21.5 — Autoimmune and Rheumatic Disease

In 1990, a person diagnosed with rheumatoid arthritis could expect deformed hands within a decade. The photographs in old textbooks show it.

Those photographs are now historical. Treating early and aggressively with drugs that were not available then means most people diagnosed today never develop joint deformity at all.

This is one of the largest improvements in outcome anywhere in medicine, and it happened because of two changes: treating early, before damage occurs, and treating to a target rather than to comfort.

What autoimmune disease is

The immune system's core task is telling self from non-self (Chapter 13.5).

Autoimmune disease is that discrimination failing — the immune system attacking the body's own tissue as though it were an invader.

Why it happens, as far as it is understood:

Genetic susceptibility, particularly in the HLA genes that present fragments of protein to immune cells. Certain HLA types carry markedly raised risk of specific conditions.

An environmental trigger — infection is the commonest suspect, and molecular mimicry is the mechanism: a microbe carries a protein fragment resembling one of ours, the immune response against it cross-reacts, and the attack continues after the infection is gone.

Loss of tolerance — the mechanisms that normally delete or suppress self-reactive immune cells failing.

And a striking pattern: around 80 percent of people with autoimmune disease are women. The likely explanations involve sex hormones, and the fact that women carry two X chromosomes — which hold a disproportionate number of immune genes. It is not fully explained.

Rheumatoid arthritis

Around 1 percent of people. Immune attack on the synovium — the lining of the joints — which thickens, becomes inflamed, and erodes the cartilage and bone beneath.

Symptoms:

Pain, swelling and stiffness in the joints, symmetrically.

Typically the small joints of the hands and feet first — the knuckles and the middle finger joints, and characteristically sparing the joints at the fingertips, which is one of the clearest distinctions from osteoarthritis.

Morning stiffness lasting more than an hour, and this is the key discriminator. Inflammatory stiffness is worst on waking and eases with movement. Mechanical joint pain is worst with use and eases with rest. That single question separates the two categories more reliably than almost anything else.

Fatigue, which people consistently rank among the worst symptoms, and which is frequently under-treated.

And it affects more than joints: lung disease, inflammation around the heart, eye dryness, nodules under the skin, anaemia, and substantially increased cardiovascular risk from chronic inflammation — which is why cardiovascular prevention is part of treatment.

Diagnosis: the clinical picture, rheumatoid factor and anti-CCP antibodies — the latter being more specific and frequently present years before symptoms, inflammatory markers, and imaging.

Treatment, and the strategy matters more than the individual drug:

Treat early. There is a window in the first months where treatment prevents damage that cannot be undone later, which is why suspected inflammatory arthritis is referred urgently rather than watched.

Treat to target. Aim for remission or low disease activity, measure it, and escalate if it is not achieved — rather than settling for improvement.

Methotrexate is the anchor drug, taken weekly. Weekly, not daily — and daily dosing by mistake has killed people, which is why the weekly instruction is emphasised repeatedly. Folic acid is given alongside to reduce side effects, and blood monitoring is required.

Other conventional agents: sulfasalazine, hydroxychloroquine, leflunomide.

Biologic therapies — targeting specific molecules: anti-TNF agents, anti-IL-6, B-cell depletion, and T-cell co-stimulation blockers.

JAK inhibitors — oral targeted drugs.

Steroids — for rapid control while slower drugs take effect, and not as long-term treatment, because the cumulative harm is substantial.

And on the risks of these drugs, honestly: they increase infection risk, including reactivation of tuberculosis and hepatitis B, which is why screening is done before starting. The risks are real, and they are smaller than the risks of uncontrolled inflammation, which damages joints, blood vessels and lungs permanently.

Osteoarthritis

And it is worth putting here because it is constantly confused with rheumatoid arthritis, and it is far commoner — the leading cause of joint pain in the world.

Not primarily an inflammatory disease. Cartilage wearing and failing to repair, with changes in the underlying bone, and a degree of low-grade inflammation.

Pain worse with use, better with rest, with brief stiffness after inactivity lasting under 30 minutes.

Affecting weight-bearing joints — knees and hips — and the fingertip joints and thumb base, which is the mirror image of rheumatoid arthritis.

The most effective treatments are not drugs:

Exercise, and this is the strongest evidence in the field. Strengthening the muscles around the joint reduces pain and improves function, and it is consistently more effective than analgesics. The common belief that exercise wears the joint out further is wrong.

Weight loss — a substantial effect on knee pain, because the load through the knee is several times body weight during walking.

Then: topical NSAIDs, oral analgesics used carefully, steroid injections for short-term relief, and joint replacement, which is one of the most successful operations in medicine for people whose function and sleep are significantly affected.

Not supported: glucosamine and chondroitin, where large trials found little benefit; and arthroscopic surgery for degenerative knee disease, which trials found no better than sham.

Lupus

Systemic lupus erythematosus — the condition that can affect almost any organ, which is why it is so hard to diagnose.

Nine times commoner in women, typically starting between 15 and 45, and more common and more severe in people of African, Asian and Hispanic ancestry.

