BIOS222 Pathology and Clinical Science 2

Andrea Morales
Word Count: 1073
Systemic Lupus Erythematosus (SLE)
Case B: Katherine
 1. Systemic Lupus Erythematosus (SLE) is a multiorgan systemic disease and can

manifest as a wide variety of symptoms (Cojocaru et al., 2011). As seen in Katherine’s case, it can

affect the musculoskeletal system causing body aches and weakness, can affect the kidneys,

causing swelling in her legs, the cardiovascular system thereby causing hypertension,

tachycardia and can affect the lungs, increasing her respiratory rate (Cojocaru et al., 2011).

Additionally, the malar skin rash along her nose and cheeks, referred to as a “butterfly” rash is

commonly seen in SLE as well as fatigue (Cojocaru et al., 2011). Furthermore, SLE can cause

mouth ulcers and worsening of depression (Cojocaru et al., 2011). Her frequent influenza

infections and a mild fever are commonly seen in SLE as her body has a reduced ability to fight

infection (Cojocaru et al., 2011). Further questions to ask Katherine to confirm diagnosis are

seen in Table 1.

Table 1. Further questions to confirm diagnosis of SLE.

Question Reasoning
Do you take other medications? Medications such as Hydralazine,
procainamide, isoniazid, minocycline and
propylthiouracil can cause Drug-Induced Lupus
Erythematosus. Therefore, it is important to
rule this out before proceeding with diagnosis
(Choi et al., 2012).
Have you had an Antinuclear Antibody (ANA) ANA test, examines possible ANA antibodies in
Test?
the blood. If the test finds ANA antibodies, then

it may mean that an autoimmune disorder is

present (Nashi & Shmerling 2021). Although,

ANA is present in the majority of SLE patients, it

is not specific for this condition and therefore

appropriate clinical features need to be present

 for diagnosis (Nashi & Shmerling 2021).

Have the symptoms worsened with pregnancy
or progressively worsened within the last 8
weeks since falling pregnant?
With regards to your body pain, where in the
body is it?
Do you suffer from any other autoimmune
conditions?
There is an increased prevalence of SLE in
females and can be exacerbated in pregnancy
due to elevation of oestrogen, whereby there is
a rapid rise in the first trimester of pregnancy
(Pan et al., 2019). Therefore, this question is
needed to determine pregnancy and worsening
symptoms of SLE.
Arthritis involving two or more peripheral joints
is classified as a symptom in the American
Rheumatism Association criteria of SLE
(Cojocaru et al, 2011).
This is important to rule out other conditions
such as rheumatoid arthritis, scleroderma,
thyroid issues that may present with similar
signs and symptoms.

2. Three disease conditions that could present with signs and symptoms similar to SLE

include, scleroderma, Sjögren syndrome and rheumatoid arthritis (RA) (Touma & Urowitz, 2019).

All these conditions will most likely show a positive ANA test as they are all autoimmune

conditions (Touma & Urowitz, 2019).

3. Scleroderma is an autoimmune disease that can affect the skin and can become

systemic, whereby the immune system produces too much collagen, causing the skin to tighten,

harden and toughen (Walker et al., 2014). It can manifest as symptoms of urticaria, erythema

with dermographism (Walker et al., 2014). It can slowly progress systemically, affecting the

internal organs such as heart, lungs and kidneys. Like SLE, patients with scleroderma may

present with Raynaud’s syndrome and gastrointestinal symptoms such as dyspepsia (Walker et

al., 2014). The key differences between scleroderma and SLE include, photosensitivity, as seen
with Katherine, does not appear to be part of the disease spectrum in scleroderma, whereas SLE

is worsened by UV light (Callen, 1999). Additionally, symptoms of fever commonly occurs and

nasopharyngeal ulcers (approximately 45% of SLE population) whereas this does not occur in

scleroderma (Cojocaru et al., 2011). Furthermore, skin thickening and puffiness of the fingers of

both hands as are commonly seen in scleroderma whereas in SLE this is not (Walker et al., 2014).

Additionally, to confirm differential diagnosis the scleroderma-related autoantibodies test can be

completed to further confirm diagnosis of systemic scleroderma (Walker et al., 2014).

