Rheumatology Flashcards
Osteoarthritis
Osteoarthritis is often described as “wear and tear” in the joints. It occurs in the synovial joints and results from genetic factors, overuse and injury. Osteoarthritis is thought to result from an imbalance between cartilage damage and the chondrocyte response, leading to structural issues in the joint. Risk factors include obesity, age, occupation, trauma, being female and family history.
Joints commonly affected in osteoarthritis
Hips
Knees
Distal interphalangeal (DIP) joints in the hands
Carpometacarpal (CMC) joint at the base of the thumb
Lumbar spine
Cervical spine (cervical spondylosis)
Xray changes in osteoarthritis
The four key x-ray changes in osteoarthritis can be remembered with the “LOSS” mnemonic:
L – Loss of joint space
O – Osteophytes (bone spurs)
S – Subarticular sclerosis (increased density of the bone along the joint line)
S – Subchondral cysts (fluid-filled holes in the bone)
X-ray reports might describe findings of osteoarthritis as degenerative changes. X-ray changes do not necessarily correlate with symptoms. A patient might have significant signs on an x-ray but minimal symptoms, or the reverse.
Presentation of osteoarthritis
Osteoarthritis presents with joint pain and stiffness. The pain and stiffness tend to worsen with activity and at the end of the day. This is the reverse of the pattern in inflammatory arthritis, where symptoms are worse in the morning and improve with activity. Osteoarthritis leads to deformity, instability and reduced function of the joint.
General signs of osteoarthritis are:
Bulky, bony enlargement of the joint
Restricted range of motion
Crepitus on movement
Effusions (fluid) around the joint
Osteoarthritis signs in the hands
Heberden’s nodes (in the DIP joints)
Bouchard’s nodes (in the PIP joints)
Squaring at the base of the thumb (CMC joint)
Weak grip
Reduced range of motion
The carpometacarpal joint at the base of the thumb is a saddle joint, with the metacarpal bone sitting on the trapezius bone, using it like a saddle. It gets a lot of use and is very prone to wear.
TOM TIP: Patients may present with referred pain, particularly in the adjacent joints. For example, consider osteoarthritis in the hip in patients presenting with lower back or knee pain.
Diagnosing osteoarthritis
The NICE guidelines (2022) suggest that a diagnosis can be made without any investigations if the patient is over 45, has typical pain associated with activity and has no morning stiffness (or stiffness lasting under 30 minutes).
Managing osteoarthritis
Non-pharmacological management involves patient education and lifestyle changes, such as:
Therapeutic exercise to improve strength and function and reduce pain
Weight loss if overweight, to reduce the load on the joint
Occupational therapy to support activities and function (e.g., walking aids and adaptations to the home)
Pharmacological management recommended by the NICE guidelines (2022) are:
Topical NSAIDs first-line for knee osteoarthritis
Oral NSAIDs where required and suitable (co-prescribed with a proton pump inhibitor for gastroprotection)
Weak opiates and paracetamol are only recommended for short-term, infrequent use. NICE (2022) recommend against using any strong opiates for osteoarthritis.
Intra-articular steroid injections may temporarily improve symptoms (NICE say up to 10 weeks).
Joint replacement may be used in severe cases. The hips and knees are the most commonly replaced joints.
Medication notes about osteoarthritis
NSAIDs (e.g., ibuprofen or naproxen) are very effective for musculoskeletal pain. However, they must be used cautiously, particularly in older patients and those on anticoagulants, such as aspirin or DOACs. They are best used intermittently, only for a short time during flares. They have several potential adverse effects, including:
Gastrointestinal side effects, such as gastritis and peptic ulcers (leading to upper gastrointestinal bleeding)
Renal side effects, such as acute kidney injury (e.g., acute tubular necrosis) and chronic kidney disease
Cardiovascular side effects, such as hypertension, heart failure, myocardial infarction and stroke
Exacerbating asthma
There is little evidence that opiates help with chronic pain. They are associated with side effects, risks, tolerance, dependence and withdrawal. They often result in dependence without any objective benefits.
TOM TIP: The WHO pain ladder is not helpful in chronic pain. Paracetamol and opiates are not recommended for regular use in osteoarthritis. Remember that NSAIDs cause hypertension by blocking prostaglandins (prostaglandins cause vasodilation) and should be used very cautiously with a history of high blood pressure.
Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune condition that causes chronic inflammation in the synovial lining of the joints, tendon sheaths and bursa. It is a type of inflammatory arthritis. Synovial inflammation is called synovitis. Inflammation of the tendons increases the risk of tendon rupture.
Rheumatoid arthritis tends to affect multiple small joints symmetrically across both sides of the body. This pattern is described as symmetrical polyarthritis.
Rheumatoid arthritis is 2-3 times more common in women than men. It most often develops in middle age but can present at any age. Smoking and obesity are risk factors.
A family history increases the risk of rheumatoid arthritis (although there is no clear inheritance pattern). The most common gene associated with rheumatoid arthritis is HLA DR4.
The disease course varies between patients, from mild and remitting to severe and progressive. Disease activity, positive antibodies and erosions on an x-ray predict worse disease.
Antibodies in Rheumatoid Arthritis
Rheumatoid factor (RF) is an autoantibody present in around 70% of RA patients. It targets the Fc portion of the immunoglobulin G (IgG). All antibodies (immunoglobulins) have an Fc portion that interacts with other parts of the immune system. Rheumatoid factor causes immune system activation against the patient’s own IgG, resulting in systemic inflammation. Rheumatoid factor is most often IgM but can be other types of immunoglobulin.
Anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) are more sensitive and specific than rheumatoid factor. They are positive in around 80% of patients with rheumatoid arthritis. They often pre-date the development of rheumatoid arthritis and indicate that a patient will develop the condition at some point.
Presentation of Rheumatoid Arthritis
The speed of onset can vary from rapid (e.g., overnight) to gradual (e.g., over months). The three joint symptoms are:
Pain
Stiffness
Swelling
Rheumatoid arthritis typically causes symmetrical distal polyarthritis affecting the small joints of the hands and feet. The most commonly affected joints are:
Metacarpophalangeal (MCP) joints
Proximal interphalangeal (PIP) joints
Wrist
Metatarsophalangeal (MTP) joints (in the foot)
On palpation of the joints, there will be tenderness and synovial thickening, giving them a “boggy” feeling.
TOM TIP: Rheumatoid arthritis very rarely affects the distal interphalangeal joints. Enlarged and painful distal interphalangeal joints are more likely to represent Heberden’s nodes due to osteoarthritis.
Large joints such as the ankle, knee, hips, and shoulders can also be affected. It can affect the cervical spine (but not the lumbar spine).
Associated systemic symptoms include:
Fatigue
Weight loss
Flu-like illness
Muscles aches and weakness
TOM TIP: Inflammatory arthritis symptoms are worse with rest and improve with activity. They are worst in the morning. Symptoms of mechanical problems (e.g., osteoarthritis) are worse with activity and improve with rest.
Palindromic Rheumatism
Palindromic rheumatism involves self-limiting episodes of inflammatory arthritis, with pain, stiffness and swelling typically affecting only a few joints. The symptoms last days, then completely resolve. Joints appear normal between episodes. Rheumatoid factor or anti-CCP antibodies may indicate that it will progress to rheumatoid arthritis.
Hand signs in advanced rheumatoid arthritis
In patients with advanced disease, the hand signs include:
Z-shaped deformity to the thumb
Swan neck deformity (hyperextended PIP and flexed DIP)
Boutonniere deformity (hyperextended DIP and flexed PIP)
Ulnar deviation of the fingers at the MCP joints
Boutonniere deformity is caused by a tear in the central slip of the extensor components at the proximal interphalangeal (PIP) joint. The central slip connects to the middle phalanx at the PIP, and the lateral bands go around the PIP and connect to the distal phalanx. When the patient tries to straighten their finger, the lateral bands pull on the distal phalanx, causing the distal interphalangeal (DIP) joint to hyperextend and the PIP joint to flex.
Swan neck deformity is the opposite of Boutonnieres deformity. It is caused by an extensor mechanism imbalance, causing flexion of the DIP joint and extension of the PIP joint.
TOM TIP: Effective treatments means it is unusual for rheumatoid arthritis to get to this stage. However, it is worth becoming familiar with these examination findings as they make great patients for OSCEs.
Atlantoaxial subluxation in rheumatoid arthritis
Atlantoaxial subluxation occurs in the cervical spine. Synovitis and damage to the ligaments around the odontoid peg of the axis (C2) allow it to shift within the atlas (C1). Subluxation can cause spinal cord compression and is an emergency. This needs to be considered when a patient is having a general anaesthetic and requires intubation. MRI can be used to visualise changes in these areas as part of a pre-operative assessment.
