Measles, Mumps and Rubella

What are vaccines?

Vaccines provide long term protection against a disease. Thanks to vaccines, we have been able to eradicate many life threatening diseases from our society. They work by introducing weakened (attenuated) or dead forms a a pathogen, a live form of a milder pathogen or a preparation of the toxins or antibodies of a pathogen. This triggers an immune response and the body produces antibodies (proteins produced by white blood cells) specific to the antigens that coat the pathogen. these antibodies can then neutralise the pathogen by attaching to white blood cells, allowing them to engulf the pathogen by phagocytosis; or bind to many pathogens, preventing them from entering and so infecting body cells. This response also creates memory cells which stay in the blood (as antibodies do not) so that the next time the pathogen is detected the body can mount a faster immune response. Some vaccines require regular boosters (e.g. tetanus boosters every 10 years) in order to maintain the levels of these memory cells in the blood.

Vaccination programmes can either involve ring vaccination, where the inhabitants of the region where a disease outbreak occurs are all vaccinated so that the disease cannot spread and is isolated (this method was used to control the outbreak of Aphthae epizooticae/foot-and-mouth disease in 2001), or herd vaccination, where the majority of the population is vaccinated so enough people are protected and so cannot carry the disease (usually this means over 85% but is dependent on the disease, e.g. measles requires up to 94%).

Measles

Measles is a disease caused by a virus and is highly infectious, it is spread through droplets in coughs and sneezes. Measles is common in children between 1 and 4 years old. Measles is characterised by an itchy and spotty rash starting behind the ears and spreading over the face and then body with a red-brown colour. The rash is often preceded by red -eyes, cough, fever and white spots inside the mouth. Adults are more likely to have severe complications when they develop measles, these can include diarrohea, pneumonia (1 in 20 child measles cases), severe ear infection and deafness, encephalitis (swelling of the brain which can cause seizures), it can also cause miscarriages and low birth-weight babies of infected women.Rarely people with childhood measles can go on to develop subacute sclerosing panencephalitis (or, less of a mouthful, SSPE) around 7 years after infection which is a degenerative disease of the nervous system and leads to changes in personality, muscle spasms and mental deterioration.

Mumps


Mumps is again a viral infection and is spread in the same way as measles, colds and flu. Mumps causes swelling of the parotid (saliva) glands, causing pain and difficulty swallowing. people with mumps also often have headaches, fever and joint pain. Complications of mumps include: if caught around puberty the painful swelling of the testicles in males or the ovaries and/or breasts in females which can lead to fertility problems in the future; deafness; and the swelling of the brain (encephalitis) and/or spinal cord (meningitis) which if untreated, can go on to cause severe neurological damage.

Rubella

Rubella (or German Measles) is a viral infection, spread by droplets, and often has a two week lag period before symptoms manifest, with sufferers becoming infectious, a week after catching the disease. Rubella has a characteristic red skin rash which lasts several days, as well as swollen glands, fever and runny nose.Rubella is particularly dangerous if caught by pregnant women in the first 16 weeks of pregnancy, as can cause birth defects in the developing baby such as cataracts, deafness, heart defects, brain damage and liver and spleen damage, together these problems are known as congenital rubella syndrome (CRS).

The MMR vaccine

In 1988 a vaccine was developed against Measles, mumps and rubella, known as the MMR vaccine. The vaccine contains attenuated forms of the measles mumps and rubella viruses and is given as a single injection into the arm or thigh. It is administed to babies aged between 12 and 13 months and a booster is given before starting primary school in the hope of providing herd immunity to the entire population. The three-in-one injection minimises the risk of children developing any of the illnesses in the time between separate jabs.  Due to the effects of rubella on pregnant women, non vaccinated women hoping to get pregnant are also given the vaccine.The vaccine provide lifelong immunity and thanks to the vaccine, levels of all three disease fell to an all time low.

Side affects of the injection include: after a week of vaccination, a mild form of measles that lasts for 2 or 3 days and usually includes a rash and fever; after a month of vaccination, a mild form of mumps that again lasts around 2 days and includes swollen glands; stiff and swollen joints of adult women who take the vaccine to protect against rubella; very rarely bruise-like spots may appear this is known as idiopathic thrombocytopenic purpura (ITP) which is linked to the rubella vaccine, however, ITP is far more common in people who catch live forms of measles or rubella that from the vaccine, and there is treatment for the disease. Some children have an allergic reaction immediately after the vaccine, however medical staff who give vaccines are trained to deal with this and can ensure quick treatment of the reaction. People who have been vaccinated with MMR are unable to infect others with any of the diseases.

