Three in One: Systemic Lupus Erythematosus, HELLP Syndrome, and Antiphospholipid Syndrome: A Case Report with Literature Review

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease commonly affecting women of reproductive age. Its overlap with HELLP syndrome (Hemolysis, Elevated Liver Enzymes, and Low Platelet Count) and antiphospholipid syndrome (APS) during pregnancy is rare and presents diagnostic and therapeutic challenges due to shared clinical and laboratory features. Case presentation A 26-year-old female with known SLE who presented with right upper quadrant pain and hypertension two days following a mid-trimester abortion at 22 weeks of gestation. Laboratory evaluation revealed thrombocytopenia, elevated liver enzymes, and hemolysis, consistent with HELLP syndrome.The presence of lupus anticoagulant and anticardiolipin antibodies, in conjunction with her obstetric history, supported the diagnosis of antiphospholipid syndrome (APS).. The patient was treated with high-dose corticosteroids and anticoagulation, resulting in significant clinical improvement. Literature review A review of literature highlights the consistent presentation of nonspecific symptoms such as abdominal pain, nausea, and hypertension in patients with overlapping SLE, HELLP syndrome, and APS. Laboratory findings often reveal thrombocytopenia, elevated liver enzymes, and hemolysis, reflective of underlying microangiopathic processes. Therapeutic strategies typically involve corticosteroids and anticoagulation, with plasmapheresis reserved for severe cases. Conclusion This case highlights the rare coexistence of SLE flare, HELLP syndrome, and APS in pregnancy, emphasizing the importance of early recognition, comprehensive diagnostic evaluation, and a multidisciplinary approach to optimize outcomes. Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multisystem involvement, affecting approximately 20 to 150 per 100,000 individuals worldwide, with a strong female predominance [1,2]. It commonly presents with fatigue, arthralgia, skin manifestations, and renal or hematological complications, but its presentation can vary widely depending on disease activity [3]. Pregnancy in patients with SLE is considered high-risk due to increased risks of preeclampsia, fetal loss, and preterm delivery [4]. Antiphospholipid syndrome (APS) is another autoimmune disorder that frequently overlaps with SLE. It is characterized by the presence of antiphospholipid antibodies and is associated with thrombotic events and pregnancy complications such as recurrent miscarriage and intrauterine growth restriction [5,6]. HELLP syndrome (Hemolysis, Elevated Liver Enzymes, and Low Platelet Count) is a severe form of preeclampsia that can develop in up to 0.9% of pregnancies, usually leading to hepatic dysfunction, hypertension, and coagulopathy [7]. These conditions exhibit overlapping clinical and laboratory features such as thrombocytopenia, elevated liver enzymes, and hemolysis, making diagnosis and management particularly challenging [8]. This report a rare case of a 26-year-old female with diagnosis of SLE who presented with the simultaneous occurrence of SLE flare, HELLP syndrome, and APS during pregnancy. This report adheres to the CaReL guidelines to ensure comprehensive documentation and references validated through the Kscien list for reliability and scientific integrity [9,10]. Case Presentation Patient information A 26-year-old female presented with right upper quadrant abdominal pain for one week. She had history a second-trimester abortion at 22 weeks of pregnancy via normal vaginal delivery two days prior. Her medical history included systemic lupus erythematosus (SLE) diagnosed eight years ago following a miscarriage. She had been on aspirin during pregnancy due to a history of abortions. Clinical findings The patient exhibited severe epigastric tenderness on superficial palpation. She also reported radiating back pain and was found to be hypertensive, with a known history of gestational hypertension. There was no vomiting or alteration in mental status. Diagnostic approach Laboratory investigations showed markedly elevated liver enzymes (ALT: 2500 U/L, AST: 3000 U/L), thrombocytopenia (platelet count: 50,000/mm³), and a prolonged prothrombin time (PT) with a high international normalized ratio (INR). D-dimer levels were significantly elevated at 2500 ng/mL, and fibrinogen was reduced to 50 mg/dL. A blood film revealed the presence of schistocytes, suggesting