Reactions 1193 - 15 Mar 2008

Table 3. Minocycline persistence, outcome SMinocyclinePatient Minocycline* Treatment Reaction

(plasma/skin) duration+DRESS in patients with dark skin pigmentation:9 case reports 1 Y/Y Prednisone, interferon-α 18 (died)

Nine patients with dark skin pigmentation developed a drug 2 Y/N Topical corticosteroid 1rash with eosinophilia and systemic symptoms (DRESS) [see 3 N/N Prednisone 8tables] after receiving minocycline [dosages not stated] for

4 Y/N Prednisone 5acne; patient 1 subsequently died due to severe lung5 not stated not stated not statedinvolvement.6 Y/N Prednisone 6 (died)7 Y/Y Prednisone 3

Table 1. Patient characteristics 8 Y/Y Topical corticosteroid 1Patient Sex/age (y) Phototype* Total dose** (g) 9 N/Y Topical corticosteroid 3

1 F/45 V not stated * Persistent > 4 days after withdrawal2 F/31 VI 3 + months3 F/24 V 1.24 M/22 V 3 Author comment: "[Minocycline] should not be detectable5 F/24 V not stated in the plasma after 5 half-lives, i.e. 4 days, after6 F/15 VI 2.4 withdrawal. . . One can hypothesize that type III

[minocycline-related] pigmentation is promoted in patients7 F/34 VI 3. . . whose skin contains more melanin. The formation and8 F/19 V 3.15accumulation of a melanin-minocycline complex could also9 F/29 V 6.75explain the increased frequency of severe and prolonged

* skin pigmentation level, on a scale of I to VI DRESS in this population."** minocycline

Maubec E, et al. Minocycline-induced DRESS: evidence for accumulation of theculprit drug. Dermatology 216: 200-204, No. 3, 9 Jan 2008 - France 801103144

At presentation, all patients had skin eruption, facialoedema, fever and lymphadenopathy, and all but patient 2 hadeosinophilia; they were diagnosed with DRESS. Histologicalfindings were consistent with type III minocycline-relatedpigmentation. Atypical lymphocytes were detected in allpatients, except for patient 5, who was not assessed for thisparameter.

Table 2. Time to reaction onset, reaction detailsPatient Onset* Organ involvement Eosinophils

1 60 Liver, kidneys, lungs, 14 000pericardium

2 30 Liver, kidneys 03 25 Liver, kidneys, lungs 22004 30 Liver, kidneys, lungs 41305 21 Kidneys, pericardium, 2500

myocardium6 16 Liver, kidneys, lungs 87307 21 Liver, kidneys, lungs 32008 19 Liver, kidneys, lungs 16609 60 Liver, lungs 3300

* days after minocycline initiation

In most patients, minocycline persisted at detectableconcentrations at timepoints of > 4 days after minocyclinewithdrawal. Patient 1 died, due to severe lung involvement,after persistence of DRESS for 18 months, and patient 6 died,due to a diabetic coma secondary to corticosteroid-induceddiabetes, after DRESS persistence for 6 months [outcomes forother patients not clearly stated].

1

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