This is an HTML version of an attachment to the Freedom of Information request 'Atos doctors directives'.

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Tuberculosis & Sarcoidosis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Document control 
 
Version history 
Version Date 
Comments 
1a Draft 
October 2008 
Initial Draft 
1b (rev) 
March 2009 
Reformatted and re-ordered 
1c (rev) 
April 2009 
Inter author review 
1d with int. QA  May 2009 
Dr Gill Buchanan’s comments incorporate 
1e draft 
Jan 2010 
External review comments by Dr Munro 
1 Final 
14 October 2010 
Signed off by CMMS 
 
 
 
Changes since last version 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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A.   TUBERCULOSIS 
 
 
 
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Introduction 
Definition 
 
Tuberculosis is a chronic, progressive infection with a period of latency 
following initial infection. It occurs most commonly in the lungs. Pulmonary 
symptoms include productive cough, chest pain, and dyspnoea. Diagnosis is 
by sputum culture and smear. Treatment is with multiple antimicrobial agents.  
 
 
Tuberculosis (TB) is an infectious disease caused by the bacterium 
Mycobacterium tuberculosis, also known as 'the tubercle bacillus'.   
 
TB commonly affects the lungs, but can reach any part of the body. 
 
It is usually spread by the coughs or sneezes of an infected person, but is    
       not highly contagious. 
 
Prolonged close contact with a person with TB, for example, living in the       
       same household is usually necessary for infection to be passed on. 
 
It may take many years before someone infected with TB develops the full    
       disease. 
 
 
Tuberculosis is a ‘Notifiable Disease’ under the Public Health (Infectious 
Diseases) Regulations 1988 and must be reported to the Health Protection 
Agency. 
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Description 
Epidemiology 
 
Tuberculosis (TB) has been identified in human remains more than 9,000 years 
old. 
 
It is the leading infectious cause of morbidity and mortality in adults worldwide, 
killing about 2 million people every year. 
 
About 1.6 billion are infected worldwide. Of these, only 15 million have active 
disease at any given time. Case rates vary widely by country, age, race, sex, 
and socioeconomic status. 
 
According to WHO figures 26 of the 30 countries with the greatest TB load are 
in Africa, and many of these have a prevalence 10 times more than the 40 
cases per 100,000 per year figure required to qualify as a ‘high load country’. 
 
HIV infection is the greatest single medical risk factor because  
cell-mediated immunity, which is impaired by HIV, is essential for defence 
against TB; other immunosuppressive illnesses (e.g. diabetes) or therapies 
(e.g. corticosteroids) are risks but less so than HIV. 
 
TB is still a major problem in many countries. It has been on the increase in the 
developed world in recent years, probably because of increased air travel and 
movement of people from areas where it is common. 
 
In the UK from September 2005, a new targeted programme of BCG 
vaccination was introduced. Only those people at high risk of contracting TB 
will be vaccinated, as opposed to all school children. 
Prevalence 
 
TB worldwide is a massive problem and large numbers die annually.  
In England cases fell progressively until the mid-1980s but started to rise again 
in the early 1990s.  
 
In 2006, there were 8497 cases of TB reported in the UK (14.0 per 100,000) 
and the London region accounted for 40% of cases (44.8 per 100,000). TB is 
potentially curable with a course of specific antibiotics taken for at least 6 
months.  
 
         About 8000 new cases of TB are currently reported each year in the United       
         Kingdom. Most cases occur in major cities, particularly in London1
 
The most important part of controlling TB is identifying and treating those who 
already have the disease, to shorten their infection and to stop it being passed 
on to others.2  
 
 
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Aetiology 
 
TB properly refers only to disease caused by Mycobacterium tuberculosis (M. 
tuberculosis).  
 
Similar disease occasionally results from M. bovisM. africanum, and  
M. microti
 
In the United Kingdom TB occurs almost exclusively from inhalation of droplet 
nuclei containing M. tuberculosis. They disperse primarily through coughing, 
singing, and other forced respiratory manoeuvres by a person with active 
pulmonary disease. 
 
People with cavitating pulmonary lesions are especially infectious. Droplet 
nuclei containing tubercle bacilli may float on room-air currents for several 
hours, increasing the chance of spread. About 25% of household contacts 
acquire infection. Healthcare practitioners who have close contact with active 
cases have increased risk. 
 
Transmission is enhanced by overcrowding; thus, people living in poverty or in 
institutions are at particular risk. Once effective treatment begins, however, 
cough rapidly decreases, and after two  weeks, TB is no longer contagious. 
Fomites (e.g. clothes or bedding) do not appear to facilitate spread. 
Pathophysiology
 
Tubercle bacilli initially produce a primary infection, followed by a latent 
(dormant) phase and then, in some cases, by active disease. Infection is not 
transmissible in the primary and latent phases. 
 
 
Primary infection:  
Airborne droplet nuclei lodge in sub-pleural terminal airspaces, predominantly 
in the lower lung, usually in only one site. Tubercle bacilli replicate inside 
macrophages, ultimately killing them. Inflammatory cells are attracted to the 
area, causing a tubercle to form and in some cases pneumonitis. In the early 
weeks of infection, some infected macrophages are carried to regional lymph 
nodes (eg, hilar, mediastinal). Haematogenous spread to any part of the body, 
particularly the apical-posterior portion of the lungs, epiphyses of the long 
bones, kidneys, vertebral bodies, and meninges, may occur. 
 
In 95% of cases, after about 3 weeks of uninhibited growth, the immune system 
suppresses bacillary replication.  This may happen before symptoms or signs 
develop. Foci of infection in the lung or other sites resolve into epithelioid cell 
granulomas, which may have caseous and necrotic centres; tubercle bacilli can 
survive in this material for years, the host's resistance determining whether the 
infection ultimately resolves without treatment, remains dormant, or becomes 
active. 
 
Foci may leave nodular scars in the apices of one or both lungs (Simon foci), 
calcified scars from the primary infection (Ghon foci), or calcified hilar lymph 
nodes. The tuberculin skin test is positive. 
 
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Rarely, the primary focus immediately progresses especially in infants or young 
children with other debilitating diseases, causing acute, potentially fatal, illness 
with pneumonia, pleural effusion, and marked mediastinal or hilar lymph node 
enlargement (which in children may compress bronchi). Small pleural effusions 
are predominantly lymphocytic, typically contain few organisms, and clear 
within a few weeks. 
 
Primary extra-pulmonary TB at any site can sometimes present without 
evidence of lung involvement. While TB lymphadenopathy is the most common 
extra-pulmonary presentation, meningitis is the most feared because of its high 
mortality in the very young and very old. 
 
Active disease: 
 
In about 10% of patients overall, latent infection develops into active disease, 
although the percentage varies significantly depending on age and other risk 
factors. In 50 to 80% of those who develop active disease, TB reactivates 
within the first 2 years, but it can occur decades later. Any organ initially 
seeded may be a site of reactivation, but reactivation occurs most often in the 
lung apices, where O2 tension is highest.  
 
Ghon foci and affected hilar lymph nodes are much less likely to be sites of 
reactivation. 
 
Conditions that facilitate activation include: 
 
impaired immunity (particularly HIV infection) 
 
certain immunosuppressant drugs (eg, corticosteroids, infliximab and other 
       tumour necrosis factor blockers (TNF antagonists) 
 
gastrectomy, jejunoileal bypass surgery, silicosis, renal insufficiency,          
       stress, diabetes, head or neck cancer, 
 
Adolescence, and advanced age (> 70 yr). 
 
