Systemic Lupus Erythematosus: Common Complications and Emergency Medicine Pearls

Authors: Rebecca Kaufman, MD (EM Chief Resident, Georgetown/Washington Hospital Center Emergency Medicine Residency, Washington, DC) and Kevin Reed, MD (Vice-Chair, Department of Emergency Medicine, MedStar Harbor Hospital, Baltimore, MD, Assistant Professor of Emergency Medicine, MedStar Georgetown University) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW Medical Center / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician at SAUSHEC)

Case

32-year-old African American female with a history of systemic lupus erythematosus (SLE), asthma, and hypertension presented to the emergency department (ED) with dyspnea, chest tightness, and wheezing not responsive to home albuterol treatments.  Her medication history included hydroxychloroquine, albuterol, and frequent bursts of prednisone. She had no recent hospital admissions, but she recently finished a course of steroids for inflammatory joint pain as an outpatient. On ED presentation the patient’s vital signs showed tachycardia (HR 120s), tachypnea (RR 28), blood pressure (110/60), and an oxygen saturation of 96% on 2L nasal cannula. Her temperature was 37.1 C but was obtained orally and not thought to be accurate due to the tachypnea. Physical exam showed a 32- year-old female with a malar rash and dyspnea with diminished breath sounds at the bases. EKG showed sinus tachycardia with non-specific ST changes. The patient was started on an hour-long nebulizer treatment and methylprednisolone. Breathing improved slightly. Blood work drawn to include a BMP, CBC, lactate, blood cultures, and troponin. Imaging included a portable chest x-ray, and the resident performed a bedside echocardiogram. The differential diagnosis for this patient was large, and the initial presentation clearly indicated that this woman was sick.

Introduction

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease of unknown cause with multi-organ involvement. The disease causes uncontrolled activation of the immune system with widespread inflammation manifested by vague and varied symptoms. It is one of the connective tissue diseases attributed to immunologic abnormalities and associated with a variety of different antinuclear antibodies. Women are more commonly affected than men. It is estimated that 1/1000 white women and 1/250 African American women during child bearing years have this disease.  There is a variety of organ damage including skin, musculoskeletal, renal, central nervous system, and more. The course among many patients includes periods of remissions spaced between acute and chronic relapses (1). SLE is generally thought to have genetic predisposition when other family members have a connective tissue disorder, although it doesn’t have to be specifically SLE. There is also a drug induced SLE-like syndrome from drugs such as hydralazine, isoniazid, minocycline, procainamide, and quinidine. This disease differs from classic SLE in antibody profile and generally spares the CNS and renal systems.

For emergency medicine physicians, the acute and potentially life threatening complications of SLE are important to identify and intervene upon.

The American Rheumatism Association Revised Criteria for Classification of Lupus (2) requires greater than or equal to four criteria from two categories of markers or biopsy-proven lupus nephritis with positive ANA or Anti-DNA.  The criteria are provided in Table 1 below:

However, in the emergency department the classic triad that should concern a provider for SLE patient is fever, joint pain and rash in a young female.

Rheumatologic Manifestations of SLE

Polyarthralgias and myalgias are present in up to 90% of patients. The proximal interphalangeal and metacarpophalangeal joints tend to be involved symmetrically and are not erosive. Joint deformity is less commonly found, although it may be seen in patients with rheumatoid arthritis in addition to lupus. Due to chronic steroids and a possible predisposition to weaker tendons, these patients may present with tenosynovitis and tendon rupture. Presentations for acute hip pain should concern the provider for avascular necrosis of the femoral head. Additionally, 30% of patient with SLE have a concomitant diagnosis of fibromyalgia (3).

Dermatologic Manifestations of SLE

The classic facial rash of SLE is the malar or butterfly rash. This is seen in 50% of SLE patients. It may be the first sign of the disease or accompany a patient’s lupus flairs. It may also be classified as acute cutaneous lupus erythematosus (ACLE). The rash is described as a maculopapular rash over the cheeks extending over the bridge of the nose. It is worsened by sun exposure (3,4).

Discoid lupus erythematosus (DLE) is described as raised plaques with scales on the face, head, or neck.  DLE can occur in the absence of systemic disease. This is also called cutaneous lupus erythematosus and is associated with the chronic cutaneous findings of lupus (5,6).

Mucous membrane ulcerations are seen in between 8-45% of the SLE patients (7). This is one of the clinical criteria eligible to help make the diagnosis. The appearance may be similar to canker sores and can be present over the hard palate, the lips, and gingiva.

