A disease involving abnormal collections of inflammatory cells that form granulomas.
The cause of sarcoidosis is not known, but is theorized to occur in genetically susceptible individuals through an alteration to the immune response after exposure to an environmental, occupational, or infectious agent.
Its development requires both of genetic and environmental predisposition, and sometimes occupational exposure to an unknown substance or microbial antigen.
Gene variants of chromosome 6 show substantially increased risk of sarcoidosis in persons exposed to pesticides.
An inflammatory, multisystemic disease of unknown cause with a wide range of clinical manifestations.
Some cases may be caused by treatment with tumor necrosis factor (TNF) inhibitors.
Occupations that involve inhalation exposure to metals and silica, shipping automotive workers, firefighters, and gardeners have associated higher incidence of sarcoidosis.
Some World Trrade center workers exposed to debris on 911 experienced sarcoidosis or sarcoidosis like disease.
Microbes such as Propionibacterium species and mycobacterium have been associated with the presence of sarcoidosis.
Auto immunity may contribute to the development of sarcoidosis.
Vimentin, a structural proteins may be implicated in the development of sarcoidosis.
The disease usually begins in the lungs, skin, or lymph nodes.
The lungs are usually involved, with symptoms such as cough, shortness of breath, chest pain, and pronounce fatigue.
The lungs are usually involved, with symptoms such as cough, shortness of breath, chest pain, and pronounced fatigue. Symptoms vary widely depending upon the organ involvement.
Less commonly sarcoidosis affects the eyes, liver, heart, and brain, and skin.
Clinical symptoms vary widely, depending on which organs are affected.
Patients often have a wide spectrum of systemic, non-specific symptoms, which are not related to single organ and cannot be explained by the granulomas, but likely to be caused by the systemic release of inflammatory mediators.
Nonspecific symptoms of fatigue, exercise limitations, cognitive impairment, and symptoms associated with small fiber neuropathy impaired well-being.
It can be asymptomatic and is discovered by accident in about 5% of cases.
The Clinical presentation depends on the intensity and duration of the inflammation and organs involved.
Evidence siggests the genetic risk of sarcoidosis links its clinical manifestations and outcome.
The presence of cardiac, neurologic, renal and progressive fibrotic pulmonary involvement with respiratory insufficiency is associated with increase mobility and mortality.
Fewer than 10% of patients die from sarcoidosis.
Sarcoidosis has a mortality rate of approximately 7% within a five year follow-up.
Sarcoidosis predominantly involves the lungs and intrathoracic lymph nodes: chest x-rays are abnormal and 80% to more than 90% of patients with sarcoidosis.
30 to 40% 60% of patients with pulmonary sarcoidosis are asymptomatic.
More than 10% of patients with pulmonary sarcoidosis develop progressive disease and more than 60% of the deaths are due to advanced pulmonary sarcoidosis.
Pulmonary sarcoidosis typically presents between the ages of 30 and 60 years, with a bimodal distribution.
Pulmonary sarcoidosis histologically shows discrete, non-necrotizing granulomas composed of epithelioid histiocytes and multinucleated giant cells surrounded by lymphocytes, plasma cells, and fibroblasts in the periphery.
Physical examination of the chest is often remarkable and pull my function test so normally more than 80% of patients without parenchymal infiltrates on chest x-rays.
There may be destruction of normal tissue architecture, along with fibrosis.
Granulomas are typically distributed along broncovascular bundles and lymphatics.
Most patients with fatal disease have had advanced lung disease followed by cardiac complications.
Sarcoidosis an increased risk of death by a factor of 0.9 to 2.4.
Most patients are asymptomatic or have acute symptoms with spontaneous resolution, but chronic disease develops in approximately 1/3 of patience with waxing and waning or relentlessly progressive disease.
It is suspected a dysregulated immune response against environmental antigens occurs and result in sustained granulomatous inflammation and failure to clear the offending antigens.
Genes involved in antigen presentation in the HLA class II region and butyrophilin gene 2 link to development of sarcoidosis.
Onset usually begins between the ages of 20 and 50.
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.
