AUTOIMMUNE DISEASES – GENERAL POINTS
Causes
Autoimmune diseases are those caused due to a self-recognition error by the body’s immune system. In such cases, a particular protein is misrecognized as being foreign (antigenic), and the immune system mounts an attack on it. This causes inflammation and damage to the concerned tissue or organ, leading to symptoms and disease. The antibodies produced by the immune system in such cases are called ‘auto antibodies’.
The exact cause is not known, and there are no well-defined risk factors, that may be a combination of genetic, ethnic, nutritional, and environmental factors. Overall, autoimmune diseases are more common in females. The condition may manifest itself in childhood itself but sometimes may appear only in teens or adulthood.
Clinical Course and Diagnosis
Most autoimmune diseases have periods of exacerbation (flare-up of symptoms), and remission (symptoms are controlled). Stress and infections can be triggers. Autoimmune diseases may affect one organ or many different organs.
Diagnostic tests include imaging and a biopsy from the involved organ/s, and some immune blood markers or antibodies (like antinuclear antibody ANA, rheumatoid factor RF, anti-cyclic citrullinated peptide antibodies anti-CCP, etc.). A strong clinical suspicion and detailed medical evaluation is required for diagnosis.
Management
Overall, a well-balanced diet, regular physical exercise (with physiotherapy where needed) and stress management are important aspects.
MEDICINES
Generally, autoimmune conditions require management of flare-ups with drugs that suppress immunity (immunosuppressive drugs). These include corticosteroids (like prednisolone), and other disease-modifying drugs like antimetabolites azathioprine and methotrexate, cyclosporine, leflunomide, chloroquine or hydroxychloroquine, etc. and the drugs called JAK inhibitors (tofacitinib and baricitinib).
NSAIDs like ibuprofen, diclofenac, naproxen, etc. or sometimes opiate medicines like tramadol, may be given to manage pain. Other medicines for individual symptoms may also be prescribed.
Biologicals (monoclonal antibodies -MAbs) are an advanced class of medicines that act by blocking specific immune mediators called cytokines (like TNF-A blockers etanercept, infliximab, adalimumab, certolizumab, golimumab, IL-6 blocker tocilizumab, and IL-17 inhibitors secukinumab, ixekizumab). For some of the conditions, specific biological medicines have been developed.
Intravenous immunoglobulin (IVIG) is a biological consisting of pooled normal antibodies given to normalize the functioning of the immune system.
PROCEDURES
Therapeutic plasma exchange (TPE), also sometimes known as plasmapheresis, removes and replaces a patient’s plasma (liquid part of blood containing antibodies and immune mediators) to treat certain autoimmune diseases.
Surgery may be required in some conditions to correct bone-joint deformity or bowel obstruction.
TYPES OF AUTOIMMUNE DISEASES
Sometimes more than one autoimmune disease can occur in the same person. There are over 100 autoimmune diseases identified, and listed below are the 15 most well-known, studied and diagnosed ones.
Systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE), commonly referred to as lupus, manifests as inflammation and pain in multiple organs including skin, joints, kidneys (glomerulonephritis), heart and brain. The most common signs and symptoms of flare-ups include:
- Fever
- Fatigue
- Headache
- Breathlessness and/or chest pain
- Joint and muscle pain, stiffness and swelling
- Rashes on face and body (Butterfly-shaped rash on the face that covers the cheeks and bridge of the nose, is typical). Skin lesions that appear or worsen with sun exposure
- Bluing or whitening of fingers and toes on cold exposure or during a stressful period (Raynaud’s phenomenon)
- Dryness of eyes and mouth, and sometimes mouth sores
- Hair loss
- Weight changes
- Blood in urine
- Anxiety-depression
It is treated with immunosuppressive and symptomatic medicines. Among biologicals, belimumab given intravenously is the first new drug for SLE.
Sjögren’s disease
In this condition, the immune system attacks the glands that provide lubrication to the eyes (lacrimal) and mouth (salivary). Therefore, it manifests as dry eyes (decreased tears) and dry mouth (decreased saliva) as the hallmark symptoms.
Dry eyes cause itchy, gritty, irritable eyes, and can be so severe that it can cause damage to the cornea leading to reduced vision. Dry mouth can cause mouth ulcers, make eating and speaking difficult, and sometimes accompanied by swollen salivary glands. It also increases risk of dental cavities, and oral thrush (yeast) infection. Dryness of skin and vagina may also be present.
