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Aspen-Marie Tong

Mr. Donald

Writing for College

12 February 2018

Life of Pain: The Devastating Effects of Lupus

The military is supposed to protect and defend, but when the military falls, the nation

may fall as well. Just as the military defends a country, the immune system protects the body.

The immune system detects infection and fights it, but in particular cases, it may create cells

designed to attack healthy organs. Lupus is an autoimmune disease affecting millions of people

worldwide. Lupus is a chronic illness of painful symptoms that can last a lifetime. Women

between the ages of sixteen and forty are most likely to be diagnosed. Lupus causes

inflammation throughout the body, but is commonly treated with conventional and alternative

medicines.

Lupus patients experience inflammation problems throughout the body. Lupus occurs

when white blood cells attack healthy tissue. As white blood cells attack, inflammation occurs to

assist the immune system in protecting the body from invaders. Although inflammation can

preserve the body, it can also cause pain and permanent scarring. In lupus patients, white blood

cells are continually attacking tissue, triggering perpetual inflammation and pain. Patients

experience a variety of symptoms, making it difficult for doctors to diagnose. Known as the

“great imitator,” Lupus’ symptoms mirror those of many other illnesses. As there is no specific

diagnostic test, doctors are often cautious when pinpointing Lupus. Common symptoms include

joint pain, face rashes, and sensitivity to sun exposure. The first sign to look for in Lupus is

fatigue. Fatigue makes everyday activities troublesome, as it acts as a warning a flare-up will
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occur. Fatigue is a common symptom of many diseases; therefore, more signs are needed to

diagnose lupus (Goldman).

The most prominent characteristic of Lupus is inflammation. The inflammation is the

result of the immune system attacking healthy tissue. This malfunction of the immune system is

believed to be related to B-cell maturity. In lupus patients B-cells mature incorrectly, resulting in

the promotion of inflammation, rather than fighting it. B-cells are white blood cells designed to

stop germs and alerts the body to create a substance to fight them off. In the general public

“anti-inflammatory B cells appear to prevent excessive production of a protein called interferon-

alpha,” but in lupus patients, there is an excess amount of interferon-alpha, which boosts the

number of antibody-producing B-cells (Norton). With more antibody-producing B-cells present

in a lupus patient’s immune system, more antibodies are released, resulting in painful

inflammation around the joints.

The inflammation caused, results in major joint pain. Lupus arthritis causes joint pain

and swelling. It is estimated “[m]ore than 90 percent of people with lupus will experience joint

and/or muscle pain at some time during the course of their illness” (Quismorio). Lupus arthritis

causes pain, swelling, and stiffness in the joints. Joint pain frequently affects knees, elbows,

finger, or joints far from the center of the body. In most cases, patients experience pain when

waking up, but the pain gradually decreases throughout the day. Although pain usually fades

throughout the day, patients may still experience days of agony; they cannot stand up from chairs

or walk upstairs. Lupus arthritis is painful, but is not as damaging as rheumatoid arthritis:

“Fewer than 10 percent of people with lupus arthritis will develop deformities of their hands and

feet associated with weakening of cartilage and bone” (Quismorio). In chronic cases of lupus,
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patients can experience a decline in bone and muscle strength. Lupus arthritis causes an

immense amount of pain and can make menial tasks difficult (Quismorio).

Inflammation can cause not only joint pain but also muscle pain and weakness. Many

lupus patients often have myalgia and myositis. Myalgia is a muscle disease that causes muscle

pain and aches. Myositis is the inflammation of the muscles, resulting in weakness and swelling.

Both myalgia and myositis are classified as muscle diseases but are often caused by lupus. The

compromised immune systems leave patients at a higher risk of developing muscle diseases.

Lupus myositis is prevalent in the neck, pelvis, thigh, shoulder, and arm muscles. Pain in these

areas can make picking up small objects difficult. The combination of joint and muscle pain,

make simple tasks exhausting (Sundbom).

