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=Pulmonary alveolar proteinosis=


==Overview==
'''Pulmonary alveolar proteinosis''' -(PAP) is a rare [[lung]] [[disease]] in which abnormal accumulation of [[surfactant]] occurs within the [[alveoli]], interfering with [[gas exchange]].  PAP can occur in a primary form or secondarily in the settings of malignancy (especially in myeloid [[leukemia]]), pulmonary infection, or environmental exposure to dusts or chemicals.  Rare familial forms have also been recognized, suggesting a [[genetics|genetic]] component in some cases. <ref>Rosen SH, Castleman B, and Liebow AA. Pulmonary alveolar proteinosis. New England Journal of Medicine 1958; 258: 1123-1142.</ref> <ref>Seymour JF and Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. American Journal of Respiratory and Critical Care Medicine 2002; 166: 215-235.</ref> <ref>Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis; clinical aspects and current concepts on pathogenesis. Thorax 2000; 55: 67-77.</ref> <ref>Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc. Natl. Acad. Sci. USA 1994; 91: 5592-5596.</ref>
==Historical Perspective==
PAP was first described in 1958 by the physicians Samuel Rosen, Benjamin Castleman, and Averill Liebow.  In their case series published in the [[New England Journal of Medicine]] on June 7th of that year, they described 27 patients with pathologic evidence of [[periodic acid Schiff]] positive material filling the alveoli.  This [[lipid]] rich material was subsequently recognized to be [[surfactant]]. 
==Pathophysiology==
Although the cause of PAP remains obscure, a major breakthrough in the understanding of the [[etiology]] of the disease came by the chance observation that mice bred for experimental study to lack a hematologic [[growth factor]] known as [[Granulocyte-colony stimulating factor|granulocyte-macrophage colony stimulating factor (GM-CSF)]] developed a pulmonary [[syndrome]] of abnormal surfactant accumulation resembling human PAP.  The implications of this finding are still being explored, but significant progress was reported in February, 2007.  Researchers in that report discussed the presence of anti-[[GM-CSF]] [[autoantibodies]] in patients with PAP, and duplicated that [[syndrome]] with the infusion of these [[autoantibodies]] into mice. <ref>{{cite journal |author=Uchida K, Beck D, Yamamoto T, Berclaz P, Abe S, Staudt M, Carey B, Filippi M, Wert S, Denson L, Puchalski J, Hauck D, Trapnell B |title=GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis |journal=N Engl J Med |volume=356 |issue=6 |pages=567-79 |year=2007 |pmid=17287477}}</ref>
==Causes==
Pulmonary alveolar proteinosis is an idiopathic disease, but studies have linked causes to production of antibodies that neutralize GM-CSF, [[granulocyte-macrophage colony-stimulating factor]]. Occasionally, development of pulmonary alveolar proteinosis is related to exposure of toxic substances, such as inorganic dusts, infection with [[Pneumocystis jirovecii]], certain cancers, and immunosuppressants. It rarely occurs in newborns.
There are several types of clinical forms of [[Pulmonary alveolar proteinosis]]; primary, secondary, and congenital. Primary PAP involves high levels of antibodies that neutralize GM-CSF, [[granulocyte-macrophage colony-stimulating factor]]. Secondary PAP occurs from clinical conditions that reduce the numbers and functions of alveolar macrophages. Congenital PAP is due to genetic mutations in the genes encoding surfactant proteins of the receptor for [[granulocyte-macrophage colony-stimulating factor]].<ref name="pmid14695413">{{cite journal| author=Trapnell BC, Whitsett JA, Nakata K| title=Pulmonary alveolar proteinosis. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 26 | pages= 2527-39 | pmid=14695413 | doi=10.1056/NEJMra023226 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14695413  }} </ref>
==Causes==
===Common Causes===
*[[Pneumocystis jirovecii]]
*[[Respiratory failure]]
*Uncontrolled infection
*Respiratory Pathogens
*Opportunistic Pathogens: [[Nocardia]]
*[[Sirolimus]]
*[[Prednisone]]
*Inorganic dusts
*Inhalation of [[silica]] dust
*Exposure to [[insecticides]]
*aluminum dust
*[[titanium dioxide]]
*[[Haematological]] malignancies
*[[HIV]] infection.
===Causes by Organ System===
{|style="width:80%; height:100px" border="1"
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" |No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Chemical / poisoning'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dermatologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
|bgcolor="Beige"|[[Sirolimus]], [[Prednisone]]
|-
|-bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Endocrine'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Environmental'''
|bgcolor="Beige"| Inorganic dusts, Inhalation of [[silica]] dust, Exposure to [[insecticides]], aluminum dust, [[titanium dioxide]]
|-
|-bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Genetic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Hematologic'''
|bgcolor="Beige"| [[Haematological]] malignancies
|-
|-bgcolor="LightSteelBlue"
| '''Iatrogenic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Infectious Disease'''
|bgcolor="Beige"| Uncontrolled infection, Respiratory Pathogens, [[Nocardia]], [[HIV]] infection
|-
|-bgcolor="LightSteelBlue"
| '''Musculoskeletal / Ortho'''
|bgcolor="Beige"| [No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Neurologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Nutritional / Metabolic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Oncologic'''
|bgcolor="Beige"| [[Haematological]] malignancies
|-
|-bgcolor="LightSteelBlue"
| '''Opthalmologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Overdose / Toxicity'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Psychiatric'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Pulmonary'''
|bgcolor="Beige"|[[Pneumocystis jirovecii]], [[Respiratory failure]]
|-
|-bgcolor="LightSteelBlue"
| '''Renal / Electrolyte'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Rheum / Immune / Allergy'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Sexual'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Trauma'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Urologic'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Dental'''
|bgcolor="Beige"| No underlying causes
|-
|-bgcolor="LightSteelBlue"
| '''Miscellaneous'''
|bgcolor="Beige"| No underlying causes
|-
|}
===Causes in Alphabetical Order===
{{col-begin|width=80%}}
{{col-break|width=33%}}
*Aluminum dust
*[[Haematological]] malignancies
*[[HIV]] infection
*Inorganic Dusts
*[[Insecticides]]
*Opportunistic Pathogens: [[Nocardia]]
*[[Pneumocystis jirovecii]]
*[[Prednisone]]
*[[Respiratory failure]]
*Respiratory Pathogens
*[[Silica]] dust
*[[Sirolimus]]
*[[Titanium dioxide]]
*Uncontrolled infection
{{col-end}}
==Natural History==
The clinical course of PAP is unpredictable. Spontaneous remission is recognized; some patients have stable symptoms.
==Complications==
Death may occur due to progression of PAP or due to the underlying disease associated with PAP. Individuals with PAP are more vulnerable to [[pneumonia|infection of the lung]] by [[bacterium|bacteria]] or [[fungi]].
==Prognosis==
==History and Symptoms==
The [[symptoms]] of PAP include:
*[[Dyspnea]]<ref name="pmid14695413">{{cite journal| author=Trapnell BC, Whitsett JA, Nakata K| title=Pulmonary alveolar proteinosis. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 26 | pages= 2527-39 | pmid=14695413 | doi=10.1056/NEJMra023226 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14695413  }} </ref>
*[[Cough]]
*[[Sputum]]
*[[Fatigue]]
*[[Fever]]
*[[Anorexia]]
*[[Hemoptysis]]
*[[Crackles]]
*[[Cyanosis]]
*[[Clubbing]]
==Chest X Ray==
Classic radiographic finding is bilateral, symmetric [[alveolar]] [[consolidation]] or ground-glass opacity, particularly in a [[perihilar]] or [[hilar]] distribution resembling [[pulmonary edema]].
==CT==
* CT typically shows diffuse ground-glass attenuation with superimposed crazy-paving pattern (intra- and interlobular septal thickening, often in polygonal shapes representing the secondary pulmonary lobule).
'''Patient#1'''
<gallery>
Image:
Pulmonary-alveolar-proteinosis-001.jpg
Image:
Pulmonary-alveolar-proteinosis-002.jpg</gallery>
'''Patient #1: Proven PAP but not quite the classic crazy-paving pattern'''
<gallery>
Image:
Pulmonary alveolar proteinosis 201.jpg
Image:
Pulmonary alveolar proteinosis 202.jpg
Image:
Pulmonary alveolar proteinosis 203.jpg
Image:
Pulmonary alveolar proteinosis 204.jpg
</gallery>
==Other Diagnostic Studies==
[[Diagnosis]] is generally made by surgical or endoscopic [[biopsy]] of the lung, revealing the distinctive pathologic finding.
=== Histopathological Findings: Pulmonary alveolar proteinosis===
{{#ev:youtube|L9fVRzcPkEQ}}
==Medical Therapy==
The use of [[GM-CSF]] injections has also been attempted, with variable success.
==Surgery==
The standard treatment for PAP is whole-lung [[lavage]], in which sterile fluid is instilled into the lung and then removed, along with the abnormal [[surfactant]] material.  This is generally effective at ameliorating symptoms, often for prolonged periods. Lung [[transplantation]] can be performed in refractory cases.
==References==
{{reflist|2}}




