Case:

A 33 year old woman with a past medical history of lupus presenting to the emergency department with chest pain and shortness of breath that began last night. She states she was seated watching television when it started. She took Tums without relief and thought it would subside but the pain persisted when she woke up this morning. She denies fever, cough, abdominal pain, leg swelling, nausea, vomiting, and diarrhea. She does not smoke. She has had no recent travel. She does not take oral contraceptives or any hormone therapy and is not currently on medications for her lupus. On remainder of review of systems, she states her knees have been bothering her more than usual lately but denies any trauma. On exam, her vitals are significant for a heart rate in the 120s, blood pressure 130/80, afebrile, oxygen saturation 95% on room air, respiratory rate 13. She has an erythematous raised rash on her face that she didn’t notice last night. Her cardiac exam is significant for tachycardia but regular rhythm. Lungs are clear to auscultation bilaterally. On the extremity exam, she has 2+ radial and dorsalis pedis pulses. No unilateral leg swelling or evidence of joint swelling or decreased ROM.  Otherwise normal exam. Labs and imaging significant for elevated erythrocyte sedimentation rate (ESR) and c reactive protein (CRP) and mild acute kidney injury (AKI) with a creatinine of 1.7, up from 1.0. Troponin was WNL. D-dimer positive. COVID negative. CT angiogram pulmonary embolism significant for segmental pulmonary embolism. No right heart strain. 

Diagnosis: 

Pulmonary embolism

Discussion:

As emergency medicine physicians, we know how to manage a pulmonary embolism. This patient was started on heparin and admitted to the hospital. I quickly realized my knowledge on lupus, what to order, and what to do was very limited. 

The questions I had were: 

Is this patient having a lupus flare? 

Are there urgent/emergent presentations that I need to consider? 

Are there specific lab tests I need to order to help my inpatient colleagues? 

Do I need to give steroids? 

According to the CDC, systemic lupus erythematosus (SLE) is an autoimmune disease where the immune system attacks its own tissues, causing widespread inflammation and tissue damage to the affected organs. The exact etiology of lupus is unknown. [1] The inflammation is mediated by a type III hypersensitivity reaction where there is an immune complex formed (antigen and antibody), which is too large to be cleared by the body and therefore, deposits in the tissues. This deposit of immune complex leads to the inflammation and ultimate damage. [2] Common body parts affected include the skin, brain, joints, lungs, kidneys and blood vessels. [1]  

When the disease is active and a patient symptomatic, it is often referred to as a flare, although there is no common definition for what constitutes a flare. When the disease is dormant and a patient is not experiencing symptoms, it is referred to as a remission. Frequent monitoring of symptoms and labs help determine disease activity and severity, which in turn determines appropriate treatment. [3]

The widespread inflammation of SLE manifests in diffuse symptoms. The most common symptoms of SLE are fatigue, fever, weight loss, arthralgias, myalgias, malar rash, photosensitive rash and oral ulcers. [4] Emergent considerations of lupus are renal failure from lupus nephritis; hypercoagulability resulting in acute coronary syndrome, pulmonary embolism, cerebrovascular accident; vasculitis, particularly if it involves the cerebral or renal blood vessels; or thrombocytopenia resulting in alveolar hemorrhage or intracranial hemorrhage. [5] A lupus complication can present with altered mental status, seizure, coma, respiratory distress, chest pain, arrhythmias as well as many other common ED presentations. It will be up to you as the clinician to have a high level of suspicion when lupus patients come to the ED because the symptomatology and presentation are widespread and vary from patient to patient. [6] If you are concerned a patient is having a lupus flare or a presentation in the ED is lupus related, you should order the following labs: complete blood count with differential (CBC), basic metabolic panel (BMP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urinalysis with sediment, urine protein creatinine ratio. These labs will tell you if a patient is having hematologic manifestations of lupus, such as anemia or thrombocytopenia, or kidney dysfunction. Comparing ESR/CRP to the patient’s prior labs to see if there are increasing signs of inflammation is a helpful tool as well. More specific labs recommended by rheumatology to help with ongoing management include anti double stranded DNA (anti-dsDNA) and complement levels (C3 and C4). When there is significant inflammation secondary to a lupus flare, complement is activated and levels are consumed resulting in low complement levels in the blood. Also during flares, the autoantibody, anti dsDNA antibodies are found in high concentration in the bloodstream. These will not come back within an hour so emergent decisions will not be made on these levels. Of note, after initial diagnosis, antinuclear antibody (ANA) is no longer used as a screening marker for disease activity. [7]

