Acute Lupus Erythematosus

Article Author:
Angel Justiz Vaillant
Article Editor:
Matthew Varacallo
12/19/2018 6:16:02 AM
PubMed Link:
Acute Lupus Erythematosus


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.[1]


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.[2]

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.[3] 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:

  • Complement deficiency, especially C2 and C4
  • HLA-A1, B8 and DR3 and other HLA genes
  • DQw1, DQw2 with anti-Ro
  • DQw6, 7 and 8 with antiphospholipid antibodies


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%.[4]


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.[5][6]

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:

  • Fibrinoid necrosis at the dermo-epidermal junction along with liquefactive degeneration and atrophy of the epidermis
  • Edema, small hemorrhages, and a mild infiltrate of inflammatory cells (principally lymphocytes in the upper dermis) accompanying small hemorrhages and edema
  • Fibrinoid material deposits in the dermis close to capillary blood vessels, on collagen, and in the interstitium
  • There is more mucin deposit in the reticular dermis in acute SLE than discoid lupus

History and Physical

American College of Rheumatology Revised Criteria for the Classification of SLE[4]


  • Malar rash: Red, flat, or raised over the cheeks, sparing the nasolabial folds
  • Discoid rash: Red raised patches with keratotic scales, atrophy, and scarring may occur in older lesions
  • Photosensitivity: Presence of skin rash due to sunlight exposure
  • Oral ulcers: Painless ulcers in the mouth or nasopharyngeal areas   
  • Arthritis: Nonerosive arthritis (pain, swelling or effusion) is greater than or equal to 2 peripheral joints
  • Serositis: Pleuritis (pleuritic pain or rub or pleural effusion) or pericarditis (ECG or rub or evidence of effusion)


  • Renal: Proteinuria (greater than 500 mg daily) persistent or cellular casts (RBC, granular, tubular, or mixed)  
  • CNS: Seizures or psychosis in the absence of an alternative explanation (e.g., drugs or metabolic disorders such as electrolyte abnormality or uremia) 
  • Hematologic: Hemolytic anemia (with reticulocytosis) or leucopenia (less than 4000/mm) on 2 or more occasions or lymphopenia (less than 1500/mm) on 2 or more occasions or thrombocytopenia (less than 100,000) in the absence of medications known to decrease platelets
  • Immunologic: Antiphospholipid antibodies present based on either an abnormal serum level of IgM or IgG anticardiolipin antibodies or a tested positive result for lupus anticoagulant or Anti-DNA antibody or anti-Sm antibody or false positive VDRL (or RPR).  
  • Antinuclear antibodies: An elevated level of ANA, in the absence of drugs known to cause "drug-induced lupus"

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.

  • Antinuclear antibodies (ANA) can perform by indirect immunofluorescence. Most cases of SLE show positive ANA results.
  • The second step is the confirmation of the antigenic specificity. It includes testing for auto-antibodies such as anti-double-stranded DNA (dsDNA), anti-Smith, ENA, anti-cardiolipin, and anti-beta2 GP-I. A high serum level of this anti-dsDNA and anti-Smith suggests SLE. These 2 antibodies can be considered as immunological markers for SLE. Other autoantibodies present in this systemic illness are anti-Ro, anti-La, anti-RNP, and rheumatoid factor.
  • SLE can also associate with other autoimmune disorders, e.g., autoimmune thyroid disease (5% to 10%) and Sjogren syndrome (15% to 20%). Other organ-specific autoantibodies must be ruled out, including those that affect the thyroid, gastric parietal cells, anti-erythrocytes, and others clinically essential antibodies.
  • Detection of C3 and C4, serum immunoglobulins, electrophoresis, and cryoglobulins (if Raynaud is present) are additional tests that should be done as part of the routine testing in SLE patients.
  • Biopsies (lupus band test) shows deposits of IgG and C3/C4 along the dermo-epidermal junction in a lumpy-bumpy distribution. They may be deposits around cutaneous blood vessels. Renal biopsy may be helpful in showing immune complexes deposition involving IgM, IgG, and C3/C4.

