Patient Presentation
An intern in her continuity clinic shared a teenage patient she had admitted to the inpatient floor with only facial swelling. “She really didn’t have anything else on physical exam, but her labs were off and she just didn’t look right,” he said. “That’s an odd one. Entire facial swelling, not just the eyes or a more localized edema? No other areas of body edema either?” asked the attending. “No nothing else really on physical exam. No specific rashes, no fever, no weight loss, no urinary or GI problems. Her hemoglobin was a little low as was her WBC count. UA was normal,” the intern said. “We’ll I’m thinking that if she is still in the hospital, then it isn’t straight forward. You must have all looked at renal or allergic disease with the swelling. A localized cancer doesn’t seem to fit and it doesn’t seem like something metastatic. Autoimmune problems and unusual infectious diseases most likely a virus are big categories, but there could be lots of things. Two diseases that have a wide range of presentations that sometimes don’t seem logical are EBV virus and SLE,” the attending remarked. “I talked with the intern this morning and their working diagnosis is SLE, but they are not sure. Viruses and EBV were negative. They are still in the process of evaluating her. They even did some test where they use snake venom,” she said. “That is why you need a rheumatologist and maybe even a couple of other specialists to help you when it is that specific. Just remember that some of your best differentials may come from the person with a wide viewpoint like a generalist, or even a radiologist or pathologist. These people don’t think of things by just one specialty. There are some really good specialists who also take that wide viewpoint too and can really help when things are not clear,” the attending stated. She went on, “I hope they figure it out soon so that she can start to get better. It’s hard not feeling well and not really knowing too.”
Discussion
Lupus erythematosus is one of the classic autoimmune diseases. Its presentations, evaluation and management can be challenging for even seasoned practitioners. Cutaneous lupus erythematosus as it implies involves the skin but can progress to systemic involvement. Systemic lupus erythematosus (SLE) usually involves multiple organ systems concurrently. Childhood (sometimes called juvenile) SLE is usually defined as occurring before age 18 years. Estimates are 15-20% of patients with SLE started having symptoms before age 18 years, with most occurring after age 10 years. Childhood SLE often has a more aggressive course and high incidence of end organ damage especially kidney disease.
As the presentations and problems can be diverse and there are other potential diagnoses, especially other autoimmune problems, professional groups have used criteria which can aid diagnosis, treatment and further research. Current criteria from Europe and the US (EULAR/ACR criteria) from 2019 include:
- ANA antibodies at a titre of ≥1:80 or HEp-2 cells or equivalent positive test (Must be present to diagnosis SLE) [Note: ANA antibodies are present in ~99% of patients with SLE. Anti ds-DNA and anti-Smith antibodies have good specificity for SLE.]
- If ANA is present then a variety of domains with different additive criteria are used and a total score of ≥10 or more is needed to make the diagnosis of SLE. There are caveats about how to apply the criteria as well.
- Domains evaluated include constitutional symptoms, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal, antiphosolipid antibodies, complement proteins and SLE-specific antibodies.
Neonatal lupus is not the same as SLE. Neonatal lupus is due to maternal antibodies crossing the placenta during gestation which then affect the fetus and neonate, especially cardiac, liver and hematological problems. As the autoantibodies wane, symptoms, if any, disappear with time. A review can be found here.
New treatment guidelines for SLE from the American College of Rheumatology became available in 2025. “Hydroxychloroquine should be standard therapy for all people with SLE unless contraindicated.” Glucocorticoids are to be used for initial treatment and flares with tapering as soon as possible. Other commonly used medications include azathioprine, cyclophosphamide, calcineurin inhibitors and a variety of biological medications. SLE can go into remission and also recur. Therefore ongoing daily treatment with these medications can be tapered or stopped in the right circumstances, but patients need to be monitored. Likewise life- or organ-threatening disease may require intense, prolonged treatment. Ten-year survival rates are very high (90% +) and often are related to the intensity of the kidney disease the patient has.
Learning Point
Problems associated with SLE are due to its inflammatory or thrombotic tendencies. However it is important to note, that the treatment drugs can cause side effects which can be the same or similar to the disease itself. Living with any disease can also have problems that may overlap with the disease itself. For example, painful joints may decrease activity, which can cause overall deconditioning which can cause fatigue. Depression can be caused by living with SLE, SLE disease itself, or some of the drugs used to treat it. This highlights how difficult it can be to diagnose and manage problems associated with SLE.