Extra-articular manifestations in rheumatoid arthritis
There are many extra-articular manifestations of rheumatoid arthritis:
Pulmonary fibrosis
Felty’s syndrome (a triad of rheumatoid arthritis, neutropenia and splenomegaly)
Sjögren’s syndrome (with dry eyes and dry mouth)
Anaemia of chronic disease
Cardiovascular disease
Eye manifestations
Rheumatoid nodules (firm, painless lumps under the skin, typically on the elbows and fingers)
Lymphadenopathy
Carpel tunnel syndrome
Amyloidosis
Bronchiolitis obliterans (small airway destruction and airflow obstruction in the lungs)
Caplan syndrome (pulmonary nodules in patients with rheumatoid arthritis exposed to coal, silica or asbestos dust)
Eye manifestations related to rheumatoid arthritis and its treatment include:
Dry eye syndrome (keratoconjunctivitis sicca)
Episcleritis
Scleritis
Keratitis
Cataracts (secondary to steroids)
Retinopathy (secondary to hydroxychloroquine)
Diagnosing rheumatoid arthritis
The NICE clinical knowledge summaries (updated 2020) recommend an urgent rheumatology referral for patients with persistent synovitis (to be seen within three weeks). They suggest considering an NSAID and arranging baseline bloods while waiting for the specialist assessment.
The investigations that help in the initial assessment are:
Rheumatoid factor
Anti-CCP antibodies
Inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
X-rays of the hands and feet for bone changes
Ultrasound or MRI can be used to detect synovitis (useful when clinical findings are unclear)
The diagnosis is based on clinical findings and blood results. The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria from 2010 can be used to make the diagnosis.
Xray changes in rheumatoid arthritis
Periarticular osteopenia
Boney erosions
Soft tissue swelling
Joint destruction and deformity (in more advanced disease)
Scoring rheumatoid arthritis
The Health Assessment Questionnaire (HAQ) measures functional ability. The NICE guidelines (updated 2020) recommend a baseline HAQ score at diagnosis to assess the response to treatment.
The Disease Activity Score 28 Joints (DAS28) score is used in monitoring disease activity and response to treatment. It involves assessing 28 joints and assigning points for:
Swollen joints
Tender joints
The ESR or CRP result
Managing rheumatoid arthritis
Treatment involves the multidisciplinary team, including rheumatologists, specialist nurses, GPs, physiotherapists, occupational therapists, psychologists and podiatrists.
Starting treatment early improves outcomes. The aim is to induce remission or get as close to remission as possible. C-reactive protein and DAS28 are used to monitor the success of treatment.
Short-term steroids (oral or intramuscular) may be used at initial presentation, when initiating a new treatment and during flares to settle the inflammation and control symptoms quickly.
Treatment is with conventional disease-modifying anti-rheumatic drugs (cDMARDs) and biologic DMARDs:
Monotherapy with methotrexate, leflunomide or sulfasalazine
Combination treatment with multiple cDMARDs
Biologic therapies (usually alongside methotrexate)
Hydroxychloroquine may be used in mild disease and palindromic rheumatism. It is the “mildest” DMARD.
Other cDMARDs include azathioprine, ciclosporin, cyclophosphamide and mycophenolate.
NSAIDs are helpful for pain relief but have associated risks and side effects.
Pregnancy can improve symptoms, but some pregnant women experience a symptom flare. Hydroxychloroquine and sulfasalazine are considered the safest DMARDs in pregnancy (extra folic acid is required with sulfasalazine). Methotrexate and leflunomide are very harmful in pregnancy (teratogenic).
Biological therapies interact with the immune system to reduce inflammation. They have various targets:
Tumour necrosis factor (TNF) inhibitors (e.g., adalimumab, infliximab, etanercept, golimumab and certolizumab)
Anti-CD20 on B cells (e.g., rituximab)
Anti-interleukin-6 inhibitors (e.g., sarilumab and tocilizumab)
JAK inhibitors (e.g., upadacitinib, tofacitinib and baricitinib)
T-cell co-stimulation inhibitors (e.g., abatacept)
Tumour necrosis factor is a cytokine involved in stimulating inflammation. Blocking TNF reduces inflammation.
