Skin reaction to adalimumab.

The tumor necrosis factor alpha (TNFalpha) inhibitors etanercept and infliximab have shown good clinical results in the treatment of rheumatoid arthritis and other autoimmune disorders. With these novel fusion proteins, immune-mediated side effects, among them various cutaneous reactions, have been encountered. We report herein the case of an erythema multiforme-like skin reaction to treatment with the monoclonal anti-TNFalpha antibody adalimumab in a patient with rheumatoid arthritis. The reaction occurred after the sixth injection and affected the palms and soles as well as the injection site. Discontinuation of the adalimumab therapy resulted in rapid improvement of the condition. Although this patient was receiving concomitant immunomodulatory therapy with methotrexate and leflunomide, these medications were not discontinued when the reaction developed, and no other potential pathogenetic mechanisms were identified. We believe the reaction is most likely attributable to adalimumab.

Desensitization of the pulmonary adenylyl cyclase system: a cause of airway hyperresponsiveness in congestive heart failure?

OBJECTIVES: This study was designed to investigate whether the adrenergic signal transduction in the lung and the responsiveness of airway smooth muscle to adrenergic stimulation are modulated in congestive heart failure. BACKGROUND: Wheezing and airway hyperresponsiveness are often present in heart failure. In the failing heart, chronic adrenergic stimulation down-regulates beta-adrenergic receptors and adenylyl cyclase. We hypothesized that airway dysfunction in heart failure could be due to a similar modulation of pulmonary adrenergic signal transduction. METHODS: Heart failure was induced in rats by aortic banding, resulting in increases in plasma norepinephrine, lung wet weight indicating congestion and left ventricular end diastolic pressure after four weeks. Beta-receptor densities in pulmonary plasma membranes were measured by radioligand binding using [125I]iodocyanopindolol. The G protein levels were determined by Western blot. Adenylyl cyclase activities in lung membranes were quantified as [32P]cAMP (cyclic adenosine-5'-monophosphate) synthesis rate. To functionally assess airway smooth muscle relaxation, carbachol-precontracted isolated tracheal strips were used. RESULTS: Beta-receptor density was significantly decreased in heart failure from 771 +/- 89 to 539 +/- 44 fmol/mg protein without changes in receptor affinities. The beta1-/beta2-subtype ratio, however, remained constant. The G(i and alpha) and G(s alpha) protein expression was unchanged. Adenylyl cyclase activity stimulated directly with forskolin was decreased by 28%. Relaxation of tracheal strips in response to isoproterenol and forskolin, but not to papaverin, was diminished by 30%. CONCLUSIONS: In heart failure, the down-regulation of pulmonary beta-receptors and concomitant decrease in adenylyl cyclase activity result in a significant attenuation of cAMP-mediated airway relaxation. These mechanisms may play a pivotal role in the pathogenesis of"cardiac asthma."