Pseudogout and Calcium Crystal Diseases
An Information Booklet
What is in this booklet?
This booklet explains how calcium crystals can cause sudden attacks of inflammation (where the tissues of the body become hot, swollen and painful). When this happens in joints it is called 'pseudogout'. This literally means 'false-gout', so-called because the attack of inflammation resembles gout, a condition which is caused not by calcium but by urate crystals. When calcium crystals cause attacks of inflammation in tendons it is called 'calcific tendinitis'. This booklet describes how these short-lived, painful 'attacks' in joints and tendons are investigated and treated. It also explains why calcium crystals often get deposited in joints which have osteoarthritis, and the result this can have in terms of joint inflammation and damage. Terms which appear in italics when they are first used are explained in the glossary at the end of the booklet.
What is a crystal?
All crystals are special in the way they are made. The very small particles (atoms) that make a crystal are arranged in a regular repeating pattern. This makes crystals very hard and strong. This is put to good use in nature – for example, the strength and hardness of seashells and human and animal bones come mainly from the fact that they contain a lot of calcium crystals. Crystals of the same chemical make-up tend to have repeating geometric shapes, as shown in Figure 1.
However, the hard, sharp angles of crystals make them abrasive – that is, they rub and grind down things which are in contact with them. That is, they are good abrasive agents. Also their surface can give out a strong electrical charge, which can make them more likely to interact with body tissues. For these reasons crystals can cause inflammation and injury in certain parts of the body.
Which calcium crystals occur in the body?
A substance called 'apatite' (a mixture of various calcium phosphate crystals) forms the normal mineral in human bones. In healthy adults apatite occurs only in our bones and teeth and there are no calcium crystals elsewhere.
Sometimes, however, calcium crystals form in other body tissues. For example, apatite can form in tendons (the fibrous cords that attach muscles to bones). This condition is called 'calcific tendinitis'. The usual site for this is the shoulder, in the tendon of the supraspinatus muscle that helps move the shoulder joint (see Figure 2). But tendons around the hip, hand, or occasionally other places in the body can also be affected.
Rather than forming in tendons, however, it is much more common for the abnormal formation of calcium crystals to be in the cartilage within joints. This is called 'cartilage calcification', or 'chondrocalcinosis'. This can affect the soft, slippery gristle attached to the bone ends (hyaline cartilage), or the tougher form of cartilage (fibrocartilage) which makes up the free 'spacers' (menisci) in some joints, such as the knee. This is shown in Figure 3.
The crystal which usually causes chondrocalcinosis is calcium pyrophosphate. Apatite can also cause it, but this happens much less frequently. Table 1 shows a summary of the various conditions caused by crystals.
| Table 1. Conditions caused by crystals | ||
|---|---|---|
| Condition |
Condition also known as: | Type of crystal usually involved |
| Calcific tendinitis |
- | Apatite |
| Acute calcific tendinitis | Acute periarthritis | Apatite |
| Chondrocalcinosis | Cartilage calcification | Calcium pyrophosphate |
| Pseudogout | Acute pyrophosphate arthritis | Calcium pyrophosphate |
| Osteoarthritis with crystals | Chronic pyrophosphate arthritis | Calcium pyrophosphate (and sometimes apatite) |
| Gout | - | Urate |
The knee is by far the most common place for chondrocalcinosis, but it can also occur at the wrist, shoulder, and occasionally other joints. Other calcium crystals, such as calcium oxalate, may also get deposited within joints, but this is rare and usually only happens in people who have needed 'blood-washing' treatment (dialysis) for long-standing kidney failure.
What happens when there is abnormal calcium crystal formation?
In many cases chondrocalcinosis and calcific tendinitis occur in otherwise normal cartilage and tendons, without causing any symptoms at all. It seems that the calcium crystals, when embedded deep within the cartilage or tendon, usually do not interfere with the working of these tissues. It is possible for a huge deposit of apatite to swell the tendon so that it gets in the way of normal movements, but this is unusual. Also, being deep-seated within compact tissues the crystals so not come into contact with blood cells or the proteins involved in the body's defence mechanism. Therefore they do not cause any inflammation and remain 'inert' (inactive). Many people have these crystal deposits for years without any problems at all.
