Diffuse plane xanthoma and monoclonal gammopathies

ARTICLE

Auteur(s) : Marta Carlesimo¹, Alfredo Rossi², Mauro La Pietra¹, Alessandra Narcisi¹, Emanuele Verga¹, Annalisa Arcese¹, Claudio Cacchi³, Germana Camplone¹

¹UOC Dermatology, II Unit University of Rome “Sapienza” Via di Grottarossa, 1039, 00189 Rome, Italy
²Department of Dermatology, I Unit University of Rome “Sapienza”, Viale del Policlinico, 00189 Rome, Italy
³Department of Histopathology, II Unit University of Rome “Sapienza”, Via di Grottarossa, 1039, 00189 Rome, Italy

Plane xanthoma is a rare dermatosis frequently associated with haematological disfunctions (monoclonal gammopathies, multiple myeloma or, less often, other lymphoproliferative diseases, such as myeloid leukemias, lymphomas and Castleman disease). It was first described by Altman and Wincklemann in 1962 and is characterized clinically by the presence of yellow to cream-colored patches or plaques, associated with xanthelasma palpebrum but not with alterations of lipid metabolism [1, 2]. Histopathological findings include the presence of foamy xanthoma cells grouped in clusters in the dermis, around blood vessels and follicles. These cells are CD 68 positive and CD 1a negative [4, 5].

Herein we describe the case of an 80-year-old woman who was referred in our Department for a two month eruption of yellow or cream-colored oval patches and plaques, with well demarcated borders, undetermined limits and a mild desquamation, localized on the trunk and extremities, associated to a severe itching. The patient had been under treatment with topical corticosteroids and antihistamines for the past two months, with unsatisfactory results. Her personal history was unremarkable except for a monoclonal gammopathy of undetermined significance (MGUS), diagnosed about two years before, hypertension and diabetes. There were no associated general symptoms. Routine blood tests, abdomen and pelvic ultrasonography and chest-X-ray were all normal, except for immunoelectrophoresis that revealed a κ type of M-bow in the IgG-fraction, confirmed by a slightly high concentration of IgG at 1850 mg/dL, and a mild elevation of lipid levels (total cholesterol 294 mg/dL, low-density lipoprotein fraction 171 mg/dL, triglycerides 332 mg/dL) associated to elevation of apolipoprotein A1-B, from which we made the diagnosis of familial iper-β lipoproteinemia of IIb phenotype in the classification of Fredrickson (1967).

A skin biopsy specimen showed an inflammatory infiltrate in the reticular dermis, composed of macrophages and giant cells, associated with mild fibrosis (figure 1A). These macrophages are mostly foamy cells associated with evident Touton-like giant cells (figure 1B). Diagnosis of diffuse plane xanthoma was finally made.

Monoclonal gammopathies (paraproteinemias or dysproteinemias) represent a spectrum of conditions characterized by clonal proliferation of plasma cells with the production of a monoclonal immunoglobulin protein. A large variety of skin manifestations can be associated with haematological conditions; they can be classified into four groups: 1) infiltrative diseases, such as primary cutaneous plasmacytoma and Waldenstrom macroglobulinemia; 2) skin manifestations induced by deposition of immunoglobulin (M protein), including amyloidosis, macroglobulinemia cutis and crioglobulinemia; 3) dermatoses anecdotally reported in association with monoclonal gammopathies, divided into highly associated (> 50%, i.e. scleromyxedema, scleredema, necrobiotic xanthogranuloma, plane xanthoma, Schnitzler syndrome) and weakly associated (< 50%, i.e. neutrophilic dermatoses); 4) aspecific skin conditions, symptoms and complications, including pruritus, xerosis, drug reactions and infections [3].

The pathogenesis of plane xanthoma is not yet well understood; it has been hypothesized that monoclonal IgG antibodies bind low-density lipoprotein (LDL) and form a complex. These complexes are then phagocitized by macrophages with an affinity superior to non-complexed LDL. This phenomenon can lead to a different pattern of foam histiocyte accumulation and can activate immunological reactions. The histiomacrophages (CD 68 + cells) have a central role in this process and some authors consider this disease a non-X histiocytosis, supported by the evidence that some cases evolved in necrobiotic xanthogranuloma [1].

We describe this case for the rarity of this skin condition, and to underline the concept that skin lesions, frequently under-evaluated by physicians, can be the first manifestation of systemic pathologies. In fact, the production of M proteins, essential for the diagnosis of monoclonal gammopathies, can precede, be concomitant with or follow the dermatological manifestations, and can lead to the correct diagnosis of the underlying haematological disease, in association with the recruitment of characteristic histopathological findings [3].

Acknowledgements

References

2 Harati A, Brockmeyer NH, Altmeyer P, Kreuter A. Skin disorders in association with monoclonal gammopathies. Eur J Med Res 2005; 10: 93-104.

3 Rongioletti F, Patterson JW, Rebora A. The histological and pathogenetic spectrum of cutaneous disease in monoclonal gammopathies. J Cutan Pathol 2008; 35: 705-21.

4 Bragg J. Diffuse plane xanthoma. Dermatol Online J 2005; 11: 4-6.

5 Marcoval J, Moreno AM, Bordas X, Gallardo F, Peyri J. Diffuse plane xanthoma: clinicopathologic study of 8 cases. J Am Acad Dermatol 1998; 39: 439-42.

  All the authors contributed equally to this report