LUPUS ERYTHEMATOSUS 1

Lupus Erythematosus: An Insight into Unique Disease

Muhammad Qassim

European University Cyprus

20222434

Basic Immunology and Microbiology MD245

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Table of Contents
Abstract....................................................................................................................................... 3

Introduction ............................................................................................................................... 4

History ........................................................................................................................................ 4

Different Types of LE ................................................................................................................ 5

Aetiology of Disease .................................................................................................................. 6

Causes ................................................................................................................................... 6

Risk Factors ..................................................................................................................... 6

Symptoms .................................................................................................................. 6

Complications ...................................................................................................... 7

Diagnosis .................................................................................................................................... 9

Laboratory Tests ................................................................................................................... 9

Imaging Tests .................................................................................................................. 9

Biopsy ...................................................................................................................... 10

Treatment ................................................................................................................................. 11

Stem Cell Therapy .............................................................................................................. 11

CAR-T Cell Therapy ..................................................................................................... 12

Ongoing Clinical Trial ............................................................................................ 13

Conclusion ............................................................................................................................... 14

Bibliography ............................................................................................................................ 15
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Abstract

Lupus is a fatal autoimmune disease there is no current cure for it. This essay will take a deeper look

into a) characteristics of the disease, b) the current, and novel treatments for it, c) clinical trials which

have taken place, and d) Stem-cell treatments which are currently in development for it.

Keywords: Autoimmune, Autoantibody, NSAIDs, Immunosuppressants, Stem Cell Therapy,

CAR-T Cell Therapy, Obinutuzumab

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Introduction

Lupus is an autoimmune disease where the immune system of the body mistakenly attacks

healthy tissues affecting organs which include the skin, kidneys, brain and other organs. This is

mainly characterised by inflammation and damage to said organs.

There is an estimation that at least 5 million worldwide suffer from Lupus, striking mostly women of

child-bearing age. In addition to this, 33% of Lupus patients suffer from multiple autoimmune

disease.

It is a complex disease with a wide range of symptoms, that affects each individual differently, and

has no cure. It’s difficulty to diagnose and likeness with other diseases makes it harder to treat.

History

Hippocrates was the first to identify cutaneous ulcers under the pretence of herpes

esthiomenos. However, it wasn’t until the early 10th century where Herbernus of Tours applied the

term Lupus to a skin disease. Robert Willian, a 19th century scientist expanded the classification of

skin disease by distinguishing herpes for vesicular diseases and Lupus for destructive and ulcerative

diseases of the face. First distinguishable description of Lupus Erythematosus was created by Biet,

and also reported by his student Cazenave under the term Erythema Centrifugum in 1833.

Additionally in 1846, Hebra described “disc-shaped” patches and introduced the butterfly smile for

malar rash. In 1851, Cazenave renames Erythema Centrifugum to Lupus Erythematosus. By 1872,

Lupus was subdivided into discoid and systemic forms by Kaposi, he also introduced the idea of

systemic diseases with a potentially fatal outcome.

In the late 19th century, a scientist by the name of Payne used Quinnie to treat patients with Lupus,

while also postulating the presence of vascular disturbances. Between 1895 and 1904, Sir William

Olsen published 29 cases of what was then termed Erythema group of diseases, showing that skin

diseases are also accompanied by a variety of systemic manifestation, however in reality only 2

patients actually suffered from Lupus.

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Different Types of Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) – This is the most common type of Lupus, whereby

70% of the people have this type. It can affect many different organs or organ systems in the body,

kidney, liver, joints, skin. It is characterised by acute or chronic inflammation of the different organ

systems; indeed cardiovascular and nervous systems can also be affected.

Skin Lupus – This refers to Lupus which is restrained to only damage of the Skin organ. This can

exist in those who do not have Systemic Lupus Erythematosus. However around 5% of those with

CCLE, can later also develop SLE. There are three types of skin Lupus: Chronic Cutaneous Lupus

Erythematosus, Subacute Cutaneous Lupus Erythematosus, and Tumid Lupus.

Skin Biopsy usually obtained to diagnose, as each form has its own characteristic lesions and patterns.

Drug-Induced Lupus Erythematosus – Certain drugs will induce Lupus-like symptoms; however,

this is usually temporary and in most cases the symptoms cease after the patient stops taking the drug,

which may have caused this type of Lupus.

Neonatal Lupus Erythematosus – Lupus which presents in infants will occur in the same manner as

it would in adults but is passively transferred from mother to fetus. It usually affects certain organs

such as kidneys to a greater extent, the incidence is 2-time greater in children than adults.
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Aetiology of Disease

Causes

As mentioned earlier, Lupus Erythematosus is an autoimmune disease, which attacks healthy

tissues in your body. There is a likelihood that Lupus arises from a combination of genetic and

environmental factors. People who have inherited Lupus, will activate the disease when they come

into contact with something in the environment. The cause of Lupus in most cases is unknown,

however there could be a number of triggers which include:

- Sunlight – Exposure to UV rays may bring on Lupus skin lesions or trigger an internal

response to those who could be prone to this.

