This is the second of a two-part series (Perry, 2022) looking at some of the well-known autoimmune diseases, of which there are many, each with different signs and symptoms and affecting single tissues or organs or multiple parts of the body. Each individual autoimmune disease can have variable degrees of severity with the potential to have an impact on daily living activities and affect quality of life. This article will give a brief overview of systemic lupus erythematosus (SLE), coeliac disease and ulcerative colitis and hopes to give practice nurses and non-medical prescribers an understanding of how these diseases arise, their treatment and management and prognosis.
Basic pathophysiology
The basic underlying process of autoimmune diseases was discussed in part 1 of this series (Perry, 2022). In a healthy person, the immune system is able to destroy any invading organisms before they have the opportunity to cause problems. Specialised systems in the immune system function to ensure host tissue is not attacked, and in healthy individuals the body is able fight off and defend itself against foreign bodies such as bacteria and viruses. However, sometimes this mechanism fails and the body begins to attack its own organs or tissues. The process by which this occurs differs with each autoimmune disease and will be explained in more detail for each condition discussed.
Systemic lupus erythematosus
SLE is a complex chronic inflammatory autoimmune disease that can affect multiple systems, resulting in an array of unpleasant symptoms, ranging in severity from mild to severe. The disease can affect people of any age, but 70–90% of cases occur in women (usually of child-bearing age) and it is more common among those of black or Asian ethnicity (Nevares, 2020).
Pathophysiology
The underlying process leading to disease onset is highly complex and poorly understood. It is thought that activation of autoreactive B cells and CD4 T cells in secondary lymphoid organs (such as the spleen and lymph nodes), leads to the production of pathogenic autoantibodies that, together with inflammatory cytokines, promote the tissue injury seen in the disease (Choi et al, 2012). Both environmental and genetic factors have been studied to assess their influence on the development of symptoms. Family history seems to be important, with more than a six-fold increased risk of developing the disease found in patients with a first-degree relative with SLE (Bengtsson et al, 2002). In addition, hypertension, drug allergies and smoking were also found to be influential, but alcohol was a potential protective factor (Bengtsson et al, 2002).
Signs and symptoms
Symptoms of SLE can be vague and non-specific, making diagnosis difficult as patients may give a clinical picture that can easily be confused with a number of other conditions. Typically, SLE patients present with (Shaw, 2021):
- Fever, fatigue and weight loss (90% of patients with SLE experience these symptoms)
- An erythematous rash is common and frequently occurs over the nasal bridge and across the cheeks
- Some patients will develop a discoid rash, usually in sun-exposed areas
- Many patients experience musculoskeletal symptoms with early morning stiffness and non-erosive arthritis of the hands and feet, which occurs bilaterally
- Multiple organs can be affected, including the heart (causing pericarditis or coronary artery disease)
- Involvement of the gastrointestinal tract may result in abdominal discomfort and vomiting, occurring as a result of enteritis, mesenteric vasculitis or pancreatitis
- Pulmonary manifestations include pleuritis and pulmonary hypertension.
Diagnosis
The American College of Rheumatology suggest that classification of SLE can be made when the affected person has four or more of a number of symptoms, which do not have to be present at the same time but may be cumulative over several years (Tidy, 2020a). See Table 1 for more information.
Table 1. Diagnosis of systemic lupus erythematosus
| Any four of the symptoms listed below |
|---|
| Discoid lupus |
| Oral or nasopharyngeal ulcers |
| Malar rash |
| Photosensitivity |
| Pleuritis or pericarditis |
| Seizures or psychosis |
| Non-erosive arthritis involving two or more peripheral joints |
| A positive antinuclear antibody result |
| Anti-DNA antibodies or antiphospholipid antibodies |
| Haematological abnormalities, eg leukopenia, thrombocytopenia, haemolytic anaemia or lymphopenia |
Anic et al, 2014
Treatment and management
Treatment for SLE can have both pharmacological and non-pharmacological elements.
