Overview of Sarcoidosis

Overview of Sarcoidosis

• Sarcoidosis may be classified as an autoimmune disease, involving both genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in HLA gene, specifically HLA-DRB1.
• Higher incidence observed in individuals with a family history of the disease or of African American descent.

Environmental Factors

• Unknown antigen believed to play a role in disease development.
• Potential candidate antigens include:
  • Mycobacterium tuberculosis: Associated with tuberculosis.
  • Borrelia burgdorferi: Causative agent of Lyme disease.
  • Human herpes virus type 8: Possible involvement as an antigen.
  • Propionibacterium acnes: Suggested relationship with sarcoidosis.

Immune Response Mechanism

• Antigens lead to exposure of antigen-presenting cells (APCs) like macrophages and dendritic cells.
• APCs perform phagocytosis, encapsulating the antigen into a vesicle known as a phagosome.
• Phagosome merges with lysosomes, forming a phagolysosome where hydrolytic enzymes break down the antigen.

Role of HLA Genes

• HLA genes located on chromosome 6 contribute to immune response through the presentation of antigens.
• HLA-DRB1 polymorphisms may result in inappropriate immune responses when exposed to specific antigens.
• Process involves the production of major histocompatibility complex (MHC) class II proteins which present the antigen on cell membranes.

T Cell Activation

• Antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• T cell receptors (TCRs) on CD4+ T cells bind to the antigen presented by MHC class II.
• Successful binding activates the T cell, leading to the release of various cytokines.
• Interleukin-1 is released by the macrophage to further stimulate the naïve T cell.
• Activation culminates in the production of Interleukin-2, promoting T cell proliferation and differentiation.

Summary of Key Processes

• Sarcoidosis arises from a combination of genetic susceptibility (HLA-DRB1) and environmental triggers (potential antigens).
• The immune response involves antigen presentation, T cell activation, and cytokine signaling, which are critical for the pathophysiology of the disease.### Interleukin and Naive T Cells
• Interleukin-2 (IL-2) binds to naive T cells, triggering their proliferation.
• This mechanism is called autocrine signaling, where a cytokine acts on the same cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes, primed to bind specific antigens.
• Activated Th1 cells release interferon-gamma (IFN-γ), which enhances macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release cytokines (e.g., IFN-γ, tumor necrosis factor-alpha) to recruit more macrophages, lymphocytes, and fibroblasts.
• Certain macrophages differentiate into epithelioid cells, which have structures playing roles in immune responses.

Granuloma Formation

• Aggregation of macrophages leads to the formation of multinucleated giant cells and non-caseating granulomas, characteristic of sarcoidosis.
• Granulomas comprise macrophages, lymphocytes (often T cells), fibroblasts, and can lead to tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Non-caseating granulomas can deposit in various organs and cause specific conditions:
  • Hypothalamus: Damages neurons affecting ADH production, leading to diabetes insipidus.
  • Pituitary Gland: Can result in hypopituitarism due to decreased hormone production.
  • Eyes: Deposits can cause anterior (painful, redness) or posterior uveitis (painless visual changes).
  • Parotid Gland: Can lead to parotitis, potentially causing facial nerve palsy.
  • Heart: Deposits can cause restrictive cardiomyopathy or arrhythmias (e.g., AV block).
  • Liver and Spleen: May cause hepatosplenomegaly due to granuloma deposition.
  • Joints: Commonly affects ankles, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy is a classic sign, possibly leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on lower extremities.
• Lupus pernio: Rash on the face, resembling lupus, considered a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Triad of arthralgias, bilateral hilar lymphadenopathy, and skin manifestations (erythema nodosum or lupus pernio) indicative of sarcoidosis.

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells increase the expression of 1-alpha hydroxylase, leading to elevated active vitamin D and subsequent hypercalcemia.
• High calcium levels can precipitate kidney stones, leading to flank pain and potential nephrolithiasis.

