Department of Medicine, Groote Schuur Hospital, J47 Old Main Building, Cape Town, South Africa,
1 Directorate of Pathology, Royal United Hospital, Bath BA1 3NG and
2 Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, UK
Correspondence to:
Y. I. Patel.
Sir, Since antiphospholipid syndrome (APS) was first described in 1983 [1], many complications have been reported which result from vascular occlusion as a result of thrombosis [2]. More recently, a few cases have been described where a proliferative vasculopathy appears to have been the major mechanism of vascular occlusion rather than thrombosis or vasculitis [35]. Relatively few cases have been described with intestinal infarction as a result of vascular occlusion from this `proliferative vasculopathy' of APS [69]. We describe one such patient who had massive intestinal infarction as a result of a proliferative vasculopathy involving the coeliac, superior mesenteric (SMA), and inferior mesenteric arteries (IMA).
A 43-yr-old female was first referred to us in January 1994 when she was diagnosed as having systemic lupus erythematosus with APS. The clinical features up to that point (developing over a 10 yr period) included polyarthralgia, immune thrombocytopenia necessitating a splenectomy, livedo reticularis, Raynaud's phenomenon, photosensitive skin disease, myocardial dysfunction with evidence of a left ventricular thrombus, and neurological events including initial transient facial weakness followed years later by a right sided middle cerebral artery stroke. She recovered from the neurological deficits except for a dysarthria for which she used an electronic communicator. Over the years the patient also developed hypertension with small smooth kidneys but normal renal function and no proteinuria. Interestingly, she had no history of fetal wastage (three sons and no miscarriages). Blood results included a positive antinuclear antibody (1/2560, homogeneous pattern) and DNA binding (237 IU/ml, normal <100 IU/ml). IgG anticardiolipin antibodies were mildly elevated at 1012 GPL and IgM always negative (on repeated measurement). Antibodies to ß2-GP1 were also negative. Protein C, protein S and complement levels were normal. Of interest, there was a mild prolongation of the PTT (partial thromboplastin time) at the time of the stroke, suggesting the presence of a lupus anti-coagulant. The platelet count always remained stable but depressed at around 120x109/l.
The patient remained well for a year on therapy with lisinopril, nifedipine, hydroxychloroquine, erythromycin and warfarin at optimal doses (INR always maintained at 34). However, in April 1996 she developed symptoms ascribed to an irritable bowel syndrome. Within 2 months she lost 6 kg in weight and was having symptoms of mesenteric angina. Endoscopy revealed multiple haemorrhagic areas in the small and large bowel, biopsies of which showed no vasculitis or thrombosis. However, histological features were in keeping with mucosal ischaemia. In the interim the patient developed an `acute abdomen' and required urgent laparotomy. She was found to have extensive infarction involving the jejunum, ileum and large bowel extending to the sigmoid region, all of which required resection. Although inspection of the intestinal vessels appeared normal at surgery, intra-operative angiography revealed total occlusion of coeliac, SMA and IMA at their origins (with the right renal artery resembling radiological features of fibromuscular hyperplasia at its origin; Fig. 1). There was very extensive collateral vessel formation from the iliac and internal thoracic arteries indicating chronicity of the vascular disease. Despite intensive surgical and medical efforts including bowel resection, SMA revascularization by venous grafting, parenteral feeding, intravenous antibiotics, and total anti-coagulation, the patient continued to deteriorate with ongoing features of ischaemia in the residual bowel. It was thus decided to embark on immunosuppression with pulse cyclophosphamide and steroids, but after a very brief and marginal improvement the patient developed pulmonary complications and died 6 weeks later.
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There is some controversy as to whether the pattern of vascular involvement in APS with intimal/medial hyperplasia (histologically) and fibromuscular hyperplasia (radiologically) entails a distinct vasculopathy [35, 10]. It is possible that any vasculitis that may be present constitutes a feature of coexistent connective tissue disease and may not be responsible for the proliferative changes seen in the intima and media of the vessels. In addition, the current evidence is insufficient to exclude the possibility that the proliferative vasculopathy is part of a recanalization process secondary to thrombosis [11]. Interestingly, there is a striking similarity in the intimal and medial hyperplasia to the vascular remodelling that accompanies hypertension [12]. Further research is required in order to dissect out the relative contributions to the pathogenesis of the vasculopathy by the hypertension, thrombosis and recanalization, and endothelial dysfunction (due to current or remote vasculitis). Clearly, the implications for our management of these patients are immense. At present, therapy is largely restricted to anticoagulation and the use of immunosuppression and/or plasmapheresis where indicated. Immunosuppressive therapy is often associated with disastrous consequences as a result of infection. The role of fibrinolytic therapy is unknown, but it is unlikely that fibrinolytic drugs would have influenced the vascular proliferative changes seen in our patient.
This case demonstrates the importance of early recognition of mesenteric angina, a symptom that must be actively sought in any patient with APS. Appropriate investigations at an early stage may help to define the frequency of vascular proliferative changes in the pathogenesis of the disease, and may also direct relevant intervention with modalities such as balloon angioplasty in an attempt to avert the disastrous consequences associated with late detection of bowel infarction. However, further systematic analysis of patients with APS and bowel ischaemia is indicated in order to understand fully the relative roles of the proliferative vasculopathy vs thrombosis.
We acknowledge the multiple team members involved in the management of the patient, specifically Drs M. Harron (surgery), J. Rademaker (medicine), I. Bailey (surgery), and C. J. Meehan and Professor S. Love (pathology).
References