The incidence peaks at 30-50 years of age in men and 50-60 years of age in women.
There is a slight predominant among women.
Occurs throughout the world in all races.
The incidence of sarcoidosis per 100,000 each year is three among Asian individuals, four among Hispanic individuals, eight among white individuals and 18 among black individuals.
The triggering antigen likely varies according to race/ethnic group, geographic location, and individual genetic background.
The role of genetic factors in sarcoidosis is supported by clustering of familiar cases and the manifestations in the course of disease across racial and ethnic groups.
Has an average incidence of 16.5 per 100,000 in men and 19 per 100,000 in women.
Disease signs and symptoms depend on the organ involved.
Often, patients experience no or mild symptoms.
Pulmonary involvement they be associated with wheezing, coughing, shortness of breath, or chest pain
Some sarcoid patients have Lofgren syndrome with fever, large lymph nodes, arthritis, and a rash known as erythema nodosum.
Lofgren syndrome arthritis occur most frequently in the ankles, followed by the knees, wrists, elbows, and metacarpophalangeal joints.
Lofgren syndrome arthritis is a periarthritis that appears as a swelling in the soft tissue around the joints.
The combination of hilar lymphadenopathy and ankle periarthritis can be considered as a variant of Lofgren syndrome.
Symptoms and findings relate to organ involvement:
Lungs: wheezing, cough, shortness of breath, chest pain
Skin: lumps, ulcers, discolored skin
Children: weight loss, bone pain, feeling tired
Usual onset 20-50 year old women.
Duration runs from a few years to long term.
Cause-Unknown.
Risk factors-Family history.
The diagnosis is based on three major criteria: comparable clinical characteristics, identification of non-necrotizing granulomas in one and more tissues, and the ruling out of other causes of granulomatous disease.
Patients most commonly present with sub acute or chronic respiratory symptoms and the diagnosis is considered on the basis of typical features on a chest x-ray or a CT scan of the chest.
CT findings of bilateral hilar lymphadenopathy with a perilymphatic, micronodular pattern are highly specific for sarcoidosis.
Biopsy specimens from the lungs or mediastinal lymph nodes provide the best diagnostic material.
Differential diagnosis:
Tuberculosis, lymphoma, infectious mononucleosis, pulmonary eosinophilia.
TREATMENT:
Ibuprofen, prednisone, methotrexate
Mortality 1.7%.
Frequency approximately 1.9 million with interstitial lung disease, worldwide.
Deaths estimated 122,000 with interstitial lung disease, globally.
Patients with affected family members are at greater risk: For persons with affected firstdegree relative, the risk is increased by a factor of 3.7.
Diagnosis is based on signs and symptoms, which may be supported by biopsy.
Findings include: large lymph nodes at the root of the lung on both sides, high blood calcium with a normal parathyroid hormone level, or elevated levels of angiotensin-converting enzyme in the blood.
The diagnosis is one of exclusion.
It may resolve without any treatment within a few years.
Some patients may have long-term or severe disease.
Some symptoms may be improved with the use of anti-inflammatory drugs.
When the condition causes significant health problems, steroids are indicated.
No discernible benefits exist for outcomes with higher doses of steroids versus lower doses, particularly for maintenance therapy.
Additional drugs such as methotrexate, chloroquine, hydroxtchloroquine or azathioprine may occasionally be used in an effort to decrease the side effects of steroids.
If the disease is severe and progressive and unresponsive to the usual agents, third line treatments with biologic agents or advanced immuno modulating agents may be considered- infliximab and adalimumab.
Only a small subgroup of patients require long-term treatment to prevent progressive organ damage.
Lung transplantation for sarcoidosis is rarely performed but is effective therapy.
The chance of recurrence of disease returning in someone who has had it previously is less than 5%.
It is most common in Scandinavians.
The risk is greater among Black people as opposed to white people.
It occurs more often in women than men.
Signs and symptoms:
Predominantly involves the lungs, lymphatic system, skin, or eyes or a combination of these sites and is characterized by the formation of noncaseating granulomas.