Diagnosis of Sarcoidosis

• Suspected based on systemic symptoms (e.g., cough, shortness of breath) and demographic factors (e.g., African-American ethnicity).
• Chest x-ray may reveal bilateral hilar lymphadenopathy or fibrosis patterns.
• Blood tests may show elevated calcium, vitamin D, ACE levels, and inflammatory markers like CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage can help assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis, highlighting increased T helper (Th1) lymphocyte activity.### Sarcoidosis Overview
• Sarcoidosis is characterized by non-caseating granulomas and may be differentiated from hypersensitivity pneumonitis based on CD4/CD8 ratio.
• A CD4/CD8 ratio less than 2 is indicative of hypersensitivity pneumonitis; greater than 2 suggests sarcoidosis.

Pathological Findings

• Biopsies for sarcoidosis typically reveal non-caseating granulomas.
• Asteroid bodies and Schaumann bodies are histological findings:
  • Asteroid bodies may contain lipids and cytoskeletal components (microtubules, microfilaments).
  • Schaumann bodies are composed of calcium and proteins.

Pulmonary Function Tests (PFTs)

• PFTs assess lung function; in restrictive lung diseases like sarcoidosis:
  • Total lung capacity is decreased due to poor lung compliance.
  • Residual volume is lower than average, indicating reduced air remaining after exhalation.
  • FEV1 and FVC are both decreased, with FEV1/FVC ratio potentially greater than or equal to 80%, due to FVC dropping more significantly.
• Diffusion capacity of carbon monoxide is impaired, reflecting reduced gas exchange due to thickened alveolar walls from fibrosis.

Treatment Approaches

• Asymptomatic patients with mild sarcoidosis typically require no treatment and are monitored.
• Corticosteroids (e.g., prednisone, prednisolone, methylprednisolone) are prescribed for moderate symptoms to reduce inflammation.
• For corticosteroid-resistant symptoms, DMARDs are introduced:
  • Common DMARDs include methotrexate and azathioprine, acting as strong immunosuppressive agents.
• In cases with high calcium levels or neurological complications, hydroxychloroquine may be added to the treatment regimen.

Severe Cases

• If the disease progresses to interstitial lung disease causing respiratory distress or failure, lung transplant is considered as the definitive treatment for end-stage disease.

Overview of Sarcoidosis

• Sarcoidosis is classified as an autoimmune disease influenced by genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in the HLA gene, notably HLA-DRB1.
• Higher incidence occurs in individuals with a family history of sarcoidosis and those of African American descent.

Environmental Factors

• An unknown antigen is believed to contribute to sarcoidosis development.
• Potential candidate antigens include Mycobacterium tuberculosis, Borrelia burgdorferi, Human herpes virus type 8, and Propionibacterium acnes.

Immune Response Mechanism

• Exposure to antigens activates antigen-presenting cells (APCs) such as macrophages and dendritic cells.
• APCs engulf the antigen via phagocytosis, forming phagosomes which merge with lysosomes to create phagolysosomes for antigen breakdown.

Role of HLA Genes

• HLA genes on chromosome 6 are crucial for immune response through antigen presentation.
• Polymorphisms in HLA-DRB1 can lead to inappropriate immune responses, involving MHC class II proteins that present antigens on cell membranes.

T Cell Activation

• The antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• CD4+ T cell receptors bind to presented antigens, activating T cells and leading to cytokine release.
• Interleukin-1 from macrophages further stimulates naïve T cells, culminating in Interleukin-2 production for T cell proliferation.

Summary of Key Processes

• Sarcoidosis is a product of genetic susceptibility (HLA-DRB1) and environmental antigens, leading to immune response and disease pathophysiology.

Interleukin and Naive T Cells

• Interleukin-2 triggers proliferation of naïve T cells, showcasing autocrine signaling where the cytokine affects the cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes and release interferon-gamma (IFN-γ) to enhance macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release various cytokines, attracting more immune cells and facilitating the formation of epithelioid cells for immune response.