RA is an autoimmune inflammatory joint disease which can present with muscle, pain

and joint swelling of small joints of the hands, feet and wrists and can also affect other organs

causing pleural effusion, pericarditis, nephropathy and fever and fatigue all of which are

potential clinical presentations of SLE (Walker et al., 2014). The main difference in diagnosis is

that testing for RA can be confirmed through positive detection of the rheumatoid factor

(Walker et al., 2014). Additionally, SLE can cause a malar skin rash, whereas RA does not usually

do so (Walker et al., 2014). Unlike RA, muscle stiffness and joint deformity is not a prominent

symptom of SLE, however joint pain is a symptom of both. Additionally, as SLE is more likely to

affect internal organs compared to RA, there is a higher risk to have kidney failure (proteinuria),

clotting problems and seizures which are not commonly seen in RA (Cojocaru et al., 2011).

4. The pathogenesis of SLE is due to the production of pathogenic autoantibodies,

directed against nucleic acids and their binding protein, contributing both to tissue injury via

release of inflammatory cytokines as well as abnormal activation of autoreactive CD4 T and B

cells leading to a loss of self-tolerance (Choi et al., 2012). Consequently, immune dysregulation

occurs with defects in apoptosis resulting in end-organ injury (Walker et al., 2014). SLE can be

triggered by environmental factors such as UV light, which may cause the malar rash, as well as

Epstein-Barr virus, silica dust, smoking with a higher predisposition in females compared to
males (Choi et al., 2012). These environmental factors combined with genetic factors and

stochastic events contribute to the development of SLE (Choi et al., 2012). As SLE supresses her

immune system, she is more prone to frequent infections such as the flu. Katherine’s fatigue

could be as a result of stress, depression and anaemia, which is worsened with SLE. Additionally

systemic inflammation in SLE may increase susceptibility to a rash, joint pain, muscle aches and

pain and an abnormal heart beat due to increase risk of pericarditis, myocarditis and ischemic

heart disease, resulting in hypertension and tachycardia (Choi et al., 2012).

Katherine being female and pregnant has a higher risk of developing SLE due to

higher oestrogen production (Mok & Lau, 2003). Abnormal oestrogen metabolism and low

androgenic hormone production has been demonstrated in SLE patients (Mok & Lau, 2003).

Oestrogens have been shown to prolong the survival of autoimmune cells, increasing T

helper type 2 cytokine production, and stimulating B cells to produce autoantibodies, thus

worsening SLE symptoms (Mok & Lau, 2003). These high levels of oestrogen may worsen

flare ups and increase risk of mouth ulcers (Mok & Lau, 2003).

Lupus nephritis is caused by the production of nephritogenic anti-dsDNA antibody

which regulates gene and protein expression of inflammatory and fibrotic mediators and

binds directly or indirectly to resident renal cells (Yung & Chan, 2015). Consequently,

destruction of the normal kidney parenchyma occurs, subsequently replaced by fibrous

tissue. Clinical manifestation of kidney damage includes proteinuria, oedema and

hypertension (Yung & Chan, 2015).

5. The ANA test which is positive in 99% of individuals diagnosed with SLE is

important. However, this test alone is not accurate for SLE diagnosis (McKeon & Jiang, 2020).

Therefore, the ANA test in combination with either the anti-ds-DNA antibodies detection
 test (positive in 70% of SLE patients) whereby the above reference range of >2-fold, if tested

by ELISA may confirm SLE diagnosis and/or Anti-Smith antibodies specific for lupus and

associated with nephritis and cytopenia’s can be conducted (only positive in 5% of SLE

patients) (McKeon & Jiang, 2020). Furthermore, ANA test with antiphospholipid antibodies

(positive in 40% of SLE patients) associated with a higher risk of thrombosis and miscarriage

should be conducted to confirm possible diagnosis (McKeon & Jiang, 2020). In addition to at

least one positive laboratory result, patient must be positive in at least > 3 of the following

clinical criteria (Table 2) to rule out other rheumatic conditions such as RA and scleroderma.

Table 2: Clinical Diagnostic Criteria for SLE

Criteria Types
Skin Malar rash, photosensitivity, bullous lupus,
toxic epidermal necrolysis, chilblains lupus,
discoid lupus (McKeon & Jiang, 2020).
Oral or nasal ulcers In the mouth or in the nasal cavity and should
be in the absence of other causes (McKeon &
Jiang, 2020.
Alopecia Absence of other causes, i.e., hypothyroidism.
Must do thyroid testing TSH, T4, T3 (McKeon &
Jiang, 2020).
Serositis Plural effusion, chest pain. Pericardial effusion,
pericarditis by ECG (McKeon & Jiang, 2020.)
Renal involvement This is typical in SLE patients. Proteinuria
>500mg/24 hours or red cell casts. These
results are typical in SLE patients (McKeon &
Jiang, 2020).
Bloods Haemolytic anaemia, leucopenia,
thrombocytopenia, in the absence of other
causes (McKeon & Jiang, 2020).
Arthritis Involving two or more joints (McKeon & Jiang,
 2020).
CNS Non-drug induced nor metabolic derangement
changes causing seizure or psychosis (McKeon
& Jiang, 2020).

