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Generalized skin drug eruption to natalizumab in a patient with multiple sclerosis

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Letter: Generalized skin drug eruption to natalizumab in a patient with multiple sclerosis
Marisa C André MD, David Pacheco MD, Joana Antunes MD, Raquel Silva MD, Paulo Filipe MD PhD, L M Soares de Almeida MD PhD
Dermatology Online Journal 16 (6): 14

Clínica Universitária de Dermatologia, Hospital de Santa Maria, Lisbon, Portugal.


We report a generalized skin eruption in a young man being treated with natalizumab, a new drug used in patients with multiple sclerosis.


Multiple sclerosis is a leading cause of chronic neurologic disability, characterized by the presence of multiple foci of inflammation and demyelization within the central nervous system. The glycoprotein α4β1-integrin, also known as very late antigen 4, or VLA-4, is expressed on the surface of lymphocytes and monocytes infiltrating brain parenchyma of patients with multiple sclerosis and is an important mediator of cell adhesion, and transendothelial migration, and a regulator of immune-cell activation within inflamed tissue. Natalizumab, a second-line therapy for multiple sclerosis, is a humanized monoclonal antibody directed against the α4-integrin and has been increasingly used in treating these patients.

Figure 1Figure 2

We report a 29-year-old male with a 12 year history of multiple sclerosis being treated with natalizumb for 30 days prior to the onset of a generalized erythematous pruriginous eruption, edema, and nausea (Figures 1 and 2). He had no mucosal involvement.

Prior treatments had included mexazolam, amitriptyline, clorazepate dipotassium, alfuzosin hydrochloride, and carbamazepine, which were stopped 5 months earlier. He also had been treated with interferon β-1a for 2 months and then glatiramer acetate injections, which had been stopped 2 years prior to presentation.

In addition, he had eosinophilia (2150/L), thrombocytopenia (148 000/L), increased liver enzymes (AST 79 U/L; ALT 185 U/L; GGT 320 U/L) and lactate dehydrogenase (647 U/L). Abdominal ultrasonography showed no abnormalities. Cutaneous histopathology showed aspects of a drug eruption (Figures 3 and 4).

Determination of anti-natalizumab antibodies is not routinely available, but frozen serum from this patient was sent to the Royal London Hospital; our patient’s serum tested positive for these antibodies. Therapy with natalizumab was interrupted and both cutaneous lesions as well as analytical changes disappeared 3 weeks later.

Figure 3Figure 4

This case report illustrates a very rare skin reaction to natalizumab that is not yet described in the literature.

We thank Dr. Diane Wright of The Royal London Hospital for determination of anti-natalizumab serum antibodies.


1. Miller D., M.D., Omar A. Khan, M.D. et al, for the International Natalizumab Multiple Sclerosis Trial Group. A Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. 2003. N Engl J Med. 348; 1: 15-23. [PubMed]

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