TB damages tissues through delayed hypersensitivity, typically producing: 
 
Granulomatous necrosis with a caseous histological appearance. 
 
Cavitating Lung lesions 
 
Pleural effusions. This is less common than in progressive primary TB but  
       may occur from direct extension or haematogenous spread. 
 
Rupture of a large tuberculous lesion into the pleural space may produce   
       empyema with or without broncho-pleural fistula; it sometimes causes        
       pneumothorax. 
 
The course varies greatly, depending on the virulence of the organism and the 
state of host defences. The course may be rapid among African Americans, 
Afro-Caribbeans and American Indians who have not had as many centuries of 
selective pressure to develop innate or natural immunity. 
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Diagnosis
Symptoms and Signs 
In active pulmonary TB, even with moderate or severe disease, the patient 
may have no symptoms except ‘not feeling well’ or may have more specific 
symptoms. 
 
 
Cough is most common. 
       At first, it may be minimally productive of yellow or green sputum, usually 
       on rising, but cough may become more productive as the disease             
       progresses. 
 
 
Drenching night sweats are a classic symptom but are neither common in 
       nor specific for TB. 
 
 
Dyspnoea may result from lung parenchymal involvement, spontaneous   
       pneumothorax, or pleural involvement with effusion. 
 
 
Haemoptysis occurs only with cavitating TB. 
 
 
Weight Loss 
Recommended investigations 
Latent TB 
To diagnose latent TB: 
  
  Mantoux testing should be performed 
 
  Those with positive results (or in whom Mantoux testing may be less 
reliable) should then be considered for interferon-gamma immunological 
testing, if available. 
 
  If testing is inconclusive, the person should be referred to a TB specialist.  
Active TB 
To diagnose active respiratory TB: 
  a posterior–anterior chest X-ray should be taken; chest X-ray 
appearances suggestive of TB should lead to further diagnostic 
investigation 
  multiple sputum samples (at least three, with one early morning 
sample) should be sent for TB microscopy and culture for suspected 
respiratory TB before starting treatment if possible or, failing that, 
within 7 days of starting 
  spontaneously produced sputum should be obtained if possible. 
Otherwise induction of sputum (by inhalation of saline) or 
bronchoscopy and lavage should be used 
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  in children unable to expectorate sputum, induction of sputum should 
be considered if it can be done safely, with gastric washings 
considered as third line  
If there are clinical signs and symptoms consistent with a diagnosis of TB, 
treatment should be started without waiting for culture results. The standard 
recommended regimen should be continued in patients whose subsequent 
culture results are negative 
Samples may be sent for TB culture from autopsy samples if respiratory TB is a 
possibility 
Active non-respiratory TB: 
The advantages and disadvantages of both biopsy and needle aspiration 
should be discussed with the patient, with the aim of obtaining adequate 
material for diagnosis. 
 
If non-respiratory TB is a possibility, part or all of any of the following samples 
should be placed in a dry pot (and not all placed in formalin) and sent for TB 
culture:  
 
 lymph 
node 
biopsy 
 
pus aspirated from lymph nodes 
 pleural 
biopsy 
 
any surgical sample sent for routine culture 
 
any radiological sample sent for routine culture 
 
histology sample  
 
aspiration sample (from pleural or pericardial effusions) 
 autopsy 
sample 
 
TB culture should routinely be performed on the above samples. 
The appropriate treatment regimen should be started without waiting for 
culture results if the histology and clinical picture are consistent with a 
diagnosis of TB. 
All patients with non-respiratory TB should have a chest X-ray to exclude 
or confirm co-existing respiratory TB 
The appropriate drug regimen should be continued even if subsequent 
culture results are negative.  
 
 
 
 
 
 
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Table 1 Suggested site-specific investigations in the diagnosis and 
assessment of non-respiratory TB  

 
Site Imaging 
Biopsy 
Culture 
Lymph node 
 
 Node 
  Node or aspirate 
Bone/joint 
 Plain X-ray and 
  Site of disease 
 Biopsy or 
computed tomography 
paraspinal 
(CT) 
abscess  
 Magnetic resonance 
  Site or joint fluid 
imaging (MRI)  
Gastrointestinal 
 Ultrasound 
 Omentum 
 Biopsy 
 
 CT abdomen 
 Bowel 
 Ascites 
Genitourinary 
  Intravenous urography  
  Site of disease 
 Early morning 
 
 Ultrasound 
 
urine (x3) 
  Site of disease 
 Endometrial 
curettings 
Disseminated 
 High-resolution CT 
 Lung 
 Bronchial wash 
thorax 
 Liver 
 Liver 
 Ultrasound abdomen 
 Bone marrow 
 Bone marrow 
 Blood 
Central nervous 
 CT brain 
 Tuberculoma 
 Cerebrospinal 
system 
 MRI 
 
fluid  
Skin  
  Site of disease 
  Site of disease 
Pericardium 
 Echocardiogram  
 Pericardium 
 Pericardial fluid 
Cold/liver 
 Ultrasound 
  Site of disease 
  Site of disease 
abscess 
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Treatment 
Management of respiratory TB4 
 
Respiratory TB is defined as active TB that is affecting any of the following: 
 
lungs 
 
pleural cavity 
 
mediastinal lymph nodes 
 
larynx 
Drug treatment 
Once a diagnosis of active TB is made, the clinician responsible for care should refer 
the person with TB to a physician with training in, and experience of, the specialised 
care of people with TB.  
 
TB in children should be managed either by a paediatrician with experience and 
training in the treatment of TB, or by a general paediatrician with advice from a 
specialised physician. 
 
A 6-month, four-drug initial regimen (6 months of Isoniazid and Rifampicin 
supplemented in the first 2 months with Pyrazinamide and Ethambutol) should be 
used to treat active respiratory TB in: 
  adults not known to be HIV-positive 
  adults who are HIV-positive  
  children 
This regimen is referred to as ‘standard recommended regimen’. 
Fixed-dose combination tablets should be used as part of any TB treatment 
regimen. 
Cure is possible in Multi-drug Resistant T B (MDRTB) using prolonged 
treatment with less effective, more expensive and more toxic drugs.  However, 
further resistance may develop and there is a high risk of treatment failure. 
Infection control 
  All patients with TB should have risk assessments for drug resistance and for 
            HIV.  
  A significant proportion of patients with TB do not require to be admitted to 
hospital.  Others require admission because they are seriously ill or require 
inpatient investigations.  In addition admission may be indicated for socio-
economic reasons perhaps where there are doubts about drug compliance 
due to learning difficulties or severe mental health problems including 
addictions. 
  If admitted to hospital, patients with suspected respiratory TB should be 
           given a single room. 
  Patients with respiratory TB should be separated from immuno-              
           compromised patients, either by admission to a single room on a            
           separate ward, or to a negative-pressure room on the same ward.  
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  Any visitors to a child with TB in hospital should be screened as part of  
           contact tracing, and kept separate from other patients until they have      
           been excluded as the source of infection. 
  Smear-positive TB patients without risk factors for Multi-Drug Resistant  
           TB (MDR TB) should be cared for in a single room, until:  
 
they have completed 2 weeks of the standard recommended regimen, or 
 
they are discharged from hospital  
 
  Aerosol-generating procedures such as bronchoscopy, sputum induction or    
            nebuliser treatment should be carried out in an appropriately engineered and 
            ventilated area for: 
  all patients on an HIV ward, regardless of whether a diagnosis of TB has    
    been considered 
     all patients in whom TB is considered a possible diagnosis, in any setting 
 
  Healthcare workers caring for people with TB should not use masks, gowns or 
           barrier nursing techniques unless: 
 
MDR TB is suspected 
 
aerosol-generating procedures are being performed 
                When such equipment is used, the reason should be explained to the         
                person with TB.  
The equipment should meet the standards of the Health and Safety Executive.  
  TB patients admitted to a setting where care is provided for HIV-positive or     
            other immunocompromised patients should be considered infectious and        
            should stay in a negative-pressure room until:  
(a) For people who were sputum smear positive at admission: 
1. 
they have had had at least 2 weeks of appropriate multiple drug                
            therapy, and 
2.  if moving to accommodation (inpatient or home) with HIV-positive or           
         immunocompromised patients, have had at least three negative                  
         microscopic smears on separate occasions over a 14-day period, and 
3.  are showing tolerance to the prescribed treatment and an ability and           
         agreement to adhere to treatment, and either 
4.  any cough has resolved completely, or 
5.  there is definite clinical improvement on treatment, for example remaining  
         afebrile for a week 
 
(b) For people who were sputum smear negative at admission (that is, three     
      negative samples were taken on separate days; samples were spontaneously   
      produced sputum if possible, or obtained by bronchoscopy or lavage if sputum   
      samples were not possible):  
all of 1, 2, 3 and 5 above should apply.  
 
  Inpatients with smear-positive respiratory TB should be asked (with                 
            explanation) to wear a surgical mask whenever they leave their room until      
            they have had 2 weeks of drug treatment. 
Management of non-respiratory TB - See Appendix A 
  
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Prognosis 
In immuno-competent patients with drug-susceptible pulmonary TB, even 
severe disease and large cavities usually heal if appropriate therapy is 
instituted and completed.  
 
TB still causes or contributes to death in about 10% of cases, often in those 
who are debilitated for other reasons.  
 
Disseminated TB and TB meningitis may be fatal in up to 25% of cases despite 
optimal treatment. TB is much more aggressive in immuno-compromised 
patients and, if not properly and aggressively treated, may be fatal in as little as 
2 months from its initial symptom. This is especially true of Multi-Drug Resistant 
TB (MDR- TB), in which mortality can approach 90%. 
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Main Disabling Effects 
Severe disability is uncommon unless the claimant has been ineffectively 
treated or is immunocompromised but can arise e.g. following TB affecting the 
CNS, pericardium or urogenital tracts.         
Respiratory TB 
Even in active pulmonary TB with moderate disease, the patient may have few 
symptoms and only very minimal disability due to a general malaise.  
Occasionally there may be a cough and/or night sweats which affect sleep and 
so add to the general malaise. 
 
Dyspnoea may result from lung parenchymal involvement and in this situation 
disability is unlikely to be more than mild to moderate. 
 
Spontaneous pneumothorax may give rise to an acute episode of 
breathlessness but should resolve with the appropriate treatment. 
 
Pleural involvement with effusion is likely to produce the longest period of 
breathlessness while any significant effusion is present. 
 
Pulmonary TB would normally be expected to respond to the anti-tuberculous 
medication with progressive reduction and complete resolution of symptoms 
over a period of 3 months. 
Non-respiratory TB 
 
Lymph Nodes 
Affected nodes are swollen and may be mildly tender or drain.  Adjacent nodes 
sometimes coalesce into an irregular mass. Usually the hilar lymph nodes are 
involved. Other nodes generally are not involved unless disease is poorly 
contained, allowing organisms to reach the thoracic duct, where they 
disseminate into the bloodstream. Most infected nodes heal, but reactivation 
commonly occurs. Infection in supraclavicular nodes may inoculate anterior 
cervical nodes, eventually resulting in Scrofula - TB lymphadenitis in the neck.   
  
TB peritonitis
Symptoms may be mild, with fatigue, abdominal pain, and tenderness, or 
severe enough to mimic acute abdomen.  
 
The “doughy abdomen” referred to in old textbooks is rarely present. 
 
TB pericarditis: 
Pericardial infection may develop from foci in mediastinal lymph nodes or from 
pleural TB. In some high incidence parts of the world, TB pericarditis is a 
common cause of heart failure. 
 
In Africa TB pericarditis is a common feature of AIDS. 
Constrictive pericarditis or tamponade may occur, producing dyspnoea, neck 
vein distension, paradoxical pulse, muffled heart sounds, and possibly 
hypotension
  

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TB of bones and joints
 
Symptoms include progressive or constant pain in involved bones and chronic 
or subacute arthritis (usually monoarticular). In Pott's disease, spinal cord 
compression produces neurological deficits, including paraplegia; paravertebral 
swelling may result from an abscess.  Weight-bearing joints are most 
commonly involved, but bones of the wrist, hand, and elbow also may be 
affected, especially after injury. 
 
Gastrointestinal TB: 
Gastrointestinal TB is usually caused by swallowing infected sputum. Intestinal 
invasion generally produces hyperplasia and an inflammatory bowel syndrome 
with pain, diarrhoea, obstruction, and melaena. It may also mimic appendicitis. 
Ulceration and fistulae are possible. 
 
TB of the liver:
 
Liver infection is common with advanced pulmonary TB and widely 
disseminated or miliary TB. However, the liver generally heals without sequelae 
when the principal infection is treated. TB in the liver occasionally spreads to 
the gallbladder, leading to obstructive jaundice 
 
TB meningitis: 
Meningitis often occurs in the absence of infection at other extra-pulmonary 
sites.  At any age, meningitis is the most serious form of TB and has high 
morbidity and mortality. It is the one form of TB believed to be prevented in 
childhood by vaccination with BCG. 
 
Symptoms are low-grade fever, unremitting headache, nausea, and 
drowsiness, which may progress to stupor and coma.  
 
Kernig's and Brudzinski's signs may be positive. 
Stages are: 
  clear sensorium with abnormal CSF, 
  drowsiness or stupor with focal neurological signs, and 
 Coma. 
 
 
Stroke may develop due to thrombosis of a major cerebral vessel. Focal 
neurological symptoms suggest a tuberculous mass intracranial lesion 
(tuberculoma). 
 
Genitourinary TB: 
Infection of the kidney may present as pyelonephritis (e.g. fever, back pain, 
pyuria) without the usual urinary pathogens on routine culture (“sterile pyuria”). 
Infection commonly spreads to the bladder and, in men, to the prostate, 
seminal vesicles, or epididymis, causing an enlarging scrotal mass. Infection 
may spread to the perinephric space and down the psoas muscle, sometimes 
causing an abscess on the anterior thigh. 
 
In women, salpingo-oophoritis can occur after menarche, when the fallopian 
tubes become vascular. Symptoms include chronic pelvic pain and sterility or 
ectopic pregnancy from tubal scarring. 
 
 
 
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Miliary TB: 
Also known as generalized haematogenous TB, miliary TB occurs when a 
tuberculous lesion erodes into a blood vessel, disseminating millions of 
tubercle bacilli into the bloodstream and throughout the body. The lungs and 
bone marrow are most often affected, but any site may be involved.  
 
Miliary TB is most common in children under 4 years old, immuno-
compromised people, and the elderly. 
 
Symptoms include fever, chills, weakness, malaise, and often progressive 
dyspnoea. Intermittent dissemination of tubercle bacilli may lead to a prolonged 
PUO (Pyrexia of Unknown Origin). Bone marrow involvement may produce 
anaemia, thrombocytopenia, or a leukaemoid reaction. 
 
Other sites: 
Rarely, TB may develop on abraded skin in a patient with cavitating pulmonary 
TB. TB may infect the wall of a blood vessel and has even ruptured the aorta. 
Adrenal involvement, leading to Addison's disease, formerly was common but 
now is rare. Trauma to a tendon sheath may cause tuberculous tenosynovitis in 
a patient with tuberculous involvement of any organ.  
 
 
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B.   SARCOIDOSIS 
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Introduction 
Definition 
 
Sarcoidosis is characterized by non-caseating granulomas in one or more 
organs and tissues and is of unknown aetiology.  
 
The lungs and lymphatic system are most often affected, but sarcoidosis may 
affect any organ.  
 
Diagnosis usually is first suspected because of pulmonary involvement and is 
confirmed by chest x-ray, biopsy, and exclusion of other causes of 
granulomatous inflammation.  
 
First-line treatment is corticosteroids.  
 
Prognosis is excellent for limited disease but poor for more advanced 
disease.  
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Description 
Epidemiology 
 
Sarcoidosis primarily affects people aged 20 to 40 but occasionally affects 
children and older adults.  
Prevalence 2, 4 
         Worldwide, prevalence is greatest in black Americans and northern Europeans, 
         especially Scandinavians, who have one of the highest incidence rates at 64     
         cases per 100,000 population. This contrasts with Poland, where the incidence 
         is reported as 3 cases per 100,000 population.  
 
The disease is rare in Eskimos, Southeast Asians, New Zealand Maoris, and 
native Canadian populations. 
 
Disease presentation varies widely by racial and ethnic background, with black 
Americans and Puerto Ricans demonstrating more frequent extra thoracic 
manifestations.  
 
Sarcoidosis is slightly more prevalent in women.  
 
Incidence increases in winter and early spring, for unknown reasons. 
Although sarcoidosis can appear at any age, a bimodal age distribution is seen, 
which peaks between ages 25-35 and 45-65 years. 
Aetiology
 
The cause of sarcoidosis remains obscure. One hypothesis is that sarcoidosis 
is an inflammatory response to an environmental agent (including infectious) 
which occurs in a susceptible host. Susceptibility is influenced by genetic 
predisposition. 
 
Several potential infectious agents have been proposed as causes of 
sarcoidosis. Although non-caseating, the granulomatous reaction reminds 
many of tuberculosis, and much effort has been expended trying to identify a 
mycobacterial cause. Several studies using polymerase chain reaction (PCR) 
and similar molecular biological techniques have been employed, but there is 
still no convincing evidence that Mycobacterium tuberculosis causes most 
cases of sarcoidosis. It may lead to an occasional case of sarcoid-like reaction. 
Other mycobacteria have been identified in some cases. Cell wall-deficient 
mycobacteria have been grown from the blood of patients with sarcoidosis. 
However, a recently completed control trial failed to demonstrate a difference in 
the incidence of cell wall-deficient mycobacteria between those with 
sarcoidosis and controls. 
 
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Pathophysiology 
 
Sarcoidosis is defined by its immunological reaction, the granuloma.  
Original immunological studies stressed a lack of systemic immune response 
by the patient with sarcoidosis. This includes anergy, the lack of reaction to any 
skin test, which is a common feature of active sarcoidosis. A reduction in 
circulating leucocytes, especially lymphocytes, is an important feature of the 
disease. 
 
In the 1970s, new techniques helped in the understanding of sarcoidosis. The 
most important tool introduced at the time was bronchoalveolar lavage, which 
provided a sample of the inflammatory cells in the lower respiratory tract. In 
normal lavage fluid, alveolar macrophages are the usual resident inflammatory 
cell retrieved; lymphocytes and neutrophils are found much less frequently. In 
lavage fluid from patients with active sarcoidosis, the preponderance of T 
lymphocytes is usually increased. These lymphocytes are often T-
helper/inducer cells (CD4+), and the ratio of CD4 to CD8 lymphocytes is 
increased from that normally found in the blood (0.8 to 2.2), often to greater 
than 3.5. 
 
The CD4 lymphocyte is a crucial cell in cell-mediated immunity. The CD4 
lymphocytes are activated and release several cytokines, including interleukin 
2 (IL-2) and γ-interferon. The T lymphocyte can mount either a TH1 or TH2 
response. The TH1 response is associated with granuloma formation, while 
TH2 is associated with an eosinophilic response and fibrosis. The initial 
response of sarcoidosis follows a TH1 pattern. The lymphocytes release IL-2 
spontaneously, and γ-interferon is released by both lymphocytes and 
macrophages. An increase in IL-12 and lower levels of IL-10 have also recently 
been described, consistent with a TH1 response. 
 
The resolution of sarcoidosis has also been studied with serial lavages. The T 
lymphocytes remain elevated for some time, but the proportion of CD4 to CD8 
decreases to the normal ratio found in blood (0.8 to 2.2). The amount of 
cytokines released also decreases. This return to normal of the inflammatory 
response has been shown to occur during treatment of sarcoidosis with 
corticosteroids or methotrexate. 
Genetic factors  
 
Familial clustering of cases has been reported. Monozygotic twins are 
2-4 times as likely to have the disease as dizygotic twins.  
 
Certain HLA associations have been demonstrated; the most 
common allele found in sarcoidosis is HLA-B8. Other associated 
alleles include HLA-A1 and HLA-DR3. 
Affected organs 
Commonly affected organs include the lung, skin, and eyes.  
Less commonly, the liver, heart, and brain are affected by the disease. 
Individual organ involvement by sarcoidosis can be proved by a biopsy 
showing non-caseating granuloma.  
 
Presumed organ involvement is assumed if certain criteria are met.  
Table 2 lists some of the criteria suggested for definite or probable organ 
involvement for some of the more commonly affected organs in sarcoidosis. 
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Lung 
Radiological evidence of respiratory involvement has been described in more 
than 90 per cent of patients. The lung involvement includes both the lymph 
nodes and the lung parenchyma.  
 
Scadding and Wurm independently described four stages of the chest 
radiograph: 
 
stage 1 is hilar adenopathy alone, 
 
stage 2 is adenopathy and parenchymal disease, 
 
stage 3 is parenchymal disease alone, and 
 
stage 4 is fibrosis 
 
Fibrotic changes due to sarcoidosis are usually in the upper lobe, with 
retraction. 
 
The staging system has proved useful in standardizing reports of pulmonary 
level of involvement. It has also proved a useful prognostic measure.  
Patients with stage 1 disease have a 90 per cent rate of resolution within 2 to 
3 years, while patients with stage 3 disease possess only a 30 per cent chance 
of resolution.  
 
However, it does not predict the degree of extra-pulmonary disease. The 
choice of the term ‘stage’ is therefore unfortunate. However, it is so standard 
that it will not be easily replaced. 
 
The use of the CT scan has changed our evaluation of many interstitial lung 
diseases.  
 
In sarcoidosis, peribronchial thickening is often seen in the upper lobe. 
Adenopathy is usually seen in sarcoidosis, making the staging system only 
applicable for plain radiographs. The CT scan may identify adenopathy in a 
patient with possible extra-pulmonary sarcoidosis. This may help in deciding 
where to proceed with a tissue diagnosis (lung biopsy or mediastinoscopy). 
Pulmonary function studies in patients with sarcoidosis classically demonstrate 
a restrictive pattern, with reduction of lung volumes. The transfer factor is 
usually reduced out of proportion to the loss of lung volume, as one would 
expect in an interstitial lung disease.  
 
In advanced cases, the oxygen level will be reduced, especially during 
exercise.  
 
Obstructive disease can also occur in sarcoidosis. This can be due to airway 
involvement by the sarcoidosis or associated with cough, a common complaint 
in the condition. 
 
Skin 
The skin is the second most commonly affected organ in sarcoidosis. There are 
six major manifestations.  
 
Hyperpigmentation, hypopigmentation, and keloid reaction may demonstrate 
granulomas on biopsy. However, their appearance is not always specific. 
Waxy, maculopapular lesions, which occur on the extremities, back, and face, 
are usually raised, with the majority less than 2 cm in diameter.  
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When these occur on the face, especially on the cheeks and nose, they are 
called lupus pernio.  
 
Erythema nodosum (red nodular lesions on the extremities which are acutely 
tender) usually involves the legs. The constellation of erythema nodosum, 
arthritis (in the ankles), hilar adenopathy, and uveitis is referred to as Lofgren’s 
syndrome and is a diagnostic manifestation of sarcoidosis. It is associated with 
a good prognosis. Interestingly, the skin lesions from erythema nodosum do 
not contain granulomas, but are considered to be due to circulating immune 
complexes from the disease. 
 
Eye 
The eye can be affected in more than 20 per cent of patients with sarcoidosis. 
The most common findings are uveitis and lacrimal gland involvement.  
Anterior uveitis is often self-limiting, and can be treated topically; however, 
posterior uveitis is a more chronic form of the disease and may require 
injections of corticosteroids or systemic therapy.  
 
Sicca (dry eyes) and glaucoma are long-term complications which are 
encountered in patients often years after other sarcoidosis symptoms have 
resolved. They are consequences of the fibrotic changes in the lacrimal glands 
and eye. They do not respond to anti-inflammatory therapy.  
 
Optic nerve involvement can be seen with sarcoidosis, with idiopathic disease 
and multiple sclerosis being the other major causes of this sight-threatening 
complication.  
 
Retinal disease has also been reported.  
Fortunately, blindness from sarcoidosis is rare, and usually a consequence of 
untreated uveitis, retinitis, or optic neuritis. 
 
Neurological 
Neurological disease from sarcoidosis includes cranial nerve, central nervous 
system, and peripheral nerve involvement.  
 
Bell’s palsy (seventh cranial nerve) is a common complaint in neurosarcoidosis. 
Central nervous system lesions can lead to a lymphocytic meningitis. 
Hypothalamic involvement is a characteristic finding, with diabetes insipidus as 
a resulting complaint.  
 
The use of contrast-enhanced magnetic resonance imaging is the most 
sensitive method for detecting central nervous system disease. The lumbar 
puncture is complementary, with increased protein and lymphocytes often seen 
in active disease. Detection of angiotensin-converting enzyme in the spinal fluid 
is suggestive but not diagnostic of neurosarcoidosis. 
 
Other manifestations 
Liver and spleen involvement may be found in over half of patients with 
sarcoidosis. However, symptomatic disease occurs in less than 10 per cent of 
patients. Often, elevated liver function tests (especially the alkaline 
phosphatase and γ-glutamyl transferase) are seen, suggesting an obstructive 
pattern. Hyperbilirubinaemia is relatively rare, but implies extensive disease 
and is usually an indication for therapy. Massive splenomegaly can occur, and 
occasionally splenectomy is performed to avoid rupture. 
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Hypercalcaemia and hypercalcinuria are seen with sarcoidosis.  
The mechanism is related to the effect of the granuloma on vitamin D3.  
The granuloma itself converts the vitamin D3 to the biologically active form 
1,25-D3. This form of the vitamin has immunological activity as well as 
enhancing calcium absorption from the gastrointestinal tract. In some patients 
with sarcoidosis, the 1,25-D3 can leak into the bloodstream and produce a 
systemic effect. Increased sunlight exposure also increases the levels of 1,25-
D3.  
 
In America, hypercalcaemia is far more common in Caucasian than African-
American individuals. Because of the effect of increased calcium absorption, 
urolithiasis may also be seen in patients with sarcoidosis. Recently, it has been 
rwecognised to be a marker for chronic disease. 
 
A less common, but serious complication of sarcoidosis is cardiac involvement. 
Direct involvement of the heart can lead to arrhythmias such as heart block and 
ventricular ectopy. This can lead to sudden death. If the problem is recognized, 
the use of an implanted defibrillator may reduce this risk.  
 
Cardiomyopathy is also seen, and cardiac sarcoidosis should be considered in 
a young patient who presents with unexpected heart failure. Endomyocardial 
biopsy rarely makes a diagnosis, since the granulomas are patchy. The 
technetium scan showing non-segmental fixed defects is the most sensitive 
test. Gallium uptake of the heart is more specific than a thallium scan. 
 
Sarcoidosis granulomas can involve virtually any organ of the body. Rare 
manifestations include bone cysts, usually in the distal portion of the fingers, 
sinus invasion, pleural disease, breast disease, and ovarian or testicular 
masses. 
 
The multi-organ involvement of sarcoidosis distinguishes it from other 
diseases. Lymphoma and tuberculosis are two diseases often considered in 
the differential diagnosis of patients with possible sarcoidosis.  
 
Table 2 
Organ  
Suggestive features 
Possible features  
Lung 
Positive biopsy of lung 
Lymphocytic alveolitis by bronchoalveolar 
lavage 
 
Chest radiograph characteristic for sarcoidosis (hilar 
Any other pulmonary infiltrate 
adenopathy, diffuse infiltrates, or upper lobe fibrosis) 
 
Pulmonary function tests showing restriction 
Isolated reduction of DLCO 
Skin 
Positive biopsy of skin 
Macular/papular lesion 
 
Lupus pernio 
New nodules (including subcutaneous) 
 
 
Erythema nodosum 
 
 
Annular lesion 
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Eyes 
Positive biopsy of eye 
Blindness 
 
 
Lacrimal gland swelling 
 
 
Uveitis 
 
 
Optic neuritis 
Liver 
Positive biopsy of liver 
Compatible CT scan 
 
Liver function tests more than 3 times normal  
Elevated alkaline phosphatase 
Neurological 
Positive biopsy of nerve tissue 
Other abnormalities on MRI 
 
MRI with gadolinium uptake in meninges, brainstem, or 
Unexplained neuropathy 
mass lesion 
 
Cerebral spinal fluid with increased lymphocytes or protein 
Positive electromyogram 
 
 
 
Organ  
Possible features  
Suggestive features  
 
Diabetes insipidus 
Neurological    
(con’d 
 
 
Cranial seventh nerve paralysis 
 
 
Other cranial nerve dysfunction 
Cardiac 
Positive cardiac biopsy 
Cardiomyopathy or ventricular arrhythmias 
without other cardiac problems 
 
Treatment-responsive cardiomyopathy 
 
 
ECG showing intraventricular or nodal block 
Positive thallium scan 
 
 
Positive gallium scan of heart 
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Diagnosis 
Symptoms and Signs
 
Patients with sarcoidosis may have a variety of presentations. 
 
Lung Symptoms  
 
Shortness of breath  
 
An unproductive cough  
 
Wheezing 
 
Pain in the middle of the chest that gets worse when breathing 
deeply or coughing (rare).  
 
Lymph Node Symptoms  
 
Enlarged and sometimes tender lymph nodes—most often those in 
the neck and chest but sometimes those under the chin, arm pits, 
or in the groin.  
 
Skin Symptoms  
 
Various types of bumps, ulcers, or, rarely, flat areas of discoloured 
skin, that appear mostly near the nose, eyes, back, arms, legs, 
and scalp. They usually itch but aren't painful. They may last a 
long time.  
 
Painful bumps that usually appear on the ankles and shins and 
can be warm, tender, red or purple-to-red in colour, and slightly 
raised (erythema nodosum).  These bumps may be associated 
with fever and swollen ankles and joint pain.  
 
Disfiguring skin sores that may affect the nose, nasal passages, 
cheeks, ears, eyelids, and fingers (lupus pernio). The sores tend to 
be ongoing and can return after treatment is over.  
 
Eye Symptoms  
 
Burning, itching, tearing, pain  
 
Red eye  
 
Sensitivity to light  
 
Dryness  
 
Floaters (i.e., seeing black spots)  
 
Blurred vision  
 
Reduced colour vision  
 
Reduced visual acuity  
 
Blindness (in rare cases). 
  
Heart Symptoms  
 
Shortness of breath  
 
Swelling in the legs  
 
Wheezing  
 
Coughing  
 
Irregular heartbeat,   
 
Sudden loss of consciousness  
 
Sudden death.  
 
 
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Joint and Muscle Symptoms  
 
Joint stiffness or swelling—usually in the ankles, feet, and hands.  
 
Joint pain.  
 
Myalgia.  
 
Muscle pain, a mass in a muscle, or muscle weakness.  
 
Painless arthritis that can last for months or even years. It should 
be treated.  
 
Bone Symptoms  
 
Painless holes in the bones.  
 
Painless swelling, most often in the fingers.  
 
Anaemia from granulomas affecting the bone marrow. This usually 
requires treatment.  
 
Liver Symptoms   
 
Fatigue  
 
Itching  
 
Pain in the upper right quadrant of the abdomen, under the right 
ribs  
 
Enlarged liver.  
 
Parotid and Other Salivary Gland Symptoms  
 
Swelling  
 
Excessive dryness in the mouth and throat.  
 
Blood, Urinary Tract, and Kidney Symptoms  
 
Increased calcium in the blood or urine, which can lead to kidney 
stones  
 
Confusion  
 
Polyuria which may be due to hypercalcaemia/renal impairment or 
diabetes insipidus 
 
Nervous System Symptoms  
 
Headaches.  
 
Vision problems.  
 
Weakness or numbness of an arm or leg.  
 
Coma (rare).  
 
7th nerve palsy. This can be confused with Bell's palsy, a disorder 
that may be caused by a virus.  
 
Paralysis of the arms or legs, from spinal cord involvement.  
 
Weakness, pain, or parasthesia in areas where many nerves are 
affected.  
 
Pituitary Gland Symptoms (Rare)  
 
Headaches  
 
Vision problems  
 
Weakness or numbness of an arm or leg  
 
Coma (rare).  
 
Other Symptoms  
 
Nasal obstruction or frequent bouts of sinusitis.  
 
Enlarged spleen, which leads to a decrease in platelets in the 
blood and splenic pain.  
 
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Sarcoidosis may also cause more general symptoms, including:  
 
Uneasiness, feeling sick (malaise), an overall feeling of ill health  
 
Tiredness, fatigue, weakness  
 
Loss of appetite or weight  
 
Fever  
 
Night sweats  
 
Sleep problems  
(All these general symptoms are often caused by other conditions.)  
Differential Diagnosis of Sarcoidosis 
 
Infectious  
Bacterial 
o Mycobacterial 
o TB 
 

Atypical mycobacteria  
o Syphilis 
 
Fungal  
o Aspergillosis 
o Blastomycosis 
o Coccidioidomycosis 
o Cryptococcal 
infection 
o Histoplasmosis 
 
Other 
o Brucellosis 

Cat-scratch disease (lymph nodes only) 
o Mycoplasmal 
infection 

Pneumocystis jiroveci (formerly P. carinii) 
 
Rheumatological  
o Juvenile 
RA 

Kikuchi's lymphadenitis (lymph nodes only) 
o Sjögren's 
syndrome 
o Wegener's 
granulomatosis 
 
Haematological malignancy 
o Hodgkin 
lymphoma 
o Non-Hodgkin 
lymphoma 
o Splenic 
lymphoma 
 
Hypersensitivity  
Occupational metals  
o Aluminium, 
Berylliosis 
o Titanium 
o Zirconium 
 
 
Organic antigens producing hypersensitivity pneumonitis  
o Actinomycetes 
o Atypical 
mycobacterial 
antigens 

Fungi Mushroom spores 

Other bio aerosols 
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Inorganic antigens producing hypersensitivity pneumonitis  
o Isocyanates 
o Pyrethrins 
o Drug 
reaction 
 
Other 

Inflammatory bowel disease 

foreign body aspiration or inoculation 
o granulomatous 
hepatitis 

granulomatous lesion of unknown significance 

lymphoid interstitial pneumonia 
 
Investigations 
 
Because the cause of sarcoidosis is unknown, one can never be absolutely 
confident of the diagnosis, which is always one of exclusion. However, the 
finding of non-caseating granulomas in two or more organs is considered 
diagnostic. Cultures and special stains for tuberculosis and deep-seated fungal 
infections should be taken to rule out infection as the cause of granulomas. 
Close examination should also be made for foreign bodies and malignancy, 
both of which can lead to a granulomatous reaction.  
 
Serum angiotensin-converting enzyme (ACE) levels 
In 1976, Lieberman reported that ACE level was elevated in the blood of some 
patients with sarcoidosis. 
 
Determining the significance of the ACE level in sarcoidosis can be difficult for 
a variety of reasons.  
 
Sixty per cent of patients with acute disease will have elevated values, whilst 
only 10 per cent of patients with disease for more than 2 years will continue to 
have an elevated level.  
 
The ACE level will decrease in response to treatment or disease resolution, 
and it has therefore been proposed as a marker for disease activity.  
 
Tests of the lung 
Bronchoalveolar lavage
: findings can be characteristic in sarcoidosis. The 
finding of increased lymphocytes, especially an increased CD4 to CD8 ratio, 
has been interpreted by some groups as enough to make the diagnosis of 
sarcoidosis, and in a patient with a compatible clinical history and no evidence 
for infection or malignancy, the lavage findings may be considered sufficient. 
 
Bronchoscopy: includes a transbronchial biopsy showing non-caseating 
granulomas. In over 60 per cent of patients with a stage 1 chest radiograph the 
biopsy should be positive, rising to 80 per cent in patients with stage 2 or 3 
disease. 
 
 
 
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Transbronchial needle aspiration: has recently been used to sample hilar 
lymph nodes, but raises the problem of incomplete sampling in patients with a 
malignancy and granulomatous response to the lesion.  
 
Mediastinoscopy and video-assisted thoracoscopy provide a minimally 
invasive method to obtain more tissue. 
 
Gallium scan can reveal increased activity in patients with sarcoidosis. 
Unfortunately, interpreting the uptake in the lung may be difficult as it is non-
specific and occurs with other inflammatory lung diseases. It also rapidly 
returns to normal with corticosteroid therapy. On the other hand, the uptake in 
the parotid and conjunctiva (the ‘panda’ sign) and the uptake in the hilar nodes 
(the ‘lambda’ sign) are fairly characteristic for sarcoidosis and are useful 
confirmation in difficult cases. 
 
Other tests 
The Kveim–Siltzbach agent is a suspension of spleen tissue from a patient 
with confirmed sarcoidosis. Six weeks after an intradermal injection of the 
agent, the site is inspected for a reaction, which will occur in over 60 per cent of 
patients with acute sarcoidosis. On biopsy, the reaction will show non-
caseating granulomas, consistent with sarcoidosis. Properly prepared Kveim–
Siltzbach agent has a less than 1 in 500 chance of causing a false positive. 
However, because of the difficulties in preparing the agent and concerns 
regarding the risk of transmission of an infectious agent, the test is rarely used 
except in those centres with a well established reagent. 
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Management 
The natural course of sarcoidosis is unclear, since corticosteroids are 
normally used to treat symptomatic patients. For the patient with no 
symptoms on presentation, the prognosis is often good and no treatment 
is indicated. This also applies to patients in whom spontaneous resolution 
can be anticipated. Spontaneous resolution commonly occurs within a 
year or two of diagnosis, but the disease can also take a chronic form, 
with symptoms for many years. The concept of acute disease, which lasts 
for less than 2 years, as opposed to chronic disease has been a useful 
method for considering patients, especially in terms of therapy.  
The table below lists several factors associated with resolution within 2 to 
5 years as well as those predicting chronic disease. 
 
Table 3 
Organ  
Acute  
Chronic  
Chest radiograph 
Stage 1 
Stage 4 
Skin 
Erythema nodosum 
Lupus pernio 
Eyes 
Anterior uveitis 
Posterior uveitis 
 
 
Pars planitis 
 
Joint involvement 
Bone cysts 
Calcium metabolism 
Hypercalcaemia 
Renal stones 
 
Cardiac 
Cardiomyopathy 
Neurological 
Cranial seventh nerve palsy 
Central nervous system mass 
 
Sinus 
Sinus involvement 
  
The major indication for therapy in sarcoidosis is symptoms. 
 
Hypercalcaemia should be treated, even if the patient is asymptomatic. 
 
An eye examination should be performed in all patients with sarcoidosis. 
Uveitis may be misdiagnosed as sicca (dry eyes). The former will require 
anti-inflammatory agents, while the latter will only need a wetting agent. 
If possible, treatment should be topical. Corticosteroid creams and eye 
drops are effective if inflammation is superficial.  
 
It is not clear whether corticosteroids change the natural course of the 
disease. Early randomized trials found no difference in the long-term 
outcome of patients who received corticosteroids compared with controls. 
A British Thoracic Society randomized study did demonstrate a small 
benefit for corticosteroids over placebo for patients with persistent, but 
not severe, disease. One of the difficulties in assessing this and other 
trials is that the more severely affected patients were treated with 
corticosteroids and excluded from the study. 
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Once systemic steroids are initiated a prolonged course is usually 
necessary.  
 
In the beginning, doses may be changed every 1 to 3 months, but after a 
patient remains stable on a lower dose (equivalent to less than 10 mg of 
prednisolone per day), tapering may be prolonged. The use of alternate-
day corticosteroids is strongly advocated by some, but others are less 
enthusiastic. Rarely will alternate-day therapy be sufficient for initial 
control of the disease. 
 
The toxicity of corticosteroids is well known. Unfortunately, most patients 
will require more than a year of treatment. 
 
Several alternatives to systemic corticosteroids have been proposed over 
the years.  
 
Table 4 
Drug  
Dosage  
Efficacy 
Toxicity  
Usage  
(%)  
Prednisone/ 
5–40 mg/day 
90 
Weight gain, diabetes, hypertension, 
Acute, chronic, 
osteoporosis, psychiatric 
refractory 
prednisolone 
Methotrexate 
10–25 mg once a week 
60–80 
Haematological, gastrointestinal, Chronic, 
lung, hepatic, mutagenic 
refractory 
Hydroxychloroquine 
200–400 mg/day 
30–50 
Gastrointestinal, retinal 
Acute, chronic 
Azathioprine 
50–200 mg/day 
50–80 
Haematological, gastrointestinal, Chronic, 
carcinogenic, mutagenic 
refractory 
Pentoxyfylline 
400 mg three times a 
50 
Gastrointestinal 
Acute 
day 
Cyclophosphamide 
50–150 mg/day orally, 
80 
Gastrointestinal, haematological, 
Chronic, 
refractory 
 
 
 
500–2000 mg every 2 
carcinogenic, bladder, teratogenic 
weeks intravenously 
Thalidomide 
50–100 mg/day 
80 
Teratogenic, somnolence, peripheral 
Chronic, 
neuropathy 
refractory 
 
The commonly prescribed antimalarial agents chloroquine and 
hydroxychloroquine possess anti-inflammatory activity with their major 
toxicities being eye and gastrointestinal. Because hydroxychloroquine, 
especially at 400 mg a day or less, is unlikely to cause eye toxicity, it is 
more frequently prescribed. However, some experts feel chloroquine is a 
more effective agent. These drugs concentrate in the skin and are most 
efficacious for skin disease and hypercalcaemia. They are less 
successful in the treatment of pulmonary disease.  
 
 
 
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In sarcoidosis, methotrexate has been most studied as a treatment for 
chronic disease. This probably reflects the fact that it may require 6 
months for the drug to become effective. The usual dose is 10 to 15 mg 
orally each week, adjusted if this proves toxic. Acute toxicity including 
mucositis and nausea can be minimized with supplements of folic acid at 
1 mg/day. The long-term toxicity of methotrexate can include 
hypersensitivity pneumonitis and cirrhosis. The latter is a concern, 
because 50 per cent of patients with chronic disease will have sarcoid 
granulomas in a liver biopsy, and thus liver biopsies are recommended 
every 2 years for patients requiring the drug long term. 
 
The response rate to methotrexate in chronic sarcoidosis is 60 to 80 per 
cent. Most patients who respond can be treated with methotrexate alone. 
Approximately 20 per cent of patients will require additional low-dose 
corticosteroids. In most patients skin lesions can be easily controlled with 
methotrexate, but studies have also reported benefit for disease in the 
lungs, eyes, and nervous system. 
 
Azathioprine has been used for many years as an immunosuppressant 
for patients receiving solid-organ transplants and those with idiopathic 
pulmonary fibrosis. However, its use in sarcoidosis has been more 
sporadic, usually reserved for chronic cases. Its major side-effects are 
gastrointestinal and haematological. 
 
Other drugs have been used for refractory sarcoidosis. 
 
  Cyclophosphamide is used in the treatment of many 
vasculitic diseases and has been reported as very useful in 
neurological and cardiac sarcoidosis, but it has more 
gastrointestinal, haematological, and bladder toxicity than 
methotrexate or azathioprine. 
 
  Cyclosporin has been used with limited success in some 
neurological cases. A recent randomized trial failed to show 
additional benefit over corticosteroids alone in patients with 
pulmonary sarcoidosis. The drug is relatively expensive, 
causes hypertension and renal failure, and requires blood 
levels to be monitored.  
 
  Pentoxyfylline has been shown by one centre to provide 
some benefit in acute sarcoidosis. It is associated with 
significant gastrointestinal toxicity, which is dose dependent. 
 
There is no single treatment for all patients with sarcoidosis
 
It is important to determine whether the patient requires treatment.  
The decision to treat is usually based on the patient’s symptoms.  
 
