Systemic Lupus Erythematosus

Introduction

Systemic lupus erythematosus is a chronic autoimmune disease that has the potential to affect almost any organ in the body and cause generalised and systemic symptoms. We think its driven by an immune response to fragments of DNA and proteins from the cell’s nucleus. Consequently, inflammation can arise all of the body, causing a breadth of symptoms.

Ultimately, its aetiology or cause, is not exactly known but is likely triggered by environmental agents in a genetically susceptible host. There are a number of predisposing genes that we’ve identified as well as associated drug and infection factors like Epstein-Barr virus.

As mentioned, its pathophysiology revolves around the development of antibodies to DNA and nuclear proteins. An immune response is probably provoked when we

fail to rapidly clear cells through apoptosis – which usually prevents exposure of nuclear antigens to the immune system
or have an issue with the process of establishing immune tolerance in the first place.

First, consider bedside tests like urinalysis. Even in the absence of symptoms, all patients with lupus nephritis have proteinuria and you can easily screen for this.

Next, consider blood tests. An FBC will quickly demonstrate haematological dyscrasias. A clotting screen might indicate the presence of lupus anticoagulant and prompt further investigation. UECs may also indicate renal involvement.

Finally, and probably most importantly, lets discuss serological investigations.

The three main ones I’ll focus on are antinuclear factor, anti-dsDNA, and anti-Smith.

ANA is very sensitive for SLE but not diagnostic. However, Anti-dsDNA and anti-Smith antibodies are highly specific for SLE and often are confirmatory of the diagnosis, if present. High titres of anti-dsDNA antibodies are also markers of disease activity.

Let’s discuss management by focusing on non-pharmacological, pharmacological, and symptom specific treatment. Keep in mind the management of SLE is best undertaken by a multidisciplinary approach with specialist involvement.

All patients should be encouraged to focus on sun protection, improve their diet, participate in exercise, have psychological help as needed, and be given smoking cessation assistance.

Some common pharmacological treatments include NSAIDs, antimalarial therapy, corticosteroids, immunosuppressive agents, and biological agents. Although I won’t go into it in depth, hydroxychloroquine has been shown to reduce the risk of flare and is recommended for most patients with SLE.

As a brief overview, mucosal and cutaneous features may benefit form topical steroids. In mild serositis, (NSAIDs) may be sufficient to control pain.

For immune-mediated cytopenia, immunomodulatory therapy may help using steroids, azathioprine, cyclophosphamide and / or mycophenolate. This is very similar to the management of renal and glomerular involvement in SLE.

Lupus can cause a huge number of clinical features. The American College of Rheumatology developed a classification criteria for SLE which highlights these. It’s also been internationally reappropriated as a diagnostic tool. There are eleven criteria and four are required for a diagnosis of SLE.

Its hard to remember all of them so, I do cluster them into a couple of core groups.

There are three dermatological features:

A malar rash which is an erythematous lesion that spans across the bridge of the nose and cheeks, usually sparing the nasolabial folds.
A discoid rash. These are dry red patches that evolve to form red plaques mostly on the scalp and face.
Finally, photosensitivity, causing unusual reactions to sunlight.

Next there are three membranous issues:

Oral ulcers which are usually painless.
Arthritis, which is non-erosive and often in peripheral joints.
Finally, serositis. This is typically inflammation of the pericardium, aka pericarditis, or of the lung linings resulting in pleurisy.

There are three issues that you can note in the blood:

Haematological cell line issues like haemolytic anaemia, leucopenia, or thrombocytopenia.
Immunological features including positive serology for a specific antibody like Anti DS DNA
Finally, having a positive antinuclear antibody. This gets its own special mention because other criteria won’t even let you classify the disease as SLE unless its positive.

The last two are neuropsychiatric issues including seizures or psychosis and renal features like persistent proteinuria or cellular casts.

Keep in mind there are no internationally validated diagnostic criteria for SLE. But out of all of them, I just like this one because it highlights the breadth of issues SLE can cause.

"I'M DAMN SHARP" is helpful in remembering all of the features of lupus. I stands for immunoglobulins present. M stands for malar rash. D represents discoid rash, A for antinuclear antibodies, M for mucositis, and N for neurological disorders, making DAMN. SHARP is made up by S for serositis, H for hematologic disorders, A representing arthritis, R standing for renal disorders and P for photosensitivity.