Choroidal involvement in patients with catastrophic anti-phospholipid syndrome: Two case reports

Abstract

Purpose

To describe choroidal involvement in catastrophic antiphospholipid syndrome (CAPS).

Methods

We report here two cases of bilateral CAPS choroidopathy in two female patients.

Results

Case report 1: A thirty-five-year-old female patient, with history of primary anti-phospholipid syndrome (APS), treated with anticoagulants, presented an acute renal failure following a salpingectomy. She complained of bilateral acute blurred vision. Ophthalmologic evaluation revealed visual acuity (VA) of 5/10, extensive serous retinal (SRD) detachment, areas of hypofluorescence on fluorescein angiography (FA), and non-perfusion areas in the choriocapillaris, on optical coherence tomography angiography (OCT-A), in both eyes. Considering the diagnosis of probable CAPS, the patient received intravenous pulse steroids, plasmapheresis, intravenous anticoagulation and haemodialysis, with favourable evolution. Case report 2: A thirty-three-year-old female patient, with history of systemic lupus erythematosus (SLE) and secondary APS, treated with corticosteroids, immunosuppressive agents and anti-coagulation, presented a myocardiac infarction. She complained of bilateral acute blurred vision. Ophthalmologic evaluation revealed VA of 1/10 in the RE and 6/10 in LE, bilateral extensive SRD, leakage points on FA and non-perfusion areas in the choriocapillaris on OCT-A. Criteria of probable CAPS were fulfilled. Treatment with intravenous pulse steroids, anticoagulation and reanimation modalities allowed VA improvement. Alveolar haemorrhage and cardiogenic shock led to fatal evolution.

Conclusion

Our case reports highlight the importance of early diagnosis and ophthalmic evaluation in CAPS. Multidisciplinary approach and rapid initiation of effective treatment, based on corticosteroids, anticoagulation and plasmapheresis, allow better vital and visual prognosis.

Introduction

Catastrophic antiphospholipid syndrome (CAPS) is a rare auto-immune menacing condition that causes microthrombosis in multiple organs, mainly the kidneys, the lungs, the gastrointestinal tract, the brain and the heart, leading to acute systemic failure. ¹

This pathology ought to be distinguished from antiphospholipid antibody syndrome (APS) by its acute onset and small vessels involvement. It may be primary, or secondary to underlying disorders, most frequently systemic lupus erythematosus (SLE), ² rheumatoid arthritis or other rheumatologic diseases. ¹

Surgery, pregnancy, post-partum, trauma, infection, oral contraceptive medication or anti-coagulation withdrawal are the most identified trigger factors. CAPS diagnostic criteria, according to Asherson et al., are based on the involvement of three or more organ systems, the histopathological evidence of intravascular thrombosis, and the positivity of antiphospholipid antibodies. ¹

Ophthalmologic manifestations in APS include amaurosis fugax, retinal arterial or venous occlusions, and even optic neuropathy. Ocular involvement in CAPS is rare. To the best of our knowledge, there are few cases in literature describing association between CAPS and retinal occlusions and ischemia, and less commonly, vaso occlusive choroidopathy.

Purpose

To describe choroidal involvement in patients with CAPS.

Case reports

The case notes of the patients were reviewed. We have obtained all patients consent.

*Clinical case 1

A thirty-five-year-old female patient, gravid 6, para 1, with history of four recurrent spontaneous abortions and deep venous thrombosis in the left leg, was diagnosed with primary anti-phospholipid syndrome (APS) and treated with anticoagulants thereafter.

No clinical manifestations of connective tissue disorders or rheumatic diseases were noted. Investigations revealed raised anticardiolipin antibodies levels.

She presented to emergency complaining of abdominal pain. The diagnosis of extra uterine pregnancy was made, and the patient was emergently admitted to gynaecology department for surgical management: a salpingectomy was urgently performed.

A week later, she was hospitalised in nephrology for acute renal failure. Simultaneously, she developed a bilateral sudden blurred vision, and was referred during her hospitalisation episode for an ophthalmologic examination.

The patient's best corrected visual acuity (BCVA) was 5/10 bilaterally. Intraocular pressure and anterior segment examination were unremarkable. Posterior segment evaluation revealed bilateral extensive serous retinal detachments (SRDs) of 4 to 5 papillary diameters (Figure 1a; b).

Figure 1.

Multimodal imaging of the patient 1: a: Fundus photography of the RE showing extensive serous retinal detachment (SRD) of 5 papillary diameters (PD); b: Fundus photography of the LE showing extensive SRD of 4 PD; c/d :Swept source optical coherence tomography (SS-OCT) of the RE/LE revealing giant neurosensory retinal elevation; e/f: Fluorescein angiography (FA) of the RE/LE at early times exhibiting areas of hypo fluorescence, suggesting choroidal hypoperfusion; g/h: SS-OCT of the RE / LE showing regression of extensive SRD, with residual sub-retinal fluid; i/j: OCT-angiography(OCT-A) of the RE/LE revealing non-perfusion areas in the choriocapillaris.

