Hyperhomocysteinemia is present in approximately 15% of patients with systemic lupus erythematosus (SLE) [9]. One proposed mechanism of elevated homocysteine is a deficiency of folate, B6, and B12, vitamins noted to be essential to homocysteine metabolism [11]. Another route for pathogenesis stems from diminished renal function, such as chronic kidney disease (CKD) [12]. Approximately 70% of accumulated homocysteine is eliminated through the kidneys each day, primarily via the transsulfuration (TS) pathway [13, 14], and patients with CKD have demonstrated impaired metabolic clearance of homocysteine by both TS and remethylation (RM) pathways [15]. Lastly, severe levels of hyperhomocysteinemia are seen in patients with a genetic mutation of the enzyme cystathionine β-synthase or methylenetetrahydrofolate reductase [10], which further implicates processes of TS, RM, and transmethylation in the roll of pathogenesis. Although there is still debate about the exact mechanism by which SLE commonly produces elevated homocysteine levels, one of the aforementioned pathways is likely involved.

SLE stands as the disease most commonly associated with Antiphospholipid Syndrome (APS), present in approximately 35 percent of cases [33]. APS manifests clinically with recurring venous, arterial, and/or small vessel thrombosis (e.g., DVTs, stroke, TIAs), along with specific pregnancy complications such as recurrent miscarriages, and premature births. A clinical diagnosis of APS is supported by the presence of at least one or more types of antiphospholipid antibody (e.g., lupus anticoagulant, anticardiolipin antibodies, Anti-β2-glycoprotein antibodies) in symptomatic patients [34,35]. The management of acute thrombotic events (e.g., stroke) varies depending on the individual patient’s clinical presentation. In contrast, long-term management of APS concentrates on initiating thromboprophylaxis through systemic antiplatelet and anticoagulation therapy, such as low-dose aspirin, warfarin, or heparin therapy [35,36].

Prompt and individualized treatment is required in SLE patients to treat the variable nature of the disease properly. SLE affects an array of organs, including the kidneys, musculoskeletal system, central nervous system, and cardiovascular system. The 10-year survival rate for patients with SLE has gradually increased over time and is currently at about 90%, suggesting that the management of the condition has improved [18,19]. Mortality in patients with SLE typically occurs due to cardiovascular complications, neoplasm, active SLE, and infectious disease [16,18]. The goals in the treatment of SLE are to promote prolonged survival, safeguard against organ impairment, and enhance overall quality of life. This objective is achieved by effectively managing disease activity, reducing the occurrence of comorbidities, and mitigating adverse effects associated with medications. Regular monitoring of the disease process and its response to medication is required [17].

Treatment regimens will depend on the severity of the disease status. Several indices have been developed to aid with the assessment of SLE status in patients. The SEDAI-2K, BILAG, and SLAM-R are SLE scales useful for the assessment of global disease, systemic involvement, and disease severity, respectively, and have demonstrated validity and reliability [20]. A hallmark of the management of SLE especially for patients currently asymptomatic, in disease remission, or with mild symptoms is to focus on preventative care, which includes the avoidance of triggers for flare-ups as well as screening for conditions commonly associated with SLE. Patients should seek to mitigate triggers such as UV light exposure and smoking [21,22]. Likewise, patients should be sure to acquire necessary immunizations and screen for complications of SLE such as CVD, osteoporosis, and malignancy [23] while also maintaining a healthy diet and exercising regularly.

Regardless of disease status, there is strong evidence supporting the pharmacological use of antimalarials, especially hydroxychloroquine, as a first-line option for the prevention and treatment of disease [24]. Further treatment is tailored to the individual's presenting symptoms, organ involvement, and severity and may necessitate corticosteroids, NSAIDS, and antiproliferative immunosuppressants. Stepwise increases in pharmacological treatment should be provided as disease severity intensifies while using the lowest necessary dose of corticosteroids to minimize medication toxicity. This judicious use of corticosteroids is to prevent the likelihood of osteoporosis and CVD. The starting suggested dosage of corticosteroids in patients with mild cases is 7.5mg daily and then titrated as needed to control the disease. When hydroxychloroquine and corticosteroids are insufficient, antiproliferative immunosuppressants such as azathioprine, methotrexate, and mycophenolate should be used [33]. Special consideration is needed to treat specific organ involvement and symptoms due to the variable nature of disease manifestation.

Monitoring of SLE after diagnosis should take place every 3 to 6 months depending on severity and even more frequently in patients with lupus nephritis. Regular monitoring should include a review of medical history, physical exam, and screening for comorbidities related to disease and medication regimen. Laboratory values useful in disease monitoring include CBC, acute phase reactants ESR and CRP, UA with sediment, creatinine, protein to creatinine ratio, dsDNA, and C3 and C4 complement levels [26]. Hyperhomocysteinemia has been documented to be associated with several adverse conditions, especially vascular complications such as coronary heart disease and stroke [27,28]. Normal homocysteine concentrations range between 5 and 15 micromol/L whereas hyperhomocysteinemia is classified as moderate from 15 to 30 micromol/L, intermediate from 30 to 100 micromol/L, and severe >100 micromol/L [32]. Folate, cobalamin, and betaine have been shown to correct elevated levels of homocysteine [29]. However, it has not been shown that correction of homocysteine levels improves a patient’s risk for coronary artery disease, peripheral artery disease, or thrombus formation and is only minimally beneficial in stroke prevention [30,31].

Based on the patient’s records, the patient’s status should be considered mild and stable. The acute kidney injury has resolved, the WBC and platelets are trending positive toward baseline, and the patient’s mental status has returned to baseline. In the future, the patient must follow up regularly with a rheumatologist and any additional healthcare provider as required by disease presentation. Periodic immunological measurements must be taken to monitor the patient’s disease condition, along with clinical evaluation and interviews detailing disease status. Additionally, the patient should adhere to the medication regimen prescribed by their team of healthcare providers which will likely be adjusted as needed for adequate control of their condition and to ensure medication tolerance.