Lupus causes both internal and external symptoms. A typical external symptom of lupus

is skin sensitivity. Many patients get malar or butterfly rashes. The butterfly rash is a

distinguished mark of lupus, as it stretches across nearly the entirety of the face. The outbreak

occurs if a patient is in direct sunlight over a period. The butterfly rash occurs in almost fifty

percent of all lupus patients: “A facial rash that extends across the forehead, cheeks, and nose,

shaped like to a butterfly, occurs in about half of all cases” (LaMotte). Dry, red spots may

appear on knuckles, neck, and back. Other patients may notice scaly, eczema-like rashes on the

scalp, ears, arms, and chest. These rashes can appear in either red or purple. Rashes need to be

regulated, or it could leave permanent scarring on the body, so it is essential lupus patients are

careful of ultra-violet light (LaMotte).

The momentary effects of lupus are painful, but the long-term effects are alarming.

Lupus increases the chances of developing other health scares. Lupus increases pregnancy

complications. Lupus patients have a higher chance of miscarriage, as “ten percent of

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pregnancies currently end in miscarriage” (Petri). Patients may also experience pre-eclampsia

which is indicated by high blood pressure. It hypothesized pre-eclampsia is a result of “a change

in the mother’s immune response to fetal/placental tissue” (“Planning a Pregnancy”). Pre-

eclampsia can cause premature births and intrauterine growth retardation. Michelle Petri, a

professor at Johns Hopkins School of Medicine, estimates “7% of the pregnancies [of lupus

patients] are characterized by a severe maternal complication” (Petri). These complications are

severe, but pregnancy is possible with planning and monitoring.

Other than pregnancy risks, lupus patients are also at a higher risk of developing cancer.

Lupus patients have a high chance of developing lymphoma, believed to be due to the

overstimulation of B-cells and immunosuppression medications. The increased levels of

estrogen in patients with lupus may also lead to the development of breast cancer. Cervical

cancer is also prevalent in lupus patients. The weak immune system prevents the body from

fighting HPV (human papillomavirus), which causes cervical cancer. Lastly, patients are at risk

of developing lung cancer. Studies prove “lung cancer is about 1.4 times more common in

people with lupus than in the general population” (Petri). Due to this threat, lupus patients

mustn’t smoke tobacco. Although more research is needed to confirm the connection between

lupus and cancer patients must be proactive in their self-examinations and treatments (Petri).

There is no cure for lupus, but the symptoms are reduced through medicine. The

symptoms of lupus are eased through conventional medicine and prescription drugs. A common

practice of lupus treatment is drug repositioning. According to the authors of Drug

Repositioning in SLE: Crowd-sourcing, Literature-mining, and Big Data Analysis:

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Lupus patients and the rheumatologists that care for them are unconsciously familiar with

the concept of ‘repurposed drugs’ since SLE patients are routinely treated with drugs that

were initially employed for other diseases. (Grammer et al.)

Drug repositioning analyzes medications explicitly made for other diseases and applies them to

treat the symptoms of lupus. Researchers look for common chemical structures to find a match

for lupus’ symptoms. The most common medications were initially created for malaria, cancer,

transplant rejection, and lymphoma. These drugs take a few months to fully kick in and improve

symptoms (Grammar et al.).

As the body adjusts to the medications, some patients experience serious side effects.

These side effects include headaches, upset stomach, and changes in skin color. Despite the

effectiveness of the medication to relieve specific symptoms, drug repositioning “lack[s] the

necessary precision to target lupus pathways specifically” (Grammer et al.). Drug repositioning

provides an option to ease the painful symptoms of lupus, but it is not a cure. Despite it being a

temporary fix, drug repositioning lowers the risks of adverse toxicology and helps researchers

make advancements in finding a cure for lupus (Grammer et al.).

Other conventional treatments besides drug repositioning includes FDA approved

medications. The FDA has most recently approved of the distribution of Benlysta (belimumab).

This is the most recent breakthrough in lupus treatment. Benlysta is the first prescription drug

made for lupus to be approved by the FDA in over fifty years. Benlysta is also the first drug

approved that fights the abnormal immune activities that cause inflammation in lupus patients.

About an hour is needed for a full dose of Benlysta to be received through IV infusion. The

medication is classified as “a human monoclonal antibody, belimumab, which has been shown to

reduce autoantibody levels associated with lupus” (Hunte). Lowering the autoantibody levels,
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allows patients to suppress lupus and its symptoms over a period, through a single medication

(Hunte).