Features: fatigue; joint pain; the butterfly rash across the cheeks and bridge of the nose, sparing the folds beside the nose; photosensitivity, where sun exposure triggers rashes and flares; mouth ulcers; hair loss; and pleurisy or inflammation around the heart.

And the one that determines the outlook: lupus nephritis — kidney involvement, which affects a substantial proportion and is why kidney function and urine protein are checked at every visit (Chapter 21.3).

Blood abnormalities — low white cells, low platelets, and anaemia.

Neurological involvement — including seizures and psychosis.

Diagnosis: antinuclear antibodies are almost always positive, and are not specific — many healthy people have them. Anti-double-stranded DNA and anti-Smith antibodies are specific to lupus. Complement levels fall during active disease.

Treatment: hydroxychloroquine for everyone, and this deserves emphasis — it reduces flares, reduces organ damage and improves survival, and it is the one drug essentially all patients stay on. Its main risk is retinal toxicity at high cumulative doses, which is why eye monitoring is done.

Then steroids for flares, immunosuppressants for organ involvement, and newer biologics including belimumab and anifrolumab.

Sun protection, which is genuinely preventive rather than cosmetic.

Antiphospholipid syndrome — often occurring with lupus, and important because it causes blood clots and recurrent miscarriage. Treated with anticoagulation, and in pregnancy with aspirin and heparin, which substantially improves outcomes.

And the outlook has changed enormously: five-year survival was around 50 percent in the 1950s and is now over 90 percent at fifteen years.

The other rheumatic conditions

Ankylosing spondylitis and axial spondyloarthritis — inflammation of the spine and sacroiliac joints.

Typically starting in young men in their twenties, with back pain that is worse at rest, wakes them in the second half of the night, improves with exercise and is accompanied by prolonged morning stiffness — the exact opposite pattern to mechanical back pain, which is why the history is diagnostic.

Strongly associated with HLA-B27.

Treated with exercise and physiotherapy, which are central rather than adjunctive, plus NSAIDs and anti-TNF or anti-IL-17 biologics, which have transformed severe disease.

Average diagnostic delay is around 8 years, largely because young people with back pain are assumed to have mechanical pain.

Psoriatic arthritis — occurring in around 20 to 30 percent of people with psoriasis (Chapter 14.5). Can affect the fingertip joints and cause whole-digit swelling, and nail changes are a clue.

Gout — not an autoimmune disease but an inflammatory one, caused by uric acid crystals forming in joints.

Sudden, severe, exquisitely painful joint inflammation, classically the base of the big toe, often starting at night, with the joint red, hot and too tender to bear a bedsheet.

Treated acutely with NSAIDs, colchicine or steroids.

And the important part: long-term uric acid lowering with allopurinol, which prevents attacks entirely. It is substantially under-used, and treating each attack while never lowering the uric acid is the commonest mistake in gout management. Treat to a target uric acid level.

Polymyalgia rheumatica — in people over 50, with severe shoulder and hip girdle pain and stiffness, worst in the morning, raised inflammatory markers, and a dramatic response to low-dose steroids that is close to diagnostic.

And it is linked to giant cell arteritis — inflammation of the temporal arteries, causing headache, scalp tenderness, jaw pain on chewing, and sudden irreversible blindness if untreated. This is an emergency: high-dose steroids the same day, before any biopsy (Chapter 20.1).

Sjögren's syndrome — dry eyes and dry mouth from immune attack on the tear and salivary glands, with fatigue and joint pain. Dry mouth causes rapid tooth decay, so dental care matters more than people expect.

Systemic sclerosis — thickening and fibrosis of skin and internal organs, with Raynaud's phenomenon almost universal. The organs that determine outcome are the lungs and kidneys, both of which now have effective treatments where they previously had none.

Vasculitis — a family of conditions where blood vessels are inflamed, varying by the size of vessel affected. Some are life-threatening and all are now treatable with immunosuppression, which changed the outlook from frequently fatal to usually controlled.

Living with an autoimmune condition

Fatigue is real, it is a symptom of inflammation, and it is not resolved by resting more. Pacing, exercise within tolerance, and treating the inflammation are what help.

Exercise improves nearly all of these conditions, including the inflammatory ones, contrary to the intuition that inflamed joints should be rested.

Vaccination matters more than usual, and live vaccines are avoided on immunosuppression.

Cardiovascular risk is raised by chronic inflammation, so blood pressure, lipids and smoking deserve attention.

Bone protection for anyone on long-term steroids (Chapter 21.6).

And infection needs a lower threshold for seeking help, because immunosuppression blunts the usual signs.

Why this chapter is genuinely optimistic

Understanding the specific molecules driving inflammation produced drugs that target them precisely, which is why the last two decades changed these conditions more than the preceding century.

Deformity from rheumatoid arthritis is now largely preventable.

Lupus survival has gone from a coin flip to the large majority.

Vasculitis went from usually fatal to usually controlled.

And the direction of travel is toward predicting who will develop these conditions before they do — the antibodies appear years in advance — and preventing them from ever starting. Trials of exactly that are underway.

What the next page fixes

Chapter 21.6 covers bone, joint and muscle problems — osteoporosis, back pain, and the everyday injuries that most people will meet at some point.