Rare yet catastrophic presentation of undiagnosed antiphospholipid syndrome

Abstract

A previously well 31-year-old woman initially presented to the emergency department with pneumonia, however, was found to be hypertensive and have new-onset cardiomegaly. She was admitted for intravenous antibiotics and concurrently a series of investigations were conducted to investigate hypertension and cardiomegaly. During the course of admission, she developed acute kidney injury and was found to have acute chronic occlusion in the abdominal aorta. She was diagnosed with catastrophic antiphospholipid syndrome. This is a rare form of antiphospholipid syndrome with a high mortality rate. Thus, it is important that clinicians are aware of this syndrome to facilitate early diagnosis and initiation of treatment.

Background

Catastrophic antiphospholipid syndrome (CAPS) is a rare, life-threatening condition occurring in approximately 1% of patients with antiphospholipid syndrome (APS).¹ It is characterised by diffused microvascular thrombosis and as a result, has diverse clinical manifestations based on the organ system involved.² Due to its rarity and broad clinical features, diagnosis is often difficult. Without treatment, CAPS has a high mortality rate.³ The most widely accepted treatment for CAPS is ‘triple therapy’ with anticoagulation, glucocorticosteroid and intravenous immunoglobulin and/or plasmapheresis.^{3 4} This report presents a case of CAPS in an otherwise healthy young woman, as her first presentation of APS.

Case presentation

A 31-year-old indigenous woman presented to a rural hospital in New South Wales, Australia with a 6 week history of respiratory symptoms. The patient was an otherwise well woman with no significant medical history. Her obstetrical history is significant for one medically terminated pregnancy and two uncomplicated pregnancies.

On admission, her blood pressure was elevated (198/120 mm Hg) and heart rate was 100 beats per minute. The rest of the vital signs were within the normal limits. The patient had bronchial breath sounds on the right side on auscultation. The rest of the physical examination was unremarkable. Chest X-ray on admission revealed new-onset cardiomegaly with diffused air space opacity within the mid to lower zones bilaterally with multiple lateral interstitial lines and pulmonary venous congestion (figure 1). CT of the chest showed ground-glass opacities with mediastinum lymphadenopathy consistent with potential viral pneumonia such as COVID-19. Initially, her white cell count (WCC), C reactive protein (CRP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) were elevated at 21.3×10⁹/L, 212 mg/L and 16 788 ng/L, respectively. Her renal and liver functions were unremarkable with creatinine of 72 µmol/L on admission.

Figure 1.

Chest X-ray on admission.

Subsequently, the patient was commenced on azithromycin and ceftriaxone for pneumonia and concurrently, a series of investigations including a transthoracic echocardiogram (TTE) and renal vascular ultrasound were performed to investigate hypertension and raised pro-BNP.

The TTE showed mild mitral regurgitation and severe systolic dysfunction with an ejection fraction of 32%. Furosemide, ramipril, spironolactone and bisoprolol were commenced.

The initial renal Doppler ultrasound did not show any renal artery stenosis; however, there was an incidental finding of aortic occlusion below the superior mesenteric artery. CT scan of the abdomen performed on day 4 of admission confirmed a 7 cm filling defect in the abdominal aorta inferior to the left renal artery with apparent occlusion of the right renal artery. There were extensive collateral vessels from the distal abdominal aorta, thoracic, pelvic vessels and femoral vessels, suggestive of the chronicity (figure 2). Retrospectively, the patient had symptoms of claudication of lower limbs for some time. Furthermore, the patient’s renin level was elevated at 116 mU/L, consistent with renovascular hypertension.

Figure 2.

CT angiogram of the abdomen showing occlusion in the abdominal aorta with extensive collateral vessels.

Concurrently, the patient developed bilateral ear pain associated with discolouration of the helix (figure 3), symptoms she had experienced previously but was new to her admission.

Figure 3.

Relapsing polychondritis.

A provisional diagnosis of large vessel vasculitis and relapsing polychondritis were made. The patient was commenced on azathioprine and pulse therapy with methylprednisone, which improved the patient’s auricular inflammation clinically and biochemically. She was also commenced on therapeutic anticoagulation with low molecular weight heparin and was screened for vasculitis and thrombophilia including antiphospholipid antibodies.

On day 5 of admission, the patient developed acute kidney injury (AKI) with an increase in creatinine to 124 µmol/L. The patient’s renal function continued to deteriorate with a creatinine rise to 328 µmol/L and progression to anuria and fluid overload by day 10. The renal vascular ultrasound was repeated, which demonstrated likely extension of the aortic occlusion to involve the coeliac axis and no arterial venous flow within the renal vessels, accounting for the worsening renal function. Other causes of AKI were considered such as drug-induced renal injury; however, it was deemed less likely to be the main cause of AKI given worsening renal function despite the withdrawal of nephrotoxic medications such as loop diuretic and angiotensin-converting enzyme (ACE) inhibitor. Furthermore, the association of contrast to AKI was also considered. While it is possible that the use of contrast exacerbated the kidney injury particularly in the setting of already reduced perfusion to the kidneys and use of nephrotoxic, contrast-induced nephropathy was not deemed likely to be the main cause of the initial decrease in renal function as the development of AKI occurred within 24 hours of contrast use.

