History
Vasospastic or vaso-occlusive events can occur in any organ system in patients with antiphospholipid antibody (aPL) syndrome (APS); thus, a thorough history should be taken, and an organ-specific review of systems should be performed. A broad spectrum of involvement ranging from rapidly progressive to clinically silent and indolent may be present, as follows [4, 5, 6, 7, 8, 13] :
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Head, ears, eyes, nose, and throat
Blurred or double vision
Visual disturbance ("wavy lines,” “flashing lights")
Visual loss (field cuts, total vision loss)
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Cardiorespiratory
Chest pain
Radiating arm pain
Shortness of breath
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Gastrointestinal
Abdominal pain
Abdominal distension (bloating)
"Abdominal migraine"
Emesis
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Peripheral vascular
Leg pain
Leg swelling
Claudication
Digital ulcerations
Leg ulcerations
Cold-induced finger pain, toe pain, or both
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Musculoskeletal
Bone pain
Joint pain
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Cutaneous
Purpuric rashes, petechial rashes, or both
Persistent or transient lacy rashes of livedo reticularis
Dusky fingers, dusky toes, or both
Blanching of fingers, blanching of toes, or both
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Endocrine - Weakness, fatigue, arthralgia, abdominal pain (Addisonian features)
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Genitourinary/renal
Hematuria
Peripheral edema
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Pregnancy-related history - Not expected to be of frequent concern in the field of pediatrics but may be significant in teenagers
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Family history
A strong family history is more pertinent to most pediatric patients and may assist in identifying patients at risk.
Family history may include the following:
Frequent miscarriage, premature birth, intrauterine growth retardation (IUGR), oligohydramnios, chorea gravidarum, placental infarction, preeclampsia, toxemia of pregnancy, or neonatal thromboembolism
Myocardial infarction or stroke in persons younger than 50 years
Deep vein thrombosis (DVT), phlebitis, or pulmonary embolus
Strong family history of migraine, Raynaud phenomenon, or transient ischemic attacks (TIAs)
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Medication history - Use of oral contraceptives at the time of a clinical event
Physical Examination
Physical findings are specific to the affected organ and can involve any organ system. [45] Catastrophic antiphospholipid antibody syndrome (CAPS) is a multisystem failure secondary to thrombosis, infarction, or both and has a picture of microangiopathy on histology. [46, 47, 48, 49, 20, 50] Possible findings are as follows:
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Peripheral vascular
Point tenderness to palpation of bone or joints (bone infarction), as shown below
CAPS, Bone Infarction - MRI (High Resolution Proton Density and STIR images) and Nuclear Bone Scan - Patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. MRI shows multiple infarctions in the distal tibia, tarsal bones and metatarsal bones (extensive bone marrow edema and increased T1 with fat saturation signal in the calcaneus bones). Flow and early blood pool images of technetium 99m bone scan show increase in activity in both heel regions with focal areas of decreased activity in the center of each calcaneus.
Pain on range of motion of joints without arthritis (avascular necrosis)
Limb swelling (DVT)
Peripheral edema (DVT, renal vein thrombosis)
Decreased capillary refill (arterial thrombosis, vasospasm)
Decreased pulses (arterial thrombosis, vasospasm)
Decreased perfusion (arterial thrombosis, vasospasm)
Gangrene (arterial thrombosis, infarction), as shown below
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Extensive involvement of all digits is noted, some with distal infarction and dry gangrene, others healing with residual eschar (and undermining epithelialization), and some with re-epithelialization and scarring. Healed superficial epidermal damage and desquamation is also present.
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Eschar is still present on first digit bilaterally. More superficial lesions are shown here, with evolution and healing of lesions on all other toes.