Multiple reddish-brownish papules and plaques on the left mandibular region of an adult face, fatigue despite sleep, lack of energy, weight loss, joint aches and pains, arthritis, dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions.
Hemoptysis may occur.
Skin lesions vary: rashes and nodules to erythema nodosum, granuloma annulare, or lupus pernio.
May mimic cancer.
The prognosis is highly variable and ranges from spontaneous resolution to chronic inflammation complicated by fibrosis or irreversible organ failure or both.
The combination of erythema nodosum, bilateral hilar lymphadenopathy, and joint pain is called Lofgren syndrome, which has a relatively good prognosis.
Lofgren syndrome occurs significantly more often in Scandinavian patients.
Al least 90% of affected persons experience lung involvement.
About 50% develop permanent pulmonary abnormalities, and 5 to 15% have progressive fibrosis of the lung parenchyma.
Sarcoidosis of the lung is primarily an interstitial lung disease in which the inflammatory process involves the alveoli, small bronchi, and small blood vessels.
With sarcoidosis of the lung physical examination usually reveals dry crackles.
Approximately 5% of persons with sarcoidosis of the lung develop pulmonary arterial hypertension.
In addition to pulmonary involvement,5-10% of the time the upper respiratory tract, including the larynx, pharynx, and sinuses, may be affected by sarcoidosis.
The four stages of pulmonary involvement by sarcoidosisare based on radiological stage of the disease:
Stage I: bilateral hilar lymphadenopathy alone
Stage II: bilateral hilar lymphadenopathy with pulmonary infiltrates
Stage III: pulmonary infiltrates without bilateral hilar lymphadenopathy.
Stage IV: fibrosis
Skin involvement in sarcoidosis occurs between 9 and 37% of patients.
Skin involvement with sarcoidosis is more common in African Americans than Caucasians.
Dermatologic involvement in sarcoidosis is the second most commonly affected organ after the lungs.
Common dermatological lesions are: erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules, and lupus pernio.
Dermatological lesions are usually self limited and spontaneously resolve in 2-4 weeks and do not require treatment.
Cutaneous sarcoidosis rarely causes significant problems, bit scalp involvement may be associated with diffuse or patchy hair loss.
Cardiac involvement in sarcoidosis varies significantly influenced by race;
Cardiac sarcoidosis is the second leading cause of death among affected patients, after pulmonary disease.
Sarcoidosis in Japanese associated in more than 25% of persons with symptomatic cardiac involvement.
In the US and Europe, only about 5% of sarcoidosis cases present with cardiac involvement.
Autopsy studies show higher rates of cardiac involvement by sarcoid than noted by clinical findings: US frequency about 20-30%, and Japan have shown a frequency of 60%.
Cardiac arrhythmia manifestations can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia, and can include conduction abnormalities.
Ventricular arrhythmias, are found in about 23% of cases with cardiac involvement.
Sudden cardiac death is a rare complication of cardiac sarcoidosis.
Cardiac sarcoidosis can cause: fibrosis, granuloma, or edema in the interstitium of the heart, or a combination of the two.
Granulomas cause myocardial fibrosis and scarring and CHF.
Congestive heart failure affects 25-75% of persons with cardiac sarcoidosis.
Pulmonary arterial hypertension may occur: reduced left heart function due to granulomas weakening the heart muscle or from impaired blood flow.
Eye involvement commonly occurs: uveitis, uveoparotitis, and retinal inflammation.
Uveitis is the most common eye manifestation of sarcoidosis.
Heerfordt syndrome refers to the combination of anterior uveitis, parotiditis and VII cranial nerve paralysis, along with fever (Uveoparotid fever).
The combination of anterior uveitis, parotitis, VII cranial nerve paralysis and fever is called uveoparotid fever or Heerfordt syndrome.
Any area of the nervous system can be involved with sarcoidosis and its involvement is known as neurosarcoidosis.
In neurosarcoidosis the cranial nerves are most commonly affected, accounting for about 5-30% of cases.
The central nervous system involvement is present in 10-25% of sarcoidosis cases.
A peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of sarcoidosis.
