Diverse, any organ system can be involved; nonspecific signs and symptoms of fatigue, joint pain, rash, and fever at onset can be common and may delay diagnosis.

• Skin/Mucosa: “Discoid” lesions with red, sharply demarcated coin-shaped plaques with scale, follicular plugging, telangiectasias, and scarring on sun-exposed areas are the most common cutaneous finding in children with childhood-onset systemic lupus erythematosus (cSLE); butterfly (malar) rash common though may be absent in children and may involve chin and ears; may also be hypopigmented, especially in children with darker pigmentation; oral and/or nasal ulcers; nonscarring alopecia; can be diffused; scalp inflammation may be absent.Children may also develop limited systemic involvement with lupus erythematosus tumidus associated with red, edematous, nonscarring plaques in sun-exposed areas and subacute cutaneous lupus with urticarial plaques with telangiectasias, scaling, and follicular plugging also in sun-exposed areas.
  
• Constitutional: Low-grade fever, fatigue, anorexia, and lymphadenopathy common at onset; may not help to differentiate SLE from other systemic illnesses.
  
• Musculoskeletal: Arthritis and arthralgias, large and small joints; may be asymptomatic; osteopenia, osteoporosis, and osteonecrosis also possible.
  
• Cardiac: Pericarditis is the most common cardiac abnormality in cSLE, often within first six months of diagnosis; increased risk of developing atherosclerotic disease in cSLE; lower extremity edema.
  
• Pulmonary: Pleuritis in 30% to 35%; acute pulmonary hemorrhage (<5%) and pulmonary hypertension (<2%).
  
• GI: ~20% of children; pain from ascites, pancreatitis, and asymptomatic mild hepatitis.
  
• Renal: ~2/3 of children; hematuria, proteinuria, nephrotic syndrome, or acute renal failure.
  
• Hematologic: Anemia, leukopenia, lymphopenia, and thrombocytopenia.
  
• Neuropsychiatric: Headache very common; also cognitive impairment, transverse myelitis, psychosis, seizures, mood disorders, anxiety disorders, and cerebrovascular disease.

American College of Rheumatology (ACR) criteria, Systemic Lupus International Collaborating Clinics (SLICC) criteria to aid diagnosis; the new European League Against Rheumatism (EULAR)/ACR criteria have sensitivity and specificity of 96.1% and 93.4%. EULAR/ACR system requires an antinuclear antibody (ANA) titer or 1:80 or higher.

• Rheumatology
  
• Nephrology
  
• Ophthalmology if on long-term hydroxychloroquine
  
• Neurology/psychiatry
  
• Referral to a tertiary care facility for multidisciplinary care

Avoid sunlight as much as possible; liberal use of SPF-30, broad-spectrum sunscreen, consider vitamin D supplementation.

Hydroxychloroquine for cutaneous and musculoskeletal symptoms, can be considered as steroid-sparing therapy (monitor for retinal pigment changes); systemic corticosteroids as needed for flare-ups; corticosteroids and cyclophosphamide for nephritis with mycophenolate mofetil as an alternate; cyclosporine, methotrexate are also alternative treatments; B-cell therapy to reduce autoantibody production (belimumab), approved for 5 years and older.