However, if the crystals move from their protected site within the cartilage or tendon they become exposed to the body's defence systems and can cause attacks of severe inflammation. This movement of crystals out of surrounding tissues into the joint cavity, or out of a tendon into the surrounding soft tissues, is called 'crystal shedding' (see Figures 4 and 5). The spell of very noticeable inflammation caused by shedding of calcium pyrophosphate crystals into a joint is called 'pseudogout' or 'acute pyrophosphate arthritis'. The attack caused by shedding of apatite from a tendon is called 'acute calcific tendinitis'. It is also sometimes known as 'acute periarthritis', meaning inflammation not inside, but near a joint. 'Acute', when used to describe a condition or attack, means one that comes on suddenly and severely and is relatively short-lasting.
What is an attack of pseudogout usually like?
Pseudogout most commonly affects the knee, usually in someone who is in late middle age or elderly. It is rare under the age of 60. Men and women are equally affected. The painful attack can happen 'out of the blue' in a knee that has never caused any problems before. However, more often it happens in a knee that is already affected by osteoarthritis which has caused intermittent stiffness and pain, especially on walking, over the previous months or years. It is unusual for more than one joint to develop an attack at the same time. (See arc booklets 'Osteoarthritis', 'Osteoarthritis of the Knee'.)
The attack starts suddenly, reaching its worst in just 6–12 hours. It is extremely painful, and your knee, or other affected joint, quickly becomes obviously swollen, hot, and tender to touch. The swelling is mainly due to fluid collecting in the joint. This build-up of pressure makes the knee very tense, stiff and painful to move – it will usually be least painful when you hold it in a bent (flexed) position. The overlying skin often appears reddened, tight and shiny. Because of the inflammation in the joint you may feel generally unwell and sweaty and have a raised temperature. An affected knee is shown in Figure 6.
The typical attack gradually settles on its own, even without any treatment. The swelling usually starts going down within a week, though your joint may be very painful for the first few days of the attack and take up to 2–3 weeks to return to normal.
What is an attack of acute calcific tendinitis usually like?
This is similar in some ways to an attack of pseudogout. It usually differs, however, in that it affects younger people, causes painful swelling around rather than within joints, and usually affects parts of the body other than the knee. Acute calcific tendinitis most often affects the shoulder of a young or middle-aged adult. Men and women are equally affected. Often your shoulder will have felt completely normal before the attack. Sometimes, especially if you have a very large crystal deposit that causes a bulge in the tendon, you may have had intermittent discomfort in the shoulder and upper arm over a long period of time, especially when raising the arm outwards. This would be noticeable, for example, when raising your arm to put on a jumper or reaching up to get something off a shelf. This action jams the swollen tendon between the bones (as shown in Figure 7) and makes it difficult for the arm to move fully outwards and upwards.
The acute attack starts when some of the crystals are shed from the tendon into the surrounding tissues, causing inflammation, pain and swelling. This painful attack usually develops very quickly, often getting to its worst within 12–36 hours of starting. You feel pain mainly over the upper arm and shoulder, which is made much worse by trying to raise your arm outwards. You may have visible swelling, redness and tenderness over the angle of the shoulder (as shown in Figure 8), and the swelling may occasionally extend down into the upper arm. It is possible, in some cases, for the subacromial bursa (the fluid-filled sac below the acromion) to burst. In this case you would see bruising right down the arm to the elbow. The acute pain gradually settles on its own, but it may take 2–4 weeks before your shoulder gets back to normal.
What triggers acute attacks?
