Systemic lupus erythematosus x ray: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Systemic lupus erythematosus}} | {{Systemic lupus erythematosus}} | ||
{{CMG}} | {{CMG}} {{AE}} {{MIR}} | ||
==Overview== | ==Overview== | ||
On X ray imaging, systemic lupus erythematosus (SLE) may be characterized by different features regarding the present complication. | On X-ray imaging, systemic lupus erythematosus (SLE) may be characterized by different features regarding the present complication. The most common characteristic findings of SLE in X-ray include [[Thumbprinting|thumb printing sign]] in the abdominal X ray, blunting of the [[costophrenic angle]] due to [[pleural effusion]], [[cardiomegaly]], [[hepatomegaly]], [[Osteoporosis|osteoprosis]], tenosinovitis, and other manifestations based on the complications. | ||
==X Ray== | ==X Ray== | ||
Findings on an X ray imaging for systemic lupus erythematosus (SLE) depends on the organ system involvement and may include the following features.<ref name="pmid23812167">{{cite journal |vauthors=Appenzeller S |title=Magnetic resonance imaging in systemic lupus erythematosus: where do we stand? |journal=Cogn Behav Neurol |volume=26 |issue=2 |pages=53–4 |year=2013 |pmid=23812167 |doi=10.1097/WNN.0b013e31829d5b60 |url=}}</ref><ref name="pmid26309728">{{cite journal |vauthors=Thurman JM, Serkova NJ |title=Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus |journal=F1000Res |volume=4 |issue= |pages=153 |year=2015 |pmid=26309728 |pmc=4536614 |doi=10.12688/f1000research.6587.2 |url=}}</ref><ref name="pmid26038342">{{cite journal |vauthors=Lin K, Lloyd-Jones DM, Li D, Liu Y, Yang J, Markl M, Carr JC |title=Imaging of cardiovascular complications in patients with systemic lupus erythematosus |journal=Lupus |volume=24 |issue=11 |pages=1126–34 |year=2015 |pmid=26038342 |pmc=4567427 |doi=10.1177/0961203315588577 |url=}}</ref><ref name="pmid26236469">{{cite journal |vauthors=Sarbu N, Bargalló N, Cervera R |title=Advanced and Conventional Magnetic Resonance Imaging in Neuropsychiatric Lupus |journal=F1000Res |volume=4 |issue= |pages=162 |year=2015 |pmid=26236469 |pmc=4505788 |doi=10.12688/f1000research.6522.2 |url=}}</ref><ref name="pmid24696368">{{cite journal |vauthors=Qin H, Guo Q, Shen N, Huang X, Wu H, Zhang M, Bao C, Chen S |title=Chest imaging manifestations in lupus nephritis |journal=Clin. Rheumatol. |volume=33 |issue=6 |pages=817–23 |year=2014 |pmid=24696368 |doi=10.1007/s10067-014-2586-2 |url=}}</ref><ref name="pmid22901453">{{cite journal |vauthors=Goh YP, Naidoo P, Ngian GS |title=Imaging of systemic lupus erythematosus. Part II: gastrointestinal, renal, and musculoskeletal manifestations |journal=Clin Radiol |volume=68 |issue=2 |pages=192–202 |year=2013 |pmid=22901453 |doi=10.1016/j.crad.2012.06.109 |url=}}</ref><ref name="pmid23943987">{{cite journal |vauthors=Gal Y, Twig G, Mozes O, Greenberg G, Hoffmann C, Shoenfeld Y |title=Central nervous system involvement in systemic lupus erythematosus: an imaging challenge |journal=Isr. Med. Assoc. J. |volume=15 |issue=7 |pages=382–6 |year=2013 |pmid=23943987 |doi= |url=}}</ref><ref name="pmid1448334">{{cite journal |vauthors=Shirato M, Hisa N, Fujikura Y, Ohkuma K, Kutsuki S, Hiramatsu K |title=[Imaging diagnosis of lupus enteritis--especially about sonographic findings] |language=Japanese |journal=Nihon Igaku Hoshasen Gakkai Zasshi |volume=52 |issue=10 |pages=1394–9 |year=1992 |pmid=1448334 |doi= |url=}}</ref><ref name="pmid25275093">{{cite journal |vauthors=Adachi JD, Lau A |title=Systemic lupus erythematosus, osteoporosis, and fractures |journal=J. Rheumatol. |volume=41 |issue=10 |pages=1913–5 |year=2014 |pmid=25275093 |doi=10.3899/jrheum.140919 |url=}}</ref><ref name="pmid21718325">{{cite journal |vauthors=Curiel R, Akin EA, Beaulieu G, DePalma L, Hashefi M |title=PET/CT imaging in systemic lupus erythematosus |journal=Ann. N. Y. Acad. Sci. |volume=1228 |issue= |pages=71–80 |year=2011 |pmid=21718325 |doi=10.1111/j.1749-6632.2011.06076.x |url=}}</ref><ref name="pmid22901452">{{cite journal |vauthors=Goh YP, Naidoo P, Ngian GS |title=Imaging of systemic lupus erythematosus. Part I: CNS, cardiovascular, and thoracic manifestations |journal=Clin Radiol |volume=68 |issue=2 |pages=181–91 |year=2013 |pmid=22901452 |doi=10.1016/j.crad.2012.06.110 |url=}}</ref><ref name="pmid11571369">{{cite journal |vauthors=Rockall AG, Rickards D, Shaw PJ |title=Imaging of the pulmonary manifestations of systemic disease |journal=Postgrad Med J |volume=77 |issue=912 |pages=621–38 |year=2001 |pmid=11571369 |pmc=1742125 |doi= |url=}}</ref> | |||
=== More common | === More common findings === | ||
{| class="wikitable" | {| class="wikitable" | ||
! style="background: #4479BA; color: #FFFFFF; " |Organ | ! style="background: #4479BA; color: #FFFFFF; " |Organ | ||
! style="background: #4479BA; color: #FFFFFF; " |Disease | ! style="background: #4479BA; color: #FFFFFF; " |Disease | ||
! style="background: #4479BA; color: #FFFFFF; " |Description | ! style="background: #4479BA; color: #FFFFFF; " |Description | ||
! style="background: #4479BA; color: #FFFFFF; " |Preview | |||
|- | |- | ||
| | | style="background: #DCDCDC; " |<small><small>[[Gastrointestinal system]]</small></small> | ||
![[Enteritis]] | |||
| | | | ||
*[[ | * [[Small bowel]] wall thickening | ||
**[[ | ** [[Thumbprinting|Thumbprinting sign]] | ||
| | |||
| | | | ||
[[File:Thumbpronting.gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
| rowspan=" | | rowspan="4" style="background: #DCDCDC; " |<small><small>[[Pulmonary|Pulmonary involvement]]</small></small> | ||
![[Pleural effusion]] | |||
| | | | ||
* Lateral decubitus | * Lateral decubitus view: | ||
** | ** Visible small amounts of fluid layering against the dependent [[parietal pleura]] | ||
* PA and AP CXR: | * PA and AP CXR: | ||
** Blunting of the [[costophrenic angle]] | ** Blunting of the [[costophrenic angle]] | ||
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** Fluid within the [[Horizontal fissure of right lung|horizontal]] or [[Oblique fissure|oblique fissures]] | ** Fluid within the [[Horizontal fissure of right lung|horizontal]] or [[Oblique fissure|oblique fissures]] | ||
** [[Mediastinal]] shifts with large amounts of fluid | ** [[Mediastinal]] shifts with large amounts of fluid | ||
| | |||
[[File:Pleural effusion.gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |||
![[Pulmonary fibrosis]] | |||
| | |||
* Diffuse increased interstitial markings | |||
* Reduce in lung volume | |||
* [[Pulmonary nodule|Pulmonary nodularity]] may be seen | |||
* Shaggy outline to the heart | |||
** Due to adjacenet [[Pulmonary Fibrosis|lung fibrosis]] so the outline of the heart is less well delineated | |||
* Tracheomegaly | |||
| | |||
[[File:Pulmonary fibrosis.gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Pulmonary hypertension]] | |||
| | | | ||
*Elevated [[cardiac apex]] due to [[right ventricular hypertrophy]] | *Elevated [[cardiac apex]] due to [[right ventricular hypertrophy]] | ||
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* Prominent pulmonary outflow tract | * Prominent pulmonary outflow tract | ||
* Enlarged [[pulmonary arteries]] | * Enlarged [[pulmonary arteries]] | ||
| | |||
[[File:PHTN.gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Pneumonitis|Acute pneumonitis]] | |||
| | | | ||
*[[Bilateral]] patchy airspace opacification | *[[Bilateral]] patchy airspace opacification | ||
| | |||
[[File:Webp.net-gifmaker (2).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
| rowspan="2" style="background: #DCDCDC; " |Cardiac involvement | | rowspan="2" style="background: #DCDCDC; " |<small><small>[[Cardiac|Cardiac involvement]]</small></small> | ||
![[Cardiomegaly]] | |||
| | | | ||
*[[Cardiac enlargement]] | |||
| rowspan="2" | | |||
[[File:270780927951f0155ba941fe2264d1 big gallery.jpg|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Mitral stenosis]] | |||
| | | | ||
*[[Cardiomegaly]] | |||
*Double right heart border (enlarged [[left atrium]] and normal [[right atrium]]) | |||
*Prominent [[left atrial]] appendage | |||