Vasculitic lesions are also seen. Small vessel vasculitis is most commonly seen in SLE, but presentations range from ulcerations to purpura to digital infarcts (8).

Rarely patients can present with digital gangrene. This starts as small ischemic lesions but can quickly progress. An elevated CRP is sometimes useful in this diagnosis. Treatment ranges from calcium channel blockers, topical nitrates, and intravenous prostaglandin with a goal of vasodilation. Low dose aspirin and heparin are also required. If lupus vasculitis is present, they will need methylprednisolone 1,000 mg daily for three days and possible surgical intervention (15). Only certain patients will progress to surgical intervention. In one study, prompt steroid use decreased the risk of surgical intervention (15).  All decision for treatment should be made in discussion with the patient’s rheumatologist.

Renal Manifestations of SLE

Lupus nephritis is defined by persistent proteinuria and is present in up to 50% of lupus patients (3). The renal complications of lupus may be mild, evidenced only by routine laboratory work-up, or be severe leading to end-stage renal failure. Generally, less severe processes, such as membranous lupus nephritis, may present only on routine lab evaluation. Focal proliferative and diffuse proliferative lupus nephritis presents with severe systemic symptoms and more commonly as an acute complication in the emergency department (9). See Table 2 for presentation variation. Patients with systemic complications from SLE nephritis may present with hypertension, peripheral edema, and cardiac compromise such as tamponade and heart failure. Angiotensin-converting enzyme inhibitors (ACEIs) are preferred medications to treat proteinuria. The use of calcium channel blockers and beta-blockers are also effective for lowering blood pressure in hypertensive emergency. The goal blood pressure for these patients is systolic blood pressure less than 130 mmHg (17).

Neurologic Manifestations of SLE

While rarely the initial presenting sign of SLE, neurologic complications are vast and present in up to 50% of the patients.  Seizures are a common presenting co-morbidity of lupus patients. They are also more susceptible to stroke, psychiatric complications, and peripheral neuropathy. Most commonly, patients with SLE (up to 80%) will have some sort of cognitive impairment after 10 years of the disease (3).  Neurologic manifestations of SLE are most commonly attributed to organic encephalopathies, which can present as confusion, lethargy, depression, mania, psychosis, or coma.

Histologic examination shows degenerative changes in small vessel walls. It is unclear what causes the vasculitis; however, one possible explanation is immune complex deposition in the vessel walls. Another possible cause is the cytokine-mediated effect on vascular endothelium or local brain parenchyma (10).  Inflammatory changes are also seen in the medium and large vessels. This is the likely source of stroke syndromes from local thrombosis or emboli. Another possible etiology of local thrombosis is from antiphospholipid antibodies. This rarely can involve the venous sinuses, further complicating a CNS presentation of a patient with lupus (10). Emboli can occur as a result of Libman-Sacks endocarditis (see Cardiac Manifestations of SLE).

Dural sinus thrombosis is a rare complication of SLE-associated hypercoagulability and will be missed with the usual CT imaging in patients presenting with headache to the emergency department. Consider MRI and MR venous angiography in the setting of a lupus patient with a history of thrombotic disease (10).

Spinal cord involvement is rare but devastating. It is important to consider transverse myelitis and abrupt vascular occlusive events (e.g., spinal artery thrombosis) when evaluating lupus patients with vague neurologic complaints. Rapid onset suggests transverse myelitis, infarction, or compression by a rapidly expanding lesion (e.g., epidural abscess) (10) Management of these patients in facilities that have the capabilities is emergent MRI and consultation with both neurosurgery and rheumatology. If the presentation is acute and the neurologic compromise is evident, facilities without emergent MRI capacity should transfer patients to a higher level of care.

Cardiac Manifestations of SLE

All the anatomical structures of the heart can be affected in SLE. Patients are susceptible to endocarditis, myocarditis, and pericarditis (11). Anti-phospholipid antibodies have been associated with thrombotic events associated with coronary arteries, heart valves, and intra-myocardial vessels. Cardiovascular investigations have found a prevalence of cardiac involvement in > 50% of lupus patients.

Pericarditis is the most common cardiac manifestation. These patients should have classic findings associated with pericardial inflammation, and the management will be the same. Myocarditis is also seen in patients with SLE. Immunofluorescence studies demonstrate fine granular immune complexes and complement deposition in the walls and perivascular tissues of the myocardial blood vessels (11). The history of autoimmune disorder becomes crucial in these patients because the treatment course changes from an infectious target to an anti-inflammatory one.