Many attacks of pseudogout and acute calcific tendinitis occur for no obvious reason and it is not clear why the crystals have been shed. Sometimes, however, there will be something that has provoked the attack. For example, an injury to the knee or shoulder may shake the crystals loose, setting off an attack of pseudogout or calcific tendinitis a day or two afterwards. The most common thing which seems to set off attacks is a generalised illness, especially if it causes a fever (a high temperature) – e.g. having flu or a chest infection. A major stress to the body – e.g. having an operation or a heart attack – may also trigger an attack. For some reason such illnesses encourage crystal shedding and may trigger an acute attack within a few days.
What is the treatment for acute attacks?
Acute attacks of pseudogout and calcific tendinitis eventually settle on their own without any treatment. However, because they are painful and distressing the attacks need treatment aimed at relieving pain, reducing inflammation, and shortening the length of the attack.
Pseudogout
A number of measures can reduce the severe pain and inflammation of pseudogout:
- The use of a needle by your doctor to draw off fluid from the joint ('aspiration') can quickly reduce the high pressure in the joint which is causing the extreme pain. This is a relatively simple, quick procedure and may be all that is needed to bring relief quickly. Sometimes, once the fluid has been drawn out your doctor will inject a small volume (1–2 ml) of a long-acting steroid back into the joint through the same needle. This helps to reduce inflammation in the lining of the joint and prevent the build-up of more fluid.
- Simple painkillers ('analgesics') such as paracetamol may take the edge off the pain. But 'combined analgesics' – paracetamol combined with a codeine derivative – may be more helpful. Combined analgesics, however, can have troublesome side-effects such as headache or constipation which do not occur with paracetamol. Non-steroidal anti-inflammatory drugs (NSAIDs) – e.g. ibuprofen, naproxen, diclofenac – may also give more pain relief than paracetamol, though again they can cause side-effects such as indigestion and ankle-swelling, especially in elderly or medically unfit people. Very occasionally NSAIDs may cause dangerous side-effects such as a bleeding stomach ulcer. Newer forms of NSAIDs ('coxibs' or COX-2-specific NSAIDs) are safer on the stomach but can still cause the other side-effects of NSAIDs. (For more information see the arc drug information sheet 'Non-Specific Anti-Inflammatory Drugs'.) Your doctor will prescribe a standard NSAID, coxib or combined analgesic if it is appropriate and unlikely to cause upset.
- Treatments which are rarely needed include colchicine (a drug derived from the autumn crocus) taken by mouth, and washing out the knee joint ('lavage') in hospital.
Acute calcific tendinitis
Acute calcific tendinitis is mainly treated with painkillers and NSAIDs. If there is a large accumulation of fluid in the subacromial or subdeltoid bursa (fluid-filled sacs in the shoulder) this can be aspirated, and occasionally injected with steroid.
Once an attack of pseudogout or calcific tendinitis has been satisfactorily controlled it is important that you get the affected joint and muscles moving through their normal range of motion as soon as possible. Frequent, small amounts of appropriate exercise will prevent any weakening or wasting of surrounding muscle and help the inflamed tissues return to their normal state. Your physiotherapist can help you with this and give expert advice.
Are any tests necessary?
Acute pseudogout, acute gout (due to urate crystals), and an infection within the joint can all look very similar. Therefore at a first attack, to make the correct diagnosis the doctor will usually need to remove some fluid from the joint and send it to the microbiology laboratory to look for bacteria and to identify which crystals are present (calcium pyrophosphate or urate). An x-ray can also be helpful in showing calcification in the joint cartilage (this is obvious in most cases of pseudogout) or in the tendon (calcific tendinitis). Occasionally a repeat x-ray is taken a few weeks later and may show that the calcification in the cartilage or tendon has decreased. This is because the crystals have been shed and dispersed. Blood tests are often taken during the attack to assess the level of inflammation and to check that the problem is not caused by an infection.
If you develop pseudogout and are younger than most people who get the disease (under 55), or if you have significant widespread chondrocalcinosis in many joints, other blood tests and x-rays may be taken to find out if there are any other problems that may have helped cause the crystal deposits. Anyone with calcific tendinitis will usually be given a blood test to check calcium levels and to check that the kidneys are working normally.
