Abnormal presentation of pregnancy and postpartum initial-onset systemic lupus erythematosus combined with diffuse alveolar hemorrhage: A case report

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that most commonly occurs in women of childbearing age. However, cases of SLE with abnormal pregnancy as the initial manifestation, involving the development of diffuse alveolar hemorrhage (DAH), have rarely been reported. Herein, we report the case of a young woman who underwent a cesarean section for fetal distress and growth restriction at 35 + 1 weeks’ gestation. Following discharge, she experienced progressive worsening of anemia and chest tightness, which was later diagnosed as SLE complicated by DAH.

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease that commonly affects young women of childbearing age. Clinical manifestations are diverse, ranging from mild arthritis to diffuse alveolar hemorrhage (DAH). Its main manifestations include dyspnea, cough, fever, bloody sputum, and hemoptysis, which are closely related to the active state of the disease. DAH is a rare and devastating complication of SLE, seen in only 1%–5% of cases; it has a mortality rate of up to 50% despite aggressive treatment. ¹

Case report

A 19-year-old woman was hospitalized for 10 days following a cesarean section due to a 2-day history of dizziness and weakness. The patient had a small amount of vaginal bleeding 10 days after delivery and no abdominal pain. One day prior, the patient felt dizzy and weak and was immediately admitted under the diagnosis of “severe anemia; post-cesarean section.” She had a dry cough, no sputum, slight shortness of breath, poor appetite, an inability to lie down at night, and experienced poor sleep. She had normal bowel movements and no nausea, vomiting, chills, fever, nor history of recent sexual intercourse or bathing. Moreover, the patient had no history of rash, arthralgias, hair loss, oral ulcers, or photosensitivity.

On admission, the patient’s vital signs were stable and she was conscious; however, fine wet rales could be heard over both lungs. Her abdomen was flat and soft, the abdominal incision had properly healed, the fundus of the uterus was one transverse finger above the pubic symphysis, the vagina was patent, the cervix was smooth, and only a small amount of blood was observed. We compared the pre- and post-admission findings (Table 1).

Table 1.

Laboratory test results before and after admission.

	WBC	Neutrophils	Hb	PLT	D-Dimer	FDP	CRP	Serum albumin
Pre-admission	15.12 × 109/L	9.52 × 109/L	56 g/L	126 × 109/L
After admission	12.43 × 109/L		50 g/L	97 × 109/L	5.24 ug/uL	14.1 ug/uL	3.90 mg/L	24.8 g/L

WB, white blood cell; Hb, hemoglobin; PLT, platelet; FDP, fibrin degradation products; CRP, C-reactive protein.

A cardiac ultrasound showed low pericardial effusion, while an abdominal pelvic gynecological ultrasound showed a postpartum uterus with fluid in the uterine cavity and an enlarged spleen with abnormal internal hypovolemia. A computed tomography (CT) scan of the chest showed a diffuse high-density shadow with blurred borders in both lungs (Figure 1). The relevant laboratory tests after admission are shown in Table 2.

Figure 1.

Computed tomography of the chest.

Table 2.

Relevant laboratory tests after admission.

Inspection items	Laboratory results
Urinalysis	Protein 2+
Complement C3	0.29 g/L
Complement C4	0.02 g/L
24-h urine protein quantification	3.95 g/24 h
Immunoglobulin IgG	22.98 g/L
Serum ferritin	2000.0 ug/L
Coomb's experiment	(−)
ANA Quantification	1:10000
Anti-DNA	(+)
Anti-cardiolipin antibody	(−)
Anti-Ro antibodies	(−)

ANA, anti-nuclear antibody.

On admission, she was treated with red blood cell infusion, cardiac paralysis, diuresis, and dilation by our obstetrics department. However, her condition gradually worsened, and respiratory distress developed. After being transferred to the intensive care unit (ICU) the next day, she was given non-invasive, ventilator-assisted ventilation (oxygen concentration of 80%), cardiac strengthening with cetiran and digoxin, diuresis with furosemide, and prophylactic anti-infection comprising cefuroxime and sputum chemotherapy. However, her chest tightness and anemia did not improve, and she developed a fever of 39°C overnight. Her chest tightness and dyspnea gradually worsened, necessitating emergency tracheal intubation to be performed. Dark, bloody sputum was aspirated via the airway. Subsequently, alveolar hemorrhagic syndrome was considered, and an urgent multidisciplinary consultation was requested (rheumatology, nephrology, respiratory and critical care medicine, hematology, and infectious diseases). She was treated with methylprednisolone 500 mg/day IV shock for 3 days, followed by human immunoglobulin 20 g/day IV shock for 5 days. Subsequently, she was transitioned to a regimen of methylprednisolone at 80 mg intravenously once daily and a single intravenous dose of cyclophosphamide at 0.8 g. The patient eventually died after 2 weeks of treatment in the ICU. Based on her status as a woman of childbearing age presenting with decreased hemoglobin levels (peripheral blood smear shows no abnormality), plasma cavity effusion, proteinuria, decreased complement levels, positive anti-nuclear antibody (ANA) 1:10,000 and anti-dsDNA, tests for ANCA antibodies and anti-cardiolipin antibodies returned negative results. Furthermore, she exhibited severe anemia, significant airway bleeding symptoms, and CT imaging changes in the lungs. The patient was diagnosed with “systemic lupus erythematosus, lupus nephritis, and alveolar hemorrhage” based on the ANA positivity, anti-dsDNA positivity, decreased complement, plasma lumen fluid, proteinuria, thrombocytopenia, alveolar hemorrhage, and the lack of history of related diseases and autoimmune disorders in the patient’s family (see Table 3 for the specific criteria for the diagnosis of SLE). The patient was assigned a SLEDAI score of 14. However, due to the critical progression of the patient's condition, a renal biopsy was not performed, and we diagnosed “lupus nephritis” based on the patient's clear diagnosis of systemic lupus erythematosus and quantitative proteinuria greater than 500 mg/24 hours at 24 hours. Reporting of this case was approved by the Ethics Committee of Anqing Municipal Hospital.

