Immature dendritic cells (DCs) are scattered throughout peripheral tissues and act as sentinels that sample the antigenic environment. After activation, they modify their chemokine receptor profile and migrate toward lymphoid tissues. On arrival, they have matured into chemokine-producing DCs that express co-stimulatory molecules and can prime naive T cells. Normal temporal arteries contain immature DCs that are located at the media-adventitia border. In temporal arteries affected by giant cell arteritis, DCs are highly enriched and activated and have matured into fully differentiated cells producing the chemokines, CCL18, CCL19, and CCL21. In keeping with their advanced maturation, DCs in the granulomatous lesions possess the chemokine receptor, CCR7. CCR7 binds CCL19 and CCL21, causing the highly activated DCs to be trapped in the peripheral tissue site. The co-stimulatory molecule, CD86, which is critical for DC/T-cell interaction, is expressed by a subset of DCs captured in the arterial wall. DC/T-cell interaction does not involve interleukin-12; transcripts for interleukin-12 p40 are absent in the vasculitic infiltrates. We propose that differentiation of DCs and the autocrine and paracrine actions of chemokines in granulomatous lesions misdirect DCs away from their usual journey to lymphoid organs and are critical in maintaining T-cell activation and granuloma formation in giant cell arteritis.

BackgroundInjection of fibrin glue mixed with blood into the epidural space to reliably and effectively treat medically refractory orthostatic headache caused by spinal cerebrospinal fluid (CSF) leaks and subsequent intracranial hypotension has recently been described. The study described in this article utilizes an analogous technique to gauge the therapeutic reproducibility of this novel technique.MethodsEight patients with medically refractory headache resulting from intracranial hypotension caused by spinal CSF leaks received epidural injections of combined fibrin glue, autologous blood, and Isovue contrast at the L1—2 vertebral level using intermittent fluoroscopic guidance. Pre-procedure, 1-week post-procedure, and 3-month post-procedure headache pain scores were collected and used for comparison.ResultsThree out of 8 patients reported relief at 1 week, although 1 of these 3 patients had returned to their baseline pain intensity at 3 months. Four patients reported no change at 1 week, though 2 of these patients had reduction of their chronic headache pain at 3 months. A single patient reported increased pain 1 week after the procedure, which persisted at 12 weeks. Overall, 4 out of the 8 patients had decreased pain scores at 3-month follow-up.ConclusionsWe did not achieve a similar frequency of headache resolution as reported in prior original studies. However, a subset of patients did appear to receive substantial benefit from the combined fibrin glue-blood patching procedure. This technique may prove to be useful in medically refractory cases, including those patients who continue to have symptoms despite the prior administration of conventional epidural blood patches.

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