In 1988 a study was published linking the MMR vaccine to autism and bowel disease, these findings based on the study of a sample of 12 children has since been discredited and recent studies have shown that there is no link between the vaccine and the conditions. There was also worry about the fact that a three-in-one vaccine would put too much strain on a child's immune system. Unfortunately, the study put parents in a very difficult situation as the claims were spread by the media and so many were insure whether to vaccinate their children. This has left an estimated 2 million people at risk from the diseases and the current epidemic in Swansea has seen a man dead due to measles.

http://www.nhs.uk/Conditions/vaccinations/Pages/mmr-vaccine.aspx
http://www.cdc.gov/measles/
http://www.cdc.gov/mumps/
http://www.cdc.gov/rubella/
http://news.bbc.co.uk/1/hi/health/1808956.stm

Atopic dermatitis, what is eczema all about?

Atopic dermatitis or eczema is an inflammatory skin disease which often occurs in the skin creases (backs of knees, elbow creases, armpits, neck and on the face). Atopic dermatitis is characterised by itchy, red, dry and/or cracked skin eruptions. It is a chronic (long-term) condition that is not contagious, but the a tendency to have the condition is genetic .The condition affects males and females equally, affecting 15-20% of school children and 2-3% of adults in the UK as around 65% of cases clear up by age 16. Prevalence of atopic dermatitis symptoms has increased over the last ten years, perhaps due to the increased use of soaps, detergents and frequency of bathing as well as better diagnosis and more awareness.

The symptoms of atopic dermatitis can vary depending on severity of the condition, mild eczema often involves small areas of dry skin that are often itchy. Eczema in the skin creases is said to have a flexural pattern, but other visual symptoms include coin sized areas of inflammation/rash (a discoid pattern) or bumps of inflammation in hair follicles (follicular pattern). Peaks of severity of symptoms are known as flare-ups and skin often becomes very itchy, hot, red and inflamed; because of scratching the skin can bleed or weep and become swollen; skin is also susceptible to staphylococcus aureus infection and impetigo. Repeated scratching can lead to lichenification where the skin is hard and even itchier.

Suffers of atopic dermatitis have a decreased barrier function of the skin, the largest organ of the body, which has the normal role to protect the internal organs of the body from infection and toxins. The loss of this function causes an exacerbation of the Th2 allergic immune response and changes to the lipids (fats) and so the loss of water from the skin tissue. This change is due to abnormal filaggrin expression, filaggrin is a protein which binds to keratin fibres in epidermal (the top layer of skin) cells and encourages the activities of lipid producing enzymes. Filaggrin affects the keratinocytes (skin cells), making them flatten and so affects the amounts of lipid surrounding the cells and how tightly  packed the cells are together (this can also be caused by changes in skin pH (acidity) which is linked to filaggrin expression). This increases the permeability of the skin and increases the number of allergens and pathogens that can penetrate the skin. The inflammation in eczema is due to an allergic response of immune cells, T-lymphocytes (white blood cells). By allowing more allergens into the skin a more severe response occurs and by allowing more pathogens, there is an infection risk and also more immune cells migrate to the skin, so again reactions are severe.  Scratching the skin also attracts neutrophils another type of immune cell which secretes a lipid called leukotriene B4, triggering T-lymphocytes and cause inflammation (blocking the production of this lipid or the immune cell receptors can prevent the development of an eczema reaction in mice).

The loss of the skin barrier function is thought to be due to problems in the gene for Ctip2, which is responsible for controlling synthesis of lipid in the skin and suppresses a protein called TSLP which triggers inflammation, when the gene is faulty, it could lead to skin complaints such as atopic dermatitis.

Th2 cells are a type of T lymphocyte involved in allergic reactions and produces IgE antibodies which cause redness and itching (as well as inhibiting TH1 cells). Scratching damages skin cells opening them up to infection and causing them to secrete chemical messengers encouraging Th2 cells to migrate to the area and cause inflammation. Our immune system develops in the first 6 months of life, and this is when atopic dermatitis symptoms usually manifest, in some people there is an imbalance of Th1 (immunity against infection) and Th2 (immunity against allergens and parasites) cells. People with atopic dermatitis often have Th2 dominance whereas those with TH1 dominance suffer from diseases such as rheumatoid arthritis, MS and Type 1 Diabetes. Due to this TH2 dominance, people with atopic dermatitis are also likely to have asthma, hay fever and allergic rhinitis, however, some people believe that through eczema and so being exposed to allergens that get into the skin is actually what causes sensitivity and lead to these conditions.

