pulmonary alveolar microlithiasis

Pulmonary Alveolar Microlithiasis (PAM): A Rare Lung Disease

Pulmonary alveolar microlithiasis (PAM) is a rare and chronic lung disease characterized by the deposition of small calcium and phosphate stones, known as microliths, within the airspaces of the lungs. This condition affects both lungs and is more prevalent in the lower and mid-zones.

Causes and Genetics

PAM is an inherited disorder that results from mutations in the SLC34A2 gene [1][2]. The loss of a key sodium-phosphate co-transporter, Npt2b, expressed in distal alveolar type II cells, leads to the accumulation of calcium phosphate microliths. This genetic defect is responsible for the development of PAM.

Symptoms and Presentation

The presenting symptoms of PAM include recurrent abdominal pain, recurrent haematuria (blood in the urine), and infertility [3]. Patients typically present with these symptoms in their third or fourth decade of life.

Characteristics and Diagnosis

PAM is characterized by widespread intra-alveolar deposition of spherical calcium phosphate microliths. The condition is often diagnosed incidentally on chest imaging, such as computed tomography (CT) scans, which reveal the characteristic microliths [4][5].

References:

[1] Martín Granizo IF, Vara Cuadrado F, Duque Fraile J. Infantile familial pulmonary alveolar microlithiasis. Description of 5 cases in 2 families.

[2] Mutations in the gene SLC34A2 result in loss of a key sodium-phosphate co-transporter (called Npt2b), known to be expressed in distal alveolar type II cells, as well as in the mammary gland, and to a lesser extent in ...

[3] Presenting symptoms include recurrent abdominal pain, recurrent haematuria and infertility. Affected patients typically present in the third and fourth decades.

[4] Pulmonary alveolar microlithiasis is characterized by widespread intra-alveolar deposition of spherical calcium phosphate microliths.

[5] The condition is often diagnosed incidentally on chest imaging, such as computed tomography (CT) scans, which reveal the characteristic microliths.

Pulmonary alveolar microlithiasis (PAM) is a rare genetic disorder that can cause widespread deposition of calcium-phosphate crystals in the alveolar space, leading to various signs and symptoms. Here are some common features associated with PAM:

• Chest pain: Chest pain that worsens when coughing, sneezing, or taking deep breaths is another common feature [2].
• Dyspnea on exertion: People with pulmonary alveolar microlithiasismay also experience shortness of breath when engaging in physical activities [10][15].
• Dry cough: A dry cough can be a symptom of PAM, although it may not always be present [14].
• Hemoptysis: In some cases, people with PAM may experience coughing up blood or blood-tinged sputum [3].
• Finger clubbing: Finger clubbing, which is a condition where the fingers become enlarged and have a characteristic shape, can also be associated with PAM [14].
• Cyanosis and clubbing: Cyanosis (a bluish discoloration of the skin) and clubbing are the first detected signs in some cases [14].

It's worth noting that many people with PAM may not experience any symptoms at all, or they may be mild and only become apparent later in life. The disease typically takes a long-term progressive course, with symptoms worsening slowly over many years.

References:

[1] Context result 4 [2] Context result 2 [3] Context result 5 [10] Context result 10 [14] Context result 14 [15] Context result 15

Pulmonary alveolar microlithiasis (PAM) can be challenging to diagnose, but various diagnostic tests can help confirm the condition.

Imaging Studies

• Chest Computed Tomography (CT): A chest CT scan is often the most useful radiologic modality for diagnosing PAM. It typically reveals diffuse hyperdense micronodular calcifications throughout both lung fields [3].
• Chest X-ray: Routine chest radiographs may show a fine, "sandstorm-like" micronodular pattern that is more pronounced in the bases than in the apices [7].

Other Diagnostic Tests

• Lung Biopsy: In cases with atypical features or when genetic testing is inconclusive, lung biopsy can be undertaken to definitively establish the diagnosis. Alternatively, genetic testing can be sent prior to biopsy [8].
• Genetic Testing: Mutations in the SLC34A2 gene are responsible for PAM. Genetic testing can confirm the presence of these mutations and provide a definitive diagnosis [11].

Monitoring Progress

• Pulmonary Function Tests (PFTs): PFTs are normal at the time of diagnosis, but regular monitoring every 3 months may be necessary to assess disease progression [2].
• Echocardiography: Regular echocardiography every 6 months can help rule out pulmonary hypertension, a potential complication of PAM [14].

It's essential to note that the diagnostic algorithm for PAM suggests lung biopsy as a reasonable option if the patient has

Current Status of Drug Treatment for Pulmonary Alveolar Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disease characterized by the accumulation of intra-alveolar calcium phosphate microliths. While there are no proven treatments for PAM, research has explored various pharmacological interventions to manage the condition.

• Systemic steroids: Systemic corticosteroids have been tried in some cases, but they have shown limited efficacy in reducing disease progression [6][8].
• Calcium-chelating agents: Calcium-chelating agents such as disodium etidronate have been investigated for their potential to inhibit microcrystal growth of hydroxyapatite and reduce microlith formation [1]. However, the effectiveness of these agents remains uncertain.
• Allendronate sodium: A study on allendronate sodium, a bisphosphonate, reported some benefits in treating PAM, but more research is needed to confirm its efficacy [13].
• Other treatments: Other treatments such as systemic corticosteroids, calcium-chelating agents, and serial bronchoalveolar lavage have been tried with limited success.

Current Limitations

Despite these attempts, there is currently no effective drug treatment for pulmonary alveolar microlithiasis. The only truly effective therapy available is lung transplantation [6][12].

Future Directions

Further research is needed to explore new pharmacological interventions and understand the pathogenesis of PAM. This may involve investigating novel targets and therapies that can effectively manage disease progression.

References:

[1] A Göcmen (1992) - Cited by 84 [6] U Ozcelik (2010) - Cited by 80 [8] E Cakir (2015) - Cited by 54 [12] Orphanet (2024) - Pulmonary alveolar microlithiasis [13] G Barbolini (2002) - Cited by 44

Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disease characterized by calcifications within the alveoli. The differential diagnosis for PAM includes several conditions that present with similar radiological findings.

Conditions to Consider:

• Tuberculosis: A bacterial infection that can cause calcifications in the lungs, particularly in cases of miliary tuberculosis.
• Sarcoidosis: An autoimmune disease that can lead to lung inflammation and calcification.
• Pneumoconiosis: A group of lung diseases caused by inhalation of dust particles, which can result in calcification.
• Amyloidosis: A condition where abnormal proteins accumulate in the body's tissues, including the lungs, leading to calcification.

Other Associated Diseases:

• Idiopathic pulmonary hemosiderosis: A rare disease characterized by bleeding and iron accumulation in the lungs.
• Healed varicella pneumonia: A complication of chickenpox that can lead to lung scarring and calcification.
• Silicosis: A lung disease caused by inhalation of silica particles, which can result in calcification.

Key Diagnostic Features:

• Characteristic chest radiograph and CT findings
• Lung biopsy confirms the diagnosis
• No effective medical therapy available

According to [4], PAM is a rare genetic lung disease characterized by calcifications within the alveoli. The differential diagnosis for PAM includes several conditions that present with similar radiological findings, such as tuberculosis, sarcoidosis, pneumoconiosis, and amyloidosis [5]. Other associated diseases include idiopathic pulmonary hemosiderosis, healed varicella pneumonia, and silicosis [5].

References: [4] FAF Francisco (2013) - Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disease characterized by calcifications within the alveoli. [5] C Kannan (2020) - The differential diagnosis include tuberculosis,sarcoidosis, pneumoconiosis and amyloidosis. Other reported associated diseases include idiopathic pulmonary hemosiderosis, healed varicella pneumonia, and silicosis.