Medicine – Clinical Features of Reiter’s Syndrome

Reiter’s syndrome, now more commonly referred to as reactive arthritis, is an inflammatory arthritis that develops after certain infections, particularly gastrointestinal or genitourinary infections. It belongs to the seronegative spondyloarthritis group and has a strong association with HLA-B27, which is present in a substantial proportion of affected patients. The classic presentation consists of a triad of arthritis, conjunctivitis, and urethritis, although many patients do not develop all three features simultaneously.

Classic Triad

1. Arthropathy

The arthritis of reactive arthritis typically presents as an acute, asymmetrical oligoarthritis involving mainly the lower limbs. The knees, ankles, and feet are commonly affected, and patients may experience pain, swelling, stiffness, and reduced joint movement. Enthesitis may also occur, particularly at the heel, and some patients can develop inflammatory back pain due to sacroiliac or spinal involvement.

2. Conjunctivitis

Conjunctivitis is a common extra-articular manifestation and usually causes redness, irritation, watering, and discomfort of the eyes. It is often mild and self-limiting, although more significant ocular inflammation such as anterior uveitis can occur in some patients and may cause pain, photophobia, or blurred vision.

3. Urethritis

Urethritis is another classical feature and may present with dysuria, urinary frequency, or urethral discharge. In sexually acquired cases, the condition may follow infection with organisms such as Chlamydia trachomatis. Some patients have only mild urinary symptoms or may be asymptomatic despite preceding infection.

Other Clinical Features

1. Sacroiliitis

Inflammation of the sacroiliac joints may occur and can cause lower back or buttock pain, particularly in patients with HLA-B27 positivity. The pain is typically inflammatory in nature, often worse after rest and improved with movement.

2. Plantar Fasciitis

Plantar fasciitis may develop as part of enthesitis, which is inflammation at the site where tendons or ligaments attach to bone. Patients commonly experience pain around the heel or sole of the foot, especially during walking or after periods of rest.

3. Circinate Balanitis

Circinate balanitis is a characteristic mucocutaneous lesion involving the glans penis. It usually appears as shallow, painless, well-defined erythematous lesions and may occur even in the absence of marked urethral symptoms.

4. Keratoderma Blennorrhagicum

Keratoderma blennorrhagicum is a distinctive skin manifestation consisting of hyperkeratotic, scaly lesions, most often affecting the soles of the feet and palms of the hands. These lesions can resemble pustular psoriasis and may occur alongside other features of reactive arthritis.

5. Oral Ulceration

Patients may develop painless oral ulcers, usually involving the oral mucosa. These lesions are generally transient and may go unnoticed unless specifically looked for during examination.

6. Pericarditis

Although uncommon, pericarditis can occur as a systemic inflammatory complication. Patients may present with central chest pain that is worse on inspiration or lying flat and relieved by sitting forward. Cardiac involvement is much less common than the musculoskeletal, ocular, and genitourinary manifestations.

Key Clinical Pattern

Reactive arthritis is classically remembered by the triad of arthritis, conjunctivitis, and urethritis, with additional features such as sacroiliitis, plantar fasciitis, circinate balanitis, keratoderma blennorrhagicum, oral ulcers, and occasionally pericarditis. The condition is strongly associated with HLA-B27, particularly in patients with more persistent or axial disease.

Medicine – Patterns of Disease in Psoriatic Arthropathy

Psoriatic arthropathy, more commonly called psoriatic arthritis (PsA), is a chronic inflammatory arthritis associated with psoriasis. It belongs to the spondyloarthritis group of disorders and can affect peripheral joints, the spine, sacroiliac joints, digits, and entheses. The pattern of joint involvement varies considerably between patients and may also change during the course of the disease. Traditionally, psoriatic arthritis has been divided into several characteristic patterns, including peripheral oligoarthritis or polyarthritis, spondylitis, distal interphalangeal joint disease, rheumatoid-like arthritis, and arthritis mutilans.

1. Peripheral Oligoarthritis or Polyarthritis

Peripheral oligoarthritis or polyarthritis is the most common pattern and has traditionally been reported in approximately 60% of patients. Oligoarthritis involves only a few joints, whereas polyarthritis affects a larger number of joints. The arthritis may involve both small and large peripheral joints and is often asymmetrical, particularly when relatively few joints are affected.

Patients may develop pain, swelling, stiffness, and reduced movement of the affected joints. Involvement of an entire finger or toe can produce dactylitis, giving the characteristic appearance of a “sausage digit.” Enthesitis, caused by inflammation where tendons or ligaments attach to bone, may accompany the peripheral arthritis.

2. Spondylitis

Approximately 15% of patients in traditional classifications have a predominantly spondylitic pattern. Inflammation affects the spine and sacroiliac joints, producing symptoms similar to other forms of axial spondyloarthritis. Patients may experience chronic inflammatory back pain, morning stiffness, and reduced spinal mobility.

Sacroiliitis may be asymmetrical, particularly during the earlier stages of psoriatic arthritis. Spinal involvement can progress and eventually produce significant restriction of movement. Some patients have axial disease together with peripheral arthritis.

3. Distal Interphalangeal Joint Disease

A predominantly distal interphalangeal (DIP) joint pattern has traditionally been described in approximately 10% of patients. The DIP joints are the joints closest to the fingernails and toenails, and their involvement is particularly characteristic of psoriatic arthritis.

DIP arthritis is frequently associated with psoriatic nail disease, including nail pitting, separation of the nail from the nail bed (onycholysis), and other dystrophic nail changes. The close anatomical relationship between the nail apparatus and DIP joint helps explain this association. DIP involvement can be useful in distinguishing psoriatic arthritis from rheumatoid arthritis, in which these joints are usually spared.

4. Rheumatoid-Type Polyarthritis

Approximately 10% of patients in older classifications develop a rheumatoid-like pattern of arthritis. This consists of a more symmetrical polyarthritis involving multiple small peripheral joints and may clinically resemble rheumatoid arthritis.

Despite the similarities, several features can suggest psoriatic arthritis, including coexisting psoriasis, nail changes, dactylitis, DIP joint involvement, and enthesitis. Most patients with psoriatic arthritis are also negative for rheumatoid factor, although rheumatoid factor positivity can occasionally occur and therefore does not completely exclude the diagnosis.