Macular optical coherence tomography (OCT) showed giant neurosensory retinal elevation (RE/LE) (Figure 1c;d). Bilateral widespread areas of hypo fluorescence with macular involvement were seen on fluorescein angiography (FA) at early times, suggesting choroidal occlusions (RE/LE) (Figure 1e;f).

At systemic evaluation, cardiac and pulmonary functions were normal. The systolic blood pressure (BD) was 150 mm Hg, and the diastolic BP was 90 mm Hg. Creatinine and uraemia levels were elevated. Blood cell counts revealed thrombocytopenia and anaemia. Ancillary immunologic tests showed positive antinuclear antibodies, anti-DNA and anti-SSA (ANA+/Anti-DNA+/Anti-SSA+), positive anticardiolipin and negative lupus anti-coagulant antibodies. Renal echography was normal. Kidney biopsy was not performed because of patient's condition.

In view of the severe visual acuity loss, and multiorgan involvement, including the kidney, the genital tract and the eye, the diagnosis of probable catastrophic antiphospholipid antibody syndrome was made, according to Asherson et al. criteria.

Management of this condition, in collaboration with internists and nephrologists, included high doses intravenous infusions of methylprednisolone (1000 mg each), plasma exchange (6 sessions), intravenous immunoglobulins, dialysis and systemic anticoagulation.

Final stage renal failure due to bilateral cortical necrosis proven on MRI was rapidly developing in our patient. Therefore, the patient required undergoing haemodialysis two times a week for end-stage renal disease. She developed hypertension due to chronic renal dysfunction.

She received oral prednisone, anticoagulation with apixaban and a weekly perfusion of rituximab.

Two weeks after initial evaluation, an improvement in ocular symptoms, a visual acuity of 10/10 and a regression of SRDs were observed after treatment. These clinical findings were confirmed with OCT (Figure 1g; h). OCT-A revealed non-perfusion areas in the choriocapillaris, OU (Figure 1i; j).

One month after, the patient presented for control examination. BCVA was 10/10 bilaterally. Adnexal, oculomotor and anterior segment examination was normal. Fundus examination showed no abnormalities.

OCT revealed resolution of subretinal fluid (Figure 2a, b). A decrease in capillary vascular densities in the deep capillary plexus on OCT-A was noted (Figure 2c, d).

Figure 2.

Multimodal imaging of the patient 1: a/b: SS-OCT of the RE /LE showing resolution of sub-retinal fluid; c/d: OCT-A of the RE/LE revealing choriocapillaris non-perfusion areas and decrease in vascular densities in the deep capillary plexus.

Therefore, the patient was referred to nephrologists and internists to control BP levels.

*Clinical case 2

A thirty three-year-old female patient was diagnosed in internal medicine with SLE, manifesting as arthritis, “butterfly” skin rash, leukopenia, myocarditis, lupus nephritis, and secondary APS.

Investigations revealed positive ANA+, anti-DNA+, anti-SSA + and anti-SSB + . Anticardiolipin and lupus anti-coagulant antibodies levels were high. The patient was treated with corticosteroids, cyclophosphamide, hydroxychloroquine and anti-coagulants.

She suddenly presented with fatigue, syncope, hypotension and tachycardia. She was diagnosed with myocardial infarction secondary to SLE myocarditis, and was admitted in internal medicine.

She was referred for acute bilateral blurry vision. Ophthalmological examination found a BCVA of 1/10 in the RE and 6/10 in the LE. Anterior segment evaluation was without abnormalities. Intraocular pressure was normal. Funduscopy revealed multifocal and bilateral SRDs, associated to cotton-wool-spots in the RE/LE (Figure 3a/b). These clinical features were confirmed by SS-OCT, revealing neurosensory retinal elevation in the RE/LE (Figure 3c/d). FA showed multiple choroidal leakage points in the RE/LE (Figure 3e/f). Non-perfusion areas in the choriocapillaris were noted, suggesting choroidal ischemia, on OCT-A in the RE/LE (Figure 3g/h).

Figure 3.

Multimodal imaging of the patient 2: a/b: Fundus photography of the RE/LE showing SRD and cotton-wool spots; c/d: SS-OCT of the RE/LE revealing elevation of neurosensory retina; e/f: FA of the RE/LE showing multiple choroidal leakage points in the RE/LE; g/h:SS-OCT A of the RE/LE exhibiting nonperfusion areas in the choriocapillaris; i/j : SS-OCT of the RE/LE: Partial regression of serous retinal detachment, with residual sub-retinal fluid is noted.

Five days after, the patient was admitted in intensive care unit for acute dyspnea and oliguria. Considering multiorgan involvement including the heart, the lungs and the eye, our patient fulfilled the criteria of probable CAPS. No trigged factor was clearly identified.

Management consisted of intravenous steroids, immunosuppressants, anticoagulation and reanimation modalities including oxygenotherapy and noradreanline.

