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.
In April 2013, a 42-year-old male was diagnosed with stage IIIB testicular cancer in accordance with the American Joint Committee on Cancer Staing Classification () at the Kangwon National University Hospital (Chuncheon, Korea). The histology revealed non-seminomatous germ cell tumor (NSGCT) comprising seminoma (60%), yolk sac tumor (25%), embryonal carcinoma (10%) and teratoma (5%). Following orchiectomy, serum α-fetoprotein (αFP) levels were 20 ng/ml and lactate dehydrogenase (LDH) levels were 298 U/l (normal, <190 U/l). Computed tomography (CT) scanning showed pre- and para-aortic lymphadenopathy ≤3.6 cm. There was no medical history of note and, specifically, no history of dermatological disorders or allergy. The pateint’s pulmonary function test results were normal. The patient was commenced on bleomycin, etoposide and cisplatin chemotherapy, intravenously from May 20, 2013 in the outpatient clinic. Bleomycin (30 units) was scheduled to be administered on days 2, 9 and 16, while etoposide (100 mg/m2) and cisplatin (20 mg/m2) were administered for 5 days from day 1. Treatment was intended to be repeated every three weeks. After 10 days from the start of treatment, the patient subsequently developed a generalized pruritus and erythematous linear rash that was most prominent on the trunk and upper and lower extremities. The patient visited the emergency room (ER) and was given antihistamine. The patient then revisited the clinic for bleomycin treatment on day 16, and the rash in which the patient appeared to have been whipped over multiple body areas was observed. Physical examination showed the appearance of an erythematous popular rash on the whole body, with evidence of dermatographia (). There were no scales or lichenification, and the patient’s vital signs were normal. Laboratory tests at ER showed a white blood cell count of 3,800/mm3 (normal range, 3,800–10,000/mm3) (segmented neutrophils, 70%; lymphocytes, 24%; and eosinophils, 3%), hemoglobin levels of 13.7 g/dl (normal range, 13.3–16.5 g/dl), a platelet count of 313,000/mm3 (normal range, 140,000–400,000/mm3), serum LDH levels of 208 U/l (normal range, <190 U/l) and C-reactive protein levels of 5.35 mg/dl (normal range, <0.75 mg/dl). Prothrombin time and activated prothrombin time were 11.5 (normal range, 12.1–14.5 sec) and 36.7 sec (normal range, 31.0–43.7 sec), respectively.\nA skin biopsy of a right forearm lesion was taken. Bleomycin treatment on day 16 was cancelled. Pathological examination of the skin biopsy showed endothelial swelling and perivascular mononuclear cell infiltration present in the superficial and deep dermis (). The findings were considered to be consistent with a systemic hypersensitivity reaction. Given the patient’s clinical history and the gross appearance of the lesions, the diagnosis was most compatible with a severe bleomycin-induced flagellate erythema reaction. The patient was commenced on a short course of oral prednisolone, 20 mg daily, and antihistamine. The itching sensation was improved, but mild hyperpigmentation remained.\nConsequently, bleomycin was withheld from the treatment regimen. As the patient’s NSGCT was intermediate-risk, we recommended that the regimen should be changed to etoposide, ifosfamide and cisplatin. However, the patient refused to add ifosfamide following a discussion of the possible toxicities. Tumor markers, such as αFP and LDH levels, were normalized within 3 weeks of the first cycle of chemotherapy. Following a further three cycles of etoposide 100( mg/m2, days 1–5) and cisplatin (20 mg/m2, days 1–5), without bleomycin, every three weeks, no remnant mass was visible in the abdomen on positron emission tomography-CT.