What is Necrobiotic Xanthogranuloma?
The Necrobiotic Xanthogranuloma is a type of Orbital Xanthogranulomatous disorder. It is a rare, chronic, progressive form of Non-Langerhan Histiocytosis. It is characterized by the yellowish plaques, lesions and nodules. The Necrobiotic Xanthogranuloma commonly occurs in the periorbital area.
Necrobiotic Xanthogranuloma Symptoms
The Necrobiotic Xanthogranloma, a type of Non-Langerhan cell histiocytosis, is a yellow xanthomatous plaque on the skin that can ulcerate and scar. The pain and burning occur in the majority of the asymptomatic cases. The symptoms of the Necrobiotic Xanthogranloma are associated with the skin, eyes, blood, heart, and some are systemic.
The subcutaneous skin lesion of Necrobiotic Xanthogranuloma most commonly occurs in the periorbital region, but it can also be presented on the face, trunk, or limbs. The skin lesion can ulcerate and cause scaling. The lesions are usually in the form of hard papules, plaque or nodules having either yellow, red-orange or violet colour. The asymptomatic lesions are generally pruritic. The lesion in the periorbital region can also lead to the ocular symptoms depending upon the severity of the disease.
The Periorbital lesions can affect one or both eyes, that is it can either be unilateral or bilateral. The nearby ocular structures are affected by the hard callous ulcerated lesion. If the roots of the lesion enter deep into the ocular region, the patient may complain about the itching, burning, blurred vision, pain and diplopia. Some patients also complain of conjunctivitis, keratitis, blepharitis and proptosis. Some patients develop myeloma due to the monoclonal gammopathy. Therefore the examination of the multiple myeloma is made through biopsies.
The disorder such as the multiple myeloma, Non- Hodgkin’s lymphoma and chronic lymphocytic leukaemia may occur before or after the onset of skin lesions. The extracutaneous regions like lungs, heart, kidneys, larynx, skeletal muscles and intestine are also affected. The patient with Necrobiotic Xanthogranloma often suffers from Giant-cell myocardial diseases. So their proper cardiac screening should be done regularly. The patients with Necrobiotic Xanthogranloma often have paraproteinemia; therefore, they have a chance of developing lymphoproliferative disorders. The patients follow up should be done regularly because patients have a chance of developing splenomegaly or hepatomegaly.
Necrobiotic Xanthogranuloma Causes
The pathophysiology of Necrobiotic Xanthogranuloma is not known. There are multiple theories related to the pathophysiology of the Necrobiotic Xanthogranloma. According to one of the hypotheses, the paraproteins acts as lipoproteins and binds to the monocyte’s lipoprotein receptors, thereby leading to the formation of Xanthoma.
Xanthoma is yellow coloured skin lesions compromising of cholesterol and fats. Another theory states that the orbital xanthogranulomatous diseases result from the increased number histiocytes in the body. These diseases are the type of Non-Langerhans cell Histiocytosis. The circulating monocytes produce histiocytes. Monocytes are made in the bone marrow, and then they enter into the tissues where they undergo maturity either in the mononuclear-phagocytic system or the dendritic cell system.
The mononuclear-phagocytic system gives rise to the Necrobiotic Xanthogranloma. The mononuclear-phagocytic system consists of phagocytic monocytes and free macrophages. These free macrophages are thought to be responsible for the Necrobiotic Xanthogranloma due to their reactive free tissue proliferation. One more theory states that the monocytes activation in the body is responsible for the intracellular accumulation of the fat and cholesterol in the skin. It is generally thought that paraproteins and the immunological complexes are responsible for provoking the xanthogranulomatous responses. Necrobiosis, the degradation and death of the cell, occurs due to lack of oxygen that is due to hypoxia or ischemia.
Necrobiotic Xanthogranuloma Treatment
The treatment interventions for Necrobiotic Xanthogranloma are quite limited. The treatment of Necrobiotic Xanthogranuloma is often fruitless; therefore, it is quite challenging. The treatment is performed to reduce the risk of skin ulcers and scars. There is no approved therapeutic treatment for the Necrobiotic Xanthogranuloma because of the rarity of the disease. The treatment strategies of the Necrobiotic Xanthogranuloma are based on whether Necrobiotic Xanthogranuloma is being treated alone or with multiple myeloma or systemic involvement.
In the case of Necrobiotic Xanthogranuloma with myeloma is often treated with Alkylating agents such as Melphalan, Chlorambucil and Cyclophosphamide. These Alkylating agents are usually given with systemic steroids. When treating Necrobiotic Xanthogranuloma alone, Alkylating agents such as Melphalan, Chlorambucil and Cyclophosphamide are used along with systemic steroids. Besides, other agents such as Methotrexate, Thalidomide and Immunoglobulins are also used. Some agents such as Azathioprine, Interferon-alpha-2b, Corticosteroids, Antibiotics such as Tetracyclines and Dapsone are also for the treatment of Necrobiotic Xanthogranuloma. Another intervention for the treatment of the Necrobiotic Xanthogranuloma Is the Autologous Stem Cell Transplant.
The targeted therapy is also done in case of localized disease either through Radiation therapy, Phototherapy and Psoralen + UVA (PUVA) photochemotherapy. Surgical excision is done when a single and small lesion is present. Intralesional steroids injections are also used for the Necrobiotic Xanthogranuloma.