5. Arthritis Mutilans

Arthritis mutilans is the rarest and most severe traditional pattern, historically accounting for approximately 5% of cases. It is characterised by aggressive osteolysis and destruction of the small joints, particularly those of the hands and feet.

Progressive destruction of bone can result in marked shortening, instability, and deformity of the digits. Severe resorption of the phalanges may produce a characteristic “telescoping” appearance, in which the affected digit can be shortened or extended because of extensive loss of supporting bone. Although arthritis mutilans represents a particularly destructive manifestation of psoriatic arthritis, it is uncommon in modern clinical practice.

Key Clinical Pattern

The traditional patterns of psoriatic arthropathy can be remembered as peripheral oligoarthritis/polyarthritis (60%), spondylitis (15%), DIP-predominant disease (10%), rheumatoid-type polyarthritis (10%), and arthritis mutilans (5%). These categories can overlap, and an individual patient’s pattern of joint involvement may change as the disease progresses.

Medicine – Treatment of Spondyloarthropathies

The spondyloarthropathies, now commonly referred to as spondyloarthritis (SpA), are a group of inflammatory rheumatic diseases that predominantly affect the spine, sacroiliac joints, peripheral joints, and entheses. Management aims to reduce pain and inflammation, maintain mobility and posture, preserve physical function, and prevent structural complications. Treatment depends on whether the disease is predominantly axial or peripheral and on the severity of the patient’s symptoms.

1. Physiotherapy

Physiotherapy and regular exercise are fundamental components of treatment, particularly in patients with axial spondyloarthritis or ankylosing spondylitis. Exercise programmes are designed to maintain spinal mobility, flexibility, muscle strength, and good posture. Stretching and range-of-motion exercises can help reduce stiffness and prevent progressive loss of movement. Breathing exercises may also be useful for maintaining chest expansion when the thoracic spine and costovertebral joints are affected.

2. Local Steroid Injections

Local corticosteroid injections may be useful when inflammation is confined to a particular peripheral joint or enthesis. Injection directly into the affected area can reduce local pain, swelling, and inflammation while limiting the systemic adverse effects associated with prolonged oral corticosteroid therapy. Repeated injections into the same site should generally be used cautiously.

3. Non-Steroidal Anti-Inflammatory Drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used as initial pharmacological treatment for pain and stiffness, especially in axial spondyloarthritis. They reduce inflammation and can improve back pain, morning stiffness, and overall mobility. Treatment should be individualised because prolonged NSAID use can produce gastrointestinal, renal, and cardiovascular adverse effects.

4. Systemic Corticosteroids

Systemic corticosteroids can suppress inflammation rapidly and may occasionally be used for severe inflammatory manifestations or particular extra-articular complications. However, prolonged systemic steroid treatment is generally not preferred for predominantly axial disease because of limited long-term benefit and the considerable adverse effects associated with chronic corticosteroid exposure.

5. Sulfasalazine

Sulfasalazine is a conventional disease-modifying antirheumatic drug that can be useful in patients with persistent peripheral arthritis associated with spondyloarthritis. It has considerably less benefit for inflammation that is predominantly confined to the spine and sacroiliac joints. Adverse effects include gastrointestinal disturbance, skin reactions, liver abnormalities, cytopenias, and reversible reduction in sperm count.

6. Methotrexate

Methotrexate is another conventional disease-modifying antirheumatic drug that may be considered in selected patients with significant peripheral joint involvement. Like sulfasalazine, it has little established benefit for purely axial manifestations. Patients receiving methotrexate require monitoring for important adverse effects, particularly hepatotoxicity and bone marrow suppression.

Modern treatment of persistently active spondyloarthritis may also involve biologic or targeted therapies, particularly when symptoms remain inadequately controlled despite NSAIDs and appropriate non-pharmacological management. These include agents targeting TNF or IL-17, with treatment selected according to the type of spondyloarthritis and associated manifestations.

7. Antibiotics

Antibiotics are not routine treatment for most forms of spondyloarthritis. They should be used when there is an identifiable active bacterial infection requiring antimicrobial therapy. This is particularly relevant when an infection has triggered reactive arthritis. Treating the acute infection is important, although antibiotic therapy does not necessarily eliminate established joint inflammation once reactive arthritis has developed.

Key Treatment Principle

Management of spondyloarthritis combines regular exercise and physiotherapy with appropriate anti-inflammatory treatment. NSAIDs are particularly useful for axial symptoms, while sulfasalazine or methotrexate may have a role in peripheral arthritis. Local steroid injections can control focal inflammation, antibiotics are reserved for appropriate active infections, and biologic or targeted therapy may be required for persistently active disease.

Medicine – Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune connective tissue disease characterised by the production of numerous autoantibodies and the formation of immune complexes. These immune abnormalities can produce inflammation and tissue damage in almost any organ system. The clinical presentation is therefore highly variable, ranging from relatively mild skin and joint manifestations to severe renal, neurological, cardiovascular, or haematological disease. SLE typically follows a course of flares and remissions, with periods of increased disease activity alternating with periods of relative stability.

American College of Rheumatology Revised Criteria for SLE

The 1982 revised American College of Rheumatology (ACR) criteria were historically used to classify SLE. According to these criteria, the presence of four or more of eleven criteria, occurring either simultaneously or at different times, strongly supported classification as SLE. These criteria have subsequently been replaced by newer classification systems, but the original ACR criteria remain useful for understanding the major manifestations of the disease.

1. Malar Rash

The malar or butterfly rash is an erythematous eruption occurring over the cheeks and bridge of the nose. It typically follows the shape of a butterfly and often spares the nasolabial folds. Exposure to sunlight may trigger or worsen the rash because photosensitivity is common in SLE.

2. Discoid Rash

A discoid rash consists of raised, well-defined erythematous plaques with adherent scaling. As the lesions heal, they may leave scarring, pigmentary changes, and areas of skin atrophy. When lesions involve the scalp, permanent scarring alopecia may occur.