6. Disease Modifying Anti-Rheumatoid Drugs (DMARDs) such as

hydroxychloroquine, and methotrexate are immunosuppressive and immunomodulatory

agents which aim to prevent flares and their symptomatic impact and reduce chronic

accumulation of organ damage (McKeon & Jiang, 2020). Furthermore, corticosteroid

medications such as prednisolone or dexamethasone are used short-term to control flare

ups of SLE but their use is limited due to their toxicity with long-term use (McKeon & Jiang,

2020).

As UV light is a trigger for SLE flare ups the first non-pharmacological intervention

is to wear SPF 50+ sunscreen, covering up with clothes and hat as well as avoiding exposure

during peak hours (McKeon & Jiang, 2020). In addition to smoking cessation for reducing

cardiovascular risk, supplementation with fish oil 2.25g of EPA and DHA per day for six

months significantly reduced inflammation and cardiovascular risk in SLE patients (Akbar et

al., 2017). Furthermore, improvement in fatigue and a reduced need for NSAID use was

seen, suggesting a therapeutic effect of fish oil in SLE (Akbar et al., 2017).

References
Akbar, U., Yang, M., Kurian, S., & Mohan, C. (2017). Omega-3 Fatty Acids in Rheumatic Diseases – A

critical review. Journal of Clinical Rheumatology, 6(23), 330-339.

https://doi.org/10.1097/RHU.0000000000000563

Callen., J, P. (1999). Photosensitivity in collagen vascular diseases. Seminars in Cutaneous Medicine

and Surgery, 18(4), 293-296. https://doi.org/10.1016/s1085-5629(99)80028-5

Choi, J., Kim, S., & Craft, J. (2012). The pathogenesis of systemic lupus erythematosus – An

update. Current Opinion in Immunology, 6(24), 651-657. https://doi.org/10.1016/j.coi.2012.10.004

Cojocaru, M., Cojocaru, I., Silosi, I., & Vrabie C. (2011). Manifestations of Systemic Lupus

Erthematosus. A journal of Clinical Medicine, 6(4), 330-336.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391953/

McKeon, K., & Jiang, S. (2020). Treatment of systemic lupus erythematosus. The Australian

Prescriber, 43, 85-90. https://doi.org/10.18773/austprescr.2020.022

Mok, C., & Lau, C. (2003). Pathogenesis of systemic lupus erythematosus. Journal of Clinical

Pathology, 56, 481-490.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769989/pdf/jcp05600481.pdf
Nashi, R., & Shmerling, R. (2021). Antinuclear antibody testing for the diagnosis of Systemic Lupus

Erythematosus. The Medical Clinics of North America, 105(5), 387-396.

https//doi.org/10.1016/j.mcna.2020.10.003

Pan, Q., Chen, X., Liao, S., Chen, X., Zhao, C., Xu, Y., & Liu, H. (2019). Updated advances of linking

psychosocial factors and sex hormones with systemic lupus erythematosus susceptibility and

development. Peer J Life and Environment, 7, 1-17. https://doi.org/10.7717/peerj.7179

Touma, Z., & Urowitz, M. (2019). Dubois’ Lupus Erythematosus and Related Syndromes (9th ed.).

Elsevier. https://doi.org/10.1016/B978-0-323-47927-1.00047-5

Walker, B., Colledge, N., Ralston, S., & Penman, I. (Eds.) (2014). Davidson's Principles and Practice of

Medicine E-Book (23rd ed.). Elsevier. edited by. https://ebookcentral-proquest-

com.ezproxy.endeavour.edu.au/lib/endeavour/detail.action?docID=1746328.

Yung, S., & Chan. T. (2015). Mechanisms of Kidney Injury in Lupus Nephritis – the role of anti-dsDNA

antibodies. Frontiers in Immunology, 6, 1-11. https://doi.org/10.3389/fimmu.2015.0047