Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is the prototype of multisystemic autoimmune diseases, affecting all organ systems. Its severity can range from mild to severe and life-threatening.

SLE affects 20 – 100/100 000 in Europe. It more frequently affects women in the ages 16 – 55, being 12x more common in women. Affected men have a worse prognosis. SLE more frequently affects Black and Hispanic ethnicities than White. The 10-year survival rate is 90%.

The most important poor prognostic factors are affection of the kidneys and CNS, and so these are among the most common causes of mortality in SLE patients. SLE doubles the cardiovascular risk as well, which is another common cause of mortality. In the first years, the most common cause of death is infection due to immunosuppression.

Etiology

The exact etiology is unknown, but several risk factors are known:

• HLA-DR2 or -DR3
• High oestrogenic state (oral contraceptives, endometriosis)
• Smoking
• Certain drugs

Drug-induced lupus erythematosus is an SLE-like syndrome caused by certain drugs. The most commonly identified drugs are procainamide, hydralazine, and TNF-α inhibitors. The first two have the highest risk but aren’t widely used anymore.

Pathomechanism

The pathomechanism is not fully understood, but involves the following mechanisms under the influence of environmental factors as triggers:

• Expression of own antigens on the cell surface
• Loss of T-cell tolerance
• Formation of autoreactive B cells
• Formation and deposition of immune complexes

Clinical features

Clinical features in SLE occur in phases of remission and relapse. SLE can affect virtually any organ system, but it most frequently affects:

• Skin
• Musculoskeletal system
• Kidney
• CNS
• Cardiovascular system
• Pulmonary system
• Serous membranes
• Haematological system
• Gastrointestinal system

In addition to these, there may be non-specific symptoms like fatigue, fever, weight loss, lymphadenopathy, and splenomegaly. Skin and musculoskeletal symptoms are the most common, affecting almost all patients with SLE. The other organs are less frequently affected.

The most classical skin symptom in SLE is the malar rash (butterfly rash), which is an erythematous rash on both malar eminences which spares the nasolabial folds. Other skin symptoms include Raynaud phenomenon, photosensitivity, discoid rash, oral ulcers, and alopecia.

The most common musculoskeletal symptom is non-erosive symmetrical polyarthritis affecting distal joints.

The renal manifestation of lupus is called lupus nephritis, which is covered in detail in nephrology. It’s a severe complication and a major cause of death in SLE. 50% of SLE patients develop lupus nephritis at some point, but only 20% have it at the time of diagnosis. The presence of lupus nephritis in a patient with SLE means a worse prognosis and usually alterations in treatment. There are six different classes (types) of lupus nephritis with very variable prognosis. Class I (minimal mesangial type) has the best prognosis, while class IV (diffuse proliferative) has the worst. Clinically, lupus nephritis may present as isolated proteinuria or haematuria, or any nephrological syndrome.

CNS manifestations may be anything from headaches to psychosis and seizures. Cardiovascular manifestations may be myocarditis, valvular disease, and accelerated atherosclerosis. Pulmonary manifestations include interstitial lung disease, pneumonitis, and pulmonary hypertension. Any serous membrane may be inflamed.

Any haematological cell line may be affected, causing anaemia, leukopaenia, lymphocytopaenia, or thrombocytopaenia. GI manifestations include abdominal pain, peritonitis, ascites, pancreatitis, and hepatitis.

Diagnosis and evaluation

SLE is a clinical diagnosis based the presence of certain diagnostic criteria. Previously, the ACR or SLICC criteria were used. However, in 2019, a comprehensive and more sensitive and specific set of criteria was released, the ACR/EULAR criteria. These criteria give points based on typical clinical features, laboratory findings, serology, and renal biopsy findings. The “entry criterion” is an ANA titre of > 1:80, meaning that this is an obligatory finding for the diagnosis (98% sensitive).

Typical laboratory findings include:

• Leukocytopaenia
• Thrombocytopaenia
• Autoimmune haemolysis
• Elevated ESR (normal CRP)
• Decreased level of complement
• ANA titre > 1:80
• Presence of antiphospholipid antibodies
  • Anti-cardiolipin
  • Lupus anticoagulant
• Presence of SLE-specific antibodies
  • Anti-dsDNA
  • Anti-Sm

Treatment

For the best possible treatment of SLE, it’s important to determine the severity of the disease. There exist countless indexes for this purpose, but the most frequently used is the SLEDAI-2K index. The presence of renal or CNS manifestations necessitates more intensive treatment, and so detection of these complications is important.

Important lifestyle changes include appropriate sun protection, smoke cessation, exercise, and adherence to vaccination protocols. NSAIDs can provide symptomatic relief.

Pharmacological treatment can be considered in three different forms: induction of remission, maintenance of remission, and supportive treatment. Side effects of pharmacological therapy is unfortunately a major cause of SLE-related morbidity and mortality, mostly due to corticosteroids.

For induction of remission, corticosteroids are used. In cases of renal or CNS affection, other immunosuppressants like cyclophosphamide or mycophenolate mofetil may also be necessary.

For maintenance of remission, hydroxychloroquine is indicated in all patients as it effectively reduces morbidity and mortality. Other immunosuppressants, like azathioprine, methotrexate, and sometimes even long-term low-dose glucocorticoids, may be required. Belimumab and rituximab are the only biological therapies indicated for SLE.

Supportive treatment includes medications like ACE inhibitors, ARBs, statins, antiepileptics, bisphosphonates, etc.