Probable diffuse retinopathy caused by adalimumab in a patient with Crohn's disease

Adalimumab is a tumor necrosis factor-α (TNF-α) antagonist used to treat several immunologic diseases. It is believed that unexpected adverse events related to anti-TNF drugs will occur as administration of this drug becomes more widespread. We report the case of a 37-year-old woman who complained of nonspecific abnormalities of vision in both eyes one month after beginning treatment with adalimumab for Crohn's disease. The results of the initial ophthalmologic examination were normal. The visual fields showed diffuse and severe depression in both eyes. Other diseases that could have caused the visual field defects were ruled out. The results of electrophysiological tests were compatible with diffuse bilateral retinopathy. Treatment with adalimumab was discontinued. Six months later, visual field loss persists, although it has improved slightly. To our knowledge, this is the first report of diffuse retinopathy probable caused by systemic administration of adalimumab. This form of retinal toxicity should be considered in patients with disorders of vision treated with this drug.     

Stevens-Johnson syndrome complicating adalimumab therapy in Crohn＇s disease

The anti-tumor necrosis factor （TNF）α medications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions. With the increasing number of patients receiving anti-TNFα agents, however, less common adverse reactions will occur. Cutaneous eruptions complicating treatment with an anti-TNFα agent are not uncommon, occurring in around 20% of patients. Adalimumab, a fully humanized antibody against TNFα, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody, infliximab. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn＇ s disease （CD）. In this case report, a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis, peripheral rash and desquamation, fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab therapy. Skin biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Desquamating skin reactions have now been described in three of the TNFα antagonists （infliximab, etanercept and adalimumab）. These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents, especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.     

Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn's disease

A 61 year old woman with active luminal Crohn's disease was successfully treated with infliximab induction therapy followed by 5 infusions every 8 weeks. However, symptoms returned in the weeks preceding the 7th and 8th infusions. The 9th infusion was therefore given only 4 weeks after the 8th infusion, but an acute severe anaphylactoid reaction occurred immediately after start of the infusion. Anti-infliximab IgG antibody concentration was high (100 U/ml) prior to the 8th infusion and up to 1 year after infliximab discontinuation (81 U/ml). Anti-infliximab IgE antibodies were not found, and the anti-infliximab antibodies did not cross react with adalimumab. One week after the anaphylactoid reaction to infliximab, adalimumab therapy was initiated. Twelve days after the first adalimumab administration (80 mg), a delayed hypersensitivity reaction occurred. This was likely caused by rapidly generated anti-adalimumab IgG antibodies (45 U/ml), as these antibodies appeared to be specific for adalimumab in that infliximab failed to compete with adalimumab/anti-adalimumab antibody binding ex vivo. In conclusion, immunogenicity to infliximab and adalimumab may be associated with both acute anaphylactoid reactions and delayed hypersensitivity reactions. Reactions may be precipitated by newly induced specific anti-drug antibodies rather than by cross-reactivity of previously generated antibodies.     

Pyloric stenosis associated Crohn's disease responding to adalimumab therapy

Gastroduodenal Crohn’s disease (CD) is rare and the response to standard medical therapy is often poor. Anti-tumor necrosis factor therapy has revolutionised the treatment of CD. We present a patient with pyloric stenosis associated with CD which improved with Adalimumab therapy. We recommend considering anti-tumor necrosis factor therapy in symptomatic gastroduodenal CD.