Routine treatment of lupus includes lifestyle modifications such as diet and exercise as well as medications. Medications used include antimalarial drugs (hydroxychloroquine), corticosteroids, immunosuppressants and biologics. [8] Emergent treatment often includes short term treatment with high doses of systemic glucocorticoids referred to as “pulse dose” methylprednisolone 0.5-1g/day for three days for severely ill patients OR oral prednisone 1-2mg/kg/day in more stable patients. [9] When to treat, what route, and what dose of steroids are not standardized due to very limited data on use and efficacy. Use caution when making this decision as high dose steroids come with significant risk for complications such as infections. [10]

As emergency department physicians, it will not be our job to determine if a patient is having a lupus flare and when to start common treatments. Our main question will be is this patient suffering from a severe and life threatening manifestation of lupus? If so, steroids need to be considered and consultation with a rheumatologist. 

Case Resolution: 

Rheumatology was consulted in the ED. They recommended sending anti-dsDNA, C3, C4 levels in addition to basic blood work. Given the patient was not in acute renal failure or demonstrating other emergent signs of lupus manifestation, they did not think starting systemic steroids would be beneficial at this time. The patient was admitted to the floor and rheumatology followed along for ongoing care. 

Takeaways: 

• Lupus is an autoimmune disease with widespread symptoms 

• Emergent considerations in lupus patients include renal failure, thromboembolic events (stroke, ACS, PE), cerebral vasculitis, and life-threatening bleeding 

• Labs helpful in diagnosis of flare include complement and anti-dsDNA, as well as basic blood work - CBC, BMP, ESR/CRP, UA. 

• Systemic steroids are considered gold standard if life threatening lupus manifestation is suspected

• Call your friendly rheumatologist if in doubt 

Author: Katie Miller, PGY4 Brown Emergency Medicine Residency

Faculty Reviewer: Kristina McAteer, MD

References:

[1] Centers for Disease Control and Prevention. (2022, July 5). Systemic lupus erythematosus (SLE). Centers for Disease Control and Prevention. Retrieved November 18, 2022, from https://www.cdc.gov/lupus/facts/detailed.html#sle 

[2] Science Direct. (2022). Type III hypersensitivity. Type III Hypersensitivity - an overview | ScienceDirect Topics. Retrieved November 18, 2022, from https://www.sciencedirect.com/topics/medicine-and-dentistry/type-iii hypersensitivity#:~:text=Type%20III%20hypersensitivity%20is%20common,formation%20of%20immunocomplexes%20in%20situ. 

[3] Centers for Disease Control and Prevention. (2022, July 5). Managing lupus. Centers for Disease Control and Prevention. Retrieved November 18, 2022, from https://www.cdc.gov/lupus/basics/managing.htm#:~:text=What%20are%20lupus%20flares%3F,seen%20only%20with%20laboratory%20tests. 

[4] Lupus Foundation of America. (2022). Lupus symptoms. Lupus Foundation of America. Retrieved November 18, 2022, from https://www.lupus.org/resources/common-symptoms-of-lupus 

[5] https://cdn.mdedge.com/files/s3fs-public/Document/January-2018/em050010006.pdf

[6] Marco, J. L., & Chhakchhuak, C. L. (2018, January). Complications of Systemic Lupus Erythematosus in the Emergency Department. MDEdge Emergency Medicine. Retrieved November 18, 2022, from https://cdn.mdedge.com/files/s3fs-public/Document/January-2018/em050010006.pdf 

[7] Johns Hopkins Medicine. (2019, March 27). Lupus blood tests. Johns Hopkins Lupus Center. Retrieved November 18, 2022, from https://www.hopkinslupus.org/lupus-tests/lupus-blood-tests/ 

[8] American College of Rheumatology. (2022). Lupus. Retrieved November 19, 2022, from https://www.rheumatology.org/i-am-a/patient-caregiver/diseases-conditions 

[9] Porta, S., Danza, A., Arias Saavedra, M., Carlomagno, A., Goizueta, M. C., Vivero, F., & Ruiz-Irastorza, G. (2020). Glucocorticoids in Systemic Lupus Erythematosus. Ten Questions and Some Issues. Journal of clinical medicine, 9(9), 2709. https://doi.org/10.3390/jcm9092709

[10] Badsha, H., & Edwards, C. J. (2003). Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Seminars in arthritis and rheumatism, 32(6), 370–377. https://doi.org/10.1053/sarh.2002.50003