3. Photosensitivity

Photosensitivity refers to an abnormal skin reaction following exposure to ultraviolet radiation. Sunlight may provoke or worsen lupus rashes and can sometimes contribute to a more general disease flare. Patients are therefore usually advised to minimise excessive ultraviolet exposure and use appropriate sun protection.

4. Oral Ulcers

Patients may develop recurrent oral or nasopharyngeal ulcers, which are often painless. Ulcers may occur on the palate, buccal mucosa, or other mucosal surfaces and can appear during periods of active disease.

5. Arthritis

Arthritis is one of the most common manifestations of SLE. It is usually a non-erosive inflammatory arthritis affecting two or more peripheral joints. Patients commonly experience joint pain, swelling, tenderness, and morning stiffness, particularly involving the small joints of the hands, wrists, and knees.

6. Serositis

Inflammation of serosal membranes may produce pleuritis or pericarditis. Pleuritis commonly causes sharp chest pain that becomes worse with deep inspiration, while pericarditis may produce central or positional chest pain. Pleural or pericardial effusions may also develop.

7. Renal Disease

Renal involvement is an important cause of morbidity in SLE. Under the older ACR criteria, renal disease was demonstrated by persistent proteinuria greater than 0.5 g per day or the presence of cellular casts. Lupus nephritis can vary considerably in severity, ranging from mild urinary abnormalities to rapidly progressive renal dysfunction.

8. Neurological Disorder

Neurological involvement under the traditional criteria included seizures or psychosis when these could not be explained by medications, metabolic abnormalities, or another identifiable cause. SLE can also produce many other neurological and psychiatric manifestations.

9. Haematological Disorder

Several blood abnormalities may occur as a consequence of autoimmune destruction or bone marrow effects. These include haemolytic anaemia, leukopenia, lymphopenia, and thrombocytopenia. The abnormalities may occur individually or in combination and can fluctuate with disease activity.

10. Immunological Disorder

The older ACR immunological criterion included characteristic autoimmune laboratory abnormalities such as anti-double-stranded DNA (anti-dsDNA) antibodies, anti-Smith (anti-Sm) antibodies, and antiphospholipid antibodies. Historically, LE cells and a false-positive serological test for syphilis, such as VDRL, were also included.

11. Antinuclear Antibody

A positive antinuclear antibody (ANA) test is highly sensitive for SLE and is present in the great majority of patients. However, ANA is not specific for lupus and may occur in several other autoimmune diseases and even in some healthy individuals.

Clinical Features of SLE

1. Mucocutaneous Manifestations

Mucocutaneous abnormalities are very common, traditionally reported in approximately 81% of patients. Characteristic skin manifestations include malar, discoid, and photosensitive rashes. Alopecia may occur and can be diffuse or associated with discoid lesions.

Patients may also develop oral, nasal, or genital ulcers. Vascular manifestations include Raynaud’s phenomenon, which has historically been reported in approximately half of patients, as well as livedo reticularis and cutaneous vasculitis. Features of Sjögren’s syndrome, particularly dry eyes and dry mouth, may coexist in some patients.

2. Musculoskeletal Manifestations

Musculoskeletal symptoms are among the most frequent manifestations of SLE and occur in the majority of patients. Arthritis is typically non-erosive and may be migratory. Persistent ligament and tendon laxity can occasionally produce reversible joint deformities known as Jaccoud arthropathy, despite the absence of the typical erosions seen in rheumatoid arthritis.

Patients may also experience myalgia, while inflammatory myositis can occasionally cause objective muscle weakness and elevated muscle enzymes. Joint and muscle symptoms can contribute substantially to pain and functional impairment even when other organs are unaffected.

3. Renal Manifestations

Renal involvement, particularly lupus nephritis, is one of the most clinically significant complications of SLE. Immune-complex deposition within the glomeruli can produce various patterns of glomerulonephritis, resulting in haematuria, proteinuria, cellular casts, and impaired renal function.

More severe disease may produce nephrotic syndrome and hypertension. Progressive renal injury can eventually result in chronic kidney disease and, in a minority of patients, end-stage renal failure. Early recognition and appropriate treatment of lupus nephritis are therefore essential.

4. Respiratory Manifestations

Pulmonary involvement may include pleurisy, often accompanied by pleural effusion. Patients can also develop inflammatory lung disease such as pneumonitis, although infection must always be considered in an immunosuppressed patient with new respiratory symptoms.

Other complications include pulmonary hypertension and the uncommon shrinking lung syndrome, which is characterised by unexplained reduction in lung volumes and respiratory symptoms without extensive pulmonary fibrosis.

5. Cardiovascular Manifestations

Pericarditis is one of the most frequent cardiac manifestations of SLE. Inflammation may also involve the myocardium, resulting in myocarditis or cardiomyopathy, which can impair cardiac function.

Another characteristic cardiac abnormality is Libman–Sacks endocarditis, a form of sterile non-bacterial endocarditis involving the heart valves. Patients with SLE also have an increased long-term risk of cardiovascular disease, including accelerated atherosclerosis.

6. Central and Peripheral Nervous System Manifestations

SLE can affect both the central and peripheral nervous systems. Neurological manifestations may include headaches or migraine, seizures, chorea, and psychiatric disturbances such as psychosis. The mechanisms are varied and may involve autoantibodies, inflammation, vascular injury, or thrombosis.

Cerebrovascular events such as stroke may occur, particularly in patients with associated antiphospholipid antibodies. Peripheral nervous system involvement may produce disorders such as mononeuritis multiplex, in which multiple individual peripheral nerves become affected.

7. Haematological Manifestations

Haematological abnormalities are common and include leukopenia, neutropenia, lymphopenia, and thrombocytopenia. Autoimmune haemolytic anaemia may also develop because antibodies are directed against circulating red blood cells.

Some patients develop lymphadenopathy or splenomegaly, particularly during active systemic disease. SLE is also strongly associated with antiphospholipid antibodies and antiphospholipid syndrome, which can cause recurrent arterial or venous thrombosis and pregnancy complications.

8. Gastrointestinal and Hepatic Manifestations

Gastrointestinal involvement may result from inflammation or vascular disease. Mesenteric vasculitis can compromise intestinal blood flow and produce abdominal pain, gastrointestinal bleeding, or more severe bowel complications.

