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Sarcoidosis is a condition in which the immune system forms tiny clumps of inflammatory cells (granulomas) in the body, most often in the lungs and lymph nodes. Symptoms vary widely — from none at all to cough, breathlessness, fatigue, and skin or eye problems — and it can affect several organs. Many cases settle on their own, while others need medicines such as steroids to calm the inflammation. Treatment is guided by which organs are involved and how active the disease is. This page explains sarcoidosis and how it is managed.
Sarcoidosis is a multisystem granulomatous disease that most commonly affects the lungs and intrathoracic lymph nodes but can involve almost any organ. The 2020 ATS/ERS/JRS/ALAT clinical practice guideline is the current international reference.
Definition
Sarcoidosis is a systemic disorder of unknown aetiology characterised by the formation of non-caseating granulomas in affected tissues. Pulmonary involvement is present in over 90% of cases and is the most common cause of morbidity.1
Pathophysiology
A genetically susceptible host mounts an exaggerated CD4+ T-helper-cell response to an as-yet unidentified antigen (proposed candidates include mycobacterial proteins, propionibacterium species, and environmental dusts). The result is granuloma formation with subsequent fibrosis in a subset of patients.
Co-morbidities
Common co-morbidities include depression and fatigue (often disproportionate to physical findings), obstructive sleep apnoea, and metabolic complications of corticosteroid therapy (osteoporosis, diabetes, weight gain).
Prevalence
International prevalence estimates range widely: most non-Nordic Western data cluster nearer 10–20 per 100,000, while Nordic cohorts report 50–60 per 100,000. Australian-specific prevalence data are limited. Peak incidence is between 25 and 45 years, with a second smaller peak in women over 50. African and Scandinavian populations have higher prevalence and more severe disease.
Causes and risk factors
The cause remains unknown. Environmental triggers (mould, insecticides, agricultural exposures, work in the World Trade Center clean-up cohort) and infectious triggers (mycobacterial, propionibacterial) have been implicated. Familial clustering occurs in 4–10% of cases.
Symptoms
Pulmonary: dry cough, dyspnoea, chest discomfort. Constitutional: fatigue, weight loss, low-grade fever, night sweats. Extra-pulmonary: skin lesions (erythema nodosum, lupus pernio, cutaneous plaques), uveitis, peripheral or cranial neuropathy, arrhythmia, hypercalcaemia, arthralgia.
Löfgren syndrome (bilateral hilar lymphadenopathy, erythema nodosum, ankle arthritis, with or without fever) is an acute presentation with a high spontaneous remission rate.
Scadding radiographic stages
Stage 0: normal chest radiograph. Stage I: bilateral hilar lymphadenopathy alone. Stage II: bilateral hilar lymphadenopathy with parenchymal infiltrates. Stage III: parenchymal infiltrates without lymphadenopathy. Stage IV: pulmonary fibrosis. Spontaneous resolution is more likely in earlier stages.
Diagnosis
Why diagnosis matters
Sarcoidosis is a diagnosis of exclusion that requires clinical, radiological and histopathological correlation. Misdiagnosis as tuberculosis, lymphoma, or hypersensitivity pneumonitis is common and leads to inappropriate treatment.
How the diagnosis is made
Diagnosis requires a compatible clinical and radiological picture, histopathological evidence of non-caseating granulomas, and exclusion of alternative causes (especially tuberculosis, fungal infection, beryllium disease, and lymphoma).
Radiology
Chest radiograph (Scadding staging) and HRCT chest. Typical HRCT features include perilymphatic micronodules, hilar and mediastinal lymphadenopathy, upper-zone predominance, and in advanced disease fibrosis with traction bronchiectasis and architectural distortion. FDG-PET is useful for identifying active disease sites and guiding biopsy.
Lung function
Pulmonary function may be normal in early disease. Restrictive pattern with reduced DLCO is characteristic in established parenchymal disease, but obstructive and mixed patterns also occur, particularly with endobronchial involvement.