Atopic dermatitis flare ups can be caused by many factors. Rough clothing, dry weather, soaps and detergents may irritate the skin; dust, pet hair and pollen may trigger allergic reactions, as might food allergens such as nuts or dairy products. Exercise or hot weather can cause problems due to sweat in the area where eczema is most common. Stress is known to be a trigger of eczema, as are hormonal changes in women, especially in pregnancy (around half of pregnant women who suffer from atopic dermatitis feel their symptoms worsen). Environmental factors such as changes in the seasons and hard/soft water can cause changes to the skin and affect atopic dermatitis.

For people with atopic dermatitis, psychological support may be needed, for people with severe skin irritation, especially in visible areas. In children bullying is a common problem for people with eczema as are self-confidence problems associated with poor self image. In addition, the itchiness of atopic dermatitis can often interfere with sleep which affects concentration and mood; this can have an impact on a child’s school performance, which again can lead to self-confidence issues.

One of the first steps in treating atopic dermatitis is to have a skin test and blood tests, to identify any particular allergies and so plan preventative measures (e.g. I am allergic to grass pollen, so stay inside when grass has been recently mowed). As well as avoiding triggers there are other things that can be done at home, keeping nails short to prevent scratching that can lead to infection, wearing loose fitting clothing of soft fabric, keeping the house free from dust mites and avoiding strong detergents.

Treatment includes emollients which are important in keeping skin moist and can be used liberally all the time (if skin is very dry, should be used every 2/3 hours). Emollients provide a protective film over the skin, this prevents water loss. Emollients are often used after bathing to retain the moisture of the skin. There are many types of emollient, some can be brought over the counter and other prescribed, there are some emollients which can be used a soap substitutes and others to add to bath water. Emollients should be used throughout the year, not only during flare ups, but can over time become ineffective. Emollients should not be shared with other and should have applicators or a pump dispenser in order to minimise infection. During a flare up, emollients should be used very frequently, alongside anti-inflammatory treatment.

When skin is inflamed, topical corticosteroids can be applied directly to the skin; however different strengths may need to be applied to different areas of the body (i.e. milder treatment for the face and strong ointments for flare ups). This treatment should not be used for more than several weeks (a sign that stronger treatment may be needed) and used a maximum of twice daily (applied half an hour after applying emollient to the affected area). Corticosteroids are measured in fingertip units (see below) which, as they must be spread thinly, can cover a large area of skin. When applied, they can often sting or burn and are not suitable for long term treatment as can have side effects such as thinning of the skin (especially around creases), acne, increased visibility of blood vessels (in particular the cheeks) and increased hair growth on the skin.

Other treatments include antihistamines which can reduce the itching associated with atopic dermatitis as they prevent the release of histamine which triggers allergic responses when in contact with allergens, some antihistamines are sedating and cause drowsiness, these are for short term use only and people should not drive or operate heavy machinery when on this treatment. Similarly topical immunosuppressants reduce the immune response to a particular area. For severe flare-ups, oral corticosteroids can be prescribed to reduce inflammation (these also are used to treat asthma). The course of treatment is about two weeks long, one tablet a day. This medication can have severe side effects if used for an extended period of time, such as hypertension (high blood pressure), osteoporosis (easily broken bones), fluid retention (and so swollen ankles/legs) and in children can affect their growth. To prevent scratching and allow the skin to heal, medicated dressings (which also prevent itchiness) are used but only on uninfected skin. If the skin becomes infected usually antibiotic treatment is prescribed, this is usually tablets, but could involve antibiotic creams applied to the infected area. If infected with herpes simplex virus (which causes cold sores) antiviral treatment will be given. In the long term, people prone to infection use antiseptic creams, as antibiotic treatment could lead to resistance. Dermatologists could also offer phototherapy which involves ultraviolet light to treat the affected area.