Liver abnormalities may also occur. Although older descriptions include chronic active hepatitis, abnormal liver function in a patient with SLE requires consideration of several possibilities, including medication toxicity, infection, fatty liver disease, vascular complications, and overlapping autoimmune liver disease.

Typical Investigation Results in SLE

1. Anaemia

Patients with active SLE commonly develop normocytic, normochromic anaemia, particularly as a manifestation of chronic inflammation. Other causes include renal impairment, iron deficiency, medication effects, and autoimmune haemolysis.

2. Leukopenia and Lymphopenia

Leukopenia and lymphopenia are common haematological abnormalities and may reflect active autoimmune disease. Their severity can also be influenced by immunosuppressive treatment or infection.

3. Raised ESR

The erythrocyte sedimentation rate (ESR) is frequently elevated during active SLE because of increased circulating inflammatory and immunological proteins. ESR is nonspecific but can contribute to the assessment of inflammatory activity.

4. C-Reactive Protein

An interesting laboratory pattern in SLE is that the C-reactive protein (CRP) may remain relatively normal despite active disease. A substantial CRP elevation should raise particular concern for infection, although CRP can also increase with significant serositis or synovitis.

5. Positive ANA

Approximately 95% or more of patients with SLE have a positive ANA, making it a highly sensitive screening marker. However, because ANA positivity occurs in numerous other conditions, it cannot establish the diagnosis by itself.

6. Anti-dsDNA Antibodies

Anti-dsDNA antibodies are considerably more specific for SLE than ANA. Their concentrations may fluctuate with disease activity in some patients and are particularly useful when evaluating lupus nephritis.

7. Raised Immunoglobulins

Patients may demonstrate polyclonal hypergammaglobulinaemia, reflecting chronic activation of B lymphocytes and increased antibody production.

8. Low Complement Levels

During active immune-complex disease, complement components are consumed, producing reduced serum C3 and C4 concentrations. Falling complement levels, particularly when accompanied by rising anti-dsDNA titres, may indicate increasing disease activity in some patients.

9. Antiphospholipid Antibodies

Antiphospholipid antibodies occur in a substantial proportion of patients with SLE, historically quoted at around 30–40%. Persistent clinically significant antibodies may increase the risk of arterial or venous thrombosis and adverse pregnancy outcomes.

10. Coombs-Positive Haemolytic Anaemia

Some patients develop autoimmune haemolytic anaemia, in which antibodies bind to red blood cells and accelerate their destruction. The direct antiglobulin (Coombs) test may consequently be positive.

Causes of a Positive ANA

A positive ANA is not unique to SLE. It is frequently found in SLE, but may also occur in Sjögren’s syndrome, polymyositis or dermatomyositis, rheumatoid arthritis, systemic sclerosis, mixed connective tissue disease, and autoimmune hepatitis. ANA positivity can also occur in healthy individuals, particularly at low titres, so the result must always be interpreted in the appropriate clinical context.

Treatment of SLE

1. Sun Protection

Because ultraviolet radiation can provoke cutaneous lesions and potentially trigger disease activity, patients with photosensitivity should use broad-spectrum sunscreen, protective clothing, and appropriate avoidance of excessive sunlight.

2. NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) may provide symptomatic relief for selected patients with musculoskeletal pain or mild inflammatory manifestations. Their use must take into account gastrointestinal, cardiovascular, and renal risks, particularly when lupus nephritis is present.

3. Hydroxychloroquine

Hydroxychloroquine is a central treatment for most patients with SLE unless contraindicated. It is particularly helpful for skin manifestations, arthritis, and constitutional symptoms and also reduces the risk of disease flares. Long-term treatment requires appropriate ophthalmological monitoring because of the risk of retinal toxicity.

4. Corticosteroids

Corticosteroids are used to rapidly suppress inflammation during significant disease flares. The required dose depends on the severity and organs involved. Severe organ-threatening disease may require high-dose or intravenous corticosteroids, whereas lower doses may be used for shorter periods when necessary. Modern management aims to minimise prolonged corticosteroid exposure because of its substantial long-term adverse effects.

5. Immunosuppressive and Immunomodulatory Therapy

More severe disease may require additional immunosuppressive or immunomodulatory drugs. Depending on the manifestation, these may include azathioprine, methotrexate, mycophenolate, cyclophosphamide, or biologic therapies. Severe lupus nephritis and other organ-threatening manifestations generally require more intensive treatment than uncomplicated skin or joint disease.

6. Plasma Exchange

Plasma exchange is not routine treatment for SLE, but it may occasionally be considered in selected severe complications or overlapping conditions where rapid removal of pathogenic circulating factors is thought to be beneficial.

7. Anticoagulation

Patients with SLE who develop antiphospholipid syndrome with recurrent or significant thrombosis may require long-term anticoagulant therapy. Management depends on whether thrombosis is venous or arterial and the patient’s individual risk of recurrence and bleeding.

8. Treatment of Raynaud’s Phenomenon

Raynaud’s phenomenon can initially be managed by maintaining warmth and avoiding smoking and other vasoconstrictive factors. Persistent symptoms may require vasodilator therapy, particularly calcium channel blockers. More severe digital ischaemia may require additional vasodilator treatments such as prostacyclin analogues.

9. Antihypertensive Treatment

Hypertension should be identified and treated carefully, particularly in patients with renal involvement. Effective blood-pressure control helps reduce cardiovascular risk and may slow further renal damage.

Important Note on Classification

The 1982 ACR criteria described above are historical classification criteria rather than the current standard. Modern practice commonly uses the 2019 EULAR/ACR classification criteria, in which a positive ANA is an entry requirement followed by weighted clinical and immunological criteria. Nevertheless, the older eleven-point ACR framework remains useful for learning the classic multisystem manifestations of SLE.

Medicine – Essential Features of Antiphospholipid Antibody Syndrome

Antiphospholipid antibody syndrome (APS) is an acquired autoimmune thrombophilic disorder characterised by the presence of persistent antiphospholipid antibodies together with recurrent arterial or venous thrombosis and/or characteristic pregnancy complications. The syndrome may occur as a primary disorder or in association with another autoimmune disease, particularly systemic lupus erythematosus (SLE). An important feature of APS is the apparent paradox that some antiphospholipid antibodies produce an anticoagulant effect in laboratory tests but promote thrombosis within the body.

