Immunosuppression Health Dictionary

A combined vaccine o?ering protection against MEASLES, MUMPS and RUBELLA (German measles), it was introduced in the UK in 1988 and has now replaced the measles vaccine. The combined vaccine is o?ered to all infants in their second year; health authorities have an obligation to ensure that all children have received the vaccine by school entry – it should be given with the pre-school booster doses against DIPHTHERIA, TETANUS and POLIOMYELITIS, if not earlier – unless there is a valid contra-indication (such as partial immunosuppression), parental refusal, or evidence of previous infection. MMR vaccine may also be used in the control of measles outbreaks, if o?ered to susceptible children within three days of exposure to infection. The vaccine is e?ective and generally safe, though minor symptoms such as malaise, fever and rash may occur 5–10 days after immunisation. The incidence of all three diseases has dropped substantially since MMR was introduced in the UK and USA.

A researcher has suggested a link between the vaccine and AUTISM, but massive studies of children with and without this condition in several countries have failed to ?nd any evidence to back the claim. Nonetheless, the publicity war has been largely lost by the UK health departments so that vaccine rates have dropped to a worryingly low level.

(See IMMUNISATION.)... mmr vaccine

An agent that experimentally inhibits the proliferation and viability of infectious viruses. In our domain of herbal medicines, some plants will slow or inhibit the adsorption or random initial attachment of viruses, extend the lifespan of infected target cells, or speed up several aspects of immunity, including complement, antibody, and phagocytosis responses. Herbal antivirals work best on respiratory viruses such as influenza, adenoviruses, rhinoviruses, and the enteric echoviruses. Touted as useful in the alphabet group of slow viruses (HIV, EBV, CMV, etc.), they really help to limit secondary concurrent respiratory infections that often accompany immunosuppression.... antiviral

A CYTOTOXIC and an immunosuppressive drug (see IMMUNOSUPPRESSION). In the ?rst of these capacities it is proving to be of value in the treatment of acute leukaemia. As an immunosuppressive agent it reduces the antibody response of the body (see ANTIBODIES), and is thereby helping to facilitate the success of transplant operations (see TRANSPLANTATION) by reducing the chances of the transplanted organ (e.g. the kidney) being rejected by the body. Azathioprine is also proving to be of value in the treatment of AUTOIMMUNE DISORDERS.... azathioprine

(Cytomegalovirus) This subtle, worldwide microorganism is a member of the herpes virus group. It is large for a virus, contains DNA, and has a complex protein capsid. It forms latent, lifelong infections, and, except for occasional serious infections in infants and malnourished youngsters, seldom produced a disease state. With increased use of immunosuppression therapies for conditions ranging from arthritis to cancer to organ transplants, the incidence of adults with major infections of CMV increases yearly.... cmv

A large, ubiquitous, and normally benign, herpes-like virus with both DNA and capsid. It is sometimes implicated in mononucleosis and at least two types of lymphomas. Recently it has been become connected with the symptom picture called chronic fatigue syndrome (as has been CMV) and can produce many ill-defined (but subjectively distressful) symptoms, including fatigue, fevers of an unknown origin (FUO...love those acronyms!), and emotional lability. Immunosuppression, from whatever cause, allows the syndrome to occur. Many people in and out of medicine have come to regard it as both another form of Multiple Chemical Sensitivities (MCS, naturally) and a sequel to excessive medical use of immunosupressant anti­inflammatories.... epstein-barr virus

A small group of capsid-forming DNA viruses, sometimes divided into Type I (forming vesicles and blisters on the mouth, lips-generally above the waist) and Type II (usually sexually transmitted, with symptoms mostly below the waist). Both types form acute initial outbreaks, go dormant, reactivate, and so forth. For most folks, frequent outbreaks are clear signs of stress or immunosuppression. Both types are EQUALLY dangerous for infants.... herpes

