Sarcoidosis 1

Sarcoidosis
Sarcoidosis
Classification and external resources

Chest X-ray showing the typical nodularity of sarcoidosis in the base of the lungs.

ICD-10 [1]
D86

ICD-9 [2]
135

OMIM [3]
181000

DiseasesDB [4]
11797

MedlinePlus [5]
000076

eMedicine [6]
med/2063

MeSH [7]
D012507

Sarcoidosis, also called sarcoid, is a disease involving abnormal collections of inflammatory cells (granulomas) that
can form as nodules in multiple organs. The granulomas are most often located in the lungs or its associated lymph
nodes, but any organ can be affected. Sarcoidosis seems to be caused by an immune reaction to an infection or some
other trigger (called an antigen, which may be from one's environment) that continues even after the initial infection
or other antigen is cleared from the body. In most cases it clears up by itself without any medical intervention, but
some cases go on to affect the person long-term or become life-threatening and require medical intervention, most
often with medications. The average mortality rate is less than 5% in untreated cases.
Treatment is usually designed to help relieve the symptoms and hence do not directly alter the course of the disease.
This treatment usually consists of drugs like ibuprofen or aspirin. In cases where the condition develops on a
progressive and/or life-threatening course the treatment is most often steroid treatment with prednisone or
prednisolone. Alternatively, drugs that are most commonly used to treat cancer and suppress the immune system,
such as methotrexate, azathioprine and leflunomide, may be used.
In the United States it most commonly affects people of Northern European (especially Scandinavian or Icelandic) or
African (especially African American) ancestry between the ages of 20 and 29, although any race or age group can
be affected. Japan has a lower rate of sarcoidosis than the United States, although in these people the disease is
usually more aggressive in its course with the heart often affected. Japanese individuals also have a different peak
Sarcoidosis 2

age for sarcoidosis, namely 25–40 years of age. It occurs about twice as often in women, where it usually takes a
more aggressive course. In developing countries it often goes misdiagnosed as tuberculosis (TB) as its symptoms
often resemble those of TB.
Sarcoidosis was first described in 1877 by an English doctor named Dr. Jonathan Hutchinson as a skin disease
causing red, raised lesions on the arms, face and hands.

Name
The word "sarcoidosis" comes from Greek [σάρκο] sarcο meaning "flesh", the suffix -(e)ido (from the Greek εἶδος
-eidos [usually omitting the initial e in English for euphonic reasons]) meaning "type", " resembles" or "like", and
-sis, a common suffix in Greek meaning "condition". Thus the whole word means "a condition that resembles crude
flesh".

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 66% of cases), lack of
energy, weight loss, joint aches and pains (which occur in about 70%
of cases), arthritis (14–38% of persons), 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. 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 commonly in Scandinavian patients, than in those of
non-Scandinavian origin.

Respiratory tract
Localization to the lungs is by far the most common manifestation of Signs and symptoms of sarcoidosis.
sarcoidosis. At least 90% of affected persons experience lung
involvement. Overall, 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. In acute and subacute cases, physical
examination usually reveals dry rales. At least 5% of persons will
suffer pulmonary arterial hypertension. Less commonly, the upper
respiratory tract (including the larynx, pharynx and sinuses) may be
affected, which occurs in between 5 and 10% of cases. Systemic sarcoidosis
Sarcoidosis 3

Sarcoidosis of the lungs can be divided into four stages. Stage 0 — No intrathoracic involvement. Stage I —
Bilateral hilar adenopathy. Stage II — Pulmonary parenchyma involved. Stage III — Pulmonary infiltrates with
fibrosis. Stage 4 is end-stage lung disease with pulmonary fibrosis and honeycombing.[8]

Skin
Main article: Cutaneous manifestations of sarcoidosis
Sarcoidosis involves the skin in between 9 and 37% of persons and is more common in African Americans than in
their white counterparts. The skin is the second most commonly affected organ, after the lungs. The most common
lesions are erythema nodosum, plaques, maculopapular eruptions, subcutaneous nodules and lupus pernio. Treatment
is not required, since the lesions usually resolve spontaneously in two to four weeks. Although it may be disfiguring,
cutaneous sarcoidosis rarely causes major problems. Sarcoidosis of the scalp presents with diffuse or patchy hair
loss.