- Infections – An infection may initiate or cause a relapse in some people.

- Medications – Specific type of Blood-pressure and anti-seizure medications as well as some

antibiotics can trigger an onset of Lupus. Usually those with drug induced lupus get better

after they stop the medications.

Risk Factors

Certain factors may increase your risk of Lupus, these include:

- Gender – It is more common in women than men.

- Age – Can affect people of all ages, most commonly diagnosed between the ages of 15 – 45.

- Race – More common in African American, Hispanics and Asian Americans.

- Genetics – Family history of Lupus may predispose individuals, due to presence of certain

genes.

- Stress – Not a direct risk but can exacerbate symptoms of Lupus.

Symptoms

For Lupus Erythematosus, there are no two cases that are exactly alike. Signs and symptoms

can present itself overtime or suddenly, they may be mild or severe, and may be permanent or
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temporary. Majority of patients have episodes, called flares, whereby the symptoms get worse for a

period of time and then gradually improve or possibly disappear.

The signs and symptoms that are experienced will depend on the part of the body that is being

affected. Most common symptoms include:

- Fatigue

- Fever

- Joint pain, stiffness and swelling.

- Butterfly-shaped rash presenting on the face and covering the cheeks or bridge of nose.

- Rashes elsewhere on the body.

- Skin lesions that worsen with sun exposure

- Fingers and toes that turn white/blue when experience cold or stressful periods.

- Shortness of breath

- Chest Pain

- Dry Eyes

- Headaches, confusion and memory loss

As you can see, Lupus Erythematosus has a wide range of signs and symptoms, making it a disease

that is difficult to diagnose at first, and may be mistaken for other, more common, diseases.

Complications

Inflammation that is caused by Lupus has the ability to affect many different areas of your body,

including:

- Kidneys – Around half of the patients with Lupus will suffer from complications related to

the kidneys. Inflammation in the kidneys can cause symptoms such as swelling, high blood

pressure or even blood/protein in the urine. Ultimately this could lead to kidney failure.

- Brain & CNS – If Lupus affects the brain the patient will feel headaches, dizziness, behaviour

and vision problems. In more serious cases it could lead to strokes or seizures.
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- Blood Vessels – Lupus could lead to a reduced number of blood cells, hence when anaemia is

tested for. There is also an increased risk of bleeding or clotting, also a risk of inflammation

of blood vessels.

- Lungs – Increased chances for inflammation in the lungs will make breathing more difficult

and also painful. Additionally, there is also a possibility of bleeding into the lungs and

pneumonia developing.

- Heart – Inflammation of the heart does increase the risk of cardiovascular diseases and heart

attacks.

- Pregnancy – Women with Lupus while pregnant will have an increased chance of a

miscarriage. This is due to an increased risk of high blood pressure during pregnancy and

preterm birth.
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Diagnosis

No single test is able to diagnose a patient with Lupus, the doctor will be able to find out

using a number of different techniques.

Laboratory Tests

Complete Blood Count – Test for the number of red blood cells and amount of hemoglobin.

The results of these tests may indicate that the patient may have anemia, which is a common

occurrence in Lupus. Additionally, a low white blood/platelet count may also occur in Lupus due to

the autoimmune nature of the disease.

Erythrocyte Sedimentation Rate – This blood test determines the rate at which red blood cells will

settle at the bottom of a test tube. This is a result of the weight of the red blood cells. A faster than

normal rate may indicate a system disease, such as Lupus. There is no specific number, an elevated

number indicates an infection, an inflammatory condition, cancer or Lupus.

Kidney/Liver Assessment – As Lupus affects both your liver and kidneys, impaired function can, not

in all cases, indicate Lupus.

Urinalysis – Increases levels of protein/red blood cells in the urine may present as kidney

dysfunction, another sign of Lupus.

Antinuclear Antibody Test – A positive test for the presence of the ANA produced by the immune

system will indicate a stimulated immune system. However, testing positive for ANA doesn’t show

definite Lupus, a doctor will advise to complete more specific tests.

Imaging Tests

Chest X-Ray – Imaging of chest may reveal abnormal shadows which can suggest a build up

of fluid or inflammation in the lungs.

Echocardiogram – Sound waves are used to produce real-time images of the heart. This is able to

check for problems with heart valves, chambers and major vessels.
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Biopsy

As mentioned before, Lupus can harm the patients’ kidneys in a number of different ways and

treatments can vary, dependent on the type of damage. In some cases, when the previous tests are

inconclusive, a small sample os kidney tissues are acquired. This is to determine what the best type of

treatment is required.

Additionally, a skin biopsy can also be determined to confirm a diagnosis of lupus that is affecting the

skin.