Additional manifestations of neurosarcoidosis include: optic nerve dysfunction, papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary abnormalities, chronic meningitis, myelopathy and peripheral neuropathy.
Myelopathy is often associated with the poorest prognosis of the neurosarcoidosis subtypes.
Facial nerve palsies and acute meningitis secondary to sarcoidosis tend to have the most favourable prognosis.
Sarcoidosis affecting the neuroendocrine system accounts for about 5-10% of neurosarcoidosis cases and can lead to diabetes insipidus, altered menstrual cycle and hypothalamic dysfunction.
Prolactin levels are frequently increased in sarcoidosis, between 3 and 32% of cases have hyperprolactinemia.
Prolactin level elevation frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women with
Sarcoidosis frequently causes an increase in 1,25-dihydroxy vitamin D.
1,25-dihydroxy vitamin D is the active metabolite of vitamin D, which is usually hydroxylated within the kidney.
In sarcoidosis, hydroxylation of vitamin D can occur outside the kidneys, namely inside the immune cells found in the granulomas the associated with the disease.
1,25-dihydroxy vitamin D is the main cause for hypercalcemia in sarcoidosis- overproduction by sarcoid granulomata.
Hypercalciuria and hypercalcemia are seen in <10% of individuals and likely results from the increased 1,25-dihydroxy vitamin D production.
Hypercalcemia in sarcoidosis is typically due to elevated circulating levels of 1:25-dihydroxy vitamin D (calcitriol), which are generated by macrophages that convert 25 hydroxyvitamin D to the more active metabolite, calcitriol.
Increased levels of calcitriol increase calcium absorption from the duodenum causing hypercalciuria and nephrolithiasis.
There is a higher incidence of nephrolithiasis in sarcoidosis.
Clinically significant hepatic sarcoidosis occurs in approximately 5 to 25% of patients with sarcoidosis.
Thyroid dysfunction is seen in 4.2-4.6% of cases of sarcoidosis.
Parotid enlargement occurs in about 5-10% of persons with sarcoidosis; it is usually bilateral.
Dry mouth can occur.
The eyes, their glands, or the parotid glands are affected in 20-50% of cases of sarcoidosis.
Symptomatic gastrointestinal (GI) involvement occurs in less than 1% of cases, with GI involvement in less than 10% of people.
At autopsy 1-3% of patients have evidence of pancreatic involvement.
Symptomatic kidney involvement occurs in just 0.7% of cases, but autopsy findings of renal involvement in up to 22% of people.
Symptomatic kidney involvement is usually related to nephrocalcinosis.
Rarely, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus, or the vulva may be affected.
About 5-15% of cases affect the bones, joints, or muscles with musculoskeletal complaints.
At autopsy about 5% have testicular involvement and it may lead to infertility.In males.
Around 70% of people have granulomatous liver lesions, but
only in about 20-30% of cases, are LFTs abnormal.
About 5-15% of patients with sarcoidosis have hepatomegaly.
Raised levels of alkaline phosphatase is the most common liver function test anomaly seen in persons with sarcoidosis.
Lymphopenia is the most common blood abnormality scene in sarcoidosis.
Anemia occurs in about 20% of patients .
Leukopenia is less common but is rarely severe, and thrombocytopenia and hemolytic anemia are rare.
Leukopenia may be a result of the redistribution of blood T cells to sites of disease.
Monocytosis, occurring in the majority of sarcoidosis cases.
Commonly associated are increased hepatic enzymes or alkaline phosphatase.
Patients with sarcoidosis often have immunologic anomalies like allergies to test antigens such as Candida or purified protein derivative.
Polyclonal hypergammaglobulinemia is common: occurs in more than 40% of patients with sarcoidosis.
Hypercalcemia affects approximately 3 to 12% of patients with sarcoidosis.
Lymphadenopathy is present in in 15% of cases.
Intrathoracic nodes are enlarged in 75 to 90%, and usually involve the hilar nodes, but the paratracheal nodes are commonly involved.
Peripheral lymphadenopathy is very common, particularly involving the cervical region, as well as axillary, epitrochlear, and inguinal nodes.
