The acute form of systemic lupus erythematosus (SLE) differs from the chronic form. It disseminates differently, and it is highly fatal. Kaposi first recognized SLE in 1872, and then Pernet described it in 1908. SLE mimics other diseases, and therefore, its diagnosis may be difficult. It is a multisystemic, autoimmune disease in which the immune system produces autoantibodies against a variety of autoantigens, for example, antinuclear antibody (ANA) and anti-blood cell antibody. It affects vital organs such as kidneys, heart, central nervous system (CNS), the skin, and the reproductive system. Clinical criteria defined by the American Rheumatism Association (ARA) define SLE, and 4 out of the 11 criteria confirm the diagnosis.
SLE is a multifactorial disease. Genetic, immunological, endocrine, and environmental factors influence the loss of the immunological tolerance against self-antigens. With SLE, the pathogenic autoantibodies can cause tissue damage through multiple mechanisms including deposition of immune complexes, complement fixation, and neutrophil activation. Among genetic triggers is a mutation in the gene encoding for protein kinase Cd (PKCd). One study showed that this mutation caused monogenic SLE in the 3 siblings of an endogamous Pakistani family. They responded well to B-cell depletion using ofatumumab.
Several immunological factors implicate SLE. Several studies showed the pathogenic role of T-helper, type 17 (Th17) axis, while regulatory T cells mediated protection. An environmental factor thought to prevent SLE etiology is the disturbance of gut microbiota (dysbiosis). It can lead to the development of autoimmunity. The elements and composition of gut microbiota have significant roles in human B cells (antibody production) and the homeostasis and balance of various subpopulations of helper T cells. Endocrine factors may play an essential role in the lupus etiology. These factors involve estrogens in the pathogenesis of SLE. Recently, in 2016, Xue and colleagues investigated the functions and mechanisms of 17beta-estradiol in tumor necrosis factor-like weak inducer of apoptosis (TWEAK) expression in Lupus nephritis (LN). They concluded that 17beta-estradiol plays a critical role in upregulating TWEAK expression in LN, possibly through an ERa-dependent pathway, that ends in kidney damage. SLE is more prevalent in women than men (9:1) since female produce a large concentration of estrogens. Drugs may also trigger SLE for example, hydralazine, because they are associated with anti-histone antibodies.
Other contributing factors in the etiology of SLE include association with:
The prevalence of SLE is approximately 0.2%. The female to male ratio is 9 to 1. SLEIt mainly affects women of child-bearing age. African-Caribbeans and Asians are mostly affected. Individuals with HLA-B8, DR-2, and DR-3 are highly susceptible to this disease. Epstein-Barr virus (EBV) may trigger SLE. This is an environmental factor. Among identical twins, the likelihood of both twins having SLE is 24%.
A type III-hypersensitivity reaction mediates SLE. Soluble immune complexes deposit in several tissues and organs including the kidneys, the joints, the heart, the CNS, the skin, the lungs, and others. After that, the classical pathway of the complement system activates. Chemotactic factors including C3a attract neutrophils to the site of inflammation, and they release proteolytic enzymes to process the immune complexes but eventually they cause damage to surrounding organs and tissues. SLE is an immune complex disease caused in part by a reduction of the CR1 receptors on red blood cells. Some autoantibodies can penetrate the cells of patients with lupus and interfere with an intracellular target enzyme, e.g., anti-ribosomal P antibodies, anti-RNP, and anti-dsDNA antibodies. There is evidence of complement consumption that is associated with disease activity.
Another immunopathologic finding is the association of SLE to FcRIIA polymorphism that impairs immunocomplexes binding and accumulates in the kidneys causing glomerulonephritis. This also affects other organs.
The following characterize SLE histopathology:
American College of Rheumatology Revised Criteria for the Classification of SLE
More than 4 criteria need to be present during observation. These criteria are 95% sensitive for the diagnosis of SLE, but only 84% specific.
The immunodiagnosis of acute systemic lupus erythematosus includes testing for autoantibodies and complement proteins, which form the mainstay of diagnosis.
Acute SLE, if treated promptly, has a prognosis of approximately 80% survival at 15 years. It can increase the long-term risk of cardiovascular disease and osteoporosis. The prognosis varies with clinical features of the disease, in patients with renal involvement SLE may progress to renal failure and may need kidney transplantation. Here the prognosis is guarded. However, patients with mild disease have a better prognosis.
The most common SLE complications are:
The rheumatologist or family medicine physician must strictly monitor these complications. Hematological diseases may require blood product transfusion and dosage change of immunosuppressive drugs.
Clinicians must educate patients to be compliant with immunosuppressive drugs needed to treat SLE for achieving improvement of the quality of life. Patients must also comply with the treatment of comorbidities. Psychological support should be available to carry out the necessary management of these patients.
Several drugs can cause acute SLE that may improve once the patient stops taking them (within 6 months to a year). Below is a list of those drugs reported as SLE inducers:
An interprofessional team should educate and manage patients with acute SLE. Their family physician can monitor patients with less severe form of the disease that does not involve important organ systems. Physicians should refer patients with complications, increased disease activity, or drug reactions from treatment to a rheumatologist. It is vital that the specialist coordinates closely with the patient's family physician to optimize treatment and carry out preventive health services.