Granuloma Formation

• Macrophage aggregation results in multinucleated giant cells and non-caseating granulomas, hallmarks of sarcoidosis, containing macrophages, lymphocytes, and fibroblasts which may cause tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Granulomas can affect multiple organs, leading to:
  • Hypothalamus: Neuron damage affecting ADH, resulting in diabetes insipidus.
  • Pituitary Gland: Hypopituitarism from decreased hormone production.
  • Eyes: Anterior or posterior uveitis causing vision changes.
  • Parotid Gland: Parotitis potentially causing facial nerve palsy.
  • Heart: Restrictive cardiomyopathy or arrhythmias.
  • Liver and Spleen: Hepatosplenomegaly from granulomas.
  • Joints: Ankles commonly affected, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy, potentially leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on the legs.
• Lupus pernio: Facial rash resembling lupus, recognized as a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Characterized by a triad of arthralgias, bilateral hilar lymphadenopathy, and skin lesions (erythema nodosum or lupus pernio).

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells elevate active vitamin D production, leading to hypercalcemia, which can result in kidney stones and flank pain.

Diagnosis of Sarcoidosis

• Diagnosis suggested by systemic symptoms (e.g., cough, breathlessness) and demographic factors.
• Chest x-rays may reveal bilateral hilar lymphadenopathy or fibrosis.
• Blood tests can indicate elevated calcium, vitamin D, ACE levels, and inflammatory markers such as CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis.

Sarcoidosis Overview

• Differentiates from hypersensitivity pneumonitis by CD4/CD8 ratio, where a ratio under 2 suggests hypersensitivity pneumonitis.

Pathological Findings

• Sarcoidosis biopsies generally reveal non-caseating granulomas with potential histological findings like asteroid bodies (lipids and cytoskeleton) and Schaumann bodies (calcium and proteins).

Pulmonary Function Tests (PFTs)

• In restrictive lung diseases, PFTs indicate reduced total lung capacity, lower residual volume, and decreased FEV1 and FVC, with an FEV1/FVC ratio potentially ≥80%.
• Diffusion capacity of carbon monoxide is reduced, indicating impaired gas exchange due to alveolar fibrosis.

Treatment Approaches

• Asymptomatic with mild sarcoidosis: Generally monitored without treatment.
• Moderate symptoms: Corticosteroids (prednisone, prednisolone) reduce inflammation.
• Corticosteroid-resistant cases: DMARDs like methotrexate and azathioprine used as immunosuppressants.
• High calcium levels or neurological issues may require hydroxychloroquine.

Severe Cases

• Lung transplantation is considered for patients progressing to respiratory distress or end-stage interstitial lung disease.

Overview of Sarcoidosis

• Sarcoidosis is classified as an autoimmune disease influenced by genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in the HLA gene, notably HLA-DRB1.
• Higher incidence occurs in individuals with a family history of sarcoidosis and those of African American descent.

Environmental Factors

• An unknown antigen is believed to contribute to sarcoidosis development.
• Potential candidate antigens include Mycobacterium tuberculosis, Borrelia burgdorferi, Human herpes virus type 8, and Propionibacterium acnes.

Immune Response Mechanism

• Exposure to antigens activates antigen-presenting cells (APCs) such as macrophages and dendritic cells.
• APCs engulf the antigen via phagocytosis, forming phagosomes which merge with lysosomes to create phagolysosomes for antigen breakdown.

Role of HLA Genes

• HLA genes on chromosome 6 are crucial for immune response through antigen presentation.
• Polymorphisms in HLA-DRB1 can lead to inappropriate immune responses, involving MHC class II proteins that present antigens on cell membranes.

T Cell Activation

• The antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• CD4+ T cell receptors bind to presented antigens, activating T cells and leading to cytokine release.
• Interleukin-1 from macrophages further stimulates naïve T cells, culminating in Interleukin-2 production for T cell proliferation.

Summary of Key Processes

• Sarcoidosis is a product of genetic susceptibility (HLA-DRB1) and environmental antigens, leading to immune response and disease pathophysiology.

Interleukin and Naive T Cells

• Interleukin-2 triggers proliferation of naïve T cells, showcasing autocrine signaling where the cytokine affects the cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes and release interferon-gamma (IFN-γ) to enhance macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release various cytokines, attracting more immune cells and facilitating the formation of epithelioid cells for immune response.