TOM TIP: The main biologics to remember are adalimumab, infliximab and etanercept (TNF inhibitors), and rituximab (a monoclonal antibody that targets the CD20 proteins on the surface of B cells). They cause immunosuppression, increasing the risk of infection, certain cancers (e.g., skin) and reactivation of latent TB.
Orthopaedic surgery used to be an important aspect of management when joint deformities developed. However, cDMARDs and biologics have dramatically reduced the number of patients getting to this stage.
Methotrexate
Methotrexate interferes with folate metabolism and suppresses the immune system. It is given once a week. Folic acid 5mg is taken once a week (on a different day to the methotrexate). Side effects include:
Mouth ulcers and mucositis
Liver toxicity
Bone marrow suppression and leukopenia (low white blood cells)
Teratogenic (harmful to pregnancy) and needs to be avoided before conception in both women and men
Leflunomide
Leflunomide is an immunosuppressant medication that interferes with the production of pyrimidine. Pyrimidine is an important component of RNA and DNA. Side effects include:
Mouth ulcers and mucositis
Increased blood pressure
Liver toxicity
Bone marrow suppression and leukopenia (low white blood cells)
Teratogenic (harmful to pregnancy) and needs to be avoided before conception in both women and men
Peripheral neuropathy
Sulfasalazine
Sulfasalazine is an immunosuppressive and anti-inflammatory medication. The exact mechanism is not clear. Side effects include:
Orange urine
Reversible male infertility (reduced sperm count and quality)
Bone marrow suppression
Hydroxychloroquine
Hydroxychloroquine is traditionally an antimalarial medication. It suppresses the immune system by interfering with Toll-like receptors, disrupting antigen presentation and increasing the pH in the lysosomes of immune cells. Side effects include:
Retinal toxicity (reduced visual acuity (macular toxicity)
Blue-grey skin pigmentation
Hair lightening (bleaching)
Side effects of medications used in RA
TOM TIP: The unique side effects worth remembering are:
Methotrexate: Bone marrow suppression and leukopenia, and highly teratogenic
Leflunomide: Hypertension and peripheral neuropathy
Sulfasalazine: Orange urine and male infertility (reduces sperm count)
Hydroxychloroquine: Retinal toxicity, blue-grey skin pigmentation and hair bleaching
Anti-TNF medications: Reactivation of tuberculosis
Rituximab: Night sweats and thrombocytopenia
Psoriatic arthritis
Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. It can vary in severity from mild stiffening and soreness in the joints to complete joint destruction in arthritis mutilans.
Psoriatic arthritis occurs in 10-20% of patients with psoriasis, usually within 10 years of developing the skin condition. Arthritis can occur before the skin changes. It is most common in middle age but can occur at any age.
Psoriatic arthritis is part of the seronegative spondyloarthropathy group of conditions. It may be associated with extra-articular manifestations, particularly uveitis and inflammatory bowel disease.
Patterns of psoriatic arthritis
There are 5 recognised patterns. Asymmetrical oligoarthritis and symmetrical polyarthritis are the most common.
Asymmetrical oligoarthritis affects 1-4 joints at any given time, often on only one side of the body.
Symmetrical polyarthritis presents similarly to rheumatoid arthritis. More than four joints are affected, such as the hands, wrists and ankles.
Distal interphalangeal predominant pattern primarily affects the DIP joints. However, the DIP joints can be affected across all types of psoriatic arthritis.
Spondylitis presents with back stiffness and pain. It involves the axial skeleton (spine and sacroiliac joints).
Arthritis mutilans is the most severe form of psoriatic arthritis. It affects the phalanges (the bones of the fingers and toes). There is osteolysis (destruction) of the bones around the joints, leading to progressive shortening of the digits. The skin folds as the digit shortens, giving an appearance described as a telescoping digit.
TOM TIP: Psoriatic arthritis tends to affect the distal interphalangeal (DIP) joints and axial skeleton, whereas rheumatoid arthritis tends not to affect these joints. This can help you distinguish them.
Signs in psoriatic arthritis
Plaques of psoriasis on the skin
Nail pitting (tiny indents in the fingernails and toenails)
Onycholysis (separation of the nail from the nail bed)
Dactylitis (inflammation of the entire finger)
Enthesitis (inflammation of the entheses, which are the points of insertion of tendons into bone)
Psoriasis epidemiological screening tool
The NICE guidelines on psoriasis (2017) suggest the Psoriasis Epidemiological Screening Tool (PEST) as a way of screening for psoriatic arthritis in patients with psoriasis. It involves questions about joint pain, swelling, a history of arthritis and nail pitting. A high score triggers a referral to a rheumatologist.
