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Pulmonary Sarcoidosis

Disease Details

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Description: Pulmonary sarcoidosis is an inflammatory disease characterized by the formation of granulomas (small clumps of inflammatory cells) in the lungs, which can lead to compromised respiratory function.
Type: Pulmonary sarcoidosis is a type of inflammatory disease that primarily affects the lungs. The exact cause of sarcoidosis is unknown, but it is believed to result from an abnormal immune response to an unknown trigger, such as an infection or environmental factors. It is not considered a directly inherited disorder, but genetic factors may contribute to an individual's susceptibility. There is evidence that a family history of sarcoidosis can increase the risk, suggesting a potential hereditary component, although the disease does not follow a clear Mendelian pattern of inheritance.
Signs And Symptoms: Sarcoidosis is a systemic inflammatory disease that can affect any organ, although it can be asymptomatic and is discovered by accident in about 5% of cases. Common symptoms, which tend to be vague, include fatigue (unrelieved by sleep; occurs in up to 85% of cases ), lack of energy, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis (14–38% of cases), dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions. Less commonly, people may cough up blood. Sarcoidosis is also accompanied by psychological distress and symptoms of anxiety and depression, which are also associated with fatigue. The cutaneous symptoms vary, and range from rashes and noduli (small bumps) to erythema nodosum, granuloma annulare, or lupus pernio. Sarcoidosis and cancer may mimic one another, making the distinction difficult.The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Löfgren syndrome, which has a relatively good prognosis. This form of the disease occurs significantly more often in Scandinavian patients than in those of non-Scandinavian origin.
Prognosis: The disease can remit spontaneously or become chronic, with exacerbations and remissions. In some cases, it can progress to pulmonary fibrosis and death. In benign cases, remission can occur in 24 to 36 months without treatment but regular follow ups are required. Some cases, however, may persist several decades. Two-thirds of people with the condition achieve a remission within 10 years of the diagnosis. When the heart is involved, the prognosis is generally less favourable, though corticosteroids appear effective in improving AV conduction. The prognosis tends to be less favourable in African Americans than in white Americans. In a Swedish population-based analysis, the majority of cases who did not have severe disease at diagnosis had comparable mortality to the general population. The risk for premature death was markedly (2.3-fold) increased compared to the general population for a smaller group of cases with severe disease at diagnosis. Serious infections, sometimes multiple during the course of disease, and heart failure might contribute to the higher risk of early death in some patients with sarcoidosis.Some 1990s studies indicated that people with sarcoidosis appear to be at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected in sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is followed by the development of a lymphoproliferative disorder such as non-Hodgkin lymphoma. This may be attributed to the underlying immunological abnormalities that occur during the sarcoidosis disease process. Sarcoidosis can also follow cancer or occur concurrently with cancer. There have been reports of hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia associated with sarcoidosis. Sometimes, sarcoidosis, even untreated, can be complicated by opportunistic infections although these are rare.
Onset: Pulmonary sarcoidosis typically has an onset in young adulthood, most commonly between the ages of 20 and 40. The condition can present either suddenly with acute symptoms or gradually with a more chronic progression.
Prevalence: Pulmonary sarcoidosis is a type of sarcoidosis that primarily affects the lungs. It is characterized by the formation of granulomas, which are small clusters of inflammatory cells. The prevalence of sarcoidosis varies widely depending on the population and region. In the United States, the prevalence is estimated to be about 10-40 cases per 100,000 people, with higher rates observed in African-Americans compared to Caucasians.
Epidemiology: Sarcoidosis most commonly affects young adults of both sexes, although studies have reported more cases in females. Incidence is highest for individuals younger than 40 and peaks in the age-group from 20 to 29 years; a second peak is observed for women over 50.Sarcoidosis occurs throughout the world in all races with an average incidence of 16.5 per 100,000 in men and 19 per 100,000 in women. The disease is most common in Northern European countries and the highest annual incidence of 60 per 100,000 is found in Sweden and Iceland. In the United Kingdom the prevalence is 16 in 100,000. In the United States, sarcoidosis is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9 per 100,000, respectively. Sarcoidosis is less commonly reported in South America, Spain, India, Canada, and the Philippines. There may be a higher susceptibility to sarcoidosis in those with celiac disease. An