Heart
The frequency of cardiac involvement varies and is significantly influenced by race; in Japan over 25% of persons
with sarcoidosis experience symptomatic cardiac involvement, whereas in the US and Europe only about 5% of
cases present with cardiac involvement. Autopsy studies in the US have revealed a frequency of cardiac involvement
of about 20–30%, whereas autopsy studies in Japan have shown a frequency of 60%. The presentation of cardiac
sarcoidosis can range from asymptomatic conduction abnormalities to fatal ventricular arrhythmia. Conduction
abnormalities are the most common cardiac manifestations of sarcoidosis among persons and can include complete
heart block. Second to conduction abnormalities, in frequency, are ventricular arrhythmias and occurs in about 23%
of persons with cardiac involvement. Sudden cardiac death, either due to ventricular arrhythmias or complete heart
block is a rare complication of cardiac sarcoidosis. Cardiac sarcoidosis can cause fibrosis, granuloma formation or
the accumulation of fluid in the interstitium of the heart or a combination of the former two.

Eye
Eye involvement occurs in about 11–83% of cases. Manifestations in the eye include uveitis, uveoparotitis, and
retinal inflammation, which may result in loss of visual acuity or blindness. The most common ophthalmologic
manifestation of sarcoidosis is uveitis. The combination of anterior uveitis, parotitis, VII cranial nerve paralysis and
fever is called uveoparotid fever (D86.8 [9]). Development of scleral nodule associated with sarcoidosis have been
observed.

Nervous system
Main article: Neurosarcoidosis
Any of the components of the nervous system can be involved. Sarcoidosis affecting the nervous system is known as
neurosarcoidosis. Cranial nerves are most commonly affected, accounting for about 5–30% of neurosarcoidosis
cases, and peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation of
sarcoidosis. It occurs suddenly and is usually transient. The central nervous system involvement is present in
10–25% of sarcoidosis cases. Other common manifestations of neurosarcoid include optic nerve dysfunction,
papilledema, palate dysfunction, neuroendocrine changes, hearing abnormalities, hypothalamic and pituitary
abnormalities, chronic meningitis, and peripheral neuropathy. Myelopathy, that is spinal cord involvement, occurs in
about 16–43% of neurosarcoidosis cases and is often associated with the poorest prognosis of the neurosarcoidosis
subtypes. Whereas facial nerve palsies and acute meningitis due to sarcoidosis tends to have the most favourable
prognosis. Another common finding in sarcoidosis with neurological involvement is autonomic or sensory small
fiber neuropathy. Neuroendocrine sarcoidosis accounts for about 5–10% of neurosarcoidosis cases and can lead to
diabetes insipidus, changes in menstrual cycle and hypothalamic dysfunction. The latter can lead to changes in body
Sarcoidosis 4

temperature, mood and prolactin (see the endocrine and exocrine section for details).

Endocrine and exocrine

Prolactin is frequently increased in sarcoidosis, between 3% and 32% of cases have hyperprolactinemia this
frequently leads to amenorrhea, galactorrhea or nonpuerperal mastitis in women. It also frequently causes an increase
in vitamin D production outside the kidney, namely inside the immune cells found in the granulomas the condition
produces. Hypercalciuria (excessive secretion of calcium in one's urine) and hypercalcemia (an excessively high
amount of calcium in the blood) are seen in <10% of individuals and likely results from the increased vitamin D
production. Thyroid dysfunction is seen in 4.2–4.6% of cases.
Parotid enlargement occurs in about 5–10% of persons. Bilateral involvement is the rule. The gland is usually not
tender, but firm and smooth. Dry mouth can occur; other exocrine glands are affected only rarely. The eyes, their
glands or the parotid glands are affected in 20%-50% of cases.