Pathology and biomarkers
Tissue biopsy demonstrating non-caseating granulomas is required (most commonly via endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal nodes — EBUS-TBNA). Serum ACE has poor sensitivity and specificity and is no longer recommended for diagnosis. Serum and urinary calcium, vitamin D metabolites, and inflammatory markers may aid monitoring.
Investigations for extra-pulmonary involvement
All patients require baseline ECG, ophthalmology review (slit-lamp examination), full blood count, liver function tests, calcium, and urinalysis. Cardiac MRI, FDG-PET, and ambulatory ECG monitoring are indicated if cardiac sarcoidosis is suspected (palpitations, syncope, conduction abnormality).
Management
Treatment goals
Goals are to prevent organ damage from active inflammation, alleviate symptoms, preserve quality of life, and minimise treatment toxicity. Asymptomatic patients with stable disease may not require treatment and can be monitored.
When to treat
Treatment is indicated for symptomatic or progressive pulmonary disease, cardiac, neurological, ocular, or renal involvement, hypercalcaemia, and disfiguring or functionally limiting skin disease. Asymptomatic stage I disease usually does not require treatment.
First-line therapy
Oral corticosteroids (prednisolone 20–40 mg daily, tapered over 6–12 months) remain first-line for organ-threatening or symptomatic disease. Inhaled corticosteroids have a limited role for cough-predominant disease.2
Second- and third-line therapy
Steroid-sparing agents (methotrexate, azathioprine, mycophenolate, leflunomide) are added for steroid-dependent or refractory disease. Biologic agents (infliximab, adalimumab) are reserved for severe refractory cases under specialist supervision.
Monitoring and exacerbation
Disease activity is assessed clinically and with serial pulmonary function testing, imaging, and disease-specific outcome measures (King’s Sarcoidosis Questionnaire, FAS for fatigue). Exacerbations are usually managed with corticosteroid dose increase.
Medications
Anti-inflammatory and immunosuppressive
Prednisolone, methotrexate, azathioprine, mycophenolate, hydroxychloroquine (particularly for cutaneous and hypercalcaemic disease), infliximab.
Supportive medications
Bone protection (calcium, vitamin D, bisphosphonate if appropriate), proton pump inhibitor, prophylaxis against Pneumocystis when on high-dose immunosuppression, vaccinations as appropriate.
Multi-system manifestations
Cardiac sarcoidosis
Clinically apparent in 5–10% but found at autopsy in 20–30%. Presentations include conduction disease, ventricular arrhythmia, heart failure, and sudden cardiac death. Cardiac MRI and FDG-PET are key investigations and management often requires combined cardiology and respiratory input.3
Neurosarcoidosis
Cranial neuropathy (especially facial nerve), aseptic meningitis, hypothalamic-pituitary dysfunction, peripheral neuropathy, and small fibre neuropathy. Small fibre neuropathy is an important and under-recognised contributor to fatigue and pain.
Ocular sarcoidosis
Anterior or posterior uveitis, retinal vasculitis, optic neuropathy. Untreated ocular sarcoidosis can cause permanent vision loss. All patients require formal ophthalmology assessment at diagnosis.
Hypercalcaemia and renal involvement
Granulomatous activation of vitamin D causes hypercalcaemia, hypercalciuria, and nephrocalcinosis. Sun exposure and high dietary calcium and vitamin D should be moderated.
Fatigue and small fibre neuropathy
Disabling fatigue is reported by 60–80% of patients and often persists despite radiographic disease control. It is frequently associated with small fibre neuropathy, sleep disturbance, and depression rather than active granulomatous disease.4,5,6
Warning signs
Living with sarcoidosis
Exercise and pulmonary rehabilitation
Pulmonary rehabilitation reduces fatigue and improves exercise capacity and quality of life in sarcoidosis. Programmes are similar in structure to those for ILD, with attention to symptom-limited progression and management of post-exertional fatigue.7,8,9
Nutrition
Moderate dietary calcium and vitamin D intake (particularly during active disease and high sun exposure). Steroid-related weight gain and metabolic effects warrant proactive nutritional input.
