Drug-induced lupus associated with COL-3: report of 3 cases.
BACKGROUND
Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus.


METHODS
Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up.


CONCLUSIONS
COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.
Ghate
J V
JV
Dermatology Branch, National Institutes of Health, Bldg 10, Room 12N238, Bethesda, MD 20892-1908, USA.
Turner
M L
ML
Rudek
M A
MA
Figg
W D
WD
Dahut
W
W
Dyer
V
V
Pluda
J M
JM
Reed
E
E
D000287:Administration, Topical; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002990:Clobetasol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009824:Ointments; D011241:Prednisone / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects*; D013754:Tetracyclines / Q000009:adverse effects*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D061965:Matrix Metalloproteinase Inhibitors; D009824:Ointments; D011480:Protease Inhibitors; D013754:Tetracyclines; C117155:tetracycline CMT-3; D002990:Clobetasol; D011241:Prednisone