Connective Tissue Disorders

Systemic lupus erythematosus (SLE)

This is a chronic systemic autoimmune disease, which is classically seen in middle-aged women, particularly in black and Hispanic demographic groups.

Whilst the exact cause is unknown, poorly cleared apoptotic debris activates autoimmune lymphocytes leading to the generation of immune complexes.

Inadequate clearance (due to deficient complement proteins) means that these immune complexes are deposited in multiple tissues, leading to inflammation.

It can also be drug induced, which is associated with higher anti-nuclear antibodies than anti-double stranded DNA antibodies.

It typically displays a relapsing and remitting pattern of disease.

Symptoms

Inflammatory signs – fever, weight loss, fatigue

Malar “butterfly rash” on exposure to sunlight

Oral/nasal ulcers

Polyarthritis (> 2 joints), pleurisy, pericarditis

Neurological symptoms – seizures, psychosis

Renal damage – lupus nephritis causes a glomerulonephritis and can cause renal failure

Lymphadenopathy

Key tests

Raised inflammatory markers e.g., ESR, CRP and low C3/C4 complement levels

Raised anti-nuclear (ANA), anti-extractable nuclear antigen (anti-ENA) antibodies

Anti-double stranded DNA antibodies (anti-dsDNA) are highly specific for SLE

Urinalysis should be performed to assess renal involvement

CXR to assess for any cardiopulmonary symptoms

Lymph node biopsy may be performed if diagnosis unclear

Management

Conservative measures – avoid exposure to sunlight, psychological therapies

1st line medical therapy is hydroxychloroquine.

If severe, requires immunosuppression, e.g., steroids, biologics

Sjogren’s syndrome

This is an autoimmune disorder which is characterised by lymphocyte infiltration and fibrosis of the exocrine glands, usually the lacrimal and salivary glands.

Primary – this occurs more in middle-aged females (around 40–50 years old)

Secondary – due to rheumatoid arthritis or other connective tissue disorders

The major risk of this condition is the development of non-Hodgkin’s lymphoma

Symptoms

Dry eyes (keratoconjunctivitis sicca)

Joint and muscle pain

Dry mouth (xerostomia)

Renal tubular acidosis

Raynaud’s phenomenon

Sensory neuropathy

Key tests

Blood tests show raised autoantibodies, including rheumatoid factor, ANA, anti-Ro (SSA) antibodies and anti-La (SSB)

Schirmer’s test uses filter paper to measure tear formation in eyes. The test is positive if less than 5 mm of paper is wetted after 5 minutes.

Management

1st line is symptom control, e.g., artificial tears drops and saliva stimulants

If severe with arthralgia, immunosuppressants (hydroxychloroquine) are considered

Dermatomyositis

This is an autoimmune condition which leads to inflammation of striated muscle as well as an involvement of the skin.

It can solely affect the musculature without skin involvement (polymyositis).

It can be associated with cancer and so it is important to investigate for an underlying malignancy.

Symptoms

Inflammatory signs – low grade fever, lethargy, weight loss

Progressive symmetrical proximal muscle weakness

Weakness is profound and maybe accompanied with mild pain (though not always)

Gottron papules – red marks on knuckles, elbows and knees

Heliotrope rash – rash of the upper eyelids

Associated with interstitial lung fibrosis and myocarditis

Key tests

Blood tests – raised creatinine kinase levels (up to 50Å~ upper limit of normal)

Muscle biopsy – shows endothelial hyperplasia in the intramuscular blood vessels and perifascicular atrophy

If diagnosis unclear, can also do electromyogram or imaging (MRI of the muscle)

Management

Acute flares are usually managed with steroids

Mainstay of treatment is immunosuppression, e.g., methotrexate

Screen for underlying cancer and organise investigations accordingly

Systemic sclerosis/scleroderma

This is an autoimmune disorder characterised by sclerosis (hardening) of the skin and fibrosis of visceral organs, which is more common in middle-aged females.

Fibroblast activation leads to deposition of collagen, causing progressive fibrosis and organ damage. 

Limited type

In this type, skin involvement is limited to hands and face with later organ fibrosis.

This type is associated with anti-centromere antibodies.

Called CREST syndrome: Centromere antibodies, Raynaud’s, Esophagus dysmotility, Sclerodactyly (finger thickening), skin Telangiectasia (capillary dilation)

Diffuse type

In this type, there is early visceral involvement and widespread skin changes.

It can lead to pulmonary fibrosis/hypertension as well as Raynaud’s and GI problems.

It is associated with antibodies to DNA topoisomerase I.

Management

Immunosuppressants

Fibromyalgia

This is a condition which is characterised by chronic widespread pain and a heightened pain response to pressure stimuli, which is more common in women.

Its aetiology is not fully understood, and the pain appears to result from the way pain signals are processed by the central nervous system.

The condition is referred to as a “central sensitisation syndrome”.

It is a clinical diagnosis based on ruling out other pathologies. Investigations are typically normal, so the pain cannot be attributed to any other organic cause.

Symptoms

Pain that is chronic (>3 months) and widespread (bilateral, proximal and distal)

Profound fatigue, difficulty concentrating, poor sleep, low mood, headaches

Key tests

Diagnosis of exclusion as investigations will be normal

Management

Multidisciplinary approach to improve overall functioning.

CBT – psychological support

Neuropathic agents, e.g., amitriptyline, pregabalin, gabapentin etc.

Chronic fatigue syndrome

This is like fibromyalgia, but the prominent problem is fatigue, rather than pain.

It is characterised by persistent fatigue lasting > 6 months and present more than 50% of the time. It is also associated with poor sleep, low mood etc.

The management is similar to fibromyalgia with a MDT approach used, except from the use of pharmacological agents.