Sarcoidosis: Symptoms, Causes & Treatment Guide

What Is Sarcoidosis and What Causes It?

Sarcoidosis is an inflammatory disease where the immune system forms clusters of cells called granulomas in various organs, most commonly the lungs and lymph nodes. The exact cause remains unknown, but it appears to result from an abnormal immune response to an unidentified trigger in genetically susceptible individuals.

Sarcoidosis is a relatively uncommon disease that can affect almost any organ in the body. The hallmark of sarcoidosis is the formation of granulomas, which are tiny clusters of immune cells that form when the immune system attempts to wall off substances it perceives as foreign. Unlike granulomas caused by infections such as tuberculosis, sarcoidosis granulomas are non-caseating, meaning they do not show the characteristic necrosis or death of tissue in their centers.

The disease was first described in the late 19th century and has been known by several names, including Besnier-Boeck-Schaumann disease. Today, we understand that sarcoidosis represents an exaggerated immune response, but the triggering factors remain elusive. Research suggests that both environmental factors (such as certain infections, dust, or chemicals) and genetic predisposition play important roles in disease development.

Most people who develop sarcoidosis are between 25 and 40 years of age. The condition is rare in individuals younger than 20 years. Interestingly, there appears to be a second peak of incidence in women over 50 years of age in some populations. The disease affects people of all racial and ethnic backgrounds, but prevalence and severity vary significantly between different groups.

What happens in the body?

In sarcoidosis, the immune system does not function properly. Instead of responding appropriately to threats, it creates inflammation that leads to granuloma formation. These granulomas are essentially swellings composed of tightly packed immune cells, primarily macrophages that have transformed into specialized cells called epithelioid cells and giant cells.

Over time, granulomas can either resolve completely, leaving no lasting damage, or they can develop into fibrous scar tissue. When scarring occurs in vital organs like the lungs, it can lead to permanent impairment of organ function. The unpredictable nature of whether granulomas will resolve or progress to fibrosis is one of the challenging aspects of managing sarcoidosis.

The inflammation and granulomas can develop in various parts of the body. The most commonly affected areas include:

• Lungs and lymph nodes - affected in approximately 90% of cases
• Skin - involved in 20-35% of patients
• Eyes - affected in 10-50% of cases
• Liver - granulomas found in up to 70% on biopsy, though often without symptoms
• Heart - clinically apparent in 2-5% but may be present in up to 25% on autopsy
• Nervous system - affected in 5-10% of cases

Lofgren syndrome vs. non-Lofgren syndrome

Sarcoidosis manifests in two main clinical patterns that have important implications for prognosis and treatment.

Lofgren syndrome is an acute presentation of sarcoidosis characterized by the sudden onset of three classic features: erythema nodosum (painful red nodules on the shins), bilateral hilar lymphadenopathy (enlarged lymph nodes in the chest visible on X-ray), and arthritis or joint pain. Patients with Lofgren syndrome often experience fever and significant fatigue. Despite the dramatic initial presentation, the prognosis is excellent, with 60-90% of patients experiencing complete resolution within 2 years without treatment.

Non-Lofgren syndrome represents the more insidious chronic form of sarcoidosis. In this presentation, symptoms develop gradually over time and may initially be quite subtle. Patients might notice progressive shortness of breath, persistent dry cough, or gradual weight loss. Non-Lofgren syndrome is more likely to involve multiple organs and carries a higher risk of developing chronic disease requiring long-term treatment.

What causes sarcoidosis?

Despite decades of research, the exact cause of sarcoidosis remains unclear. The current understanding is that sarcoidosis develops when genetically susceptible individuals are exposed to specific environmental triggers that provoke an abnormal immune response.

Several potential triggers have been investigated, including infectious agents (such as mycobacteria and propionibacteria), inorganic particles (like silica, aluminum, and zirconium), and organic antigens (including mold and pollen). The ACCESS study and other epidemiological investigations have identified occupational exposures in certain industries, including agricultural, healthcare, and manufacturing settings, as potential risk factors.

Genetic factors clearly play a role, as sarcoidosis clusters in families and shows strong associations with certain HLA (human leukocyte antigen) types. Having a first-degree relative with sarcoidosis increases the risk of developing the disease by approximately 4-5 fold. However, most people with genetic predisposition never develop sarcoidosis, highlighting the importance of environmental factors.

What Are the Symptoms of Sarcoidosis?