Libman-Sacks endocarditis (LSE) is a sterile endocardial inflammation that produces vegetation on the heart valves (10). This is most commonly seen on the tricuspid valve, although the largest transthoracic echocardiography studies reported 32-38% prevalence of valve lesions involving the mitral and aortic valves (11). The valvular abnormalities resulting from LSE lesions may predispose patients to bacterial endocarditis as well (11).

Atherosclerotic diseases are more prevalent in SLE patients than the general population. Coronary artery disease (CAD) is described with a prevalence ranging from 6-10% in SLE patients; the risk of developing any CAD is 4-8 times higher than in controls (12).  In young women with SLE, the risk of MI is increased 50-fold (12). It is important to have a low-threshold of observation and possible early provocative testing for these patients.

Pulmonary Manifestations of SLE

Pulmonary involvement in SLE includes the lung, pulmonary vasculature, pleura, and the diaphragm. Most commonly, patients will have pleuritic chest pain with or without effusions. Pleuritis occurs in 17-60% of patients at some point during their disease course (13). Possible acute pulmonary complications are acute lupus pneumonitis, progressive cavitary pulmonary nodules, acute on chronic pulmonary hypertension leading to right heart failure, pulmonary embolism, alveolar hemorrhage (reflecting diffuse endothelial injury), bronchiolitis obliterans (BO) (with or without organizing pneumonia), opportunistic pulmonary infections, or drug toxicity from immunosuppressive therapy (13).

Acute lupus pneumonitis presents as cough, dyspnea, pleuritic pain, hypoxemia, and fever. Infiltrates on chest radiographs may be unilateral or bilateral. Even the histologic features of this disease process are non-specific and include alveolar wall damage and necrosis, as well as other non-specific findings. The histologic evaluation findings are similar to acute alveolar hemorrhage. This diagnosis is not easily made, and treatment has not be optimized at this point.  Emergency management should be focused on ruling out reversible disease processes and cardiopulmonary support.

After reviewing the literature, the life threatening pulmonary complications of SLE are vast. The addition of high dose steroids, methylprednisolone 1,000 mg, in the management of an undifferentiated toxic lupus patient with pulmonary complications appears to be indicated (13).

Gastrointestinal Manifestations of SLE

Identifying the frequent gastrointestinal manifestations of SLE is a clinical challenge secondary to the vague symptoms with which patients present (14). Dysphagia is a frequent gastrointestinal complaint and can present with symptoms of retrosternal chest pain, heartburn, regurgitation, or odynophagia. The dysphagia is thought to be secondary to esophageal dysmotility. Gastritis is also common, possibly due to long standing anti-inflammatory medication usage. Additionally, patients can suffer from intestinal pseudo-obstruction, spontaneous bacterial peritonitis, pancreatitis, liver dysfunction, and intestinal vasculitis.

Intestinal pseudo-obstruction is a disorder of intestinal peristalsis with resulting ineffective bowel propulsion causing symptoms similar to small bowel obstruction (14).  The evaluation and work-up will also be similar, and the patient may not have easily identifiable risk factors other than lupus.  Treatment, however, varies and requires high dose steroids in the management.

Lupus enteritis is inflammation of the small bowel and presents with nausea, vomiting, and diarrhea. Evaluation may reveal a potential ileus, edema of the bowel wall in a distinct “accordion-like” appearance on ultrasound, or a target lesion on CT scan (14).  SLE is rarely associated with Crohn’s disease and ulcerative colitis.

Lupus serositis causes inflammation of the peritoneum resulting in an inflammatory, exudative ascites found on paracentesis. Although rare, patients with lupus on chronic immune-suppression presenting with ascites should have their peritoneal fluid sent for cell count and culture to evaluate for spontaneous bacterial peritonitis.

Vasculitis involving the vessels of the GI system is a potentially deadly complication of SLE. This can affect every portion of the GI tract from the esophagus to the rectum. The incidence of this in the lupus population is about 1%. These patients generally present very toxic in appearance and have evidence of vasculitis in other body systems such as skin, kidneys, and CNS.

The mortality rate of SLE patients presenting with an acute surgical abdomen approaches 50%.  Treatment is aggressive and often involves immediate assessment for intestinal perforation.  The literature recommends early specialty involvement with both surgery and rheumatology (14).

