A 64-year-old woman presented with left axillary lymphadenopathy in December 2014. Metastatic infiltrating ductal carcinoma of the left breast and left axillary and pectoral lymph nodes was diagnosed. The tumor was clinical stage III T2N2, estrogen receptor negative, progesterone receptor negative, and HER2 overexpressed.\nShe began treatment in 2015 with triple therapy on February 24, March 17, and April 7: paclitaxel, pertuzumab, and trastuzumab. She also received monotherapy with paclitaxel on March 3, March 10, March 24, and March 31. Following her treatment on April 7, she developed eyelid ptosis and peripheral neuropathy with ataxia that was attributed to paclitaxel.\nMonotherapy with trastuzumab was resumed on May 9, 2015. On June 1, 2015, 3 days after receiving trastuzumab on May 29, 2015, she developed pruritus. She also noted a rash developing on her chest, abdomen, arms, and legs.\nCutaneous examination on June 3, 2015 showed erythematous, distinct and intermingled (in a lacy pattern), linear streaks on her arms (Figs. , ), chest, and abdomen (Fig. ). The morphology of the clinical lesions was a flagellate erythema. Similar linear streaks—both erythematous and hemorrhagic—were also noted on her legs (Figs. , ).\nA skin biopsy from her left arm showed basket-weave orthokeratosis overlying a spongiotic epidermis. There was edema in the dermis with a predominantly lymphocytic inflammatory infiltrate that is present around blood vessels in the papillary dermis. There was exocytosis of small lymphocytes into the overlying epidermis (Fig. ). The pathologic findings were those of a spongiotic dermatitis, compatible with a medication reaction.\nCorrelation of the clinical history, symptoms and findings in concert with the pathologic features observed established the diagnosis of drug-induced flagellate erythema. In this patient, the causative agent was trastuzumab.\nShe was treated systemically with prednisone (60 mg each morning for 3 days, followed by 40 mg each morning for 2 days and 20 mg in the morning for 1 day), and antihistamines for 2 weeks: Fexofenadine 180 mg each morning and diphenhydramine 25 mg each evening. Topical therapy was also initiated: Clobetasol propionate 0.05 % cream twice daily for 10 days and then once daily for 4 days.\nWithin 2 days, the itching had resolved and the skin eruption had nearly cleared. Follow-up examination after 2 weeks, on June 17, 2015, showed complete clearing of the flagellate erythema on her chest, abdomen, and arms. The erythematous hemorrhagic linear streaks on her distal legs were less prominent and asymptomatic.\nThe patient has subsequently had a left breast lumpectomy and complete lymph node dissection. There was no residual carcinoma in the breast and 26 lymph nodes were negative for malignancy. She has also received adjuvant radiation therapy.\nHer oncologist decided that she would need to receive treatment with trastuzumab, every 3 weeks, for 1 year. She has been receiving dexamethasone prior to each trastuzumab treatment to prevent recurrence of the adverse skin event. Neither pruritus nor flagellate erythema has occurred with the subsequent administration of trastuzumab.
A 35-year-old pregnant woman at 36 weeks of gestation with a 23 × 11-mm mass and multiple lymph nodes in the left axillary up to 23 × 10-mm involvement in ultrasonography was included in this study. After performing core needle biopsy, she had been diagnosed with invasive ductal carcinoma grade II in the upper outer quadrant of her left breast. Accordingly, this tumor was characterized as negative by immunohistochemistry for estrogen and progesterone receptors, but it resulted as positive for HER2 and Ki67 positive in >25% of tumor cells. The patient at 38 weeks of gestation delivered, and then the assessment for metastasis was done. Fortunately, no metastases were found, and her cancer stage was found to be II.\nThe patient included in this study received neoadjuvant chemotherapy with both adriamycin and cyclophosphamide 4 courses. Following the breast ultrasound, clear reductions were observed in the size of the mass and axilla lymph nodes. Thereafter, the patient received paclitaxel and AryoTrust (TH) for a 12-week duration, and then AryoTrust was continued once per 3 weeks. Of note, the generic name of the trastuzumab biosimilar used for the patient was AryoTrust. Afterward, left breast quadrectomy was done, showing no tumor residue, and left axillary sentinel lymph node excisional biopsy also resulted as negative (which is a very good response to neoadjuvant chemotherapy). After performing breast-conserving surgery, radiation therapy to the whole breast and regional lymphatics were considered. This technique contains tangential fields that is performed using the 3-dimensional conformal radiation therapy. The dose provided to the whole breast was between 45 and 50 Gy over 5–6 weeks (1.8–2 Gy tumor dose daily, 5 weekly fractions), with an additional boost dose or 10–16 GY in 2 Gy fractions to the tumor bed with the patient treated with 6-MV photons.\nThe overall treatment was well tolerated by the patient. After performing 5 cycles of AryoTrust (6 mg/kg every 3 weeks), she complained of swollen eyes and urticarial lesions. By conducting the physical examination, periorbital swelling and erythema (heliotrope rash) were revealed (Fig. ). An erythematous rash on the arms (Fig. ) and chest was also observed. Also, muscle strength of the lower limbs decreased (4/5), while it was normal in all upper limbs. The laboratory examination revealed moderately elevated serum muscle enzymes (a creatine phosphokinase value: 492 IU/L with a normal laboratory range of 38–176 IU/L;lactatedehydrogenase value: 510 IU/L with a normal laboratory range of 140–280 IU/L), but fluorescent antinuclear antibody, anti-double-stranded DNA, and antibodies to histidyl tRNA synthetase were negative. Skin lesion biopsy diagnosed papillary edema, epidermal spongiosis with few eosinophilic infiltrations, and a mild interstitial mucin deposition. Since the interval between radiotherapy and the onset of the symptoms was about 6 months and a recent screening for disease recurrence resulted as negative, the observed DM symptoms were attributed to trastuzumab. For this reason, the practitioner discontinued the use of trastuzumab. With Rheumatologic consult, prednisolone and hydroxychloroquine were started. Subsequently, the patient's symptoms improved, and 1 month later, she was free of any related symptom, and CPK was found in the normal range. In the first week, AryoTrust was started with 4 mg/kg, which was then followed by 2 mg/kg weekly for 3 weeks. Afterward, the dose of AryoTrust was increased to 6 mg/kg every 3 weeks. Fortunately, the patient had no complications.