1. Antiphospholipid Antibodies

Patients with APS have circulating autoantibodies directed against phospholipid-binding proteins. Clinically important laboratory antibodies include lupus anticoagulant, anticardiolipin IgG or IgM antibodies, and anti-β2-glycoprotein I antibodies. These antibodies interfere with normal phospholipid-dependent coagulation reactions and are responsible for many of the characteristic laboratory and clinical findings of the syndrome.

2. False-Positive VDRL Test

Antiphospholipid antibodies can produce a false-positive Venereal Disease Research Laboratory (VDRL) test for syphilis. The VDRL test uses cardiolipin-containing antigen, and anticardiolipin antibodies present in APS may therefore react with the test despite the absence of syphilis. A positive VDRL result in this setting should consequently be confirmed with an appropriate specific treponemal test.

3. Anticoagulant Effect In Vitro

In laboratory testing, the lupus anticoagulant can interfere with phospholipid-dependent coagulation assays and cause prolongation of the activated partial thromboplastin time (APTT). When a mixing study is performed by adding normal plasma to the patient’s plasma, the prolonged clotting time may fail to correct, suggesting the presence of an inhibitor rather than a simple clotting-factor deficiency.

This produces an important apparent paradox. Although the lupus anticoagulant can prolong clotting tests in vitro, patients are generally not anticoagulated clinically. Instead, these antibodies are associated with an increased tendency to develop thrombosis in vivo.

4. Recurrent Thrombosis In Vivo

The major clinical consequence of APS is a predisposition to recurrent thrombosis. Thrombotic events can involve either the venous or arterial circulation and may affect vessels of different sizes. Recurrent episodes are particularly suggestive when thrombosis occurs in younger patients or in the absence of conventional thrombotic risk factors.

Clinical Features

1. Venous Thrombosis

Venous thromboembolism is one of the most common manifestations of APS. Deep vein thrombosis (DVT) of the lower limbs is particularly characteristic and may present with unilateral leg pain, swelling, warmth, and tenderness. A thrombus may embolise to the pulmonary circulation and cause a pulmonary embolism, resulting in acute breathlessness, chest pain, or haemodynamic compromise.

2. Arterial Thrombosis

APS can also produce arterial thrombosis, potentially affecting the cerebral, coronary, or peripheral circulation. Cerebral arterial thrombosis may result in a stroke (cerebrovascular accident) or transient ischaemic attack, while coronary artery thrombosis can contribute to myocardial infarction. The precise clinical manifestation depends on the artery involved and the degree of vascular obstruction.

3. Recurrent Miscarriage and Pregnancy Complications

Pregnancy morbidity is an important manifestation of APS. Placental vascular thrombosis and abnormal placental function can contribute to recurrent miscarriage, fetal loss, placental insufficiency, fetal growth restriction, and premature delivery. The combination of recurrent pregnancy loss and persistent antiphospholipid antibodies should therefore raise suspicion of obstetric APS.

4. Thrombocytopenia

Patients may develop thrombocytopenia, usually as a result of increased platelet activation and consumption associated with the autoimmune process. The reduction in platelet count is often mild to moderate. Despite the thrombocytopenia, the predominant clinical problem in APS is generally thrombosis rather than spontaneous bleeding.

5. Livedo Reticularis

Livedo reticularis is a vascular skin manifestation that produces a characteristic mottled, violaceous, net-like pattern on the skin. It results from abnormalities in the cutaneous circulation and may provide an external clue to the underlying vascular abnormalities associated with APS.

6. Pulmonary Hypertension

Pulmonary hypertension may occur in patients with APS, particularly as a consequence of recurrent pulmonary thromboembolism or chronic thromboembolic obstruction of the pulmonary vessels. Progressive elevation of pulmonary arterial pressure can produce exertional breathlessness, fatigue, chest discomfort, syncope, and eventually right-sided heart failure.

Key Clinical Concept

Antiphospholipid antibody syndrome is characterised by the important paradox of prolonged phospholipid-dependent clotting tests in vitro but an increased risk of thrombosis in vivo. The major clinical manifestations are recurrent venous or arterial thrombosis and pregnancy morbidity, while associated findings can include thrombocytopenia, livedo reticularis, and pulmonary hypertension.

Medicine – Systemic Sclerosis (Scleroderma)

Systemic sclerosis, also known as scleroderma, is a chronic autoimmune connective tissue disease characterised by vascular dysfunction, immune activation, and progressive fibrosis of the skin and internal organs. The disease is broadly divided into diffuse systemic sclerosis and limited systemic sclerosis, depending mainly on the extent of skin involvement and the pattern of internal organ disease.

Diffuse Systemic Sclerosis

Diffuse systemic sclerosis is characterised by more extensive skin involvement, typically affecting the trunk, upper arms, forearms, and other proximal areas in addition to the hands and face. Internal organ involvement may occur relatively early and can affect the lungs, kidneys, heart, and gastrointestinal tract.

A proportion of patients have anti-Scl-70 antibodies, also known as anti-topoisomerase I antibodies. These are particularly associated with diffuse disease and with an increased risk of interstitial lung disease and pulmonary fibrosis. Older teaching sources describe anti-Scl-70 antibodies in approximately 30% of patients with diffuse systemic sclerosis.

Limited Systemic Sclerosis

Limited systemic sclerosis generally causes skin thickening confined to the distal extremities and face, particularly the hands, feet, face, and forearms, with little or no truncal involvement. Internal organ disease may still occur, but it often develops more slowly than in diffuse systemic sclerosis.

This form includes CREST syndrome, which is an acronym for calcinosis, Raynaud’s phenomenon, oesophageal involvement, sclerodactyly, and telangiectasia. Limited systemic sclerosis has a strong association with anti-centromere antibodies, which are found in a high proportion of patients, traditionally quoted at around 70–80%.