Granuloma Formation

• Macrophage aggregation results in multinucleated giant cells and non-caseating granulomas, hallmarks of sarcoidosis, containing macrophages, lymphocytes, and fibroblasts which may cause tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Granulomas can affect multiple organs, leading to:
  • Hypothalamus: Neuron damage affecting ADH, resulting in diabetes insipidus.
  • Pituitary Gland: Hypopituitarism from decreased hormone production.
  • Eyes: Anterior or posterior uveitis causing vision changes.
  • Parotid Gland: Parotitis potentially causing facial nerve palsy.
  • Heart: Restrictive cardiomyopathy or arrhythmias.
  • Liver and Spleen: Hepatosplenomegaly from granulomas.
  • Joints: Ankles commonly affected, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy, potentially leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on the legs.
• Lupus pernio: Facial rash resembling lupus, recognized as a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Characterized by a triad of arthralgias, bilateral hilar lymphadenopathy, and skin lesions (erythema nodosum or lupus pernio).

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells elevate active vitamin D production, leading to hypercalcemia, which can result in kidney stones and flank pain.

Diagnosis of Sarcoidosis

• Diagnosis suggested by systemic symptoms (e.g., cough, breathlessness) and demographic factors.
• Chest x-rays may reveal bilateral hilar lymphadenopathy or fibrosis.
• Blood tests can indicate elevated calcium, vitamin D, ACE levels, and inflammatory markers such as CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis.

Sarcoidosis Overview

• Differentiates from hypersensitivity pneumonitis by CD4/CD8 ratio, where a ratio under 2 suggests hypersensitivity pneumonitis.

Pathological Findings

• Sarcoidosis biopsies generally reveal non-caseating granulomas with potential histological findings like asteroid bodies (lipids and cytoskeleton) and Schaumann bodies (calcium and proteins).

Pulmonary Function Tests (PFTs)

• In restrictive lung diseases, PFTs indicate reduced total lung capacity, lower residual volume, and decreased FEV1 and FVC, with an FEV1/FVC ratio potentially ≥80%.
• Diffusion capacity of carbon monoxide is reduced, indicating impaired gas exchange due to alveolar fibrosis.

Treatment Approaches

• Asymptomatic with mild sarcoidosis: Generally monitored without treatment.
• Moderate symptoms: Corticosteroids (prednisone, prednisolone) reduce inflammation.
• Corticosteroid-resistant cases: DMARDs like methotrexate and azathioprine used as immunosuppressants.
• High calcium levels or neurological issues may require hydroxychloroquine.

Severe Cases

• Lung transplantation is considered for patients progressing to respiratory distress or end-stage interstitial lung disease.

Overview of Sarcoidosis

• Sarcoidosis is classified as an autoimmune disease influenced by genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in the HLA gene, notably HLA-DRB1.
• Higher incidence occurs in individuals with a family history of sarcoidosis and those of African American descent.

Environmental Factors

• An unknown antigen is believed to contribute to sarcoidosis development.
• Potential candidate antigens include Mycobacterium tuberculosis, Borrelia burgdorferi, Human herpes virus type 8, and Propionibacterium acnes.

Immune Response Mechanism

• Exposure to antigens activates antigen-presenting cells (APCs) such as macrophages and dendritic cells.
• APCs engulf the antigen via phagocytosis, forming phagosomes which merge with lysosomes to create phagolysosomes for antigen breakdown.

Role of HLA Genes

• HLA genes on chromosome 6 are crucial for immune response through antigen presentation.
• Polymorphisms in HLA-DRB1 can lead to inappropriate immune responses, involving MHC class II proteins that present antigens on cell membranes.

T Cell Activation

• The antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• CD4+ T cell receptors bind to presented antigens, activating T cells and leading to cytokine release.
• Interleukin-1 from macrophages further stimulates naïve T cells, culminating in Interleukin-2 production for T cell proliferation.

Summary of Key Processes

• Sarcoidosis is a product of genetic susceptibility (HLA-DRB1) and environmental antigens, leading to immune response and disease pathophysiology.

Interleukin and Naive T Cells

• Interleukin-2 triggers proliferation of naïve T cells, showcasing autocrine signaling where the cytokine affects the cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes and release interferon-gamma (IFN-γ) to enhance macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release various cytokines, attracting more immune cells and facilitating the formation of epithelioid cells for immune response.