*Splaying of the subcarinal angle (>120 degrees) | |||
|- | |- | ||
| rowspan="2" style="background: #DCDCDC; " |Musculoskeletal involvement | | rowspan="2" style="background: #DCDCDC; " |<small><small>[[Musculoskeletal system|Musculoskeletal]] involvement</small></small> | ||
![[Arthritis]] | |||
| | | | ||
*Soft tissue swelling of the involved joints | *Soft tissue swelling of the involved joints | ||
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*Widened forefoot | *Widened forefoot | ||
*[[Hallux valgus]] | *[[Hallux valgus]] | ||
| | |||
[[File:Webp.net-gifmaker (3).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Osteoporosis]] | |||
| | | | ||
*Periarticular [[osteoporosis]] | *Periarticular [[osteoporosis]] | ||
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**[[Periosteal reaction]] progressing to callus formation in diaphyseal fractures | **[[Periosteal reaction]] progressing to callus formation in diaphyseal fractures | ||
**Linear [[sclerosis]] and cortical thickening more frequent in [[metaphyseal]] and [[epiphyseal]] [[fractures]] | **Linear [[sclerosis]] and cortical thickening more frequent in [[metaphyseal]] and [[epiphyseal]] [[fractures]] | ||
*Decrease | |||
| | |||
[[File:Webp.net-gifmaker (4).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|} | |} | ||
=== Less common | === Less common findings === | ||
{| class="wikitable" | {| class="wikitable" | ||
! style="background: #4479BA; color: #FFFFFF; " |Organ | ! style="background: #4479BA; color: #FFFFFF; " |Organ | ||
! style="background: #4479BA; color: #FFFFFF; " |Disease | ! style="background: #4479BA; color: #FFFFFF; " |Disease | ||
! style="background: #4479BA; color: #FFFFFF; " |Description | ! style="background: #4479BA; color: #FFFFFF; " |Description | ||
! style="background: #4479BA; color: #FFFFFF; " |Preview | |||
|- | |- | ||
| rowspan=" | | rowspan="3" style="background: #DCDCDC; " |<small><small>[[Gastrointestinal]] system</small></small> | ||
![[Intestinal pseudo-obstruction]] | |||
| | | | ||
*Dilated [[bowel]] loops with or without the presence of fluid levels | *Dilated [[bowel]] loops with or without the presence of fluid levels | ||
* | *Upright [[chest]] radiographs for [[perforation]] evaluating | ||
| | |||
[[File:Webp.net-gifmaker (5).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Autosplenectomy]] | |||
| | | | ||
* Calcified [[spleen]] may be visible in the left upper quadrant | * Calcified [[spleen]] may be visible in the left upper quadrant | ||
| | |||
|- | |||
![[Hepatomegaly]] | |||
| | |||
* Enlargement of liver silhouette | |||
* Medially displaced bowel loops | |||
| | |||
[[File:Webp.net-gifmaker (6).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
| rowspan="4" style="background: #DCDCDC; " |Pulmonary involvement | | rowspan="4" style="background: #DCDCDC; " |<small><small>[[Pulmonary]] involvement</small></small> | ||
![[Respiratory failure|Respiratory muscle dysfunction]] | |||
| | | | ||
* Elevated hemidiaphragms at [[CXR]] | *Elevated hemidiaphragms at [[CXR]] | ||
* Linear [[atelectasis]] and an ill-defined juxtadiaphragmatic areas of increased opacity | *Linear [[atelectasis]] and an ill-defined juxtadiaphragmatic areas of increased opacity | ||
| | |||
[[File:Webp.net-gifmaker (7).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Pulmonary hemorrhage]] | |||
| | | | ||
*Patchy bilateral and acinar areas of increased opacity, predominantly in the lower lungs | *Patchy bilateral and acinar areas of increased opacity, predominantly in the lower lungs | ||
| | |||
[[File:Webp.net-gifmaker (8).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Pulmonary emboli]] | |||
| | | | ||
*[[Fleischner sign|Fleishner sign]]: Enlarged [[pulmonary artery]] | |||
*[[Hampton's hump|Hampton hump]]: Peripheral wedge of airspace opacity and implied [[lung infarction]] | |||
*[[Westermark sign]]: Regional oligoemia | |||
*[[Pleural effusion]] | |||
| | |||
[[File:Webp.net-gifmaker (9).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
!Shrinking lung syndrome | |||
| | | | ||
*Small but clear [[lungs]] with [[diaphragmatic elevation]] | *Small but clear [[lungs]] with [[diaphragmatic elevation]] | ||
*Basal [[atelectasis]] | *Basal [[atelectasis]] | ||
| | |||
|- | |- | ||
| rowspan="2" style="background: #DCDCDC; " |Cardiac involvement | | rowspan="2" style="background: #DCDCDC; " |<small><small>[[Cardiac]] involvement</small></small> | ||
![[Mitral regurgitation]] | |||
| | | | ||
* [[Left atrial enlargement]] | *[[Left atrial enlargement]] | ||
** Convexity or straightening of the [[left atrial appendage]] just below the main [[pulmonary artery]] (along left heart border) | **Convexity or straightening of the [[left atrial appendage]] just below the main [[pulmonary artery]] (along with left heart border) | ||
** Double density sign: An addition contour superimposed over the [[right heart]] due to [[Left atrial enlargement|left atrium enlargement]] | **Double density sign: An addition contour superimposed over the [[right heart]] due to [[Left atrial enlargement|left atrium enlargement]] | ||
** Elevation of the left main [[bronchus]] and splaying of the [[carina]] | **Elevation of the left main [[bronchus]] and splaying of the [[carina]] | ||
* Upper zone venous enlargement due to [[pulmonary hypertension]] | *Upper zone venous enlargement due to [[pulmonary hypertension]] | ||
* Left [[ventricular]] enlargement is also eventually present due to volume overload | *Left [[ventricular]] enlargement is also eventually present due to volume overload | ||
| | |||
[[File:Webp.net-gifmaker (10).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
![[Pericardial effusion]] | |||
| | | | ||
* Globular enlargement of the cardiac shadow giving a water bottle configuration | *Globular enlargement of the cardiac shadow giving a water bottle configuration | ||
* Lateral [[CXR]]: | *Anteroposterior [[CXR]]: | ||
** Vertical opaque line ([[pericardial fluid]]) separating a vertical lucent line directly behind [[sternum]] ([[Epicardial fat pad|epicardial fat]]) anteriorly | **Enlarged cardiac silhouette | ||
*Lateral [[CXR]]: | |||
**Vertical opaque line ([[pericardial fluid]]) separating a vertical lucent line directly behind [[sternum]] ([[Epicardial fat pad|epicardial fat]]) anteriorly | |||
| | |||
[[File:Webp.net-gifmaker (11).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|- | |- | ||
| style="background: #DCDCDC; " |Musculoskeletal involvement | | style="background: #DCDCDC; " |<small><small>[[Musculoskeletal system|Musculoskeletal involvement]]</small></small> | ||
![[Osteonecrosis]] ([[Avascular necrosis]]) | |||
| | | | ||
*Initial minor [[osteopenia]], followed by variable density | *Initial minor [[osteopenia]], followed by variable density | ||
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*Collapse of the [[articular]] surface | *Collapse of the [[articular]] surface | ||
*Crescent sign of [[AVN]] | *Crescent sign of [[AVN]] | ||
| | |||
[[File:Webp.net-gifmaker (12).gif|thumb|300px|<SMALL><SMALL>''[https://radiopaedia.org/ Adapted from Radiopaedia]''</SMALL></SMALL>]] | |||
|} | |} | ||
Latest revision as of 16:19, 1 February 2018
Systemic lupus erythematosus Microchapters |
Differentiating Systemic lupus erythematosus from other Diseases |
---|
Diagnosis |
Treatment |
Case Studies |
Systemic lupus erythematosus x ray On the Web |
American Roentgen Ray Society Images of Systemic lupus erythematosus x ray |
Directions to Hospitals Treating Systemic lupus erythematosus |
Risk calculators and risk factors for Systemic lupus erythematosus x ray |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]
Overview
On X-ray imaging, systemic lupus erythematosus (SLE) may be characterized by different features regarding the present complication. The most common characteristic findings of SLE in X-ray include thumb printing sign in the abdominal X ray, blunting of the costophrenic angle due to pleural effusion, cardiomegaly, hepatomegaly, osteoprosis, tenosinovitis, and other manifestations based on the complications.
X Ray
Findings on an X ray imaging for systemic lupus erythematosus (SLE) depends on the organ system involvement and may include the following features.[1][2][3][4][5][6][7][8][9][10][11][12]
More common findings
Organ | Disease | Description | Preview |
---|---|---|---|
Gastrointestinal system | Enteritis |
|
|
Pulmonary involvement | Pleural effusion |
|
|
Pulmonary fibrosis |
|
||
Pulmonary hypertension |
|
||
Acute pneumonitis |
|
||
Cardiac involvement | Cardiomegaly | ||
Mitral stenosis |
| ||
Musculoskeletal involvement | Arthritis |
|
|
Osteoporosis |
|
Less common findings
Organ | Disease | Description | Preview |
---|---|---|---|
Gastrointestinal system | Intestinal pseudo-obstruction |
|
|
Autosplenectomy |
|
||
Hepatomegaly |
|
||
Pulmonary involvement | Respiratory muscle dysfunction |
|
|
Pulmonary hemorrhage |
|
||
Pulmonary emboli |
|
||
Shrinking lung syndrome |
|
||
Cardiac involvement | Mitral regurgitation |
|
|
Pericardial effusion |
|
||
Musculoskeletal involvement | Osteonecrosis (Avascular necrosis) |
|
References
- ↑ Appenzeller S (2013). "Magnetic resonance imaging in systemic lupus erythematosus: where do we stand?". Cogn Behav Neurol. 26 (2): 53–4. doi:10.1097/WNN.0b013e31829d5b60. PMID 23812167.
- ↑ Thurman JM, Serkova NJ (2015). "Non-invasive imaging to monitor lupus nephritis and neuropsychiatric systemic lupus erythematosus". F1000Res. 4: 153. doi:10.12688/f1000research.6587.2. PMC 4536614. PMID 26309728.
- ↑ Lin K, Lloyd-Jones DM, Li D, Liu Y, Yang J, Markl M, Carr JC (2015). "Imaging of cardiovascular complications in patients with systemic lupus erythematosus". Lupus. 24 (11): 1126–34. doi:10.1177/0961203315588577. PMC 4567427. PMID 26038342.
- ↑ Sarbu N, Bargalló N, Cervera R (2015). "Advanced and Conventional Magnetic Resonance Imaging in Neuropsychiatric Lupus". F1000Res. 4: 162. doi:10.12688/f1000research.6522.2. PMC 4505788. PMID 26236469.
- ↑ Qin H, Guo Q, Shen N, Huang X, Wu H, Zhang M, Bao C, Chen S (2014). "Chest imaging manifestations in lupus nephritis". Clin. Rheumatol. 33 (6): 817–23. doi:10.1007/s10067-014-2586-2. PMID 24696368.
- ↑ Goh YP, Naidoo P, Ngian GS (2013). "Imaging of systemic lupus erythematosus. Part II: gastrointestinal, renal, and musculoskeletal manifestations". Clin Radiol. 68 (2): 192–202. doi:10.1016/j.crad.2012.06.109. PMID 22901453.
- ↑ Gal Y, Twig G, Mozes O, Greenberg G, Hoffmann C, Shoenfeld Y (2013). "Central nervous system involvement in systemic lupus erythematosus: an imaging challenge". Isr. Med. Assoc. J. 15 (7): 382–6. PMID 23943987.
- ↑ Shirato M, Hisa N, Fujikura Y, Ohkuma K, Kutsuki S, Hiramatsu K (1992). "[Imaging diagnosis of lupus enteritis--especially about sonographic findings]". Nihon Igaku Hoshasen Gakkai Zasshi (in Japanese). 52 (10): 1394–9. PMID 1448334.
- ↑ Adachi JD, Lau A (2014). "Systemic lupus erythematosus, osteoporosis, and fractures". J. Rheumatol. 41 (10): 1913–5. doi:10.3899/jrheum.140919. PMID 25275093.
- ↑ Curiel R, Akin EA, Beaulieu G, DePalma L, Hashefi M (2011). "PET/CT imaging in systemic lupus erythematosus". Ann. N. Y. Acad. Sci. 1228: 71–80. doi:10.1111/j.1749-6632.2011.06076.x. PMID 21718325.
- ↑ Goh YP, Naidoo P, Ngian GS (2013). "Imaging of systemic lupus erythematosus. Part I: CNS, cardiovascular, and thoracic manifestations". Clin Radiol. 68 (2): 181–91. doi:10.1016/j.crad.2012.06.110. PMID 22901452.
- ↑ Rockall AG, Rickards D, Shaw PJ (2001). "Imaging of the pulmonary manifestations of systemic disease". Postgrad Med J. 77 (912): 621–38. PMC 1742125. PMID 11571369.