Efficiency of colchicine and corticosteroids in a leg ulceration with cholesterol embolism in a woman with rheumatoid arthritis

L. Verneuil, R. Ze Bekolo, A. Dompmartin, F. Comoz1, C. Marcelli2 and D. Leroy

Departments of Dermatology,
1 Anatomo-Pathology and
2 Rheumatology, CHRU Caen, Avenue Côte de Nacre, 14000 Caen, France

SIR, We report a case of a leg ulceration caused by cholesterol embolism, with an aspect of a vascular ulcer, improved by colchicine and corticosteroids.

A 71-yr-old woman, with a rheumatoid arthritis stabilized with methotrexate and salazopyrine, was hospitalized for a 2 yr history of an ulceration of the right leg. The ulcer was 12 cm in diameter, fibrinous, painful and with inflammatory margins, but no livedo, nodule or purpura. She had palpable pulses. Duplex ultrasonography showed an incompetence of the sapheno-femoral junction and an haemodynamically significant superficial femoral arterial stenosis in the Hunter area. Standard biology, proteinuria, antithrombin III, protein C, S, homocystein, factor V Leiden and cryoglobulin were normal or negative. IgM rheumatoid factors were positive (208 IU; normal value <10 IU; ELISA) as well as a anti-ß2GP1 IgG antibody (27 AU). Erythrocyte sedimentation rate (ESR) was 26 mm/h and C reactive protein (CRP) 40 mg/l. A biopsy of the ulcer revealed a lymphocytic infiltrate in the dermis without vasculitis and capillary thrombosis. Treatment with vacuum-assisted closure followed by a skin graft failed and the margins of the ulcer became necrotic. A bilateral femoral arteriogram showed the right femoral stenosis. A percutaneous transluminal angioplasty was realized, but the ulcer enlarged and was nearly circumferential. The positivity of anti-ß2GP1 antibody was confirmed (31 AU), so the patient received an anticoagulant therapy to treat a possible thrombosis, but the ulcer enlarged. After a few months, she was hospitalized for asthenia, weight loss and increase of the pain of the ulcer. The ulceration was enlarged with the tendon tibialis anterior denuded (Fig. 1A). ESR was 132 mm/h and CRP 152 mg/l. A biopsy of the ulcer showed cholesterol clefts within the lumen of dermal blood vessels (Fig. 2). Anticoagulation was stopped and colchicine 2 mg/day was started. The ulcer improved. Because of a serious diarrhoea, colchicine was discontinued and switched for prednisolone 40 mg/day. When the gastrointestinal side-effects diminished, colchicine was started again and amount of prednisolone was lowered. Healing of the ulcer was dramatic, with granulation tissue covering the tendon and epithelialization of the edges. Four months later, three-quarters of the ulcer was healed with colchicine 2 mg/day and prednisolone 10 mg/day (Fig. 1BGo).



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FIG. 1.
 
This leg ulcer without livedo is an unusual cutaneous manifestation of cholesterol crystal embolization. This clinical presentation closely resembles a stasis ulcer. In a review of 223 patients presenting with cholesterol crystal embolization, Falanga et al. [1] found that the skin is involved in 35% of cases. These manifestations are usually painful, and occur in the presence of palpable pulses. Livedo reticularis is the most common (49%), followed by gangrene, purple toes, ulcerations, nodules and purpuric lesions. Ulcers were mainly confined to the toes and feet, and rarely involved the legs. They appear in the centre of a nodule, and are small and well delineated [1].Go



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FIG. 2. Cutaneous biopsy taken from the edge of the ulceration. (A) Necrosis of the right part of the epidermis. (B) Obliteration of an arterial by several cholesterol crystals by thrombotic material in the deep dermis. (Haematoxylin and eosin stain; original magnifications: A, x2.5; B, x10.)