Xray changes in psoriatic arthritis
Characteristic x-ray changes in psoriatic arthritis include:
Periostitis (inflammation of the periosteum, causing a thickened and irregular outline of the bone)
Ankylosis (fixation or fusion of the bones at the joint)
Osteolysis (destruction of bone)
Dactylitis (inflammation of the whole digit, seen as soft tissue swelling)
The classic x-ray finding in the digits is a “pencil-in-cup” appearance. There is erosion of the bones at the joint. There is central erosion on one side of the joint, giving a cup-like appearance. The other bone becomes pointed and looks like a pencil in the cup. This appearance is associated with arthritis mutilans.
Managing psoriatic arthritis
There is a crossover between the systemic treatments used to treat the skin condition and psoriatic arthritis. Treatment is coordinated between dermatologists, rheumatologists and other multidisciplinary team members.
Depending on the severity, treatment may involve:
Non-steroidal anti-inflammatory drugs (NSAIDs)
Steroids
DMARDs (e.g., methotrexate, leflunomide or sulfasalazine)
Anti-TNF medications (etanercept, infliximab or adalimumab)
Ustekinumab is a monoclonal antibody that targets interleukin 12 and 23
Reactive arthritis
Reactive arthritis involves synovitis in one or more joints in response to an infective trigger. Typically it causes acute monoarthritis, affecting a single joint (most often the knee), presenting with a warm, swollen and painful joint.
A significant differential is septic arthritis, where an infection is inside the joint. Patients with reactive arthritis do not have an infection in the joint.
The most common triggers of reactive arthritis are gastroenteritis or sexually transmitted infections. Chlamydia may cause reactive arthritis. Gonorrhoea typically causes septic arthritis rather than reactive arthritis.
Reactive arthritis is a seronegative spondyloarthropathy. There is a link with the HLA B27 gene. It is more common in patients with HIV (HIV needs to be excluded in patients with reactive arthritis).
Conditions associated with reactive arthritis
Bilateral conjunctivitis (non-infective)
Anterior uveitis
Urethritis (non-gonococcal)
Circinate balanitis (dermatitis of the head of the penis)
TOM TIP: The classic triad of conjunctivitis, urethritis and arthritis are remembered with the mnemonic, “can’t see, pee or climb a tree”.
Managing reactive arthritis
Patients presenting with an acute warm, swollen, painful joint need to be treated according to the local hot joint policy. Septic arthritis needs to be excluded. Antibiotics may be given until septic arthritis is excluded.
Joint aspiration is required. Synovial fluid is sent for microscopy, culture and sensitivity testing for infection, and crystal examination for gout and pseudogout.
Management of reactive arthritis (after septic arthritis is excluded) involves:
Treatment of the triggering infection (e.g., chlamydia)
NSAIDs
Steroid injection into the affected joints
Systemic steroids may be required, particularly where multiple joints are affected
Most cases resolve within 6 months and do not recur. Recurrent cases may require DMARDs or anti-TNF medications.
Ankylosing spondylitis
Ankylosing spondylitis (AS) is an inflammatory condition affecting the axial skeleton (mainly the spine and sacroiliac joints), causing progressive stiffness and pain. It is also known as axial spondyloarthritis. It is part of the seronegative spondyloarthropathy group of conditions, also including psoriatic arthritis and reactive arthritis.
The main affected joints are the sacroiliac joints and the vertebral column joints. Inflammation causes pain and stiffness in these joints. It can progress to spine and sacroiliac joint fusion.
There is a strong link with the HLA-B27 gene. Around 90% of AS patients have the HLA-B27 gene. It is thought that less than 10% of people with the gene will get AS. It is more common in men (but women can also be affected).
Presentation of ankylosing spondylitis
The typical presentation is a young adult male in their 20s. Symptoms develop gradually over at least three months.
The main presenting features are
Pain and stiffness in the lower back
Sacroiliac pain (in the buttock region)
The pain and stiffness is worse with rest and improves with movement. The pain worsens at night and in the morning and may wake them. The stiffness takes at least 30 minutes to improve in the morning. Symptoms improve with activity and worsen with rest.