Non-pharmacological
Patients often need an approach which targets multiple issues, and this may include counselling to help them deal with their symptoms, diagnosis and prognosis, and in addition lifestyle advice such as using sun screens and avoiding the sun whenever possible. Underlying problems such as depression or anaemia will also require treatment. Regular exercise is thought to have many benefits in patients suffering with SLE and the Lupus Foundation of America (2022) cite these as:
- Can help to regulate some of the chemicals involved in the inflammatory process, reducing inflammation
- Can help reduce weight gain associated with corticosteroid medications if prescribed
- Can strengthen organs, bones and joints that may have been affected by the disease
- Even low impact exercise, such as walking, can help to reduce muscle stiffness
- Can also be beneficial for improving mental health and wellbeing.
Pharmacological treatment
There are a number of medications which can be used to help manage SLE. Analgesia such as paracetamol and ibuprofen may be sufficient to control joint and muscle aches and pains, but if this is insufficient more intensive treatment may be needed and is guided by symptom severity. See Table 2 for more information.
Table 2. Management of systemic lupus erythematosus
| Severity of symptoms | Treatment options | Additional information |
|---|---|---|
| Mild | Disease modifying drugs (hydroxychloroquine or methotrexate)Non-steroidal anti-inflammatory drugs (NSAIDs) (short courses)Prednisolone | The use of any of these options allows for avoidance, or dose reduction, of corticosteroidsLow dose of up to 7.5 mg may be given for maintenance therapy or topically for skin problems or intra-articular for joint problems |
| Moderate | Patients may need a higher daily dose of prednisolone (up to 0.5 mg/kg/day)Immunosuppressive agents (eg azathioprine, TNF-alpha inhibitors)Patient with arthritis, vasculitis, cutaneous disease where hydroxychloroquine has been ineffective | Some may need intramuscular or intravenous methylprednisoloneUsed to control active disease and can reduce the risk of long-term damageMethotrexate, azathioprine, mycophenolate mofetil, ciclosporin and other calcineurin inhibitors should be considered |
| Severe | Patients with severe SLE, including renal and neuropsychiatric manifestations, need thorough investigation to exclude other aetiologies including infectionTreatment of severe active SLE may require intravenous methylprednisolone or high dose oral prednisolone (up to 1 mg/kg/per day) to induce remission | Treatment is dependant on the underlying aetiology and may require immunosuppression and/or anticoagulationMay be given alone or in combination with another immunosuppressive drug |
Gordon et al, 2018
Coeliac disease
Coeliac disease in an autoimmune disease, causing inflammation of the small intestine when the intestine is exposed to dietary gluten. Although the disease can affect people of any age, it is most commonly diagnosed in people aged between 50 and 69 and often runs in families, with current estimates suggesting that about 1 in 100 people in the UK are affected (Payne, 2018). For those who have a close family member affected (sister, brother or parent), there is a 1 in 10 chance of developing the condition (Payne, 2018).
Pathophysiology
In coeliac disease, gliadin, a component of gluten, is not broken down properly, so it is able to continue to pass through the intestinal epithelial layer, triggering an immune response (Martin, 2021). Poorly digested gliadin protein will bind to the human leukocyte antigen class II DQ2 or DQ8 molecules (responsible for the presentation of antigens to immune cells), which then activates CD4 T cells in the intestinal mucosa, leading to chronic inflammation of the proximal small bowel intestinal mucosa and malabsorption (Pelkowski and Viera, 2014). The severity of symptoms is influenced by the extent of the inflammation that has occurred in the small intestine.
Signs and symptoms
The most common symptoms include (Goebel, 2019):
- Watery diarrhoea occurs in 45–85% of those affected and this can have a foul odour
- Flatulence is caused by gas produced by bacterial flora feasting on undigested, unabsorbed food
- Bloating and abdominal cramps may be symptoms when flatulence is excessive
- Weakness and fatigue are common (up to 80% of patients are affected) and may be due to anaemia or poor nutritional intake
- Weight loss may occur as a result of malnutrition
- In addition to the symptoms shown above there are a number of extra-intestinal symptoms. These are shown in Table 3.