Granuloma Formation

• Macrophage aggregation results in multinucleated giant cells and non-caseating granulomas, hallmarks of sarcoidosis, containing macrophages, lymphocytes, and fibroblasts which may cause tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Granulomas can affect multiple organs, leading to:
  • Hypothalamus: Neuron damage affecting ADH, resulting in diabetes insipidus.
  • Pituitary Gland: Hypopituitarism from decreased hormone production.
  • Eyes: Anterior or posterior uveitis causing vision changes.
  • Parotid Gland: Parotitis potentially causing facial nerve palsy.
  • Heart: Restrictive cardiomyopathy or arrhythmias.
  • Liver and Spleen: Hepatosplenomegaly from granulomas.
  • Joints: Ankles commonly affected, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy, potentially leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on the legs.
• Lupus pernio: Facial rash resembling lupus, recognized as a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Characterized by a triad of arthralgias, bilateral hilar lymphadenopathy, and skin lesions (erythema nodosum or lupus pernio).

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells elevate active vitamin D production, leading to hypercalcemia, which can result in kidney stones and flank pain.

Diagnosis of Sarcoidosis

• Diagnosis suggested by systemic symptoms (e.g., cough, breathlessness) and demographic factors.
• Chest x-rays may reveal bilateral hilar lymphadenopathy or fibrosis.
• Blood tests can indicate elevated calcium, vitamin D, ACE levels, and inflammatory markers such as CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis.

Sarcoidosis Overview

• Differentiates from hypersensitivity pneumonitis by CD4/CD8 ratio, where a ratio under 2 suggests hypersensitivity pneumonitis.

Pathological Findings

• Sarcoidosis biopsies generally reveal non-caseating granulomas with potential histological findings like asteroid bodies (lipids and cytoskeleton) and Schaumann bodies (calcium and proteins).

Pulmonary Function Tests (PFTs)

• In restrictive lung diseases, PFTs indicate reduced total lung capacity, lower residual volume, and decreased FEV1 and FVC, with an FEV1/FVC ratio potentially ≥80%.
• Diffusion capacity of carbon monoxide is reduced, indicating impaired gas exchange due to alveolar fibrosis.

Treatment Approaches

• Asymptomatic with mild sarcoidosis: Generally monitored without treatment.
• Moderate symptoms: Corticosteroids (prednisone, prednisolone) reduce inflammation.
• Corticosteroid-resistant cases: DMARDs like methotrexate and azathioprine used as immunosuppressants.
• High calcium levels or neurological issues may require hydroxychloroquine.

Severe Cases

• Lung transplantation is considered for patients progressing to respiratory distress or end-stage interstitial lung disease.

Overview of Sarcoidosis

• Sarcoidosis is classified as an autoimmune disease influenced by genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in the HLA gene, notably HLA-DRB1.
• Higher incidence occurs in individuals with a family history of sarcoidosis and those of African American descent.

Environmental Factors

• An unknown antigen is believed to contribute to sarcoidosis development.
• Potential candidate antigens include Mycobacterium tuberculosis, Borrelia burgdorferi, Human herpes virus type 8, and Propionibacterium acnes.

Immune Response Mechanism

• Exposure to antigens activates antigen-presenting cells (APCs) such as macrophages and dendritic cells.
• APCs engulf the antigen via phagocytosis, forming phagosomes which merge with lysosomes to create phagolysosomes for antigen breakdown.

Role of HLA Genes

• HLA genes on chromosome 6 are crucial for immune response through antigen presentation.
• Polymorphisms in HLA-DRB1 can lead to inappropriate immune responses, involving MHC class II proteins that present antigens on cell membranes.

T Cell Activation

• The antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• CD4+ T cell receptors bind to presented antigens, activating T cells and leading to cytokine release.
• Interleukin-1 from macrophages further stimulates naïve T cells, culminating in Interleukin-2 production for T cell proliferation.

Summary of Key Processes

• Sarcoidosis is a product of genetic susceptibility (HLA-DRB1) and environmental antigens, leading to immune response and disease pathophysiology.

