Introduction:
The human body comprises several body fluids that perform a multitude of functions. Blood and blood elements are crucial components that maintain the integrity and vitality of the body. Blood consists of various cells, each specialized for specific functions. Of the different types of cells, white blood cells are an integral part of our immune system. They are the primary defense tool that helps fight infections in the body. There are many white blood cells specific to certain organs or tissues. Histiocyte is a type of white blood cell that helps fight infection and foreign bodies. It is an immune cell most commonly found in blood, bone marrow, skin, liver, lymph nodes, spleen, and lungs.
What Is Langerhans Cell Histiocytosis?
An abnormal increase in the histiocyte cell results in a rare disorder known as Langerhans cell histiocytosis (LCH). It most commonly affects toddlers; however, young children and adults can be affected. LCH tends to form tumorous growth and can spread to other body parts, suggesting that it is a cancer-like condition. LCH may be classified as a single system disease when it affects a single body part or a multisystem disease when more than one body part is affected.
What Are the Causes of Langerhans Cell Histiocytosis?
The exact cause of LCH is unknown; however, mutation of certain genes may lead to the development of abnormal histiocyte cells, thereby causing the accumulation of these cells in different body parts. However, other factors, such as viral infections and toxins, can also contribute to the development of this disorder. There are certain risk factors for the development of LCH; they are listed below:
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Familial exposure to environmental toxins.
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Exposure to metal, granite, or wood dust (occupational hazard).
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Familial history of LCH.
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Thyroid disorder.
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Smoking.
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Unvaccinated child.
What Are the Symptoms of Langerhans Cell Histiocytosis?
The signs and symptoms of LCH depend on the site affected. A single system LCH affects just one body part, whereas multisystem LCH affects several body parts. The most common symptom is abnormal growth, also called granulomas. These granulomas may occur on the skin, bone, or other organs. They are usually not symptomatic; however, larger granulomas or those in proximity to a neurovascular structure may result in pain. A bone granuloma may even cause a fracture of the affected bone. The symptom pertaining to the sites are given below:
1. Skin and Nails:
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Flaking of the skin, especially the scalp, perineum, or the inner part of the elbow.
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Brownish or purplish raised bumps on the skin.
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Itchy or painful rash.
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Ulcers over the skin.
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Discolored and flaky fingernails that shed off easily.
2. Bone:
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Lump over any bone such as the skull, jaw, ribs, spine, leg, or hands.
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Painful swelling.
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Swelling in the leg bones may affect mobility resulting in limping or difficulty walking.
3. Mouth:
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Swelling and bleeding gums.
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Teeth may become loose and even fall out.
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Ulcers in the tongue, lips, or any part of the oral cavity.
4. Lymph Nodes:
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LCH may affect the lymph nodes and the thymus (the organ that produces and maintains the immune cells).
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Swelling of the lymph nodes and the thymus.
5. Central Nervous System:
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Abnormal vision.
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Persistent headache.
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Vomiting.
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Frequent urination.
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Excessive thirst.
6. Ear:
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Chronic infections.
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Discharge with a foul smell.
7. Gastrointestinal System:
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Dysfunction of the liver and spleen.
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Easy bruising and yellowing of the skin due to liver dysfunction.
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Bloody stools.
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Itching of the skin.
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Fluid accumulation in the abdomen and liver.
8. Lung:
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Fluid accumulation in the lung.
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Difficulty in breathing.
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Cough.
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Chest pain.
9. Bone Marrow:
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Recurrent infections.
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Easy bleeding or bruising.
10. Endocrine System:
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Delayed onset of puberty.
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Thyroid dysfunction.
How Is Langerhans Cell Histiocytosis Diagnosed?
Physical examination and medical history usually lead to certain diagnostic tests. Imaging is crucial in LCH to determine whether it is a single-system or multisystem disease. The treatment and prognosis vary significantly with either type. Though imaging tests may conclude the diagnosis, a biopsy yields a confirmatory diagnosis. Image-guided biopsy is more specific to retrieving the tissue from a specific site. The diagnostic workup is as given below:
1. Physical Examination and Medical History: A detailed medical history can indicate the risk factors associated with LCH. Signs such as lumps, bruises, skin rashes or bumps, and other physical signs may be indicators of LCH, thus triggering further diagnostic tests.
2. Blood Tests: A routine blood test may indicate abnormal blood cell count, deranged hemoglobin levels, white blood cells, and platelets. In multisystem disease, the thyroid and liver function tests may also show abnormality.
3. Neurological Examination: A neurologic examination is needed to assess the neurological status of the patient. This would include the sensory factors, such as mental status, senses, and the reflex and motor aspects, such as the inability to walk, lack of coordination, and motor imbalances.
4. Urine Analysis: The presence of sugar, proteins, or blood cells in urine indicates an abnormality requiring further ancillary tests.
5. Genetic Testing: Since gene mutation is the primary cause of LCH, genetic testing, in particular, to identify the BRAF (protein called B-Raf) gene changes may lead to a more confirmatory diagnosis.
6. X-Ray: X-ray is the simplest and most non-invasive technique to diagnose LCH. It uses a form of radiation to create images of various parts of the body. A skeletal X-ray is very beneficial to confirm LCH. It shows a characteristic punched-out appearance of the tumors in the bone. A chest X-ray may show diffuse nodules over the rib cage, and advanced cases may show fluid accumulation within the lungs.
7. Computed Tomography: Computed tomography (CT) is an imaging technique that helps create a series of images of body parts. The advantage of CT is acquiring high-resolution images in multiple planes, which provides more diagnostic accuracy. A chest CT may indicate the following:
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Multiple small nodules.
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Cystic cavitation of nodules if present.
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Mediastinal lymphadenopathy (lymph node enlargement).
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Fluid accumulation in the lungs.
8. Nuclear Imaging: A PET (positron emission tomography) is considered of more diagnostic value and the preferred imaging technique in LCH. This procedure involves injecting a small amount of radiotracer material into the vein. The radiotracer material most commonly used is 18-fluorodeoxyglucose (FDG). This tracer has an increasing affinity to glucose molecules which are abundantly found in tumor cells. Hence this tracer tends to accumulate more in the tumor, which can be easily visualized in the imaging method. PET CT is more specific and sensitive than other imaging modalities in diagnosing LCH.
9. Magnetic Resonance Imaging (MRI): MRI uses magnetic fields and radio waves to create images of the structures within the body. A contrast MRI is more specific to diagnosing LCH. However, the contrast agent used in MRI is gadolinium-based, a potent nephrotoxic. Hence patients with compromised renal functions or advanced renal diseases are contraindicated for contrast MRI as it could result in complete renal failure.
10. Ultrasound: Ultrasound examination is a non-invasive technique that uses sound waves to create images of body parts. An abdominal ultrasound is hugely beneficial in LCH to determine the involvement of the gastrointestinal organs such as the liver and spleen. It can also detect fluid accumulation in the abdomen and liver.
11. Pulmonary Function Test: A pulmonary function test can be used to determine lung function and the severity of lung damage.
12. Biopsy: Biopsy is a confirmatory test for diagnosing LCH. Biopsy of a tissue sample from the skin, lymph nodes, bone, liver, or other sites can be done. An imaging technique such as X-ray, CT, or ultrasound may aid in retrieving the precise tissue sample, thereby creating a more accurate diagnosis. The pathological examination of sample tissue will reveal the histiocytic cells.
Conclusion:
LCH is a rare disease requiring multidisciplinary treatment. It has an increasing tendency to spread or recur, requiring aggressive treatment modes. Diagnostic imaging is critical to assess the severity and involvement of various body parts. Targeted therapies are beneficial; however, the prognosis remains questionable due to the uncertain nature of the disease.
