A 75-year-old female patient was admitted with sudden-onset dizziness on April 8, 2017. She had a medical history of hypertension, diabetes mellitus, pulmonary tuberculosis and chronic obstructive pulmonary disease with an FEV1 of 62% of normal predicted (1.39 L). This patient did not report any allergies from the past. Brain magnetic resonance imaging indicated an infarction in the posterior inferior cerebellar artery territory. Atrial fibrillation was also found. Edoxaban and bisoprolol were administered together with amlodipine, gliclazide, metformin, and atorvastatin.
The patient became drowsy and dyspneic on May 4, 2017. Her body temperature was 37.6  C with a white blood cell (WBC) count of 7530/mm3 and D-dimer level of 0.89 mug/ml. Enterobacter cloacae was grown on blood and urine cultures. She received ertapenem for 15 days. However, she continued to experience dyspnea until May 18 and the D-dimer level increased to 5.52 mug/ml. Multiple PTEs were found at the segmental pulmonary arteries of the right lower lobe and left lung with focal deep vein thromboses at the infrarenal inferior vena cava, left popliteal vein and calf vein on three-dimensional angiography computed tomography scans. The activated partial thromboplastin time was 38.4 s (29.0-44.0 s); the prothrombin time, 14.5 s (international normalized ratio, 1.17) and WBC count, 7440/mm3. We stopped edoxaban and started intravenous heparin injection.
Rivaroxaban 15 mg twice a day was started from May 30. Non-blanching erythematous palpable petechiae and purpura (Fig. 1) were found on both thighs, both arms, and the lower abdomen on June 16. Complete blood count (CBC), erythrocyte sedimentation rate (ESR), and the biochemical profile with liver and renal function, coagulation studies, and urine analysis were within normal limits. Chest X-ray (CXR) showed no active parenchymal lesion. Further studies, including antinuclear antibody (ANA), rheumatoid factor (RF), antineutrophil cytoplasmic antibodies (ANCA) (cytoplasmic and perinuclear), complement levels (C3, C4), serum cryoglobulins, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus test, yielded normal results. We performed punch biopsies on the abdomen on June 20. The biopsy specimen showed superficial perivascular neutrophilic infiltration with leukocytoclastic debris, and interstitial infiltration of a few eosinophils and melanophages, consistent with LCV. Direct immunofluorescence (DIF) staining demonstrated granular deposition of immunoglobulin A and C3 in dermal blood vessels (Fig. 2).
We stopped rivaroxaban on July 12 and started dabigatran 110 mg twice a day instead. The skin lesions improved within 2-3 days. We administered rivaroxaban 20 mg daily again from July 19 to confirm that the skin lesions were caused by it. Similar skin lesions developed again on July 29, and rivaroxaban was stopped on July 31. We started dabigatran 110 mg daily again from August 1. The skin lesions improved within 2-3 days again but they began to reappear on August 13. Dermatological assessment performed at that time indicated that this was the same disease. Since the patient was not receiving any concomitant medication that could be suspected as the cause of LCV, we stopped dabigatran on August 15, and started edoxaban 15 mg daily from August 16. The skin lesions improved over several days. We did not administer rivaroxaban and dabigatran anymore, and the skin lesions also did not develop again subsequently. However, the patient developed hospital-acquired pneumonia and died of it on September 11, 2017.