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Health and Disease

The Increasing Prevalence of Autoimmune Diseases

By Swetha Babu

Published 11:16 PM EST, Mon August 16, 2021

Introduction

NIH (National Institutes of Health) have revealed that up to 23.5 million American citizens have an autoimmune disease and the prevalence is increasing. 80-100 various autoimmune diseases have been identified by scientists who also assume that at least 40 other diseases could potentially have an autoimmune basis.

Classifications of Autoimmune Diseases

No tissue or organ is exempt from autoimmune diseases: these diseases can affect various organs and organ systems, varying greatly among the individuals who have them, in terms of severity and responsiveness to therapy.

Autoimmune diseases can be either localized or systemic:

–       Systemic autoimmune diseases affect many organs and tissues simultaneously. Examples of systemic autoimmune diseases include scleroderma (affecting the skin, intestines, and less commonly lungs and kidneys) and Sjogren’s Syndrome (affecting salivary glands, tear glands, and joints.) 

–       Localised autoimmune diseases are organ-specific and remain in only a certain part of the body, but often can develop into systemic diseases. Examples of localized autoimmune diseases include Hashimoto’s disease (affecting the thyroid) and Discoid Lupus Erythematosus (affecting the skin). Discoid LE is an example of a localized disease that can progress into Systemic LE, affecting various organs such as the kidneys.

Increasing Prevalence

In the UK alone, the incidence of various autoimmune diseases is increasing at ranges between 3% and 9% year on year. This includes:

•       7.0% increase per year of rheumatic diseases such as rheumatoid arthritis

•       6.3% increase of endocrinological conditions such as type 1 diabetes

•       3.7% increase of neurological such as Multiple Sclerosis (MS)

•       4–9% increase per year of coeliac disease

In the United States of America, the prevalence of autoimmunity is also rising. According to researchers at the Allergy and Immunology section at Yale School of Medicine, in the last 25 years, there has been a 44% increase in ANA antibodies (antinuclear antibodies), which are antibodies that target themselves, with over 41 million people affected. These ANA antibodies presage autoimmune diseases such as lupus and autoimmune arthritis.

Image 1 –  ANA antibodies with fluorescent dye

Costs for hospitals to aid affected individuals continue to rise as the incidence of these diseases increases. Direct and indirect costs for just three autoimmune diseases alone (type 1 diabetes, rheumatoid arthritis, and multiple sclerosis) currently add up to more than £13 billion per year in the UK. The costs are significantly high due to the absence of treatments that cure autoimmune diseases and the likelihood for patients to develop major secondary diseases. Treatment of autoimmune disease focuses on controlling the autoimmune reaction with immunosuppressants: Corticosteroids are often used to control inflammation and suppress the immune response. Another medication such as pain medication is often prescribed to suppress symptoms of the disease.

Causes and Possible Reasons for Increasing Cases

The immune system is exceedingly complex, and research has revealed some potential triggers for excess immune responses.

Genetics, and Environmental Factors

The most simple theory is that as a result of a mutation, an individual inherited a faulty allele (a version of a gene, which codes for a specific protein). Hence, the protein does not form correctly and fails to function effectively. E.g., In Type I Diabetes mellitus, a mutation in particular protein results in the destruction of beta cells in the Islets of Langerhans, as the cells are wrongfully targeted and destroyed, which results in the inability to produce insulin.

Another genetic-related theory is that a certain genetic background makes an individual more likely to have a sensitive immune system, which, upon an encounter with a certain trigger (such as an infection or climate), sets off an autoimmune disease. Chilblain Lupus Erythematosus is an example of a disease that can be inherited but may only be expressed when an affected individual inhabits a colder climate.

Smoking and Drugs

Certain substances, particularly blood pressure medications or antibiotics, can trigger the onset of drug-induced lupus, which is a more benign form of the disease but can still greatly affect an individual’s daily activities. Statins can trigger the onset of statin-induced myopathy, which causes muscle weakness.

Weight and Obesity

Being overweight or obese raises the risk of developing autoimmune diseases such as rheumatoid arthritis or psoriatic arthritis. The greater fat content and greater weight put stress on the joints, particularly the knees, and intruding fat tissues encourage further inflammation. The increasing global epidemic of obesity can contribute to the rising incidence of autoimmune diseases.