association between the two disorders has been suggested.There also has been a seasonal clustering observed in sarcoidosis-affected individuals. In Greece about 70% of diagnoses occur between March and May every year, in Spain about 50% of diagnoses occur between April and June, and in Japan it is mostly diagnosed during June and July.The differing incidence across the world may be at least partially attributable to the lack of screening programs in certain regions of the world, and the overshadowing presence of other granulomatous diseases, such as tuberculosis, that may interfere with the diagnosis of sarcoidosis where they are prevalent. There may also be differences in the severity of the disease between people of different ethnicities. Several studies suggest the presentation in people of African origin may be more severe and disseminated than for Caucasians, who are more likely to have asymptomatic disease. Manifestation appears to be slightly different according to race and sex. Erythema nodosum is far more common in men than in women and in Caucasians than in other races. In Japanese people, ophthalmologic and cardiac involvement are more common than in other races.It is more common in certain occupations, namely firefighters, educators, military personnel, those who work in industries where pesticides are used, law enforcement, and healthcare personnel. In the year after the September 11 attacks, the rate of sarcoidosis incidence went up four-fold (to 86 cases per 100,000).
Intractability: Pulmonary sarcoidosis is not considered intractable in most cases. It is a condition characterized by the formation of granulomas in the lungs, which can lead to symptoms such as cough, shortness of breath, and chest pain. Although the exact cause is unknown, many patients experience spontaneous remission or can manage the disease effectively with treatments like corticosteroids and immunosuppressive medications. However, a subset of patients may develop chronic or severe forms that are more resistant to treatment.
Disease Severity: For pulmonary sarcoidosis, disease severity can vary widely among individuals. It can range from mild cases, where individuals may be asymptomatic and experience minimal lung involvement, to severe cases, where there is significant lung damage, respiratory impairment, and potential complications such as pulmonary fibrosis. The variability in severity necessitates individualized evaluation and management plans for affected persons.
Healthcare Professionals: Disease Ontology ID - DOID:13406
Pathophysiology: Granulomatous inflammation is characterized primarily by the accumulation of macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, tumor necrosis factor alpha (TNF), interferon gamma, interleukin 2 (IL-2), IL-8, IL-10, IL-12, IL-18, IL-23 and transforming growth factor beta (TGF-β), indicative of a T helper cell-mediated immune response.
Sarcoidosis has paradoxical effects on inflammatory processes; it is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, but immune response to antigen challenges such as tuberculin is suppressed. This paradoxic state of simultaneous hyper- and hypoactivity is suggestive of a state of anergy. The anergy may also be responsible for the increased risk of infections and cancer. The regulatory T-lymphocytes in the periphery of sarcoid granulomas appear to suppress IL-2 secretion, which is hypothesized to cause the state of anergy by preventing antigen-specific memory responses.While TNF is widely believed to play an important role in the formation of granulomas (this is further supported by the finding that in animal models of mycobacterial granuloma formation inhibition of either TNF or IFN-γ production inhibits granuloma formation), sarcoidosis can and does still develop in those being treated with TNF antagonists like etanercept.
B cells also likely play a role in the pathophysiology of sarcoidosis. Serum levels of soluble human leukocyte antigen (HLA) class I antigens and angiotensin converting enzyme (ACE) are higher in people with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in people with pulmonary sarcoidosis (usually >3.5), although it can be normal or even abnormally low in some cases. Serum ACE levels have been found to usually correlate with total granuloma load.Cases of sarcoidosis have also been reported as part of the immune reconstitution syndrome of HIV, that is, when people receive treatment for HIV, their immune system rebounds and the result is that it starts to attack the antigens of opportunistic infections caught prior to said rebound and the resulting immune response starts to damage healthy tissue.
Carrier Status: Carrier status is not applicable to pulmonary sarcoidosis. Pulmonary sarcoidosis is not a genetic disorder that is passed through carrier genes but is an inflammatory disease that affects the lungs and other parts of the body, characterized by the formation of granulomas. The exact cause is unknown, though it is believed to involve a combination of genetic and environmental factors.
Mechanism: Pulmonary sarcoidosis is an inflammatory disease characterized by the formation of granulomas—small clusters of immune cells—in various organs, predominantly the lungs. The precise mechanism of pulmonary sarcoidosis is not fully understood, but it appears to involve a combination of genetic, environmental, and immunological factors.

