Elsevier

Clinics in Dermatology

Volume 24, Issue 5, September–October 2006, Pages 348-362
Clinics in Dermatology

Lupus erythematosus: systemic and cutaneous manifestations

https://doi.org/10.1016/j.clindermatol.2006.07.014Get rights and content

Abstract

Skin and joint involvements are the most commonly occurring manifestations of systemic lupus erythematosus. There are 3 forms of cutaneous lupus: chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. Joint manifestations are usually not associated with warmth of the joints and may be only associated with pain and swelling. Painful or swollen joints respond rapidly to small or moderate doses of corticosteroids, whereas cutaneous manifestations usually respond to antimalarial drugs. Anti-Ro is associated closely with a photosensitive rash and with subacute lupus.

Introduction

Systemic lupus erythematosus (SLE) is a multisystem disease of unknown cause that is characterized by the presence of multiple autoantibodies. Typically, it affects the skin, joints, kidneys, lungs, nervous system, serous membranes, and other systems. The autoantibodies are typically antinuclear antibodies. The clinical course is extremely variable and ranges from life-threatening to mild diseases that never require hospitalization. The disease is predominantly present in women, especially those who are in their 20s and 30s, but it may occur in children and in elderly individuals.

Cutaneous manifestations of SLE are present in 85% of patients during the course of the disease, and musculoskeletal abnormalities are present in approximately 95%.1 Joint and skin manifestations thus occur in nearly all patients with SLE. The disease tends to mimic the manifestations present at onset during subsequent exacerbations.

Musculoskeletal manifestations are the most common feature of SLE.1 Arthritis with objective evidence of pain on motion, tenderness, effusion, or periarticular soft-tissue swelling is present at the time of diagnosis in 88% of patients. Some patients develop arthritis after the diagnosis had been made, such that 89% of patients have arthritis during the disease. Other patients have arthralgia without objective evidence of arthritis, such that 95% of patients have either arthritis or arthralgia.

In some patients, arthralgia or arthritis may precede the onset of multisystem disease by many years. The most common joints involved are the proximal interphalangeal joints (present in 82% of patients). The distribution is nearly always symmetrical. The knees are involved in 76% of patients, followed by the wrists and metacarpophalangeal joints. The ankles, elbows, and shoulders are involved less frequently. Knee effusions can be moderately severe. Aspiration reveals a clear fluid with less than 3000 white blood cells per microliter. Most cells are small lymphocytes, and there is a low protein level. Antinuclear antibodies and lupus erythematosus (LE) cells may be found in the fluid. Serum complement proteins are usually low, reflecting similarly low levels in the serum. Synovial histopathology is nonspecific with diffuse proliferation of lining cells and some perivascular mononuclear cells, enlarged endothelial cells, and thrombi. The arthritis disappears completely within a few days after treatment with corticosteroids for systemic diseases.

If a patient presents with a single swollen or painful joint, one should suspect an alternate diagnosis, such as infectious or crystalline arthritis, for which appropriate diagnostic (eg, joint aspiration) and therapeutic measures should be instituted.

During the course of the disease, patients may develop deformities, but these are not related to joint destruction. Typical swan-neck deformities with ulnar deviation of the fingers develop after 3 to 4 years of disease in approximately 10% of patients who continue to have mild intermittent joint pains. Radiographs of the hands reveal no bony erosion or loss of joint space. Joint subluxation is a result of involvement of the tendons and spasm of the small muscles of the fingers.

Morning stiffness is present in 50% of patients, and typical subcutaneous nodules occur in 10%. Tenosynovitis occurs in approximately 10% of patients, with some patients experiencing rupture of the infrapatellar, deltoid, or Achilles tendons.

Avascular necrosis occurs in approximately 15% of patients after prolonged treatment with high doses of corticosteroids. Avascular necrosis is most common in the femoral heads and presents as anterior groin pain, trochanteric bursal pain, or anterior thigh pain. Radiographs may be negative early after the onset of pain, but magnetic resonance imaging may allow early diagnosis.

Muscle pain is present in approximately 30% of patients, with enzyme abnormalities occurring in approximately 20% of patients before treatment.

Fibromyalgia is common in patients with SLE and must be distinguished from the joint and muscle pain associated with the disease.

Section snippets

Pathophysiology

The pathophysiologic mechanisms of LE-specific skin disease continue to be elucidated.2 It is thought that development of skin disease is related to the same autoimmune abnormalities responsible for the systemic components of LE. Current theories discuss the relationship between genetic susceptibility, autoimmune induction and subsequent expansion, and injury to the immune system.3 Genetic susceptibility is probably related to genes that decrease the threshold for self-reactivity and allow a

General features

Fatigue is present in nearly all patients with SLE during periods of disease activity and can precede the appearance of rashes or joint swelling. Fever is present in approximately 80% of patients at the time of diagnosis and may be of low grade or spiking. Fever in a treated patient with SLE should be considered to be a result of infection until proven otherwise. Weight loss is present in approximately 85% of patients at the time of diagnosis unless the nephrotic syndrome is present.

Cardiovascular manifestations

Clinically

Laboratory findings

One or more hematologic abnormalities are present in nearly all patients with SLE who have active disease. Most commonly, mild to moderate normocytic and normochromic anemia is present. Coombs' test–positive hemolytic anemia occurs in approximately 10% of patients. Mild to moderate leukopenia is present in 17% of patients, and lymphopenia is also usually present during disease activity. Mild thrombocytopenia is present in approximately one third of patients, but less than 100,000 platelets/mm3

Precipitating factors

Sun exposure may induce the onset of SLE and cause exacerbations of the disease. Infections, especially bacterial infections, may occur before the onset of the disease or cause an exacerbation. Infections especially occur before clotting episodes in patients with antiphospholipid antibodies. Surgery or any trauma that induces necrosis of tissue and the release of nuclear antigens may cause an exacerbation of SLE. Pregnancy is associated with the onset of lupus during the last trimester or the

Conventional agents

Systemic glucocorticoids are the standard form of treatment for patients with SLE. Some patients require very low doses of prednisone (≤10 mg) to alleviate manifestations of the disease. Patients with nephritis, central nervous system lupus, or pulmonary hemorrhage may require very high doses, and intravenous therapy is frequently recommended to them. Cyclophosphamide and mycophenolate may be used in conjunction with high doses of glucocorticoids. Author, Naomi Rothfield treats patients with

Treatment: cutaneous manifestations

Comments here will be directed at the treatment of LE-specific skin diseases such as SCLE and CCLE. The second author (RDS) has recently addressed this subject more comprehensively elsewhere.67, 68 Acute cutaneous LE (eg, facial butterfly-shaped erythema reactions) and LE-nonspecific skin lesions (eg, cutaneous vasculitis) are typically seen in the context of active SLE. The systemic immunomodulatory/immunosuppressive treatments required to control the SLE activity will typically in a parallel

Acknowledgment

Dr Sontheimer's contribution to the preparation of this work was supported by the Richard and Adeline Fleischaker Chair in Dermatology Research of the University of Oklahoma Health Sciences Center.

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