A 23-year-old woman (gravida 1, para 0) weighing 60 kg was transferred to our hospital due to persistent fever up to 39 C for three days with bilateral edema of the lower limbs at 24 weeks of gestation. She had no history of autoimmune disease, and her family history was unremarkable. Upon examination, the following vitals were obtained: a temperature of 38.1  C (febrile), a resting heart rate of 105 beats/min (tachycardic), and a blood pressure of 97/58 mmHg (hypotensive). She received fluid resuscitation and empiric antibiotics. The dermatological and neurological examinations were unremarkable. A physical examination showed marked hepatosplenomegaly; however, no arthritis was noted. Pertinent laboratory findings indicated pancytopenia including the following: hemoglobin (HGB) of 9.3 g/dl; platelet (PLT) count of 80 x 109/L; and leukocyte (WBC) count of 3.45 x 109/L; slight liver dysfunction and elevated lactate dehydrogenase (LDH) level of 477 U/L (normal range [NR], 91-245); C-reactive protein (CRP) level of 17.26 mg/dl; and decreased albumin (ALB) level of 26 g/L (NR, 35-55). The following findings were also obtained: positive antinuclear antibody (1:1,000), anti-SSA >200 AU/ml (NR, 0-20), antidouble-stranded DNA antibody of 34.5 IU/ml (NR, 0-20), and negative anticardiolipin antibodies; complement C3 level of 0.32 g/L (NR, 0.9-1.8), C4 level of 0.1 g/L (NR, 0.1-0.4); EB virus capsid antigen IgA/IgM/IgG antibody, early antigen IgM, and nuclear antigen IgG negative. Serological investigations showed no evidence of active Epstein-Barr virus (EBV), cytomegalovirus disease (CMV), herpes simplex, leptospira, tuberculosis, hepatitis B, hepatitis C, VDRL, and human immunodeficiency virus (HIV); immunoglobulin IgE markedly elevated to 588 IU/ml (NR, 0-100); and urine occult blood and proteinuria. Other active infections were excluded. Abdominal ultrasound demonstrated a splenic swelling of 5.8 cm thick. Transthoracic echocardiography showed no obvious abnormalities. A diagnostic procedure for active SLE was purchased. The patient fulfilled the 2019 American College of Rheumatology (ACR) classification criteria: 24 points for SLE with a high activity index (SLEDAI of 15). As the patient was listless, we performed relative tests to rule out lupus encephalopathy. Neurological examinations, cerebrospinal fluid tests, magnetic resonance imaging, and electroencephalography were normal. The patient also showed no symptoms of lupus encephalopathy. Treatments including broad-spectrum antibiotics, intravenous immunoglobulin (15 g/day) with maintenance of high-dose prednisolone (40 mg/day), hydroxychloroquine 200 mg twice a day, and aspirin 50 mg once a day were started. However, the condition of the patient did not improve. Three days after admission, she developed butterfly erythema on her face and palm, and intermittent hyperpyrexia. Furthermore, the leukocyte count and hemoglobin decreased progressively; serum levels of alanine aminotransferase and aspartate aminotransferase were elevated to 59 U/L and 127 U/L, respectively; and serum ferritin, 1,859.80 ng/ml (NR, 11.0-306.8), NT-pro BNP, PCT, and D-Dimer were also elevated (Table 1). The 24-hour urine protein was 2.737 g/24 h (NR, 0-0.15). The SLEDAI score was estimated to be 17. The multidisciplinary consultation is recommended to replace prednisone with methylprednisolone pulse therapy (40 mg/day) in addition to 80 mg/day in the next 2 days. Moreover, the antibiotics were upgraded to meropenem. Although optimal management was provided, there was no relief of symptoms.
On the sixth hospital day, the patient still suffered from daily fever (Figure 1) with further pancytopenia and elevated D-Dimer. The ALB decreased to 25.5 g/L. The dosage of methylprednisolone was adjusted to 80 mg and 40 mg in the morning and evening, respectively, according to the conditions for three consecutive days. Enoxaparin was administered to prevent thrombosis. She was transfused with red blood cells for anemia and was given albumin intravenously along with other symptomatic support treatments. A bone marrow biopsy revealed hemophagocytic cells (Figure 2). From these findings, a tentative diagnosis of SLE presenting as reactive HLH was made. Therefore, we organized the second multidisciplinary consultation. According to the laboratory findings, immunosuppressive therapy with dexamethasone at 15 mg/day (since methylprednisolone had been given 80 mg in the morning) and 30 mg/day on the first day and next 2 days, respectively, was found to be effective. The response to steroids was not immediately stimulated; hence, etoposide was considered. Since she was classified under US FDA pregnancy category D, the family of the patient refused its accompanied treatment options. Cyclosporine A is classified under class C, and informed consent was obtained to initiate 100 mg twice a day through oral administration. Afterwards, the fever, blood cell count, liver function, and coagulation dysfunction subsided gradually.
Owing to the use of multiple drugs during pregnancy and the unpredictable prognosis of the fetus, the patient decided to terminate her pregnancy and gave up rescuing the newborn. A drug induced labor operation was successfully completed under close monitoring. On the day of labor induction, the patient developed high blood pressure, and oral labetalol and nifedipine failed to control it. Therefore, intravenous pumping of Urapidil hydrochloride injection was performed to control hypertension. Enoxaparin was administered to prevent thrombosis at 12 h postpartum. Unfortunately, chest discomfort and suffocation appeared in the first day after abortion. Transthoracic echocardiography showed tricuspid regurgitation (mild-moderate), pulmonary valve regurgitation (mild-moderate), pulmonary hypertension (mild), pericardial effusion (mild), and pleural effusion (mild). A third multidisciplinary consultation was established to develop a better plan. Since pulmonary embolism was considered, the experts suggested that corticosteroids, cyclosporine, hydroxychloroquine, and enoxaparin should be continued on the basis of the original therapeutic schedule. Furthermore, the following laboratory tests improved soluble CD25 by 4,027.91 pg/ml (NR, 458-1,997) and low natural killer (NK) cell activity by 1.00 (NR, 8.1%-25.6%). Genetic tests described the STX11 mutations. It was found to be positive for an exon 2, c.646C >A (p.R216s) heterozygous mutation. The placenta showed no microscopic abnormalities. Fortunately, the condition of the patient did not deteriorate further. The SLEDAI score was decreased to 10, including proteinuria, hematuria, and low complement protein3. Under our close supervision and careful treatment, the patient was discharged 2 weeks after the termination of the pregnancy. She chose to go to the local hospital for re-examination and continued to take prednisone 10 mg/day and cyclosporine 50 mg/day orally for 8 weeks, following the advice of the doctor. She has remained in remission for 7 months until now.