Systemic Lupus Erythematosus

Thank you to Megan Himmel and Dr. Rodrigo Cavalcanti for facilitating a fascinating case of a new diagnosis of systemic lupus erythematosus (SLE).

Epidemiology:

As Dr. Cavalcanti pointed out, SLE is more common in women of childbearing age, and also in individuals of African-American or African-Caribbean descent.  The overall incidence in the US population was 5.1 cases per 100 000 per year, and the prevalence is 52 per 100 000, which is increasing likely due to improved survival and increased recognition and diagnosis.

Prognosis:

With effective treatment, the 10 year survival is reported at 92%.  The major causes of death in the first 5 years were SLE  and infections, and in the remaining 5 years, thrombosis was the most common cause of death.

Diagnostic Criteria:

I like the classic MD SOAP BRAIN mnemonic as a memory tool to remember the ACR diagnostic criteria for SLE.  Although the diagnostic criteria were recently updated in 2012 by the Systemic Lupus International Collaborating Clinics (SLICC)

ACR - Clinical Criteria -  (SLICC criteria in brackets)

M = Malar rash - (acute cutaneous lupus, malar rash, photosensitive lupus rash)
D = Discoid Rash - (chronic cutaneous lupus, hypertrophic lupus, panniculitis)

S = Serositis - (pericarditis, pleuritis, etc.)
O = Oral ulcers - (oral or nasal ulcers)
A = Arthritis - (synovitis involving two or more joints, and >30 min. morning stiffness)
P = Photosensitivity - (included in the M in the SLICC criteria)

B = Blood - hematologic manifestations - (Leukopenia, Thrombocytopenia, Haemolytic Anemia)
R = Renal - (proteinuria, glomerulonephritis)
A = ANA - (Anti-nuclear Antibody) - 95-98% sensitive for SLE 
I = Immunologic Criteria - (Anti-Ds-DNA, Anti-Smith, APLA, Low complement)
N = Neurologic - (seizures, psychosis, mononeuritis multiplex, confusion)

Lab Testing:
Sensitive = (negative - rule out) - ANA - 95-98% Sensitive
Specific = (positive - rule in) - Anti-ds-DNA - 95-98% Specific

Based on the ACR criteria for a diagnosis of definite lupus, a patient required 4 of the 11 criteria.  In the SLICC criteria, there are 17 criteria and a diagnosis of definite lupus is made if 4 of 17 are present.

Treatment:
The treatment of lupus is usually undertaken by specialists from rheumatology and/or nephrology depending on the degree of renal involvement.  The mainstay of treatment is immunomodulating/ steroid sparing agents, steroids, and increasingly biologic therapy.

Hydroxychloroquine (plaquenil) is the usual first line agent for mild lupus.  It is a immunomodulator and is useful for arthritis, skin rashes and systemic symptoms.  It is also the treatment of choice for lupus in the context of pregnancy.

NSAIDs - Are often used in combination with other agents for their analgesic and anti-pyretic properties.

Corticosteroids - Prednisone is often used for moderate to severe SLE flares as it is an extremely potent immunosuppressive.  For moderate flares, you will often see doses in the 0.5 - 1 mg/kg range.  For severe lupus flares, occasionally steroid pulses and high dose regimens are used.

Steroid sparing agents - Mycophenolate mofetil, Azathioprine, Methotrexate, Cyclophosphamide - All of these agents in various mechanisms target DNA synthesis at various steps in the synthetic pathway.  A rheumatologist will choose between the various agents depending on the severity of the flare, the prsence of renal involvement, and other clinical factors.

Biologic Agents - Rituximab has been investigated in a couple of randomized control trials (EXPLORER and LUNAR).  It has shown beneficial effects in certain sub-populations of patients, and will likely have an increasing role in the management of patients with difficult to control lupus.

Final Thoughts:  
SLE is a complex multi-system disease that requires consultation from a number of specialists, including rheumatology, nephrology, dermatology, and often psychiatry for the psychosocial aspects.

 It can mimic many common clinical presentations, and is on the differential diagnosis for almost any clinical presentation (from dyspnea to confusion).  The TWH is a world renowned site for SLE management and research, it is definitely worth an elevator ride down to the first floor of TWH whenever you are managing a patient with SLE!

Reference:
Lisnevskaia, L., et. al. Systemic Lupus Erythematosus. Lancet. Volume 384. November 22, 2014.