ongoing microangiopathy. Autoimmune markers confirmed active SLE with positive ANA and high anti-dsDNA titers. Imaging studies, including an abdominal CT, demonstrated severe hepatic necrosis without evidence of rupture or hematoma. These findings confirmed the coexistence of SLE flare, HELLP syndrome, and antiphospholipid syndrome, a rare and complex presentation. Therapeutic intervention and follow-up The patient was admitted to the ICU for supportive care and initiated methylprednisolone pulse therapy for three consecutive days, resulting in significant improvement. Liver enzymes normalized, platelet counts increased, and symptoms resolved. Anticoagulation with warfarin was started for antiphospholipid syndrome, and hydroxychloroquine was continued for SLE management. At discharge, she was stable and referred to rheumatology for long-term follow-up. Discussion Systemic lupus erythematosus is a chronic autoimmune disease that primarily affects women of reproductive age. Its global prevalence ranges from 20 to 150 cases per 100,000 individuals, with a strong female predominance [3,4]. Pregnancy in patients with SLE carries an increased risk of adverse maternal and fetal outcomes, including preeclampsia, fetal loss, and preterm birth, particularly in cases complicated by active disease [5]. The presence of APS, a thrombotic disorder defined by antiphospholipid antibodies, further increases pregnancy risks by promoting thrombosis, recurrent miscarriages, and placental insufficiency [6]. HELLP syndrome, a severe form of preeclampsia, presents with hepatic dysfunction, endothelial injury, and hematologic abnormalities, leading to substantial maternal and fetal morbidity [7]. The present case, a 26-year-old female with known SLE, developed HELLP syndrome and APS following a mid-trimester abortion at 22 weeks, reflecting the complex interplay of these conditions and the challenges in diagnosis and management. As seen in Table 1, all cases occurred in young females aged 26 to 39 years, reinforcing the well-documented female predominance of SLE, APS, and HELLP syndrome [5]. Pregnancy is a known trigger for SLE flares, and the additional presence of APS further increases the risk of obstetric complications. The present case aligns with these findings, as the patient’s history of SLE with pregnancy loss placed her at an elevated risk for developing APS and HELLP syndrome. The most common symptoms reported in Table 1 were right upper quadrant pain, hypertension, nausea, and dyspnea, which are classic signs of HELLP syndrome. One case reported tachypnea and dyspnea, which can indicate pulmonary involvement or preeclampsia-related respiratory distress [7]. Another case reported synovitis, butterfly rash, and confusion, suggesting neurological lupus manifestations or eclampsia [4]. Some cases presented with vision disturbances and chest discomfort, which may indicate APS-related microvascular thrombotic events [5]. While some patients in Table 1 had neurological involvement, the present case exhibited a severe hypertensive episode, reinforcing the complexity of these overlapping conditions. Table 1. Summary of the review case report of SLE, APS, and HELLP. Author name/year Age (years) Gender Country Associated conditions Symptoms Key laboratory findings Therapeutic approach Outcome Follow-up (months) Sakhel et al., 2006[7] 39 F Lebanon SLE, APS Severe upper abdominal pain, tachypnea, dyspnea Elevated liver enzymes, thrombocytopenia, hemolytic anemia Methylprednisolone, heparin Improved 6 Osmanagaoglu et al., 2004[4] 33 F Turkey SLE, HELLP Synovitis, butterfly rash, confusion, convulsions Elevated liver enzymes, proteinuria, low platelets Prednisolone, therapeutic abortion Died - Veres et al., 2007[5] 26 F Hungary APS, HELLP Hypertension, chest discomfort, vision changes Elevated ALT, AST, LDH, low platelets, hemolysis Plasmapheresis, anticoagulation Recovered 24 Yamamoto et al., 2004[6] 26 F Japan SLE, HELLP Severe epigastric pain, hypertension Elevated liver enzymes, microangiopathic hemolysis Plasma exchange, steroids Recovered 12 Appenzeller et al., 2011[3] Various F Multiple APS, HELLP Nausea, vomiting, right quadrant pain Elevated liver enzymes, hemolysis, low platelets Aspirin, anticoagulation, corticosteroids Variable Variable Laboratory investigations across cases demonstrated consistent hematologic abnormalities, including thrombocytopenia, elevated liver enzymes, and hemolysis, which are defining features of HELLP syndrome [3]. One case reported proteinuria, which is more suggestive of SLE nephritis or preeclampsia-related renal dysfunction [4]. In another case, hemolysis was confirmed through microangiopathic findings rather than an immune-mediated mechanism [6]. Patients with APS frequently exhibited prolonged prothrombin time (PT/INR), elevated D-dimer levels, and thrombocytopenia, reflecting the hypercoagulable state of APS [5]. The present case demonstrated severe thrombocytopenia, elevated ALT/AST, and hemolysis, with positive lupus anticoagulant and anticardiolipin antibodies confirming APS and elevated anti-dsDNA titers indicating active SLE. This profile closely mirrors the cases summarized in Table 1, emphasizing the diagnostic overlap between HELLP syndrome, SLE flares, and APS. Although imaging findings were not reported in all cases, hepatic involvement was a significant feature in those with severe HELLP syndrome or APS-associated thrombosis. One case reported hepatic infarctions and subcapsular hematomas, suggesting vascular damage secondary to HELLP syndrome or APS-related thrombosis [7]. Another case demonstrated hepatic microangiopathic changes without infarction, reinforcing the diverse spectrum of hepatic injury in these patients [5]. The present case exhibited hepatic involvement in imaging, consistent with hepatic dysfunction in severe HELLP syndrome, reinforcing the value of imaging studies in distinguishing these conditions. Management strategies varied depending on the severity of the disease, but high-dose corticosteroids were universally used to suppress SLE flares and reduce systemic inflammation [6]. APS patients received anticoagulation therapy with heparin or warfarin to prevent thrombotic complications. In severe cases, plasmapheresis and intravenous immunoglobulin (IVIG) were administered to manage catastrophic APS (CAPS) or refractory hemolysis [5]. One case required therapeutic abortion due to the severity of maternal complications, highlighting the need for individualized obstetric decision-making in these high-risk pregnancies [4]. The present case was treated with methylprednisolone for SLE flare and heparin for APS, leading to significant clinical improvement, mirroring the treatment success seen in cases summarized in (Table 1). Outcomes among reported cases varied based on disease severity and timing of intervention. While most patients in Table 1 responded well to treatment, one case resulted in maternal mortality, particularly due to multi-organ failure and delayed diagnosis [4]. Other cases reported full recovery following corticosteroid therapy and anticoagulation [5,6]. One patient showed partial resolution of symptoms but continued to require long-term monitoring due to APS-related complications [3]. Early intervention played a crucial role in improving prognosis, as seen in cases that received timely corticosteroid and anticoagulation therapy. The present case, diagnosed early and treated promptly, achieved clinical stabilization, underscoring the critical role of timely diagnosis and multidisciplinary management in improving maternal outcomes. Conclusion The coexistence of SLE flare, HELLP syndrome, and APS during pregnancy is a rare and complex condition that requires careful evaluation. Overlapping clinical and laboratory findings can complicate diagnosis, emphasizing the importance of a multidisciplinary approach. Early recognition and appropriate management are essential to achieve favorable maternal and fetal outcomes. Declarations Conflicts of interest: The authors have no conflicts of interest to disclose. Ethical approval: Not applicable. Patient consent (participation and publication): Written informed consent was obtained from the patient for publication. Funding: The present study received no financial support. Acknowledgements: None to be declared. Authors' contributions: SHS and RSA were significant contributors to the conception of the study and the literature search for related studies. KAN and HAN were involved in the literature review, study design, and manuscript writing. DTG, NHA, HRA, HMM, JIH, and KFH were involved in the literature review, the study's design, and the critical revision of the manuscript, and processing of the table. RSA and HAN confirm the authenticity of all the raw data. All authors approved the final version of the manuscript. Use of AI: ChatGPT-4 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript. Data availability statement: Not applicable.