Table 3. Extra-intestinal symptoms of coeliac disease
| Symptom | Additional information |
|---|---|
| Skin disorders | Approximately 10–20% will have dermatitis herpetiformis (red, raised, itchy rash) often affecting the extensor surfaces of the extremities, trunk, buttocks, scalp and neck |
| Anaemia | Found in 10–15 % of patients |
| Hormonal disorders | Delayed onset of periods and amenorrhoea in females or infertility which can affect both males and females |
| Neurological symptoms | Approximately 8–14% of patients may experience symptoms including motor weakness, paraesthesia (tingling sensation), loss of co-ordination (ataxia) |
| Osteoporosis and osteopenia | May develop in 1–34 % of patients |
Goebel, 2019
Diagnosis (NICE, 2020a)
- Tissue transglutaminase antibody (tTGA) blood test and serum IgA are recommended as first-line tests. The patient should be advised to continue eating foods containing gluten in more than one meal per day for at least 6 weeks prior to testing
- If the above tests are unavailable or show a weakly positive result, then serum IgA endomysial antibody (EMA) may be requested
- Referral to a gastroenterologist will be needed for endoscopy and biopsy to confirm or exclude the diagnosis.
Treatment
A confirmed diagnosis will require the affected person to follow a gluten-free diet for life. Patients will need to check food labels prior to purchase to avoid problems. Wheat, barley and rye, and food containing these items such as bread, pastries, cakes and some cereals, to name but a few, should be avoided and referral to a dietician may be helpful to support patients with this.
Ulcerative colitis
Ulcerative colitis is a chronic autoimmune condition affecting the rectum and colon, which follows a relapsing and remitting pattern. The disease can develop at any age but most commonly develops between the age of 10 and 40 years, but approximately 1 in 7 cases are diagnosed in those over the age of 60 (Tidy, 2020b). The condition is classified as an inflammatory bowel disease along with Crohn's disease, and although they share some symptoms there are differences between the two conditions. These are shown in Table 4.
Table 4. Differences between ulcerative colitis and Crohn's disease
| Crohn's disease | Ulcerative colitis |
|---|---|
| Can occur anywhere along the GI tract but most commonly affects the large and small intestines | Limited to the colon |
| Can occur in all the layers of the bowel walls | Affects mostly the inner lining of the colon |
| Diagnosed in 1 in 10 000 every year and most commonly starts in those aged 15–30 years | Affects 2 in every 1000 and is most common in those aged between 10 and 40 |
Tidy, 2017; Tidy, 2020b; UCLA, 2022
Pathophysiology
Ulcerative colitis usually begins in the rectum and in 25% of cases the disease remains confined to this area, but in some cases it can extend to involve the whole of the colon (pancolitis) (Walfish and Companioli, 2022). Pancolitis occurs in 10% of patients (Rowe, 2020). Early in the disease, the mucous membrane is erythematous, finely granular and friable, while more severe disease is characterised by large ulcers and copious purulent exudate (Walfish and Companioli, 2022).
Signs and symptoms
Symptoms are linked to the disease severity, but the most common symptoms are diarrhoea (often watery and mixed with blood), cramping abdominal pains and a feeling of urgency but not able to pass anything (tenesmus), or pain when actually passing stools (Tidy, 2020b). In addition, patients may feel generally unwell with tiredness and some patients will have a fever.
Severity can be graded as follows (Basson, 2022):
- Mild: rectal bleeding with fewer than four bowel motions per day
- Moderate: rectal bleeding with more than four bowel motions per day
- Severe: rectal bleeding with more than four bowel motions per day and systemic illness.
Diagnosis
Several investigations can be done in the primary care setting (Table 5) prior to referral to secondary care for further assessment. A sigmoidoscopy or colonoscopy is usually performed and biopsies taken during the procedure will confirm the diagnosis.
