Connective tissue disease (UCTD & MCTD)

The connective tissue diseases described here are autoimmune: the body's defences are directed at healthy tissue, and the inflammation that follows affects the joints, skin, muscles and blood vessels, and sometimes the internal organs. With the undifferentiated and mixed forms, what that misdirected immunity leaves is an antibody pattern that can be recognised, and a defined disease may or may not follow it.

Its root cause is not well understood. The usual explanation is a genetic predisposition that some trigger sets off: an infection, or an exposure in the environment, ultraviolet light or the chemicals in cigarette smoke among them. Women are affected more often than men, and the peak years are the thirties and forties, though it can begin at any age. Several genes are known to influence the risk, so heredity plays a part; in the individual, the trigger usually goes unidentified.

Several abbreviations turn up in this area, and each marks a place on a spectrum of autoimmune conditions:

• CTD (connective tissue disease) is the broadest of the three terms. Any autoimmune condition of the connective tissues sits under it, and the connective tissues are the joints, the skin, the muscles, the blood vessels and the internal organs. A CTD that clearly meets the criteria for one named diagnosis (lupus, Sjögren's syndrome, systemic sclerosis or an inflammatory myopathy, for instance) is called defined, or differentiated.
• UCTD (undifferentiated connective tissue disease) is where the antibodies and the features say connective tissue disease, but not which one: the full criteria for any single defined condition have not yet been met. The picture that typically presents is one of aching joints, Raynaud's phenomenon, tiredness, eyes or mouth that are dry, and an antinuclear antibody (ANA) test that comes back positive. Flares come and settle. Many people remain undifferentiated for years; in a smaller number the picture settles, over time, into a named condition, and that possibility is why it is kept under review.
• MCTD (mixed connective tissue disease) is an overlap condition of its own, one to which inflammatory myopathy, systemic sclerosis and lupus all contribute something. Raynaud's; puffy, swollen fingers; inflammation in the joints; muscle involvement; and a high level of the antibody anti-U1-RNP: that is the characteristic set. The ANA is usually positive, but what marks MCTD out is the strongly positive anti-RNP that almost always accompanies it. The positive ANA test guide is the place to go if you have been told your ANA, or your RNP, is positive; it sets out what those results signify, and what they do not.

Because the conditions overlap, the symptoms differ from person to person. Among the possibilities:

• Joints that ache and swell, and aching muscles
• Raynaud's phenomenon, in which cold turns the fingers white, then blue, then red
• Fatigue, and feeling generally unwell
• Dryness, changes in the skin, or any of the other features that mark out lupus, Sjögren's syndrome or systemic sclerosis

Reaching the diagnosis takes patience: symptoms, examination findings and a range of antibody tests are set alongside one another, and the picture is often given time to develop. The assessment asks which features are present, whether they fit a named condition or an undifferentiated or mixed picture, and whether anything is changing. It is an area that leans on specialist assessment.

Ultrasound helps to assess inflammation in whichever joints are affected. Point-of-care ultrasound is part of the consultation with Dr Borukhson; how the scan is done is covered on the ultrasound clinic page.

Management is shaped by what is happening to you: inflammation is brought under control, symptoms are relieved, and a watch is kept for organ involvement and for any change as time passes. Depending on the picture, that can mean anti-inflammatory painkillers and hydroxychloroquine for the joints and the skin, steroids to settle a flare, a medicine that widens the blood vessels for Raynaud's and, where the symptoms are severe or an organ is involved, an immunosuppressant such as methotrexate, azathioprine or mycophenolate, medicines that make infection likelier and are monitored with regular blood tests. Things can change over time, and that alone justifies regular specialist review. You and Dr Borukhson settle the plan together.

A connective tissue disease may stop at the joints and skin or go on to the internal organs, the lungs (interstitial lung disease) among them, and when it does the care can need a second specialty. Dr Borukhson practises within a world-renowned tertiary centre, with ready access to consultant colleagues in the other specialties this condition may call on. Where it helps, she can bring those specialists in directly, and particularly complex cases can go to a multidisciplinary team meeting (MDT) with minimal delay. Whenever more than one kind of expertise is needed, the strands of your care can be drawn together and decisions reached promptly.

A full, active life is what most people have, and for many an undifferentiated picture stays stable for years, flaring and settling as it goes. Some practical measures help:

• Raynaud's phenomenon eases when the hands and feet are kept warm and sudden cold avoided; giving up smoking helps considerably.
• Let fatigue set the pace: gentle regular exercise balanced with rest, and sleep that is protected.
• If sunlight aggravates your skin or your symptoms in general, sunscreen and covering up help.
• Follow-up appointments and blood tests are worth keeping when you feel well as much as when you do not, because that monitoring is how any change gets noticed in good time.

Pregnancy needs planning with your team: the condition can flare or change during it, and some medicines, methotrexate and mycophenolate among them, have to be stopped well beforehand, as our guide to arthritis, autoimmune conditions and pregnancy describes. Before any new medicine, a vaccination or an operation, the clinician involved needs to know about your diagnosis. The outlook for overlapping conditions is generally reassuring, with the qualification that it depends on which organs are involved.