Gastrointestinal and genitourinary

Symptomatic GI involvement occurs in less than 1% of persons (note that this is if one excludes the liver), and most
commonly the stomach is affected, although the small or large intestine may also be affected in a small portion of
cases. Studies at autopsy have revealed GI involvement in less than 10% of people. These cases would likely mimic
Crohn's disease, which is a more commonly intestine-affecting granulomatous disease. About 1–3% of people have
evidence of pancreatic involvement at autopsy. Symptomatic kidney involvement occurs in just 0.7% of cases,
although evidence of kidney involvement at autopsy has been reported in up to 22% of people and occurs
exclusively in cases of chronic disease. Symptomatic kidney involvement is usually nephrocalcinosis, although
granulomatous interstitial nephritis that presents with reduced creatinine clearance and little proteinuria is a close
second. Less commonly, the epididymis, testicles, prostate, ovaries, fallopian tubes, uterus or the vulva may be
affected, the latter may cause vulva itchiness. Testicular involvement has been reported in about 5% of people at
autopsy. In males, sarcoidosis may lead to infertility.
Around 70% of people have granulomas in their livers, although only in about 20–30% of cases liver function test
anomalies reflecting this fact are seen. About 5–15% of persons exhibit hepatomegaly, that is an enlarged liver. Only
5–30% of cases of liver involvement are symptomatic. Usually, these changes reflect a cholestatic pattern and
include raised levels of alkaline phosphatase (which is the most common liver function test anomaly seen in persons
with sarcoidosis), while bilirubin and aminotransferases are only mildly elevated. Jaundice is rare.

Hematologic and immunologic

Abnormal clinical blood tests are frequent, accounting for over 50% of cases, but is not diagnostic. Lymphopenia is
the most common hematologic anomaly in sarcoidosis. Anemia occurs in about 20% of people with sarcoidosis.
Leukopenia is less common and occurs in even fewer persons but is rarely severe. Thrombocytopenia and hemolytic
anemia are fairly rare. In the absence of splenomegaly, leukopenia may reflect bone marrow involvement, but the
most common mechanism is a redistribution of blood T cells to sites of disease. Other nonspecific findings include
monocytosis, occurring in the majority of sarcoidosis cases, increased hepatic enzymes or alkaline phosphatase.
People with sarcoidosis often have immunologic anomalies like allergies to test antigens such as Candida or purified
protein derivative (PPD). Polyclonal hypergammaglobulinemia is also a fairly common immunologic anomaly seen
in sarcoidosis.
Lymphadenopathy (swollen glands) is common in sarcoidosis and occurs in 15% of cases. Intrathoracic nodes are
enlarged in 75 to 90% of all people; usually this involves the hilar nodes, but the paratracheal nodes are commonly
involved. Peripheral lymphadenopathy is very common, particularly involving the cervical (the most common head
and neck manifestation of the disease), axillary, epitrochlear, and inguinal nodes. Approximately 75% of cases show
microscopic involvement of the spleen, although only in about 5–10% of cases does splenomegaly appear.
Sarcoidosis 5

Bone, joints and muscles

Bone involvement in sarcoidosis has been reported in 1–13% of cases. About 5–15% of cases affect the bones, joints
or muscles.

Causes
The exact cause of sarcoidosis is not known. The current working hypothesis is, in genetically susceptible
individuals, sarcoidosis is caused through alteration to the immune response after exposure to an environmental,
occupational, or infectious agent. Some cases may be caused by treatment with TNF inhibitors like etanercept.

Genetics
The heritability of sarcoidosis varies according to race, about 20% of African Americans with sarcoidosis have a
family member with the condition, whereas the same figure for whites is about 5%. Investigations of genetic
susceptibility yielded many candidate genes, but only few were confirmed by further investigations and no reliable
genetic markers are known. Currently, the most interesting candidate gene is BTNL2; several HLA-DR risk alleles are
also being investigated. In persistent sarcoidosis, the HLA haplotype HLA-B7-DR15 are either cooperating in disease
or another gene between these two loci is associated. In nonpersistent disease, there is a strong genetic association
with HLA DR3-DQ2.