Why do people get calcium crystal deposits?
If a chemical is dissolved in water in a laboratory there is a certain concentration at which crystals start to develop. Even in healthy people, certain chemicals may be present in the blood, urine or soft tissues at levels which in other circumstances would be high enough for crystals to form. The reason crystals do not usually occur in body tissues and fluids is that there are other substances, mainly proteins, which prevent them developing. These are called 'inhibitors'. Other substances can actually increase the likelihood of crystals forming – these are called 'promoters'. This applies to the basic materials needed to make calcium crystals (calcium and pyrophosphate or phosphate). In someone with chondrocalcinosis or calcific tendinitis the levels of these chemicals in the body may well be the same as for anyone else. The most likely reason crystals form is because the balance between inhibitor and promoter substances changes. This balance tends to alter as part of normal ageing, but also because of osteoarthritis.
The common form of chondrocalcinosis that is associated with ageing and osteoarthritis usually involves just a few joints, mainly the knees. Occasionally the tendency to develop chondrocalcinosis and pseudogout may run in families. In some cases chondrocalcinosis affects many rather than just a few joints in up to half the blood relatives, which suggests a strong genetic cause. Recently it has been found that an abnormality of a particular gene (the ANKH gene) may lead to excessive production of pyrophosphate, which can result in widespread chondrocalcinosis and a type of pseudogout which starts young (in the early 20s or even late teens) in some of these families. In other families different genetic factors may be involved, which we do not yet understand.
Far less commonly, chondrocalcinosis may be due to a metabolic disease which interferes with the regulation of calcium or pyrophosphate levels. Examples are conditions such as hyperparathyroidism (overactivity of the parathyroid glands), haemochromatosis ('iron-storage disease') and hypomagnesaemia (magnesium deficiency).
Similarly, there can be other uncommon causes of calcific tendinitis, such as diabetes, the kidneys not working properly, or high calcium levels. There are some types of calcific tendinitis which seem to run in families, but at present the reasons for this are not understood.
Is there any need for long-term treatment?
Once the attack is over there is no need for any long-term treatment for chondrocalcinosis or calcific tendinitis. If pseudogout keeps recurring and the attacks are particularly troublesome, low-dose daily colchicine can reduce their frequency and severity. This, however, is rarely needed. Occasionally operations are performed to remove very large crystal deposits from tendons, but this is only when they are physically getting trapped when the joint is moved.
Can changing my diet help?
There is nothing in the diet that you should avoid or take in increased amounts that will much affect apatite or calcium pyrophosphate crystal deposition. Special diets and supplements are needed only for the very few people who have a metabolic disease (such as magnesium deficiency – see above) or kidney problems which might make them more likely to develop crystals. For general health and well-being, however, you should eat a well-balanced diet and avoid becoming overweight.
Is osteoarthritis with calcium crystals different from osteoarthritis without calcium crystals?
Many, but not all, people with osteoarthritis have calcium pyrophosphate crystals in their osteoarthritic joint cartilage. This is particularly common with osteoarthritis of the knee. Osteoarthritis with crystals is sometimes called 'chronic pyrophosphate arthritis'. The presence of calcium pyrophosphate crystals tends to cause the osteoarthritis to be more troublesome and severe. The joints are likely to become more painful and stiff than an osteoarthritic joint without calcium crystals. The narrowing of cartilage and thickening of bone associated with osteoarthritis are also more likely to progress, rather than stay the same, over several years. (These changes can be seen on x-rays.) These joints, of course, may also develop acute attacks of pseudogout, as well as the less dramatic and more long-standing symptoms caused by osteoarthritis.
Osteoarthritic joints often contain small amounts of apatite within the cartilage and joint fluid. This does not appear to cause any problems, and does not lead to acute attacks of joint inflammation. Occasionally, large amounts of apatite are found in osteoarthritic joints that are severely damaged. In these cases the apatite probably comes from bone that is being exposed due to the loss of a lot of cartilage from the joint. Apatite in this instance simply indicates the severity of the osteoarthritis.