The disease can also damage other parts of your body, such as joints, nerves, skin, thyroid, kidneys, liver and lungs, presenting with symptoms like joint pain, swelling and stiffness, tingling, numbness and burning in hands and feet (neuropathy), rashes, fatigue, reduced kidney function, hepatitis and cirrhosis, and dry cough with pneumonia or bronchitis. There is an increased risk of developing cancer of lymph nodes (lymphoma).
It is treated with immunosuppressive medicines. Lubricating agents are needed for supportive care like artificial tears, pilocarpine or cevimeline to stimulate tear/saliva production, along with skin moisturizers and vaginal lubricants.
Type 1 Diabetes
It is also called insulin-dependent diabetes, and occurs due to destruction of pancreatic cells that produce insulin. Therefore, the body is unable to regulate blood sugar levels, and with time this causes damage to various organs like blood vessels, heart, kidney, nerves, eyes, etc. Insulin has to be substituted in these patients as the main treatment.
Read: Diabetes – Understanding Types, Diagnosis and Management
Rheumatoid arthritis (RA)
It is a form of joint inflammation (arthritis) that occurs due to the immune system attacking proteins in the joint cartilage. This leads to swelling, pain, stiffness and impaired mobility, especially of the smaller joints of hand and feet. There may also be general symptoms like fever, night sweats, weight loss, and fatigue. When it sets in at 16 years or younger, it is called juvenile rheumatoid arthritis (JRA) or juvenile idiopathic arthritis (JIA).
Read: Arthritis – Types and Management
Ankylosing Spondylitis (AS)
Autoimmune arthritis has been seen in the backbone which leads to damage and chronic inflammation of the intervertebral discs (in between cartilage pads) and adjoining vertebra. This leads to ‘fusing’ of the vertebrae (sometimes clearly seen in X-ray to appear like a ‘bamboo spine’). Main symptoms are stiff and painful back, worst in the morning or after periods of inactivity.
AS is also called axial spondyloarthritis and may be occasionally associated with similar arthritis of other peripheral joints as well like hip, shoulder and sternum-ribs, as well as inflammation inside the eye (uveitis). Treatment includes medications (pain relievers, immunosuppressants, and biologicals in severe cases), physiotherapy and in rare cases, surgery.
Read: Back Pain – Understanding and Management
Autoimmune Skin and Hair Diseases
Psoriasis is the most common autoimmune skin condition where the skin cells multiply fast and form inflamed and scaly, often itchy patches on the skin that appear as red-silver plaques. Psoriasis affects both skin and the nails, and also can manifest as joint inflammation (Psoriatic arthritis) due to some shared proteins between skin and cartilage.
Psoriasis is treated with topical creams, gels or ointments that contain medicines modulating the immune system: corticosteroids, vitamin D analogs (calcipotriene or calcipotriol), retinoids (tazorotene), and calcineurin inhibitors (tacrolimus). Salicylic acid and coal tar/anthranil may be used to manage scales and plaques. In severe cases, oral corticosteroids or retinoids may be needed. Apremilast is a new class of oral medicine for psoriasis. Biologicals, given as injections are used in severe cases like adalimumab, ustekinumab, secukinumab, ixekizumab, and certolizumab. UV light and laser therapies are other treatment modalities available.
Other skin diseases known to have an autoimmune cause include lichen planus, pemphigus and scleroderma.
Read: Inflammatory and Pruritic Conditions of the Skin
Alopecia areata is an autoimmune disorder that causes patchy balding.
Read: Hair loss and Balding
Multiple Sclerosis (MS)
Multiple Sclerosis is a condition in which the protective coating surrounding nerve cells (myelin sheath) is damaged, and that slows the nerve transmission speed. It manifests as numbness, weakness, and reduced walking and balancing ability.
Read: Multiple Sclerosis
Guillain Barre Syndrome (GBS)
It is a condition in which the immune system attacks the nerves. The condition is usually triggered by an acute viral or bacterial infection (rarely by vaccination). Symptoms start as weakness and tingling in the feet and legs that then spread to the upper body in the next 2 weeks or so, and paralysis can occur. Other symptoms are unsteady walking, inability to walk or climb stairs, leg cramps worsening at night, difficulty in speaking, chewing or swallowing, eye muscle paralysis causing double vision or loss of bladder/bowel control.