There is currently no cure for eczema, however new studies into the genetics behind skin problems could lead to epigenetic cures in the future and there are many treatments that can alleviate or control the symptoms. In the majority of cases, children ‘grow out’ of eczema and their symptoms subside naturally in their teenage years.

http://www.nhs.uk/Conditions/Eczema-(atopic)/Pages/Introduction.aspx

http://www.sciencedaily.com/search/?keyword=atopic+eczema

http://www.britishskinfoundation.org.uk/SkinInformation/AtoZofSkindisease/Eczema.aspx

Multiple Myeloma

Myeloma or Multiple myeloma is a type of blood cancer; it affects the plasma cells which are made in your bone marrow.  Myeloma patients make up about 1% of cancer patients in the UK. Myeloma does not exist as a lump like other cancers, but divides within the bone marrow, often replacing the bone marrow cells. It is known as multiple myeloma as it often occurs in more than one area in the body.

Myeloma cancerous cells take the place of important stem cells which are present in the bone marrow. The bone marrow is the factory that makes all of your blood cells, the red blood cells (erythrocytes) which carry oxygen and carbon dioxide around the body, the platelets (thrombocytes) which are involved in clotting and the white blood cells (leucocytes) which help you fight infection. The cells at severely damaged by myeloma would normally go on to become a type white blood cells called plasma cells (originally ß-lymphocytes)which produce proteins known as antibodies to fight infection.

Myeloma occurs due to a genetic mutation in cells, these cells bind to others in the bone marrow (called stromal cells).  This causes the stromal cells to produce a cytokine (chemical messengers) called IL-6 this leads to the uncontrolled growth of the myeloma cells. The cells over-activate osteoclasts which break down the bone and produce growth factors which allow new blood vessels to be made (a process known as angiogenesis) to bring nutrients to the affected region.

Antibodies or immunoglobulins are proteins which are released in the immune response and are specific to the antigens (cell markers) present in disease causing micro-organisms. In myeloma, instead of antibodies, the damaged cells produce paraproteins, which have no use in fighting infection but can thicken the blood and take the place of infection fighting molecules (so reduce immunity).

Myeloma normally occurs in the skull, pelvis, ribs, shoulders and spine (where it can cause spinal cord compression and tingling/numbness of limbs). Some symptoms of myeloma include bone pain, fatigue, bone fractures, anaemia (reduction in oxygen carrying capacity of the blood), hypercalcaemia (excess calcium in the blood as is released by affected bones, could lead to problems with the heart and have an effect on behavior/personality). People with myeloma can also sustain kidney damages
due to paraproteins or a build up of calcium blocking the narrow tubes that are used by the kidneys to filter the blood of toxic waste products, increased fluid intake can help to alleviate these problems. People with myeloma are also very susceptible to infection due the problems with the white blood cells which stimulate an immune response (people on cancer treatments such as chemotherapy are also immunosuppressed so are at a high risk of infection)

Myeloma is a fairly rare disease, and has quite general symptoms which can be associated with other illness. Blood tests showing a low blood count (though this is indicative of several blood conditions) abnormal antibodies/proteins (using a serum protein electrophoresis test and testing immunoglobulin levels), high calcium levels are indicators of myeloma as well as urine tests with paraproteins present. Bone marrow biopsy tests (which are quite painful) are usually used to confirm myeloma if there are too many plasma cells and myeloma cells present.

Treating myeloma involves removing the cancerous cells and treating the symptoms caused by myeloma. Myeloma is not yet curable and will often reoccur several times. All myeloma patients begin with induction treatment of a combination of three myeloma drugs. Suitable patients may go on to have intensive treatment such as high-dose chemotherapy and stem cell transplants, but for some patients, this could be too toxic or dangerous.

Induction treatment includes a chemotherapy drug, a steroid and one of  thalidomide or bortezomib. Chemotherapy drugs include melphalan and cyclophosphamide which are given orally; these
medications are generally well tolerated by patients but side effects include hair loss (due to the effect on dividing cells such as the myeloma cells but also hair and nail cells), nausea and infection. The role of steroids is not entirely clear, but they appear to prevent new myeloma cells from growing and the success of treatment improves the longer steroid treatment continues. Dexamethasone and prednisolone are steroids often used and are usually given orally. Side effects of steroids include indigestion, difficulty sleeping and water retention (so swollen ankles and feet). Bortezomib is a brand new class of anti-cancer medication known as proteasome inhibitors (this means it blocks the

