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 45-year-old woman was admitted to our heart center with severe mitral stenosis and left atrial clot. The patient gave a history of shortness of breath on minimal exertion for one week and no cerebral symptoms, including headache, dizziness, transient ischemic attacks, or strokes. She was found to be fully conscious, alert, and oriented with stable vital signs. Blood pressure was 110/80 mmHg, and diastolic murmur was audible over the mitral area. Physical examination revealed intact cranial nerves, motor power, and sensation. There was no evidence of vasculitis such as Osler’s nodes, Jane way pad, palmer erythema, or cyanosis of fingers. Blood investigation showed an erythrocyte sedimentation rate (ESR) of 4 mm with no leukocytosis and a white blood cell (WBC) of 10.000 mm3. The electrolytes and kidney and liver function were within normal limits. Chest X-ray showed prominence of the left cardiac border due to left atrial enlargement. Electrocardiography was indicative of no change, but two–dimensional echocardiography revealed a large bulky non-mobile thrombosis in the left atrium with severe mitral stenosis. The mitral valve area was 0.6 cm2, and the other cardiac valves were normal. Pre- and postoperative laboratory measurements included negative antinuclear antibodies and rheumatoid factor, and elevation of C4 & C3 components of complement; in addition, HBS Antigen (especially in polyarteritis nodosa) was negative.\nThe patient underwent open heart surgery via the ascending aorta and bicaval cannulation. The aorta was cross-clamped, and the heart was arrested with cold cardioplegia by achieving systemic hypothermia at 30 °C on the cardiopulmonary bypass. Intraoperatively, the stenotic mitral valve was found to have a bulky clot attached to the valve and wall of the left atrium. The diseased mitral valve and the clot were excised, and the left atrial cavity was irrigated with copious amounts of normal saline and a valve was thereafter implanted. The left ventricle was then filled completely with saline and blood and fully deaired. The patient was weaned successfully off cardiopulmonary bypass with inotropic support and transferred to the intensive care unit. After 6 hours, blood pressure dropped and central venous pressure elevated and the extremity became cool and cyanotic. Inotropic support was commenced with dobutamine and adrenaline (2 and 1 mic/kg/min, respectively). On the third postoperative day, the inotropic drugs were tapered and blood pressure stabilized. By this point, however, the cyanosis had changed to gangrene and on the 12th postoperative day the acral part of the extremity was amputated and the specimen was sent for histopathological examination. In the histopathological examination, there was only non-specific vasculitis with thrombosis. The patient did not regain full consciousness on the following morning and was found to be quadriplegic with non-voluntary movements of the four limbs and face. The eyes could move only on the vertical plane, with both pupils having become small and fixed. After 72 hours, she managed to respond to questions only by blinking or moving her eyes vertically. Brain MRI revealed multiple infarction of the brainstem. Prolonged ventilatory support was maintained and eventually a tracheostomy was performed to facilitate tracheobronchial suctioning and weaning. Acute renal failure with anemia was managed and the kidneys recovered completely. However, the patient remained in this locked-in state for 4 weeks with no neurological improvement despite all ventilatory, nutritional, and nursing support. She eventually expired from hepatic failure and generalized sepsis.