Adult Onset Xantogranulomatous Disease Associated with Vitiligo.

Adult Onset Xanthogranulomatous Disease represents an umbrella term encompassing 4 distinct entities with partially overlapping clinicopathological features: adult-onset xanthogranuloma, adult-onset asthma with periocular xanthogranuloma, Erdheim-Chester disease, and necrobiotic xanthogranuloma. They are characterized by a predilection to affect the orbit and ocular adnexa and special histopathological features, in particular infiltrates comprising non-Langerhans-derived foamy histiocytes and Touton giant cells. The appearance of the eyelid lesions is virtually diagnostic, producing readily recognisable diffuse, yellow plaques. Affected patients should be investigated and reviewed regularly for systemic disease. We would like to present a case of 35-year-old male patient with Adult-onset xanthogranulomatous disease [AOXG] associated with vitiligo. This case is reported for its rarity. Copyright:

Case History

A 35-year-old man presented with a 2 year history of painless swellings, first noted in the left peri-orbital region, slowly growing in size and later involving the periorbital area of right eye. He was a known case of vitiligo vulgaris on treatment since 5 years. Physical examination revealed skin coloured plaques below the left eye. At the same time, similar but less conspicuous lesions were also noted around the medial canthus and below the left eye [Figure 1]. Multiple well-defined depigmented patches were present over face, lips, hands and feet. On palpation, the lesions were found to be non-tender, firm and involving the subcutaneous plane. Histopathological examination of the incisional biopsy from the infiltrated plaque below eyelid on the left side revealed a diffuse inflammatory infiltrate extending up to deep dermis [Figure 2]. The inflammatory infiltrate was composed of histiocytes intermingled with aggregates of lymphocytes, plasma cells, eosinophils and scattered Touton giant cells. The histiocytes were large, polygonal and with abundant xanthomatous cytoplasm. The overlying epidermis was unremarkable [Figure 3a and b]. Immunohistochemical staining demonstrated the expression of CD68 [Figure 4], S100 [Figure 5] in the foamy histiocytes and negative for CD1a.

Figure 1

Bilateral indurated non ulcerated skin coloured plaques below the eyelids

Figure 2

(a): Diffuse infiltration of mostly xanthomatous histiocytes, intermingled with aggregates of lymphocytes and eosinophils. (H and E) 10X. (b): Diffuse infiltration of mostly xanthomatous histiocytes, intermingled with aggregates of lymphocytes and eosinophils. Touton giant cells are seen.(H and E) 40X

Figure 3

Immunohistochemistry showing S100 Positive

Figure 4

Immunohistochemistry showing CD68 Positive

Figure 5

Immunohistochemistry showing CD1a Negative

Laboratory evaluation revealed hemoglobin: 14.4 g/dl, total leucocyte count: 6600 cells/cumm with differential count of 56% neutrophils, 32% lymphocytes, 2% monocytes, 8.9% eosinophils and 0.2% basophils. Platelet count was 90000/cumm. Peripheral blood smear showed normocytic normochromic blood picture with thrombocytopenia and eosinophillia. Opthalmological examination was normal. Serum lipids, immunoglobulin E and protein electrophoresis were within the normal range. Based on the clinical and histopathological findings, the patient was diagnosed with adult-onset orbital xanthogranuloma [AOXG]. Conservative multi-step surgical excision combined with intralesional corticosteroid injections into the residual lesions were planned as treatment.

Discussion

Adult-onset orbital xanthogranuloma is a rare disorder affecting patients from 17 to 85 years of age with no significant sex preference. The significance of recognising this entity is that it is often self-limited and does not require aggressive therapy.[1] Necrobiotic xanthogranuloma typically presents with ulcerated nodules which are histopathologically characterized by the presence of necrobiosis surrounded by palisading epithelioid histiocytes, more numerous Touton giant cells and cholesterol clefts. It is commonly associated with paraproteinemia and multiple myeloma.[2] Erdheim-Chester disease is notable for the progressive fibrosclerosis of the orbit and carries the worst prognosis within this spectrum due to the frequent impairment of visual acuity and fibrotic involvement of internal organs.[12] Adult-onset asthma with periocular xanthogranuloma, on the other hand, is frequently associated with lymphadenopathy and elevated levels of polyclonal IgG in addition to its hallmark feature of adult-onset asthma.[2] The distinctive histopathological finding in this disorder is the presence of large lymphoid aggregates with reactive germinal centres in the cutaneous lesions.[12] Adult-onset orbital xanthogranuloma presents with isolated orbital involvement without accompanying immune dysfunction, asthma or paraproteinemia; however, hematological abnormalities such as thrombocytopenia, eosinophilia, anemia and lymphopenia have been anecdotally reported.[3]

Clinically, the absence of paraproteinemia, asthma, lymphadenopathy or internal organ involvement was consistent with adult-onset xanthogranuloma. Thrombocytopenia in this case may be an independent finding or related to the xanthogranulomatous disease, similar to previously reported cases accompanied by hematological abnormalities.[23]

Tang et al. speculated that adult-onset xanthogranuloma and necrobiotic xanthogranuloma possibly represent two poles of a spectrum with the latter representing the severe form.[3]

Vitiligo is strongly associated with a number of autoimmune disorders such as autoimmune thyroiditis, Insulin dependent diabetes mellitus, Addison's disease, pernicious anemia, systemic lupus erythematosus, inflammatory bowel disease and Autoimmune polyendocrinopathies. Unlike other cases, this is the first case of vitiligo associated with AOXG to our limited knowledge.[4]

Immunohistochemically, the foamy histiocytes are strongly positive for CD68, CD163 and factor XIIIa but are usually negative for CD21, CD35, S100, and CD1a (not shown). However, rarely, these foamy histiocytes can be positive for S100 and negative for factor XIIIa, as in rare cases of juvenile xanthogranuloma. Therefore, neither a negative factor XIIIa nor a positive S100 result should preclude the diagnosis of AOXGDs.[5]

Although progression to necrobiotic xanthogranuloma has not been documented in a small case series of adult-onset xanthogranuloma, we think that long-term follow-up for paraproteinemia appears prudent in cases such as ours.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.