Minocycline-Induced DRESS: Evidence for Accumulation of the Culprit Drug

Maubec, Ève; Wolkenstein, Pierre; Loriot, Marie‐Anne; Wechsler, Janine; Mulot, Claire; Beaune, Philippe; Revuz, J.; Roujeau, Jean‐Claude

doi:10.1159/000112926

Cited by 48 publications

(27 citation statements)

References 35 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…18 Minocycline-induced DRESS occurs mainly in patients with Fitzpatrick skin phototypes V and VI. 19 The plasma half-life of minocycline is approximately 18 hours. In a group of 9 patients with minocycline-induced DRESS syndrome with skin phototypes V and VI; 6 patients had significant plasma and skin levels of minocycline ranging from 11 days to as long as 17 months after discontinuation of minocycline therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Formation of a melanin-minocycline complex in patients with skin phototypes V and VI may explain why these patients typically experience a more severe and prolonged course of DRESS syndrome. 19 The genetic predisposition to minocycline-induced DRESS syndrome in patients of African descent may be related to a variation in detoxification enzyme activity. Minocycline is metabolized in the liver, and current research is focused on identifying genetic variants in major histocompatibility complex haplotypes, cytochrome P450, and glutathione S-transferase that may be shared by individuals with DRESS syndrome.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis

Shaughnessy

Bouchard

Mohr

et al. 2010

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis

Shaughnessy

Bouchard

Mohr

et al. 2010

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

“…7,58,71,78,90 The drugs incriminated were retained after chronology, signs, and symptoms had been analyzed according to the methodology described by Bégaud et al 3 For each patient, 1 or 2 drugs were finally considered at least possibly (positive response to its/their withdrawal with no further investigation) or probably (positive rechallenge) responsible. This interval was chosen based on previous reports on DIHS.…”

Section: Search For Putative Drugsmentioning

confidence: 99%

Drug-Induced Hypersensitivity Syndrome

et al. 2009

View full text Add to dashboard Cite

Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DRESS), is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 1-8 weeks after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although no consensus has been reached as to its etiology. The skin, hematopoietic system, and liver are frequently involved. DIHS can mimic severe sepsis, viral infection, adult-onset Still disease (AOSD), or lymphoproliferation.We describe 24 consecutive patients with DIHS who were hospitalized between September 2004 and March 2008. Criteria for inclusion in this observational study were suspected drug reaction, eosinophilia >or=500/microL and/or atypical lymphocytes, involvement of at least 2 organs (skin being 1 of them), with suggestive chronology and exclusion of other diagnoses. Our cohort of 12 women and 12 men had a median age of 49 years (range, 22-82 yr), and 11 had skin phototype V or VI. Patients with mild or no rash were immunocompromised (7/24)- defined as treatment with prednisone (>or=10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized edema, 7 had pharyngitis, 8 had lymphadenopathy, 22 had hepatitis, 4 had nephritis, 2 had noninfectious and nonlithiasic angiocholitis or cholecystitis. Ten patients were hypotensive, 5 of whom had associated laboratory signs and/or imaging findings suggestive of acute myocardial dysfunction. Half of the patients had hemogram abnormalities, including eosinophilia. Nine DIHS patients fulfilled the Fautrel criteria for AOSD diagnosis, including glycosylated ferritin <20% in 4/11, with or without laboratory characteristics of hemophagocytosis. Twenty DIHS episodes occurred during the less sunny months of October to March.We determined 25-hydroxyvitamin D3 (25[OH]D3) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or <10 microg/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D3 levels were inversely correlated with ferritin values. After culprit-drug withdrawal, outcomes were favorable for all patients, including those with cardiac abnormalities under slow tapering of glucocorticoids.We recommend looking for the frequent but underdiagnosed hypersensitivity myocarditis with noninvasive diagnostic tools, such as N-terminal probrain natriuretic peptide, and promptly withdrawing the culprit drug and starting glucocorticoids. Vitamin D deficiency might be a DIHS risk or severity factor, especially for patients with high skin phototype and during the winter. Because DIHS clinical and laboratory patterns share similarities with AOSD and hemophagocytosis, DIHS should be included in their differential diagnoses.

show abstract

“…[90] The mechanism of hypersensitivity reactions could be identified as a cytotoxic immune reaction against alveolar macrophages containing minocycline [91] or the drug accumulated in the skin. [92] In systemic reactions, it is thought that minocycline acts as a super-antigen. [93] …”

Section: Autoimmune Phenomena and Hypersensitivity Reactionsmentioning

confidence: 99%

Minocycline in Acne Vulgaris

Ochsendorf

2010

American Journal of Clinical Dermatology

View full text Add to dashboard Cite

Minocycline is a semi-synthetic, second-generation tetracycline. It was introduced in 1972 and has both antibacterial and anti-inflammatory properties. Minocycline is used for a variety of infectious diseases and in acne. Even today, new indications beyond the antibacterial indications are being investigated such as its use in neurologic diseases. Formerly, minocycline was thought to have a superior efficacy in the treatment of inflammatory acne, especially with respect to antibacterial-resistant Propionibacterium acnes. A thorough review of the literature, however, shows that minocycline is not more effective in acne than other tetracyclines. Compared with first-generation tetracyclines, minocycline has a better pharmacokinetic profile, and compared with doxycycline it is not phototoxic. However, minocycline has an increased risk of severe adverse effects compared with other tetracyclines. It may induce hypersensitivity reactions affecting the liver, lung, kidneys, or multiple organs (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] syndrome) in the first weeks of treatment and, with long-term treatment, may cause autoimmune reactions (systemic lupus erythematosus, autoimmune hepatitis). In addition, CNS symptoms, such as dizziness, are more frequent compared with other tetracyclines. Long-term treatment may induce hyperpigmentation of the skin or other organs. Resistance of P. acnes to minocycline also occurs, dependent on the prescribing behavior. Considering the aspects of efficacy, its adverse effect profile, resistance, price, and alternatives, minocycline is no longer considered the first-line antibacterial in the treatment of acne.

show abstract

Minocycline-Induced DRESS: Evidence for Accumulation of the Culprit Drug

Cited by 48 publications

References 35 publications

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome with persistent myocarditis

Drug-Induced Hypersensitivity Syndrome

Minocycline in Acne Vulgaris

Contact Info

Product

Resources

About