Sarcoidosis

Original Editors - Jordan Bormann from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Jordan Bormann, Elaine Lonnemann, Lucinda hampton, Admin, Kim Jackson, Mohit Chand, Wendy Walker, Mariam Hashem, WikiSysop and Adam Vallely Farrell

Introduction

Sarcoidosis is a systemic inflammatory disease characterized by granuloma formation affecting multiple organs. The etiology remains unknown, with proposed theories including genetic factors, immune responses, infections, or environmental exposures. Note: A granuloma is a small cluster of immune cells that forms when the body's immune system tries to wall off substances it perceives as foreign but cannot eliminate. In Sarcoidosis Specifically:

• Non-necrotizing granulomas: Unlike other diseases, sarcoidosis granulomas don't have a dead tissue center
• Location: Form in lungs, lymph nodes, skin, eyes, and other organs
• Composition: Made up of immune cells (mainly macrophages and T-cells) clumped together
• Size: Microscopic clusters visible only under a microscope

Clinical Impact:

• Inflammation: Granulomas cause swelling and irritation in affected organs
• Function loss: Can interfere with normal organ function (e.g., breathing, vision)
• Scarring: Over time, may lead to permanent tissue damage and fibrosis
• Diagnosis: Finding these specific granulomas in tissue samples helps confirm sarcoidosis

What This Means for Physiotherapy:

• Granulomas in lungs → breathing problems, reduced exercise tolerance
• Multiple organ involvement → varied symptoms requiring individualized treatment
• Inflammation level affects patient fatigue and functional capacity
• Treatment aims to reduce granuloma formation and prevent scarring

Clinical Presentation:

• 90% of cases involve pulmonary manifestations
• Granulomas form in lung parenchyma and lymph nodes, causing stiffness and impaired gas exchange
• Can affect skin, eyes, liver, heart, CNS, and bones
• Symptoms: fatigue, fever, weight loss, plus organ-specific manifestations

Diagnosis:

• No specific diagnostic test available
• Based on clinical examination and patient history
• Must exclude tuberculosis, lymphoma, fungal diseases, and other granulomatous conditions
• CNS and pulmonary involvement often diagnosed late

Physiotherapy Management: Primary goals include restoring organ function and improving ventilation, endurance, and strength.

Pulmonary sarcoidosis interventions:

• Breathing exercises
• Strength training (upper and lower extremity)
• Endurance exercises
• Aimed at reducing dyspnea, increasing functional capacity, and decreasing fatigue

Treatment is individualized based on specific symptoms and affected systems. Many acute cases regress spontaneously and require no intervention, while chronic cases need targeted management approaches..

Etiology/Causes

Sarcoidosis has no known cause. However, some researchers believe the course of the disease may have genetic connections or result from an immune response. Others possible causes include viruses, bacterias, dust particles, or chemical exposure. Due to the vast nature of the manifestation, other researchers have led one to believe that there may be several causes.

Prevalence

Patients most commonly affected by sarcoidosis are 20-40 years of age. Women are more affected than men (6.3 per 100,000; 5.9 per 100,000) listed, respectively. African Americans are the most diagnosed ethnic group in the United States and have a prevalence of four times that of the diagnosis for Caucasians (2.4%; 0.85%). In the United Kingdom, 5-10 per 100,000 individuals are diagnosed with sarcoidosis. It is the most common interstitial lung disorder in the western part of the world and has an increased incidence in Irish, West Indian, and Scandinavian people.

Characteristics/Clinical Presentation

Patient presentation is dependent on organ involvement and severity of the disease process. Almost 33% of patients present with non-specific symptoms, which may include fever, weight loss, weakness, and/or malaise. Organ involvement is one of the most important determiners for presentation. Individuals who have pulmonary involvement often time present with a dry cough, dyspnea, and chest pain/discomfort. Patients of this type will often times have a sudden remission or quick and progressive loss of pulmonary function due to fibrosis of lung tissues. Another important factor that plays into the presentation of patients includes the stage in which they present to the clinic. Sarcoidosis has 4 stages, with stages I and II being less involved with less severe or no symptoms at all. The later stages, III and IV, include more severe symptoms and a further decrease in organ function. For pulmonary patients, increased tissue fibrosis, decreased airflow, persistent cough, and a possibility of bronchiectasis. Of the stages, remission periods vary greatly. Stage I has a remission period of 55-90% while stage II has been recorded from 40 to 70%. The more severe stages have been recorded as follows, 10-20% and 0-5% respectively. Other common organ involvement includes the liver, which may show granulomas from testing. However, liver function may not be severely affected by the inflammatory process. Skin involvement is present in over 1/4 of patients diagnosed with sarcoidosis. The most common lesions include plaques, nodules, erythema nodosum, and lupus pernio. Common presentation of lupus pernio includes the involvement of plaques around the individual's lips, cheeks, nose, and ears indicating a more chronic stage of the disease.