Revision as of 20:38, 1 June 2016

Pulmonary alveolar proteinosis

Overview

Pulmonary alveolar proteinosis -(PAP) is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy (especially in myeloid leukemia), pulmonary infection, or environmental exposure to dusts or chemicals. Rare familial forms have also been recognized, suggesting a genetic component in some cases. [1] [2] [3] [4]

Historical Perspective

PAP was first described in 1958 by the physicians Samuel Rosen, Benjamin Castleman, and Averill Liebow. In their case series published in the New England Journal of Medicine on June 7th of that year, they described 27 patients with pathologic evidence of periodic acid Schiff positive material filling the alveoli. This lipid rich material was subsequently recognized to be surfactant.

Pathophysiology

Although the cause of PAP remains obscure, a major breakthrough in the understanding of the etiology of the disease came by the chance observation that mice bred for experimental study to lack a hematologic growth factor known as granulocyte-macrophage colony stimulating factor (GM-CSF) developed a pulmonary syndrome of abnormal surfactant accumulation resembling human PAP. The implications of this finding are still being explored, but significant progress was reported in February, 2007. Researchers in that report discussed the presence of anti-GM-CSF autoantibodies in patients with PAP, and duplicated that syndrome with the infusion of these autoantibodies into mice. [5]

Causes

Pulmonary alveolar proteinosis is an idiopathic disease, but studies have linked causes to production of antibodies that neutralize GM-CSF, granulocyte-macrophage colony-stimulating factor. Occasionally, development of pulmonary alveolar proteinosis is related to exposure of toxic substances, such as inorganic dusts, infection with Pneumocystis jirovecii, certain cancers, and immunosuppressants. It rarely occurs in newborns.

There are several types of clinical forms of Pulmonary alveolar proteinosis; primary, secondary, and congenital. Primary PAP involves high levels of antibodies that neutralize GM-CSF, granulocyte-macrophage colony-stimulating factor. Secondary PAP occurs from clinical conditions that reduce the numbers and functions of alveolar macrophages. Congenital PAP is due to genetic mutations in the genes encoding surfactant proteins of the receptor for granulocyte-macrophage colony-stimulating factor.[6]

Causes

Common Causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical / poisoning No underlying causes
Dermatologic No underlying causes
Drug Side Effect Sirolimus, Prednisone
Ear Nose Throat No underlying causes
Endocrine No underlying causes
Environmental Inorganic dusts, Inhalation of silica dust, Exposure to insecticides, aluminum dust, titanium dioxide
Gastroenterologic No underlying causes
Genetic No underlying causes
Hematologic Haematological malignancies
Iatrogenic No underlying causes
Infectious Disease Uncontrolled infection, Respiratory Pathogens, Nocardia, HIV infection
Musculoskeletal / Ortho [No underlying causes
Neurologic No underlying causes
Nutritional / Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic Haematological malignancies
Opthalmologic No underlying causes
Overdose / Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary Pneumocystis jirovecii, Respiratory failure
Renal / Electrolyte No underlying causes
Rheum / Immune / Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Dental No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

Natural History

The clinical course of PAP is unpredictable. Spontaneous remission is recognized; some patients have stable symptoms.

Complications

Death may occur due to progression of PAP or due to the underlying disease associated with PAP. Individuals with PAP are more vulnerable to infection of the lung by bacteria or fungi.

Prognosis

History and Symptoms

The symptoms of PAP include:

Chest X Ray

Classic radiographic finding is bilateral, symmetric alveolar consolidation or ground-glass opacity, particularly in a perihilar or hilar distribution resembling pulmonary edema.

CT

  • CT typically shows diffuse ground-glass attenuation with superimposed crazy-paving pattern (intra- and interlobular septal thickening, often in polygonal shapes representing the secondary pulmonary lobule).

Patient#1

Patient #1: Proven PAP but not quite the classic crazy-paving pattern

Other Diagnostic Studies

Diagnosis is generally made by surgical or endoscopic biopsy of the lung, revealing the distinctive pathologic finding.

Histopathological Findings: Pulmonary alveolar proteinosis

{{#ev:youtube|L9fVRzcPkEQ}}

Medical Therapy

The use of GM-CSF injections has also been attempted, with variable success.

Surgery

The standard treatment for PAP is whole-lung lavage, in which sterile fluid is instilled into the lung and then removed, along with the abnormal surfactant material. This is generally effective at ameliorating symptoms, often for prolonged periods. Lung transplantation can be performed in refractory cases.




References

  1. ↑ Rosen SH, Castleman B, and Liebow AA. Pulmonary alveolar proteinosis. New England Journal of Medicine 1958; 258: 1123-1142.
  2. ↑ Seymour JF and Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. American Journal of Respiratory and Critical Care Medicine 2002; 166: 215-235.
  3. ↑ Shah PL, Hansell D, Lawson PR, et al. Pulmonary alveolar proteinosis; clinical aspects and current concepts on pathogenesis. Thorax 2000; 55: 67-77.
  4. ↑ Stanley E, Lieschke GJ, Grail D, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc. Natl. Acad. Sci. USA 1994; 91: 5592-5596.
  5. ↑ Uchida K, Beck D, Yamamoto T, Berclaz P, Abe S, Staudt M, Carey B, Filippi M, Wert S, Denson L, Puchalski J, Hauck D, Trapnell B (2007). "GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis". N Engl J Med. 356 (6): 567–79. PMID 17287477.
  6. ↑ 6.0 6.1 Trapnell BC, Whitsett JA, Nakata K (2003). "Pulmonary alveolar proteinosis". N Engl J Med. 349 (26): 2527–39. doi:10.1056/NEJMra023226. PMID 14695413.


Encephalitis Table

Reference list includes:[1][2]

Disease Similarities Differentials
Meningitis Classic triad of fever, nuchal rigidity, and altered mental status Photophobia, phonophobia, rash associated with meningococcemia, concomitant sinusitis or otitis, swelling of the fontanelle in infants (0-6 months)
Brain abscess Fever, headache, hemiparesis Varies depending on the location of the abscess; clinically, visual disturbance including papilledema, decreased sensation; on imaging, a lesion demonstrates both ring enhancement and central restricted diffusion
Demyelinating diseases Ataxia, lethargy Multiple sclerosis: clinically, nystagmus, internuclear ophthalmoplegia, Lhermitte's sign; on imaging, well-demarcated ovoid lesions with possible T1 hypointensities (“black holes”)

Acute disseminated encephalomyelitis: ; on imaging, diffuse or multi-lesion enhancement, with indistinct lesion borders

Substance abuse Tremor, headache, altered mental status Varies depending on type of substance: prior history, drug-seeking behavior, attention-seeking behavior, paranoia, sudden panic, anxiety, hallucinations
Electrolyte disturbance Fatigue, headache, nausea Varies depending on deficient ions; clinically, edema, constipation, hallucinations; on EKG, abnormalities in T wave, P wave, QRS complex; possible presentations include arrhythmia, dehydration, renal failure
Stroke Ataxia, aphasia, dizziness Varies depending on classification of stroke; presents with positional vertigo, high blood pressure, extremity weakness
Intracranial hemorrhage Headache, coma, dizziness Lobar hemorrhage, numbness, tingling, hypertension, hemorrhagic diathesis
Trauma Headache, altered mental status Amnesia, loss of consciousness, dizziness, concussion, contusion


References

  1. ↑ Eckstein C, Saidha S, Levy M (2012). "A differential diagnosis of central nervous system demyelination: beyond multiple sclerosis". J Neurol. 259 (5): 801–16. doi:10.1007/s00415-011-6240-5. PMID 21932127.
  2. ↑ De Kruijk JR, Twijnstra A, Leffers P (2001). "Diagnostic criteria and differential diagnosis of mild traumatic brain injury". Brain Inj. 15 (2): 99–106. doi:10.1080/026990501458335. PMID 11260760.
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