Dr Toni Hazell Offers 10 Top Tips for Primary Care Practitioners on the Identification, Referral, and Long-term Care of Patients with this Rare, Multisystem Disease
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Sarcoidosis is a multisystem disease that can present with a variety of symptoms and is characterised by the development of granulomas in affected areas of the body.1 The aetiology of sarcoidosis is not fully understood, but it likely has both environmental and genetic components.1–3 It is thought to be an autoimmune condition associated with an overactive type-IV (delayed) inflammatory response to infectious or environmental triggers.1,4,5 The triggering antigens are then enclosed by non-caseating granulomas, which form in the affected system—most often in the lungs.1,4,5
Its non-specific presentation and rarity—sarcoidosis is estimated to affect around one in 10,000 people in the UK3—means that diagnosis can be slow. In a recent survey by SarcoidosisUK, 16% of respondents received a diagnosis more than 2 years after their first presentation.6
This article provides 10 top tips on the role of primary care in identifying, investigating, and managing suspected sarcoidosis, discussing the diagnosis and management of rare diseases in general, then focussing on common presenting features of sarcoidosis and the role of the GP in its management.
1. Recognise that Rare Diseases Are More Common than They Seem
A rare disease is defined as a condition that affects fewer than one in 2000 people,7 and a GP may only make one diagnosis of a specific rare disease in their career. However, around one in 17 people (equating to 3.5 million people in the UK) will experience a rare disease at some point in their life,7 so practices will undoubtedly have many patients on their list who are affected by rare diseases (and likely also by their lack of associated research funding). The UK Rare Diseases Framework aims to speed up diagnosis by increasing awareness among healthcare professionals and improving access to specialist care and unlicensed medicines when there is a clear need.7
2. Be Aware of the Signs and Symptoms of Sarcoidosis
Cough, dyspnoea, and fatigue are the most common symptoms among presentations of sarcoidosis, and the lungs are affected in over 90% of cases.2,3,8 However, sarcoidosis can present with a range of symptoms anywhere in the body, including:1–3,8
- night sweats
- eye pain, often resulting from uveitis
- joint pain
- weight loss
Figure 1: Organ Involvement in Sarcoidosis9
3. Tailor Your Assessment to the Presenting Symptoms
History taking should include asking about common pulmonary and extrapulmonary symptoms of sarcoidosis, in particular eye symptoms and rashes—it is important that sarcoidosis affecting the eye is identified early, and a patient may not think to mention a rash that has resolved.2,4,10 Erythema nodosum can be a presenting feature of sarcoidosis,2,4 but usually resolves without treatment over a period of up to 6 weeks.11 If the patient is known to have other respiratory conditions, such as asthma, it may also be beneficial to enquire into the management of these and whether they are well controlled.
The examination should be tailored to the patient’s symptoms and any potential differential diagnoses,3,4,8 but would almost always include examination of the abdomen and lymph nodes to look for hepatosplenomegaly and lymphadenopathy.4 If there are eye symptoms, referral to an eye specialist is usually necessary,4,10,12 in part because the lack of a slit lamp limits the examinations that can be done in primary care.
4. Consider Exposure and Occupational History
When considering a diagnosis of sarcoidosis, taking occupational history into account is important because certain metals and minerals, such as silica and titanium, can be environmental triggers, and a history of exposure at work should raise suspicion of the disease.13,14 Other potential noninfectious environmental triggers include insecticides, industrial organic dusts, and man-made mineral fibres.13 An occupational history can also help to exclude berylliosis and silicosis, which are conditions that may present in a similar manner to sarcoidosis.2
5. Investigate Symptoms and Consider a Chest X-ray in Patients with Dyspnoea or Fatigue
Dyspnoea and fatigue are common presentations in general practice, and have a wide range of causes. Many patients presenting with fatigue will not have any identifiable pathology, and spotting the ‘needle-in-the-haystack’ case of sarcoidosis presenting with fatigue is not easy.
NICE recommends offering an urgent chest X-ray (CXR) within 2 weeks to patients aged 40 years or older who present with two or more of dyspnoea, fatigue, cough, chest pain, weight loss, and appetite loss to assess for lung cancer.15,16 Furthermore, the British Thoracic Society (BTS) recommends CXR in all patients with suspected sarcoidosis.2 Bilateral hilar lymphadenopathy, paratracheal lymphadenopathy, and any suggestion of lung fibrosis should all raise suspicion of sarcoidosis, with differentials of these CXR findings including tuberculosis and lymphoma.2,4,17
The primary investigations to consider are included in Box 1.
|Box 1: Possible Investigations for Suspected Sarcoidosis1–4,8,15,17–22|
CXR=chest X-ray; FBC=full blood count; ACE=angiotensin-converting enzyme; LFT=liver function test; TFT=thyroid function test; ECG=electrocardiogram
6. Refer Suspected Cases to Secondary Care, and Consider Referral to a Specialist Centre
The appropriate referral pathway will depend on what is available locally, and on your clinical suspicions. For example, if there is strong suspicion of lymphoma, a 2-week-wait referral may be appropriate; or, if the main symptom is weight loss, referral to a rapid diagnostic centre for non-specific symptoms of cancer may be appropriate.16
Any hospital should be able to make a diagnosis of sarcoidosis, which is usually confirmed via a combination of positron-emission tomography (PET), bronchoscopy, and endobronchial ultrasound (with or without needle biopsies).2,3,8 However, once the diagnosis has been established, it may be appropriate for the patient to be referred to a specialist centre for sarcoidosis. The charity SarcoidosisUK maintains a directory of specialist centres across the UK (bit.ly/40db13G).23 Ideally, the patient’s initial consultant would make a direct referral, but sometimes a patient may ask their GP for a second opinion, in which case the online directory may be useful. Treatment decisions should be made by a multidisciplinary team.
