Sandbox:M.Romo

Introduction

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.

Case Presentation

A 75-year-old (race?) female presented for evaluation of an asymptomatic rash in her extremeties. Her past medical history was significant for discoid lupus erythematosus diagnosed (when?) achieving drug-induced remission with (treatment?) and (any other commorbidity?). Other chronic medications included (medications?). She was diagnosed with neuromyelitis optica (subtype) one year earlier and was initially managed with Rituximab by another provider. When she arrived to the clinic at physical examination she had residual bilateral numbness from the chest down to the extremities, strength was (description?), in addition to residual vision loss (what type of vision loss?) from a previous optic neuritis attack. No dermatologic lesions were observed. Her last labs exhibited (CBC, antibodies, etc?).

(Time?) after the initial evaluation, the patient had an NMO exacerbation and was admitted to the hospital for (IV/PO?) steroid treatment. The patient recovered, nevertheless, had another exacerbation (number) months after. A decision was made to switch her maintanance treatment from Rituximab to Soliris. She was started with an increasing dose of at 900 mg four times every other week. After the fourth dose, she developed rash in all four extremities, excluding the torso. Cutaneous examination showed erythematous papules and scaly patches on four extremities. Soliris was discontinued and topical steroids were given. After one week evaluation via telemedicine, clinical worsening was observed; lesions continued to increase in number and location during the following week.

She was seen by dermatology service, which after correlating the history, clinical presentation, and laboratory studies concluded it was an exacerbation of discoid lupus erythematosus. She was started with prednisone 50 mg four times per day for four days. After (number) weeks, a clinical improvement in her lesions was observed.

Her last She had no history of sores in her mouth, Raynaud’s phenomenon, or lupus erythematosus. Three months earlier, she had been diagnosed with stage II estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative T2N1M0 invasive ductal carcinoma of her left breast. Her breast cancer was initially managed with a left breast lumpectomy and sentinel lymph node biopsy. Systemic chemotherapy with Taxotere (Sanofi, Paris, France) and cyclophosphamide was started; however, she experienced a hypersensitivity reaction within 90 seconds after starting the first infusion of Taxotere.

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).