Human immunodeficiency virus, the retrovirus that is at least partially responsible for AIDS. At this time it is not clear what other disorders besides AIDS may come from HIV infections. AIDS is a syndrome, partially (perhaps totally) produced by HIV. As with EBV, it is quite possible that the virus may cause only moderate immunosuppression in some people, while in others it will progress further to AIDS. the jury (all of them/us) is still out.... hiv

Sometimes described as thrombocytopenia, this is an autoimmune disorder in which blood PLATELETS are destroyed. This disturbs the blood’s coagulative properties (see COAGULATION) and spontaneous bleeding (PURPURA) occurs into the skin. The disease may be acute in children but most recover without treatment. Adults may develop a more serious, chronic variety which requires treatment with CORTICOSTEROIDS and sometimes SPLENECTOMY. Should the disease persist despite these treatments, intravenous immunoglobulin or immunosuppressive drugs (see IMMUNOSUPPRESSION) are worth trying. Should the bleeding be or become life-threatening, concentrates of platelets should be administered.... idiopathic thrombocytopenic purpura (itp)

A genus of gram-positive, acid-resistant bacteria in the Lactobacillaceae family. We know of lactobacillus because of its use in making yogurt and the conventional wisdom of taking it in one form or another after antibiotic therapy, but it is an integral part of the colon and mouth flora, and is the critical acidifying agent in vaginal flora. There is a growing body of rather ignored data showing the value of regular consumption of a lactobacillus-containing food in immunosuppression, slow virus, and candidiasis conditions.... lactobacillus

A neoplasia of the lymph tissue, such as Hodgkin’s Disease. Although it is frequently useful to stimulate immunity when a person is undergoing chemotherapy for cancer, since the resultant immunosuppression is a major side effect of the treatment, in lymphatic cancer this the POINT of the therapy...let it be.... lymphoma

Before the advent of small-bowel transplants, long-term intravenous feeding (total parenteral nutrition or TPN) was the last option for patients with chronic intestinal failure. Most recipients are children, and small-bowel transplantation is currently reserved for patients unable to continue on long-term parenteral nutrition. The main constraints to small-bowel transplantation are the intensity of rejection (necessitating high levels of immunosuppression), and the lack of donors who are the same size as the recipient (a particular problem for children).... small-bowel transplantantion

An IMMUNOSUPPRESSANT drug used for primary immunosuppression in recipients of kidney or liver transplants (see TRANSPLANTATION) where the natural rejection process has been resistant to conventional immunosuppression regimens such as CORTICOSTEROIDS, AZATHIOPRINE and CICLOSPORIN A. It is also used, with caution, in some severe cases of eczema (see DERMATITIS).... tacrolimus

a rare autoimmune illness with production of antibodies directed against the glomerular basement membrane (anti-GBM antibodies). Classically patients present with lung haemorrhage and a rapidly progressive glomerulonephritis. Most cases will respond to aggressive treatment with plasma exchange and immunosuppression. [E. W. Goodpasture (1886–1960), US pathologist]... goodpasture’s disease

In?uenza is an acute infectious disease, characterised by a sudden onset, fever and generalised aches and pains. It usually occurs in epidemics and pandemics (see EPIDEMIC; PANDEMIC).

Cause The disease is caused by a VIRUS of the in?uenza group. There are at least three types of in?uenza virus, known respectively as A, B and

C. One of their most characteristic features is that infection with one type provides no protection against another. Equally important is the ease with which the in?uenza virus can change its character. It is these two characteristics which explain why one attack of in?uenza provides little, if any, protection against a subsequent attack, and why it is so di?cult to prepare an e?ective vaccine against the disease.