7. Be Wary About Treating Low Vitamin D in Patients with Sarcoidosis
Patients with sarcoidosis will often have a raised calcium level, and this may prompt clinicians to check their vitamin D level and treat any apparent deficiency. However, patients with sarcoidosis should only have their vitamin D checked by a specialist, as it is the active metabolite that is deranged in sarcoidosis.2,24 Usually, this test has to be sent to a specialist laboratory for analysis, and can take months to come back. Vitamin D supplementation should not be given to patients with sarcoidosis unless under specialist guidance, as there is a risk of hypercalcaemia.2,24
8. Understand How Sarcoidosis Is Managed, and the Role of the GP
Sarcoidosis management is the remit of secondary care, and decisions about treatment are not always straightforward. The BTS guideline recommends that treatment is started in patients who have advanced or dangerous disease, or are at high risk of progression to this state.2 Decisions about treatment to aid quality of life must be made using the principles of shared decision making, with the patient weighing up the benefits of treatment against the possible adverse effects.2
Steroids, such as prednisolone, are the most common first-line agent, with other classical immunosuppressants, such as methotrexate, forming second-line therapy.2 Some patients will eventually need a lung transplant.2 Sarcoidosis-associated fatigue affects up to 80% of patients with sarcoidosis and also requires quantification and management, which can be particularly difficult as it may be multifactorial in origin.2
The Role of Primary Care
Patients who are under the care of a consultant still attend primary care for their day-to-day medical needs. To support sarcoidosis management, it is crucial that those who smoke are offered smoking-cessation support.2 Having a chronic disease can also be very stressful, and this may impact a patient’s mental health—in most cases, management of any associated depression or anxiety would be undertaken in primary care.2,3
Many patients will be prescribed disease-modifying drugs that will be monitored in primary care under a resourced shared-care protocol, and the recommended flu, pneumococcal, and COVID-19 vaccinations for these patients will be delivered in primary care.2,12 For women with sarcoidosis who want to conceive, particularly if they are taking disease-modifying drugs, discussion with their consultant—or a preconception referral to maternal medicine networks—is important.2,12 Therapy started in secondary care may also cause adverse effects that need to be managed in primary care, such as diabetes, hypertension, osteoporosis, or sleep apnoea related to the use of oral steroids.2
Patients may also present to the GP with concerns about the effect of their symptoms on their quality of life or ability to work—in many cases, a ‘may be fit to work’ fit note is appropriate for those who would benefit from an occupational health referral or a reduction in hours.25 SarcoidosisUK has a leaflet that can be given to employers in these cases (bit.ly/3ZT6ymL),26 and patients who are having trouble accessing the help that they need at work may wish to involve their union, or the Advisory, Conciliation and Arbitration Service.26
9. Ensure that Secondary-Care Drugs Are Coded in Patients’ Notes
All GP computer systems have an option to add drugs to the medicines screen but indicate that they are given in hospital—this may include biologic drugs or disease-modifying antirheumatic drugs that are not prescribed in primary care. It is vital to record the use of these drugs. As well as ensuring that interactions with primary-care-prescribed drugs are picked up, this coding may help a patient with sarcoidosis to access antivirals for COVID-19 if their immunosuppressive drugs make them eligible.27
10. Know that Sarcoidosis Has Significant Mortality Rates, and that Cardiac Involvement Is Especially Serious
Sarcoidosis is associated with a reduction in life expectancy in approximately 6–8% of patients; around 30% of patients with sarcoidosis have clinically significant major organ involvement, and sarcoidosis causes long-term mortality in approximately 20–25% of these patients.2 Most patients who die of sarcoidosis do so because of respiratory or cardiac complications2—this should be considered in those who have levels of breathlessness that seem disproportionate. A baseline electrocardiogram (ECG) is important at the time of diagnosis, and may show a ventricular tachycardia, atrioventricular block, long QT interval, or another arrhythmia.2 Further investigations could include an echocardiogram or 24-hour ECG (in those presenting with palpitations), performed in either primary or secondary care, and other secondary-care tests such as PET or cardiac magnetic resonance imaging.2 All patients with cardiac sarcoidosis should be managed by a multidisciplinary team with experience in both sarcoidosis and other forms of cardiac disease.2
GPs play a vital role in the identification and investigation of rare diseases, and sarcoidosis is no exception. By investigating common presentations and referring patients appropriately, GPs can improve their patients’ quality of life, and support them to attain the diagnosis and support they deserve.
|Note: At the time of publication (April 2023), some of the drugs discussed in this article did not have UK marketing authorisation for the indications discussed. Prescribers should refer to the individual summaries of product characteristics for further information and recommendations regarding the use of pharmacological therapies. For off-licence use of medicines, the prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices for further information.|