QuestionSBA
QuestionChoice
CRP can be raised in any infection or conditions that cause inflammation in the body. It is a non-specific marker which would not be helpful in determining the cause of this patient's symptoms, since it may be raised in conditions such as sarcoidosis,  but also other inflammatory conditions, including pneumonia.
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C-reactive protein
QuestionChoice
This scan can be requested later on by a specialist within the hospital setting. A CT chest is useful to further characterise how the sarcoidosis has affected the patient's lungs. This would be requested after a CXR, since starting with simple, least invasive/harmful investigations is most appropriate in the first instance.
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CT chest
QuestionChoice
This is a specialist investigation which would not be requested by the GP.  This investigation can be diagnostic for sarcoidosis, but it does not represent the next best investigation. Typically, you would find non-caseating granulomas on a biopsy.
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Lung biopsy
QuestionChoice
This patient has sarcoidosis which explains her long-term symptoms. In the early stages, a CXR may show evidence of bilateral hilar lymphadenopathy and fibrosis in the later stages. It can also rule out other causes of shortness of breath and crepitations, such as pneumonia.
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a
Chest X-Ray
QuestionChoice
Serum ACE levels are raised in sarcoidosis, however it would not be the next best investigation since ACE is neither specific to, nor diagnostic of, sarcoidosis.
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Angiotensin-converting enzyme (ACE) levels
QuestionComment
If patient is in GP would they not do a blood test first? Agree CXR is the 'better' investigation, but 'next' would be a blood test?
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RNA Relapse
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ngl i thought it was TB with spinal infection :/
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Pudendal Syndrome
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what is causing the tingling down her legs?
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QuestionComment
It can cause neuro Sx such as peripheral neuropathy, ( meningitis, bilateral Bell’s palsy)
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Fibrillation RNA
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Amnesia Syndrome
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# Summary

Sarcoidosis is an inflammatory disease characterised by granuloma formation in various organs, with the most commonly affected being the lungs. Symptoms include fever, polyarthralgia, erythema nodosum, dry cough, dyspnoea, fatigue and weight loss. Investigations include blood tests (with calcium and serum ACE being important), chest X-ray and biopsy of a granuloma. Management depends on the severity of disease and may include NSAIDs, corticosteroids and other immunosuppressants.

# Definition

Sarcoidosis is a multi-system disease that is characterised by the formation of non-caseating granulomas around the body. This leads to inflammation and scarring in the organs affected, most commonly the lungs and skin. Other organs affected include the nerves, the brain, the heart, the liver and the eyes.

# Epidemiology

In the UK, there are approximately 4,500 new diagnoses of sarcoidosis each year, with a prevalence around 1 in 10,000 people. Prevalence varies significantly depending on region, with the highest rates seen in Northern Europe (e.g. Sweden, Finland and Denmark). Some ethnicities are more at risk than others, with people of African descent being affected more often and with more severe disease.

Peak onset is in adults aged between 30 and 55 years old, and it is slightly more common in women than men.

# Aetiology

The cause of sarcoidosis is not known, with the main theories being that it is an inflammatory response to a yet unidentified environmental exposure or infection, or that is is caused by autoimmunity.

A small percentage of cases are familial and the wide variation in prevalence across different populations suggests that genetic factors are likely to contribute to its development.

# Signs and Symptoms

**Pulmonary manifestations**

- Dry cough
- Dyspnoea
- Reduced exercise tolerance
- Chest pain
- Clubbing
- Fine crackles on auscultation

**Dermatological manifestations**

- Erythema nodosum (inflammation of subcutaneous fat leading to tender nodules especially on the shins)
- Lupus pernio (red/purple plaques and nodules on the face)
- Hyper or hypopigmentation of the skin

**Neurological manifestations**

- Meningitis
- Peripheral neuropathy
- Facial nerve palsy (may be bilateral)
- Headache
- Seizures/encephalopathy

**Ocular manifestations**

- Uveitis
- Keratoconjunctivitis sicca
- Glaucoma

**Cardiac manifestations**

- Arrhythmias
- Restrictive cardiomyopathy
- Syncope

**Abdominal manifestations**

- Hepatomegaly
- Splenomegaly
- Renal stones

**Systemic manifestations**

- Fatigue
- Weight loss
- Arthralgia
- Low-grade fevers
- Lymphadenopathy
- Enlarged parotid glands

**Lofgren's syndrome** refers to the acute onset of:

- Fever
- Polyarthralgia
- Erythema nodosum
- Bilateral hilar lymphadenopathy (seen on chest X-ray)

**Heerfordt's syndrome** refers to the combination of:

- Fever
- Uveitis
- Parotid swelling
- Facial nerve palsy

# Differential Diagnosis

- **Tuberculosis:** may present very similarly with chronic cough, night sweats, weight loss, bilateral hilar lymphadenopathy so important to rule out (see investigations).
- **Lymphoma:** also may present with unexplained weight loss, fever, night sweats and lymphadenopathy, pulmonary symptoms less predominant, can be distinguished on biopsy.
- **Other causes of interstitial lung disease:** similar pulmonary features of dyspnoea, cough and chest pain, and may have weight loss and malaise. Extrapulmonary features (e.g. rashes and hypercalcaemia) seen in sarcoidosis help to differentiate.