Infectious agents
Several infectious agents appear to be significantly associated with sarcoidosis, but none of the known associations is
specific enough to suggest a direct causative role. The major implicated infectious agents include: mycobacteria,
fungi, borrelia and rickettsia. A recent meta-analysis investigating the role of mycobacteria in sarcoidosis found it
was present in 26.4% of cases, but the meta-analysis also detected a possible publication bias, so the results need
further confirmation. Mycobacterium tuberculosis catalase-peroxidase has been identified as a possible antigen
catalyst of sarcoidosis. The disease has also been reported by transmission via organ transplants.

Autoimmune
Association of autoimmune disorders has been frequently observed. The exact mechanism of this relation is not
known, but some evidence supports the hypothesis that this is a consequence of Th1 lymphokine prevalence. Tests of
delayed cutaneous hypersensitivity have been used to measure progression.

Pathophysiology
Granulomatous inflammation is characterized primarily by accumulation of monocytes, macrophages and activated
T-lymphocytes, with increased production of key inflammatory mediators, TNF, IFN-γ, IL-2, IL-8, IL-10, IL-12,
IL-18, IL-23 and TGF-β, indicative of a Th1-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. Schaumann bodies seen in sarcoidosis are calcium and protein inclusions inside
of Langhans giant cells as part of a granuloma. While TNF is widely believed to play an important role in the
formation of granulomas (which 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 do still develop in persons being treated with TNF antagonists like etanercept. B cells also likely play a role in
Sarcoidosis 6

the pathophysiology of sarcoidosis. Serum levels of soluble HLA class I antigens and ACE are higher in persons
with sarcoidosis. Likewise the ratio of CD4/CD8 T cells in bronchoalveolar lavage is usually higher in persons 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.

Sarcoidosis in a lymph node Asteroid body in sarcoidosis Micrograph showing pulmonary

sarcoidosis with granulomas with
asteroid bodies, H&E stain

Diagnosis
Diagnosis of sarcoidosis is a matter of exclusion, as there is no specific test for the condition. To exclude sarcoidosis
in a case presenting with pulmonary symptoms might involve chest X-ray, CT scan of chest, PET scan, CT-guided
biopsy, mediastinoscopy, open lung biopsy, bronchoscopy with biopsy, endobronchial ultrasound and endoscopic
ultrasound with FNA of mediastinal lymph nodes (EBUS FNA). Tissue from biopsy of lymph nodes is subjected to
both flow cytometry to rule out cancer and special stains (acid fast bacilli stain and Gömöri methenamine silver
stain) to rule out microorganisms and fungi.
Serum markers of 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 (of at least 3.5) CD4/CD8 T cell ratio,
which is indicative (but not proof) of pulmonary sarcoidosis. In at least one study the induced sputum ratio of
CD4/CD8 and level of TNF was correlated to those in the lavage fluid.
Differential diagnosis includes metastatic disease, lymphoma, septic emboli, rheumatoid nodules, Wegener's
granulomatosis, varicella infection, tuberculosis and atypical infections, such as Mycobacterium avium complex,
cytomegalovirus and cryptococcus. Sarcoidosis is confused most commonly with neoplastic diseases, such as
lymphoma, or with disorders characterized also by a mononuclear cell granulomatous inflammatory process, such as
the mycobacterial and fungal disorders.
Sarcoidosis 7

Chest X-ray changes are divided into four stages:

• Stage 1: bihilar lymphadenopathy
• Stage 2: bihilar lymphadenopathy and
reticulonodular infiltrates
• Stage 3: bilateral pulmonary infiltrates
• Stage 4: fibrocystic sarcoidosis typically with
upward hilar retraction, cystic and bullous changes
Although people with stage 1 X-rays tend to have the
acute or subacute, reversible form of the disease, those
with stages 2 and 3 often have the chronic, progressive
CT scan of the chest showing lymphadenopathy (arrows) in the
disease; these patterns do not represent consecutive
mediastinum due to sarcoidosis
"stages" of sarcoidosis. Thus, except for epidemiologic
purposes, this X-ray categorization is mostly of historic
interest.
In sarcoidosis presenting in the Caucasian population, hilar adenopathy and erythema nodosum are the most
common initial symptoms. In this population, a biopsy of the gastrocnemius muscle is a useful tool in correctly
diagnosing the person. The presence of a noncaseating epithelioid granuloma in a gastrocnemius specimen is
definitive evidence of sarcoidosis, as other tuberculoid and fungal diseases extremely rarely present histologically in
this muscle.

Classification
Sarcoidosis may be divided into the following types:
• Annular sarcoidosis
• Erythrodermic sarcoidosis
• Ichthyosiform sarcoidosis
• Hypopigmented sarcoidosis
• Löfgren syndrome
• Lupus pernio
• Morpheaform sarcoidosis
• Mucosal sarcoidosis
• Neurosarcoidosis
• Papular sarcoid
• Scar sarcoid
• Subcutaneous sarcoidosis
• Systemic sarcoidosis
• Ulcerative sarcoidosis

Treatment
Most persons (>75%) only require symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) like
ibuprofen or aspirin. For persons 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. 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. Despite their widespread use, the evidence supporting
Sarcoidosis 8

corticosteroid use is weak at best.

Severe symptoms are generally treated with corticosteroids although steroid-sparing agents such as azathioprine,
methotrexate, mycophenolic acid and leflunomide are often used as alternatives. Of these methotrexate is most
widely used and studied. Methotrexate is considered a first-line treatment in neurosarcoidosis, often in conjunction
with corticosteroids. Long-term treatment with methotrexate is associated with liver damage in about 10% of people
and hence may be a significant concern in people with liver involvement and requires regular liver function test
monitoring. Methotrexate can also lead to pulmonary toxicity (lung damage), although this is fairly uncommon and
more commonly it can confound the leukopenia caused by sarcoidosis. Due to these safety concerns it is often
recommended that methotrexate is combined with folic acid in order to prevent toxicity. Azathioprine treatment can
also lead to liver damage. Leflunomide is being used as a replacement for methotrexate, possibly due to its
purportedly lower rate of pulmonary toxicity. Mycophenolic acid has been used successfully in uveal sarcoidosis,
neurosarcoidosis (especially CNS sarcoidosis; minimally effective in sarcoidosis myopathy) and pulmonary
sarcoidosis.
As the granulomas are caused by collections of immune system cells, particularly T cells, there has been some
success using immunosuppressants (like cyclophosphamide, cladribine, chlorambucil and cyclosporine),
immunomodulatory (pentoxifylline and thalidomide) and anti-tumor necrosis factor treatment (such as infliximab,
etanercept, golimumab and adalimumab).
In a clinical trial cyclosporine added to prednisone treatment failed to demonstrate any significant benefit over
prednisone alone in people with pulmonary sarcoidosis, although there was evidence of increased toxicity from the
addition of cyclosporine to the steroid treatment including: infections, malignancies (cancers), hypertension and
kidney dysfunction. Likewise chlorambucil and cyclophosphamide are seldom used in the treatment of sarcoidosis
due to their high degree of toxicity, especially their potential for causing malignancies. Infliximab has been used
successfully to treat pulmonary sarcoidosis in clinical trials in a number of persons. Etanercept, on the other hand,
has failed to demonstrate any significant efficacy in people with uveal sarcoidosis in a couple of clinical trials.
Likewise golimumab has failed to show any benefit in persons with pulmonary sarcoidosis. One clinical trial of
adalimumab found treatment response in about half of subjects, which is similar to that seen with infliximab, but as
adalimumab has better tolerability profile it may be preferred over infliximab.
Ursodeoxycholic acid has been used successfully as a treatment for cases with liver involvement. Thalidomide has
also been tried successfully as a treatment for treatment-resistant lupus pernio in a clinical trial, which may stem
from its anti-TNF activity, although it failed to exhibit any efficacy in a pulmonary sarcoidosis clinical trial.
Cutaneous disease may be successfully managed with antimalarials (such as chloroquine and hydroxychloroquine)
and the tetracycline antibiotic, minocycline. Antimalarials have also demonstrated efficacy in treating
sarcoidosis-induced hypercalcemia and neurosarcoidosis. Long-term use of antimalarials is limited, however, by
their potential to cause irreversible blindness and hence the need for regular ophthalmologic screening. This toxicity
is usually less of a problem with hydroxychloroquine than with chloroquine, although hydroxychloroquine can
disturb the glucose homeostasis.
Recently selective phosphodiesterase 4 (PDE4) inhibitors like apremilast (a thalidomide derivative) and roflumilast
and the less subtype-selective PDE4 inhibitor, pentoxifylline, have been tried as a treatment for sarcoidosis, with
successful results being obtained with apremilast in cutaneous sarcoidosis in a small open-label study. Pentoxifylline
has been used successfully to treat acute disease although its use is greatly limited by its gastrointestinal toxicity
(mostly nausea, vomiting and diarrhea). Case reports have supported the efficacy of rituximab, an anti-CD20
monoclonal antibody and a clinical trial investigating atorvastatin as a treatment for sarcoidosis is under-way.
Nicotine patches have been found to possess anti-inflammatory effects in sarcoidosis patients, although whether they
had disease-modifying effects requires further investigation. Antimycobacterial treatment (drugs that kill off
mycobacteria, the causative agents behind tuberculosis and leprosy) has also proven itself effective in treating
chronic cutaneous (that is, it affects the skin) sarcoidosis in one clinical trial. Quercetin has also been tried as a
Sarcoidosis 9

treatment for pulmonary sarcoidosis with some early success in one small trial.
Because of its uncommon nature, the treatment of male reproductive tract sarcoidosis is controversial. Since the
differential diagnosis includes testicular cancer, some recommend orchiectomy, even if evidence of sarcoidosis in
other organs is present. In the newer approach, testicular, epididymal biopsy and resection of the largest lesion has
been proposed.

Prognosis
The disease can remit spontaneously or become chronic, with
exacerbations and remissions. In some persons, it can progress to
pulmonary fibrosis and death. About half of cases resolve without
treatment or can be cured within 12–36 months, and most within five
years. 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, although, corticosteroids appear effective in improving AV
conduction. The prognosis tends to be less favourable in African Gross pathology image showing sarcoidosis with
honeycombing: Prominent honeycombing is
Americans, compared to white Americans. Persons with sarcoidosis
present in the lower lobes accompanied by
appear to be at significantly increased risk for cancer, in particular lung fibrosis and some honeycombing in the upper
cancer, lymphomas, and cancer in other organs known to be affected in lungs. Honeycombing consists of cystically
sarcoidosis. In sarcoidosis-lymphoma syndrome, sarcoidosis is dilated airways separated by scar tissue
resembling the honeycomb of bees. It is a
followed by the development of a lymphoproliferative disorder such as
nonspecific end stage of many types of interstitial
non-Hodgkin lymphoma. This may be attributed to the underlying lung disease.
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.

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. See 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
Sarcoidosis 10

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 persons, ophthalmologic and
cardiac involvement are more common than in other races.
It is more common in certain occupations, namely firefighters, educators, military personnel, persons 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).

