Systemic Lupus Erythematosus (Disorders of Immune-Mediated Injury) (Rheumatology) Part 2

Diagnosis

The diagnosis of SLE is based on characteristic clinical features and autoantibodies. Current criteria (2006) for classification are listed in Table 4-3 (new criteria are being developed), and an algorithm for diagnosis and initial therapy is shown in Fig. 4-2. The criteria are intended for confirming the diagnosis of SLE in patients included in studies; the author uses them in individual patients for estimating the probability that a disease is SLE.Any combination of >4 of 11 criteria, well documented at any time during an individual’s history, makes it likely that the patient has SLE. (Specificity and sensitivity are ~95% and ~75%, respectively.)

TABLE 4-3

If >4 of these criteria, well documented, are present at any time in a patient’s history, the diagnosis is likely to be SLE. Specificity is ~95%; sensitivity is ~75%.

Note: ANA, antinuclear antibodies; dsDNA, double-strand DNA; ECG, electrocardiography.

In many patients, criteria accrue over time. Antinuclear antibodies (ANA) are positive in >98% of patients during the course of disease; repeated negative tests suggest that the diagnosis is not SLE, unless other autoantibodies are present (Fig. 4-2). High-titer IgG antibodies to double-stranded DNA and antibodies to the Sm antigen are both specific for SLE and, therefore, favor the diagnosis in the presence of compatible clinical manifestations. The presence in an individual of multiple autoantibodies without clinical symptoms should not be considered diagnostic for SLE, although such persons are at increased risk since clinical SLE begins in most patients years after autoantibodies appear.

Interpretation of Clinical Manifestations

When a diagnosis of SLE is made, it is important to establish the severity and potential reversibility of the illness and to estimate the possible consequences of various therapeutic interventions. In the following paragraphs, descriptions of some disease manifestations begin with relatively mild problems and progress to more life-threatening ones.

Overview and Systemic Manifestations

At its onset, SLE may involve one or several organ systems; over time, additional manifestations may occur (Tables 4-3 and 4-4). Most of the autoantibodies characteristic of each person are present at the time clinical manifestations appear (Tables 4-1 and 4-3). Severity of SLE varies from mild and intermittent to severe and fulminant. Most patients experience exacerbations interspersed with periods of relative quiescence; permanent complete remissions (absence of symptoms with no treatment) are rare. Systemic symptoms, particularly fatigue and myalgias/ arthralgias, are present most of the time. Severe systemic illness requiring glucocorticoid therapy can occur with fever, prostration, weight loss, and anemia with or without other organ-targeted manifestations.

Musculoskeletal Manifestations

Most people with SLE have intermittent polyarthritis, varying from mild to disabling, characterized by soft tissue swelling and tenderness in joints, most commonly in hands, wrists, and knees. Joint deformities (hands and feet) develop in only 10%. Erosions on joint x-rays are rare; their presence suggests a non-lupus inflammatory arthropathy such as rheumatoid arthritis (Chap. 5); some experts think that erosions can occur in SLE. If pain persists in a single joint, such as knee, shoulder, or hip, a diagnosis of ischemic necrosis of bone should be considered, particularly if there are no other manifestations of active SLE.The prevalence of ischemic necrosis of bone is increased in SLE, especially in patients treated with systemic glucocorticoids. Myositis with clinical muscle weakness, elevated creatine kinase levels, positive MRI scan, and muscle necrosis and inflammation on biopsy can occur, although most patients have myalgias without frank myositis. Glucocorticoid therapies (commonly) and antimalarial therapies (rarely) can also cause muscle weakness; these adverse effects must be distinguished from active disease.

Cutaneous Manifestations

Lupus dermatitis can be classified as discoid lupus erythematosus (DLE), systemic rash, subacute cutaneous lupus erythematosus (SCLE), or “other.” Discoid lesions are roughly circular with slightly raised, scaly hyperpig-mented erythematous rims and depigmented, atrophic centers in which all dermal appendages are permanently destroyed.

FIGURE 4-2

Algorithm for diagnosis and initial therapy of SLE. ANA, antinuclear antibodies; CBC, complete blood count.

Lesions can be disfiguring, particularly on the face and scalp. Treatment consists primarily of topical or locally injected glucocorticoids and systemic antimalarials. Only 5% of people with DLE have SLE (although half have positive ANA); however, among individuals with SLE, as many as 20% have DLE.The most common SLE rash is a photosensitive, slightly raised erythema, occasionally scaly, on the face (particularly the cheeks and nose—the “butterfly” rash), ears, chin,V region of the neck, upper back, and extensor surfaces of the arms. Worsening of this rash often accompanies flare of systemic disease. SCLE consists of scaly red patches similar to psoriasis or circular flat red-rimmed lesions. Patients with these manifestations are exquisitely photosensitive; most have antibodies to Ro (SS-A). Other SLE rashes include recurring urticaria, lichen planus-like dermatitis, bullae, and panniculitis (“lupus profundus”). Rashes can be minor or severe; they may be the major disease manifestation. Small, painful ulcerations on the oral or nasal mucosa are common in SLE; the lesions resemble aphthous ulcers.

Renal Manifestations

Nephritis is usually the most serious manifestation of SLE, particularly since nephritis and infection are the leading causes of mortality in the first decade of disease. Since nephritis is asymptomatic in most lupus patients, urinalysis should be ordered in any person suspected of having SLE. The classification of lupus nephritis is primarily histologic.Patients with dangerous proliferative forms of glomerular damage (ISN III and IV) usually have microscopic hematuria and proteinuria (>500 mg per 24 h); approximately one-half develop nephrotic syndrome, and most develop hypertension.

TABLE 4-4

^aNumbers indicate percent of patients who have the manifestation at some time during the course of illness.

If diffuse proliferative glomerulonephritis (DPGN) is untreated, virtually all patients develop ESRD within 2 years of diagnosis. Therefore, aggressive immunosuppression is indicated (usually systemic glucocorticoids plus a cytotoxic drug), unless damage isirreversible (Fig.4-2, Table 4-5).AfTicanAmeri-cans are more likely to develop ESRD than are Caucasians, even with the most current therapies. Overall in the United States, ~20% of individuals with lupus DPGN die or develop ESRD within 10 years ofdiagnosis. Such individuals require aggressive control of SLE and of the complications of renal disease and of therapy. A small proportion of SLE patients with proteinuria (usually nephrotic) have membranous glomerular changes without proliferation on renal biopsy. Their outcome is better than for those with DPGN, but proteinuria is less likely to improve on lupus nephritis immunosuppressive therapies. Lupus nephritis tends to be an ongoing disease, with flares requiring retreatment over many years. For most people with lupus nephritis, accelerated atherosclerosis becomes important after several years ofdisease; attention must be given to control of blood pressure, hyperlipidemia, and hyperglycemia.