GeneHealth - Your precision medicine

Sarcoidosis

Disease Details

Family Health Simplified

Buy Membership

Description: Sarcoidosis is an inflammatory disease characterized by the formation of tiny clumps of inflammatory cells (granulomas) in various organs, most commonly the lungs and lymph nodes.
Type: Sarcoidosis is an inflammatory disease that primarily affects the lungs and lymph nodes but can involve multiple organs. It is not classified as a single-gene genetic disorder and does not follow a clear-cut Mendelian pattern of inheritance. Instead, it has a complex genetic component with multiple genes likely contributing to susceptibility, and it appears to aggregate in families, suggesting a possible polygenic or multifactorial mode of inheritance. Environmental factors also play a significant role in the development of the disease.
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: Sarcoidosis often has an insidious onset, meaning its symptoms appear gradually. The age of onset typically ranges from 20 to 40 years, although it can occur at any age. The cause of the disease remains unknown (etiology is not well understood), but it involves an abnormal immune response and possibly genetic factors.
Prevalence: Sarcoidosis is a relatively rare condition, with an estimated prevalence of about 10 to 40 cases per 100,000 people in the general population. Prevalence can vary significantly based on geographical location and ethnicity, with higher rates reported in Scandinavian countries and among African Americans.
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: Sarcoidosis can be challenging to manage but is not always considered intractable. Many patients experience improvement or remission, often without the need for treatment. However, some cases can be severe and chronic, requiring long-term medical management to control symptoms and prevent complications. Treatment plans are tailored to the individual's disease severity and organ involvement.
Disease Severity: Sarcoidosis can vary significantly in severity. In some individuals, it may be asymptomatic or cause mild symptoms that resolve without treatment. In others, it can become chronic and lead to severe complications, potentially affecting organs such as the lungs, heart, eyes, and skin. The severity often depends on the extent and organs involved, as well as the individual's overall health and response to treatment. There is no current evidence linking sarcoidosis directly to any involvement with nanomaterials (nan).
Healthcare Professionals: Disease Ontology ID - DOID:11335
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: Sarcoidosis is not a disease with a carrier status, as it is not directly inherited in a simple genetic manner like some other conditions. Instead, it is a complex inflammatory disease that can involve multiple organs, most commonly the lungs and lymph nodes. The exact cause of sarcoidosis is unknown, but it is believed to result from an abnormal immune response, possibly triggered by environmental factors in a genetically predisposed individual.
Mechanism: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas in various organs, most commonly the lungs and lymphatic system.

**Mechanism:**
The exact cause of sarcoidosis is unknown, but it is believed to involve an exaggerated immune response to an unidentified environmental or infectious agent in genetically susceptible individuals. The disease triggers an immune reaction that leads to the accumulation of T cells, macrophages, and other immune cells, resulting in granuloma formation.

**Molecular Mechanisms:**
1. **Antigen Presentation:** Unknown antigens are thought to be presented by antigen-presenting cells, such as macrophages and dendritic cells, to CD4+ T-helper (TH1) cells.
2. **Cytokine Release:** Activated CD4+ T cells release cytokines, including interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), which further stimulate macrophages and perpetuate the immune response.
3. **Granuloma Formation:** Activated macrophages differentiate into epithelioid cells and multinucleated giant cells, forming granulomas. Granulomas are a result of the immune system's attempt to isolate and contain the antigen.
4. **Genetic Factors:** Genetic predisposition plays a role, with variants in genes such as HLA-DRB1 associated with an increased risk of developing sarcoidosis. Genes involved in immune regulation and inflammation, such as BTNL2, may also be implicated.

The interplay between these molecular mechanisms results in the characteristic granulomatous inflammation seen in sarcoidosis. Understanding these processes helps in developing targeted therapies to manage the disease.
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: For sarcoidosis, compassionate use treatments and off-label or experimental treatments may include:

1. **TNF-alpha Inhibitors**: Medications such as infliximab and adalimumab are used off-label for severe sarcoidosis, especially when the disease affects the lungs or is refractory to standard treatments like corticosteroids and immunosuppressants.

2. **Antimalarials**: Hydroxychloroquine and chloroquine are sometimes used off-label for treating skin manifestations and hypercalcemia associated with sarcoidosis.

3. **Methotrexate**: This is an immunosuppressant that may be used off-label for sarcoidosis, particularly when patients do not respond to corticosteroids.

4. **Mycophenolate Mofetil**: Another immunosuppressive agent that can be used off-label, especially for those with pulmonary or extrapulmonary sarcoidosis.

5. **Leflunomide**: Often used in rheumatoid arthritis, this drug is sometimes used off-label in sarcoidosis patients with refractory disease.

6. **Antifibrotic Agents**: Drugs such as pirfenidone and nintedanib are being researched for their potential use in treating pulmonary fibrosis in sarcoidosis patients.

