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.
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.