Article, Cardiology

Hyperbaric oxygen therapy in a case of cholesterol crystal embolization

established; and medical treatment is mostly supportive. In this report, we describe the case of a 56-year-old man who developed CCE syndrome after coronary artery angioplasty with stent implantation and who was successfully treated with Hyperbaric oxygen (HBO) therapy.

A 56-year-old man was admitted to our hospital with an acute myocardial infarction. A successful primary angio- plasty with bare metal stent implantation on intermediate branch was immediately performed. At fifth hospital day, the patient was discharged in good clinical conditions. Two weeks later, he was readmitted to our hospital with complaints of severe pain on legs associated with extensive livedo reticularis and Purplish discoloration of toes. Physical examination revealed ecchymotic nodules with central necrosis, acrocyanosis, and livedo reticularis on bilateral legs and feet (Fig. 1A). Peripheral pulses were intact, and the feet were warm to the touch. On admission, laboratory blood tests revealed a significant deterioration of renal function with a raise in serum creatinine (2.1 mg/dL) and blood urea nitrogen (57 mg/dL), and elevated creatine kinase (510 U/L), creatine kinase MB mass (54.59 ng/mL), Pancreatic enzymes (total amylase, 150 U/L; lipase, 380 U/L), aspartate aminotransferase (129 U/L), alanine aminotransferase (80 U/L), ?-glutamyltransferase (176 U/L), C-reactive protein (1.4 mg/dL), velocity of erythrocyte sedimentation (59 mm h), and white blood cell count of 9.46/mm3 with 20.1% of eosinophils; urinalysis showed proteinuria. Testing for cryoglobulin, antinuclear antibodies, anticardiolipin immunoglobulin M and G, lupus anticoagulants, cytoplas- matic and perinuclear types of antineutrophil cytoplasmatic antibodies, and complement 3 and 4 showed no abnormal- ities. Peripheral artery Doppler ultrasonography revealed no hemodynamically significant artery disease of the lower limbs, including the toes. Renal ultrasonography revealed symmetrical and normal-sized kidneys with distinct cortico- medullary junctions. Both kidneys were of normal size, but the parenchyma showed slightly increased echogenicity. An abdominal computerized axial tomography demonstrated the presence of ulcerated plaque in the descending aorta with diffuse atherosclerotic lesions in the abdominal aorta extending to the iliacal arteries (Fig. 2). A deep cutaneous biopsy was obtained from an ecchymotic area of the left leg. histopathologic examination of the specimen showed slight

0735-6757/$ – see front matter (C) 2011

Fig. 1 Cutaneous manifestations of CCE: A, Physical lesions at presentation with livedo reticularis of the ball of the foot and acrocyanosis (A1) of fifth toe. B, Worsening of the lesions after 1 month of treatment of iloprost; evidence of necrosis of the left (B) and right (B1) toes and the right heel (B2). C, Complete resolution of the necrotic lesions after 1 months of HBO therapy with autoamputation of the left fifth toe.

hyperkeratosis of epidermis associated with a modest perivascular inflammatory infiltration in superficial and deep dermis and presence of cholesterol crystal clefts within the lumen of small arterioles (Fig. 3). On the basis of histopathologic findings, CCE syndrome was diagnosed. Prednisone at a daily dose of 25 mg (0.3 mg/[kg d]) and atorvastatin at a daily dose of 80 mg were started in addition to aspirin, clopidogrel, losartan, and amlodipine that the

Fig. 2 Image of the abdominal aortic plaque. Abdominal comput- erized axial tomography showed the presence of ulcerated plaque in the descending aorta.

patient assumed at home. Moreover, narcotic therapy with tramadol chlorhydrate was added to relieve severe leg pain of which the patient had complained. After 3 weeks, the patient reported a markedly decreased intensity of tender- ness. In addition, most skin lesions had improved; but the

Fig. 3 Cholesterol’s crystal clefts. At medium magnification in the central portion of the picture, the presence of cholesterol’s crystals clefts can be noted in a small blood vessel of subcutaneous tissue (note the portion of dermal tissue in lower part of the picture) (hematoxylin and eosin stain; original magnification x400).