Treatment / Management

  • Mild disease can treat with non-steroidal anti-inflammatory drugs (NSAIDs).  
  • Skin problems including rashes and vasculitis can manage with topical steroid creams. 
  • Antimalarials, e.g., hydroxychloroquine, can use to treat arthralgia and skin disease. 
  • Acute SLE with hemolytic anemia, nephritis, CNS disease, or severe pericarditis requires urgent intravenous (IV) cyclophosphamide plus high dosage of prednisolone.
  • Mycophenolate mofetil can use as an alternative to azathioprine or cyclophosphamide.   
  • Methotrexate can be used for arthritis.  
  • Sunblock creams are used to protect against ultraviolet (UV) light.   
  • Lupus nephritis can be managed with intense immunosuppression with steroids and cyclophosphamide or mycophenolate.
  • The patient may need kidney transplantation if the disease progresses.
  • High blood pressure can be managed with calcium-channel blockers (e.g., nifedipine).
  • An SLE-maintenance regimen of NSAIDs and hydroxychloroquine may be used.
  • Neurological involvement is difficult to treat, and there is no clinical consensus; high-dose steroids can be used, but they may trigger a steroid psychosis.
  • Plasmapheresis along with cytotoxic drugs may be used, but never alone or the disease may worsen.   
  • In pregnancy, dexamethasone can be used to treat heart problems.  
  • Intravenous immunoglobulins (IVIG) should be used with care and avoided if rheumatoid factor is present in high titer.
  • Splenectomy may be required for thrombocytopenia. 
  • Antiphospholipid syndrome needs anti-coagulation.

Differential Diagnosis

  • Adult-onset Still disease characterized by arthralgia, fever, lymphadenopathy, and splenomegaly but no malar rash, autoimmune blood disorders, and other organ's manifestations   
  • Behcet syndrome presents with aphthous ulcers, uveitis, and arthralgia but other systemic manifestations of SLE are not present.
  • Endocarditis characterized by fever, arterial emboli, arthralgia, myalgia, and a heart murmur; may be confounded with cardiac manifestations of SLE but can rule out because of the absence of SLE common autoantibodies including anti-dsDNA and anti-Smith antibodies.
  • Rheumatoid arthritis (RA) presents with morning joint stiffness lasting over 1 hour; affected joints are usually symmetric, swollen and tender. It can rule out because of positive tests for anti-cyclic citrullinated antibodies, a positive rheumatoid factor, and synovial fluid reflecting the inflammatory state. There are serological differences between these 2 problems.
  • Systemic sclerosis characterizes by decreased joint mobility, arthralgia, myalgia, Raynaud phenomenon, and skin induration. It can distinguish from SLE testing for specific antibodies.    
  • Sarcoidosis presents with fever, cough, dyspnea, fatigue, night sweats, rash, and uveitis. It shows non-caseating granuloma on chest radiography and bilateral adenopathy, which is rarely present in SLE.[7]

Pertinent Studies and Ongoing Trials

New approaches in the management of SLE are the use of the anti-CD20 monoclonal antibody for B-cell depletion[8][9] and stem cell transplantation for severe disease.[10]


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:

  • Severe cardiovascular (e.g., pericarditis) and renal problems (glomerulonephritis)
  • Infections
  • Anemia
  • Thrombocytopenia
  • Malignancy

The rheumatologist or family medicine physician must strictly monitor these complications. Hematological diseases may require blood product transfusion and dosage change of immunosuppressive drugs.

Deterrence and Patient Education

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.

Pearls and Other Issues

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:

  1. Hydralazine
  2. Quinidine
  3. Isoniazid
  4. Minocycline
  5. Procainamide

Enhancing Healthcare Team Outcomes

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.