Associated Co-morbidities

As with many other systemic diseases, sarcoidosis has several co-morbidities. Of all the patients diagnosed, 6-35% suffer with sarcoid arthropathy. These symptoms most commonly occur in the knees and ankles symmetrically and involves many joints. The arthritic changes vary in their duration and are self-limiting within weeks to months. It is possible that these symptoms may become chronic and reoccur for periods of time, but joint changes continue to stay minimal. These symptoms vary in their timing of the disease and may become present early or late in the disease progression. Along with the arthritis, erythema nodosum and hilar adenopathy may also be present. These three symptoms combined are known as Lofgren's syndrome and can also be self-limiting. Muscle involvement may also present itself as sarcoid myositis. Other co-morbidities include nerve palsies, mononeuropathy, and polyneuropathy. Polyneuropathy is more rare than other symptoms and may present symmetrically.

Sarcoidosis Treatment: Key Points for Physiotherapists

First-Line Treatment: Corticosteroids

• Standard dose: 20-40mg prednisolone daily for 1-3 months, then taper to 10mg/day
• Mechanism: Reduces inflammation by suppressing granuloma formation and preventing fibrosis
• Major side effects: Osteoporosis, hypertension, diabetes, cataracts - requires monitoring

Second-Line: Immunomodulators (Steroid-sparing agents)

• Methotrexate: Most common alternative, reduces T-cell inflammation
• Azathioprine: Equal efficacy to methotrexate but higher infection risk
• Leflunomide: Similar effectiveness with better tolerance
• Common side effects: Liver toxicity, infections, GI upset, fatigue

Third-Line: Biologic Agents

• TNF-α inhibitors (infliximab, adalimumab): Target granuloma formation
• Effective for: Refractory cases, especially neurologic and skin involvement
• Risk: High infection rates (36% serious adverse events with infliximab)

Emerging Treatments

• Antifibrotics (nintedanib): May slow lung fibrosis progression
• Targeted therapies: Future treatments based on specific genetic mutations

Clinical Implications for Physiotherapy:

• Patients on long-term steroids need bone health monitoring
• Immunosuppressed patients have increased infection risk
• Treatment choice depends on disease severity, patient age, and comorbidities
• Combination therapy may be needed for aggressive disease variants

Sarcoidosis Diagnosis: Key Points for Physiotherapists

Diagnostic Challenge

• No definitive test exists - diagnosis based on probability, not certainty
• Requires combination of clinical presentation, imaging, and tissue samples
• Must exclude other granulomatous diseases (tuberculosis, lymphoma, etc.)

Standard Diagnostic Approach

• Chest X-ray: Abnormal in majority of patients
  • Bilateral hilar lymphadenopathy most common finding
  • Scadding stages I-IV (Stage I most prevalent at 45-65%)
• CT scan: Better detection of lung changes and lymph node calcification
• Tissue biopsy: Confirms non-necrotizing granulomas via bronchoscopy or other methods
• PET scans: Monitor treatment response and guide therapy decisionsBlood Tests Used in Sarcoidosis

Current Blood Tests (Not Perfect)

• ACE levels: Often high in sarcoidosis patients, but can be high in other diseases too
• sIL-2R: Shows immune system is active, but many lung conditions cause this
• Inflammation markers: High levels mean the disease is more active

New Tests Being Developed

• Genetic markers: May help doctors choose the best medications
• Stress hormones in hair: Shows how tired and stressed patients are long-term
• Advanced scans: Computer analysis of CT/PET scans to confirm diagnosis

Clinical Implications for Physiotherapy:

• Diagnosis often delayed due to complexity
• Patients may have multiple biopsies/procedures before confirmation
• Disease staging affects prognosis and treatment approach
• Biomarkers help monitor treatment response and disease progression

Physical Therapy Management

Physical therapy treatment is based on the symptoms that the individual presents with. Acute sarcoidosis often times regresses spontaneously. However, more chronic stages of sarcoidosis require treatment based on the involved systems. In most cases with pulmonary involvement, physical therapy can be helpful by increasing ventilation through strategies which may include breathing exercises, strength training, and endurance exercises. The result of these treatments ay be variable, but are designed to allow the patient a more normal life by decreasing dyspnea, increasing endurance and decreasing fatigue. Both upper and lower extremity exercises can be used along with the breathing exercises for optimal treatment outcomes.

Differential Diagnosis

Most Important to Exclude:

• Tuberculosis - Most critical differential diagnosis
• Lymphoma (Hodgkin's and Non-Hodgkin's) - Can mimic sarcoidosis in multiple organs
• Fungal infections - Especially in lung involvement

Other Common Mimics:

• Drug reactions - Medication-induced granulomas
• Crohn's disease - When GI system involved
• Occupational lung disease - Beryllium exposure

Why This Matters for Physiotherapy:

• Diagnosis often delayed while ruling out other conditions
• Treatment approach differs significantly between conditions
• Patient may undergo multiple tests before sarcoidosis confirmed
• Some conditions (like TB) are infectious - affects treatment precautions

Case Reports/ Case Studies

1.Sarcoidosis - A Case of Consumption available: https://www.atsjournals.org/doi/10.1164/ajrccm.2025.211.Abstracts.A6132 accessed 11.10.2025

References

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