Hematologic Manifestations of SLE

Emergent hematologic complications of SLE include thrombocytopenia, hemolytic anemia, neutropenia, catastrophic antiphospholipid syndrome (CAPS), and thrombotic thrombocytopenic purpura (TTP).

Common precipitants of CAPS include infection, surgery, trauma, pregnancy, oral contraceptives, and cessation of warfarin.  CAPS is a true hematologic emergency, and the management includes three parts.  First, there is a cytokine storm that traditionally responds to steroids. Second, there is hypercoagulability, which requires emergent anticoagulation. Third, the patient will require an emergent reduction of the antiphospholipid antibody burden with plasmapheresis or intravenous immunoglobin (15).

Similarly, TTP is a hematologic emergency associated with lupus patients. These patients classically present with fever, thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction, and neurologic involvement. The treatment is emergent and requires plasmapheresis or plasma exchange (15).

Special Population: SLE in Pregnancy

Complications due to flares of lupus during pregnancy can cause increased morbidity, especially those with renal disease. Pregnancy in women with lupus nephritis is associated with an increased risk of fetal loss and worsening of the renal manifestations of the disease. The lupus flares generally can occur during the first or second trimester and during the first few months of the post-partum period.  These patients will also have higher rates of urinary tract infections, gestational diabetes, gestational hypertension, preterm premature rupture of membranes, and preeclampsia (16).

Pregnancy and the postpartum period is also associated with additional thrombotic risk in patients with SLE who have antiphospholipid antibodies. Patients who present to the emergency department taking warfarin due to prior thromboembolic events who are found to be pregnant should be immediately switched to heparin (15).

Emergency Department Diagnostics

Labs are required when evaluating complications of SLE, however serology testing is generally not helpful. Refer to Table 3 for common lab tests and their intended purpose in evaluating lupus patients:

Imaging is also important in the evaluation of lupus patients in the emergency department. Refer to Table 4 for common although not all encompassing imaging required and the intended purpose in the emergent evaluation:

Medications Used in SLE

Below in Table 5 is a list of commonly used medications in patients with SLE and the medication’s potential negative side effects (17).

SLE Pearls and Pitfalls

• Consider MRI for patients with lupus and severe hip pain with a negative x-ray as they are more susceptible to avascular necrosis that may be early, reversible, and not seen on plain radiographs.
• Patient with fevers, evidence of immune-compromise (such a herpes zoster), and neutropenia warrant admission.
• Otherwise low-risk chest pain in patients with SLE is never to be considered low risk. These patients have a much higher rate of CAD and an earlier age onset of CAD.
• Be cautious about holding back on imaging for patients with SLE with headaches as well as for vague neurologic complaints. See neurologic complications above.
• GI vasculitis is devastating and a patient must appear extremely well so as not to require some form of imaging when complaining about vague abdominal distress.
• Patients with SLE on chronic steroids and sepsis or shock require stress-dose steroids (hydrocortisone 100 mg IV) and broad-spectrum antibiotics. Adrenal insufficiency from abrupt discontinuation of steroids should be highly considered, especially in the patient whose blood pressure is not fluid responsive.

Case Resolution

The 32 year-old female had a small pericardial effusion on echocardiogram not thought to be causing tamponade. Chest x-ray revealed a left-lower lobe consolidation with a WBC of 5,300 cells/mm3 (80% polymorphonucleated cells). Her other cell lines were within normal limits. Lactate levels and initial troponin was also within normal limits. Discussion with her rheumatologist revealed that the patient did not carry the antiphospholipid antibody. She was diagnosed with sepsis in the setting of pneumonia associated with an asthmatic exacerbation. The patient was admitted to the hospital after broad-spectrum antibiotics, and cultures later showed MSSA in her sputum. She left the hospital on oral steroids and oral antibiotics three days later.

Conclusions

Systemic Lupus Erythematosus affects every organ system in the body with multiple life-threatening complications. Furthermore, the medical management and potentially immune-deficient state of the patient with SLE causes further complications. Although these patients do not immediately warrant admission to the hospital, their complaints should be taken seriously and thoroughly evaluated.  If a patient is to be discharged after evaluation in the emergency department, close follow-up should be arranged with rheumatology and potentially other specialists involved in the management of these patients’ chronic care.

References / Further Reading

1). Gladman, Dafna. “Overview of the Clinical Manifestations of Systemic Lupus Erythematosus in Adults.” http://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-systemic-lupus-erythematosus-in- adults?source=search_result&search=sle&selectedTitle=1%7E150 UptoDate, 10 Sept. 2015. Web. 15 Aug. 2016.