History
It was first described in 1877 by Dr. Jonathan Hutchinson, a dermatologist as a condition causing red, raised rashes
on the face, arms and hands. In 1888 the term Lupus pernio was coined by Dr. Ernest Besnier, another dermatologist.
Later in 1892 lupus pernio's histology was defined. In 1902 bone involvement was first described by a group of three
doctors. Between 1909 and 1910 uveitis in sarcoidosis was first described, and later in 1915 it was emphasised, by
Dr. Schaumann, that it was a systemic condition. This same year lung involvement was also described. In 1937
uveoparotid fever was first described and likewise in 1941 Löfgren syndrome was first described. In 1958 the first
international conference on sarcoidosis was called in London, likewise the first USA sarcoidosis conference occurred
in Washington, DC in the year 1961. It has also been called Besnier-Boeck disease or Besnier-Boeck-Schaumann
disease.

Society and culture

There exists a society on sarcoidosis and related conditions called, the World Association of Sarcoidosis and other
Granulomatous disease (WASOG), whose purpose is to organise meetings for physicians involved in sarcoidosis and
related conditions and to inform interested individuals. WASOG has its own journal too, Sarcoidosis, vasculitis, and
diffuse lung diseases. There is also an organisation called the Foundation for Sarcoidosis Research (FSR), devoted to
supporting research into sarcoidosis and its possible treatments. There has also been some concerns that rescue
workers for the World Trade Center are at a heightened risk for sarcoidosis.
In 2014, in a letter to the British medical journal The Lancet, it was suggested that the French Revolution leader
Maximilien Robespierre suffered from sarcoidosis, and suggested that the condition caused him a notable
impairment during his time as the head of the Reign of Terror.

Pregnancy
Sarcoidosis generally does not prevent successful pregnancy and delivery; the increase in estrogen levels during
pregnancy may even have a slightly beneficial immunomodulatory effect. In most cases, the course of the disease is
unaffected by pregnancy, with improvement in a few cases and worsening of symptoms in very few cases, although
it is worth noting that a number of the immunosuppressants (such as methotrexate, cyclophosphamide and
azathioprine) used in corticosteroid-refractory sarcoidosis are known teratogens.
Sarcoidosis 11

References
[1] http:/ / apps. who. int/ classifications/ icd10/ browse/ 2010/ en#/ D86
[2] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=135
[3] http:/ / omim. org/ entry/ 181000
[4] http:/ / www. diseasesdatabase. com/ ddb11797. htm
[5] http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 000076. htm
[6] http:/ / www. emedicine. com/ med/ topic2063. htm
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Article Sources and Contributors 12