7. **Experimental treatments**: These include various clinical trials exploring the efficacy and safety of new drugs or combinations of drugs. Examples include treatments targeting specific cytokines or fibrotic pathways involved in sarcoidosis.

Patients typically resort to these options when conventional therapies fail or cause significant side effects. Always consult with a healthcare provider before starting any off-label or experimental treatment.
Lifestyle Recommendations: For managing sarcoidosis, consider these lifestyle recommendations:

1. **Diet**: Eat a well-balanced diet rich in fruits, vegetables, and lean proteins to support overall health.
2. **Exercise**: Engage in regular moderate exercise to maintain lung function and overall fitness, but consult a doctor for personalized advice.
3. **Avoid Smoking**: Avoid smoking and exposure to secondhand smoke, as these can aggravate lung problems.
4. **Medication Adherence**: Strictly follow prescribed treatments and attend regular medical check-ups.
5. **Hydration**: Stay well-hydrated, especially if you are on medications that affect kidney function.
6. **Stress Management**: Practice stress-reducing techniques like yoga, meditation, or deep-breathing exercises.
7. **Rest**: Ensure adequate rest and sleep to help your body recover and maintain immune function.
8. **Vaccinations**: Stay updated on vaccinations to prevent infections that could complicate sarcoidosis.

Consult with healthcare providers for tailored advice specific to your condition.
Medication: For managing sarcoidosis, medications commonly used include:

1. **Corticosteroids**: Prednisone is often the first line of treatment to reduce inflammation.
2. **Immunosuppressive Agents**: Drugs like methotrexate, azathioprine, and leflunomide are used when corticosteroids are insufficient or for long-term management.
3. **Antimalarial Drugs**: Hydroxychloroquine is sometimes used for skin lesions and to manage symptoms in the joints.
4. **TNF-alpha Inhibitors**: Infliximab and adalimumab may be used in severe cases or when other treatments have failed.

Regular monitoring and adjusting medication based on the patient's response are crucial for managing the disease effectively.
Repurposable Drugs: Repurposable drugs for sarcoidosis include:

1. Methotrexate
2. Azathioprine
3. Leflunomide
4. Mycophenolate mofetil
5. Hydroxychloroquine

These drugs, originally developed for other conditions, have shown benefits in managing sarcoidosis by suppressing the immune response. However, their use should be closely monitored by a healthcare professional.
Metabolites: For sarcoidosis, notable metabolites include abnormal levels of angiotensin-converting enzyme (ACE), calcium, and vitamin D. Elevated ACE levels can be found in the blood and serve as a potential marker for the activity of the disease. Hypercalcemia and hypercalciuria can result from increased production of vitamin D by granulomas. These abnormalities can help in diagnosing and monitoring the disease.
Nutraceuticals: Nutraceuticals, which are products derived from food sources with extra health benefits in addition to their basic nutritional value, have been under investigation for their potential to aid in managing sarcoidosis, though robust scientific evidence is still limited. Some of the nutraceuticals studied include:

1. **Curcumin**: A compound in turmeric, curcumin has anti-inflammatory and antioxidant properties, which might help reduce inflammation associated with sarcoidosis.

2. **Omega-3 Fatty Acids**: Found in fish oil, these have anti-inflammatory properties that might benefit individuals with inflammatory conditions like sarcoidosis.

3. **Vitamin D**: Given that sarcoidosis often affects vitamin D metabolism, maintaining optimal levels through supplementation might help manage the disease, though this should be monitored by a healthcare professional due to risk of hypercalcemia.

4. **Resveratrol**: Found in grapes and berries, this compound has anti-inflammatory properties that may have potential benefits for sarcoidosis treatment.

More research is necessary before definitive recommendations can be made regarding nutraceuticals in sarcoidosis management. Always consult healthcare providers before starting any new supplement regimen.
Peptides: In the context of sarcoidosis, several peptides have been studied for their potential involvement in the disease. Specific examples include:

1. **Angiotensin-converting enzyme (ACE)**: Elevated levels of this peptide can be a marker for sarcoidosis, as ACE is often increased in individuals with granulomatous diseases.

2. **Tumor necrosis factor-alpha (TNF-α)**: This pro-inflammatory cytokine plays a crucial role in the formation and maintenance of granulomas seen in sarcoidosis.

3. **Interleukin-2 (IL-2) and Interleukin-12 (IL-12)**: Elevated levels of these cytokines have been observed in sarcoidosis, contributing to immune system activation.

Regarding nanomedicine or nanotechnology in sarcoidosis, nanoparticles represent a promising area for diagnosis and treatment but are still largely in the experimental phase. Various nanoparticles are being developed to target granulomas specifically, deliver anti-inflammatory agents, or enhance imaging for better diagnosis and monitoring of the disease.

Nanoparticles can provide a more targeted therapeutic approach, potentially reducing side effects compared to systemic treatments. Research is ongoing to fully understand and utilize these technologies effectively in sarcoidosis management.