Infective Endocarditis Complicating Adalimumab Therapy for Psoriasis

A 25-year-old man was started on adalimumab (Humira, Abbott Laboratories, IL, USA) 40 mg every 2 weeks for chronic plaque psoriasis. The patient had a history of coarctation of the aorta, which had been surgically repaired at the age of 3 years, and he had previously failed treatment with methotrexate, acitretin, ciclosporin and phototherapy for his psoriasis. Within 2 months of starting adlimumab, his Psoriasis Area and Severity Index fell from 25.3 to 7.3, and his Dermatology Life Quality Index from 20 to 5. However, 5 months into treatment, he developed severe lethargy, drenching night sweats, fever, joint pain and increasing dyspnoea on minimal exertion. On physical examination, the patient was found to be hypotensive, tachycardic and febrile. Splinter haemorrhages and Osler nodes were present. A harsh ejection systolic murmur was audible. He had a normocytic anaemia (haemoglobin 11.4 g/dL; normal ranges 13.0–18.0 g/dL), neutrophilia (9 9 10/L; normal range 1.5–7 9 10/L) and raised C-reactive protein (117 mg/L; normal < 10 mg/L). Urine dipstick showed a reading of ++ blood and + for protein. Blood cultures grew Streptococcus viridans, and a transoesophageal echocardiogram (TOE) demonstrated a mass on a functionally bicuspid aortic valve. Adalimumab was stopped, and a 4-week course of treatment with intravenous benzylpenicillin for infective endocarditis was commenced. The patient’s psoriasis deteriorated soon after discontinuing adalimumab, and was unresponsive to topical therapies. Acitretin, combined with TL01 narrowband ultraviolet B phototherapy, was started as the least immunosuppressive regimen, but the patient became erythrodermic and systemically unwell within 6 weeks (Fig. 1b). A TOE carried out following completion of the antibiotic course showed severe aortic regurgitation, with multiple masses on the aortic valve (Fig. 2). The left ventricle was volume-overloaded, with impaired systolic function. These findings had progressed since the initial echocardiogram, and an urgent aortic valve replacement was indicated. Surgery was deemed unsafe given the potential risk of the erythroderma to exacerbate the patient’s impaired haemodynamic status, the increased risk of prosthetic valve and sternal wound infection, and of poor wound healing. Intravenous antibiotics were recommenced, and diuretics were required to manage episodes of acute pulmonary oedema. It was decided to restart adalimumab (80 mg in week 1, 40 mg in week 2 and 40 mg every 2 weeks thereafter) with ciclosporin (4 mg/kg/day in two doses) to treat the patient’s psoriasis as quickly as possible. Within 2 weeks, his psoriasis had cleared and he successfully underwent aortic valve replacement, aortic root enlargement and excision of aortic membrane. At the time of surgery, the native leaflets were noted to have been destroyed by the infective process. Our patient continues on adalimumab with good clinical response, and is on lifelong warfarin for a mechanical (St Jude) aortic valve. Adalimumab is a humanized monoclonal antibody against tumour necrosis factor (TNF)-a, and is associated with an increased infection risk, particularly with intracellular organisms such as Mycobacterium tuberculosis. Treatment should be stopped in cases of serious infection, and should not be started in cases of active infection. S. viridans is an extracellular bacterium, and therefore, for our patient, the decision was made to restart adalimumab with antibiotic cover, in order to improve his psoriasis before he underwent urgent surgery. To date, most of the data regarding infection risk with anti-TNF agents has been evaluated in Correspondence: Dr Shaheen S. Haque Hussain, Department of Dermatology, Clinic 7, Box 46, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ, UK E-mail: shaheen.haque@doctors.org.uk