**Mechanism:**

1. **Immune Response:** The body's immune system becomes activated in response to an unknown antigen or trigger.
2. **T-Cell Activation:** CD4+ T-helper cells play a central role, becoming activated and releasing cytokines.
3. **Macrophage Activation:** These cytokines stimulate macrophages, leading to further release of inflammatory mediators.
4. **Granuloma Formation:** The continuous activation of macrophages and T-cells results in the formation of granulomas as a result of chronic inflammation.

**Molecular Mechanisms:**

1. **Cytokines and Chemokines:**
- **Interleukin-2 (IL-2)** and **Interferon-gamma (IFN-γ):** Promote T-cell activation and macrophage recruitment.
- **Tumor Necrosis Factor-alpha (TNF-α):** Key in granuloma maintenance and inflammation.

2. **Genetic Factors:**
- Variants in genes such as **BTNL2** (butyrophilin-like 2) and certain **HLA (Human Leukocyte Antigen)** class II alleles are associated with susceptibility.

3. **Signal Transduction Pathways:**
- The **NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)** pathway plays a role in the inflammatory response.
- The **JAK/STAT (Janus kinase/signal transducers and activators of transcription)** pathway is involved in cytokine signaling.

4. **Immune Cell Interactions:**
- Interaction between dendritic cells, T-cells, and B-cells contributes to the perpetuation of the inflammatory response.

Understanding these mechanisms is crucial for developing targeted therapies to treat pulmonary sarcoidosis effectively. Current treatments mainly focus on reducing inflammation using corticosteroids and other immunosuppressive agents.
Treatment: Treatments for sarcoidosis vary greatly depending on the patient. At least half of patients require no systemic therapy. Most people (>75%) only require symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin. For those presenting with lung symptoms, unless the respiratory impairment is devastating, active pulmonary sarcoidosis is observed usually without therapy for two to three months; if the inflammation does not subside spontaneously, therapy is instituted.Major categories of drug interventions include glucocorticoids, antimetabolites, biologic agents especially monoclonal anti-tumor necrosis factor antibodies. Investigational treatments include specific antibiotic combinations and mesenchymal stem cells. If drug intervention is indicated, a step-wise approach is often used to explore alternatives in order of increasing side effects and to monitor potentially toxic effects.Corticosteroids, most commonly prednisone or prednisolone, have been the standard treatment for many years. In some people, this treatment can slow or reverse the course of the disease, but other people do not respond to steroid therapy. The use of corticosteroids in mild disease is controversial because in many cases the disease remits spontaneously.
Compassionate Use Treatment: Pulmonary sarcoidosis may be treated with several investigational or off-label therapies when standard treatments are inadequate or not tolerated. Some of these include:

1. **Methotrexate** - An immunosuppressant often used off-label for sarcoidosis, particularly when corticosteroids are not effective.

2. **Azathioprine** - Another immunosuppressive drug used off-label for reducing steroid dependence.

3. **Leflunomide** - Sometimes used off-label for its immunosuppressive properties.

4. **Infliximab** - A TNF-alpha inhibitor that can be used off-label for severe or refractory cases of sarcoidosis.

5. **Adalimumab** - Another TNF-alpha inhibitor used off-label similar to infliximab for resistant cases.

