Blue toe syndrome caused by spontaneous cholesterol embolization syndrome

Blue toe syndrome is a severe cutaneous manifestation of cholesterol embolization syndrome (CES). Approximately 80% of CES cases are iatrogenic; however, CES can also be spontaneous. Skin biopsy of the blue toe to identify intra-arterial cholesterol clefts is useful for diagnosing CES. A 61-year-old man who presented with bilateral chromatic toe aberrations and discomfort was prescribed amlodipine (5 mg) and telmisartan (40 mg) for hypertension. His social history revealed a tobacco-smoking habit of 41 years (20 cigarettes daily). However, his medical history was devoid of invasive medical interventions. Eighteen days before his visit, the patient observed that his bilateral toes had turned white-to-purple, and he experienced cold and painful sensations. Subsequently, a segment of his toes developed a necrotic black colouration, exacerbating the pain and compelling him to seek medical attention. His vital signs were stable. The bilateral toes were blue (Figure 1a, blue toe syndrome), and the bilateral dorsal foot arteries were palpable. A comprehensive physical examination revealed no additional aberrant findings. His blood and urine test results were normal. Skin biopsy of the right fifth blue toe revealed ‘cholesterol clefts’ in the artery (Figure 1b), which was diagnosed as cholesterol embolization syndrome (CES). Subsequently, the patient experienced substantial symptom improvement after 3 weeks. (a) Blue toe syndrome findings at initial presentation: all toes of the left foot had colour changes, while the right foot had colour changes in the first, second and fifth toes. The toes with colour changes were cold and painful. (b) Skin biopsy from the right fifth toe: Elastica Masson staining with 200-fold magnification. The arterial structures displayed the presence of cholesterol clefts. CES is characterized by atherosclerotic plaque disintegration, primarily in the aortic wall.1 The resultant debris, predominantly cholesterol crystals, disseminates into the peripheral small- and medium-sized arteries, provoking ischaemia via physical blockage and consequent inflammatory responses, culminating in organ damage.1 Approximately 80% of cases are iatrogenic, and spontaneous onset is rare (1.9–13%)2,3; however, CES incidence is unknown. The clinical manifestations of CES are diverse because they depend on the embolus source and the size and proportion of cholesterol crystals.2 CES incidence is significantly greater, owing to underdiagnosis.3 Blue toe syndrome was first reported as a cutaneous finding of cholesterol embolization with one or more blue-to-purple toes; therefore, it is a crucial cutaneous finding for CES. Additionally, it can indicate other maladies such as vasculitis, antiphospholipid syndrome, hyperviscosity and endocarditis, necessitating a thorough differential diagnosis.1,4,5 In this case, the patient had blue toe syndrome without medical triggers, and a skin biopsy was performed to confirm the diagnosis. Furthermore, standard treatments for CES are unavailable, and the prognosis of patients with medically induced CES is poor because they are associated with high cardiovascular risk.6 The treatment and prognosis of spontaneous CES remain unknown; nonetheless, we explained the importance of smoking cessation and blood pressure control and advised the patient to comply with these instructions to avoid recurrence. Morika Suzuki (Conceptualization [lead], Data curation [lead], Formal analysis [lead], Investigation [lead], Methodology [lead], Project administration [lead], Resources [equal], Software [equal], Visualization [lead], Writing—original draft [lead]), and Takashi Watari (Conceptualization [equal], Investigation [equal], Methodology [equal], Project administration [equal], Resources [equal], Software [equal], Supervision [lead], Visualization [equal], Writing—original draft [equal], Writing—review & editing [lead]) Consent: Patient consent was obtained before submitting this case report. None declared.