Sleep and mood
Sleep-disordered breathing is more prevalent in sarcoidosis. Depression and anxiety are common, frequently driven by fatigue and steroid effects, and warrant active screening and management.
Travel and prognosis
Most patients have a favourable long-term prognosis, with spontaneous remission in 30–70% within 2–5 years. A minority develop chronic progressive disease requiring sustained therapy. Air travel may require pre-flight assessment in advanced disease.
Role of the physiotherapist
The physiotherapist delivers exercise rehabilitation to address the fatigue, deconditioning and breathlessness common in sarcoidosis, teaches breathing and pacing strategies, and supports self-management and confident activity.
Part 1 · References
- Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2020;201(8):e26–e51.
- Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J 2021;58(6):2004079.
- Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11(7):1305–1323.
- Hoitsma E, Marziniak M, Faber CG, et al. Small fibre neuropathy in sarcoidosis. Lancet 2002;359(9323):2085–2086.
- De Vries J, Michielsen H, Van Heck GL, Drent M. Measuring fatigue in sarcoidosis: the Fatigue Assessment Scale (FAS). Br J Health Psychol 2004;9(3):279–291.
- Drent M, Strookappe B, Hoitsma E, De Vries J. Consequences of sarcoidosis. Clin Chest Med 2015;36(4):727–737.
- Marcellis RGJ, Lenssen AF, Elfferich MDP, et al. Exercise capacity, muscle strength and fatigue in sarcoidosis. Eur Respir J 2011;38(3):628–634.
- Strookappe B, Swigris J, De Vries J, Elfferich M, Knevel T, Drent M. Benefits of physical training in sarcoidosis. Lung 2015;193(5):701–708.
- Naz I, Ozalevli S, Ozkan S, Sahin H. Efficacy of a structured exercise program for improving functional capacity and quality of life in patients with stage 3 and 4 sarcoidosis: a randomized controlled trial. J Cardiopulm Rehabil Prev 2018;38(2):124–130.
References are numbered in citation order (Vancouver/BMJ style) and were current at the time of writing. Guidelines are living documents — verify against the latest version before clinical use.
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Clinical evidence
Part 1 covers the same condition without the technical detail. What follows is the evidence base behind it, written for clinicians — the literature, the reasoning and the gaps.
For clinicians: this summary supports clinical reasoning and is not a protocol. Check current guidelines and local policy before applying it, and read it alongside the key references and guidelines directory.
Framing. Sarcoidosis is a multisystem granulomatous disease with a highly variable course — many patients remit spontaneously, and treatment is reserved for organ-threatening disease or unacceptable symptoms rather than started on radiology alone.1,2 The clinically dominant complaint, however, is frequently fatigue and reduced exercise capacity that correlate poorly with lung function or imaging, which makes physiotherapy central rather than peripheral to management.3
Medical management
- Corticosteroids remain first-line where treatment is indicated, with methotrexate as the usual second-line steroid-sparing agent and tumour necrosis factor inhibition for refractory disease.2
- Treatment is symptom- and organ-driven: the guidelines advise against treating asymptomatic stage I disease, and Löfgren syndrome carries a favourable prognosis with high spontaneous remission.1,2
- Cardiac sarcoidosis is the dangerous phenotype, presenting with arrhythmia, conduction block, heart failure or sudden death, and warranting specific screening where there are cardiac symptoms or an abnormal ECG.4
- Corticosteroid burden — proximal myopathy, weight gain, glucose intolerance, osteoporosis, mood change — frequently contributes as much to disability as the disease itself.2,5
Fatigue, muscle function and exercise
- Reduced exercise capacity, quadriceps weakness and fatigue are common and are only weakly related to pulmonary function, so they must be measured directly rather than inferred from spirometry.3
- Physical training improves exercise capacity, muscle strength and fatigue in sarcoidosis in cohort and controlled studies, with the largest gains in the most fatigued and deconditioned.5,6
- A structured exercise programme improved functional capacity and quality of life in a randomised trial in advanced (stage III–IV) pulmonary sarcoidosis.7
- Small-fibre neuropathy occurs in a substantial minority and produces burning pain, autonomic symptoms and fatigue that will not respond to conditioning alone.8
- The Fatigue Assessment Scale is validated in sarcoidosis and gives a repeatable outcome measure for the symptom patients care most about.9
Physiotherapy implications
- Measure what limits the patient: six-minute walk with desaturation profile, quadriceps and grip strength, sit-to-stand, and a fatigue score — then prescribe against those rather than against imaging stage.3,9
- Make resistance training a priority, not an adjunct: steroid myopathy and disuse weakness are often the dominant mechanical problem, and strength responds well.5,6
- Screen for cardiac involvement before intensifying exercise — palpitations, syncope, pre-syncope, disproportionate breathlessness or a known conduction abnormality all warrant cardiology assessment first.4
- Airway clearance has no routine role; reserve it for coexisting bronchiectasis or aspergillus-complicated fibrocystic disease, where sputum is genuinely present.