Interleukin and Naive T Cells

• Interleukin-2 triggers proliferation of naïve T cells, showcasing autocrine signaling where the cytokine affects the cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes and release interferon-gamma (IFN-γ) to enhance macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release various cytokines, attracting more immune cells and facilitating the formation of epithelioid cells for immune response.

Granuloma Formation

• Macrophage aggregation results in multinucleated giant cells and non-caseating granulomas, hallmarks of sarcoidosis, containing macrophages, lymphocytes, and fibroblasts which may cause tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Granulomas can affect multiple organs, leading to:
  • Hypothalamus: Neuron damage affecting ADH, resulting in diabetes insipidus.
  • Pituitary Gland: Hypopituitarism from decreased hormone production.
  • Eyes: Anterior or posterior uveitis causing vision changes.
  • Parotid Gland: Parotitis potentially causing facial nerve palsy.
  • Heart: Restrictive cardiomyopathy or arrhythmias.
  • Liver and Spleen: Hepatosplenomegaly from granulomas.
  • Joints: Ankles commonly affected, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy, potentially leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on the legs.
• Lupus pernio: Facial rash resembling lupus, recognized as a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Characterized by a triad of arthralgias, bilateral hilar lymphadenopathy, and skin lesions (erythema nodosum or lupus pernio).

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells elevate active vitamin D production, leading to hypercalcemia, which can result in kidney stones and flank pain.

Diagnosis of Sarcoidosis

• Diagnosis suggested by systemic symptoms (e.g., cough, breathlessness) and demographic factors.
• Chest x-rays may reveal bilateral hilar lymphadenopathy or fibrosis.
• Blood tests can indicate elevated calcium, vitamin D, ACE levels, and inflammatory markers such as CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis.

Sarcoidosis Overview

• Differentiates from hypersensitivity pneumonitis by CD4/CD8 ratio, where a ratio under 2 suggests hypersensitivity pneumonitis.

Pathological Findings

• Sarcoidosis biopsies generally reveal non-caseating granulomas with potential histological findings like asteroid bodies (lipids and cytoskeleton) and Schaumann bodies (calcium and proteins).

Pulmonary Function Tests (PFTs)

• In restrictive lung diseases, PFTs indicate reduced total lung capacity, lower residual volume, and decreased FEV1 and FVC, with an FEV1/FVC ratio potentially ≥80%.
• Diffusion capacity of carbon monoxide is reduced, indicating impaired gas exchange due to alveolar fibrosis.

Treatment Approaches

• Asymptomatic with mild sarcoidosis: Generally monitored without treatment.
• Moderate symptoms: Corticosteroids (prednisone, prednisolone) reduce inflammation.
• Corticosteroid-resistant cases: DMARDs like methotrexate and azathioprine used as immunosuppressants.
• High calcium levels or neurological issues may require hydroxychloroquine.

Severe Cases

• Lung transplantation is considered for patients progressing to respiratory distress or end-stage interstitial lung disease.

Overview of Sarcoidosis

• Sarcoidosis is classified as an autoimmune disease influenced by genetic and environmental factors.
• Genetic predisposition primarily linked to polymorphisms in the HLA gene, notably HLA-DRB1.
• Higher incidence occurs in individuals with a family history of sarcoidosis and those of African American descent.

Environmental Factors

• An unknown antigen is believed to contribute to sarcoidosis development.
• Potential candidate antigens include Mycobacterium tuberculosis, Borrelia burgdorferi, Human herpes virus type 8, and Propionibacterium acnes.

Immune Response Mechanism

• Exposure to antigens activates antigen-presenting cells (APCs) such as macrophages and dendritic cells.
• APCs engulf the antigen via phagocytosis, forming phagosomes which merge with lysosomes to create phagolysosomes for antigen breakdown.

Role of HLA Genes

• HLA genes on chromosome 6 are crucial for immune response through antigen presentation.
• Polymorphisms in HLA-DRB1 can lead to inappropriate immune responses, involving MHC class II proteins that present antigens on cell membranes.