Microscopic splenic involvement occurs and 75%, but only 5-10% of patients experience splenomegaly.
Enthesitis also occurs in about one-third of patients with acute sarcoid arthritis and mainly affects the Achilles tendon and heels.
Chronic sarcoid arthritis usually occurs in the ankles, knees, wrists, elbows, and hands and presents itself in a polyarticular pattern.
Dactylitis similar to that seen in psoriatic arthritis may also occur.
Bone involvement in sarcoidosis has been reported in 1-13% of cases:hands and feet primarily, and the spine is less commonly affected.
The heritability of sarcoidosis varies with ethnicity: About 20% of African Americans with sarcoidosis have a family member with the condition, and for European Americans is is about 5%.
In African Americans that experience more severe and chronic disease, siblings and parents have about a 2.5-fold increased risk for developing the disease.
Heritability in Swedish people is
39%.
If a first-degree family member has sarcoidosis, a person has a four-fold greater risk of being affected.
No reliable genetic markers are known.
Several infectious agents appear to be significantly associated with sarcoidosis: mycobacteria, fungi, borrelia, and rickettsia, but none of the known associations is specific enough to suggest a direct causative role.
Association of autoimmune disorders with sarcoidosis has been frequently observed, but the mechanism of this relationship is not known.
It is a granulomatous inflammation.
Sarcoidosis is characterized primarily by the accumulation of macrophages and activated T-lymphocytes, with increased production of key inflammatory mediators, TNF, IL-2, IL-8, IL-10, IL-12, IL-18, IL-23 and TGF-?.
Sarcoidosis is indicative of a Th1-mediated immune response.
It is characterized by increased macrophage and CD4 helper T-cell activation, resulting in accelerated inflammation, yet the immune response to antigen challenges such as tuberculin is suppressed.
Activated macrophages well regarded as drivers of the inflammatory process associated with granuloma formation.
A paradoxic state of simultaneous hyper- and hypoactivity of the immune system exist and is suggestive of anergy.
The anergy may also be responsible for the increased risk of infections and cancer that occur with sarcoidosis.
T-lymphocytes in sarcoid granulomas suppress IL-2 secretion, suggested to preventing antigen-specific memory responses of anergy.
The process is characterized by non-caseous epithelioid cell granulomas in various organs and tissues.
Granuloma findings of Schaumann bodies seen in sarcoidosis are calcium and protein inclusions inside of Langhans giant cells.
Granuloma is often resolves spontaneously, but in some patients they persist and become a nidus for the development of fibrosis, a process that depends on the nature of the offending antigen.
Activated helper T cells promote the formation of non-necrotizing epithelioid cell granulomas.
Activation of alveolar T lymphocytes is characteristic in sarcoidosis.
Serum levels of soluble HLA class I antigens and ACE are higher in patients with sarcoidosis.
HLA-DRB103, 0301, and 1501 are associated with Lofgren syndrome where is HLA-DRB107, 14, 15, 01, 03 and DQB10602 are associated with increased risk of progressive pulmonary sarcoidosis.
The ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in persons with pulmonary sarcoidosis.
Serum ACE levels usually correlate with total granuloma load.
Serum ACE concentrations are elevated in approximately 50% of patients due to the secretion of angiotensin converting enzyme from activated mono nuclear phagocytes and epithelial cells.
There is no evidence to support using ACE concentrations to diagnose sarcoidosis or to monitor therapeutic response.
Cases of sarcoidosis have also been reported as part of the immune reconstitution syndrome of HIV.
In some patients receiving treatment for HIV, their immune system is reconstituted and attacks the antigens of opportunistic infections resulting in immune response to damage healthy tissue.
DIAGNOSIS:
Diagnosis of sarcoidosis is a process of exclusion.
No specific test for diagnosis exists.
Evaluation might involve: a chest radiograph, CT scan of chest, PET scan, CT-guided biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound, and endoscopic ultrasound with fine-needle aspiration of mediastinal lymph nodes in patients with pulmonary presentation, and biopsy of lymph nodes
Serum markers present in sarcoidosis, include: serum amyloid A, soluble interleukin-2 receptor, lysozyme, angiotensin converting enzyme, and the glycoprotein KL-6.