# Investigations

**Bedside investigations include:**

- **ECG** looking for arrhythmias or changes related to hypercalcaemia (e.g. QT shortening)
- **Mantoux test** looking for evidence of exposure to tuberculosis (an important differential)
- **Lung function testing** - if pulmonary sarcoidosis suspected
- **Ophthalmological examination** if ocular sarcoidosis suspected

**Blood tests include:**

- **FBC** may show lymphopenia, anaemia or raised white cells
- **LFTs** for liver disease
- **Renal function** for renal impairment (not common in sarcoidosis)
- **Bone profile** for hypercalcaemia
- **ESR** may be raised due to chronic inflammation
- **Serum ACE** is elevated in around 60% and normalises if the disease resolves (with or without treatment)

**Imaging studies include:**

- **Chest X-ray** can be used to stage sarcoidosis as below:
	- Stage 1 - Bilateral hilar lymphadenopathy (BHL)
	- Stage 2 - BHL with peripheral infiltrates
	- Stage 3 - Peripheral infiltrates alone
	- Stage 4 - Pulmonary fibrosis
- **High-resolution CT chest** should be done if sarcoidosis suspected on chest X-ray to further assess for pulmonary fibrosis 
- **PET scanning** may be used if there is ongoing diagnostic uncertainty
- **Echocardiogram** if cardiac disease is suspected

**Other investigations include:**

- **Biopsy** is required to confirm the diagnosis in most cases (with a classic presentation of chronic pulmonary disease or a clear case of Lofgren's syndrome being exceptions) - this is looking for the classic finding of noncaseating granulomas
- **Bronchoalveolar lavage** may also be done in suspected pulmonary sarcoidosis, with classic findings of raised lymphocytes and an elevated CD4/CD8 ratio

[lightgallery]

# Management

**Conservative treatment includes:**

- Patient education and support
- Smoking cessation
- **No active treatment is needed in many cases of sarcoidosis** 

**Medical treatment includes:**

- Steroids e.g. oral prednisolone with a higher dose at induction which is then reduced to a lower maintenance dose
- Second line immunosuppressants (e.g. if steroids contraindicated or not effective) include methotrexate, mycophenolate or azathioprine
- Third line treatment is usually with biologics (e.g. infliximab)

**Note - Medical treatment should be started only if sarcoidosis symptoms are affecting quality of life or there is significant risk of morbidity or mortality from sarcoidosis**

**Surgical treatment includes:**

- Rarely in severe cases of pulmonary sarcoidosis a lung transplant may be considered
- In cases of pulmonary sarcoidosis complicated by aspergilloma, surgical management of haemoptysis is sometimes required

# Complications

- Pulmonary fibrosis (stage IV pulmonary sarcoidosis
- Cor pulmonale
- Pulmonary hypertension
- Aspergillomas can form in cavities left by granulomatous pulmonary disease
- Arrhythmias and sudden death in cardiac sarcoidosis
- Low mood and anxiety
- Complications of long-term steroid use (e.g. osteoporosis, hyperglycaemia)

# Prognosis

- In general prognosis is good, with two-thirds of people experiencing disease remission within 2-5 years (usually with no treatment required).
- Around 20% of people develop chronic disease requiring treatment
- Remission is more common in earlier stages of sarcoidosis
- Only 6-8% of people with sarcoidosis have a reduced life expectancy, with the commonest cause of death being pulmonary disease (interstitial lung disease and pulmonary hypertension)

# NICE Guidelines

[NICE CKS - Sarcoidosis](https://cks.nice.org.uk/topics/sarcoidosis/)

# References

[Patient UK - Sarcoidosis](https://patient.info/doctor/sarcoidosis-pro)

[Radiopaedia - Sarcoidosis](https://radiopaedia.org/articles/sarcoidosis-1?lang=gb)
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Sarcoidosis commonly presents with fatigue, shortness of breath, and lymphadenopathy; a chest X-ray is essential for diagnosis and assessment.
A 35-year-old female presents to the GP with a 6-month history of fatigue. During this time, she also describes feeling short of breath when running for the bus and recurrent episodes of tingling down her leg. On examination, she has swollen lymph nodes and crepitations on chest auscultation. She has a temperature of 37.7.

Which of the following is the next best investigation?
a