Epidemics of in?uenza due to virus A occur in Britain at two- to four-year intervals, and outbreaks of virus B in?uenza in less frequent cycles. Virus A in?uenza, for instance, was the prevalent infection in 1949, 1951, 1955 and 1956, whilst virus B in?uenza was epidemic in 1946, 1950, 1954 and, along with virus A, in 1958–59. The pandemic of 1957, which swept most of the world, although fortunately not in a severe form, was due to a new variant of virus A

– the so-called Asian virus – and it has been suggested that it was this variant that was responsible for the pandemics of 1889 and 1918. Since 1957, variants of virus A have been the predominating causes of in?uenza, accompanied on occasions by virus B.

In 1997 and 2004, outbreaks of Chinese avian in?uenza caused alarm. The in?uenza virus had apparently jumped species from birds

– probably chickens – to infect some people. Because no vaccine is available, there was a risk that this might start an epidemic.

Symptoms The incubation period of in?uenza A and B is 2–3 three days, and the disease is characterised by a sudden onset. In most cases this is followed by a short, sharp febrile illness of 2–4 days’ duration, associated with headache, prostration, generalised aching, and respiratory symptoms. In many cases the respiratory symptoms are restricted to the upper respiratory tract, and consist of signs of irritation of the nose, pharynx and larynx. There may be nosebleeds, and a dry, hacking cough is often a prominent and troublesome symptom. The fever is usually remittent and the temperature seldom exceeds 39·4 °C (103 °F), tending to ?uctuate between 38·3 and 39·4 °C (101 and 103 °F).

The most serious complication is infection of the lungs. This infection is usually due to organisms other than the in?uenza virus, and is a complication which can have serious results in elderly people.

The very severe form of ’?u which tends to occur during pandemics – and which was so common during the 1918–19 pandemic – is characterised by the rapid onset of bronchopneumonia and severe prostration. Because of the toxic e?ect on the heart, there is a particularly marked form of CYANOSIS, known as heliotrope cyanosis.

Convalescence following in?uenza tends to be prolonged. Even after an attack of average severity there tends to be a period of weakness and depression.

Treatment Expert opinion is still divided as to the real value of in?uenza vaccine in preventing the disease. Part of the trouble is that there is little value in giving any vaccine until it is known which particular virus is causing the infection. As this varies from winter to winter, and as the protection given by vaccine does not exceed one year, it is obviously not worthwhile attempting to vaccinate the whole community. The general rule therefore is that, unless there is any evidence that a particularly virulent type of virus is responsible, only the most vulnerable should be immunised – such as children in boarding schools, elderly people, and people who suffer from chronic bronchitis or asthma, chronic heart disease, renal failure, diabetes mellitus or immunosuppression (see under separate entries). In the face of an epidemic, people in key positions, such as doctors, nurses and those concerned with public safety, transport and other public utilities, should be vaccinated.

For an uncomplicated attack of in?uenza, treatment is symptomatic: that is, rest in bed, ANALGESICS to relieve the pain, sedatives, and a light diet. A linctus is useful to sooth a troublesome cough. The best analgesics are ASPIRIN or PARACETAMOL. None of the sulphonamides or the known antibiotics has any e?ect on the in?uenza virus; on the other hand, should the lungs become infected, antibiotics should be given immediately, because such an infection is usually due to other organisms. If possible, a sample of sputum should be examined to determine which organisms are responsible for the lung infection. The choice of antibiotic then depends upon which antibiotic the organism is most sensitive to.... influenza

adj. describing patients in whom the immune response is reduced or defective due to *immunosuppression. Such patients are vulnerable to opportunistic infections.... immunocompromised

n. a *monoclonal antibody that acts against the protein CD20, located mainly on the surface of B lymphocytes; it is used in the treatment of many lymphomas and leukaemias, including non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. It is also licensed for the treatment of severe rheumatoid arthritis and *vasculitis. Side-effects include hypersensitivity reactions and immunosuppression.... rituximab

A serious disorder in which the chief symptoms are muscular weakness and a special tendency for fatigue to come on rapidly when e?orts are made. The prevalence is around 1 in 30,000. Two-thirds of the patients are women, in whom it develops in early adult life. In men it tends to develop later in life.

