Sarcoidosis: Symptoms, Types, Causes and Treatment

Sarcoidosis is a mysterious, multisystem disease that continues to challenge both patients and healthcare professionals. It can silently affect different organs, from the lungs and skin to the heart and nervous system, often appearing with a puzzling array of symptoms. In this article, we dive into the latest understanding of sarcoidosis, exploring its symptoms, clinical types, suspected causes, and treatment strategies, with a focus on delivering clear and evidence-based insights.

Symptoms of Sarcoidosis

Sarcoidosis is known for its highly variable presentation, meaning people may experience a broad spectrum of symptoms—or sometimes, none at all. The disease can affect almost any organ, leading to both specific organ-related and general systemic complaints. Recognizing its key symptoms is essential for early diagnosis and management.

Symptom	Description	Prevalence / Examples	Source(s)
Fatigue	Persistent tiredness, often disabling	Up to 90% of patients	2 5 11
Pulmonary	Cough, dyspnea, chest pain	70–90% (cough, SOB, chest discomfort)	2 3 4 14
Skin	Rashes, nodules, erythema nodosum	25–50% (skin lesions); erythema nodosum	4 7 9
Eye	Redness, pain, blurred vision (uveitis)	Up to 25%	4 6
Joint	Arthralgia, arthritis (acute/chronic)	10–40% (joint/muscle involvement)	8 10
Nerve	Small-fiber neuropathy, cognitive issues	10–15%; SFN symptoms up to 86%	2 6 11

Table 1: Key Symptoms of Sarcoidosis

Pulmonary and Systemic Symptoms

Most patients with sarcoidosis have lung involvement. Common pulmonary symptoms include:

• Cough (usually dry)
• Shortness of breath (dyspnea)
• Chest pain or discomfort

These respiratory symptoms may appear alone or with constitutional symptoms such as fever, weight loss, and pronounced fatigue, which is one of the most disabling and persistent complaints among patients, significantly impacting quality of life. Fatigue can persist even when other symptoms improve or remit 2 5 11.

Extrapulmonary Manifestations

Sarcoidosis can affect many organs outside the lungs:

• Skin: Presents with rashes, nodules, lupus pernio (chronic, violaceous skin lesions), and erythema nodosum (tender red bumps, often on shins). Skin involvement is the second most frequent after the lungs and can sometimes be the presenting feature 4 7 9.
• Eyes: Uveitis (inflammation of the uvea) is most common, causing redness, pain, and visual disturbances. Untreated, this can lead to vision loss 4 6.
• Joints and Muscles: Many patients develop joint pain (arthralgia) or acute arthritis, especially in the ankles. Chronic arthritis and muscle involvement are less common but may be more disabling 8 10.
• Nervous System: Neurological involvement can cause peripheral neuropathy (especially small-fiber neuropathy), cognitive changes, and rarely, more severe issues like facial nerve palsy or central nervous system involvement 2 6 11.
• Other Organs: The liver, spleen, heart, kidneys, and lymph nodes can also be involved, sometimes leading to organ dysfunction 4 6.

Non-Specific Symptoms

Some symptoms are less obviously linked to a particular organ but are commonly reported, including:

• Night sweats
• Weight loss
• General malaise
• Cognitive impairment (e.g., difficulty concentrating, memory issues)
• Small-fiber neuropathy symptoms such as tingling, burning, or numbness, especially in hands and feet 2 11.

Types of Sarcoidosis

Sarcoidosis is not a single disease but rather a collection of syndromes that can be grouped by the pattern of organ involvement and symptom onset. Understanding these types helps guide diagnosis, management, and prognosis.