T Cell Activation

• The antigen-MHC class II complex is transported to lymph nodes to interact with naïve T cells.
• CD4+ T cell receptors bind to presented antigens, activating T cells and leading to cytokine release.
• Interleukin-1 from macrophages further stimulates naïve T cells, culminating in Interleukin-2 production for T cell proliferation.

Summary of Key Processes

• Sarcoidosis is a product of genetic susceptibility (HLA-DRB1) and environmental antigens, leading to immune response and disease pathophysiology.

Interleukin and Naive T Cells

• Interleukin-2 triggers proliferation of naïve T cells, showcasing autocrine signaling where the cytokine affects the cell that produced it.

T Cell Activation and Cytokine Release

• Naive T cells differentiate into Th1 lymphocytes and release interferon-gamma (IFN-γ) to enhance macrophage activation.

Macrophage Aggregation and Activation

• Activated macrophages release various cytokines, attracting more immune cells and facilitating the formation of epithelioid cells for immune response.

Granuloma Formation

• Macrophage aggregation results in multinucleated giant cells and non-caseating granulomas, hallmarks of sarcoidosis, containing macrophages, lymphocytes, and fibroblasts which may cause tissue fibrosis.

Clinical Manifestations of Sarcoidosis

• Granulomas can affect multiple organs, leading to:
  • Hypothalamus: Neuron damage affecting ADH, resulting in diabetes insipidus.
  • Pituitary Gland: Hypopituitarism from decreased hormone production.
  • Eyes: Anterior or posterior uveitis causing vision changes.
  • Parotid Gland: Parotitis potentially causing facial nerve palsy.
  • Heart: Restrictive cardiomyopathy or arrhythmias.
  • Liver and Spleen: Hepatosplenomegaly from granulomas.
  • Joints: Ankles commonly affected, causing arthralgias.
  • Lungs: Bilateral hilar lymphadenopathy, potentially leading to interstitial lung disease.

Skin Manifestations

• Erythema nodosum: Painful red bumps on the legs.
• Lupus pernio: Facial rash resembling lupus, recognized as a mnemonic for sarcoidosis.

Lofgren's Syndrome

• Characterized by a triad of arthralgias, bilateral hilar lymphadenopathy, and skin lesions (erythema nodosum or lupus pernio).

Hypercalcemia in Sarcoidosis

• Multinucleated giant cells elevate active vitamin D production, leading to hypercalcemia, which can result in kidney stones and flank pain.

Diagnosis of Sarcoidosis

• Diagnosis suggested by systemic symptoms (e.g., cough, breathlessness) and demographic factors.
• Chest x-rays may reveal bilateral hilar lymphadenopathy or fibrosis.
• Blood tests can indicate elevated calcium, vitamin D, ACE levels, and inflammatory markers such as CRP and ESR.

Bronchoscopy and Cytological Analysis

• Procedures like bronchoalveolar lavage assess CD4/CD8 T cell ratios.
• An elevated CD4/CD8 ratio (>2) is indicative of sarcoidosis.

Sarcoidosis Overview

• Differentiates from hypersensitivity pneumonitis by CD4/CD8 ratio, where a ratio under 2 suggests hypersensitivity pneumonitis.

Pathological Findings

• Sarcoidosis biopsies generally reveal non-caseating granulomas with potential histological findings like asteroid bodies (lipids and cytoskeleton) and Schaumann bodies (calcium and proteins).

Pulmonary Function Tests (PFTs)

• In restrictive lung diseases, PFTs indicate reduced total lung capacity, lower residual volume, and decreased FEV1 and FVC, with an FEV1/FVC ratio potentially ≥80%.
• Diffusion capacity of carbon monoxide is reduced, indicating impaired gas exchange due to alveolar fibrosis.

Treatment Approaches

• Asymptomatic with mild sarcoidosis: Generally monitored without treatment.
• Moderate symptoms: Corticosteroids (prednisone, prednisolone) reduce inflammation.
• Corticosteroid-resistant cases: DMARDs like methotrexate and azathioprine used as immunosuppressants.
• High calcium levels or neurological issues may require hydroxychloroquine.

Severe Cases

• Lung transplantation is considered for patients progressing to respiratory distress or end-stage interstitial lung disease.