Etiology and Pathogenesis

The cause of SLE involves a complex interplay of genetic, environmental, and immunologic factors. Several genes have been identified that confer susceptibility to SLE, including human leukocyte antigen haplotypes, complement component and receptor genes, cytokine polymorphisms, Fc receptors, and T-cell receptor polymorphisms. It is likely that a combination of these genes provides a genetic risk profile that allows the subsequent development of SLE under the appropriate conditions. Familial clustering has been reported, and the concordance rates among monozygotic and dizygotic twins are 25% and 2%, respectively

The immune dysregulation in SLE is multifactorial and includes abnormal clearance of apoptotic debris, B- and T-cell abnormalities, and autoantibody and immune complex formation. In SLE, the system of apoptotic particle removal is dysfunctional, allowing for the presentation of autoantigens to T cells. These T cells stimulate B cells to produce high-affinity autoantibodies that bind directly to cells in end organs, causing injury, or form immune complexes in the circulation that deposit in tissues and cause inflammation. Additionally, early classical complement deficiencies are associated with SLE; this association is probably secondary to delayed clearance of apoptotic debris and immune complexes.

Other factors have been hypothesized to play a role in the cause of SLE, including hormonal influences, Epstein-Barr virus and other infections, exposure to ultraviolet light, L-canavanine (a chemical in alfalfa sprouts), and silica dust inhalation. Although the precise cause of SLE is unknown, it is clear that genetic susceptibility, immunologic dysregulation, and environmental influences all contribute.

Clinical Presentation

SLE is rare in children younger than age 5 years and is uncommon before adolescence. In childhood, girls are affected approximately four times more often than boys. The presenting symptoms are widely variable. Constitutional signs and symptoms, including fever, fatigue, lymphadenopathy, hepatosplenomegaly, and weight loss, are commonly seen. The most frequently involved specific sites affected by SLE are the skin, joints, and kidneys. Symptoms often precede the diagnosis by several months and may be insidious or acute in onset. The American College of Rheumatology provides criteria which are used clinically to aid in the diagnosis of SLE (Table 29-1, Figure 29-1). The diagnosis of SLE is made if at least four of the criteria are present or have been present in the past without another diagnosis that explains the findings. The antinuclear antibody (ANA), one of the criteria for diagnosis of SLE, is not a useful general screening test for rheumatologic disease and should not be sent routinely in the absence of other criteria for SLE.

Table 29-1 American College of Rheumatology 1997 Revised Classification Criteria for Systemic Lupus Erythematosus

Criterion	Description
Malar rash	“Butterfly” erythematous rash over malar eminences; spares nasolabial folds (see Figure 29-2)
Discoid rash	Raised erythematous patches with scaling and follicular plugging on the face, scalp, and extremities; may lead to scarring
Photosensitivity	Any rash that occurs as an unusual reaction to sunlight
Oral or nasal ulcerations	Painless ulcerations of the oral or nasal mucosa (see Figure 29-2)
Arthritis	Nonerosive arthritis of two or more peripheral joints
Nephritis	Persistent proteinuria >0.5 g/d or cellular casts (red blood cell, hemoglobin, granular, tubular, or mixed)
Serositis	Pleuritis or pericarditis
Neurologic disorder	Seizures or psychosis (in the absence of offending drugs or metabolic disturbances)
Cytopenia	Hemolytic anemia with reticulocytosis or leukopenia (<4000/mm³) or lymphopenia (<1500/mm³) or thrombocytopenia (<100,000/mm³)
Positive immunoserology	Antibodies to dsDNA or antibodies to Sm nuclear antigen or anticardiolipin antibodies or presence of lupus anticoagulant or false-positive serologic test for syphilis (known to be positive for ≥6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test)
Positive antinuclear antibody	Abnormal titer of antinuclear antibodies at any point in time

Adapted from Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725, 1997.

Figure 29-1 Criteria used for the diagnosis of systemic lupus erythematosus.

Skin and Mucus Membrane Manifestations

There are four skin and mucocutaneous criteria: malar rash, discoid rash, oral or nasal ulcers, and photosensitivity. The malar rash, or classic “butterfly rash,” is typically maculopapular and photosensitive. Additionally, it classically extends across the nasal bridge, spares the nasolabial folds, and is nonscarring (Figure 29-2). Depending on the race of the child, it may be either hyper- or hypopigmented. A discoid rash is less common. These inflammatory lesions are coin shaped, raised, and erythematous. They are most commonly located on the face (especially the ears), scalp, and extremities. These lesions are scarring and lead to permanent alopecia when they occur on the scalp. The oral and nasal ulcers associated with SLE are usually painless; oral ulcers are classically located on the hard palate (see Figure 29-2). Other common skin manifestations include livedo reticularis (see Figure 29-2), alopecia, Raynaud’s phenomenon (see Figure 27-2), and digital ulcerations.