2). Petri, Michelle, et. al. “Derivation and Validation of Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus.” Arthritis and Rheumatism. U.S. National Library of Medicine, Aug. 2012. Web. 21 Aug. 2016. Accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409311/

3.) Lehrmann JF, Sercombe CT. Chapter 116 – Systemic Lupus Erythematosus and the Vasculitides in Rosen’s emergency medicine: concepts and clinical practice. 7th edition, Mosby, 2009.

5.) Eastham, Brooke. “Discoid Lupus Erythematosus.”: Background, Etiology, Epidemiology. Medscape, 26 Feb. 2016. Web. 21 Aug. 2016. Accessed at: http://emedicine.medscape.com/article/1065529-overview?pa=YSxqyh8muBNfmRRwi281JNagxcwhhOUiQoz88mEm2X5TkoBPKnaBuEgsf7D3ZOPXBbgbcKRUuE1L1qSucATOgF%2FDMAtBBAsM6eN9kpLn%2Fas%3D

6.) Discoid lupus erythematosus: disfiguring, achromic lesions… – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/264690143_fig12_Figure-1-Discoid-lupus-erythematosus-disfiguring-achromic-lesions-showing-erythema-and [accessed Aug 21, 2016]

7.) Chi, Angela, and Brad Neville. “Oral Manifestations of Systemic Disease.” – American Family Physician. American Family Physicians, 1 Dec. 2010. Web. 21 Aug. 2016. Accessed at: http://www.aafp.org/afp/2010/1201/p1381.html

8.) Pullen, Richard. “Managing Cutaneous Vasculitis in a Patient With Lupus Erythematosus.” Dermatology Nursing. Medscape, n.d. Web. 21 Aug. 2016. <http://www.medscape.com/viewarticle/554930>.

9.) Brent, Lawrence. “Lupus Nephritis.”: Practice Essentials, Background, Pathophysiology. N.p., 28 Sept. 2015. Web. 21 Aug. 2016. <http://emedicine.medscape.com/article/330369-overview>.

10.) Ramachandran, Tarakad. “CNS Lupus.”: Background, Pathophysiology, Etiology. N.p., 14 June 2016. Web. 21 Aug. 2016. <http://emedicine.medscape.com/article/1146456-overview#a5>.

11.) Rebaioli, C., M. Taglietti, Y. Shoenfeld, and A. Tincani. “Heart Involvement in Systemic Lupus Erythematosus, Anti-phospholipid Syndrome and Neonatal Lupus.” Rheumatology. Oxford Journal, 2006. Web. 14 Aug. 2016. <http://rheumatology.oxfordjournals.org/content/45/suppl_4/iv8.full>.

12.) Salmon JE, Roman MJ. Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management. Curr Opin Rheumatol 2001;13:341-4.

13.) Keane, Michael, and Joseph Lynch. “Pleuropulmonary Manifestations of Systemic Lupus Erythematosus.” Pleuropulmonary Manifestations of Systemic Lupus Erythematosus. Thorax, n.d. Web. 21 Aug. 2016. <http://thorax.bmj.com/content/55/2/159.full>.

14.) Dotan, I., and L. Mayer. “Nonhepatic Gastrointestinal Manifestations of Systemic Lupus Erythematosus.” Systemic Lupus Erythematosus (2004): 975-92. The Gastrointestinal Manifestations of Systemic Lupus Erythematosus: A Survey of the Literature. The Open Autoimmunity Journal, 2009. Web. 21 Aug. 2016. <http://benthamopen.com/contents/pdf/TOAUTOJ/TOAUTOJ-1-10.pdf>.

15.) Petri, Michelle. “Life-Threatening Complications of Systemic Lupus Erythematosus.” Autoimmune Diseases: Acute and Complex Situations. Springer, 2011. Web. 21 Aug. 2016. <http://www.springer.com/978-0-85729-357-2>.

16.) Khurana, Ritu. “Systemic Lupus Erythematosus and Pregnancy.”: Practice Essentials, Overview, Pathophysiology. Medscape, 29 Apr. 2014. Web. 21 Aug. 2016. <http://emedicine.medscape.com/article/335055-overview#a5>.

17.) Brent, Lawrence. “Lupus Nephritis.”: Practice Essentials, Background, Pathophysiology. N.p., n.d. Web. 30 Aug. 2016.< http://emedicine.medscape.co