Sandbox:M.Romo

Eculizumab (Soliris) is a fully humanized IgG2/IgG4 monoclonal antibody that inhibits the terminal complement protein C5, preventing its cleavage into C5a (proinflammatory) and C5b (membrane attack complex coordinator). Eculizumab is known to be effective in reducing the frequency of relapse in highly clinically active, AQP4-IgG–positive disease. It provided the first FDA-approved treatment for neuromyelitis optica spectrum disorder (NMOSD), which has drastically changed the natural history of patients with NMOSD.

While the survival benefit of Solaris in the setting of NMOSD is undeniable, as occurs with all proteins, there is a potential for immunogenicity. Surprisingly, very few cases of lupus reactivation have been reported, and by literature review using PubMed and MEDLINE using discoid lupus erythematosus and/or eculizumab, cero case-reports were retrieved. Among the most common adverse effects of Soliris reported are high blood pressure and headache. Only 1-10% report anaphylactic reaction and 10-15% experiment rash.

The pathophisiology of this mechanism opens discussion. The reactivation of DLE may be due to a than a immune mediated pathway by itslef. As per Soliris drug add evaluating immunogenicity using an electro-chemiluminescence (ECL) bridging assay, only two of the 96 Soliris-treated patients with NMOSD developed antibodies against Soliris.

The evidence base documenting autoimmune reactions with the use of IgG2/IgG4 monoclonal antibody therapy is exceedingly small. To our knowledge, this is the first case reported of reactivation of quiescent discoid lupus erythematosus (DLE) due to Eculizumab in the setting of NMOSD.

It cannot be said with absolute certainty that eculizumab caused this patient’s severe cutaneous complication, as we felt it was unsafe to perform a rechallenge, and the patient refused to consider such a trial. However, it seems very likely that the eculizumab was an important contributing factor. The rash developed within 24 hours of the first eculizumab dose and skin symptoms started during the infusion, skin biopsy findings were consistent with a drug-induced eruption, the patient had no history of rashes, and there was no other obvious inciting event. Could a drug–drug interaction including eculizumab have triggered the rash? The patient was also taking twice weekly trimethoprim-sulfamethoxazole (TMP-SMX) as Pneumocystis carinii prophylaxis, an agent that can cause severe dermatological complications including Stevens-Johnson syndrome. However, he had been receiving a stable dose of TMP-SMX for more than a month and had previously taken this agent multiple times without any problems. Other chronic medications included pantoprazole, levothyroxine, darbepoetin alfa, folate, vitamin B12, vitamin D plus calcium, and epsilon amino-caproic acid (because of a distant history of recurrent gastrointestinal bleeding related to mucosal arteriovenous malformations).