Summary
Crystals in tendons and joints can cause acute painful inflammation from time to time. These attacks will settle by themselves but can be greatly helped by injections and drugs from your doctor.
Glossary
Acromion – a part of the shoulder blade that can be felt on the top of the shoulder. Some of the muscles that move the shoulder are attached to this.
Acute calcific tendinitis ('acute periarthritis') – an attack of pain and inflammation caused by the shedding of crystals out of a tendon where there is already calcific tendinitis (see below).
Apatite – a shorthand term for various calcium phosphate crystals (mainly hydroxyapatite) that are present in bones but can also form in joints, tendons and occasionally other tissues.
Calcific tendinitis – inflammation of a tendon caused by apatite.
Calcium phosphate – there are various calcium phosphates (e.g. tricalcium phosphate, octacalcium phosphate, hydroxyapatite). All are more basic compounds than calcium pyrophosphate and mixtures of them are known as 'apatite'.
Calcium pyrophosphate – the crystal which is the most likely to be deposited in cartilage (chondrocalcinosis). Shedding of these crystals causes pseudogout. (See also 'pyrophosphate'.)
Chondrocalcinosis ('cartilage calcification') – the depositing of calcium crystals within cartilage (either hyaline cartilage or fibrocartilage). The crystal which usually causes this is calcium pyrophosphate.
Chronic pyrophosphate arthritis ('osteoarthritis with crystals') – a term sometimes used when a joint has both osteoarthritis and calcium pyrophosphate crystal deposits.
Fibrocartilage – tough, fibrous cartilage that occurs in some joints as loose 'spacers' or 'cartilages' (menisci).
Gout – a condition similar to pseudogout, but caused by urate crystals rather than calcium crystals. It often affects the big toe. (See arc booklet 'Gout'.)
Haemochromatosis ('iron-storage disease', or 'bronze diabetes' – a disease in which there is excessive absorption and storage of iron.
Hyaline cartilage – the smooth, slippery gristle that is attached to the ends of bones, allowing them to move smoothly against each other in the joints.
Hyperparathyroidism – overactivity of the parathyroid glands that leads to high levels of calcium in the blood and tissues.
Hypomagnesaemia – magnesium deficiency. This may result from a 'leaky' kidney (losing too much magnesium) or from bowel problems that interfere with the absorption of magnesium from our food.
Menisci (singular 'meniscus') – loose 'spacers' of fibrocartilage contained in some joints such as the knee. They act as shock absorbers and help the movement of the joint.
Osteoarthritis – the most common form of arthritis (mainly affecting fingers, knees, hips), causing cartilage thinning and bony overgrowth.
Periarthritis – inflammation near to, but just outside, a joint.
Pseudogout ('acute pyrophosphate arthritis') – severe joint inflammation which comes on suddenly, caused by calcium pyrophosphate crystals.
Pyrophosphate – this substance is produced as a by-product of cell metabolism, and may combine with calcium to form calcium pyrophosphate crystals.
Subacromial bursa – the fluid-filled sac under the acromion bone at the shoulder.
Subdeltoid bursa – the fluid-filled sac under the large deltoid muscle at the shoulder.
Tendinitis – disease or inflammation of tendons.
Tendon – tough, fibrous cord that anchors muscles into bones.
Useful addresses
The Arthritis Research Campaign (arc)
PO Box 177
Chesterfield
Derbyshire S41 7TQ
Phone: 0870 850 5000
www.arc.org.uk
As well as funding research, we produce a range of free information booklets and leaflets. Please contact the address above for a list of titles or, on this web site, see Publications for People with Arthritis.
Arthritis Care
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Helplines: 020 7380 6555 (10am–4pm Mon–Fri)
or freephone: 0808 800 4050 (12pm–4pm Mon–Fri)
www.arthritiscare.org.uk
Offers self-help support, a helpline service (on both numbers above), and a range of leaflets on arthritis.
