Lupus Erythematosus

Lupus or systemic lupus erythematosus (SLE) is a chronic autoimmune disease with complex pathogenesis (disease process or biology) and varying clinical phenotypes (physical symptoms). The clinical picture in SLE is a result of the various internal autoimmune (the body’s immune cells misidentify its own tissue as foreign material and initiate an immunologic attack against it) pathogenic events associated with the disease.

The immune impairment comprises apoptotic dysregulation (dysregulation of the default-programmed cell death, or disturbance in the process of natural, routine clearance of dead cells and toxins by the body, thereby, leading to an accumulation of dead cells and toxins), formation of immune complexes, and complement pathway dysregulation (critical processes of natural immunity-regulation in the body), that result in inflammatory pathway activation. Lupus is prevalent worldwide, with a higher prevalence in people of black ethnicity as compared to whites.

Lupus erythematosus is a chronic inflammatory autoimmune disease affecting various parts of the body.

Symptoms

The clinical manifestations of SLE include cutaneous (skin), musculoskeletal, nephrological (kidney), pulmonary (lungs), neurological (nerve), and cardiovascular (heart) symptoms. The nature and intensity of symptoms of SLE alter between flare-ups and periods of remission. These symptoms include:

• Fatigue

• Headache

• High fever

• Swelling in the joints and muscles

• Swollen glands

• Rashes on the skin

• Discolored fingers or toes

• Numbness when exposed to cold or stressful conditions

• Sensitivity to sunlight

• Chest pain upon deep breathing

• Ulcers in the mouth and mucosal linings 

• Abdominal pain

Diagnosis

Clinical findings are useful in diagnosing SLE. Malar rash (butterfly-shaped rash on the face) and other cutaneous manifestations, such as maculopapular lesions, along with musculoskeletal and neurological involvement give an early indication of SLE.

Laboratory findings such as a high erythrocyte sedimentation rate (ESR) are characteristic of active SLE along with slightly elevated C-reactive protein. A standard diagnosis of SLE is thrombocytopenia (low platelet count) and/or leukopenia (low leukocytes) and lymphopenia (low lymphocytes) or low immune cells, leading to autoimmune hemolytic anemia.

Kidney function-test findings in SLE include high serum creatinine, urinary protein, and sediments. The antinuclear antibodies (ANA) are detected by indirect immunofluorescence laboratory techniques. Anti-Smith antibody testing and anti-dsDNA antibody testing are other important requisites for the diagnosis. Complement components such as C3 and C4 are indicators of complement consumption or deficiency.All diagnostic investigations are carried out .depending on the symptoms of SLE.

Management

There is currently no cure for SLE, and the goal of treatment is to ease symptoms. The management of lupus includes three goals:

1. Preventing flares and their symptomatic impact

2. Reducing the chronic accumulation of organ damage

3. Minimizing toxicity from immunosuppression

Following generalized approaches are taken to achieve these goals:

Non-drug approaches: Exposure to ultraviolet rays can induce both cutaneous and systemic symptoms such as arthritis. Hence, patients are advised to minimize sun exposure during peak hours and use sunscreen lotions (SPF 50+). Quitting smoking may help with treatment-resistant skin lesions as well as reduce the elevated cardiovascular risk associated with lupus.

Drug-based approaches: Clinicians use a broad range of medications to treat lupus, including glucocorticoids, antimalarial agents; nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents, and B cell–targeting biologics.

(a) Hydroxychloroquine: Hydroxychloroquine, an antimalarial drug is the mainstay of SLE treatment and is used in all patients with lupus unless contraindicated. It helps in the prevention of SLE exacerbations and reduces the risk of congenital heart disease in neonatal SLE.

Hydroxychloroquine has antithrombotic effects in addition to inhibition of platelet adhesiveness, aggregation, and activation and is crucial in the treatment of SLE patients with prothrombotic tendencies or abnormal blood coagulation tendencies leading to blood clots, including those with antiphospholipid antibodies or significant proteinuria.

However, prolonged treatment of SLE with hydroxychloroquine (especially at a dose higher than recommended) with co-existing renal disease and use of the drug tamoxifen, can be a predisposing factor for retinopathy.

(b) Belimumab: It is a monoclonal antibody targeting the B cell activating factor (BAFF), and has been shown to improve musculoskeletal and mucocutaneous manifestations and immunologic parameters in lupus, primarily in non-renal disease that is unresponsive to conventional drug therapy.

When administered subcutaneously, belimumab can decrease the aggravation of SLE symptoms, and in turn permit curtailing of corticosteroid doses. This fact points towards the role of inhibitor of B lymphocyte activating factor in treating mild to moderate lupus and in providing steroid-sparing effect.

(c) Topical agents: They are commonly used for all forms of cutaneous lupus (acute, subacute, and chronic) which include tacrolimus, R-salbutamol, pimecrolimus, clobetasol, betamethasone, or photoprotection.

In the past decade, improvement in diagnosis and management has increased the median survival. But SLE continues to affect the quality of life of the patients due to its relapsing-remitting nature and associated organ damage. Further research is required to improve the well-being of patients with this chronic disorder.