GBS when severe is a medical emergency and may be accompanied by increased heart rate, blood pressure changes and breathlessness. Special blood treatments (plasma exchange and IV immunoglobulin therapy) can relieve symptoms.
Most people recover completely from Guillain-Barre syndrome, and fatality is rare but can occur in some severe cases. Recovery may take up to several years, but most people are able to walk again 6 months after symptoms began. Some may have lasting weakness, numbness or fatigue. Physiotherapy is required long-term.
Inflammatory Bowel Disease (IBD)
IBD is the inflammation of the bowel wall, and is classified according to the part of the gut involved. Crohn’s disease can inflame any part of your gastro-intestinal tract, from the mouth to the anus, while Ulcerative Colitis (UC) affects the lining of the large intestine (colon) and rectum.
IBD manifests as episodes of abdominal pain, diarrhea, blood in stools, weight loss, loss of appetite fatigue, and fever. Repeated episodes can cause scarring that can lead to bowel obstruction.
Read: Inflammatory Bowel Disease
Celiac disease
In these people, gluten, a protein found in wheat, rye, and other grain products, when ingested, is attacked by the immune system in the small intestine, causing inflammation. Symptoms include vomiting, diarrhea or constipation, abdominal uneasiness, indigestion, and sometimes blood in stools.
Coeliac Gluten Sensitivity Profile ELISA blood test is used to detect the presence of antibodies like IgG and IgA against the gluten protein. Genetic testing is also available. The solution is mainly eating gluten-free products.
Autoimmune Thyroid Diseases
GRAVE’S DISEASE
It is caused due to the immune system generating ‘thyroid stimulating antibodies’ (TSAb) that make the thyroid gland produce excess thyroid hormones leading to hyperthyroidism. What triggers the formation of these antibodies is still unclear.
Symptoms of hyperthyroidism include palpitations (rapid heart rate), weight loss, hyperactivity leading to fatigue, heat intolerance, tremors, anxiety, sleeplessness, diarrhea, and increased sweating. Loss of libido in men and scanty infrequent periods in women may be seen. The characteristic appearance is that of bulging eyeballs (exophthalmos) with retracted eyelids, often referred to as Grave’s ophthalmopathy. The thyroid gland may be visible as a neck swelling (goiter). Some people with Graves’ disease may also have thick, red skin usually on the shins or tops of the feet (Graves’ dermopathy).
Thyrotoxicosis is a term used for a highly overactive thyroid gland releasing high levels of thyroid hormones. In some cases, when thyroid hormone levels go so high as to be life-threatening, it is called a thyroid storm which can greatly increase heart rate (palpitations), BP and body temperature.
Treatment is with immunosuppressive medicines. Lubricating eyedrops should be used to prevent dry eyes. Medicines like methimazole/carbimazole and propylthiouracil act by inhibiting thyroid hormone synthesis, and may be used in severe cases, like thyrotoxicosis or thyroid storm. Other drugs like propranolol (beta-blockers) or diltiazem may be used to reduce palpitation and abnormally high heart rate.
HOSHIMOTO’S THYROIDITIS
In this condition, the immune system causes the destruction of the thyroid gland leading to the deficiency of thyroid hormones. Symptoms are those of hypothyroidism like weight gain, sensitivity to cold, fatigue and reduced activity, dry coarse hair and hair loss, constipation, and swelling of hands and feet. Women may experience heavy periods. The thyroid gland may be swollen.
Thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in blood have been used to diagnose Hashimoto’s thyroiditis. Treatment is with immunosuppressive medicines, and supplementing thyroid hormones as oral levothyroxine.
Read: Thyroid Gland Function and Disorders
Addison’s disease
The immune system attacks and damages the adrenal glands, which produce the hormones cortisol and aldosterone as well as some of the androgen (male sex) hormones. Cortisol deficiency produces weakness, fatigue, low blood sugar (hypoglycemia), fainting episodes, weight loss and low BP. Aldosterone deficiency leads to loss of sodium in urine (hyponatremia), and raised blood potassium (hyperkalemia). Other symptoms include nausea, vomiting, abdominal pain and constipation, and sometimes changes in the skin.