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Pulmonary - Respiratory distress, tachypnea (pulmonary embolism [PE], pulmonary hypertension) [51]
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Renal [52, 53, 54, 55, 56, 57]
Hypertension (renal artery thrombosis, intrarenal vascular lesions)
Hematuria (renal vein thrombosis)
Acute renal insufficiency (intrarenal vascular lesions), as shown below
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessels (periodic acid-Schiff [PAS], original magnification X40). Bottom: Thrombosed kidney vessels (PAS, original magnification X20). Lumen is filled with eosinophilic fibrin with overlying injured endothelial cells. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessel (hematoxylin and eosin [H&E] stain, original magnification X20). Lumen is occluded with fibrin. A perivascular stromal reaction with degenerating inflammatory cells is observed. Bottom: Thrombosed kidney vessel (H&E stain, original magnification X20). Lumen is occluded with fibrin. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Thrombosed kidney vessel with recanalization (arrows) (Jones stain, original magnification X20). Architectural distortion in the surrounding stroma is observed. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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GI
Right upper quadrant tenderness, hepatomegaly (Budd-Chiari syndrome, [64] hepatic small vessel thrombosis, hepatic infarction)
Abdominal tenderness (mesenteric artery thrombosis)
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Endocrine - Muscle weakness, progressive stiffening of pelvic and thigh muscles with flexion contractures associated with adrenal insufficiency (adrenal infarction/hemorrhage) [65]
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Ocular
Retinal artery occlusion
Retinal vein thrombosis
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Skin manifestations
Livedo reticularis, shown below
Palmar livedo reticularis associated with antiphospholipid antibody syndrome may range from a lacy, flat, reticulated pattern to a more confluent, nonblanching, slightly raised rash (secondary to extravasation of RBCs and plasma).
Livedo reticularis of the upper and lower extremities in a 15-year-old adolescent with primary antiphospholipid antibody syndrome. The pattern is lacy, flat, and nonblanching. The purplish hue is from stasis in the small vessel beds.
Purpuric lesions, as shown below
Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern and evolved as a confluent, nonblanching, slightly raised purpuric rash in the same reticular pattern.
Superficial thrombophlebitis
Vasospasm (ie, Raynaud phenomenon), as shown below
Muddy discoloration and mild diffuse swelling of the fingers observed as part of the Raynaud phenomenon, which is associated with antiphospholipid antibody syndrome. At room temperature, this patient still has decreased capillary refill and cold fingers despite treatment with pentoxifylline. The discoloration extends proximally onto the palms and turns blue-purple when exposed to cold.
Splinter hemorrhages (periungual, subungual), as shown below
Linear splinter hemorrhages are found under the nails of fingers and toes. These may be solitary or multiple and appear intermittently.
Peripheral infarctions (digital pitting), as below
Digital infarctions in a patient with systemic lupus erythematosus with antiphospholipid syndrome (APS) and long-standing Raynaud symptoms. Multiple and repeated digital infarctions are depicted, resulting in ulcerations and scarring. Scars and hyperpigmentation are also seen on the palmer aspect of hands and fingers.
Skin ulcerations (eg, leg ulcers)
Petechiae (associated with thrombocytopenia), as shown below
Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and thrombocytopenia. Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern, is observed.
Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern and evolved as a confluent, nonblanching, slightly raised purpuric rash in the same reticular pattern.
Bruising (associated with thrombocytopenia)
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Central or peripheral nervous system abnormalities [66, 67, 68, 69]
Stroke, cerebrovascular accident (CVA)
TIA
Paresthesia, polyneuritis, or mononeuritis multiplex (vasovasorum ischemia/infarction)
Paralysis, hyperreflexia, weakness (transverse myelitis, Guillain-Barré syndrome)
Movement disorders - Choreiform tremors (cerebral, cerebellar, basal ganglia infarction)
Multiple sclerosis–like disorder
Learning disability
Short-term memory loss
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Palmar livedo reticularis associated with antiphospholipid antibody syndrome may range from a lacy, flat, reticulated pattern to a more confluent, nonblanching, slightly raised rash (secondary to extravasation of RBCs and plasma).
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Livedo reticularis of the upper and lower extremities in a 15-year-old adolescent with primary antiphospholipid antibody syndrome. The pattern is lacy, flat, and nonblanching. The purplish hue is from stasis in the small vessel beds.