fifth digit of the patient’s left foot had worsened with appearance of gangrenous degeneration. Laboratory tests showed a significant decrease in the serum level of creatinine (1.6 mg/dL) and eosinophil count (1.3/uL). The patient was discharged with domiciliary Corticosteroid therapy. Approximately 1 month later, the patient returned to our observation with no improvement in clinical conditions. Based on few reports of clinical improvement of CCE with iloprost, a 7-day course of intravenous iloprost 2 ng/(kg min) was started. After 1 month of treat- ment, a significant improvement of cutaneous lesions was observed; and the patient reported reduction of leg pain. Iloprost infusions were then reduced to 2 times a week, but the patient’s conditions rapidly deteriorated; foot ischemic lesions progressed to necrosis with dark discol- oration of the tips of toes (Fig. 1B). hyperbaric oxygen therapy was started to halt the necrotic process on the basis of its use in nonhealing ischemic ulcers, although clinical evidences in the setting of CCE are lacking. The patient was given 100% oxygen at 2.5 ATA for 90 minutes daily,

5 days a week, with a break over the weekend. Soon after the start of HBO therapy, the patient showed significant improvement. After 2 months of HBO therapy, the necrotic lesions were completely resolved; and the patient underwent spontaneous autoamputation of the left fifth toe (Fig. 1C).

Cholesterol crystal embolism occurs most commonly after vascular procedure [2] and is caused by the disruption of atheromatous plaques with consequent release of plaque material into the blood Vessel lumen. When cholesterol emboli lodge in small arterioles, they incite an inflammatory response [3] that results in narrowing or obliteration of the lumen [4] and ischemia of the target organs. The frequency of localization to viscera is proportional to their blood flow, with major involvement of gastrointestinal, renal system, and skin. Despite the progress of radiology and vascular surgery with their Possible complications, CCE is still underdiagnosed; and its treatment is not codified. Therefore, it is very important that clinicians be aware of the risks of CCE after vascular procedure. Clinical presentation can suggest the diagnosis, and the detection of hypereosinophi- lia at laboratory test may support the advanced hypothesis. But histologic confirmation is essential for diagnosis, showing characteristic cholesterol clefts within arterioles on tissue section.

No definitive treatment of CCE has been established. Therapeutic modalities are symptomatic and preventive. Treatment with anticoagulant is contraindicated because anticoagulants may aggravate the syndrome [6]. Many antiplatelet drugs have been tried without success [5,7]. Statins have been suggested as being beneficial in the treatment of CCE; in fact, they may play a role to stabilize the cholesterol-rich atherosclerotic plaques [8]. In some reports, use of corticosteroids has been proven to be effective in improving symptoms of CCE [9-11]. In few cases, iloprost, a prostacyclin analogue, was used in

patients with CCE, with associated improvement in ischemic skin lesions and renal function [12-15]. Hyper- baric oxygen has been proven to be useful to prevent and reverse hypoxic changes in a variety of disease in which ischemic lesions are due to microvascular involvement such as diabetes [16], vasculitis [17], Purpura fulminans [18], etc. In CCE too, there is microvascular damage with associated inflammatory response that, in our hypothesis, could be sensible to HBO therapy. Hyperbaric oxygen therapy involves the inhalation of 100% oxygen in a chamber at pressures greater than at sea level. It is frequently used as adjuvant therapy for patient with ischemic nonhealing ulcers most commonly caused by diabetes and vasculitis [16,17]. The benefit of HBO are explained by hyperoxygenation of the hypoperfused tissue that induces significant positive changes in the repair process by enhancing fibroblastic replication, collagen synthesis, and neovascularization [19]. Moreover, hyper- oxia has an anti-inflammatory effect in the vascular bed, reducing rolling and adhesion of polymorphonuclear cells in the microcirculation [20]. In our patient, we observed a rapid improvement in clinical conditions and in laboratory parameters; and after 2 months, Complete recovery was obtained. We concluded that HBO may serve as an effective treatment in CCE, although the exact mechanism of action of HBO in this syndrome in still unclear. But because this is the first case in which the efficacy of HBO in CCE was tested, further studies are needed to evaluate whether HBO can be used as primary therapy for this pathology.