6. **Mycophenolate mofetil** - Used off-label to manage chronic sarcoidosis, offering an alternative to conventional immunosuppressants.

7. **Cyclophosphamide** - An experimental option for very severe or life-threatening cases, though less common due to its toxicity profile.

It's important for any treatment plan to be discussed and monitored by a healthcare professional familiar with the patient's specific condition and medical history.
Lifestyle Recommendations: For pulmonary sarcoidosis, lifestyle recommendations include:

1. **Smoking Cessation**: Avoid smoking and exposure to second-hand smoke as it can aggravate lung conditions.
2. **Healthy Diet**: Maintain a well-balanced diet rich in fruits, vegetables, whole grains, and lean proteins to support overall health and immune function.
3. **Regular Exercise**: Engage in regular physical activity to improve lung function, maintain a healthy weight, and reduce fatigue.
4. **Adequate Hydration**: Drink plenty of fluids to stay hydrated and help thin mucus in the lungs.
5. **Stress Management**: Practice stress-reducing techniques such as yoga, meditation, or deep-breathing exercises to help manage symptoms.
6. **Avoid Environmental Exposures**: Limit exposure to dust, chemicals, and other environmental pollutants that can irritate the lungs.
7. **Medication Adherence**: Follow prescribed treatment plans and take medications as directed by healthcare providers.
8. **Regular Check-ups**: Attend regular medical appointments to monitor the condition and adjust treatments as necessary.
Medication: For pulmonary sarcoidosis, treatment often involves medications to reduce inflammation and manage symptoms. The primary medications include corticosteroids like prednisone, which are typically the first line of treatment. Other medications may include immunosuppressants such as methotrexate or azathioprine, and antimalarial drugs like hydroxychloroquine, particularly if someone cannot tolerate steroids or if their condition requires additional management.
Repurposable Drugs: For pulmonary sarcoidosis, several repurposable drugs that have been considered include:

1. **Methotrexate**: An immunosuppressive drug commonly used for rheumatoid arthritis and certain cancers.
2. **Azathioprine**: An immunosuppressant often used in renal transplantation and autoimmune diseases.
3. **Hydroxychloroquine**: An antimalarial drug also used in rheumatoid arthritis and lupus.
4. **Infliximab**: A TNF-alpha inhibitor used for inflammatory conditions such as Crohn's disease and rheumatoid arthritis.

These medications are repurposed due to their ability to modulate the immune response, which is a significant aspect of treating pulmonary sarcoidosis. Always consult a specialist for personalized medical advice and treatment options.
Metabolites: Pulmonary sarcoidosis is characterized by the formation of granulomas, which are clusters of inflammatory cells, in the lungs. In terms of metabolites, the specific ones associated with pulmonary sarcoidosis can include elevated levels of calcium and angiotensin-converting enzyme (ACE). Other possible changes in metabolic profiles could involve alterations in the metabolism of vitamin D. These metabolic changes arise due to the inflammatory processes and granuloma formation that disrupt normal metabolic functions.
Nutraceuticals: There is limited scientific evidence to support the use of nutraceuticals for pulmonary sarcoidosis. While some patients may try supplements like omega-3 fatty acids, vitamins D and E, or antioxidants, these should not replace conventional treatments. Always consult a healthcare provider before starting any new supplement regimen.
Peptides: Pulmonary sarcoidosis is characterized by the formation of granulomas in the lungs. Peptides can play a role in the diagnosis and treatment of this condition. Specific peptides derived from mycobacteria or other antigens are sometimes studied for their role in granuloma formation. Additionally, therapeutic peptides targeting inflammatory pathways are under investigation.

"Nan" can refer to several things, including nanotechnology. In the context of pulmonary sarcoidosis, nanotechnology can be utilized for targeted drug delivery systems to enhance the efficacy and reduce the side effects of treatments. Nanoparticles can be tailored to deliver anti-inflammatory drugs directly to the granulomas in the lungs, offering a promising approach for managing the disease.