Table 3.

2019 EULAR/ACR classification criteria.

Clinical area	Weights
1. Whole body system
Fever ≥ 38.3°C	2
2. Skin and mucous membranes
Non-scarring hair loss	2
Canker sore	2
Subacute cutaneous or discoid lupus	4
Acute cutaneous lupus erythematosus	6
3. Arthritis
Synovitis in ≥2 joints/≥2 pressure-painful joints + morning stiffness for ≥30 min	6
4. Nervous system
Delirium	2
Psychiatric symptom	3
Seizures	5
5. Plasma membrane inflammation
Pleural or pericardial effusion	5
Acute pericarditis	6
6. Blood system
Leukopenia (<4 × 10/L)	3
Thrombocytopenia (<100 × 10/L)	4
Hemolysis due immunity	4
7. Kidney
Proteinuria > 0.5 g/24 h	4
Renal puncture pathology type II or V lupus nephritis	8
Renal puncture pathology type III or IV lupus nephritis	10

Field of immunology	Weights
1. Antiphospholipid antibodies
Anti-cardiolipin antibody IgG > 40 GPL units or anti-β2GPIIgG > 40 units or positive lupus anticoagulant	2
2. Complement
Low C3/Low C4	3
Low C3+Low C4	4
3. Highly specific antibodies
Anti-dsDNA positive	6
Anti-Sm positive	6

Discussion

SLE is common in women of childbearing age, and pregnancy and childbirth serve as significant factors that can trigger or exacerbate the condition.^2,3 Patients may present with pregnancy/delivery-induced SLE, while in some cases lupus crisis is the first symptom. A previous study ⁴ showed that among 223 mothers with SLE presenting to this hospital during 2013–2017, 68 had SLE with initial-onset in pregnancy/postpartum, while some patients had lupus crisis as their first symptom. Patients with SLE commonly experience renal involvement, and the presence of proteinuria or elevated serum creatinine levels raises suspicion for renal complications. The risk of DAH has been reported to be elevated in patients with lupus nephritis in the presence of acute pulmonary symptoms, new X-ray infiltrates, decreased erythrocyte specific gravity, and even in the absence of hemoptysis. ⁵ In some cases, alveolar hemorrhage is sufficient to cause anemia; therefore, anemia of unknown origin should exclude DAH. ⁶ In this case, acute anemia was the first symptom, and lung CT showed diffuse ground glass and solid shadows in both lungs. Hemoptysis had not been seen during the course of the disease. Hence, it is necessary to exclude the possibility of bleeding from the digestive tract, urinary tract, abdominal cavity, and hemolytic anemia. Diffuse pulmonary hemorrhage due to trauma, infectious pneumonia (tuberculosis, bacterial, viral, and fungal), bronchogenic carcinoma, choriocarcinoma, carcinoid tumors, interstitial lung disease, pulmonary hypertension, arteriovenous malformations, pulmonary embolism, congenital heart disease, acute lupus pneumonitis, granulomatous polyangiitis, Goodpasture's syndrome, and drug-induced pulmonary hemorrhage (such as that caused by cocaine, anticoagulants, and antiplatelet agents) should also be excluded. ¹ Also in patients with acute anemia, especially in combination with renal involvement and/or decreased complement and/or intestinal infections, we need to rule out hemolytic uremic syndrome (HUS), thrombotic microangiopathy (TMA) possibly.

In summary, this case underscores the possibility of SLE presenting as a lupus crisis, such as DAH. Clinicians should consider the presence of autoantibodies, such as ANAs, detected in the sera of patients with connective tissue diseases like SLE.^7,8 It is also necessary to combine the specific diagnostic criteria for SLE (see Table 3 for details) based on the patient’s clinical manifestations and family history, which can lead to early detection, diagnosis, and treatment of SLE. Hormonal changes due to pregnancy are important in triggering or exacerbating SLE, and its development is a risk factor for adverse pregnancy outcomes. ⁹ Women with SLE have an increased risk of adverse pregnancy outcomes compared to the general population. ¹⁰ In cases where a patient experiences an unexplained adverse pregnancy outcome, a multidisciplinary approach combining the opinions of experts from multiple specialties is required, and a timely diagnosis of SLE and aggressive control of the primary disease may prevent the development of DAH.