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Muddy discoloration and mild diffuse swelling of the fingers observed as part of the Raynaud phenomenon, which is associated with antiphospholipid antibody syndrome. At room temperature, this patient still has decreased capillary refill and cold fingers despite treatment with pentoxifylline. The discoloration extends proximally onto the palms and turns blue-purple when exposed to cold.
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Linear splinter hemorrhages are found under the nails of fingers and toes. These may be solitary or multiple and appear intermittently.
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One set of suggested algorithms for the workup and treatment of patients with antiphospholipid antibody syndrome. This should not be considered dogmatic because laboratory evaluation is not standardized and treatment remains empiric and controversial. Laboratory testing is not recommended in healthy asymptomatic individuals with no risk factors and a negative family history.
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Occlusion of the right middle cerebral artery in a 3-year-old child with severe headache and hemiparesis associated with anticardiolipin antibodies.
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Organizing thrombus in an aortic valve in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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High-power degenerating aortic valve in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and recurrent thrombotic events. The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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Trichrome stain of a thrombus in the intestinal serosa in a patient who has positive test results for antiphospholipid antibody and lupus anticoagulant and who has systemic lupus erythematosus (SLE) and catastrophic antiphospholipid antibody syndrome (CAPS). The authors acknowledge the help of Hannes Vogel, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessels (periodic acid-Schiff [PAS], original magnification X40). Bottom: Thrombosed kidney vessels (PAS, original magnification X20). Lumen is filled with eosinophilic fibrin with overlying injured endothelial cells. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Top: Thrombosed kidney vessel (hematoxylin and eosin [H&E] stain, original magnification X20). Lumen is occluded with fibrin. A perivascular stromal reaction with degenerating inflammatory cells is observed. Bottom: Thrombosed kidney vessel (H&E stain, original magnification X20). Lumen is occluded with fibrin. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE), World Health Organization (WHO) class IV lupus nephritis, and acute renal failure. Thrombosed kidney vessel with recanalization (arrows) (Jones stain, original magnification X20). Architectural distortion in the surrounding stroma is observed. The authors acknowledge the help of Karen W. Eldin, MD, in preparing this image.
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Antiphospholipid antibody syndrome in a patient with positive test results for antiphospholipid antibody and lupus anticoagulant who has systemic lupus erythematosus (SLE) and thrombocytopenia. Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern, is observed.
-
Livedo reticularis of the upper extremities, which developed as petechiae in the classic lacy, reticular pattern and evolved as a confluent, nonblanching, slightly raised purpuric rash in the same reticular pattern.
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Digital infarctions in a patient with systemic lupus erythematosus with antiphospholipid syndrome (APS) and long-standing Raynaud symptoms. Multiple and repeated digital infarctions are depicted, resulting in ulcerations and scarring. Scars and hyperpigmentation are also seen on the palmer aspect of hands and fingers.
-
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Extensive involvement of all digits is noted, some with distal infarction and dry gangrene, others healing with residual eschar (and undermining epithelialization), and some with re-epithelialization and scarring. Healed superficial epidermal damage and desquamation is also present.
-
A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. Eschar is still present on first digit bilaterally. More superficial lesions are shown here, with evolution and healing of lesions on all other toes.
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CAPS, Bone Infarction - MRI (High Resolution Proton Density and STIR images) and Nuclear Bone Scan - Patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. MRI shows multiple infarctions in the distal tibia, tarsal bones and metatarsal bones (extensive bone marrow edema and increased T1 with fat saturation signal in the calcaneus bones). Flow and early blood pool images of technetium 99m bone scan show increase in activity in both heel regions with focal areas of decreased activity in the center of each calcaneus.
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A patient with multisystem small vessel coagulopathy (microangiopathy) but no known underlying disease process. The technetium 99m bone scan reveals irregular multifocal areas of tracer accumulation within the left ventricle of the heart suggestive of myocardial infarction and altered calcium deposition. Irregular cutaneous and subcutaneous uptake is noted in multiple areas of the torso and upper arms (as well as in the upper thighs). High-resolution CT scanning of the chest reveals extensive calcification involving the myocardium, the mitral and tricuspid valve annuli, the aortic valve annulus, the proximal right coronary artery, and the left main coronary artery.