Treatment
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Currently there is no cure for Lupus, but there is treatment available. The goal is to manage

and minimise the symptoms and to reduce the damage done to organs, Majority of people with Lupus

require a combination of medications to prevent flare-ups. The following may be needed:

- Hydroxychloroquine – It is a disease-modifying anti-rheumatic drug that can relive the

symptoms and slow down progress.

- Non-steroidal anti-inflammatory Drugs (NSAIDs) – NSAIDs relieve pain and also reduce

inflammation. However, it can become dangerous when taking it for more than 10 days in a

row.

- Corticosteroids – These are prescription medicines that reduce inflammation. Prednisone is

one of the most common corticosteroids that is used to manage Lupus. They can be taken by

oral pills or injected directly into joints.

- Immunosuppressants – Due to the autoimmune nature of this disease, immunosuppressants

can be taken to prevent the immune system from being activated. This can help o present

tissue damage and inflammation.

Stem Cell Therapy

With novel Stem cell research, there has been promising development to slow down the

progression of Lupus or even stop it completely. The success rate of the treatment is influenced by the

patients age and the duration of the disease.

Stem cells have the ability to differentiate into cells of damaged organs when they come into contact

with said organ. Number of cells needed to be administered will be dependent on the patients age and

weight. They will be derived from mesenchymal stem cells, from the patients own adipose tissue,

bone marrow or fetal stem cells.

The treatment duration will be determined by the condition of the patient. Generally, it is performed

in 3 sessions, 45 days apart, or in 3 consecutive days. It is administered intravenously. In cases of

advanced progression of the disease, treatments may need to be repeated more than once. 99% success
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was achieved for the regression, cessation or complete treatment of the disease. Unfortunately, 60% of

the patients did have to come back the following year for another round of treatment.

CAR-T Cell Therapy

Further to the current treatment and therapy in place, there is currently new research taking place at

American College of Rheumatology that demonstrated how CAR-T cell therapy can lead to a

suppression of autoantibodies, leading to the resistance of Lupus. While currently used to treat blood

cancers, CAR-T Cells could possibly lead to a deep B Cell depletion, hence eradication of Lupus

completely.

CAR-T Cells are created by the removal of the patient’s own white blood cells, and then their genetic

modification to induce the production of chimeric antigen receptors. This will then allow the modified

T-Cells to target and destroy the antigen on the surface of a target pathogen.

In Lupus they will be able to target the CD19 protein, which is on the surface of B cells, that triggger

the flares. Currently, at 3 months, all five patients in the study had a drug-free remission of the

disease. The follow-up study is now investigating whether this would have an effect on the

effectiveness of vaccines. Even though patients experienced SLE activity of 0, the recurrence of B

cells still remained. Meaning CAR-T Cells eradicated the disease while still permitting immune

response against infections.

Although this may seem encouraging, there are still limitations, such as:

- Life-threatening toxicities

- ICANS

- Expensive

For such reasons it is still not an approved therapy for Lupus but is an important step in finding a cure

for this disease in the future.

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Ongoing Clinical Trial

Although there are current treatments available, people with Lupus Erythematosus will still be

at risk to develop other severe conditions, such as heart disease. Additionally, some patients may

suffer from the side effects of the current treatment, or it may not work anymore. Hence why there is a

need for novel immunological treatments for Lupus.

Currently, there is an ongoing clinical trial to test for the possibility of using a drug, Obinutuzumab as

a new treatment type. This trial is currently in its Recruitment stage of development, and is taking

place in over 14 countries.

The trial is a parallel-group, double-blind, placebo control study to evaluate the efficacy of

obinutuzumab. Participants involved must have an active, autoantibody positive SLE, that are

currently being treated with the standard care of therapy.

Obinutuzumab is an experimental drug, not yet approved by the health authorities as a treatment for

SLE. It is a drug that is manufactured to remove the B Cells in patients with SLE. This is done by

targeting the CD20 protein that is found on the surface of B cells. CD20 coupled with the

obinutuzumab triggers the destruction of the B Cells, this ultimately leads to a decrease in

inflammation and autoimmune activity. Side-effects are yet to be fully determined.

Conclusion
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As learnt, Lupus is a unique and complex condition. It’s unknown origin, multitude of symptoms and

lack of a cure makes it problematic for scientists. Despite many years of study, much remains to be

discovered about the disease.

With the current treatment including a plethora of immunosuppressants, corticosteroids and NSAIDs,

it still has a long way to go in finding a cure. This is mainly used for symptom management and to

suppress the immune system. However, new research is taking place in both Stem Cell therapy and

CAR-T Cell therapy which is promising in the eradication of this disease.

With continued collaboration and innovation, not just between healthcare professionals, but more

importantly with the patient, it is pivotal we strive to improve outcomes, quality of life and ultimately

a cure for Lupus Eryhtematosus.

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