Clinical Features of Systemic Sclerosis

1. Musculoskeletal Features

Musculoskeletal symptoms are common and may include polyarthralgia, with pain and stiffness affecting several joints. Some patients also develop inflammatory muscle involvement resembling polymyositis, which can produce proximal muscle weakness and contribute to reduced mobility and functional impairment.

2. Skin and Vascular Features

Raynaud’s phenomenon is one of the most common and often earliest manifestations of systemic sclerosis, occurring in almost all patients. Episodic vasospasm causes the fingers to become pale, cyanosed, and then red on reperfusion, particularly after exposure to cold or emotional stress.

Examination of the nail folds may reveal abnormal nail-fold capillaries, reflecting the underlying small-vessel disease. Sclerodactyly develops when the skin of the fingers becomes thickened, tight, and less flexible. Patients may also develop telangiectasia, particularly on the face, lips, and hands.

As fibrosis progresses, the skin may become tight, smooth, waxy, and hyperpigmented, reducing normal skin mobility. Severe vascular compromise can lead to digital or skin ulcers, particularly over the fingertips. Subcutaneous calcification, or calcinosis, may also occur, producing firm calcium deposits beneath the skin.

3. Cardiac Involvement

Systemic sclerosis can affect the heart in several ways. Cardiomyopathy may develop because of myocardial fibrosis or microvascular disease, leading to impaired cardiac function. Pericarditis may also occur and can cause chest pain or a pericardial effusion.

Patients may additionally develop hypertension, particularly in association with renal involvement. Cardiac complications are clinically important because they can contribute to heart failure, rhythm disturbances, and increased morbidity.

4. Pulmonary Involvement

The lungs are frequently affected in systemic sclerosis. Pulmonary fibrosis, usually in the form of interstitial lung disease, can cause progressive breathlessness, dry cough, and impaired gas exchange. This complication is especially associated with diffuse systemic sclerosis and anti-Scl-70 positivity.

Another major pulmonary complication is pulmonary hypertension, which may occur because of disease affecting the pulmonary vasculature. It is particularly associated with limited systemic sclerosis and can present with exertional dyspnoea, fatigue, syncope, and eventually right-sided heart failure.

5. Gastrointestinal Involvement

The gastrointestinal tract is commonly affected because fibrosis and smooth-muscle dysfunction can impair normal motility. Microstomia, or a small oral aperture, may result from tightening of the skin around the mouth and can make eating and dental care difficult.

Oesophageal involvement is particularly common. Patients may develop dysphagia because of impaired oesophageal motility or peptic strictures. Reduced lower oesophageal sphincter pressure predisposes to gastro-oesophageal reflux disease, which may be accompanied by a hiatus hernia and can lead to oesophagitis or stricture formation.

The small and large bowel may also be affected. Patients can develop intestinal diverticula, reduced motility, and stasis. These changes can encourage bacterial overgrowth, which may lead to diarrhoea, bloating, nutrient malabsorption, and weight loss.

6. Renal Involvement

Renal disease is one of the most serious complications of systemic sclerosis. Some patients develop progressive renal impairment, while others may experience an acute scleroderma renal crisis.

A hypertensive renal crisis is characterised by the sudden onset of severe hypertension and rapidly deteriorating renal function. It is a medical emergency and can progress quickly if not recognised and treated promptly. Renal crisis is particularly associated with diffuse systemic sclerosis and may be accompanied by headache, visual disturbance, heart failure, or microangiopathic haemolytic anaemia.

Key Clinical Pattern

Systemic sclerosis can be remembered as a disease of fibrosis, vasculopathy, and internal organ involvement. Diffuse disease tends to have more extensive skin involvement and a greater association with anti-Scl-70 antibodies and pulmonary fibrosis, whereas limited disease is associated with distal skin involvement, CREST features, and anti-centromere antibodies.

Medicine – Essential Features of Raynaud’s Phenomenon

Raynaud’s phenomenon is an episodic vasospastic disorder affecting the small blood vessels of the fingers and, less commonly, the toes. Attacks are usually triggered by cold exposure or emotional stress and result from excessive constriction of the digital arteries and arterioles. The condition may occur on its own, known as primary Raynaud’s phenomenon, or as a consequence of another disorder, particularly a connective tissue disease, in which case it is termed secondary Raynaud’s phenomenon.

1. Characteristic Colour Changes

A typical episode is characterised by a sequence of colour changes in the affected digits. Initially, the fingers become white and numb because of marked vasoconstriction and reduced arterial blood flow. This may be followed by a blue or cyanotic phase, which occurs as the tissues extract oxygen from the slowly circulating blood. When the vasospasm resolves, blood flow returns and the digits become red, warm, throbbing, and sometimes painful as a result of rebound hyperaemia. Not every patient experiences all three colour phases during every attack.

2. Prevalence

Raynaud’s phenomenon is relatively common and has traditionally been estimated to affect approximately 3–10% of adults. Primary Raynaud’s phenomenon is much more common than secondary disease and often begins in younger individuals, particularly women. In primary disease, the attacks are usually symmetrical and do not normally cause permanent tissue damage.

3. Association with Connective Tissue Disease

Only a minority of people with Raynaud’s phenomenon have an underlying connective tissue disorder, but recognising secondary Raynaud’s is important because it can indicate systemic autoimmune disease. Raynaud’s phenomenon is particularly associated with systemic sclerosis, but it may also occur in systemic lupus erythematosus, Sjögren’s syndrome, mixed connective tissue disease, and inflammatory myopathies. Secondary disease is more likely when attacks begin later in life, are markedly asymmetrical, or are accompanied by digital ulcers, tissue damage, or other systemic features.

Causes

1. Idiopathic Raynaud’s Phenomenon

In many patients, no underlying disease can be identified. This is known as primary or idiopathic Raynaud’s phenomenon. The condition is usually relatively benign, and patients typically experience intermittent attacks triggered by cold or stress without persistent vascular damage.

2. Connective Tissue Disorders

A number of connective tissue diseases can produce secondary Raynaud’s phenomenon. Systemic sclerosis is particularly strongly associated, although SLE, Sjögren’s syndrome, mixed connective tissue disease, and dermatomyositis or polymyositis may also be responsible. In these conditions, structural abnormalities of the blood vessels may accompany vasospasm and increase the risk of digital ischaemia and ulceration.