 
The clinical manifestations of cholesterol crystal embolism may resemble a systemic vasculitis as polyarteritis nodosa: blue toe syndrome, livedo reticularis, cutaneous nodules, arterial hypertension, altered mental status, gastrointestinal perforation, renal insufficiency or pancreatitis [2]. The ESR is often elevated even when cholesterol crystal embolism is restricted to the legs. Biopsy specimens show granuloma with giant cells, macrophages and neutrophils mixed with intravascular thrombosis and vasculitis changes [3].

Potential precipitating factors are identified in one-third of cases, and are: anticoagulant, angioplasty, vascular surgery, catheterization and fibrinolysis. In our case, the ulcer's aggravation after angioplasty and anticoagulant therapy was caused by cholesterol embolism. Initially the patient's ulceration could be secondary to arteritis and/or to cholesterol crystal embolism. However, all the features are in favour of cholesterol embolism. There is no argument for vasculitis provoked by rheumatoid arthritis. Moreover, the patient was on methotrexate, which seems to be efficacious in these cases of vasculitis [4, 5]. Our patient did not have the manifestations of Felty's syndrome in which leg ulcers are frequent, and did not have the continued rapid expansion of a pyoderma gangrenosum.

With respect to therapy, the vascular surgery of the atheromatous plaque is theoretically ideal. However, a large prospective study [6] failed to show any benefit of surgical treatment over medical therapy. Some authors have suggested that the withdrawal of anticoagulants is common and that corticosteroids may be effective in treating cholesterol embolism [7], particularly an intractable leg ulceration caused by cutaneous cholesterol embolism dramatically healed within 3 weeks treatment with prednisolone [8]. Dahlberg et al. [9] had a rapid resolution of cutaneous peripheral embolization in two patients treated with corticosteroids. Cholesterol embolism probably perpetuates the ischaemic process. Therefore, corticosteroid could reduce this local or general inflammatory response [9]. Colchicine also seems to be effective, limiting the chemotactic and phagocytic activity of polymorphonuclear lymphocytes [10]. If colchicine is not sufficient to control ischaemia or systemic inflammation, it seems logical to treat them with corticosteroids in the same way as systemic small vessels vasculitis [7].

Notes

Correspondence to: L. Verneuil. E-mail: laurence.verneuil{at}bichat.inserm.fr Back

References

  1. Falanga V, Fine MJ, Kapoor WN. The cutaneous manifestations of cholesterol crystal embolization. Arch Dermatol 1986;122:1194–8.[Abstract]
  2. Cappiello RA, Espinoza LR, Adelman H, Aguilar J, Vasey FB, Germain BF. Cholesterol embolism: A pseudovasculitic syndrome. Semin Arthritis Rheum 1989;18:240–6.[ISI][Medline]
  3. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology 1987;38:769–84.[ISI][Medline]
  4. Espinoza LR, Espinoza CG, Vasey FB, Germain BF. Oral methotrexate therapy for chronic rheumatoid arthritis ulcerations. J Am Acad Dermatol 1986;15:508–12.[ISI][Medline]
  5. Upchurch KS, Heller K, Bress NM. Low-dose methotrexate therapy for cutaneous vasculitis of rheumatoid arthritis. J Am Acad Dermatol 1987;17:355–9.[ISI][Medline]
  6. Vayssairat M, Chakkour K, Gouny P, Nussaume O. Embolies athéromateuses. Embolies de cholestérol: traitement médical. J Mal Vasc 1996;21:97–9.[ISI][Medline]
  7. Cosserat J, Bletry O, Frances C et al. Embolies multiples de cholestérol simulant une périartérite noueuse. Presse Méd 1992;21:557–64.[ISI][Medline]
  8. Davies DJ, Thurasingham K. Intractable leg ulceration caused by cutaneous cholesterol embolism. Med J Aust 1992;157:267–8.[ISI][Medline]
  9. Dahlberg PJ, Frecentese DF, Cogbill TH. Cholesterol embolism: Experience with 22 histologically proven cases. Surgery 1989;105:737–46.[ISI][Medline]
  10. Sullivan TP, King LE, Boyd AS. Colchicine in dermatology. J Am Acad Dermatol 1998;39:993–9.[ISI][Medline]
Accepted 19 December 2002





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