title: Cutaneous hyperpigmentation induced by doxycycline: histochemical and ultrastructural examination, laser microprobe mass analysis, and cathodoluminescence.
abstract: Skin hyperpigmentation induced by minocycline is a well-recognized side effect of minocycline but has rarely been reported for other tetracyclines. Based on a previously reported unusual case of chronic doxycycline abuse in a psychotic patient, we have investigated the nature of the observed pigment changes in the same patient. Histopathologic investigation of lesional skin by light microscopy disclosed hyperpigmentation of the basal keratinocytes and pigment-laden histiocytes in the dermis and subcutaneous fat. Only the pigment in the histiocytes of the upper dermis was reactive for Fontana Masson stain and could be bleached by hydrogen peroxide. The other histiocytes contained iron and calcium deposits as shown by von Kossa and Perls staining as well as by laser microprobe mass analysis. Ultrastructurally, these histiocytes contained amorphous material within the cytoplasm and stored in lysosomal structures. Comparative cathodoluminescence disclosed the presence of doxycycline in affected skin by means of overlapping emission spectra between the patient's skin and pure doxycycline. Taken together, the histomorphologic and ultrastructural changes induced by doxycycline shared several features with cutaneous hyperpigmentation caused by minocycline. Our biophysical findings further suggest a direct deposition of doxycycline, probably chelated with iron and/or calcium, within the lesional skin. Based on the presented unique case and the reviewed literature, only suprapharmacologic doses of doxycycline may be sufficient to cause such pigment changes.
authors.affiliation: Department of Dermatology, University of Münster, Germany. bohmm@uni-muenster.de
authors.forename: Markus
authors.initials: M
authors.lastname: Böhm
authors.forename: Peter Fritz
authors.initials: PF
authors.lastname: Schmidt
authors.forename: Bernd
authors.initials: B
authors.lastname: Lödding
authors.forename: Holger
authors.initials: H
authors.lastname: Uphoff
authors.forename: Gerald
authors.initials: G
authors.lastname: Westermann
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.forename: Gisela
authors.initials: G
authors.lastname: Bonsmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Metze
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000032:analysis; D004318:Doxycycline / Q000009:adverse effects* / Q000032:analysis; D006644:Histiocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017495:Hyperpigmentation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008163:Luminescent Measurements; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000295:instrumentation / Q000379:methods; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000295:instrumentation / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline