Minocycline syndrome

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

Gough, A. et al., Minocycline induced autoimmune hepatitis and systemic lupus erythe-matosus-like syndrome, Br. Med. J., 312, 169, 1996. 

Elkayam, O., Yaron, M., and Caspi, D., Minocycline-induced autoimmune syndromes An overview, Semin. Arthritis Rheum., 28, 392, 1999. 

Chiu AM, Chuenkongkaew WL, Cornblath WT, et al. Minocycline treatment and pseudotumor cerebri syndrome. Am J Ophthalmol 1998 126 116-121. 

Immunoallergic reactions have been reported with minocycline and include lupus-like syndrome, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, a serum sickness-like illness (29), and Sweet s syndrome (SEDA-21, 262) (SEDA-22, 271). Over 60 minocycline-induced cases of lupus-like syndrome and 24 cases of minocycline-induced autoimmune hepatitis were found in a review of the literature (30). In 13 patients, both disorders co-existed. These patients had symmetrical polyarthralgia/polyarthritis, raised liver enzymes, and positive antinuclear antibodies they were also generally antihistone-negative, and only two patients had p-ANCA antibodies. Minocycline-related lupus can also occur in adolescents (31). 

In a retrospective nested case-control stndy in 27 688 young patients with acne, 7136 had used minocycline, of whom 29 had the lupus-hke syndrome (36). Minocycline was associated with an 8.5-fold risk of the lupus-hke syndrome. The effect was greater in longer-term users, but the absolute risk of developing lupus-hke syndrome seemed to be relatively low. 

In a retrospective review of drug safety databases, minocychne was the only tetracychne derivative that caused drug-induced lupus (SEDA-22, 268) (38). The authors proposed that the propensity of minocycline to cause drug-induced lupus may be due to the presence of a functional group that is easily oxidized to a reactive metabolite. However, the chemicaUy modified tetracycline CMT-3, which has also reportedly caused a lupus-like syndrome (39), lacks this group, so another theory is needed. 

According to the authors, the patient fulfilled all the criteria for a diagnosis of drug-induced lupus-like syndrome, that is no history of lupus erythematosus before minocycline therapy, the presence of antinuclear antibodies, at least one clinical feature of lupus erythematosus, and prompt recovery after withdrawal of minocycline. She also had positive antihistone antibodies, compatible with drug-induced lupus-like syndrome. 

The authors reviewed some other cases of serum sickness after the use of minocycline. They suggested that the syndrome is under-reported, either because of unawareness that it can be an adverse effect or lack of willingness of physicians to document the event. 

Boudreaux JP, Hayes DH, Mizrahi S, Hussey J, Regenstein F, Balart L. Fulminant hepatic failure, hepatorenal syndrome, and necrotizing pancreatitis after minocycline hepatotoxicity. Transplant Proc 1993 25(2) 1873. 

Antunes A, Davril A, Trechot P, Grandidier M, Truchetet F, Cuny JF. Syndrome d hypersensibilite a la minocycline. [Minocycline hypersensitivity syndrome.] Ann Dermatol Venereol 1999 126(6-7) 518-21. 

Cuevas M, Fraj J. Serum sickness-like syndrome associated with minocycline therapy. Allergy 1990 45(4) 313-15. 

Graham LE, Bell AL. Minocycline-associated lupus-like syndrome with ulnar neuropathy and antiphospholipid antibody. Clin Rheumatol 2001 20(l) 67-9. 

Minocycline and lupuslike syndrome in acne patients. Arch Intern Med 1999 159(5) 493-7. 

Elkayam O, Yaron M, Caspi D. Minocycline-indnced antoimmnne syndromes an overview. Semin Arthritis Rhenm 1999 28(6) 392-7. 

Allergic reactions to tetracyclines are less than half as common as allergic reactions to penicillin. For this reason, tetracyclines are alternatives in patients with allergic reactions to other antibiotics. Exceptional observations of anaphylactic shock have been reported (37,38). In a few cases tetracychnes were assumed to be the cause of hypersensitivity myocarditis (39). Pneumonitis with eosinophiha has been described in association with tetracychnes (40). A serum sickness-hke syndrome was probably associated with minocycline in a 19-year-old man treated for acne (41). Allergic and toxic reactions may in some cases have been caused by degraded formulations or additives (42). Tumor-inducing effects have not been reported. 

Certain drugs, such as hydralazine, procainamide, isoniazid, chlorpromazine, and minocycline, can provoke lupus-like manifestations (D Cruz, 2000). Clear differences between systemic lupus erythematosus and lupus syndrome can be identified — hence the recommended different terminology. Typical clinical features of the drug-induced lupus syndrome include arthralgias, arthritis, rash, and... 

The tetracyclines block the attachment of aminoacyl tRNA to the acceptor site on the bacterial ribosome. They are broad-spectrum drugs with good activity against chlamydial and mycoplasmal species, as well as against other indicated bacteria. Doxycycline is of particular use in the treatment of prostatitis, minocycline is useful for treating meningococcal carrier states, and demeclocycline is useful for treating the syndrome of inappropriate secretion of ADH (SIADH). Their biodisposition and side effects are discussed. 

In a matched nested case-control study using data from the UK General Practice Research Database (GPRD) there were 875 cases of a lupus-like syndrome, of which 12% ( = 107) had evidence of a prescription for one or more of the suspected drugs, and they were compared with 3632 matched controls [68 ]. There was an increased risk of lupus-like syndrome with hydralazine (OR = 6.6, 95% CI = 1.03, 43), minocycline (OR = 4.2, 95% Cl = 2.7, 6.8) and carbamazepine (OR = 1.9, 95%... 

Vinson AE, Dufort EM, Willis MD, Eberson CP, Harwell JI. Drug rash, eosinophilia, and systemic symptoms syndrome two pediatric cases demonstrating the range of severity in presentation—a case of vancomycin-induced drug hypersensitivity mimicking toxic shock syndrome and a milder case induced by minocycline. Pediatr Crit Care Med 2010 11(4) e38-43. 

Observational studies Tetracyclines, especially minocycline, inhibit the matrix metal-loproteinases (MMPs), and this has been studied in patients with the so-called fragile X syndrome (MIM 300624), an inherited form of intellectual disability and autism, with an estimated prevalence of about 1 in 4000 [125. The gene responsible is located on the X chromosome (Xq27.3) and is called Fragile X Mental Retardation-1 (FMRl MIM 309550) [126 ]. Minocycline improved behavioral performance and reduced anxiety in a FMRI knockout mouse [127 ], and has been studied in an open trial in 20 patients with the fragile X syndrome, aged 13-32 years [128 ]. The... 

A lupus-like syndrome with neutropeiua has been associated with minocycline in an 18-year-old man [145 ]. 

Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 2010 10 91. 

Ahmed F, Kelsey PR, Shariff N. Lupus syndrome with neutropenia following minocycline therapy—a case report. Int J Lab Hematol 2008 30(6) 543-5. 

Brown RJ, Rother KI, Artman H, Mercuric MG, Wang R, Looney RJ, Cowen EW. Minocycline-induced drug hypersensitivity syndrome followed by multiple autoimmune sequelae. Arch Dermatol 2009 145(1) 63-6. 

Shaughnessy KK, Bouchard SM, Mohr MR, Herre JM, Salkey KS. Minocycline-induced drug reaction with eosino-philia and systemic symptoms (DRESS) syndrome with persistent myocarditis. J Am Acad Dermatol 2010 62(2) 315-8. 

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