Research Advances to Lower Number of Cases

Clinical Trials

Knowledge about various autoimmune diseases and new therapies can be gained from clinical research studies, conducted with volunteers who undergo various medical tests. Clinical trials for autoimmune diseases include studying “the Pathogenesis of Chronic Inflammatory Rheumatic Diseases’” and studying “Patients Undergoing Therapy for Immune-Mediated Inflammatory Skin Conditions.” The purpose of these clinical research trials can enable various worldwide healthcare professionals to assess the safety and effectiveness of current and future therapies and to study how the onset and severity of the diseases can be dependent on inherited or acquired traits.

Laboratory Research

Researchers in laboratories investigate the molecular mechanisms of the immune response to understand the disease progression further whilst uncovering new treatment approaches. This information can enable patients’ risk for certain diseases to be recognized earlier and to provide appropriate treatments.

Translational Research

This involves linking both laboratory and clinical research as materials and information are exchanged and shared between these two disciplines. For example, demographic data and medical data from clinical trials can be studied together with blood samples and tissue samples to understand the diseases’ pathogenesis and progression to better target treatments.

Swetha Babu, Youth Medical Journal 2021

Conclusion

The increasing prevalence of autoimmune diseases and immune-related diseases continues to exert pressure on hospitals and to increase the costs for hospital treatments, due to the chronic nature of the diseases and the regular requirement for medication.

The ultimate goal of early diagnosis and therapy is prevention – before autoimmune diseases become a clinical problem.

Swetha Babu, Youth Medical Journal 2021

References

Lovell, D., Huang, B., Chen, C., Angeles-Han, S., Simon, T., Brunner, H. (2021) Prevalence of autoimmune diseases and other associated conditions in children and young adults with juvenile idiopathic arthritis. National Centre for Biotechnology Information. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978075/

British Society for Immunology. (2018, Nov. 26) Report reveals the rising rates of autoimmune conditions. https://www.immunology.org/news/report-reveals-the-rising-rates-autoimmune-conditions

Yale School Of Medicine. (2021, May. 20) Understanding Autoimmune Diseases. https://medicine.yale.edu/news-article/understanding-autoimmune-diseases/

Image 1 – http://blog.mblintl.com/antinuclear-antibodies-and-the-ifa-test

Johns Hopkins Medicine, Johns Hopkins Arthritis Center. https://www.hopkinsmedicine.org/health/wellness-and-prevention/what-are-common-symptoms-of-autoimmune-disease

Mayo Clinic, Clinical Trials: Autoimmune Diseases. (2021) https://www.mayo.edu/research/clinical-trials/diseases-conditions/autoimmune-diseases

Benaroya Research Institute at Virginia Mason, Autoimmune Diseases.

https://www.benaroyaresearch.org/what-is-bri/disease-information/autoimmune-diseases

Categories
Health and Disease

Phantom Limb: Perceiving the Invisible

By Swetha Babu

Published 3:02 PM EST, Sat July 10, 2021

Introduction

The incidence of phantom limb is reported to be as high as 60-80% in patients post-amputation. Phantom limb pain should be differentiated from residual limb pain (RLP), as the latter originates from the actual site of the amputation.

Unlike phantom limb, RLP is often a manifestation of an underlying source, such as nerve entrapment, skin infections, surgical trauma, etc.

Onset and Symptoms

The onset of phantom limb mostly occurs immediately after amputation, however, some are documented to onset after a few weeks, although, rarely months later. The rise towards maximal sensation and pain differs between patients, often due to the contrasting extent of trauma and amputation.

Phantom pains are often described as crushing, burning, tingling, and cramping. Phantom sensations can be categorised into three different types:

–   Kinetic (movement)

–   Kinaesthetic (position and shape)

–   Exteroceptive (other stimuli such as touch, temperature and irritations)

 Image 1

Pathophysiology Theories behind phantom pain

Peripheral Nerve Changes

Amputation can result in a great trauma to nerves and tissues surrounding the site of amputation. 