The patient’s anticoagulation was changed to heparin infusion and was urgently transferred to a tertiary hospital for subspecialty review by the interventional radiology, vascular surgery, nephrology, cardiology and immunology services. She was deemed not for any interventions for her thromboses such as stenting, thrombolysis or operative management at the time due to outweighing risks. While in the tertiary hospital, the patient underwent a fluorodeoxyglucose (FDG)-positron emission tomography (PET) which showed no evidence of large vessel vasculitis and shortly after, the patient’s lupus anticoagulant, anticardiolipin antibodies and anti-beta-2-glycoprotein I antibodies all returned positive. Based on the clinical picture and antibodies, a provisional diagnosis of CAPS was made.

Outcome and follow-up

While in the tertiary hospital, the patient was commenced on intermittent haemodialysis and remained on therapeutic anticoagulation and glucocorticosteroid. Plasma exchange was trialled but was ceased after 1 week with no improvement in her renal function.

The patient had cardiac MRI performed during her admission, which showed no evidence of previous infarction. The patient did not have a coronary angiogram as it was hoped her renal function would improve.

The patient’s haemodynamic and renal function remained stable on the above treatment regime and hence was discharged home on vitamin K antagonist with a plan for ongoing dialysis and follow-up in the community.

The antiphospholipid antibody screening was repeated 16 weeks post the initial event and the patient’s anti-beta-2-glycoprotein I antibodies remained positive. Due to being anticoagulated and as the patient refused renal biopsy on multiple occasions, there is no histological confirmation of small vessel occlusion. Hence, the patient met three out of four diagnostic criteria for CAPS, confirming the initial diagnosis of probable CAPS.

Discussion

APS is an autoimmune condition, characterised by intravascular thrombosis and/or pregnancy morbidity associated with the persistent presence of at least one of the antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies and/or anti-beta-2-glycoprotein I antibodies).⁵ CAPS is its most severe form. It is rare, occurring in approximately 1% of APS patients and has a high mortality rate.^{1 3} Approximately, half of the first presentation of APS presents as CAPS.⁴

APS can coexist with another disease such as systemic lupus erythematosus (SLE). Relapsing polychondritis also commonly coexists with other conditions, most commonly with systemic vasculitis. The possible association between RPC and APS directly has been reported and this case also supports the possible link between the two conditions.^{6 7}

In contrast to APS which usually affects medium to large vessels, CAPS is characterised by diffused thrombotic microvasculopathy, developing over a short period.³ By its diagnostic criteria, thromboses in definite CAPS affect three or more organs, systems and/or tissues simultaneously or in less than 1 week. The diagnosis also requires laboratory confirmation of the persistent presence of antiphospholipid antibodies 12 weeks apart and histological confirmation of small vessel occlusion in at least one organ or tissue.² In cases of lack of histological confirmation of small vessel occlusion and hence only meeting three out of four diagnostic criteria, such as in this case presentation, diagnosis of probable CAPS is made rather than definite CAPS.

Due to its rarity, its pathogenesis is poorly understood. However, it is thought to be multifactorial involving both innate and adaptive immune systems. In patients with the presence of antiphospholipid antibodies, there is a primary, genetic susceptibility to clot formation, known as the ‘first hit’.⁸ However, this increased thrombophilic risk is not sufficient to initiate clot formation. A ‘second hit’ by environmental or inflammatory factor is needed to trigger a thrombus formation. The most widely recognised environmental factors include infections, recent surgery and malignancy.⁹

The clinical features of CAPS are diverse as they stem from the organ systems affected by the thromboses. The kidneys are the most frequently affected organ, mainly presenting as renal insufficiency and proteinuria.¹⁰ Development of cardiac problems is also commonly seen, manifested by left ventricular dysfunction, valvular insufficiency and less commonly, myocardial infarction.¹¹ The clinical manifestations also result from the development of dramatic systemic inflammatory response syndrome (SIRS). Both processes are thought to be caused by the excessive release of cytokines, presumably from the affected and necrotic tissues.¹²

The treatment of CAPS is directed towards treating the thrombotic event with anticoagulation and suppressing the cytokine cascade. In addition to treating the precipitating factors, the most widely accepted treatment of CAPS is ‘triple therapy’ with anticoagulation, glucocorticosteroid and plasmapheresis and/or intravenous immunoglobulins.³ Other immunomodulatory agents, specifically rituximab and eculizumab are considered potential treatment options for refractory and/or relapsing CAPS.⁴

Patient’s perspective.

It was horrifying. I was in the intensive care unit, having every test under the sun. I thought I was dying and I was saying goodbyes to my friends and family. I am experiencing a number of side effects from the medications I’m on at the moment, but I can’t complain. I haven’t had any flare ups of ear pain from relapsing polychondritis. I had seen my doctor (GP) about pain in the legs and I was initially told it was related to shoes I was wearing. It all makes sense now. The doctor told me she never suspected intermittent claudication because I wasn’t in the right age bracket for it and didn’t have any other risk factors. One thing I want people to take home from my case is to have a low threshold for testing people for antiphospholipid syndrome.

Learning points.

• This case presented catastrophic antiphospholipid syndrome (CAPS) in a young otherwise healthy woman, as her first presentation of antiphospholipid syndrome (APS). Approximately half of APS first presents as CAPS.

• CAPS is a rare, life-threatening condition that can present with a wide variety of clinical features making the diagnosis challenging.

• It is important for clinicians to be aware of CAPS to facilitate early recognition and initiation of management which is crucial in anyone with clinical suspicion of CAPS.

• Triple therapy with anticoagulation, glucocorticosteroid and intravenous immunoglobulin and/or plasmapheresis is the recommended empirical treatment.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).