title: Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy.
abstract: Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.
authors.affiliation: Département d'immunologie clinique, Hôpital Saint Louis, Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Szalat
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnulf
authors.forename: Lionel
authors.initials: L
authors.lastname: Karlin
authors.forename: Michel
authors.initials: M
authors.lastname: Rybojad
authors.forename: Bouchra
authors.initials: B
authors.lastname: Asli
authors.forename: Marion
authors.initials: M
authors.lastname: Malphettes
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Vignon-Pennamen
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Harel
authors.forename: Florence
authors.initials: F
authors.lastname: Cordoliani
authors.forename: Jean Gabriel
authors.initials: JG
authors.lastname: Fuzibet
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Clauvel
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Brouet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
mesh_terms: D006801:Humans; D010265:Paraproteinemias / Q000150:complications* / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology; D014973:Xanthomatosis / Q000150:complications* / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*