Antiphospholipid syndrome presenting with acute digital ischaemia, avascular necrosis of the femoral head and superior mesenteric artery thrombus

Abstract

This case illustrates a rare and unique case of a 73-year-old woman who presents with a rapidly developing digital ischaemia, superior mesenteric artery thrombus with positive-lupus anticoagulant. She then developed avascular necrosis of the femoral head. Discussion of the process of diagnosis and management of antiphospholipid syndrome and catastrophic antiphospholipid syndrome are reported.

Background

This case illustrates a rare and unique presentation of an antiphospholipid syndrome (APS). It brings together aspects of vascular surgery, vascular medicine and rheumatology.

Case presentation

A 73-year-old woman was referred to the rheumatology clinic by her general practitioner with a 5-week history of pain in her hips, knees, shoulders and elbows. She also described numbness, pain and discolouration in her hands and feet the preceding 2 weeks. On examination, the hands and feet were cold and swollen. Apart from both dorsalis pedis, all peripheral pulses were present.

The pain in her hands and feet got worse requiring admission to the hospital. Her forefoot and fingers were white, cold and numb bilaterally. There were gangrenous changes in some of her digits.

Following initial treatment described below, the symptoms in her feet and hands improved. However, after 2 weeks of treatment she described severe pain in her left hip. x-Ray of her left hip revealed avascular necrosis of the femoral head. She underwent a Girdlestone procedure to her left hip where the necrosed femoral head was excised.

Investigations

The erythrocyte sedimentation rate (ESR) was raised at 60. Blood test was negative for antinuclear antibodies, antineutrophil cytoplasmic antibody, rheumatoid factor, immunoglobulins and cryoglobulins. Anticardiolipin antibodies (both IgG and IgM) and platelet count were within normal limits. She was positive for lupus anticoagulant. CT angiogram demonstrated a 50% stenosis of the superior mesenteric artery, with eccentric thrombus seen within the origin. All vessels in the lower limbs were patent to the ankles, apart from an occlusion of the left proximal posterior tibial artery, which recannulated distally (figure 1). Echocardiogram demonstrated no valvular or intramural thrombi, and ECG was unremarkable.

Figure 1.

Digital substraction angiogram demonstrating occlusion of all digital arteries right foot.

Differential diagnosis

In the current case with the initial symptoms of joint pains and a raised ESR a possible diagnosis of polymyalgia rheumatica was considered by the rheumatologist. Later on with the presentation of digital ischaemia the differential diagnosis of vasculitis, Raynaud's disease, small vessel disease and thrombo embolisation was considered. Avascular necrosis of the femoral head is also a recognised side effect of steroid therapy, so this must also be considered.

Treatment

Initially, a short-trial treatment with low-dose prednisolone was started, which seemed to exacerbate her symptoms, and was discontinued. She was then started on intravenous heparin and iloprost. She was also started on intravenous vancomycin as there was evidence of cellulitis on her feet. She was anticoagulated with warfarin before discharge.

Outcome and follow-up

At 3-month follow-up apart from areas of dry gangrene in her digits she has recovered fully and was mobile with a frame (figures 2 and 3). After 6 months, all gangrenous toes had autoamputated, as had some of the gangrenous fingers.

Figure 2.

(A) Initial presentation of feet and (B and C) at 3-month postinitial presentation.

Figure 3.

(A) Initial presentation of hands and (B) at 3-month postinitial presentation.

Discussion

This case report describes a rare and a unique presentation of APS. The combination of mesenteric thrombus, acute ischaemia of all digits and avascular necrosis of the femoral head as presenting feature of APS to our knowledge has not been described before. Clinical presentation of APS in various forms can cause diagnostic dilemma. Early diagnosis and prompt treatment is likely to improve outcome. Clinical manifestation of APS involves multiple systems hence all medical professionals need to be vigilant of this potential life-threatening condition.

Cardiac investigations in the form of echocardiogram and ECG did not support the evidence for thrombo embolic event. Avascular necrosis of the femoral head is a well recognised, although rare, side effect from steroid use. However, it is more commonly linked with high doses of glucocorticoids, so is unlikely to be the cause of avascular necrosis in this case. Small vessel disease like Buerger's disease and diabetes present with chronic ischaemia, and are unlikely to present acutely affecting all digits simultaneously. Diagnosis of vasculitis tends to come from tissue biopsies, which show classical histological changes. In our case, the tissue biopsy was not done as the diagnosis of APS was already made. Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose¹ and PET/CT² are also useful in both diagnosis and monitoring the progression of vasculitis particularly affecting large and medium vessels. In the case described, the disease pattern predominantly affected small vessels only, hence the PET/CT was not done.

APS is an acquired thrombophilia. The diagnosis is made on clinical and laboratory criteria.³ Clinical criteria consist of venous or arterial thrombosis with or without pregnancy morbidity. Laboratory criteria are based on the presence of lupus anticoagulant, anticardiolipin antibody or β2 glycoprotein antibody; however, not all of these immunological markers need to be present to confirm the diagnosis. The patient in the case study fulfils the criteria for the diagnosis of APS. Catastrophic APS is a rapidly developing version of APS characterised by widespread microvascular thrombosis.⁴ Intra-abdominal vessels are most commonly affected, causing mesenteric ischaemia. In the current case, despite thrombus in the superior mesenteric artery, there was no evidence of mesenteric ischaemia. Cardiac, pulmonary, cerebral, renal, hepatic, splenic and adrenal manifestations have also been described.⁵ The rapid onset and progression of symptoms, combined with widespread microvascular thrombosis in the current case supports the diagnosis of catastrophic APS.

The mainstay of treatment for APS is anticoagulation.⁶ Treatment options for refractory disease include steroids, cyclophosphamide, γ-globulins and plasmaphoresis.⁷ Currently, very small numbers of patients have been treated with trials of rituxumab,⁸ defibrotide⁹ and Eculizumab,¹⁰ all of which may play a role in treatment of APS in the future. In the current case, recovery was achieved within 4 weeks with heparin, followed by warfarin therapy alone. The forefoot and fingers improved without the need for amputation. This shows that clinicians should adopt conservative measures to allow demarcation occur naturally in the first instance, unless there is evidence of sepsis.

Learning points.

• Clinicians should consider antiphospholipid syndrome (APS) as a potential cause of digital gangrene.

• Conservative measures should be adopted by clinicians unless there is evidence of sepsis.

• The mainstay of treatment for APS is anticoagulation.