Pulmonary Langerhans Cell Histiocytosis (PLCH) - Rare Disease

Introduction

In pulmonary Langerhans cell histiocytosis, the lymphocytes, plasma cells, neutrophils, and eosinophils infiltrate the bronchioles and alveolar connective tissue along with monoclonal (synthetic proteins that function similarly to antibodies within the body's immune system) Langerhans cells. This condition, known as Langerhans cell histiocytosis, which mostly affects the lungs, skin, bones, pituitary, and lymph nodes, is characterized by PLCH as its various manifestations.

Although the cause of PLCH is unknown, it affects smokers between the ages of 20 and 40 years exclusively. Both men and women are equally affected. Women experience illness beginning at a later age; however, sex-specific differences in onset age may reflect distinct smoking habits.

What Are the Signs and Symptoms?

• Dyspnea- Breathing difficulty or loss of breath accompanied by discomfort.

• A nonproductive cough.

• Lethargy.

• Fever.

• Weight loss.

• Pleuritic chest pain- chest discomfort that increases with breathing.

• Spontaneous pneumothorax- A lung that collapses suddenly and for no evident reason.

• Langerhans cell histiocytosis- A disease that has no known cause and is marked by the growth of abnormal Langerhans cells.

The most frequent signs of extrapulmonary involvement, which can affect up to of patients and are hardly ever the initial symptoms of PLCH, include:

• Bone pain due to bone cysts and rash.

• Polyuria- Excessive or abnormally enormous urine production or passage caused by central diabetes insipidus.

What Is the Diagnostic Test?

• Pulmonary Function Tests: Pulmonary function tests (PFTs) are a set of diagnostic procedures used to assess the functioning of the respiratory system. These tests provide valuable information about lung capacity. The pulmonary function abnormalities exhibit variability based on the degree of cystic involvement and the disease duration. The prevailing anomaly frequently observed is a decrease in the diffusing capacity of the lungs for carbon monoxide (DLCO). Furthermore, the pulmonary function test frequently reveals a decrease in vital capacity (VC), maintenance of total lung capacity (TLC), and either an increase or normal value for residual volume (RV) and the RV/TLC ratio. A positive correlation exists between the severity of airflow limitation observed during lung function testing and the extent of cystic lesions identified through high-resolution computed tomography (HRCT).

• Tests in the Lab: The outcomes of lab testing frequently have normal values. However, PLCH patients frequently have high blood inflammatory marker levels. Patients with diabetes insipidus exhibit low urine-specific gravities and serum and blood hyperosmolarity (where the circulation has high salt (sodium), glucose, and chemicals). The hepatic enzyme (liver enzymes) and bilirubin levels in the serum are typically elevated, which indicates liver involvement.

• Bronchoscopy and Bronchoalveolar Lavage: Bronchoscopy primarily aims to rule out other conditions, particularly during infections. Even though the disease is bronchiolocentric, the accuracy of the diagnosis of transbronchial biopsy is low. Transbronchial biopsy is most helpful in individuals with nodular lesions (a development of unusual tissue.). Still, it carries a significant risk of pneumothorax (collapsed lungs due to leakage of air into the space between the lung and chest in patients) with cystic (relates to the typical scarring or fibrosis) lesions.

• Lung Biopsies: An open lung biopsy is the most accurate method for diagnosing PLCH. It is not required to confirm pulmonary lesions in patients with LCH diagnosed with the condition through histological analysis of tissue samples taken from other foci.

• Particle-Emission Tomography: Positron emission tomography with 18F-fluorodeoxyglucose is only marginally useful for diagnosing PLCH patients. Positron emission tomography (PET) is more sensitive than detecting lesions in the bone, especially those that are subclinical and include lymph nodes, liver, spleen, or thyroid. Positron emission tomography is sensitive for determining early therapy response and disease relapse.

• Computerized Tomography: An important factor in PLCH diagnosis is high-resolution computed tomography (HRCT). The cysts become larger and develop a thin wall as the condition worsens. Lesions may be found in the lower lobes of the lungs in children who experience symmetrical lung damage. Other radiological signs of illnesses caused by smoking are frequently discernible in PLCH patients. Patients with advanced illness show symptoms such as megalocardia (a cardiac enlargement that is not normal), pulmonary (lung) enlargement, and pulmonary hypertension.

Standard chest radiography has limited utility since many lesions could be minor. The middle and upper lung fields of patients with advanced illness show various lesions. Lung volumes are normally conserved but may be reduced in patients who have had a pneumothorax or pleurodesis (a procedure in medicine that employs chemical or pharmaceutical agents to induce inflammation while adhesion between the pleural layers) in the past.

What Are the Treatment Methods?

Due to the unpredictability of PLCH in individual patients and the possibility of spontaneous remission, observation with close follow-up is the treatment of choice.

• Smoking Cessation: Individualized smoking cessation programs may be necessary for all patients who must quit smoking. In a substantial number of patients, therapy is the only treatment required. Pneumothorax management can be particularly problematic and needs almost constant drainage. Surgical pleurodesis is advisable in cases of recurrence. In a conservative approach, it is frequently necessary for cases of a single large pneumothorax due to frequent and protracted air leakage and an elevated risk of recurrence. These patients should be directed to centers with specialized knowledge of these procedures. Patients who may be possibilities for lung transplantation in the future should try to avoid pleurectomy; however, pleurectomy is sometimes unavoidable due to recurrent pneumothoraces.

• Vaccination: Lower respiratory tract infections are a common cause of deterioration in PLCH and should be treated immediately. Patients with impaired respiratory function are recommended to receive annual influenza and anti-pneumococcal vaccines.

• Systemic Therapy: Systemic therapy is a type of psychotherapy that focuses on how an individual's interpersonal relationships, behavioral patterns, and life decisions are interconnected with the problems they confront. Patients with symptoms and diminished lung function are considered for systemic therapy.

• Medications: Some physicians prescribe oral corticosteroids to patients with progressive disease despite no controlled evidence of their effectiveness in stabilizing or causing disease remission. Due to the immunosuppressive nature of this treatment, Pneumocystis jirovecii and Herpes virus prevention should also be administered for an extended time.

• Oxygen Supplementation: Oxygen supplementation is used to treat hypoxia. In many instances of pulmonary hypertension, symptomatic treatment is necessary. The role of vasodilator therapy in the treatment of PLCH/pulmonary hypertension needs to be better understood, and its use should be restricted to institutions with expertise in both vascular and advanced lung disease. Relapse of the disease in transplanted lungs has been described, particularly in individuals who have pre-operative extrapulmonary symptoms and those who recommence smoking after transplantation.

What Is the Prognosis of This Condition?

• PLCH has an unexpected and changeable natural history and prognosis. Loss of follow-up occurs for many individuals due to spontaneous regression and stabilization of the disease after quitting smoking, as well as the prevalence of addiction to drugs other than tobacco in certain patients; this may affect the evaluation of survival. When compared to those who are sex and age-matched from the general population, patients with PLCH were to have a reduced survival rate.

• Negative prognostic indicators include decreased spirometry parameters, poor lungs' ability to diffuse carbon monoxide, severe cystic lesions found on HRCT, low oxygen arterial pressure, advanced age, pulmonary hypertension, and multisystem LCH in these conditions; oxygen supplementation is indicated.

• A child's severe lung involvement significantly affects both the course of the disease and survival—Prophylaxis against viral infection and the early delivery of targeted LCH medicines.

• Pneumococcal and influenza vaccinations are advised for patients with PLCH because they are at a higher risk of infection.

Conclusion

PLCH is a rare disease characterized by pulmonary cysts, and the pathogenic mechanisms it is diagnosed with are based on the pathological characteristics of CD1a+ cell clustering. There currently needs to be a definitive treatment plan for PLCH. Quitting smoking is the primary treatment, but Cladribine, along with BRAF inhibitors medicine, is among the most effective options for treating aggressive PLCH. Individualized treatment plans based on each patient's condition are required and will enhance outcomes. PLCH cases must continue to be observed and followed up on over the long term.