Carbamazepine-induced systemic lupus erythematosus: A case-based review

Abstract

A case of carbamazepine-induced systemic lupus erythematosus (CBZ-DILE) is presented, along with a literature review, with the aim to define the clinical and serological characteristics of this group, and compare them with systemic lupus erythematosus (SLE) triggered by other drugs (DILE). A 31-year-old woman presented with a 6-month history of hand arthritis and nasal ulcers. She had been diagnosed with epilepsy at 12 years of age and had continued treatment with carbamazepine (CBZ) for the past 18 years with excellent clinical control. Laboratory data revealed antinuclear antibodies (ANA) positive to a titer of 1/1280, and positive anti-nucleosome antibodies. The patients’ clinical symptoms disappeared after the CBZ discontinuation and did not reappear during the 1-year follow-up period. A search was made in the PubMed/Medline database of the (CBZ-DILE) published cases. A total of 26 cases of CBZ-DILE were found in the search. CBZ-DILE cases are characterized by variable latency periods that often last for years and are not related to the dose of CBZ. Most frequent clinical findings of CBZ-DILE in patients are arthralgia/arthritis, mucocutaneous manifestations, constitutional symptoms, and pleuritis or pericarditis. The renal involvement has not been reported in CBZ-DILE. Antihistone antibodies were observed less frequently, and anti-dsDNA antibodies were observed more frequently than in the “classic” DILE. The ANA remained positive in over 60% of cases during the follow-up after withdrawal. The CBZ-DILE has significant clinical and laboratory manifestations that distinguish it from classic DILE or idiopathic SLE.

Oxcarbazepine-induced systemic lupus erythematosus: A rare and serious adverse drug reaction to a common anticonvulsant

“…[ 1 ] Anti-dsDNA antibodies are mostly absent in drug-induced SLE while being present in 85% of patients with idiopathic SLE, thus further contributing to the differentiation between two entities. [ 2 ] In fact, the presence of antihistone antibody in the absence of anti-dsDNA antibody suggests a diagnosis of DILE as was seen in our case.…”

“…It may take further longer time for ANA titers to turn negative, or in approximately 60% of cases on follow-up, it may not return to negative. [ 2 ] Our patient showed improvement in DILE symptoms postOXC withdrawal along with decline in ANA titers and is presently on regular follow-up.…”

“…Oxcarbazepine (OXC) is a congener of CBZ with lesser side effects and drug interactions while maintaining equal efficacy. Although 28 cases of SLE have been reported for CBZ,[ 2 ] reports of OXC causing SLE are rare with only a few cases described before this report. We herein report an elderly male being treated for seizures developing SLE-induced by OXC.…”

“…The occurrence of CBZ-induced lupus-like symptoms is rare with a reported incidence of <0.001% in treated patients or 2–3 cases per 100,000. [ 2 ] The pathogenesis of DILE due to CBZ is unclear; however, metabolism of CBZ to reactive intermediates by activated leukocytes has been widely considered to result in adverse reactions including DILE. [ 3 ] The mechanism of the action of OXC is same as CBZ-sodium channel blockage, with similar efficacy, better side effect profile and is used for the same indications such as treatment of seizure disorders, psychiatric diseases, trigeminal neuralgias, and other chronic pain syndromes.…”

The association between systemic autoimmune disorders and epilepsy and its clinical implications

“…Among people with LGI1 antibody mediated encephalitis, the use of aromatic antiseizure medication has been associated with relatively higher effectivity, but also higher rates of cutaneous drug reactions in multi-ethnic populations (Thompson et al, 2018;de Bruijn et al, 2019b). Lastly, carbamazepine, phenytoin, and phenobarbital are rarely associated with the development of clinical and serological lupus, and subsequent resolution upon discontinuation of the drug (Perucca and Gilliam, 2012;Alvarez-Lario et al, 2019). Individuals with SAD may also be at higher risk of adverse bone health outcomes with enzyme-inducing antiseizure medications, due to concurrent treatment with glucocorticoids (Frenkel et al, 2015).…”