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Efalizumab treatment associated with Candida colitis

2008; Elsevier BV; Volume: 59; Issue: 5 Linguagem: Inglês

10.1016/j.jaad.2008.06.035

1097-6787

Kory H. Kitagawa, Robert E. Kalb,

Immunodeficiency and Autoimmune Disorders

To the Editor: A 56-year-old white female with a history of palmoplantar pustular psoriasis and plaque psoriasis which were treated with efalizumab 80 mg subcutaneous weekly since January 2004 maintained complete remission until early October 2007, when she developed nausea, vomiting, profuse watery diarrhea, a weight loss of 12 pounds, and temperatures as high as 40°C (104°F) over the course of 1 week. Before admission, she had taken the following medications: efalizumab, digoxin, carvedilol, irbesartan, spirinolactone, clopidogrel, ezetimibe/simvastatin, aspirin, coenyzme Q-10, propoxyphene, and calcium. Initial blood tests revealed a profound metabolic acidosis and an elevated white blood cell count of 12.1 with 46% bands. Cultures were performed and the patient was started empirically on ceftriaxone, vancomycin, acyclovir, and metronidazole. The following day, she developed respiratory distress and multiorgan failure requiring intubation and pressor support. All studies returned negative including blood cultures, cerebrospinal fluid evaluation, urine culture, Clostridium difficile stool tests, echocardiogram, and other infectious etiologies (hepatitis panel, Epstein–Barr virus, cytomegalovirus, herpes simplex virus, and Legionella). She continued to deteriorate, and 4 days later, with the clinical impression of C difficile infection, a sigmoidoscopy was performed that revealed large white plaques covering the mucosa with confluence proximally. The biopsy specimen demonstrated focal erosion, dystrophic calcification, and fungal organisms consistent with Candida; she was immediately started on caspofungin. Gradual improvement was noted and she was discharged 1 month after admission. Efalizumab is an immunosuppressive agent approved for use in chronic moderate to severe plaque psoriasis. It is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds CD11a, a subunit of leukocyte function antigen-1 (LFA-1), preventing the binding of LFA-1 and intracellular adhesion molecule 1. This leads to decreased T lymphocyte activation, decreased adhesion of T lymphocytes to endothelial cells, and decreased migration of T lymphocytes to areas of inflammation. Given its immunosuppressive actions, efalizumab carries the potential risk of increased infection. A pooled data analysis of four phase III studies revealed no significant difference in the incidence of serious infections between efalizumab and placebo treatment, and only a 2.3% increased incidence of all infection-related events (28.6% vs. 26.3%) in the efalizumab group.1Langley R.G.B. Carey W.P. Rafal E.S. Tyring S.K. Caro I. Wang X. et al.Incidence of infection during efalizumab therapy for psoriasis: analysis of the clinical trial experience.Clin Ther. 2005; 27: 1317-1328Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 2Carey W, Toth DP, Bissonnette R, Langley R. No evidence for increased risk of infection during efalizumab treatment: a review of the clinical data. Presented at the 13th Annual Meeting of the European Academy of Dermatology and Venereology, Florence, Italy, November 18-21, 2004. Poster #79.Google Scholar, 3Papp K.A. Camisa C. Stone S.P. Caro I. Wang X. Compton P. et al.Safety of efalizumab in patients with moderate to severe chronic plaque psoriasis: review of clinical data.Part II. J Cutan Med Surg. 2005; 9: 313-323Crossref PubMed Scopus (27) Google Scholar Data from four phase III, placebo controlled pivotal trials and a 3-year open-label, phase III study revealed no increased incidence of infections associated with immunocompromised states.1Langley R.G.B. Carey W.P. Rafal E.S. Tyring S.K. Caro I. Wang X. et al.Incidence of infection during efalizumab therapy for psoriasis: analysis of the clinical trial experience.Clin Ther. 2005; 27: 1317-1328Abstract Full Text PDF PubMed Scopus (53) Google Scholar Individual case reports included Legionella pneumonia during a local outbreak, vertebral osteomyelitis with epidural abscess, disseminated cryptococcal infection (the patient was on efalizumab, methotrexate, and cyclosporine A), and a few cases of herpes zoster.1Langley R.G.B. Carey W.P. Rafal E.S. Tyring S.K. Caro I. Wang X. et al.Incidence of infection during efalizumab therapy for psoriasis: analysis of the clinical trial experience.Clin Ther. 2005; 27: 1317-1328Abstract Full Text PDF PubMed Scopus (53) Google Scholar, 3Papp K.A. Camisa C. Stone S.P. Caro I. Wang X. Compton P. et al.Safety of efalizumab in patients with moderate to severe chronic plaque psoriasis: review of clinical data.Part II. J Cutan Med Surg. 2005; 9: 313-323Crossref PubMed Scopus (27) Google Scholar, 4Tuxen A.J. Yong M.K. Street A.C. Dolianitis C. Disseminated cryptococcal infection in a patient with severe psoriasis treated with efalizumab, methotrexate and ciclosporin.Br J Dermatol. 2007; 157: 1067-1068Crossref PubMed Scopus (17) Google Scholar, 5Gaylor M.N. Duvic M. Generalized pustular psoriasis following withdrawal of efalizumab.J Drugs Dermatol. 2004; 3: 77-79PubMed Google Scholar It is likely that this patient's opportunistic infection was related to efalizumab therapy, but broad spectrum antibiotics may also have played a role. However, she developed gastrointestinal symptoms before the antibiotics were started and only improved after the initiation of antifungal therapy. Moreover, the extensive involvement of the colon was felt to be very unusual and not typical for secondary colonization of Candida after antibiotics. Although efalizumab has an excellent safety profile thus far, one should keep in mind the possibility of opportunistic infections in these immunosuppressed patients.