It is a classical example of an autoimmune disease (see AUTOIMMUNITY). The body develops ANTIBODIES which interfere with the working of the nerve endings in muscle that are acted on by ACETYLCHOLINE. It is acetylcholine that transmits the nerve impulses to muscles: if this transmission cannot be e?ected, as in myasthenia gravis, then the muscles are unable to contract. Not only the voluntary muscles, but those connected with the acts of swallowing, breathing, and the like, become progressively weaker. Rest and avoidance of undue exertion are necessary, and regular doses of neostigmine bromide, or pyridostigmine, at intervals enable the muscles to be used and in some cases have a curative e?ect. These drugs act by inhibiting the action of cholinesterase – an ENZYME produced in the body which destroys any excess of acetylcholine. In this way they increase the amount of available acetylcholine which compensates for the deleterious e?ect of antibodies on the nerve endings.

The THYMUS GLAND plays the major part in the cause of myasthenia gravis, possibly by being the source of the original acetylcholine receptors to which the antibodies are being formed. Thymectomy (removal of the thymus) is often used in the management of patients with myasthenia gravis. The incidence of remission following thymectomy increases with the number of years after the operation. Complete remission or substantial improvement can be expected in 80 per cent of patients.

The other important aspect in the management of patients with myasthenia gravis is IMMUNOSUPPRESSION. Drugs are now available that suppress antibody production and so reduce the concentration of antibodies to the acetylcholine receptor. The problem is that they not only suppress abnormal antibody production, but also suppress normal antibody production. The main groups of immunosuppressive drugs used in myasthenia gravis are the CORTICOSTEROIDS and AZATHIOPRINE. Improvement following steroids may take several weeks and an initial deterioration is often found during the ?rst week or ten days of treatment. Azathioprine is also e?ective in producing clinical improvement and reducing the antibodies to acetylcholine receptors. These effects occur more slowly than with steroids, and the mean time for an azathioprine remission is nine months.

The Myasthenia Gravis Association, which provides advice and help to sufferers, was created and is supported by myasthenics, their families and friends.... myasthenia gravis

A rare but serious type of anaemia in which the red cells, white cells, and platelets in the blood are all reduced in number. Aplastic anaemia is caused by a failure of the bone marrow to produce stem cells, the initial form of all blood cells.

Treatment of cancer with radiotherapy or anticancer drugs can temporarily interfere with the cell-producing ability of bone marrow, as can certain viral infections and other drugs. Long-term exposure to insecticides or benzene fumes may cause more persistent aplastic anaemia, and a moderate to high dose of nuclear radiation is another recognized cause. An autoimmune disorder is responsible in about half of all cases. Aplastic anaemia sometimes develops for no known reason.

A low level of red blood cells may cause symptoms common to all types of anaemia, such as fatigue and breathlessness. White-cell deficiency increases susceptibility to infections; platelet deficiency may lead to a tendency to bruise easily, bleeding gums, and nosebleeds.

The disorder is usually suspected from blood-test results, particularly a blood count, and is confirmed by a bone marrow biopsy.

Blood and platelet transfusions can control symptoms.

Immunosuppression is used to treat anaemia due to an autoimmune process.

Severe persistent aplastic anaemia may be fatal unless a bone marrow transplant is carried out.... anaemia, aplastic

been recognised from earliest times. Evidence of the condition has been found in Egyptian mummies; in the fourth century BC Hippocrates, the Greek physician, called it phthisis because of the lung involvement; and in 1882 Koch announced the discovery of the causative organism, the tubercle bacillus or Mycobacterium tuberculosis.

The symptoms depend upon the site of the infection. General symptoms such as fever, weight loss and night sweats are common. In the most common form of pulmonary tuberculosis, cough and blood-stained sputum (haemoptysis) are common symptoms.