Ophthalmological follow-up was marked by an improvement in visual acuity and partial regression of SRDs in the RE/LE (Figure 3i/j). However, the patient presented icterus, anemia, thrombocytopenia, and died due to massive alveolar haemorrhage and cardiogenic shock.

Discussion

CAPS is a systemic rare and acute condition, with multiorgan involvement. First described in 1992 by Asherson, this entity represents about 1 to 5% of APS. ¹

Classically, thrombosis involves at least three organs, mostly occurring in small vessels. ¹ Systemic symptoms develop simultaneously, within one week. Poor prognosis is usually associated to this pathology. It can cause systemic failure and high risk of death (about 50%) by disseminated intravascular coagulation (DIC), acute respiratory distress syndrome or myocardial infarctions.¹Cortical renal necrosis represents a severe manifestation of this critical affection, leading to renal dysfunction. ³

A female predominance was described in this syndrome (72% of cases).⁴This multifactorial condition includes genetic predisposition and environmental factors.⁵Its main pathophysiology consists of an acute cytokine-mediated inflammation, endothelial cells activation and thrombosis leading to vaso occlusive events.^1,5

Precipitating factors are trauma, infections, neoplasia, pregnancy or post-partum period, or surgical procedures. In the case of our first patient, obstetrical complications, surgery and anti-coagulation withdrawal were the identified trigger elements. ⁴

Blood cell count can reveal microangiopathic haemolytic anaemia, thrombocytopenia and DIC. ⁷ Patients can present proteinuria and haematuria.⁴Ancillary immunologic tests confirming the diagnosis are positive anti-phospholipid, lupus anticoagulant, anticardiolipin, and antiB2GP1 antibodies. Histological tissue micro thrombosis can be documented by anatomo-pathological findings. ¹

Classic ocular vaso occlusive findings in APS are cotton-wool spots, micro aneurysms, venous tortuosity, vitreous and pre-retinal haemorrhage, SRDs, retinal capillary abnormalities and choroidal atrophy. ⁶

Anterior segment involvement may consist of conjunctival telangiectasis, or micro aneurysms, ⁷ episcleritis, and limbal keratitis. ⁸

Posterior segment ophthalmological manifestations have rarely been reported, including ischemic optic neuropathy, ¹ retinal occlusive vasculitis and less commonly choroidal vessel occlusions. ¹

The choroidal lesions may be due to lack of choroidal auto regulatory vessel ability. Occlusions in posterior ciliary arteries result in choroidal ischemia. ⁹

Rehak et al. reported a case of choroidal occlusion in a 27-year-old female, who presented choroidal oedema in the acute stage and disturbance of choroidal circulation, with wedge shaped choroidal infarctions on FA. ¹⁰

Similarly, Keonard Pek-Kiang Ang et al. described a case of episcleritis and bilateral choroidal infarction in a 25-year-old man, with primary APS. Peripheral choroidal hypoperfusion areas were revealed on FA. Treatment with warfarin and non-steroidal anti-inflammatory agents allowed visual improvement. ¹¹

Bilateral choroidal infarction associated to CAPS was reported by Silva et al., in a 47-year-old male, who presented bilateral SRDs. Treatment with prednisone, rituximab, eculizumab, warfarin, hydroxychloroquine, plasma exchange and hemodialysis led to SRD resolution. ⁹

According to Morel et al., four among their case series of 11 patients developed CAPS choroidopathy, as areas of patchy choroid filling defects, hypofluorescent on FA, with leakage from large choroidal vessels and SRDs. These findings suggested choroidal vessel occlusions. Although elevated BP levels were revealed in three patients, authors suggested that CAPS choroidopathy shared the same pathophysiology and resembles clinically to hypertensive choroidopathy. They concluded that distinguishing these two affections could be difficult, based on other ocular or systemic manifestations. ³

This entity could be also similar to SLE choroidopathy, which indicates the disease activity and precedes SLE nephropathy. ³

Management of CAPS ought to be multidisciplinary, aggressive and urgent. Trigger factors should be controlled. Therapy bases include high doses of corticosteroids, intravenous immunoglobulins and immunosuppressive agents, to control the inflammatory and auto-immune processes. Prolonged high dose anticoagulation, fibrinolysis and plasmapheresis are highly recommended for preventing recurrences.⁴Second-line innovative modalities in refractory forms consist of rituximab, defibrotide, and eculizumab. ¹¹

Retinal photocoagulation is indicated to treat retinal ischemia and prevent retinal neovascularization.

Conclusions

As a conclusion, it is mandatory to recognise CAPS as rapidly progressive entity and a fatal form of APS. A systematic ophthalmological evaluation is warranted, in this affection, in order to detect retinal or choroidal occlusions, prevent further organ micro thrombosis and anticipate fatal evolution. Early initiation of prompt and aggressive treatment allows better recovery rates, and guarantees good vital and visual prognosis. Our cases highlight the preponderance of multidisciplinary approach in the diagnosis and management of CAPS.