action of a protein called proteasome which removes waste products and recycles others, including cyclins which need to be destroyed in order for the cell to continue to divide) this causes the death of the myeloma cells. Associated side effects include nausea, diarrhoea and fatigue. Thalidomide is a drug usually associated with the birth defects it can cause (discovered when it was prescribed as a drug to act against morning sickness in pregnant women) However, the drug is effective in killing myeloma cells, by preventing the angiogenesis which therefore prevents the development of a blood (and therefore nutrient) supply to the cancerous cells. Thalidomide comes in tablet form and should be taken with food. Obviously, the drug cannot be given to pregnant women and those of a child bearing age should ensure that they use effective contraceptives if on the medication and if not, should also avoid contact with the medication.  Thalidomide can increase the chance of blood clots; so many patients may need to take warfarin to thin their blood. Other side effects include headaches, constipation, skin rashes and numbness in hands and feet.

Intensive treatment includes high-doses of chemotherapy drugs to destroy more myeloma cells, however this can destroy healthy bone marrow severely affecting immunity. To improve this, healthy bone marrow stem cells are transplanted into the patient. These stem cells usually come from the patient (although may come from siblings or even unrelated donors). This treatment requires hospital admittance and a recovery period of several months, so is not recommended for older/frailer patients.

Radiotherapy can be used to treat the cancer by using targeted high-energy radiation. Myeloma is considered to be particularly responsive to radiotherapy. Whole body irradiation can be used for advance myeloma in just two sessions (one session for the top half another for the bottom), but some can be lengthy treatment over several weeks Monday to Friday. It can also relieve bone pain when targeted at weak areas, by reducing the number of cancerous cells, so allowing the bones to repair themselves. Often only one or two radiotherapy sessions are needed to reduce the pain. Radiotherapy can cause nausea and fatigue.

As bone pain is a common symptom of myeloma, patients are likely to be prescribed painkillers; however anti-inflammatory drugs (like ibuprofen) can further damage the kidneys of people with myeloma. Biophosphonates can be given to strengthen bones, reduce hypercalcaemia and reduce bone pain. These drugs can be taken via an IV drip once a month (which lasts 15 minutes to several hours depending on the drug) or in tablet form (which need to be taken more regularly. On this treatment you should drink lots of water in order to remove calcium from the blood. Currently these drugs are undergoing research into their ability to treat myeloma itself. Spinal cord compression can be treated with radiotherapy and steroids are used to reduce the pressure on the spine, though surgery may be needed. This surgery could involve percutaneous vertebroplasty where a ‘cement’ is injected into the vertebrae to stabilise the bone or balloon kyphoplasty where an inflatable bone tamp (which is like a balloon) is inserted into the spine to relieve pressure and return vertebrae to a normal height.  Surgery is usually considered a final option and there is a risk of infection. In other affected bones metal pins or plates may be inserted to provide strength.  A low red blood cell count due to myeloma resulting in anaemia can be treated by blood transfusions and a drug called erythropoietin to encourage red blood cell production.

Steroids and thalidomide are often used for several years as maintenance treatment to prolong the effects of the treatment. However, myeloma can return in which case, patients are often prescribed a similar course of treatment (though not intensive treatment). Bortezomib is only used in the first relapse and only is a response such as a drop by half of abnormal myeloma proteins in the blood. Another drug for relapsed patients (but not those newly diagnosed) is called lenalidomide. Lenalidomide works in a similar way to thalidomide, and can reduce the chance of progression of the cancer to only 20%, but also can reduce numbers of white blood cells (therefore patients even more vulnerable to infection) and number of platelets (increases bruising and bleeding).

As many people diagnosed with myeloma are over 60, and so likely to suffer from several conditions, the average life expectancy after diagnosis is less than 10 years. Over a third of patients will lie at least 5 years and 10% will live for more than 10 years, and recent data shows that myeloma survival rates in the UK are one of the fastest increasing f all cancer types. Although there is no cure for myeloma, various treatments can hold it in remission for many years, and over the last ten years, there has been many new drugs developed and so doubled survival rates. Clinical studies for new medications are ongoing and there is currently research into drugs with fewer side effects and could increase the outlook for patients, improving survival and quality of life.

http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Myeloma/Myeloma.aspx
http://www.myeloma.org.uk/intro-to-myeloma/what-is-myeloma/what-causes-it/
http://www.nhs.uk/Conditions/Multiple-myeloma/Pages/Introduction.aspx