Hormone (corticosteroid) replacement therapy is the mainstay of treatment. A long-acting injectable, desoxycortosterone pivalate is now available as a specific treatment.
Myasthenia gravis
It occurs due to the immune system autoantibodies attacking specific receptors (nicotinic acetylcholine receptor), at the junction of the nerves and our voluntary (skeletal) muscles, causing a block in neuromuscular transmission. This leads to a reduced functioning of these muscles causing muscle weakness (worsening with activity) and loss of movement control.
Drooping eyelids may be an early sign. There may be progressive weakness of arm and leg muscles affecting the performance of tasks and walking. Impairment is also seen in opening and closing the eye, moving the eyeball (causing double vision), swallowing and chewing, speaking, facial expressions, and holding the head up. Myasthenic crisis is a life-threatening emergency condition when the muscles that control breathing become too weak to work.
Apart from blood tests for autoantibodies, nerve stimulation and muscle function tests (electromyography) are performed. Treatment is with immunosuppressive medicines and cholinesterase inhibitors drugs like pyridostigmine that can improve communication between nerves and muscles. Biologicals like rituximab and eculizumab are used in severe cases. Plasmapheresis and intravenous antibodies are also given in some cases. Regular screening by imaging for thymus gland tumors should be performed.
Pernicious anemia
It is a type of anemia that occurs due to vitamin B12 deficiency resulting from autoantibodies produced by the immune system again the ‘Intrinsic Factor’ in the gut that is required for vitamin B12 absorption. As vitamin B12 is a crucial vitamin for the maturation of red blood cells (RBCs) that contain hemoglobin to carry oxygen, B12 deficiency leads to an increase in immature RBCs that appear as large blast cells. Therefore, this type of anemia is called macrocytic or megaloblastic anemia.
Symptoms include fatigue and weakness, with reduced work capacity. Treatment is by giving vitamin B12 injections, or large oral doses (around 1mg) of vitamin B12.
Read: Types of Anemia
Autoimmune vasculitis
It occurs when the immune system attacks blood vessels. The resulting inflammation narrows the arteries and veins, and reduces blood flow through them. Symptoms include rashes (small red bleeding spots – purpura, lumps (nodules) or sores (ulcers) on the skin, headaches, visual changes, cough, shortness of breath, joint pains, general aches and pains, fatigue, weight loss, and numbness or weakness in the hand or foot.
It is treated with immunosuppressive medicines like corticosteroids, antimetabolites, JAK inhibitors and biologicals. Avacopan is a newly approved medication used to help treat ANCA-associated vasculitis (when anti-neutrophil cytoplasmic autoantibodies are found in blood). Plasmapheresis may be sometimes performed. When advanced forms of vasculitis cause significant damage to blood vessels, vascular bypass surgery may be performed to redirect the flow of blood around the damaged vessel. Damaged organs may need transplant surgery.
Kawasaki disease is an autoimmune vasculitis that causes inflammation in the walls of medium-sized arteries and is seen in children. The inflammation tends to affect the coronary (heart) arteries, as well as skin, and the mucous membranes inside the mouth, nose, and throat. Symptoms include high fever, rash on the body, irritability, joint pain, vomiting, and abdominal pain. It is treated with intravenous gamma globulin (IVIG) and aspirin.
Other Autoimmune Disorders.
Sometimes inflammation of the liver (hepatitis), and the bile ducts (primary biliary cholangitis) may have an autoimmune etiology.
Berger’s disease or IgA Nephropathy is also considered an autoimmune disease by some, and it occurs due to the build-up of the antibody called immunoglobulin A that damages the nephrons of the kidney (glomerulonephritis) and causes fluid accumulation in the body with loss of kidney function.
Polymyositis, is an inflammatory muscle disease, possibly of autoimmune etiology, that affects the muscles closest to the trunk of the body, leading to trouble rising from a sitting position, climbing stairs, or lifting objects. In some cases, muscles that are not close to the body’s trunk become affected as the disease progresses.
There are several other, rarer autoimmune diseases, and some other known conditions that are being speculated and further researched to have autoimmune causes.
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Reference: Autoimmune Diseases NIH
1 Comment
Useful article, thank you. Top article, very helpful.