The route of infection is most often by inhalation, although it can be by ingestion of products such as infected milk. The results of contact depend upon the extent of the exposure and the susceptibility of the individual. Around 30 per cent of those closely exposed to the organism will be infected, but most will contain the infection with no signi?cant clinical illness and only a minority will go on to develop clinical disease. Around 5 per cent of those infected will develop post-primary disease over the next two or three years. The rest are at risk of reactivation of the disease later, particularly if their resistance is reduced by associated disease, poor nutrition or immunosuppression. In developed countries around 5 per cent of those infected will reactivate their healed tuberculosis into a clinical problem.

Immunosuppressed patients such as those infected with HIV are at much greater risk of developing clinical tuberculosis on primary contact or from reactivation. This is a particular problem in many developing countries, where there is a high incidence of both HIV and tuberculosis.

Diagnosis This depends upon identi?cation of mycobacteria on direct staining of sputum or other secretions or tissue, and upon culture of the organism. Culture takes 4–6 weeks but is necessary for di?erentiation from other non-tuberculous mycobacteria and for drug-sensitivity testing. Newer techniques involving DNA ampli?cation by polymerase chain reaction (PCR) can detect small numbers of organisms and help with earlier diagnosis.

Treatment This can be preventative or curative. Important elements of prevention are adequate nutrition and social conditions, BCG vaccination (see IMMUNISATION), an adequate public-health programme for contact tracing, and chemoprophylaxis. Radiological screening with mass miniature radiography is no longer used.

Vaccination with an attenuated organism (BCG – Bacillus Calmette Guerin) is used in the United Kingdom and some other countries at 12–13 years, or earlier in high-risk groups. Some studies show 80 per cent protection against tuberculosis for ten years after vaccination.

Cases of open tuberculosis need to be identi?ed; their close contacts should be reviewed for evidence of disease. Adequate antibiotic chemotherapy removes the infective risk after around two weeks of treatment. Chemoprophylaxis – the use of antituberculous therapy in those without clinical disease – may be used in contacts who develop a strong reaction on tuberculin skin testing or those at high risk because of associated disease.

The major principles of antibiotic chemotherapy for tuberculosis are that a combination of drugs needs to be used, and that treatment needs to be continued for a prolonged period – usually six months. Use of single agents or interrupted courses leads to the development of drug resistance. Serious outbreaks of multiply resistant Mycobacterium tuberculosis have been seen mainly in AIDS units, where patients have greater susceptibility to the disease, but also in developing countries where maintenance of appropriate antibacterial therapy for six months or more can be di?cult.

Streptomycin was the ?rst useful agent identi?ed in 1944. The four drugs used most often now are RIFAMPICIN, ISONIAZID, PYRAZINAMIDE and ETHAMBUTOL. Three to four agents are used for the ?rst two months; then, when sensitivities are known and clinical response observed, two drugs, most often rifampicin and isoniazid, are continued for the rest of the course. Treatment is taken daily, although thrice-weekly, directly observed therapy is used when there is doubt about the patient’s compliance. All the antituberculous agents have a range of adverse effects that need to be monitored during treatment. Provided that the treatment is prescribed and taken appropriately, response to treatment is very good with cure of disease and very low relapse rates.... nature of the disease tuberculosis has

Transplantation of tissues or organs of the body are de?ned as an allotransplant, if from another person; an autotransplant, if from the patient him or herself – for example, a skin graft (see GRAFT; SKIN-GRAFTING); and a xenotransplant, if from an animal.

The pioneering success was achieved with transplantation of the kidney in the 1970s; this has been most successful when the transplanted kidney has come from an identical twin. Less successful have been live transplants from other blood relatives, while least successful have been transplants from other live donors and cadaver donors. The results, however, are steadily improving. Thus the one-year functional survival of kidneys transplanted from unrelated dead donors has risen from around 50 per cent to over 80 per cent, and survival rates of 80 per cent after three years are not uncommon. For a well-matched transplant from a live related donor, the survival rate after ?ve years is around 90 per cent. And, of course, if a transplanted kidney fails to function, the patient can always be switched on to some form of DIALYSIS. In the United Kingdom the supply of cadaveric (dead) kidneys for transplantation is only about half that necessary to meet the demand.

