Systemic as well as organ-localised immuno-inflammatory diseases (including autoimmune disease) are an important cause of morbidity and mortality. They occur in approximately 5-7% of the population, mainly striking young women in the reproductive age. Most of them are chronic conditions characterised by remissions and exacerbation.
The immune system is capable of marshalling highly potent effector mechanisms for eliminating foreign antigens. A short burst of such activity is usually adequate to eliminate foreign antigens with minimal tissue damage. Only minor discomfort may occur that includes transient malaise, fever and signs of local inflammatory swelling at the site of foreign antigen along with tender enlargement of the draining lymph nodes. However, if immune response fails to eliminate the pathogen, it becomes chronic and persistent. Chronic immune response causes a persistent inflammatory reaction that is called immuno-inflammatory or hypersensitivity diseases.
Clinically, immune inflammation is characterised by constitutional symptoms consisting of fever, usually low grade, night sweats, loss of weight and appetite, fatigue and malaise. The associated laboratory abnormalities include high erythrocyte sedimentation rate (usually > 50 mm in 1st hour), high platelet count (> 400,000/ mm3), anaemia of chronic inflammation, high C-reactive protein, increase in total serum globulins associated with a fall in serum albumin level. Usually, there is also a mild elevation of serum alkaline phosphatase level. The best example of this situation is the failure of immune response to eliminate tubercle bacilli. This leads to a chronic persistent immune reaction accompanied by severe constitutional symptoms (referred as tuberculo-toxaemia) and laboratory features of chronic persistent inflammation.
Situations that may lead to immuno-inflammatory tissue damage may be summed up as:
- Immune inflammation due to chronic persistence of antigen. The antigen may persist when
- It is intrinsically (relatively) resistant to immune elimination (e.g. tubercle and lepra bacilli).
- Immune response is weak due to either a genetic or an acquired defect (e.g. immunodeficiencies including immunoglobulin and their subclass deficiencies, complement deficiencies, defective macrophage-monocyte system, Fc- and C3b- receptor defects, etc.)
- Inappropriate immune response: Immune response against ubiquitous environmental antigens : food items, clothing, dust, pollens, feathers, animal dander, insect particles, common chemicals of day-to-day use, etc.
- Self antigens.
- Transplanted organs or transfused blood.
The types of hypersensitivity mechanisms can also be classified according to time course. Thus, type I reaction is often called immediate hypersensitivity. The term subacute hypersensitivity has been used for types II and III reactions. Type IV hypersensitivity is called delayed or delayed-type hypersensitivity.
- Auto Sensitivity (autoimmune) diseases.
- Allo Sensitivity diseases.
- Xenosensitivity (heterosensitivity) diseases.
- Spectrum of autoimmune diseases
- Hashimoto’s thyroiditis
- Primary myxoedema
- Pernicious anaemia
- Autoimmune atrophic gastritis
- Addison’s disease
- Premature menopause (few cases)
- Insulin-dependent diabetes mellitus
- Goodpasture’s syndrome
- Myasthenia gravis
- Male infertility (few cases)
- Pemphigus vulgaris
- Sympathetic ophthalmia
- Phacogenic uveitis
- Multiple sclerosis
- Autoimmune haemolytic anaemia
- Idiopathic thrombocytopenic purpura
- Idiopathic leukopenia
- Primary biliary cirrhosis
- Chronic hepatitis (HBsAg-negative)
- Cryptogenic cirrhosis (some cases)
- Ulcerative colitis
- Sjogren’s syndrome
- Rheumatoid arthritis
- Mixed connective tissue disease
- Discoid lupus erythematosus Non-organ-specific Systemic lupus erythematosus.
Chronic thyroiditis or autoimmune thyroiditis (Hashimoto’s thyroiditis):
Chronic thyroiditis commonly affects the age group 35-45 years. It is 10-15 times more frequent in females than in males. The incidence of chronic thyroiditis is reported as high in southern India and may form up to 30% of patients attending thyroid clinics.
The patient has a goitrous swelling, characteristically defined as firm or of rubbery consistency. There may be asymmetrical enlargement or rarely nodularity of the gland. The Dalphian node may also be palpable.
Histologically, there is marked lymphocytic infiltration to the extent of formation of germinal centres. Askanazy cells are present. Acini are disrupted and a variable degree of fibrosis is observed depending on the duration of the pathological process. Finally, atrophy of the gland sets in.
The thyroid functional status is variable, though earlier it was considered that hypothyroidism is a sine qua non of Hashimoto’s thyroiditis.
The initial presentation of Hashimoto’s thyroiditis may be with frank symptoms of thyrotoxicosis. Up to 50% of patients with Hashimoto’s thyroiditis may be in a euthyroid state. Over the years, hypothyroidism supervenes and this proportion increases to include all atrophic or idiopathic hypothyroidism in this category. Serological tests are the hallmark for the diagnosis of chronic autoimmune thyroiditis. Microsomal antibody titre is very high (1:160,000); similarly, antithyroglobulin antibodies are present. IgG levels may be high. In about 10%, anti-nuclear factor (ANF) is also observed, chronic autoimmune thyroiditis being part of a systemic autoimmune involvement.
Thyroid 131 uptake may be low (acute autoimmune response or atrophic gland), normal or high. The thyroid scan shows a patchy uptake.
In an effort to suppress TSH and reduce the goitre size and immune response, patients of chronic autoimmune thyroiditis are prescribed thyroxine. TSH is monitored during maintenance therapy.
Pernicious anaemia (Megaloblastic anaemia):
Pernicious anaemia is a condition in which the body does not make enough red blood cells due to a lack of vitamin B12 in the body. It usually occurs in people whose bodies have lost the ability to absorb vitamin B12 from food.
In pernicious anaemia, the blood cells do not divide normally and are too large. They have trouble getting out of the bone marrow. The problem is due to a lack of vitamin B12 in the body. Vitamin B12 is one of the B vitamins; B vitamins are found in animal foods such as meat, fish, eggs, milk, and other dairy products. Vitamin B12 is necessary for the body to make red blood cells. It is also needed for the normal working of the nervous system.
Myasthenia gravis is an immunologically mediated disorder affecting neuromuscular transmission. It is characterised by fluctuating weakness of voluntary muscles worsened by repetitive use, with a tendency to recovery after a period of inactivity and with anticholinesterase drugs.
Multiple sclerosis (MS), though rare in India and other countries of Asia and Africa, is extremely common in the West. The disease affects young individuals, has a prolonged course and causes disability at the prime of life; its aetiology is still unknown.
Scleroderma (Systemic sclerosis):
Systemic sclerosis is a chronic systemic disorder of unknown etiology. Systemic sclerosis is characterized by thickening of the skin (scleroderma) and distinctive involvement of multiple internal organs, most notably the lungs, gastrointestinal tract, heart, and kidneys. The early stage of the disease, associated with prominent inflammatory features, is followed by the development of widespread functional and structural alterations in multiple vascular beds and progressive visceral organ dysfunction due to fibrosis (i.e excessive formation of fibrous connective tissue). The presence of thickened skin (scleroderma) distinguishes Systemic sclerosis from other connective tissue diseases.