- Pace and titrate around fatigue. Sarcoidosis fatigue is often disproportionate and fluctuating; build consistency before volume, and reassess rather than pushing through a bad fortnight.3
- Address the steroid consequences directly: weight, bone health with weight-bearing and resistance work, falls risk, and glucose-related fatigue.2
- Escalate syncope or arrhythmia symptoms, new visual symptoms (ocular sarcoidosis), progressive breathlessness with desaturation, hypercalcaemia symptoms, or neurological signs.
Clinical reasoning
- Fatigue out of proportion to lung function is the rule, not an anomaly — do not dismiss it because spirometry is preserved.3
- Distinguish deconditioning (improves predictably with training) from small-fibre neuropathy, cardiac involvement and steroid myopathy, which need different answers.4,8
- Radiological stage does not predict symptom burden or treatment need; treat the patient, not the film.1
- A patient with new palpitations or syncope is a cardiology referral before they are a rehabilitation participant.4
Evidence gaps
- Exercise trials in sarcoidosis are few, small and heterogeneous, with no defined optimal modality, intensity or duration.6,7
- No intervention has been shown to modify sarcoidosis-associated fatigue reliably, and mechanisms remain unclear.3
- Safe exercise parameters in cardiac sarcoidosis are undefined and rest on extrapolation from cardiomyopathy guidance.4
- Whether rehabilitation influences disease course, exacerbation or steroid requirement is unknown.
References for the clinical evidence summary
- Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: an official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med 2020;201(8):e26–e51.
- Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J 2021;58(6):2004079.
- Drent M, Strookappe B, Hoitsma E, De Vries J. Consequences of sarcoidosis. Clin Chest Med 2015;36(4):727–737.
- Birnie DH, Sauer WH, Bogun F, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 2014;11(7):1305–1323.
- Marcellis RGJ, Lenssen AF, Elfferich MDP, et al. Exercise capacity, muscle strength and fatigue in sarcoidosis. Eur Respir J 2011;38(3):628–634.
- Strookappe B, Swigris J, De Vries J, Elfferich M, Knevel T, Drent M. Benefits of physical training in sarcoidosis. Lung 2015;193(5):701–708.
- Naz I, Ozalevli S, Ozkan S, Sahin H. Efficacy of a structured exercise program for improving functional capacity and quality of life in patients with stage 3 and 4 sarcoidosis: a randomized controlled trial. J Cardiopulm Rehabil Prev 2018;38(2):124–130.
- Hoitsma E, Marziniak M, Faber CG, et al. Small fibre neuropathy in sarcoidosis. Lancet 2002;359(9323):2085–2086.
- De Vries J, Michielsen H, Van Heck GL, Drent M. Measuring fatigue in sarcoidosis: the Fatigue Assessment Scale (FAS). Br J Health Psychol 2004;9(3):279–291.
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