Additional symptoms and problems include:
Chest pain related to the costovertebral and sternocostal joints
Enthesitis (inflammation of the entheses, where tendons or ligaments insert into bone)
Dactylitis (inflammation of the entire finger)
Vertebral fractures (presenting with sudden-onset new neck or back pain)
Shortness of breath relating to restricted chest wall movement)
Conditions associated with ankylosing spondylitis
There is a long list of associated conditions. The key ones can be remembered with the 5 As mnemonic:
A – Anterior uveitis
A – Aortic regurgitation
A – Atrioventricular block (heart block)
A – Apical lung fibrosis (fibrosis of the upper lobes of the lungs)
A – Anaemia of chronic disease
Schober’s test
Schober’s test assesses spinal mobility. With the patient standing straight, the L5 vertebra is located, and a point is marked 10cm above and 5cm below this level (15cm apart). Then the patient bends forward as far as possible, and the distance between the points is measured. A length of less than 20cm indicates a restriction in lumbar movement and helps support a diagnosis of ankylosing spondylitis.
Investigating ankylosing spondylitis
Key investigations include:
Inflammatory markers (e.g., CRP and ESR) may rise with disease activity
HLA B27 genetic testing
X-ray of the spine and sacrum
MRI of the spine can show bone marrow oedema early in the disease before there are any xray changes
Xray changes in ankylosing spondylitis
A “bamboo spine” is the typical x-ray finding in the later stages of ankylosing spondylitis, where there is fusion of the sacroiliac and spinal joints.
X-rays in ankylosing spondylitis can show:
Squaring of the vertebral bodies
Subchondral sclerosis and erosions
Syndesmophytes (areas of bone growth where the ligaments insert into the bone)
Ossification of the ligaments, discs and joints (these structures start turning into bone)
Fusion of the facet, sacroiliac and costovertebral joints
Managing ankylosing spondylitis
The rheumatology multidisciplinary team will manage patients. Treatment aims to control symptoms and preserve function.
Medical management may involve:
Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line
Anti-TNF medications are second-line (e.g., adalimumab, etanercept or infliximab)
Secukinumab or ixekizumab are third-line (monoclonal antibodies against interleukin-17)
Upadacitinib is another third-line option (JAK inhibitor)
Intra-articular steroid injections may be considered for specific joints.
Additional management:
Physiotherapy
Exercise and mobilisation
Avoiding smoking
Bisphosphonates for osteoporosis
Surgery is occasionally required for severe joint deformity
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune connective tissue disorder. It is “systemic” because it affects multiple organs and systems. “Erythematosus” refers to the typical red malar rash across the face.
SLE can affect anyone but occurs more commonly in:
Women
Asian, African, Caribbean and Hispanic ethnicity
Young to middle-aged adults
SLE typically takes a relapsing-remitting course, with flares of worse symptoms and periods where symptoms settle. The result of chronic inflammation means SLE can shorten life expectancy (although this is mitigated with effective management). Cardiovascular disease and infection are significant complications.
Pathophysiology of SLE
SLE is characterised by anti-nuclear antibodies (ANA). These are autoantibodies against proteins within the cell nucleus. These antibodies generate a chronic inflammatory response, leading to the condition’s features.
Presentation of systemic lupus erythematosus
SLE presents with many non-specific symptoms:
Fatigue
Weight loss
Arthralgia (joint pain)
Non-erosive arthritis
Myalgia (muscle pain)
Fever
Photosensitive malar rash
Lymphadenopathy
Splenomegaly
Shortness of breath
Pleuritic chest pain
Mouth ulcers
Hair loss
Raynaud’s phenomenon
Oedema (due to nephritis)
The typical malar rash is “butterfly” shaped across the nose and cheeks. It is triggered or worsened by sunlight.
Investigating SLE
Abnormal investigation findings in SLE include:
Autoantibodies (more information below)
Full blood count may show anaemia of chronic disease, low white cell count and low platelets
CRP and ESR may be raised with active inflammation
C3 and C4 levels may be decreased in active disease
Urinalysis and urine protein:creatinine ratio shows proteinuria in lupus nephritis
Renal biopsy may be used to investigate for lupus nephritis
Autoantibodies and SLE
Around 85% of patients with SLE will be positive for anti-nuclear antibodies (ANA). These can be positive in healthy individuals and those with other autoimmune conditions (e.g., autoimmune hepatitis). A positive result needs to be interpreted in the context of their symptoms.
