The risk of interstitial lung disease during biological treatment in Japanese patients with psoriasis.

BACKGROUND: With the increasing use of biological agents for the treatment of psoriasis, the numbers of patients with interstitial lung disease (ILD) associated with biologics have also increased. Many of these cases were associated with tumour necrosis factor (TNF)-α inhibitors, but cases associated with other families of biologics have also been reported in Japan. AIM: To analyse the background factors of patients who developed ILD, and to discuss better management of biological treatment. METHOD: We reviewed 246 patients with psoriasis who were treated with biological agents in our department to identify any pulmonary adverse events (AEs). Data on patients who developed ILD were extracted to analyse background factors, clinical type of psoriasis, time to onset of ILD, pre-existing ILD, smoking habit and prescribed drugs. RESULTS: Pulmonary AEs were seen in 22 cases, of which 11 were diagnosed as drug-induced ILD. The causative drugs were mainly TNF-α inhibitors, accounting for eight cases (six treated with infliximab, two with adalimumab). The remaining three cases were associated with secukinumab, ustekinumab and ixekizumab (n = 1 each). Notably, these three cases also had a history of drug-induced ILD. CONCLUSION: Patients with a history of drug-induced ILD seem to be more susceptible to developing another ILD induced by biologics, even if treated with interleukin-17 inhibitors. Thorough screening of risk factors and evaluation for eligibility, and careful monitoring during treatment are the best solutions to avoid serious pulmonary AE. Early detection and precise diagnosis of pulmonary AEs, especially differentiation from infectious diseases, is essential for managing biological treatment.

Ultrastructural study of atrial specific granules in rat atrium after incubation with calcium ionophore (A23187).

The release mechanism of the rat atrial granules containing atrial natriuretic polypeptide (ANP) was examined. In addition, the ultrastructure of right atrial myocardiocytes incubated in a medium containing an excess calcium and calcium ionophores (A 23187) was investigated by electron microscopy. After 3-15 minute incubation in the medium, many ANP-containing atrial specific granules were detected in the vicinity of the subsarcolemmal region, and invagination of the plasma membranes occurred as well as a large number of vacuoles were observed. After incubation with an excess calcium and calcium ionophores for 40 minutes, the atrial specific granules had completely disappeared and numerous vacuoles appeared in the sarcoplasm of the atrial myocardiocytes. Thus, release of ANP and their reabsorption by membranes were accelerated by the presence of calcium and calcium ionophores.

Ultrastructure of monoaminergic terminals in the intermediolateral nucleus of the cat spinal cord.

Monoaminergic innervation of the intermediolateral nucleus of the cat spinal cord was investigated by fluorescence histochemistry and electron microscopy. Large numbers of monoaminergic terminals were labeled by prior administration of the false neurotransmitter 5-hydroxydopamine (5-OHDA). Ultrastructurally, 5-OHDA-labeled terminals fell into three types. Type I, which made up 55% of the labeled terminals, contained abundant, large and densely labeled vesicles and only a few small and unlabeled vesicles. This type was "bouton de passage". Type II, which made up 40% of the terminals, made asymmetrical synaptic contacts with typical postsynaptic structures. This type contained many small vesicles, some of which were labeled, and a few large dense-core vesicles. Type III, which made up 5% of the terminals, made close contact with presynaptic nerve endings containing abundant small unlabeled clear vesicles. The type III terminals contained many large and densely labeled vesicles and a few small flattened vesicles, most of which were unlabeled.