The clinician needs to determine the extent of the symptomatic disease 
and whether the disease is acute or chronic. Asymptomatic or minimally 
symptomatic patients with hypercalcaemia, cardiac, or central nervous 
system disease may require therapy to prevent life-threatening 
complications.  
 
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The use of systemic therapy usually means corticosteroids first. However, 
over time, the patient and the physician may need to seek alternatives. 
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Prognosis 
The course of sarcoidosis is variable, ranging from self-limiting acute 
disease to a chronic debilitating disease that may result in death. 
 
 
the majority of cases will resolve within 2 to 5 years 
 
 
Approximately 25 per cent of patients will develop residual fibrosis 
 
 
10-30% of patients have a more chronic or progressive course. 
For the patient with chronic disease, treatment can usually palliate the 
symptoms. However, organ failure, including eye, liver, cardiac, or 
respiratory, can occur as a result of disease. 
 
 
The mortality rate is 1-6%. 
Sarcoidosis can lead to death from severe involvement of lung 
parenchyma leading to pulmonary fibrosis and respiratory failure and 
from myocardial involvement leading to arrhythmias and cardiac 
failure 
 
Organ transplantation has been performed successfully in patients with 
sarcoidosis. Although sarcoidosis lesions can occur in the new organ, 
organ failure due to recurrent sarcoidosis is unlikely. 
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Main Disabling Effects 
Respiratory disease 
 
As 90% of cases involve the lungs the common disabilities arising from 
sarcoidosis are due to impaired lung function. 
 
Shortness of breath  
 
A dry cough that doesn't bring up phlegm, or mucus  
 
Wheezing 
 
Pain in the middle of the chest that gets worse when breathing       
                  deeply or coughing (rare).  
 
However as only in advanced cases will the oxygen levels be reduced by 
exercise the level of disability due to pulmonary sarcoidosis itself, in the 
majority of patients means significant disability is unlikely. 
 
Where the patient is requiring treatment for more advanced or symptomatic 
disease any disability is likely to arise either from the treatment or any extra 
pulmonary manifestation of the disease. 
 
Sarcoidosis may cause general symptoms, including:  
 
Uneasiness, feeling sick (malaise), an overall feeling of ill health  
 
Tiredness, fatigue, weakness  
 
Loss of appetite or weight  
 
Fever  
 
Night sweats  
 
Sleep problems  
Non - Respiratory 
 
Ocular involvement occurs in 25% of cases with uveitis being the most 
common manifestation causing blurred vision and photobia. 
 
Arthritis is reported in 25 – 50% with ankle, knee, wrist and elbow involvement 
being most common.  Chronic arthritis can occur. 
 
Skin involvement may cause itching, tender nodules (erythema nodosum) or 
sores on the nose, nasal passages, cheeks, ears, eyelids, and fingers in 
lupus pernio. 
 
While most other systems (including gastro-intestinal, bone, neurological 
renal and cardiac can be involved in general they are relatively rare (5%) and 
their effects have to be considered on an individual basis. 
 
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Appendix A  Management of non-respiratory TB 
Meningeal TB 
 
Patients with active meningeal TB should be offered:  
 
a treatment regimen, initially lasting for 12 months, comprising 
isoniazid, pyrazinamide, rifampicin and a fourth drug (for example, 
ethambutol) for the first 2 months, followed by isoniazid and 
rifampicin for the rest of the treatment period 
 
a glucocorticoid at the normal dose range  
  adults – equivalent to prednisolone 20–40 mg if on rifampicin, 
otherwise 10–20 mg  
  children – equivalent to prednisolone 1–2 mg/kg, maximum 
40 mg 
with gradual withdrawal of the glucocorticoid considered, starting 
within 2–3 weeks of initiation. 
 
Clinicians prescribing treatment for active meningeal TB should 
consider as first choice: 
  a daily dosing schedule 
  using combination tablets 
Peripheral lymph node TB 
 
For patients with active peripheral lymph node tuberculosis, the first 
choice of treatment should be the standard recommended regimen: 
 
use a daily dosing schedule 
 
include combination tablets 
 
Patients with active peripheral lymph node TB who have had an affected 
gland surgically removed should still be treated with the standard 
recommended regimen. 
 
Drug treatment of peripheral lymph node TB should normally be stopped 
after 6 months, regardless of the appearance of new nodes, residual 
nodes or sinuses draining during treatment. 
Bone and joint TB: drug treatment 
 
The standard recommended regimen should be planned and started in 
people with:  
 
active spinal TB 
 
active TB at other bone and joint sites 
 
Clinicians prescribing treatment for active bone and joint tuberculosis 
should consider as first choice: 
 
a daily dosing schedule 
 
using combination tablets 
 
 
 
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A computed tomography (CT) or magnetic resonance (MR) scan should 
be performed on patients with active spinal TB who have neurological 
signs or symptoms. If there is direct spinal cord involvement (for example, 
a spinal cord tuberculoma), management should be as for meningeal TB 
 
Bone and joint TB: routine therapeutic surgery 
 
 
In patients with spinal TB, anterior spinal fusion should not be 
performed routinely. 
 
In patients with spinal TB, anterior spinal fusion should be 
considered if there is spinal instability or evidence of spinal cord 
compression.  
Pericardial TB 
For patients with active pericardial TB, the first choice of treatment should 
be: 
 
the standard recommended regimen use a daily dosing schedule 
 
include combination tablets 
 
In addition to anti-TB treatment, patients with active pericardial TB should 
be offered: 
 
for adults, a glucocorticoid equivalent to prednisolone at 
60 mg/day 
 
for children, a glucocorticoid equivalent to prednisolone 
1mg/kg/day (maximum 40 mg/day) 
with gradual withdrawal of the glucocorticoid considered, starting within 
2–3 weeks of initiation. 
Disseminated (including miliary) TB 
 
For patients with disseminated (including miliary) TB, the first choice of 
treatment should be the standard recommended regimen  
 
use a daily dosing schedule 
 
include combination tablets 
 
Treatment of disseminated (including miliary) TB should be started even 
if initial liver function tests are abnormal. If the patient’s liver function 
deteriorates significantly on drug treatment, advice on management 
options should be sought from clinicians with specialist experience of 
these circumstances. 
 
Patients with disseminated (including miliary) TB should be tested for 
central nervous system (CNS) involvement by: 
 
brain scan (CT or MRI) and/or lumbar puncture for those with CNS 
signs or symptoms 
 
lumbar puncture for those without CNS signs and symptoms. 
 
If evidence of CNS involvement is detected, treatment should be the 
same as for meningeal TB. 
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Other sites of infection 
For patients with:  
 
active genitourinary TB, or 
 
active TB of any site other than:  
 
respiratory system 
 
CNS (typically meninges) 
 
peripheral lymph nodes 
 
bones and joints 
 
pericardium 
 
disseminated (including miliary) disease 
the first choice of treatment should be the standard recommended 
regimen  
 
use a daily dosing schedule  
 
include combination tablets 
 
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References 
 
                                                 
1 Health Protection Agency 
2 Department of Health 
3
erck Manual 
 M
4 NICE Guidelines 033 Clinical diagnosis and management of tuberculosis, and measures for 
its prevention and control March 2006 
5 Oxford Textbook of Medicine 
6 http://www.nhlbi.nih.gov/health/dci/Diseases/sarc/sar_signsandsymptoms.html 
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