Table 5. Primary care investigations for the assessment of ulcerative colitis
| Test requested | Additional information |
|---|---|
| Full blood count | Raised platelet count may indicate active inflammation; anaemia may be due to malabsorption, poor dietary intake or blood loss |
| C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) | May be raised if there is infection or active inflammation |
| Thyroid function | To exclude hyperthyroidism |
| Urea and electrolytes (U&Es) | May be abnormal if there is electrolyte imbalance or dehydration |
| Liver function tests | Low serum albumin may reflect nutritional status as well as disease activity and severity |
| Serum ferritin, B12 and folate and vitamin D levels | May be abnormal if the patient has malabsorption problems or is malnourished |
| Faecal calprotectin | If raised may indicate active inflammation (normal in irritable bowel syndrome) |
| Stool sample for microscopy, culture and sensitivity (MC&S) | Should include Clostridium difficile testing to exclude infective gastroenteritis (if pathogen identified it does not exclude ulcerative colitis as an infection may trigger the first episode) |
| Coeliac serology | To exclude a diagnosis of coeliac disease |
Treatment and management
When the cause of symptoms is known, medication will be given until these have settled. Treatment will be tailored to the disease severity and the area of the bowel affected and can be repeated if the patient experiences a flare up. There are several options available, which include (British National Formulary, 2022):
- Topical treatment given by enema or suppository: topical aminosalicylate is recommended as first-line for mild-to-moderate first presentation
- If remission is not achieved in 4 weeks, adding an oral aminosalicylate is an option, but if response to this remains inadequate a topical or oral corticosteroid can be added for 4–8 weeks
- Monotherapy with an oral aminosalicylate may be preferred by patients who do not want to use enemas or suppositories. If remission is not achieved in 4–6 weeks, a topical or oral corticosteroid can be added and continued for a period of 4–6 weeks, or can be an option if oral aminosalicylates are unsuitable
- Immunosuppressants such as azathioprine or ciclosporin may be needed if symptoms persist despite the above treatments
- In a patient with acute severe ulcerative colitis, an intravenous (IV) corticosteroid will be needed (eg hydrocortisone); however, if there is no improvement or worsening symptoms, a combination of IV corticosteroids and IV ciclosporin or surgery will be needed.
Preventing flare ups
Daily preventative treatment reduces the risk of a flare up from a 5–7 in 10 possibility to a 3 in 10 chance of an episode occurring (Tidy, 2020b). A low dose oral aminosalicylate (eg mesalazine, sulfasalazine) may be used or, alternatively, azathioprine or mercaptopurine (unlicensed) may be given if the patient has had two or more exacerbations in the last 12 months (requiring systemic corticosteroids) or aminosalicylates have failed to maintain remission (British National Formulary, 2022).
KEY POINTS:
- Each individual autoimmune disease can have variable degrees of severity with the potential to have an impact on daily living activities and affect quality of life
- Systemic lupus erythematosus is a complex chronic inflammatory autoimmune disease that can affect multiple systems, resulting in an array of unpleasant symptoms, ranging in severity from mild to severe
- A confirmed diagnosis of coeliac disease will require the affected person to follow a gluten-free diet for life
- Daily preventative treatment for ulcerative colitis reduces the risk of a flare up
CPD REFLECTIVE PRACTICE:
- How confident are you that you understand how common autoimmune diseases affect your patients?
- Where could you get more information on these diseases?
- How could you support your patients with autoimmune diseases?
Conclusion
Autoimmune diseases cover a wide spectrum of conditions and only a handful have been covered in this two-part series. Autoimmune diseases are highly complex and vary widely in their pathophysiology, symptom severity and treatment. This article has only touched the surface but hopes to have given general practice nurses and non-medical prescribers a better understanding of the conditions discussed to enable them to have more confidence in recognising symptoms and getting their patients earlier investigation and treatment.