3. Cervical Rib

A cervical rib or other cause of thoracic outlet compression may interfere with the vascular supply to the upper limb and produce symptoms resembling or contributing to Raynaud’s phenomenon. The symptoms may be more pronounced on one side and may occur together with other evidence of vascular or neurological compression.

4. Increased Plasma Viscosity

Disorders associated with increased blood or plasma viscosity can impair the circulation through small peripheral vessels and contribute to Raynaud-like symptoms. These conditions should be considered particularly when other haematological or systemic abnormalities are present.

5. Drugs

Several medications can aggravate peripheral vasoconstriction. β-blockers are a well-known example and may precipitate or worsen Raynaud’s symptoms in susceptible individuals. Other vasoconstrictive drugs can have similar effects, so medication history is important when evaluating a patient.

6. Vibrating Instruments

Repeated occupational exposure to vibrating tools or machinery can damage the digital circulation and nerves, producing secondary Raynaud’s phenomenon. This is sometimes called hand–arm vibration syndrome and is classically associated with prolonged use of equipment such as pneumatic drills or other high-vibration instruments.

Treatment

1. Maintaining Warmth

The first step in management is to keep the body and extremities warm and reduce exposure to sudden temperature changes. Gloves, warm clothing, and avoidance of prolonged cold exposure can reduce the frequency and severity of attacks. During an episode, gently warming the hands may help restore circulation.

2. Avoiding Smoking and Vasoconstrictive Drugs

Patients should avoid smoking, as nicotine causes peripheral vasoconstriction and can significantly worsen symptoms. Where clinically appropriate, medications that aggravate vasospasm, including some β-blockers, should also be reviewed and avoided or replaced.

3. Calcium Channel Blockers

When conservative measures are insufficient, calcium channel blockers are commonly used as first-line pharmacological treatment. Drugs such as nifedipine relax vascular smooth muscle and reduce vasospasm, thereby decreasing the frequency and severity of Raynaud’s attacks.

4. Glyceryl Trinitrate

Glyceryl trinitrate (GTN) may be used, particularly as a topical preparation, to promote vasodilatation in affected digits. It can improve local blood flow but may cause adverse effects such as headache or dizziness because of systemic vasodilatation.

5. Prostacyclin Therapy

In severe secondary Raynaud’s phenomenon, particularly when there is critical digital ischaemia or ulceration, intravenous prostacyclin analogues such as iloprost may be used. These drugs produce potent vasodilatation and inhibit platelet aggregation, helping to improve blood flow and reduce the risk of further tissue damage.

Key Clinical Concept

Raynaud’s phenomenon is best recognised by episodic digital vasospasm producing pallor, cyanosis, and subsequent painful redness on reperfusion. Most cases are primary and relatively benign, but secondary Raynaud’s should be considered when symptoms are severe, asymmetrical, associated with digital tissue injury, or accompanied by features of a connective tissue disease.

Medicine – Sjögren’s Syndrome

Sjögren’s syndrome is a chronic autoimmune connective tissue disorder characterised by lymphocytic infiltration and progressive dysfunction of the exocrine glands. The lacrimal and salivary glands are particularly affected, resulting in the characteristic combination of dry eyes and dry mouth. Other exocrine glands may also be involved, producing dryness at several mucosal surfaces. In addition to glandular manifestations, patients may develop musculoskeletal and vascular features such as arthralgia, arthritis, and Raynaud’s phenomenon.

1. Dryness Due to Exocrine Gland Involvement

Dryness is the principal clinical manifestation of Sjögren’s syndrome and results from lymphocytic infiltration, damage, and reduced secretion of the exocrine glands. Involvement of the lacrimal glands causes reduced tear production and dry eyes, known as keratoconjunctivitis sicca. Patients may complain of gritty or burning eyes, irritation, redness, or a sensation of having a foreign body in the eye.

Involvement of the salivary glands causes dry mouth, or xerostomia. Patients may have difficulty swallowing dry food, need to drink water frequently while eating, or experience difficulty speaking for prolonged periods. Reduced salivary production can also increase the risk of dental caries and oral infections.

Exocrine gland dysfunction is not necessarily restricted to the eyes and mouth. Reduced secretions within the respiratory tract may cause dryness and irritation, while involvement of the female genital tract can result in vaginal dryness, which may cause discomfort and dyspareunia. Thus, widespread mucosal dryness is an important feature of the disease.

2. Arthralgia and Arthritis

Musculoskeletal manifestations are common, with approximately 60% of patients developing arthralgia or arthritis. Patients may experience pain, stiffness, and sometimes swelling affecting several joints. The arthritis is generally inflammatory but is usually non-erosive, meaning that it does not typically produce the progressive joint destruction characteristic of rheumatoid arthritis.

3. Raynaud’s Phenomenon

Approximately 37% of patients may experience Raynaud’s phenomenon. This occurs because of episodic vasospasm of the small blood vessels supplying the fingers and, less commonly, the toes. Attacks are often precipitated by cold exposure or emotional stress, and the affected digits may sequentially become pale, blue, and then red as circulation returns. Patients may also experience numbness, tingling, or discomfort during an episode.

Key Clinical Picture

The characteristic clinical picture of Sjögren’s syndrome is therefore prominent dryness of the eyes and mouth due to autoimmune destruction of the lacrimal and salivary glands, accompanied in many patients by arthralgia or arthritis and Raynaud’s phenomenon. The combination of dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) is particularly important in recognising the disorder.

Medicine – Essential Features of Dermatomyositis and Polymyositis

Dermatomyositis and polymyositis are inflammatory muscle disorders characterised primarily by immune-mediated inflammation of skeletal muscle, leading to progressive muscle weakness. Dermatomyositis is distinguished by the presence of characteristic cutaneous manifestations, whereas polymyositis has similar muscular features but occurs without the typical skin lesions. Both conditions may be associated with systemic complications and, in some patients, underlying malignancy.