Angiotensin-converting enzyme blood levels are used in the monitoring of sarcoidosis.
A bronchoalveolar lavage can show an elevated CD4/CD8 T cell ratio, indicative of pulmonary sarcoidosis.
Differential diagnosis includes: metastases, lymphoma, septic emboli, rheumatoid nodules, granulomatosis with polyangiitis, varicella infection, tuberculosis, Mycobacterium avium complex, cytomegalovirus, and cryptococcus.
Chest radiograph changes:
bihilar lymphadenopathy
bihilar lymphadenopathy and reticulonodular infiltrates
bilateral pulmonary infiltrates
fibrocystic sarcoidosis typically with upward hilar retraction, cystic and bullous changes
Patients with stage 1 chest x-rays tend to have the acute or subacute, reversible form of the disease..
Patients with stages 2 and 3 often have the chronic, progressive disease.
In Caucasian population the presentation of hilar adenopathy and erythema nodosum are the most common initial symptoms.
Biopsy of the gastrocnemius muscle is a useful tool in correctly diagnosing the process: noncaseating epithelioid granuloma in a gastrocnemius specimen is definitive evidence of sarcoidosis.
PET scans appear to have a higher sensitivity and specificity compared to cardiac MRI for defining sarcoidosis.
PET scans are most commonly used to guide both treatment decisions and diagnosis in sarcoidosis.
Hilar adenopathy especially on the person’s left.
Sarcoidosis divided into the following types:
Annular sarcoidosis
Erythrodermic sarcoidosis
Ichthyosiform sarcoidosis
Hypopigmented sarcoidosis
Lofgren syndrome
Lupus pernio
Morpheaform sarcoidosis
Mucosal sarcoidosis
Neurosarcoidosis
Papular sarcoid
Scar sarcoid
Subcutaneous sarcoidosis
Systemic sarcoidosis
Ulcerative sarcoidosis
Treatments:
At least half of patients require no systemic therapy.
75% or more only require symptomatic treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin.
With lung symptom presentation, unless the respiratory impairment is severe, active pulmonary sarcoidosis is observed usually without therapy for two to three months.
In such cases,if the inflammation does not subside spontaneously, therapy is instituted.
Drugs utilized: glucocorticoids, antimetabolites, biologic agents especially monoclonal anti-tumor necrosis factor antibodies.
Corticosteroids have been the standard treatment.
Corticosteroids can slow or reverse the course of the disease.
Not all patients respond to steroid therapy.
Use of corticosteroids in mild disease is controversial because in many cases the disease remits spontaneously.
Antimetabolites azathioprine, methotrexate, mycophenolic acid, and leflunomide are often used as alternatives to corticosteroids.
Of these, methotrexate is most widely used.
Granulomas are caused by collections of immune system cells, particularly T cells, immunosuppressants like cyclophosphamide, cladribine, chlorambucil, and cyclosporine are utilized in sarcoidosis.
Immunomodulatory agents pentoxifylline and thalidomide, and anti-tumor necrosis factor treatment with infliximab, etanercept, golimumab, and adalimumab are also available..
Infliximab has been used successfully to treat pulmonary sarcoidosis.
Adalimumab treatment responses occur about half of subjects, which is similar to that seen with infliximab.
Ursodeoxycholic acid has been used as a treatment for cases with liver involvement.
Cutaneous sarcoid disease may be managed with antimalarials chloroquine and hydroxychloroquine and the tetracycline antibiotic, minocycline.
Antimalarials have efficacy in treating sarcoidosis-induced hypercalcemia and neurosarcoidosis.
Phosphodiesterase 4 (PDE4) inhibitors like apremilast roflumilast, and pentoxifylline, have been tried as a treatment for sarcoidosis.
Pentoxifylline has been used to treat acute sarcoid disease although its use is greatly limited by its gastrointestinal toxicity.
Case reports have supported the efficacy of rituximab, an anti-CD20 monoclonal antibody.
