. Mittal V. Panse G. Choi J.N. Kwong B.Y. Leventhal J.S. Radiation-induced morphea: association with autoimmune comorbidities, severity, and response to therapy.J Am Acad Dermatol. 2019; 81: 260-262https://doi.org/10.1016/j.jaad.2019.02.039Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar None disclosed.