The tumor necrosis factor ␣ (TNF␣) 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-TNF␣ 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.

Chronic infection with hepatitis C virus (HCV) may be complicated by the development of systemic vasculitis. Vasculitis is either caused by mixed cryoglobulinemia or a non-cryoglobulinemic vasculitis resembling polyarteritis nodosa (PAN). Antiviral treatment with interferon-alpha (IFN) and subsequent clearing of HCV mostly leads to improvement of vasculitic symptoms, but vasculitis may also be exacerbated and even cases of new onset of vasculitis may occur. Exacerbations of both cryoglobulinemic and PAN-type vasculitis in chronic HCV infection have been described under treatment with IFN. The most common symptom is vasculitic neuropathy. However, peripheral neuropathy in a HCV-infected patient treated with IFN may also be caused by direct neurotoxic or antiangiogenic effects of IFN itself, often requiring a nerve biopsy to establish the exact diagnosis. The clinical course of vasculitic complications of IFN treatment is variable and ranges from regression of symptoms despite continuation of IFN treatment to fatal exacerbations despite termination of IFN treatment and additional immunosuppressive therapy. In most cases of IFN-induced vasculitis, immunosuppressive therapy with corticosteroids has been employed, leading to improvement of symptoms. We report the case of a patient with chronic HCV infection who first developed cryoglobulinemic vasculitis after initiation of therapy with the polyethylene glycol (PEG)-conjugated form of IFN (PEG-IFN) and discuss it in the context of the relevant literature. First onset of cryoglobulinemic vasculitis after initiation of IFN therapy has not been described so far.

Background Some studies have shown an attenuated immune response in hemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against SARS-CoV-2 in a large population of hemodialysis patients from different outpatient dialysis centers. Methods We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) three to six weeks after the second mRNA vaccine dose in 179 maintenance hemodialysis and 70 non-dialysis patients (control cohort). Differences in Anti-SARS CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous COVID-19 infection, systemic immunosuppressive therapy and time on dialysis. Results We found a favorable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison to a non-dialysis cohort (median 253.5 vs. 1756 U/ml, p < 0.001). In multivariate analysis previous COVID-19 infection (p < 0.001) and female gender were associated with a significantly higher vaccine response (p 0.006) in hemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (p < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in hemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection. Conclusion We strongly argue in favor of regular antibody testing after COVID-19 vaccination in hemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

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."