These conditions do not stop at the joints, and some symptoms should not wait for a routine review.

Treat any of these as a 999 or A&E emergency: call 999 and do not drive yourself to A&E.

• Severe illness with suspected sepsis: a high fever with shaking, confusion, rapid breathing, or feeling dramatically worse over hours
• With a fever or feeling unwell, a rash that does not fade when you press it, a stiff neck with eyes that cannot bear bright light, or skin, lips or tongue turning blue, grey, pale or blotchy, since these can be signs of meningitis or sepsis, though fingers or toes that change colour in the cold, as they do in Raynaud's, are not what is meant; on black or brown skin the rash and the change of colour may be easier to see on the palms of the hands or the soles of the feet
• Chest pain that is crushing, tight or like a pressure, that spreads to an arm, the jaw, the neck, the stomach or the back, that comes with breathlessness, sweating, feeling sick or feeling light-headed, or that came on suddenly and does not go away
• Breathlessness that is severe, with gasping, choking or no breath to get words out; coughing up blood; or chest pain that catches as you breathe in, since any of these can mean the lungs or the heart are involved, or a clot on the lung where antiphospholipid antibodies are present
• Palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, since a heart whose muscle or rhythm is affected has to be checked at once
• Choking that will not clear, or breathing that is failing
• A blackout, since in a minority of people the lung's blood vessels come under raised pressure, or the heart itself is affected, and either can be behind it
• Sudden weakness or numbness on one side, a drooping face or difficulty speaking, a sudden severe headache, sudden confusion or a seizure, or sudden loss of vision, any of which can be a stroke, even if it stops after a short time
• An eye that suddenly and completely loses its sight
• Sudden severe pain in the abdomen or back, since the pancreas can react to prednisolone
• Lips, mouth, throat or tongue that suddenly swell, a throat that feels tight, very fast breathing or a struggle to breathe or to swallow, skin, tongue or lips turning blue, grey or pale (on black or brown skin this may be easier to see on the palms of the hands or the soles of the feet), becoming suddenly very confused, drowsy or dizzy, or fainting and not being able to be woken, since this can be a severe allergic reaction, anaphylaxis, which can follow a dose of any medicine, though fingers or toes that change colour in the cold, as they do in Raynaud's, are not what is meant
• Vomiting blood, or bleeding from the back passage that is heavy or will not stop, most of all with faintness, confusion or pain in the abdomen, or vomit that is black or dark brown, since a stomach ulcer on prednisolone can bleed
• Thoughts of harming yourself or ending your life, which steroids can bring on

Any of these needs an assessment that is urgent, on the same day, from your GP, your rheumatology team or NHS 111:

• A fever, or feeling generally unwell, on immunosuppressant, biologic or steroid treatment, since an infection has to be treated early
• A joint that is hot and swollen, with a fever or feeling unwell, since an infected joint has to be ruled out at once, at A&E or through NHS 111
• A joint that has become hot and very swollen suddenly, or is worsening quickly, even without a fever, since an infected joint does not always announce itself with one; a joint that will take no weight at all, or that cannot be moved, is a 999 or A&E emergency, whether or not there is a fever
• New chest pain, new palpitations, or breathlessness that is new or getting worse; palpitations happening now that do not stop, or that come with chest pain, breathlessness, feeling faint or fainting, belong to the first list; in pregnancy, breathlessness that comes on suddenly, or when you lie down, or with dizziness, is for your midwife or maternity unit straight away, as the pregnancy line below says
• A persistent dry cough with a fever, with new breathlessness, or that is worsening over hours to days
• A new red, painful eye, or sight that has blurred, dimmed or changed, which needs an eye casualty or urgent eye clinic the same day, as does an eye that light hurts, since the eye can be inflamed in these conditions; on hydroxychloroquine, a change in sight is also one to report to the team that prescribes it; in pregnancy, any change in sight, blurring or flashing lights among them, is also for your midwife or maternity unit straight away, as the pregnancy line below says, since it can be a sign of pre-eclampsia
• A calf that is swollen, hot or painful, or a limb that is painful, swollen or discoloured, which can mean a clot, likelier where antiphospholipid antibodies are present; with breathlessness, chest pain, palpitations or feeling faint, this is a 999 or A&E emergency: call 999 and do not drive yourself to A&E
• A headache that is new and persistent, or that keeps getting worse, with none of the signs above, since where antiphospholipid antibodies are present a clot can form in the veins that drain the brain
• Swallowing that is newly difficult or has got harder over days, coughing or choking on food or drink, or muscle weakness getting worse fast, since a new swallowing problem needs checking without delay, food or drink that goes down the wrong way can lead to chest infections, and muscle inflammation is part of the picture for some
• Marked swelling of the face or ankles, or frothy or bloody urine, since in a minority of people the kidneys can be involved
• A finger or toe that turns very painful, cold, dusky or numb and does not recover on warming, since the blood supply may be critically low
• A sore or ulcer on a finger or toe that is getting more painful, red or discharging, since an infection there can reach the deeper tissue and the bone, and needs treating without delay
• A marked change in mood or behaviour, confusion, or seeing or hearing things that are not there, on steroid treatment, since prednisolone can do this, the more so the higher the dose; confusion that comes on suddenly is a 999 or A&E emergency, as the first list says
• Unusual thirst or hunger, passing urine more often, or feeling sleepy or confused, on steroids, or swelling of the arms or legs, bruising or bleeding that is not normal, black or dark red stools, severe stomach pain, severe back pain, a severe upset stomach, being sick, or very bad dizziness, since each can be a steroid effect that needs checking without delay; pain in the abdomen or back that comes on suddenly and severely is a 999 or A&E emergency, as the first list says; in pregnancy, bleeding that is not normal, and stomach pain that is severe, belong to the pregnancy line below
• Contact with measles, chickenpox or shingles, since these infections can be severe on steroids and a medicine to protect you may be needed
• Being near someone with measles, chickenpox or shingles, while you take a medicine that weakens the immune system, since measles and chickenpox can be dangerous when the immune system is weakened, and you can catch chickenpox from someone with shingles if you have never had chickenpox; NHS 111 can tell you what to do that day
• In pregnancy, any bleeding, stomach pain that is severe or does not go away after a rest, reduced baby movements, a severe headache or visual disturbance, sudden swelling of the face, hands, legs or feet, or breathlessness that comes on suddenly, or when you lie down, or with dizziness: contact your midwife or maternity unit straight away, whatever the time; bleeding that is heavy, or that comes with severe pain in the tummy, pain in the shoulder, or feeling sick, faint or dizzy, or passing out, is a 999 or A&E emergency: call 999 and do not drive yourself to A&E; pain in the abdomen or back that comes on suddenly and severely is a 999 or A&E emergency, as the first list says
• A high temperature in pregnancy, whatever medicines you are taking, since a fever can be a sign of an infection that needs checking; your midwife or maternity unit can advise

A persistent dry cough on its own, or breathlessness that has drifted slowly, over weeks or months, is something to tell your team promptly, without waiting for a routine slot. A new sore or ulcer on a finger or toe, or one that is not healing, and, outside pregnancy, a fever that persists with no explanation, in someone not on immunosuppressant, biologic or steroid treatment, are reasons to get medical advice promptly, from your GP or your rheumatology team.

A flare that will not settle and in which no joint is hot or changing fast, new rashes or mouth ulcers, swallowing that has slowly got harder, ankles that have begun to swell, weight you are losing without meaning to, or marked new tiredness: for any of these, ask your GP or rheumatology team for a sooner review. A new rash in pregnancy does not wait for that review: ring your midwife or maternity unit, or your GP, straight away, because it may come from an infection that could harm the baby; our pregnancy guide covers contact with a rash illness too, and sets out what else to do and which rash is for 999 or A&E. If you cannot tell how urgent something is, asking is never a mistake.

If there is one situation in which careful, continuing specialist assessment counts most, it is the overlapping or undifferentiated condition, where that assessment is how an accurate understanding is reached and how any change is caught early. A mix of autoimmune symptoms, or an antibody result nobody has accounted for, is reason enough for a specialist review.

What goes into diagnosing a connective tissue disease?

There is no test that settles it alone. It comes together gradually, out of your symptoms, an examination and blood tests for a range of antibodies, and is looked at afresh as the picture clears. Scanning the joints for inflammation, where they are involved, adds detail: point-of-care ultrasound is part of the consultation with Dr Borukhson.

Does a positive ANA test mean I have one of these conditions?

Not by itself. A positive ANA is a common finding that on its own tells you little; what gives it meaning is the context: your symptoms, the examination and the other antibody results. A specialist review is worth having if nobody has explained your result properly: it can help to settle what the result signifies for you, and what it does not, and whether anything further, more tests or a period of monitoring, is worthwhile.

Undifferentiated or mixed: what separates the two?

UCTD, undifferentiated connective tissue disease, is the label for an autoimmune picture that has not settled: the features and antibodies point towards a connective tissue disease, but there are not yet enough of them to meet the criteria for any one named condition. Mixed connective tissue disease, MCTD, is a particular overlap in which features of lupus, systemic sclerosis and muscle inflammation come together, characteristically with a strongly positive anti-U1-RNP antibody. Where on that spectrum you sit is something a specialist assessment can work out and then keep under review.

Does UCTD go on to become something more serious?

More often than not it does not. Years can go by with the picture still undifferentiated, the symptoms flaring and settling, and that is how it stays for many people. In a smaller number a defined condition, lupus most often, or systemic sclerosis, gradually comes into view, and that possibility is the reason for regular specialist review: to read the picture as it develops and to notice any change early.