[Bronchial asthma and allergic rhinitis-The skin sample reveals a severe systemic disease]. / Asthma bronchiale und allergische Rhinitis ­ die Hautprobe offenbart eine schwerwiegende Systemerkrankung.

This article reports the case of a 30-year-old female patient who suffered for many years from initially unspecific symptoms, such as recurrent, nonallergic and noninfectious sinusitis, late-onset bronchial asthma and pronounced lymphadenopathy; however, the correct diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) could only be made by histological investigations after the appearance of skin symptoms. The EGPA is a severe systemic disease which, if left untreated, can cause multiple organ damage and even be fatal. With adequate treatment the disease is mild in more than 90% of cases and patients can even completely recover. By making the correct diagnosis, the patient could be successfully treated and the risk of late manifestations and subsequent damage with a potentially fatal outcome was reduced.

The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17 responses induced by 6-sulfo LacNAc (slan) dendritic cells.

BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs. METHODS: In vitro studies were performed analyzing the effects of apremilast on the proinflammatory function of slanDCs and their capacity to induce Th1/Th17-biased T cell responses. RESULTS: Increasing cAMP levels in slanDCs by PDE4 inhibition strongly reduced production of IL-12 and TNF-α. In line with these findings, co-culture experiments with apremilast-pulsed slanDCs and allogeneic T cells either from psoriasis patients or healthy controls, revealed a significant reduction of IFN-γ production and expression of the transcription factor T-bet. In parallel, production of IL-23 and IL-1ß by slanDCs was increased and co-cultured T cells revealed a largely augmented IL-17 production and an upregulated RORyt expression. CONCLUSIONS: We here demonstrate anti-inflammatory as well as Th17-promoting effects of apremilast when studying blood precursors of human inflammatory dermal dendritic cells. In the concert of the broad anti-inflammatory effects of apremilast on keratinocytes, fibroblasts and endothelial cells, the dual effect on slan+ inflammatory dermal DCs should be taken into account and may constrain therapeutic responses.