Type/Phenotype	Key Features	Organ/System Involved	Source(s)
Acute (Löfgren's)	Fever, erythema nodosum, arthritis	Lungs, skin, joints	4 5 8
Chronic	Slow, progressive symptoms	Lungs, other organs	1 17
Pulmonary-dominant	Cough, dyspnea, chest pain	Lungs, lymph nodes	3 4 6
Cutaneous	Skin lesions, lupus pernio, nodules	Skin	7 9
Musculoskeletal	Arthritis, myopathy, bone lesions	Joints, muscles, bones	8 10
Ocular/Cardiac	Uveitis, arrhythmias, heart failure	Eyes, heart	4 6
Neurologic	Neuropathy, meningeal signs	Peripheral/CNS nerves	6 11

Table 2: Types and Phenotypes of Sarcoidosis

Acute Sarcoidosis (Löfgren’s Syndrome)

This is a distinct, self-limited type seen more often in certain genetic backgrounds (e.g., Northern Europeans). Classic features include:

• Erythema nodosum (painful, red skin nodules)
• Bilateral hilar lymphadenopathy (enlarged lymph nodes in the chest)
• Fever and acute arthritis, usually in ankles

Löfgren’s syndrome often resolves spontaneously and has an excellent prognosis. In this form, histological confirmation may not be necessary if the clinical features are classic 4 5 8.

Chronic Sarcoidosis

Chronic sarcoidosis refers to persistent, slowly progressive disease that can affect the lungs or other organs over many years. It can lead to irreversible organ damage, particularly pulmonary fibrosis, and may require long-term management 1 17.

Phenotypes by Organ Involvement

Recent studies have identified several clinical phenotypes based on which organs are most affected:

1. Pulmonary/intrathoracic lymph node
2. Abdominal organ involvement (liver, spleen, GI tract)
3. Ocular–cardiac–cutaneous–CNS (eyes, heart, skin, brain)
4. Musculoskeletal–cutaneous
5. Extrapulmonary miscellaneous

These classifications help doctors anticipate complications and tailor therapy 6.

Other Notable Types

• Cutaneous Sarcoidosis: Can present as specific granulomatous lesions or non-specific findings like erythema nodosum. The skin may be the only organ affected or part of multisystem disease 7 9.
• Musculoskeletal Involvement: Includes acute and chronic arthritis, myopathy (muscle weakness), dactylitis, and rare bone lesions 8 10.
• Ocular/Cardiac/Neurologic Sarcoidosis: These are less common but can be life-threatening or severely disabling if unrecognized 4 6 11.

Causes of Sarcoidosis

Despite decades of research, the exact cause of sarcoidosis remains elusive. Most experts agree it results from a complex interplay of genetic, immunologic, and environmental factors.

Factor	Description	Example/Mechanism	Source(s)
Genetics	Inherited susceptibility	MHC gene variants	1 12 13
Immune Response	Exaggerated Th1/Th17 reaction	Granuloma formation	1 11 13
Environmental	Exposure to antigens or triggers	Mycobacteria, Propionibacteria, occupational exposures	12 13 14
Unknown Antigen	Persistent, unidentified trigger	Self or microbial antigens	1 11 13

Table 3: Suspected Causes of Sarcoidosis

Genetic Susceptibility

Sarcoidosis is more common among people of African American descent, Scandinavians, and certain family groups, indicating a strong genetic component. Genes within the major histocompatibility complex (MHC) region, which regulate immune responses, are especially implicated 1 12 13.

Immunological Mechanisms

The hallmark of sarcoidosis is the formation of noncaseating granulomas—clusters of immune cells (mainly T helper cells and macrophages) that wall off perceived threats. This response is thought to result from chronic antigenic stimulation, with a pronounced Th1/Th17 cytokine profile and dysregulated regulatory T-cell responses 1 11 13.

Environmental and Infectious Triggers

Environmental exposures have been linked to increased risk:

• Microbial agents: Mycobacteria and Propionibacteria have been found in some lesions, but whether they cause sarcoidosis or are incidental remains hotly debated 12 13.
• Occupational exposures: Insecticides, herbicides, agricultural dust, and bioaerosols are associated with higher risk 14.
• Other triggers: Some evidence suggests serum amyloid A aggregation within granulomas may sustain inflammation 13.

The Unknown Antigen Hypothesis

Most experts believe sarcoidosis starts with exposure to an unknown antigen—potentially infectious, occupational, or even self-derived—in a genetically susceptible person, triggering an abnormal, persistent immune response 1 11 13.