ACE inhibitors have been reported to cause remission in cutaneous sarcoidosis and improvement in pulmonary sarcoidosis.
Antimycobacterial treatments
have efficacy in treating chronic cutaneous sarcoidosis.
Physical training improves fatigue, psychological health, and physical functioning in people sarcoidosis.
Inspiratory muscle training improves functional and maximal exercise capacity and respiratory muscle strength.
Neuropathic pain in sarcoidosis treated with antidepressants, anticonvulsants and prolonged-release opioids.
Pulmonary honeycombing consists of dilated airways separated by scar tissue resembling the honeycomb of bees.
Pulmonary sarcoid can remit spontaneously or become chronic, with exacerbations and remissions.
Pulmonary sarcoid can progress to pulmonary fibrosis and death.
Two-thirds of people with pulmonary sarcoid achieve a remission within 10 years of the diagnosis.
Prognosis is generally less favorable with patients with cardiac involvement, though corticosteroids appear effective in improving AV conduction.
The prognosis tends to be less favorable in African Americans than in white Americans.
In cases without severe disease at diagnosis had comparable mortality to the general population.
The risk for premature death is markedly increased in cases with severe disease at diagnosis.
Patients with sarcoidosis are at significantly increased risk for cancer, in particular lung cancer, lymphomas, and cancer in other organs known to be affected by the disease.
Sarcoidosis can also follow cancer or can occur concurrently with cancer: hairy cell leukemia, acute myeloid leukemia, and acute myeloblastic leukemia.
It is most common in Northern European countries.
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.
It is more common in people of African descent than Caucasians, with annual incidence reported as 35.5 and 10.9 per 100,000, respectively in the US.
An association between the two celiac disease and sarcoidosis disorders exist.
There also has been a seasonal clustering observed in sarcoidosis.
There may be differences in the severity of the disease between people of different ethnicities: people of African origin may be more severe and disseminated than for Caucasians.
Erythema nodosum is far more common in men than in women and in Caucasians than in other races.
In Japanese people with sarcoidosis ophthalmologic and cardiac involvement are more common than in other races.
Occupations associated with sarcoidosis: firefighters, educators, military personnel, persons who work in industries where pesticides are used, law enforcement, and healthcare personnel.
Exposure to moldy environments, occupational exposure to insecticide, agricultural employment, metalworking, fire fighting, exposure to inorganic dust, exposure to silica dust, and handling of building supplies are associated with sarcoidosis.
Following the September 11 attacks, the rate of sarcoidosis incidence went up four-fold (to 86 cases per 100,000).
Rescue workers from WTC are at a heightened risk for sarcoidosis.
The course of the disease is unaffected by pregnancy, with improvement in a few cases and worsening of symptoms in some.
The ability to diagnose sarcoidosis is complicated by a lack of definitive laboratory blood tests.
The histologic presence of noncaseating granulomas from tissue biopsies has been the gold standard.
Bronchoalveolar lavage cellular analysis with a cell count of at least 15% and an increased CD4/CD8 T-lymphocyte ratio greater than 3.5, combined with appropriate clinical and radiological patterns, strongly support the diagnosis of sarcoidosis: CD4/CD8 ratio in sarcoidosis has a pooled sensitivity of 70% and a specificity of 83%.
There is a significantly elevated bronchoalveolar lavage CD4/CD8 ratio in patients previously treated with oral corticosteroids compared to asymptomatic, untreated patients.
Inhaled corticosteroid use appears to consistently lower CD4/CD8 ratios.
Studies are contradictory that the use of corticosteroids alters the lung immune response in unpredictable ways, making any interpretation of BALF differential cell counts unreliable.
With symptomatic sarcoidosis there is as significantly higher CD4/CD8 ratio compared with asymptomatic patients.
Transbronchial lung biopsy and lymph node biopsy are the most common invasive procedure to discover noncaseating granulomas that can confirm the clinical diagnosis of sarcoidosis.
BAL, while frequently performed during fiberoptic bronchoscopy, remains controversial in the diagnosis.