Other organs that have been transplanted with increasing success are the heart, the lungs, the liver, bone marrow, and the cornea of the eye. Heart, lung, liver and pancreas transplantations are now carried out in specialist centres. It is estimated that in the United Kingdom, approximately 200 patients a year between the ages of 15 and 55 would bene?t from a liver transplant if an adequate number of donors were available. More than 100 liver transplants are carried out annually in the United Kingdom and one-year-survival rates of up to 80 per cent have been achieved.

The major outstanding problem is how to prevent the recipient’s body from rejecting and destroying the transplanted organ. Such rejection is part of the normal protective mechanism of the body (see IMMUNITY). Good progress has been made in techniques of tissue-typing and immunosuppression to overcome the problem. Drugs are now available that can suppress the immune reactions of the recipient, which are responsible for the rejection of the transplanted organ. Notable among these are CICLOSPORIN A, which revolutionised the success rate, and TACROLIMUS, a macrolide immunosuppressant.

Another promising development is antilymphocytic serum (ALS), which reduces the activity of the lymphocytes (see LYMPHOCYTE) cells which play an important part in maintaining the integrity of the body against foreign bodies.

Donor cards are now available in all general practitioners’ surgeries and pharmacies but, of the millions of cards distributed since 1972, too few have been used. The reasons are complex but include the reluctance of the public and doctors to consider organ donation; poor organisation for recovery of donor kidneys; and worries about the diagnosis of death. A code of practice for procedures relating to the removal of organs for transplantation was produced in 1978, and this code has been revised in the light of further views expressed by the Conference of Medical Royal Colleges and Faculties of the United Kingdom on the Diagnosis of Brain Death. Under the Human Tissue Act 1961, only the person lawfully in possession of the body or his or her designate can authorise the removal of organs from a body. This authorisation may be given orally.

Patients who may become suitable donors after death are those who have suffered severe and irreversible brain damage – since such patients will be dependent upon arti?cial ventilation. Patients with malignant disease or systemic infection, and patients with renal disease, including chronic hypertension, are unsuitable.

If a patient carries a signed donor card or has otherwise recorded his or her wishes, there is no legal requirement to establish lack of objection on the part of relatives – although it is good practice to take account of the views of close relatives. If a relative objects, despite the known request by the patient, sta? will need to judge, according to the circumstances of the case, whether it is wise to proceed with organ removal. If a patient who has died is not known to have requested that his or her organs be removed for transplantation after death, the designated person may only authorise the removal if, having made such reasonable enquiry as may be practical, he or she has no reason to believe (a) that the deceased had expressed an objection to his or her body being so dealt with after death, or (b) that the surviving spouse or any surviving relative of the deceased objects to the body being so dealt with. Sta? will need to decide who is best quali?ed to approach the relatives. This should be someone with appropriate experience who is aware how much the relative already knows about the patient’s condition. Relatives should not normally be approached before death has occurred, but sometimes a relative approaches the hospital sta? and suggests some time in advance that the patient’s organs might be used for transplantation after death. The sta? of hospitals and organ exchange organisations must respect the wishes of the donor, the recipient and their families with respect to anonymity.

Relatives who enquire should be told that some post-mortem treatment of the donor’s body will be necessary if the organs are to be removed in good condition. It is ethical (see ETHICS) to maintain arti?cial ventilation and heartbeat until removal of organs has been completed. This is essential in the case of heart and liver transplants, and many doctors think it is desirable when removing kidneys. O?cial criteria have been issued in Britain to recognise when BRAIN-STEM DEATH has occurred. This is an important protection for patients and relatives when someone with a terminal condition

– usually as a result of an accident – is considered as a possible organ donor.... transplantation