A 34-Year-Old Woman With Knots on Her Leg and Reddening Skin

Padma Chitnavis, MD; Mary Maiberger, MD

Disclosures

May 19, 2023

In addition to treating the primary causative condition, thrombophlebitis can also be managed with supportive therapy. Low-molecular-weight heparins (LMWHs) are considered the drug of choice. These, along with nonsteroidal anti-inflammatory drugs (NSAIDs), have been shown to reduce the extension of thrombi into DVTs.[3,6] Direct thrombin inhibitors and the factor Xa inhibitor rivaroxaban have also been shown to be of some benefit. NSAIDs can also provide symptomatic relief and may be used in conjunction with ice and compression.[6]

In this case scenario, the patient presented with several historical and physical examination findings concerning for systemic lupus erythematosus (SLE) and APS. Both of these diseases are systemic autoimmune conditions that can have devastating manifestations in many organ systems. Although patients with APS frequently have a diagnosis of SLE, a diagnosis of SLE is not required in order for someone to have APS. In fact, numerous autoimmune, rheumatic, infectious disorders, and even medications are accompanied by and are believed to trigger APS.[7]

In order to meet the American College of Rheumatology criteria for a diagnosis of SLE, a patient must demonstrate four of the signs, symptoms, and laboratory findings. The criteria are as follows[8]:

  • Malar rash

  • Discoid rash

  • Photosensitivity

  • Oral ulcers

  • Nonerosive arthritis involving two or more peripheral joints

  • Pleuritis or pericarditis

  • Renal disorder

  • Neurologic disorder

  • Hematologic disorder

  • Other immunologic abnormalities (ie, other positive antibody titers, including ant-dsDNA, anti-Smith, and antiphospholipid antibodies)

  • Positive ANA findings

This patient met multiple clinical characteristics and immunologic criteria to fit the diagnosis of SLE.

Both clinical and laboratory criteria have been established for the diagnosis of APS. In order to meet the clinical criteria for APS, patients must demonstrate evidence of vascular thrombosis and pregnancy morbidity. The manifestations of vascular thrombosis are broad and can include any organ system including both the arterial and venous vasculature of the central nervous system, heart, lungs, and viscera, with the kidneys as a common target.

In addition to demonstrating thrombophlebitis and renal dysfunction, the patient in this case also had evidence of a prior cerebrovascular accident, as well as splinter hemorrhages and a lacy, mottled discoloration of the skin, which is called livedo reticularis. Livedo reticularis develops due to the thrombosis of small vessels. Several other cutaneous manifestations of APS are recognized, including cutaneous ulcers, digital ischemia/necrosis, gangrene of the extremities, and painful purpura. Examples of pregnancy morbidity associated with APS include more than three early spontaneous abortions (< 10 weeks estimated gestation), one late-term spontaneous abortion, and a history of preeclampsia or eclampsia.[7]

Laboratory features of APS, in addition to positive antiphospholipid antibodies (IgG and IgM), include hemolytic anemia with reticulocytosis and thrombocytopenia. Even in the setting of thrombocytopenia, patients are still hypercoagulable until platelets fall below 50,000/µL, at which count they may be at an increased risk for bleeding.[9] Anticardiolipin positivity is also associated with a false positive RPR when testing for syphilis. Literature has suggested that lupus anticoagulant positivity carries the highest risk for thrombosis.

In patients whose antiphospholipid antibody testing returns positive, confirmatory testing must be repeated in 12 weeks to establish the diagnosis. Antiphospholipid antibodies can also develop secondary to viral infections, including hepatitis.[10,11] Although anti-beta-2-GP I antibodies and anticardiolipin antibodies can be detected via immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme-linked immunoassay (ELISA), lupus anticoagulant testing involves multiple steps. Because lupus anticoagulant is directed against plasma clotting molecules, detection on laboratory testing is characterized by paradoxical elevations of the coagulation assays aPTT, kaolin clotting time, and dilute Russell viper venom time (DRVVT). The presence of lupus anticoagulant and absence of a clotting factor inhibitor is further confirmed by mixing the patient's plasma with platelet-poor plasma.[12,13]

Additional antiphospholipid antibodies not included within the diagnostic criteria are immunoglobulin A (IgA) anticardiolipin, IgA anti-beta-2-GP I, antiphosphatidylserine, antiphosphatidylethanolamine, and anti-prothrombin antibodies. The Global Antiphospholipid Syndrome Score (GAPSS) is being developed as a standardized tool for the prognostication of APS, taking into account positive serologies, cardiovascular risk factors, and the associated autoimmune conditions with which it may represent.[9]

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