Systemic Lupus Erythematosus: The Devastatingly Deceptive Disease

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that often goes undiagnosed initially. Timely detection of SLE is important, because prompt treatment can prevent its many major complications—notably, end organ damage. Here’s how to distinguish SLE from other illnesses with similar presentations and how to recognize the complications of undiagnosed SLE, which can progress rapidly and fatally.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that can involve multiple organ systems. The presence of antinuclear antibodies (ANA) is a common marker for this disease. In autoimmune diseases such as SLE, the immune system attacks the cells of healthy tissues throughout the body. Genetic, hormonal, and environmental factors (eg, ultraviolet light, infectious viruses, and even use of certain medications) have been implicated in the pathogenesis.^1-3

It is estimated that 1.5 million people in the United States and up to 5 million people worldwide have SLE.⁴ It is nine to 10 times more prevalent in women—especially those of reproductive age—than menand occurs more frequently in African-American, Hispanic, and Asian women than in non-Hispanic Caucasian women.^1,2,4-6 Siblings of SLE patients are 30 times more likely to develop the disease, compared to individuals without an affected relative.² Increased mortality in persons with SLE is attributed to accelerated atherosclerosis, infection, malignancy, and target organ damage, particularly end-stage renal disease.³ Women ages 33 to 45 with SLE are at increased risk (50x greater) for myocardial infarction due to premature atherosclerosis than age-matched women in the general population.⁷ The life expectancy of SLE ­patients with renal damage is 23.7 years less than that of the general population.⁸

Increased awareness of SLE has led to drastic improvements in associated mortality over the past five decades. The survival rate in the 1950s was 50% at 2 years, while current rates are about 95% at 5 years and about 90% at 10 years.^3,9 These improvements likely reflect earlier diagnosis and treatment on the part of well-informed clinicians, as well as more effective treatment.

SLE MANIFESTATIONS
SLE can affect any organ in the body with a broad spectrum of clinical manifestations, making it a devastatingly deceptive disease. Disease severity may vary by age, by organ involvement, and over time. Onset may be gradual and mild or rapidly progressive with severe organ involvement. Constitutional manifestations such as fatigue, weight loss, anorexia, and low-grade fever often serve as initial complaints. However, these features are common to a variety of infectious and inflammatory conditions, making early SLE easily overlooked and frequently mis­diagnosed. ²

A mix of manifestations involving the joints, skin, mouth, kidneys, lungs, heart, and nervous system offers clues to the diagnosis of SLE (see Table 1). Arthritis is the most common symptom, occurring in 85% to 90% of SLE cases.^1,10 It is typically nonerosive, inflammatory, symmetric or asymmetric, and polyarticular (involving five or more joints)and may be accompanied by constitutional symptoms.^1,2,11 The joints most commonly affected are the proximal interphalangeals, metacarpophalangeals (MCP), knees, and wrists.² Morning stiffness is a common complaint.^1,11 Jaccoud arthropathy, which is characterized by reducible, nonerosive joint subluxations (eg, swan neck deformities, ulnar deviation, boutonniere deformities, and z-shaped thumbs), can be seen in SLE patients.³ When patients present with articular and constitutional symptoms but lack other typical manifestations of SLE, such as skin rash, appropriate measures—for example, arthrocentesis—should be taken to evaluate for infection.¹¹

Cutaneous manifestations are the second most common feature at disease onset, with photosensitivity and malar rash being the most prevalent.¹⁰ Nearly all patients experience skin lesions at some point during the disease course.¹ Diagnostic, or lupus-specific, lesions can be classified into three types: acute, subacute, and chronic.

Acute cutaneous lupus erythematosus (ACLE) is almost always associated with SLE, while subacute cutaneous lupus erythematosus (SCLE) is seen in about 50% of SLE patients.¹² ACLE is usually precipitated by sunlight exposure and includes the classic erythematous, macular, “butterfly” rash located on the malar regions of the face, which may remain for days to weeks.^2,12 Diffuse or discoid alopecia also may develop in ACLE, along with oral ulcers arising in purpuric necrotic lesions on the palate, buccal mucosa, or gums. Generalized erythematous, papular, or urticarial lesions may affect the face, arms, dorsa of the hands, or “V” of the neck.¹²

SCLE tends to be sudden in onset, with annular lesions or psoriasiform plaques on the upper trunk, arms, and dorsa of the hands that often coalesce into polycyclic lesions.¹² These subacute rashes are often associated with anti-SSA/Ro antibodies.

Chronic cutaneous lupus erythematosus is usually characterized by skin disease alone.¹² Discoid lupus is the most common type, with circular scaly plaques with erythematous, hyperpigmented rims and atrophic hypopigmented centers that leave scars.^2,12 It is commonly seen on the face, neck, and scalp.

During the course of SLE, mucous membrane involvement—typically painless oral or nasal ulcers—occurs in 25% to 45% of patients.² Oral lesions are most commonly found on the hard palate and buccal mucosa.^3,12

Lupus nephritis, perhaps the most dangerous manifestation of SLE, conveys high risk for organ failure, a higher mortality rate compared to patients without renal involvement, and lower life expectancy.^8,11 Up to 60% of Asians, African Americans, and Hispanics develop renal disease during the course of their illness.⁸ The dominant feature is proteinuria, typically accompanied by microscopic hematuria.²

Neuropsychiatric SLE (NPSLE) is a clinical manifestation that is poorly understood.¹³ An estimated 28% to 40% of NPSLE manifestations develop prior to or synchronous with the diagnosis, and 63% arise within the first year of diagnosis.¹³ Mild cognitive impairment is the most common manifestation,reported in up to 20% to 30% of SLE patients.^2,13 Seizures and psychosis are reported in 7% to 10% of SLE patients, and psychosis—characterized by hallucinations or delusions—in 3.5%.²

Cardiac findings are common among SLE patients, with an estimated prevalence of 50%, but are rarely the presenting manifestation.¹⁴ Pericarditis with effusion is the most common cardiac manifestation, occurring in 25% of SLE patients.² Advancing atherosclerosis due to chronic inflammation becomes a major cause of mortality in the later years for SLE patients.¹ Compared to the general population, the incidence of myocardial infarction in SLE patients is increased fivefold.¹ Pleuritis is the most common pleuropulmonary manifestation in SLE.¹¹ Pleuritic chest pain with or without a pleural effusion occurs in 45% to 60% of SLE patients.²

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