This damage disrupts the normal nervous signals involved with the missing limb. The proximal portions of severed nerves begin to form neuromas (benign growths of nerve tissue), and the nerves become hyper-excitable, resulting in spontaneous discharges of impulses – pain and other sensations are experienced. 

Brain Changes

There has been significant research into cortical reorganisation, and it is a commonly cited factor in phantom limb pain. Cortical reorganisation refers to how the brain ‘re-maps’ the sections of the brain, adapting to significant stimuli. This can result in stimulation of nerves in the residual limb and the surrounding areas, causing the experience of pain and sensation in the missing limb. There is also a correlation between the extent of cortical reorganisation and the amount of pain that the patient experiences. 

An example of Cortical Reorganisation in response to amputation:

Psychological Factors

Sensations and pain could be influenced by memory of the incident, memory of pain proceeding the amputation, mood state, and a variety of other social concerns. In addition, circulating epinephrine within the body resulting from emotional distress can contribute to the stimulations of the peripheral nervous system, which can develop into the perception of sensations and pain in the amputated section of the limb. 

Evaluating Symptoms

The diagnosis of this phantom limb phenomenon is primarily a diagnosis of exclusion and is greatly dependent on the patient’s history, hence laboratory tests are less required.  A complete blood count (CBC) can help rule out infection as the source of paraesthesia. An ultrasound can be ordered to look for neuromas as a possible pain stimulator. However, most importantly, a psychology evaluation may be indicative if the patient is having significant extrinsic triggers that may be contributing to the patient’s pain, which could signify the requirement of psychiatric therapy.

Treatment and Prognosis

Often, when phantom limb pain and sensations continue vigorously for more than six months, the prognosis for spontaneous improvement is poor: some patients will experience a lifelong struggle with chronic pain. Phantom limb is a very difficult and complex condition to treat, particularly due to the lack of understanding of the nature of the condition, and that the cause of the phenomenon varies between patients.

The first treatment is usually conservative and should include non-pharmacological and nonsurgical methods. Prosthetists should assess the stump – the site of amputation – and should encourage the patient to use a prosthetic device for improved mobility. Psychotherapists may help identify the psychological cause of the pain and sensations experienced by the patient with the aim to mitigate the experiences and to ease anxiety and depression. In the event that neither solution is successful, pharmacists will work to select appropriate pharmacological agents. The medication should be specific to the extent of pain and/or sensations, considering its debilitation and hindrance on everyday life, as well as the history of symptoms. The patient must be aware of why the medication is being administered and educated on the different pharmacological agents available and their effectiveness and adverse effects.

Treating phantom limbs tends to be for symptomatic control, and although no medications specifically for phantom limbs exist, some drugs designed to treat other conditions have been helpful in relieving nerve pain: 

  • Antidepressants, especially Tricyclic antidepressants, help relieve the pain of phantom limb phenomena. 
  • Receptor antagonist medications, specifically NMDA receptor antagonists, are anaesthetics which bind to specific receptors on nerve cells, blocking the binding of a protein called glutamate, which has a crucial role in relaying nerve signals.

Conclusion

Research about phantom limbs is still in early stages, hence currently nothing more can be done to prevent, reduce, and cure phantom limbs. With a variety of psychotherapy options, medication, and prosthetics, alongside occupational therapy, phantom limb pain and sensations can be relieved in some, but not all, cases. As mentioned before, there is no one treatment that works reliably or consistently in all patients; the outcomes for most patients are limited and the quality of life can be poor.

Swetha Babu, Youth Medical Journal 2021

References

BJA Education. (2016) 16(3): 107–112. Pain after amputation. https://doi.org/10.1093/bjaed/mkv028

Image 1: https://medicalxpress.com/news/2018-09-theory-phantom-limb-pain-effective. html

Hanya-Deutmeter, A., Cascella, A., Varacallo, A. (2021). Phantom Limb Pain. National Centre for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK448188/

Mayo Clinic, Mayo Foundation for Medical Education and Research. (2020, Oct. 29) Phantom Pain. https://www.mayoclinic.org/diseases-conditions/phantom-pain/diagnosis-treatment/drc-20376278

Cleveland Clinic. (2016, Mar. 14). Phantom Limb Pain. https://my.clevelandclinic.org/health/diseases/12092-phantom-limb-pain