Article Sources and Contributors

Sarcoidosis Source: http://en.wikipedia.org/w/index.php?oldid=614969950 Contributors: -Anthony-, 564dude, AManWithNoPlan, Aaron.eshbach, Abe (or Abraham), Adeez, AerynPK,
Ah1532, Ajsmen91, Aleenf1, Alex.tan, Amoosa, Aranel, Arcadian, Auntof6, AxelBoldt, Axl, Bender235, Bgwhite, Bobo192, Boghog, Brianhe, Briséis, Broncko, Bruxism, CABoge,
Capricorn42, Cglion, Christopherlin, CliffC, Countincr, Craig Pemberton, Curb Chain, Cutler, Cyde, DBigXray, Dale 2009, David.Monniaux, DeathInformer, DennyColt, Derekfong,
Derekgillespie, Diptanshu.D, Discospinster, Dmdpublicity, Doctorwolfie, Docu, Download, Draeco, Dratman, Drjames1, Druep, Dryman, Duckyouintheahhhole, Earthbee24, Edward4882, Ejdjr,
EoGuy, Eras-mus, Ethethethetheth, Evanherk, Expergefactionist, Faigl.ladislav, Flameboylb, Flyer22, Foonly, Frycookonvenus, Fuse809, Gail, Gak, Giftlite, Gigemag76, GinaDana, Gmaxwell,
GoingBatty, Gongshow, Graham87, GregorB, H.gosker, HMSSolent, Haeleth, Halcionne, Harrisd5917, Headbomb, Hordaland, Hydrogen Iodide, J.delanoy, JackofOz, Jaeger5432, Jchakrav,
Jdaloner, JeLuF, Jetman, Jfdwolff, Jmarchn, Jmh649, JoeSmack, John Nevard, Juicyfendi, Jusdafax, JustAGal, Kbir1, Kesac, Killdevil, Kirkburn, LT910001, Laura1290x, Lemonflash,
Liborrateus, Lwalt, Mamaschmo, Mansell, MarcoTolo, Marcofontes, Marcok, Marek69, Marknyc, Marylauran, Maxdillon, Mfitzryan, Michael Bailes, Mikael Häggström, Mike2vil,
Mmoneypenny, Mogism, MovieMan123, Muad, My Core Competency is Competency, N2e, Nbauman, Nephron, Netha Hussain, Neurojc, Nihiltres, Nkaminski, Nono64, NuclearWarfare,
Nunh-huh, Nurg, Oanabay04, Osm agha, Patxi lurra, Pdeitiker, Permacultura, PhilKnight, Philip Trueman, Prabash.A, Pumpie, R'n'B, RDBrown, Ratel, Redrose64, Rhcameron, Rich Farmbrough,
Richiez, Rjwilmsi, Rklawton, Roman à clef, RoyBoy, Ryan-McCulloch, Rytyho usa, S h i v a (Visnu), Sarabrate, Savisha, Scarian, Scott Wilson, Scottanon, Sean William, Seaphoto, SidP,
SimmonsILD, Siouxsherat, Smith609, Snorkelman, Sohale, Some jerk on the Internet, SpecialReport, Sph.md, Spiffulent, Spitfire, Spnrhntr, Stibolt, Su-steve, Superbeecat, THEN WHO WAS
PHONE?, TLSuda, Tentinator, Thingg, Thisglad, Timur lenk, ToMMiTTo, Tom.davey, Tommy2010, Tommysalts, Toplosky, Trevmar, Trice83, Tristanb, Tumblingsky, TylerDurden8823,
Unused0026, Vedran12, Venustar84, VirtualDelight, Vogon77, VonWoland, WLU, Washburnmav, Wawot1, Widr, William Avery, Williwa, Wolters1, Wouterstomp, Zack wadghiri, Zasleep,
434 anonymous edits

Image Sources, Licenses and Contributors

File:APSarcoid.PNG Source: http://en.wikipedia.org/w/index.php?title=File:APSarcoid.PNG License: Creative Commons Attribution-Sharealike 3.0 Contributors: Jmh649
File:Sarcoidosis signs and symptoms.png Source: http://en.wikipedia.org/w/index.php?title=File:Sarcoidosis_signs_and_symptoms.png License: Public Domain Contributors: NHLBI authors.
Minor editing by Mikael Häggström (compare with original jpg-version below)
Image:Cutaneous findings in systemic sarcoidosis.JPEG Source: http://en.wikipedia.org/w/index.php?title=File:Cutaneous_findings_in_systemic_sarcoidosis.JPEG License: Creative
Commons Attribution-Sharealike 2.0 Contributors: Nowack et al.
Image:Sarcoidosis_(1)_lymph_node_biopsy.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Sarcoidosis_(1)_lymph_node_biopsy.jpg License: Creative Commons
Attribution-ShareAlike 3.0 Unported Contributors: Alex brollo, KGH, 1 anonymous edits
Image:Asteroid Body in Sarcoidosis.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Asteroid_Body_in_Sarcoidosis.jpg License: Creative Commons Attribution-Sharealike 2.0
Contributors: Ed Uthman, MD
Image:Asteroid body intermed mag.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Asteroid_body_intermed_mag.jpg License: Creative Commons Attribution-Sharealike 3.0
Contributors: Nephron
Image:Sarkoidose1 CT axial.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Sarkoidose1_CT_axial.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors:
Hellerhoff
File:Sarcoidosis - Honeycombing.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Sarcoidosis_-_Honeycombing.jpg License: Creative Commons Attribution-Sharealike 2.0
Contributors: Yale Rosen

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