خانم دکترزهرا پورنصیر

Differential diagnosis of multiple pulmonary nodules 

Infection

Abscesses:Bacteremic patients  and recurrent aspiration may develop multiple lung abscesses, which are more common in dependent areas of the lungs. Typically the lesions are between 0.5 and 3 cm in diameter, round, and well-defined.

Septic emboli : predilection for peripheral areas of the lower lobes

Fungi : histoplasmosis, coccidioidomycosis, cryptococcosis, or invasive aspergillosis in immunocompromised hosts.

Histoplasmosis

Symptomatic pulmonary histoplasmosis :

   subacute pulmonary infection weeks to months following exposure. Symptoms are usually mild, and the events causing the exposure are difficult to identify. Radiographs typically show focal infiltrates and mediastinal or hilar lymphadenopathy  .

Acute diffuse pulmonary histoplasmosis :

   the majority of patients develop acute symptomatic infection within a week or two .Diffuse reticulonodular or miliary pulmonary infiltrates are noted and the disease can progress to respiratory failure or progressive extrapulmonary dissemination 

Chronic pulmonary histoplasmosis:

    Patients susually have underlying lung disease.  Affected patients develop a productive cough, dyspnea, chest pain, fatigue, fevers, and sweats and have fibrotic apical infiltrates with cavitation on chest radiographs or CT scans .

Silicosis

Silicosis refers to a spectrum of pulmonary diseases caused by inhalation of free crystalline silica (silicon dioxide).

Silicosis can occur in many industries and work settings including mining, quarrying, sandblasting, masonry, foundry work, and ceramics

Several clinical presentations of disease have been described

Chronic silicosis: usually appearing 10 to 30 years after first exposure

Accelerated silicosis:Accelerated silicosis develops within 10 years of initial exposure. Accelerated silicosis is associated with high-level exposure to silica.

Acute silicosis : Acute silicosis is characterized by rapid onset of symptoms including cough, weight loss, fatigue, and sometimes pleuritic pain.

Inflammatory conditions

Wegener's granulomatosis,  rheumatoid arthritis, Pulmonary lymphomatoid granulomatosis, amyloidosis, and sarcoidosis.

 Sarcoidosis presents in patients between 10 and 40 years of age in 70 to 90 percent of cases.

 Younger children often present with skin rash, arthritis, and uveitis without apparent lung involvemen.

The "classic" chest roentgenogram reveals bilateral hilar adenopathy

Pulmonary AVMs 

Malignancy :Non-Hodgkin lymphoma , choriocarcinoma, renal cell carcinoma, melanoma, thyroid carcinoma and Kaposi's sarcoma,

pulmonary alveolar proteinosis

Desquamative interstitial pneumonia (DIP)

Lymphocytic interstitial pneumonia (LIP)

Miliary tuberculosis (TB)

PULMONARY ALVEOLAR MICROLITHIASIS

A rare idiopathic lung disease characterized by the presence of innumerable tiny calculi (microliths) composed primarily of calcium phosphate within alveolar air spaces.

It was not well characterized until the 1950s. Since then, interest in the disease (and the number of reports) has increased; in 1957 one report described 26 cases, and by 2005, 576 cases had been reported in the literature.

Pulmonary alveolar microlithiasis most frequently appears in Turkey, followed by Italy.

The disease can occur in individuals of any age and has been reported in stillborn twins and an 80-year-old woman.

 However, it occurs most often in adults between the ages of 30 and 50.

The familiar incidence of PAM is reported,and in more than one half of the reported case a familiar incidence has been demonstraed

PATHOGENESIS

The etiology and pathogenesis of PAM are unknown.

 Hypothetical mechanisms that have been postulated include an inborn error of metabolism, a response to a pulmonary insult or inhaled agent, and an acquired abnormality of calcium or phosphorous metabolism or a environmental factor

PAM has been reported in association with inhalation of various materials (e.g., mica, calcium-containing snuff, or sand)

Mutations in the SLC34A2 Gene Are Associated with Pulmonary Alveolar Microlithiasis

Homeostasis of inorganic phosphate in the human body is maintained by regulated absorption, metabolism, and excretion. Sodium-dependent phosphate transporters (NaPi) (mutation in the SLC34A2 gene) mediate the transport of inorganic phosphate (P(i)) in cells in response to dietary phosphate consumption, hormones, and growth factors.

Signaling pathways activated by mitogens, glucocorticoids, and metabolic factors have been implicated in regulating P(i) transport via NaPi2b.

  Inactivation of NaPi2b function by mutations has been linked to human pathologies, such as pulmonary alveolar microlithiasis.

CLINICAL PRESENTATION

Children with PAM are usually asymptomatic

chronic cough : is usually nonproductive, but sputum may be present and can contain microliths

Hemoptysis

dyspnea on exertion

Chest pain

clubbing

A number of cases have been identified by radiologic evaluation of asymptomatic relatives of an index case.

The physical examination is usually unremarkable in children and even in adults unless the disease is very advanced. In the late stages, tachypnea may be present and auscultation of the chest may reveal diminished breath sounds

DIFF DIAG

PAM must be differentiated from diffuse pulmonary calcinosis, which can be seen in :

 hyperthyroidism,

 chronic renal disease,

 and vitamin D intoxication.

PAM must also be differentiated from:

   Miliary tuberculosis

   Disseminated histoplasmosis

   Hemosidrosis

 PAM has been found in association with cases of milk alkali syndrome , mitral stenosis , in a renal transplant recipient , Primary ciliary dyskinesia (PCD)

NATURAL HISTORY

Such reports suggest that the disease begins with involvement of the lung bases and progresses slowly, toward involvement of a progressively larger fraction of the lungs, leading ultimately to death from respiratory failure, usually in early adult life.

 In contrast, the disease can be stable for long periods (up to 30 years in some patients), even when extensive radiographic changes are present initially.

Pneumothorax can occur, presumably from bullae and subpleural cysts, and can be recurrent in some patients.

DIAGNOSIS

The diagnosis is usually made by the charactreistric   sandstorm  on CXR

The HRCT can be helpful

Bronchoscopy with bronchoalveolar lavage may reveal the presence of microliths in the lavage fluid

Transbronchial biopsy reveals characteristic microliths that measure in diameter from 0.1-0.3 mm and are located almost invariably within alveolar air spaces.

Occasionally, microliths are present in the bronchial wall or interstitium and, rarely, in extrapulmonary sites (e.g., in the seminal vesicles, sympathetic ganglia, or gonads,kidney).

THERAPY

No effective medical therapy, and affected individuals may progress to end-stage lung disease requiring lung transplantation.

Therapeutic methods including systemic corticosteroids  and bronchoalveolar lavage have been shown to be ineffective

Diphosphonates(etidronate disodium)

monoclonal antibodies specific for the human sodium-dependent phosphate co-transporter NaPi2b

 

دکتررضا امیر عسگری             دکتر قاسم سعیدی

A  7-year-old man with fever, dry cough& abnormal CXR

Diffuse micronodular infiltrations

Pneumoconiosis

Silicosis

Asbestosis

Coal worker Pneumoconiosis

Alveolar form of sarcoidosis

TB (milliary)

Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

Fungal disease

Connective tissue disease

SLE,RA,wegner,MCTD,SS,Polymyositis,dermatomyositis,PAN,churg struss

Drug induced

Diffuse interstitial fibrosis

Radiotherapy

Pulmonary alveolar microlithiasis

…

Pneumoconiosis

Silicosis

Asbestosis

Coal worker Pneumoconiosis

Alveolar form of sarcoidosis

Miliary TB

Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

Fungal disease

Connective tissue disease

SLE,RA,wegner,MCTD,SS,Polymyositis,dermatomyositis,PAN,churg struss

Drug induced

Diffuse interstitial fibrosis

Radiotherapy

Pulmonary alveolar microlithiasis

…

Pericardial calcification

Constrictive pericarditis

Prior episode of Pericarditis or trauma

Infectious etiologies for pericarditis

viral agents (eg, coxsackievirus, influenza A, influenza B, varicella),

 Tuberculosis

 Histoplasmosis

Radiotherapy

CRF (uremic pericarditis)

 systemic lupus erythematosus, rheumatic heart disease

 hemopericardium (post trauma or cardiac surgery).

myocardial infarction

 Occasionally, pericardial tumors, such as intrapericardial teratomas

…

Pericardial calcification

Constrictive pericarditis

Prior episode of Pericarditis or trauma

Infectious etiologies for pericarditis

viral agents (eg, coxsackievirus, influenza A, influenza B, varicella),

 Tuberculosis

 Histoplasmosis

Radiotherapy

CRF (uremic pericarditis)

 systemic lupus erythematosus, rheumatic heart disease

 hemopericardium (post trauma or cardiac surgery).

myocardial infarction

 Occasionally, pericardial tumors, such as intrapericardial teratomas

…

Diffuse micronodular infiltrations + Pericardial calcification

TB

Fungal disease

Viral agents

CTD

Systemic lupus erythematosus

 Rheumatic heart disease 

TB

Fungal disease

Hypersensitivity pneumonitis