While the “classic” SLE presentation of malar rash, joint pain and fever is what is taught, in childhood SLE, patients frequently present with fever, fatigue and arthritis. SLE can have a variety of presentations and problems with which to manage. Unexplained fever, arthritis with rash, cytopenias, neurological disease and kidney disease should have SLE considered as a possible diagnosis. Below are some of the presentations and problems associated with SLE. Those with an asterisk are part of the EULAR/ACR criteria.
- Constitutional
- *Fever
- Fatigue
- Weight loss
- Hematologic
- *Autoimmune hemolysis
- *Leukopenia
- *Thrombocytopenia
- Lymphadenopathy
- Splenomegaly
- Thrombosis of various organs
- Neuropsychiatric
- *Delirium
- *Psychosis
- *Seizure
- Cognitive deficits
- Chorea
- Encephalopathy
- Headache
- Mood disorders
- Transverse myelitis
- Stroke
- Cranial nerve problems
- Peripheral nerve problems
- Paresthesia
- Guillain-Barre syndrome
- Myasthenia-like syndrome
- Mucocutaneous
- *Alopecia, non-scaring
- *Acute cutaneous lupus = malar or butterfly rash over nasal bridge and cheeks
- *Subacute cutaneous lupus – photosensitive
- *Discoid lupus
- *Oral ulcers (usually painless)
- Nasal ulcers
- Bullae
- Cutaneous vasculitis
- Chilblains
- Erythema nodosum
- Gangrene
- Palpable purpura
- Serosal
- *Pericardial effusion
- *Acute pericarditis
- *Pleural effusion
- Endocarditis
- Myocarditis
- Cardiac tamponade
- Peritonitis
- Musculoskeletal
- *Joint involvement both large and small
- Polyarteritis/arthralgia
- Renal
- *Proteinuria
- *Renal biopsy with specific diagnostic criteria
- Glomerulonephritis
- Interstitial nephritis
- Nephrotic syndrome
- Hypertension
- Antiphosolipid antibodies
- *Anti-cardiolipin antibodies
- *Anti-β2GP1 antibodies
- *Lupus anticoagulant
- Complement proteins
- *Low C3 and/or low C4
- SLE-specific antibodies
- *Anti-dsDNA antibody
- *Anti-Smith antibody
- Other lab testing
- DAT (Coomb’s) positive
- Dilute Russell’s Viper Venom Time
- Endocrine
- Diabetes mellitus
- Hypothyroid
- Gastroenterology
- Bowel (enteritis)
- Hepatitis
- Pancreatitis
- Hepatomegaly
- Splenomegaly
- Ocular
- Dry eyes
- Eyelids – edema, erythema, ecchymosis
- Conjunctivitis, scleritis, keratitis, uveitis
- Retinopathy and choroid changes
- Optic nerve neuropathy or neuritis
- Papilledema
Questions for Further Discussion
1. What are the criteria for diagnosing juvenile idiopathic arthritis?
2. What is in the differential diagnosis of limp? A review can be found here
3. What are indications for a renal biopsy?
Related Cases
- Disease: Lupus
- Symptom/Presentation: Edema
- Specialty: General Pediatrics | Infectious Diseases | Rheumatology
- Age: Teenager
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Lupus
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2019;71(9):1400-1412. doi:10.1002/art.40930
Mann MP, Sage AM, McKinnon E et al. Childhood Systemic Lupus Erythematosus: Presentation, management and long-term outcomes in an Australian cohort. Lupus. 2022;3(2):246-255. doi:10.1177/09612033211069765
Curtiss P, Walker AM, Chong BF. A Systematic Review of the Progression of Cutaneous Lupus to Systemic Lupus Erythematosus. Front Immunol. 2022;13:866319. doi:10.3389/fimmu.2022.866319
Chandwar K, Aggarwal A. Systemic Lupus Erythematosus in Children. Indian J Pediatr. 2024;91(10):1032-1040. doi:10.1007/s12098-023-04833-0
Nikolaidou A, Gianni T, Sandali A, Toumasis P, Benekos K, Tsina E. Ocular manifestations of Juvenile Systemic Lupus Erythematosus: a systematic review. Eye (Lond). 2025;39(6):1056-1069. doi:10.1038/s41433-025-03664-x
Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) Guideline for the Treatment of Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). Published online November 3, 2025. doi:10.1002/acr.25690
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa