Xanthoma disseminatum: improvement in disfiguring facial lesions with cladribine

Xanthoma disseminatum, a rare non-Langerhans cell histiocytosis, manifests as multiple symmetrical xanthomatous lesions with a flexural predilection, and is often refractory to treatment. We report a case of xanthoma disseminatum with disfiguring facial involvement, which improved with cladribine. A 23-year-old man had gradually progressive multiple yellow-brown papules on his face, neck and axillae for the last 5 years. History was relevant for increased thirst and frequency of micturition for the last 10 years. Clinical examination showed numerous yellowish papules coalescing to form plaques, around the lips, nasolabial folds and chin. Brown-coloured macules and papules were present symmetrically on the forehead, peri-orbital region, neck and around axillae. Skin biopsy from a neck papule was consistent with the clinical diagnosis of xanthoma disseminatum. (Fig. 1) Routine blood investigations including fasting lipid profile were within normal reference range. Water deprivation test and the non-visualization of posterior pituitary on T1-weighted magnetic resonance imaging (MRI) of the sella were suggestive of central diabetes insipidus. The patient was treated with cladribine in the dose of 0.14 mg/kg/day for 5 days every month. Diabetes insipidus was well controlled with oral desmopressin 0.1 mg daily. He stopped developing new lesions after 2 cycles of cladribine, and noticed marked improvement in all lesions, except for peri-oral papules, after the 5th cycle, while the peri-oral lesions flattened significantly by the 8th cycle. (Fig. 2) No treatment-related adverse effects were noticed in the patient. In the 3-month post-treatment follow-up so far, the skin lesions have continued to gradually flatten, without relapse. Repeat MRI was normal, however, the patient continues to require desmopressin, as before, for diabetes insipidus. Though various treatment modalities have been tried in the treatment of xanthoma disseminatum, most produce an unsatisfactory outcome. Ablative procedures like surgical excision, laser vaporization, cryosurgery or electrosurgery may improve the cosmetic appearance, but have no role in stopping the disease progression. Furthermore, large extent of involvement as in our case, also limits their use. Systemic corticosteroids, too appear not to influence the course of the disease, but may reduce recurrence of lesions following excision. Clofibrate has been effective partially in a few patients. Antimetabolites like cyclophosphamide, azathioprine and vinblastine have been associated with variable success.1-4 Recently, cladribine (2-chlorodeoxyadenosine) has been found to be effective in the treatment of xanthogranuloma forms of non-Langerhans cell histiocytosis.5 Cladribine, a purine analogue which inhibits adenosine deaminase enzyme, has been successfully used in the treatment of several haematologic malignancies.6 Encouraged by a recent report by Khezri et al.,4 demonstrating good response to cladribine in five patients, we tried this agent in our patient. In this series, the patients had received 5–8 monthly cycles of cladribine, 0.14 mg/kg/day for five consecutive days, with substantial improvement in their pre-existing lesions, with stoppage of new lesions after 3–5 cycles. The follow-up period ranged from 3 months to 8 years, during which none of the patients developed recurrence. One patient had features of pituitary stalk infiltration on MRI and diabetes insipidus, whose subsequent imaging study showed normalization of the anatomic parameters. However, the authors did not mention whether this improvement on imaging correlated with clinical improvement in diabetes insipidus. Even though the anatomic parameters may become normal, we speculate the functional damage once caused due to infiltration of the pituitary stalk may not always be reversible, and could be the reason behind persistence of diabetes insipidus in our patient. Our hypothesis is supported by a previous similar report.3 Though too early to comment, cladribine could emerge as a safe and effective treatment for xanthoma disseminatum. It remains to be seen how long the beneficial effect lasts and whether it is restricted to cutaneous manifestations alone.