Treatment of Sarcoidosis

Not all patients with sarcoidosis need treatment. When therapy is warranted, the goals are to prevent organ dysfunction and improve quality of life. Treatment decisions depend on which organs are affected, disease severity, and the risk of long-term complications.

Treatment	Indication	Notes/Side Effects	Source(s)
Glucocorticoids	First-line for symptomatic disease	Risk of toxicity with long-term use	15 16 17
Immunosuppressives	Second-line (if steroids fail/intolerant)	Methotrexate, azathioprine, leflunomide, mycophenolate	15 17 18
Biologics	Refractory/severe cases	Anti-TNF agents (e.g., infliximab)	17 18
Symptom-specific	Fatigue, skin/joint/eye involvement	Address QoL and organ-specific issues	2 15
Observation	Asymptomatic/minimal disease	No therapy, monitor for progression	16 17

Table 4: Main Treatment Options for Sarcoidosis

When to Treat

Treatment is recommended for:

• Significant organ impairment (e.g., lungs, heart, eyes, nervous system)
• Persistent, disabling symptoms (fatigue, pain)
• High risk of progression or organ failure

For asymptomatic patients with minor disease, careful observation is often preferred 15 16 17.

First-Line: Glucocorticoids

Corticosteroids (e.g., prednisone) are the mainstay for initial therapy. They are effective at reducing inflammation and granuloma formation but carry significant risks—especially with long-term use—including weight gain, diabetes, osteoporosis, and infections 15 16.

Second-Line: Steroid-Sparing Agents

If steroids are not effective, cause intolerable side effects, or long-term therapy is needed, immune-suppressing drugs may be used:

• Methotrexate (most common)
• Azathioprine
• Leflunomide
• Mycophenolate mofetil

These drugs can reduce steroid requirements and manage chronic disease, especially in lung, joint, or neurological involvement 15 17 18.

Third-Line: Biologics

For refractory sarcoidosis—disease that does not respond to steroids or immunosuppressives—biologic agents are considered:

• Anti-TNF agents (infliximab is most studied)
• Other biologics (e.g., rituximab in rare cases)

Biologics are reserved for severe, organ-threatening disease due to cost and potential side effects 17 18.

Symptom Management and Quality of Life

• Fatigue: Non-pharmacological strategies, such as exercise and sleep interventions, may be considered. Drug therapy is rarely effective 2 15.
• Joint and Muscle Symptoms: NSAIDs or low-dose steroids for acute arthritis; long-term immunosuppression as above for chronic cases 8 10 15.
• Cutaneous Disease: Topical or intralesional steroids may be used for localized skin lesions; systemic therapy for severe involvement 7 9 15.
• Eye and Cardiac Disease: Often require urgent specialist management to prevent permanent damage 4 6 15.

Monitoring and Multidisciplinary Care

Regular follow-up is essential to monitor for organ function, treatment side effects, and disease progression. A multidisciplinary approach—often involving pulmonologists, rheumatologists, dermatologists, cardiologists, and neurologists—yields the best outcomes 5 11 15.

Conclusion

Sarcoidosis is a complex, multisystem disease that remains enigmatic despite significant research advances. Its variable symptoms and unpredictable course demand a personalized, multidisciplinary approach to diagnosis and care.

Key Points:

• Sarcoidosis can present with a wide range of symptoms, most commonly affecting the lungs, skin, eyes, and joints.
• The disease can be classified into types based on symptom onset, organ involvement, and clinical course.
• Its causes remain unclear, but involve a combination of genetic, immunologic, and environmental factors.
• Not all patients require treatment; when needed, therapy is tailored to organ involvement and risk of progression, starting with corticosteroids and advancing to immunosuppressives or biologics if necessary.
• Quality-of-life issues, especially fatigue, are increasingly recognized as important treatment targets.

Understanding sarcoidosis requires ongoing research and collaboration, with hope for more effective, personalized therapies in the near future.