NECROBIOTIC XANTHOGRANULOMA
Necrobiotic xanthogranuloma is a rare skin condition
that is frequently associated with an underlying monoclonal gammopathy. It was
first described in the early 1980s. Since then, many cases have been reported
that have confirmed this to be a distinct, albeit unusual and infrequently
encountered, skin condition. The pathological findings of necrobiotic
xanthogranuloma are distinctive and are required to make the diagnosis.
Patients with this diagnosis need to be monitored routinely to watch for the
development of a monoclonal gammopathy and the possibility of multiple myeloma.
Clinical Findings: So few cases of necrobiotic xanthogranuloma have been reported that no
firm conclusion can be made on the epidemiology of the disease. However, it is
a disease of older adulthood, with almost all cases occurring after the age of
50 years. The lesions have been reported to occur anywhere on the human body,
but they are found most often on the forehead, cheeks, and temporal regions
around the eyes. The periorbital region is almost always affected. Necrobiotic
xanthogranulomas are typically yellowish to red papules and plaques. There may
be intervening atrophy between the areas of involvement. The leading edge of
the plaques may have a red or violaceous hue. Occasionally, nodules form.
Secondary ulceration is frequently reported, as are telangiectases and dilated
dermal vessels, which are most prominent in the regions of atrophy. The
ulcerations take an extended period to resolve. Most patients are distraught by
the appearance of the rash and complain of a mild pruritus, although many have
no symptoms. The clinical differential diagnosis includes forms of planar
xanthomas. A skin biopsy helps differentiate these conditions. This disease
progresses over time and typically does not spontaneously remit.
Patients almost always complain of dry eyes or have
objective findings of proptosis. In rare cases, necrobiotic xanthogranuloma
affects the lacrimal gland and retrobulbar fat tissue.
Necrobiotic xanthogranuloma is associated with an
immunoglobulin G-κ (IgG:κ) monoclonal gammopathy in most cases. The presence of
a gammopathy should make the clinician seek the advice of a hematologist to
perform a bone marrow biopsy to help evaluate for multiple myeloma. A small
percentage of patients with this gammopathy have or will develop multiple
myeloma. Other frequently abnormal laboratory tests in necrobiotic
xanthogranuloma include an elevated erythrocyte sedimentation rate (ESR), a
decreased level of complement C4, and leukopenia. Many other abnormalities have
been described, providing more evidence that this is a systemic disease and not
an isolated skin disease. Lesions of necrobiotic xanthogranuloma have also been
described to occur in the upper respiratory system and in the heart.
Pathogenesis: The
pathogenesis has been theorized to be an antibody response to a self-antigen,
most likely a form of
lipid. This is unproven, and the exact etiology is unknown.
Histology: The biopsy
findings of necrobiotic xanthogranuloma are unique and characteristic. A punch
biopsy or excisional biopsy should be performed to allow for adequate
evaluation. On first glance, the entire dermis is filled with inflammatory
cells. The inflammation is in the granulomatous category. A unique and characteristic finding, when seen, is that
of cholesterol-filled, needle-shaped clefts within the granulomatous
infiltrate. Giant cells, both the foreign body type and the Touton type, are
commonly seen. The granulomatous infiltrate surrounds and envelops necrobiotic
collagen tissue. There is usually an underlying, predominantly lobular
panniculitis without vasculitis.
Treatment: Therapy is
difficult. No randomized prospective studies have been performed on this rare condition, so only anecdotal therapies have been
reported. Topical and oral steroids have been somewhat successful.
Chemotherapeutic agents have been used with variable success, including the
alkylating agents. Results have been varied, with some patients experiencing
long-term remission. Patients all need to be screened for gammopathy and for
the development of multiple myeloma. The presence of myeloma portends a worse prognosis.
