Necrobiotic Xanthogranuloma - Symptoms, Diagnosis, and Therapeutic Approaches

Introduction

Non-Langerhans cell histiocytosis refers to a group of rare disorders where certain immune cells, other than Langerhans cells, behave abnormally. These disorders can manifest in various ways, often involving the formation of tumors or lesions in different parts of the body. The exact cause of these conditions is often unknown and can affect people of any age.

What Is Necrobiotic Xanthogranuloma?

Necrobiotic Xanthogranuloma (NXG) is an uncommon type of non-Langerhans histiocytosis distinguished by the emergence of yellowish lesions, mainly around the periorbital region. Necrobiotic xanthogranuloma is a chronic condition that affects different parts of the body. It causes firm, yellow, or orange patches and lumps, often around the eyes. These areas can develop sores and scars. This condition predominantly impacts adults and is more prevalent among individuals 40 or older. In 1980, Kossard and Winkelmann were the first to distinguish between NXG and xanthomas. NXG can also involve other organs like the heart, lungs, stomach, and liver. It is closely connected to certain blood and immune system problems.

What Causes Necrobiotic Xanthogranuloma?

The cause of necrobiotic xanthogranuloma is not completely understood.

• One theory is that proteins in the blood mix with fats, leading to deposits in the skin that cause lesions.

• Another theory involves immune cells known as macrophages, which are attracted to these deposits. However, not all NXG patients have high protein levels in their blood.

• Research also indicates that immune cells filled with fat could cause skin inflammation.

• Some studies have suggested a potential connection to infection, with Borrelia bacteria found in certain patients.

• NXG is often associated with underlying systemic conditions like monoclonal gammopathy, multiple myeloma, and other plasma cell dyscrasias. These conditions may trigger or exacerbate the development of necrobiotic xanthogranuloma.

What Are the Symptoms of Necrobiotic Xanthogranuloma?

• Necrobiotic xanthogranuloma generally appears as firm, yellow nodules and plaques on the skin, usually less than 10 inches in size. These can appear anywhere on the body but most commonly on the face, particularly around the eyes.

• Some cases involve lesions on the torso or extremities without facial involvement. These plaques often have a purplish tint with a yellowish hue, and tiny blood vessels may be visible.

• Facial lesions are a key feature, starting as small bumps similar to xanthelasma that develop into larger plaques.

• The lesions may cause itching or a burning sensation, and about 43 % of cases develop central atrophy and ulceration.

• Ocular symptoms occur in half to four-fifths of cases and can include issues with the conjunctiva, cornea, and other eye parts, such as double vision, vision loss, or bulging eyes.

• NXG is a systemic condition, which can also affect internal organs. Organs like the heart, lungs, kidneys, and intestines may be involved, sometimes without noticeable symptoms until death.

How Is Necrobiotic Xanthogranuloma Diagnosed?

• Imaging - Imaging tests such as ultrasound, MRI, or CT scans can be done to determine the size of the lesions and check if they affect any underlying structures, particularly in periorbital lesions.

• Skin Biopsy - The diagnosis of necrobiotic xanthogranuloma is often confirmed through histopathological examination of skin biopsies.

  • Granulomatous inflammation is in a band-like pattern, consisting of various inflammatory cells, including foamy histiocytes, lymphocytes, Touton giant cells, and foreign-body giant cells.

  • Involvement of the middle dermis and panniculitis (inflammation of the fatty tissue beneath the skin).

  • The presence of cholesterol clefts in areas of necrosis is common in most cases.

  • Nodular aggregates of lymphocytes or lymphoplasmacytic cells may also be seen.

• Laboratory Tests - Blood tests may be conducted to assess for underlying systemic conditions, such as monoclonal gammopathy or multiple myeloma, commonly associated with NXG. Laboratory tests may show decreased levels of complement proteins and signs of anemia and leukopenia (reduced red and white blood cell counts).

• Differential Diagnosis - Several other conditions can resemble NXG. Clinically, it is important to differentiate NXG from these conditions:

  • Chronic lupus erythematosus, especially for lesions on the face.

  • Psoriasis, particularly for lesions on the lower limbs.

  • The chalazodermic form of mycosis fungoides can resemble NXG lesions on the trunk.

  • Necrobiosis lipoidica.

  • Normolipemic plane xanthomas.

  • Xanthelasma.

  • Xanthoma disseminatum.

  • Multicentric reticulohistiocytosis, etc.

How Is Necrobiotic Xanthogranuloma Treated?

The management of necrobiotic xanthogranuloma often requires a team of specialists. The treatment options may vary with severity and involvement.

Common treatment methods for NXG are:

• Corticosteroids - These medications can help reduce inflammation and improve symptoms, especially for localized lesions.

• Immunomodulatory Therapy - Drugs like Methotrexate, Azathioprine, and Mycophenolate mofetil may be prescribed to regulate the immune response and prevent the progression of the disease.

• Plasma Exchange (Plasmapheresis) - If an underlying monoclonal gammopathy exists, plasma exchange may be considered to remove abnormal proteins from the bloodstream.

• Radiation Therapy - Localized lesions that do not respond to other treatments may benefit from radiation therapy.

• Surgical Excision - In some cases, surgical removal of lesions may be necessary to relieve symptoms or improve appearance, especially if there is ulceration or significant disfigurement.

• Monoclonal Antibody Therapy - New therapies that target specific pathways involved in developing necrobiotic xanthogranuloma, such as monoclonal antibodies, are currently being studied and may offer promising treatment options.

What Are the Complications and Prognosis of Necrobiotic Xanthogranuloma?

In the later stages of necrobiotic xanthogranuloma, issues like organ problems or death can happen. Hematologic cancer, rather than NXG, mainly causes these problems. Blindness, although uncommon, can also happen as a secondary issue.

This can be due to exposure keratopathy or severe scleritis linked to NXG. If left untreated, skin lesions from NXG can worsen. Patients may also have blood-related issues like plasma cell dyscrasia or lymphoproliferative disorders.

It is highly advised to undergo regular hematologic check-ups to catch any potential lymphoproliferative disorders, such as multiple myeloma, that may develop long after the initial diagnosis of NXG. Similarly, routine eye exams are recommended to watch out for eye surface and orbital symptoms.

Conclusion

Some patients with necrobiotic xanthogranuloma experience remission or stabilization of the disease with appropriate therapy, while others may have a more chronic and progressive course. Timely diagnosis and the quick start of suitable treatment are essential for controlling symptoms and avoiding complications. More studies are necessary to gain a deeper insight into the development of NXG and create more precise treatments for this complex condition.