1. Dermatomyositis

Dermatomyositis is an idiopathic inflammatory myopathy associated with characteristic skin changes. The muscle involvement usually affects the proximal muscles of the shoulder and pelvic girdles, while the cutaneous findings provide an important clue to diagnosis. The condition may develop gradually and can interfere with activities such as climbing stairs, rising from a chair, lifting objects, or raising the arms above the head.

2. Polymyositis

Polymyositis is also an inflammatory disorder of skeletal muscle, but unlike dermatomyositis, it occurs without the characteristic cutaneous lesions. Patients mainly present with symmetrical proximal muscle weakness and may experience muscle discomfort or fatigue. The weakness generally develops progressively and affects daily activities that require the use of the shoulder and hip girdle muscles.

Cutaneous Features of Dermatomyositis

1. Heliotrope Rash

A heliotrope rash is a characteristic violaceous or dusky discoloration around the eyelids, often accompanied by periorbital swelling. It is one of the classic skin manifestations of dermatomyositis and may be particularly noticeable over the upper eyelids.

2. Gottron’s Papules

Gottron’s papules are erythematous or violaceous, scaly papules that occur over the extensor surfaces of the joints, especially the knuckles and backs of the hands. They are highly characteristic of dermatomyositis and are useful in distinguishing it from other inflammatory myopathies.

3. Sclerodermatous Changes and Calcification

Some patients may develop sclerodermatous skin changes, with thickening or tightening of the skin. Cutaneous and muscular calcification may also occur, particularly in longstanding disease and more commonly in juvenile forms. These calcium deposits can cause pain, stiffness, and limitation of movement.

4. Raynaud Phenomenon

Raynaud phenomenon may occur, producing episodic vasospasm of the fingers or toes in response to cold or emotional stress. The digits may become pale, blue, and then red as blood flow returns. Its presence may suggest overlap with other connective tissue diseases.

5. Proximal Muscle Weakness

The most important muscular manifestation is symmetrical proximal muscle weakness. Patients may have difficulty standing from a seated position, climbing stairs, combing their hair, or lifting their arms. The weakness generally affects the shoulder and hip girdles more than the distal muscles. In severe cases, involvement of pharyngeal or respiratory muscles may lead to dysphagia or breathing difficulties.

6. Association with Malignancy

Dermatomyositis, particularly in older adults, has an important association with underlying malignancy. The risk is greater in patients over the age of 50, and older teaching sources describe malignancy in around 20% of patients in this age group. Because of this association, age-appropriate cancer screening and investigation for suspicious symptoms are important when dermatomyositis is diagnosed.

Diagnosis

1. Elevated Muscle Enzymes

Laboratory tests often demonstrate increased serum levels of muscle enzymes, reflecting ongoing muscle injury. Creatine kinase is commonly elevated, and other enzymes such as aldolase, AST, ALT, and LDH may also rise.

2. Muscle Biopsy

A muscle biopsy can demonstrate characteristic inflammatory and structural changes within skeletal muscle. The histological pattern can help confirm the presence of an inflammatory myopathy and may also assist in distinguishing between different types.

3. Autoantibodies

Autoantibodies may provide additional diagnostic support. Antinuclear antibodies (ANA) may be positive, and anti-Jo-1 antibodies can be present, particularly in patients with the antisynthetase syndrome. Anti-Jo-1 positivity is also associated with an increased risk of interstitial lung disease, inflammatory arthritis, and other systemic manifestations.

Treatment

Treatment is aimed at reducing muscle inflammation, restoring muscle strength, and preventing complications. Corticosteroids are commonly used as initial therapy, particularly in active inflammatory disease. If the response is inadequate or long-term steroid exposure needs to be reduced, immunosuppressive drugs may be added. Depending on disease severity and organ involvement, agents such as methotrexate, azathioprine, mycophenolate, or other immunomodulatory therapies may be considered. Physical rehabilitation and monitoring for complications such as dysphagia, lung disease, and malignancy are also important parts of management.

Medicine – Mixed Connective Tissue Disease

Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder characterised by an overlap of clinical features from several connective tissue diseases, particularly polymyositis, systemic sclerosis, and systemic lupus erythematosus (SLE). Rather than displaying the typical manifestations of only one autoimmune condition, patients develop a combination of features from these different disorders. The disease is strongly associated with high titres of antibodies against U1-ribonucleoprotein (anti-U1-RNP).

1. Features of Polymyositis

Patients with mixed connective tissue disease may develop manifestations resembling polymyositis, an inflammatory disorder affecting skeletal muscles. The most characteristic manifestation is symmetrical proximal muscle weakness, particularly involving the muscles around the shoulders and hips. Patients may therefore have difficulty climbing stairs, rising from a chair, lifting objects, or raising their arms above their head. Laboratory investigations may demonstrate elevated muscle enzymes when active inflammatory myositis is present.

2. Features of Systemic Sclerosis

MCTD can also produce clinical manifestations resembling systemic sclerosis (scleroderma). Raynaud phenomenon is particularly common and may occur early in the course of the disease. Patients may also develop swollen or puffy fingers, followed in some cases by sclerodactyly and tightening of the skin. Oesophageal dysmotility and other gastrointestinal manifestations may occur. Pulmonary involvement is especially important because interstitial lung disease and pulmonary hypertension can contribute substantially to morbidity.

3. Features of Systemic Lupus Erythematosus

Features resembling systemic lupus erythematosus (SLE) may also occur. These can include inflammatory joint pain or arthritis, skin manifestations, constitutional symptoms, and haematological abnormalities. However, the pattern of organ involvement varies considerably between patients, and the combination of manifestations may evolve over time.

4. Anti-RNP Antibodies

The characteristic serological finding in mixed connective tissue disease is a high titre of antibodies against U1-ribonucleoprotein (anti-U1-RNP). These antibodies are an important marker supporting the diagnosis when the appropriate overlapping clinical features are present. Anti-RNP antibodies can also occur in other autoimmune diseases, particularly SLE, so their presence alone is not sufficient to establish the diagnosis. In MCTD, they are typically found at high titres together with characteristic clinical features of overlapping connective tissue diseases.

Key Concept

Mixed connective tissue disease can therefore be remembered as an overlap syndrome combining features of polymyositis, systemic sclerosis, and SLE, associated with high-titre anti-U1-RNP antibodies.