Introduction

Lupus is frequently associated with an increased risk of morbidity and premature mortality. However, many studies have demonstrated that survival has improved dramatically since the 1970s with major reductions in the risk of death from infections and renal failure. Many challenges remain in improving the quality of life for lupus patients and reducing the risk of complications both from the disease and its treatment. This chapter considers the morbidity associated with lupus from damage accumulation, coronary artery disease and infection. Fatigue is an almost universal feature of lupus and contributes significantly to impaired quality of life. Other disorders such as Sjögren's Syndrome, overlap disease and dermatomyositis will also be described briefly.

Damage

While the concept of disease activity is widely accepted, the impact of damage both from lupus disease activity and from adverse effects of treatment are not so widely appreciated. The term damage refers to irreversible organ involvement such as renal failure, vertebral fracture, cataracts or heart failure. Damage predicts mortality and other outcomes, such as physical function, health care utilization, quality of life and disability. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is widely used to capture damage for research purposes and is a simple tool to use in clinical practice.

Damage from lupus most frequently arises from recurrent disease flares - each time that a patient has a flare, there is a risk that damage may accumulate. This is especially important in patients with renal disease: recurrent flares of lupus nephritis increase the risk of developing end stage renal disease requiring dialysis or renal transplantation.

The other major contributor to damage is the use of high dose corticosteroids which may result in osteoporosis, vertebral fractures, cataracts and diabetes mellitus. There is consensus that corticosteroids should be used very sparingly at the lowest effective dose for the shortest period of time to reduce the risk of adverse effects.

Complications

Coronary Artery Disease
In women with lupus, the risk of myocardial infarction is increased by between 10 and 50 times compared to an age and gender matched healthy population. This greatly increased risk is not fully explained by the traditional coronary artery risk factors and may be explained by chronic inflammation from lupus disease activity and long-term corticosteroid use.

Risk factor management is of vital importance in addressing the burden of cardiovascular mortality. General Practitioners are very familiar with managing this aspect in the same way that diabetes patients are assessed. Lupus patients should have regular assessments of their renal function, blood pressure, screening for diabetes mellitus including measuring lipid profiles and offering lifestyle advice such as regular exercise, smoking cessation and dietary advice to minimise weight gain. Cardiovascular risk factor management should always accompany a management strategy to control disease activity and prevent disease flares.

Osteoporosis
The adverse effects of corticosteroids are well recognised, and clinicians should attempt to minimise the dose and duration of steroid therapy by using steroid sparing agents such as anti-malarials and immunosuppressive therapies including new biological agents such as Rituximab and Belimumab. Osteoporosis is a common complication of corticosteroid therapy. Lupus patients commencing steroids should be assessed for osteoporosis risk factors such as previous fractures, family history, alcohol and smoking history and a baseline DEXA could be considered. The FRAX tool may be useful although this does not utilise lupus as a risk factor in calculating fracture risk. The use of vitamin D supplements is encouraged and, where long-term steroids may be needed, bone protection with drugs such as bisphosphonates can be considered. In post-menopausal women with lupus, HRT is not without risk especially in those who are positive for antiphospholipid antibodies where the risk of thrombosis is substantial.

Infection
Bacterial and viral infections are very common in lupus patients and may be fatal. Lupus patients should be encouraged to have vaccinations such as the 'flu vaccination. In those patients where immunosuppressive and biologic therapy is being considered, vaccinations against pneumonia should be considered. The risk of lupus flares associated with vaccinations is negligible. Live vaccines, such as the shingles vaccination, should be avoided in patients already on steroids or immunosuppressives. Patients should be screened for viral infections such as HIV and hepatitis prior to immunosuppressive and biologic therapy and screening for tuberculosis should be considered where appropriate. Infections are more common when immunosuppressive therapies and high dose corticosteroids are used and lupus patients who develop fevers should always be assessed for infection. A normal CRP in this context may be reassuring and suggests that active lupus rather than infection may be the cause of the fever. Treating infections in lupus patients in the community may follow usual guidelines, but failure to respond to standard antibiotics should prompt specialist advice.

Associated Conditions

Drug Induced Lupus
While drug induced lupus is well recognised, lupus patients are also at risk of disease exacerbations due to certain drugs. There is a long list of drugs associated with drug induced lupus and it behoves the clinician to be aware that a lupus disease flare may just be due to a newly introduced drug. Examples include terbinafine, antihypertensives, long-term use of tetracyclines and proton pump inhibitors such as omeprazole. Cutaneous lesions are the most frequent presentation often in the absence of systemic symptoms and drug withdrawal usually results in rapid resolution.

Conditions related to lupus

Primary Sjögren's Syndrome is the most common autoimmune rheumatic disease after rheumatoid arthritis. Most patients present with symptoms of dryness in the eyes and mouth and there can be systemic symptoms including fatigue, joint pains, lymphadenopathy and glandular swelling especially of the parotid and submandibular glands. Sjögren's Syndrome is characterised by the presence of antibodies to Ro and La, rheumatoid factor, high immunoglobulin G level and elevated ESR but with normal CRP. Lupus patients commonly develop secondary Sjögren's Syndrome with dry eyes and dry mouth symptoms, especially in the presence of the antibodies most commonly associated with Sjögren's Syndrome, namely anti-Ro and anti-La antibodies.

Dermatomyositis may be misdiagnosed as lupus as both conditions may present with photosensitive skin rashes and aches and pains. Muscle inflammation may be absent in the early phases of dermatomyositis and, confusingly, skin biopsies from dermatomyositis patients may be indistinguishable from lupus. The myositis autoantibody panel which includes myositis specific and myositis associated antibodies is increasingly useful in distinguishing these two autoimmune diseases.
Overlap autoimmune rheumatic diseases may be confused with lupus although these patients are more likely to have Raynaud's Phenomenon and antibodies to RNP may be detected in the serum.

Fatigue and Fibromyalgia

Fatigue is almost universal in patients with all the autoimmune rheumatic diseases and is a major contributor to impaired quality of life. The pathogenesis of chronic and severe fatigue in lupus is multifactorial and may be due to active disease as well as other factors such as anaemia, renal failure, hypothyroidism and physical deconditioning. Depression and poor sleep patterns are commonly associated with severe fatigue. Rather frustratingly for patients, fatigue often persists even when the lupus is in remission. Treatment is unsatisfactory and revolves around controlling disease activity, regular exercise and dietary measures to reduce weight gain. Fibromyalgia or chronic widespread pain may develop in 10-15% of lupus patients and, like fatigue, can be difficult to assess and treat. The treatment of chronic widespread pain is very different to that of lupus and may include graded exercise, cognitive behavioural therapy and low-dose tricyclic agents such as Amitriptyline.

Summary

Lupus is a complex disease and patients benefit most from a multidisciplinary approach. A chronic disease management strategy aiming to prevent or minimise disease flares, complications and damage accumulation will ultimately improve quality of life, reduce morbidity and reduce the risk of premature mortality.

Prof David D'Cruz MD FRCP
Consultant Rheumatologist
The Louise Coote Lupus Unit
Guys and St Thomas' Hospital
Great Maze Pond
London SE1 9RT

Revised and updated from 2009 edition by Dr Robert Bernstein