Anti-double stranded DNA (anti-dsDNA) antibodies are highly specific to SLE, meaning a positive result suggests SLE rather than other causes. Around half of patients with SLE have anti-dsDNA antibodies. The levels vary with disease activity, making them helpful in monitoring disease activity and response to treatment.
An extractable nuclear antigen panel looks for antibodies to specific proteins in the cell nucleus and helps diagnose and distinguish between specific connective tissue disorders:
Anti-Sm (highly specific to SLE but not very sensitive)
Anti-centromere antibodies (most associated with limited cutaneous systemic sclerosis)
Anti-Ro and anti-La (most associated with Sjögren’s syndrome)
Anti-Scl-70 (most associated with systemic sclerosis)
Anti-Jo-1 (most associated with dermatomyositis)
Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE in up to 40% of patients. These antibodies are associated with an increased risk of venous thromboembolism.
SLE diagnostic criteria
The European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) criteria (2019) can be used for diagnosis. This takes into account the clinical features and autoantibodies suggestive of SLE.
Complications of SLE
Cardiovascular disease is a leading cause of death. Chronic inflammation in blood vessels leads to hypertension and coronary artery disease.
Infection is more common, both from the disease process and secondary to immunosuppressant drugs.
Anaemia in SLE can be due to anaemia of chronic disease, autoimmune haemolytic anaemia, bone marrow suppression by medications or kidney disease. It can also cause leucopenia (low white cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).
Pericarditis (inflammation of the pericardial sac surrounding the heart) causes sharp chest pain that gets worse on lying flat.
Pleuritis (inflammation of the lining of the lungs) causes sharp chest pain on inspiration.
Interstitial lung disease can be caused by inflammation in the lung tissue, leading to pulmonary fibrosis.
Lupus nephritis (inflammation in the kidney) can progress to end-stage renal failure. Investigations include a urine protein:creatinine ratio and renal biopsy. The renal biopsy is often repeated to assess the response to treatment.
Neuropsychiatric SLE is caused by inflammation in the central nervous system. It can present with optic neuritis (inflammation of the optic nerve), transverse myelitis (inflammation of the spinal cord) or psychosis.
Recurrent miscarriage is more common in SLE. There is also an increased risk of intrauterine growth restriction, pre-eclampsia and pre-term labour.
Venous thromboembolism may be associated with antiphospholipid syndrome occurring secondary to SLE.
Managing SLE
Treatment aims to control symptoms and reduce complications with the least medications and side effects. Suncream and sun avoidance are essential measures in managing the photosensitive malar rash.
First-line options include:
Hydroxychloroquine
NSAIDs
Steroids (e.g., prednisolone)
Treatment options for resistant or more severe SLE include:
DMARDs (e.g., methotrexate, mycophenolate mofetil or cyclophosphamide)
Biologic therapies
Biological therapies include:
Rituximab (a monoclonal antibody that targets the CD20 protein on the surface of B cells)
Belimumab (a monoclonal antibody that targets B-cell activating factor)
Discoid lupus erythematosus
Discoid lupus erythematosus (DLE) is an autoimmune chronic skin condition. It is more common in women and typically presents between the ages of 20-50. It is more common in darker-skinned patients and smokers.
Discoid lupus is associated with an increased risk of developing systemic lupus erythematosus. However, this risk is below 5%. Rarely the lesions can progress to squamous cell carcinoma (SCC) of the skin.
Presentation of discoid lupus erythematosus
The lesions typically occur on the face, scalp and ears. They are photosensitive, meaning they are made worse by exposure to sunlight. They are associated with scarring alopecia (with scarring and hair loss in affected areas) and hyperpigmentation or hypopigmentation.
The appearance of the lesions or plaques are:
Inflamed
Dry
Erythematous (red)
Scaling
Managing discoid lupus erythematosus
A skin biopsy can be used to confirm the diagnosis.
Treatment is with
Sun protection
Topical steroids
Intralesional steroid injections
Hydroxychloroquine
Systemic sclerosis
Systemic sclerosis is an autoimmune connective tissue disease involving inflammation and fibrosis (hardening or scarring) of the connective tissues, skin and internal organs. The cause is unclear.
Scleroderma translates directly to the hardening of the skin. The terms systemic sclerosis and scleroderma are often used interchangeably. Most patients with scleroderma have systemic sclerosis. However, a localised version of scleroderma only affects the skin.
There are two main patterns of disease in systemic sclerosis:
Limited cutaneous systemic sclerosis
Diffuse cutaneous systemic sclerosis