Angela Gurgo MD Valentina Valenti MD Francesco Paneni MD Jasmine Passerini MD Marta Di Vavo MD Camilla Calvieri MD Dipartimento Cardiologia Policlinico Sant’Andrea Universita La Sapienza

00189 Roma E-mail address: [email protected]

Claudio Cacchi MD Armando Bartolazzi MD Dipartimento di Anatomia Patologica

Policlinico Sant’Andrea Universita La Sapienza

00189 Roma

Anna Sabani MD Dipartimento Scienze Anestesiologiche Medicina Critica e Terapia del Dolore Centro Medicina Iperbarica Policlinico Umberto I

Universita La Sapienza

00161 Roma

doi:10.1016/j.ajem.2010.05.023

References

Massimo Volpe MD Dipartimento Cardiologia Policlinico Sant’Andrea Universita La Sapienza

00189 Roma

  1. Woolfson R, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Br J Dermatol 2000;143:1319-20.
  2. Belenfant X, Meyrier M, Jacquot C. supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis 1999;33:840-50.
  3. Mann SJ, Sos TA. Treatment of atheroembolization with corticoster- oids. Am J Hypertens 2001;14:831-4.
  4. Graziani G, Santastasi S, Angelini C, Badalamenti S. Corticosteroids in cholesterol emboli syndrome. Nephron 2001;87:371-3.
  5. Elinave E, Chajek-Shault T, Sterm M. Improvement in cholesterol emboli syndrome after iloprost therapy. BMJ 2002;324(7332): 268-9.
  6. Grenader T, Lifschitz M, Shavit L. Iloprost in embolic renal failure. Mt Sinai J Med 2005;72:339-41.
  7. Panum PL. Experimentelle Beitrage zur Lehre von der Embolie. Virchows Arch Cell Pathol 1862;25:308-10.
  8. Parskevas KI, Koutsias S, Mikhailidis DP, Giannoukas AD. Cholestrol crystal embolization: a possible complication of peripheral endovas- cular interventions. J Endovasc Ther 2008;15:614-25.
  9. Donohne KG, Saap L, Falanga V. Cholesterol crystal embolization: an atherosclerotic disease with frequent and varied cutaneous manifesta- tion. J Eur Acad Dermatol Veneorol 2003;17:504-11.
  10. Lie JT. Cholesterol atheromatous embolism. The great masquerader revisited. Pathol Annu 1992;27:17-50.
  11. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization. Review of 221 cases in the English literature. Angiology 1987;42: 769-84.
  12. Gerates DR, Hoehms JD, Burke TG, Grover-McKay M. Thrombolyt- ic-associated cholesterol emboli syndrome: case report and literature review. Pharmacotherapy 1995;15:441-50.
  13. Kassirer J. Atheroembolic renal disease. N Engl J Med 1969;280: 812-8.
  14. Karaday B, Doventas A, Ozkan H, Erdincler DS, Bager T, Yuksel H. A case of cholesterol emboli syndrome treated with iloprost. Anadolu Kardiyol Derg 2007;7:768.
  15. Grant SM, Goa KL. Iloprost. Drugs 1992;43:889-924.
  16. Kalani M, Jorneskog G, Naderi N, Lind F, Brismar K. Hyperbaric oxygen therapy in treatment of diabetic foot ulcers. Long-term follow-up. J Diabetes Complications 2002;16:153-8.
  17. Efrati S, Bergan J, Fishlev G, Tishler M, Golik A, Gall N. Hyperbaric oxygen therapy for nonhealing vasculitic ulcers. Clin Exp Dermatol 2006;32:12-7.
  18. Kuzemko JA, Loder RE. Purpura fulminans treated with hyperbaric oxygen. Br Med J 1970;iv:157.
  19. La van FB, Hunt TK. Oxygen and wound healing. Clin Plast Surg 1990;17:463-72.
  20. Waisman D, Brod V, Wolff R, Sabo E, Chermin M, Weintraub Z, et al. Effects of hyperoxia on local and remote microcirculatory inflamma- tory response after splanchnic ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2003;285:H643-52.

Leave a Reply

Your email address will not be published. Required fields are marked *