Drug-induced Hypersensitivity Syndrome Clinical and Biologic Disease Patterns in 24 Patients

被引:129
作者
Ben m'rad, Mona [1 ,2 ]
Leclerc-Mercier, Stephanie [2 ,3 ]
Blanche, Philippe
Franck, Nathalie [3 ]
Rozenberg, Flore [2 ,4 ]
Fulla, Yvonne [2 ,5 ]
Guesmi, Myriam [2 ,6 ]
Rollot, Florence
Dehoux, Monique [7 ]
Guillevin, Loic [2 ]
Moachon, Laurence [2 ,8 ,9 ]
机构
[1] Hop Ambroise Pare, Dept Internal Med, Reference Ctr Autoimmune & Inflammatory Dis, F-92100 Boulogne, France
[2] Paris Descartes Univ, Hop Cochin, AP HP, Paris, France
[3] Hop Cochin, AP HP, Dept Dermatol, F-75674 Paris, France
[4] Hop Cochin, AP HP, Dept Virol, F-75674 Paris, France
[5] Hop Cochin, AP HP, Dept Biophys, F-75674 Paris, France
[6] Hop Cochin, AP HP, Dept Radiol, F-75674 Paris, France
[7] Hop Bichat Claude Bernard, AP HP, Dept Biochem, F-75877 Paris, France
[8] AP HP, Reg Pharmacovigilance Ctr, Paris, France
[9] AP HP, Dept Pharmacol, Paris, France
关键词
ONSET STILLS-DISEASE; CONGESTIVE-HEART-FAILURE; VITAMIN-D STATUS; REACTIVE HEMOPHAGOCYTIC SYNDROME; INFLAMMATORY-BOWEL-DISEASE; 1,25-DIHYDROXYVITAMIN D-3; SYSTEMIC SYMPTOMS; EOSINOPHILIC MYOCARDITIS; HUMAN-HERPESVIRUS-6; REACTIVATION; MACROPHAGE-ACTIVATION;
D O I
10.1097/MD.0b013e3181a4d1a1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Drug-induced hypersensitivity syndrome (DIHS), also called drug rash with eosinophilia and systemic symptoms (DR-ESS), is a severe reaction usually characterized by fever, rash, and multiogran failure, occurring 1-8 weeks after drug introduction, It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release, although 110 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 >= 500/mu L and/or atypical lymphocytes, involvement of at least 2 organs (skin being I 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 (>= 10 mg/d) and another immunosuppressant drug, or human immunodeficiency virus infection. All patients were febrile (>38 degrees C), 14 had localized or generalized cdema, 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 D-3 (25[OF]D-3) levels in 18 patients and found that 9 patients had vitamin D deficiency (<25 nmol/L or<10 mu g/L) and 5 had vitamin D insufficiency (25-50 nmol/L). Moreover, 25(OH)D-3 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. (Medicine 2009;88: 131-140)
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页码:131 / 140
页数:10
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