Despite the positive effects of Benlysta, it has serious side effects to take into

consideration. During FDA trials, many of the side effects were revealed. In most patients,

Benlysta causes headaches, nausea, trouble sleeping, and depression. The effects of depression

were highlighted in the FDA’s Benlysta (belimumab) report: “There were four cases of suicide

attempts or suicidal ideation, all in patients treated with belimumab (one each in placebo-

controlled studies L02 and C1057, and two in the safety extension period of study L02 called

study L99)” (Harper). In light of this report, financial analyst Christopher Raymond defended

the drug, stating, “[T]his patient population is known to be at higher risk for suicide, and the

trials are 2:1 skewed toward Benlysta patient” (Harper). Benlysta has also shown to increase the

development of cancer, as Benlysta lowers immune activity. The development of progressive

multifocal leukoencephalopathy (PML) is another serious side effect of Benlysta. PML is a

brain infection that can potentially result in death. Due to all the side effects, it is crucial for

patients to continue to talk with their physicians (Hunte).

Benlysta, approved in 2011, was a complicated approval process. Prescription drugs

explicitly designed for lupus are continuously in the works. Before any medication is put onto

the market, it must be approved by the Food and Drug Administration (FDA). A drug can only

be approved by the FDA when it proves that the potential benefits outweigh the potential risks.

In 2014 it was estimated “the average drug discovery and development process cost $1.4 billion”

(Millman). Typically, it takes about ten years for a drug to be approved by the FDA. The FDA

approval process is long and expensive; therefore, it is challenging for approval to be granted.

According to Dr. Gary S. Gilkeson, a professor of medicine/microbiology and immunology at

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the Medical University of South Carolina at Charleston, “There are at least three other drugs in

Phase 3 clinical trials that I’d put at a two- to three-year timeframe. And there are a number of

other drugs a little further down the pipeline, in the five-year timeframe” (Boerner). The

approval process may be treacherous, but there is hope for the advancement of lupus treatment

options (“How Drugs Are Developed and Approved”).

One of the most promising lupus treatment is the NOBILITY trial for the combination of

Gazyva (obinutuzumab) and mycophenolate mofetil. Gazyva is traditionally used as a cancer

treatment, while mycophenolate mofetil is used to prevent organ transplant rejection. The

NOBILITY trial is being conducted by biotech companies, Roche and Genentech. The purpose

of the study is to determine the effectiveness of the combination of obinutuzumab, commonly

referred to as Gazyva, and mycophenolate mofetil (MMF). The merge of Gazyva and MMF is

anticipated to treat kidney inflammation; Kidney inflammation is “associated with increased

hospitalizations and higher mortality rates among lupus patients” (Melão). Kidney failure is

most commonly associated with lupus nephritis, but kidney inflammation can appear in all forms

of lupus. This treatment option could prevent kidney failure for not just lupus nephritis patients,

but all lupus patients (Melão).

Before the combination of Gazyva and mycophenolate mofetil can be distributed to the

public, it must be approved after phases of trials. The NOBILITY trial for Gazyva and

mycophenolate mofetil is currently in its phase two trial. NOBILITY is expecting to enroll 120

adult patients to participate in the fifty-two-week trial. The study will be examining not only the

effect it has on the kidneys, but also secondary measures including “overall response rate, partial

renal response rate, and several immunological parameters, such as number of immune B and T-

cells, production of antibodies targeting obinutuzumab and anti-dsDNA levels” (Melão). The
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study is estimated to be finished entirely in December 2019. Based on those results, the biotech

companies will conduct a phase three trial and may be approved by the FDA (Melão).

Despite the effectiveness of conventional medicine, some patients prefer alternative

treatments. The side effects of prescription drugs can be excruciating; therefore, alternative

therapies are becoming more popular. Alternative practices include supplements, acupuncture,

and Chinese traditional medicine. Alternative treatments may be helpful to some patients, but a

patient should consult their doctor about adding alternative medication into their treatment plan.

Incorporating vitamins and supplements into patients’ treatment plans can improve the

quality of their lives. Popular supplements for lupus are vitamin D and Dehydroepiandrosterone

supplements. In many cases, lupus patients are sensitive to sunlight, hindering the production of

vitamin D. Vitamin D helps people to absorb calcium, reduce the risk of the flu, and reduce the

risk of diabetes (Ware). Lack of sunlight and vitamin D production can cause lupus patients to

develop osteoporosis. For this reason, patients take vitamin D supplements to strengthen their

bones and improve their overall immune system. Dehydroepiandrosterone or DHEA are sex

hormones. DHEA regulates estrogen and testosterone, as well as enhancing the immune system,

providing energy, and strengthening bones. DHEA supplements are helpful but are most useful

as an addition to conventional treatment plans (Greco).

Other than supplements, Traditional Chinese medicine (TCM) has emerged as a

beneficial alternative treatment option for lupus patients. TCM is individualized treatment plans

based on the severity of the symptoms. TCM focuses on bringing balance to the patient’s life by

considering all aspects of life:

Traditional Chinese medicine (TCM) focuses on the overall regulation of immune

function by reconstructing a stable state, and it seeks to regulate Yin and Yang, Qi and
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blood and the role of Zang Fu internal organs by enhancing the body's defensive

capabilities, improving immune function, and limiting adverse reactions. (Bo and Gao)

Restoring the balance of yin and yang in the body is believed to strengthen not only the immune

system but the entire body. There is still more research to be done on the effectiveness of TCM

to treat Lupus, but it is understood that combining TCM practices with typical treatment is

beneficial. In a 2013 trial, “combining the Lang-Chuang Medicinal Decoction with prednisone

to treat SLE resulted in efficacy of 93.33%” (Bo and Gao). This exemplifies the effective

treatments that can result from combining TCM and prescription medication. TCM treatments

lower the toxic effects of conventional medicines and reduce the frequency of reoccurring flare-

ups (Bo and Gao).

A popular form of Tradition Chinese medicine is acupuncture. Acupuncture has been

practiced for over two-thousand years. The goal of acupuncture is to renew balance by

regulating the flow of chi throughout the body. In acupuncture, needles are either inserted at

acupoints and balance is restored through channels, or needles are inserted directly where pain

occurs. The needles will be left alone for about thirty minutes and are nearly painless.

According to a theory: “the acupuncture needle stimulates small diameter nerves in muscles,

which send impulses to the spinal cord. The spinal cord and brain are then activated to release

endorphins, which are the body's natural pain relievers” (Meng). Acupuncture allows patients to

relieve pain, with only a few side effects. Minor side effects include bruising, redness, and

nausea. More severe side effects include infection, nerve injury, and organ punctures. The listed

severe side effects are not common, especially if being administered by a licensed acupuncturist.

Research on acupuncture’s effectiveness to treat symptoms of lupus, other than pain and fatigue
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are limited, so patients should use it as a complementary practice to their conventional treatment

routine (Meng).

Another Traditional Chinese medicine is the Thunder God Vine. The Thunder God Vine, also

known as lei gong tang is commonly used to treat inflammatory diseases in China:

The People's Republic of China has reported promising results using the root of the Thunder God

Vine to treat rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, chronic

hepatitis and a variety of skin disorders. (“Root Power”)

Despite its popularity in China, the Thunder God Vine is currently only available in the

Eastern hemisphere. Research on how the Thunder God Vine affects Lupus is currently being

researched at the University of Texas Southwestern Medical Center. Based on research from UT

Southwestern the Thunder God Vine restricts human immune cells from attacking healthy tissue.

Research continues to narrow down the active ingredient which blocks the cells from attacking

the body. UT Southwestern researchers have also begun to investigate the Thunder God Vine’s

cousin, found in Mexico. Based on the research found UT Southwestern is applying to

administer an FDA-approved clinical trial, to observe how the integration of the Thunder God

Vine into everyday routines will affect lupus patients (“Root Power”).

Lupus is a chronic illness that causes inflammation complications throughout the body.

Although there is no cure for Lupus, the pain can be treated through conventional medicine and

drug repositioning. Additionally, it can be treated with alternative treatments, including

supplements and traditional Chinese medicine. Do not hesitate to raise awareness about Lupus

and the pain it causes. The FDA drug approval process needs to be improved so that potential

medication can be tested affordably and timely. Also, more research is needed to find a definite
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treatment for Lupus. With more knowledge about the causes of lupus and how it affects

patients, there is hope that a cure may be found.

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