Sarcoidosis symptoms vary widely depending on which organs are affected. Common symptoms include persistent dry cough, shortness of breath, fatigue, fever, unexplained weight loss, skin rashes or nodules, swollen lymph nodes, and red or painful eyes. Some people have no symptoms at all and are diagnosed incidentally.

The symptoms of sarcoidosis can range from completely absent to severely debilitating, depending on which organs are involved and the extent of inflammation. This variability is one of the reasons why sarcoidosis can be challenging to diagnose. Some patients discover they have the disease only when a routine chest X-ray reveals abnormalities, while others present with acute, dramatic symptoms.

Constitutional symptoms, which are nonspecific symptoms affecting the whole body, are common in sarcoidosis. These include persistent fatigue that does not improve with rest, unexplained weight loss, fever (particularly low-grade), night sweats, and a general feeling of being unwell. Fatigue is one of the most troublesome symptoms for many patients and can persist even when the disease appears to be under control.

Pulmonary (lung) symptoms

Because the lungs are involved in approximately 90% of sarcoidosis cases, respiratory symptoms are among the most common presentations. The classic pulmonary symptoms include:

• Dry, persistent cough - often described as a hacking cough that does not produce much phlegm
• Shortness of breath - especially noticeable during physical activity
• Chest discomfort - may feel like tightness or vague pain behind the breastbone
• Wheezing - in some cases, sarcoidosis can cause airway obstruction

Interestingly, the severity of lung symptoms does not always correlate with the extent of disease seen on imaging. Some patients with extensive changes on chest X-ray have minimal symptoms, while others with less apparent disease experience significant respiratory impairment.

Skin symptoms

Skin involvement occurs in 20-35% of sarcoidosis patients and can take many forms. The appearance can vary considerably between individuals and even within the same person over time:

• Erythema nodosum - tender, red nodules typically on the shins; common in Lofgren syndrome
• Lupus pernio - chronic purple or red raised patches on the nose, cheeks, lips, or ears; associated with chronic disease
• Papular sarcoidosis - small, raised bumps that may be skin-colored, red, or brown
• Plaques - raised, flat patches that may be scaly
• Subcutaneous nodules - lumps under the skin that can be felt but may not be visible

Skin lesions can vary in color depending on the individual's skin tone. They may appear red-brown, purple, or darker than the surrounding skin. In people with darker skin, the lesions may appear as lighter or darker patches compared to unaffected areas.

Eye symptoms

Ocular involvement occurs in 10-50% of sarcoidosis patients and can be sight-threatening if not recognized and treated promptly. Eye symptoms include:

• Uveitis - inflammation inside the eye causing redness, pain, and light sensitivity
• Dry eyes - due to involvement of the tear glands
• Blurred vision - may indicate inflammation affecting the back of the eye
• Eye floaters - small spots or threads drifting across the visual field

Other organ involvement

Sarcoidosis can affect virtually any organ, leading to a wide range of potential symptoms:

• Heart - palpitations, irregular heartbeat, fainting, or heart failure symptoms
• Nervous system - facial numbness or weakness, tingling in arms or legs, headaches
• Joints - pain and swelling, particularly in ankles, knees, and wrists
• Kidneys - increased thirst and frequent urination (due to elevated calcium)
• Liver and spleen - often enlarged but usually without symptoms

Some people have no symptoms

It is important to recognize that a significant proportion of people with sarcoidosis have no symptoms at all. In these cases, the diagnosis is often made incidentally when a chest X-ray or CT scan is performed for an unrelated reason, such as before surgery or for another medical evaluation. The discovery of bilateral hilar lymphadenopathy (enlarged lymph nodes in the chest) or characteristic lung changes on imaging may be the first indication that sarcoidosis is present.

When Should You See a Doctor for Sarcoidosis?

See a doctor if you experience persistent dry cough, progressive shortness of breath, unexplained fatigue, skin rashes or nodules, red painful eyes, or unexplained weight loss. Seek immediate care for severe breathing difficulties, fainting, chest pain, or sudden vision changes.

Because sarcoidosis can mimic many other conditions and its symptoms are often nonspecific, knowing when to seek medical evaluation is important. Many people delay seeking care because they attribute their symptoms to aging, stress, or minor illnesses. However, early diagnosis and monitoring can help prevent complications and ensure appropriate treatment when needed.

Contact your healthcare provider if you experience any of the following symptoms that persist for more than a few weeks:

• Persistent dry cough that does not improve
• Progressive shortness of breath, especially during activities you previously tolerated
• Unexplained and persistent fatigue
• Skin rashes, bumps, or nodules that do not resolve
• Eye redness, pain, or visual changes
• Unexplained weight loss
• Persistent low-grade fever
• Swollen lymph nodes that you can feel
• Joint pain or swelling

How Is Sarcoidosis Diagnosed?

Sarcoidosis diagnosis involves a combination of clinical evaluation, imaging (chest X-ray, CT scan), pulmonary function tests, blood tests, and typically a biopsy showing non-caseating granulomas. Doctors must also exclude other conditions that can cause similar findings, such as tuberculosis and certain cancers.

Diagnosing sarcoidosis can be challenging because there is no single definitive test for the condition. Instead, diagnosis relies on a combination of clinical presentation, imaging findings, laboratory tests, and histological confirmation through biopsy. Equally important is the exclusion of other diseases that can cause similar granulomatous inflammation.

Clinical evaluation and history

The diagnostic process begins with a thorough medical history and physical examination. Your doctor will ask about your symptoms, their duration and progression, occupational exposures, family history, and any other medical conditions. Physical examination will assess your lungs, heart, skin, eyes, lymph nodes, and other organs for signs of sarcoidosis involvement.

Imaging studies

Chest X-ray is typically the first imaging study performed and can show characteristic findings such as bilateral hilar lymphadenopathy (enlarged lymph nodes in the central chest) and/or lung infiltrates. Chest X-ray findings are often used to stage pulmonary sarcoidosis:

• Stage 0: Normal chest X-ray
• Stage I: Bilateral hilar lymphadenopathy only
• Stage II: Bilateral hilar lymphadenopathy with pulmonary infiltrates
• Stage III: Pulmonary infiltrates without hilar lymphadenopathy
• Stage IV: Pulmonary fibrosis with evidence of scarring

CT scan (computed tomography), particularly high-resolution CT (HRCT), provides more detailed images of the lungs and can detect abnormalities not visible on chest X-ray. CT can show the characteristic pattern of granulomas distributed along the lymphatic vessels and bronchi, as well as enlarged lymph nodes.

PET scan (positron emission tomography) may be used to assess the extent of active inflammation throughout the body, particularly when cardiac or neurological involvement is suspected.

Pulmonary function tests

Spirometry measures how much air you can breathe out and how quickly. In sarcoidosis, spirometry may show a restrictive pattern (reduced lung volumes) or sometimes an obstructive pattern (difficulty pushing air out). Pulmonary function tests are also used to monitor disease progression and response to treatment over time.

Laboratory tests

Several blood tests may be performed as part of the diagnostic workup:

• Complete blood count - may show anemia or abnormal white blood cell counts
• Comprehensive metabolic panel - checks kidney and liver function, as well as calcium levels (often elevated in sarcoidosis)
• ACE (angiotensin-converting enzyme) - elevated in about 60% of patients with active sarcoidosis, though not specific
• Vitamin D levels - may be abnormal due to granuloma production of active vitamin D
• Inflammatory markers - ESR and CRP may be elevated

Biopsy

In most cases, a tissue biopsy is needed to confirm the diagnosis by demonstrating the characteristic non-caseating granulomas. The biopsy site is chosen based on accessibility and which organs appear to be involved:

• Bronchoscopy with transbronchial biopsy - the most common approach, allowing sampling of lung tissue and lymph nodes
• Skin biopsy - if skin lesions are present, this provides an easily accessible tissue sample
• Lymph node biopsy - if accessible lymph nodes are enlarged
• Other sites - depending on organ involvement (liver, salivary glands, etc.)

Additional tests

Depending on symptoms and suspected organ involvement, additional tests may include:

• Electrocardiogram (ECG) and cardiac MRI - to evaluate heart involvement
• Eye examination by ophthalmologist - to check for ocular sarcoidosis
• Lumbar puncture - if neurological involvement is suspected
• 24-hour urine calcium - to assess for hypercalciuria

How Is Sarcoidosis Treated?

Not all sarcoidosis requires treatment, as many cases resolve spontaneously. When treatment is needed, corticosteroids (like prednisone) are the first-line therapy. For patients who cannot tolerate steroids or need long-term treatment, immunosuppressive medications like methotrexate, azathioprine, or biologics may be used.

The decision to treat sarcoidosis depends on several factors, including the severity of symptoms, which organs are affected, whether there is evidence of progressive disease, and the risk of permanent organ damage. Treatment aims to reduce inflammation, prevent organ damage, and relieve symptoms while minimizing medication side effects.

Observation without treatment

Many patients with sarcoidosis, particularly those with Lofgren syndrome or asymptomatic disease, do not require specific treatment. Studies show that approximately 60-70% of patients with acute sarcoidosis experience spontaneous remission within 2 years. For these patients, careful monitoring with regular check-ups, pulmonary function tests, and imaging is the appropriate approach.

During the observation period, over-the-counter pain relievers such as NSAIDs (non-steroidal anti-inflammatory drugs like ibuprofen or naproxen) can help manage joint pain, fever, and general discomfort.

Corticosteroid treatment

When treatment is necessary, corticosteroids (also called steroids or glucocorticoids) are the mainstay of therapy. Prednisone is the most commonly used oral corticosteroid. The typical starting dose ranges from 20-40 mg daily, which is then gradually reduced (tapered) over several months to find the lowest effective dose.

Corticosteroids work by suppressing the immune system and reducing inflammation. They are generally very effective at controlling sarcoidosis symptoms and preventing disease progression. However, long-term use is associated with significant side effects, so doctors aim to use the lowest dose for the shortest time necessary.

Indications for starting corticosteroid treatment include:

• Significant pulmonary symptoms or declining lung function
• Eye involvement (uveitis)
• Cardiac sarcoidosis
• Neurosarcoidosis
• Severe skin involvement (especially lupus pernio)
• Hypercalcemia (elevated blood calcium)
• Significant constitutional symptoms affecting quality of life

Steroid-sparing agents

For patients who require long-term treatment, cannot tolerate corticosteroids, or do not respond adequately to steroids alone, other immunosuppressive medications may be added:

• Methotrexate - the most commonly used steroid-sparing agent; taken weekly
• Azathioprine - an alternative immunosuppressant for those who cannot tolerate methotrexate
• Mycophenolate - another option for immunosuppression
• Hydroxychloroquine - particularly useful for skin and joint involvement
• Leflunomide - may be used as an alternative to methotrexate

Biologic medications

For refractory sarcoidosis that does not respond to conventional treatments, biologic medications targeting specific immune pathways may be considered:

• TNF-alpha inhibitors (infliximab, adalimumab) - block an inflammatory cytokine involved in granuloma formation
• Other biologics - being studied in clinical trials

These medications are typically reserved for severe, treatment-resistant cases due to their cost, potential side effects, and the need for careful monitoring.

Organ-specific treatments

Depending on which organs are affected, additional specific treatments may be needed:

• Eye involvement - corticosteroid eye drops for mild uveitis; systemic treatment for severe cases
• Cardiac sarcoidosis - may require pacemaker or defibrillator; immunosuppression is critical
• Skin lesions - topical steroids, hydroxychloroquine, or systemic treatment
• Hypercalcemia - avoid excessive sun exposure and calcium/vitamin D supplements; may need hydroxychloroquine

Side effects and monitoring

Long-term corticosteroid and immunosuppressive therapy can cause various side effects that require monitoring:

• Corticosteroids: weight gain, thinning skin, mood changes, sleep problems, elevated blood sugar, osteoporosis, cataracts
• Methotrexate: liver problems, lung inflammation, mouth sores, hair thinning, low blood counts
• Biologics: increased infection risk, injection site reactions, potential for reactivation of latent infections

Regular monitoring with blood tests, bone density scans, and eye examinations helps detect and manage these potential complications early.

What Are the Complications of Sarcoidosis?

Potential complications of sarcoidosis include pulmonary fibrosis (permanent lung scarring), cardiac arrhythmias, kidney stones due to elevated calcium, blindness from untreated eye involvement, and neurological problems. Most patients do not develop serious complications, but monitoring is important.

While most people with sarcoidosis recover without lasting problems, the disease can sometimes lead to serious complications, particularly when it is chronic or affects critical organs. Understanding these potential complications helps emphasize the importance of regular medical follow-up.

Pulmonary fibrosis

Pulmonary fibrosis occurs when chronic inflammation leads to permanent scarring of the lung tissue. This can result in progressive breathing difficulties that do not improve with immunosuppressive treatment. Approximately 10-20% of patients with pulmonary sarcoidosis develop some degree of fibrosis. Severe pulmonary fibrosis is the leading cause of death in sarcoidosis patients.

Cardiac complications

Cardiac sarcoidosis can cause life-threatening arrhythmias (abnormal heart rhythms), heart block, and heart failure. Because cardiac involvement can be clinically silent, some experts recommend cardiac screening for all sarcoidosis patients. Patients with cardiac sarcoidosis may require pacemakers, implantable defibrillators, or specialized heart failure treatment.

Calcium abnormalities

Sarcoid granulomas can produce excess active vitamin D, leading to elevated calcium levels in the blood (hypercalcemia) and urine (hypercalciuria). This can result in kidney stones, kidney damage, and other complications. Patients are typically advised to avoid excessive sun exposure, calcium supplements, and vitamin D supplements.

Ocular complications

Untreated or inadequately treated eye involvement can lead to glaucoma, cataracts, and permanent vision loss. Regular ophthalmological examinations are recommended for all patients with sarcoidosis, even those without eye symptoms.

Neurological complications

Neurosarcoidosis can affect cranial nerves (causing facial paralysis or hearing loss), the brain, spinal cord, or peripheral nerves. Seizures, cognitive problems, and hormonal imbalances (from pituitary involvement) are possible complications.

What Is the Life Expectancy and Prognosis with Sarcoidosis?

Most people with sarcoidosis have a normal or near-normal life expectancy. Over 60% experience complete remission within 2-5 years. Mortality is approximately 1-5%, primarily due to pulmonary fibrosis or cardiac involvement. Lofgren syndrome has an excellent prognosis with 90% resolution.

The prognosis for sarcoidosis varies considerably depending on the clinical presentation, organ involvement, and response to treatment. Overall, the outlook is favorable for most patients.

Favorable prognostic factors include:

• Lofgren syndrome presentation (acute onset with erythema nodosum, arthritis, and bilateral hilar lymphadenopathy)
• Asymptomatic disease discovered incidentally
• Stage I chest X-ray (hilar lymphadenopathy only without lung infiltrates)
• Young age at diagnosis
• Limited organ involvement
• Resolution within the first 2 years

Factors associated with poorer prognosis include:

• Chronic progressive disease lasting more than 2 years
• Stage III or IV chest X-ray findings
• Lupus pernio (chronic skin involvement on the face)
• Cardiac or neurological involvement
• African American ethnicity (associated with more severe disease)
• Older age at onset
• Need for long-term immunosuppressive treatment

How Does Sarcoidosis Affect Daily Life?

Sarcoidosis affects daily life differently for each person. Some notice minimal impact, while others experience significant fatigue, breathing limitations, or medication side effects. Lifestyle modifications, stress management, regular exercise within your limits, and maintaining regular medical follow-up can help manage the condition.

Living with sarcoidosis can be challenging, particularly during active disease or when dealing with medication side effects. The impact on daily life varies widely between individuals and can change over time as the disease activity fluctuates.

Managing fatigue

Fatigue is one of the most common and troublesome symptoms of sarcoidosis, affecting quality of life even when the disease appears well-controlled. Strategies that may help include:

• Pacing activities and taking regular rest breaks
• Prioritizing important tasks for times when energy is highest
• Getting adequate sleep and maintaining a regular sleep schedule
• Light to moderate exercise, which can actually improve energy levels
• Discussing persistent fatigue with your healthcare provider, as it may indicate active disease

Lifestyle recommendations

Several lifestyle factors can help manage sarcoidosis and improve overall well-being:

• Avoid smoking: Smoking can worsen lung damage and makes sarcoidosis harder to manage. If you smoke, seek help to quit.
• Limit alcohol: Alcohol can affect the liver and may interact with medications. Discuss safe limits with your doctor.
• Eat a healthy diet: A balanced diet supports overall health and helps maintain a healthy weight, which is particularly important if taking corticosteroids.
• Stay active: Regular physical activity within your capabilities helps maintain lung function, reduce fatigue, and support bone health.
• Manage stress: Stress can worsen symptoms and fatigue. Consider relaxation techniques, mindfulness, or counseling.
• Get adequate rest: Sleep is essential for managing fatigue and supporting immune function.
• Sun protection: Because sarcoidosis can increase vitamin D sensitivity, some patients are advised to limit sun exposure and avoid vitamin D supplements.

Pregnancy and sarcoidosis

Many women with sarcoidosis can have successful pregnancies, but careful planning and monitoring are important. If you are considering pregnancy:

• Discuss your plans with your healthcare provider before trying to conceive
• Some medications used for sarcoidosis are not safe during pregnancy
• Sarcoidosis may improve, worsen, or remain stable during pregnancy
• High-risk obstetric care may be recommended
• There is a small increased risk of certain pregnancy complications