Cholesterol embolism associated with MPO-ANCA

ARTICLE

Auteur(s) : Hideki Maejima^1,2, Toshiyuki Noguchi³, Ryoji Tanei¹

¹Departments of Dermatology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan
²Department of Dermatology, Kitasato University School of Medicine, 1-15 Kitasato, Sagamihara, 228-8885, Japan
³Departement of Respiratory Disease, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan

The clinical presentations of cholesterol embolism and systemic vasculitis are sometimes similar. A case of cholesterol embolism with a high serum myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) titre is described.

A 76-year-old Japanese man was treated for idiopathic interstitial pneumonia and ischemic heart disease for 40 years. He occasionally had hemoptysis. A few years ago, chronic bacterial pneumonia developed, and he was treated with antibiotics (sultamicillin tosilate, piperacillin, and ceftriaxone sodium), several times (figure 1A). He noticed micro livedo and ulcers with crusts, associated with pain, bilaterally, on his soles and toes, one month earlier (figure 1B). Doppler studies of the lower extremities were compatible with normal peripheral arterial perfusion. Laboratory studies revealed increased serum MPO-ANCA titre (236 EU), C-reactive proteins (5.5 mg/dL), and pulmonary surfactant protein-D (171.4 ng/mL). Peripheral white blood cell counts, blood urea nitrogen, serum creatinine, anti-serine proteinase antineutrophil cytoplasmic antibodies, and sialylated carbohydrate antigen KL-6 were within the normal ranges. Several kinds of pseudomonas and streptococcus species were detected on sputum culture. A skin biopsy specimen demonstrated deposition of fibrinoid material with inflammatory infiltration of some neutrophils in the walls of small arteries, and numerous lymphocytes and histiocytes were seen in perivascular lesions of small arteries. There were no immunoglobulin or complement deposits on direct immunofluorescence studies (figure 1C). Microscopic polyangiitis was suspected. However, needle-shaped clefts were seen in the lumina of small vessels in the subcutaneous tissues (figure 1D). Therefore, a diagnosis of cholesterol embolism with interstitial pneumonia associated with MPO-ANCA was made. The patient was treated with oral prednisolone 30 mg daily, and the skin eruptions disappeared (figure 1A). The patient died within two months because of a ruptured, asymptomatic, abdominal aortic aneurysm.

The cutaneous manifestations of cholesterol embolism are livedo reticularis, gangrene, cyanosis, ulceration, nodules, and purpura [1]. Purpura and livedo are common cutaneous manifestations of microscopic polyangiitis [2]. Typically, cholesterol embolism occurs in elderly men with a past history of arterial surgery or instrumentation and recent treatment with anticoagulants or thrombolytic agents. Most patients have known risk factors for vascular disease. The diagnosis of cholesterol embolism is established by the histological findings of characteristic needle-shaped clefts caused by the dissolved crystals. The present patient was diagnosed as having cholesterol embolism based on the histopathological findings. He also had high serum MPO-ANCA levels and interstitial pneumonia. Elevated serum MPO-ANCA titres have been reported in patients with cholesterol embolism associated with ANCA [3]. The pathogenic role of ANCA in cholesterol embolism is not clear, but the appearance of ANCA antibodies following bacterial and viral infections has been reported. The bacterial and viral DNA produce unmethylated CPG oligonucleotides that are potential triggers for the synthesis of MPO-ANCA [4]. Chronic bacterial pneumonia probably resulted in MPO-ANCA synthesis in the present patient. MPO-ANCA activates neutrophils, which injure or activate endothelial cells [5]. Then, endothelial cells contribute to the development of a pro-coagulant environment [6].The infiltrations of neutrophils in the walls, and of lymphocytes around the walls of small arteries were probably induced by MPO-ANCA. The fibrinoid material and thrombosis may have been caused by cholesterol crystals and injured and/or activated endothelial cells induced by neutrophils that were produced by circulating MPO-ANCA. The cholesterol embolism was regarded as a pseudovasculitis, which presented with small amounts of inflammatory infiltrated neutrophils and less injury to vascular walls than occurs in vasculitis. The histopathological and clinical manifestations of cholesterol embolism associated with MPO-ANCA mimicking microscopic polyangiitis are reported.

Acknowledgements

References

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