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Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including antigen presentation in vitro. CGRP is associated with Langerhans cells (LC) in oesophageal mucosa, particularly during inflammation, is present in epidermal nerves and is associated with Merkel cells. We examined the ability of CGRP to modulate LC antigen-presenting function and asked if CGRP-containing nerves impinge on LC. We report here that CGRP-containing nerve fibres are intimately associated with LC in human epidermis and CGRP is found at the surface of some LC. In three functional assays CGRP inhibited LC antigen presentation. These findings indicate that CGRP may have immunomodulatory effects in vivo and suggest a locus of interaction between the nervous system and immunological function.

Incidence of psoriasis vulgaris in Asians is estimated at 0.05-0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G 1 monoclonal antibody, was efficacious and well-tolerated in patients with chronic plaque psoriasis. This 24-week, placebo-controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80-mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40-mg eow plus loading dose and 80-mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection-site reactions and hepatic events occurred in greater percentages of adalimumab-treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80-mg loading dose in the treatment of psoriasis.

Atopic dermatitis (AD) is a chronic or chronically-relapsing skin disorder characterized by the infiltration of T cells, eosinophils, mast cells and macrophages in lesional skin [1,2]. Enhanced serum IgE levels, specific IgE environmental allergens such as house dust mites, and blood eosinophilia are also present in the majority of AD patients. It has been proposed that Th2-type cells play a key role in the pathogenesis of AD because of the increased expression of Th2-related cytokines, such as IL-4 and IL-5, in lesional skin [3] and the high responsiveness of peripheral blood mononuclear cells to IL-4, but not IL-2 [4]. Previously, it was shown that serum soluble (s) E-selectin and serum sIL-2 receptor (R) significantly correlate with the disease activity of AD [5][6][7].Macrophage-derived chemokine (MDC), newly termed CCL22 [8], is a CC chemokine that potently serves as a chemoattractant for monocytes, monocyte-derived dendritic cells (DCs) and natural killer (NK) cells [9]. MDC is a ligand for CC chemokine receptor 4 (CCR4) [10], and is chemotactic for a fraction of CD4 + CD45RO + T cells polarized to produce Th2-type cytokines [11]. We have previously shown that in NC/Nga mice, a mouse model for human AD, dermal DCs are immunoreactive for MDC, and that the immunoreactivity of dermal DCs for MDC was abolished by topical corticosteroid treatment [12]. This indicates that the DC is a main source of MDC in lesional skin of AD. Very recently, we reported that levels of thymus and activationregulated chemokine (TARC), another ligand for CCR4, in AD sera significantly correlate with disease activity [13]. Moreover, it is reported that serum MDC levels in AD patients are higher than those in healthy controls [14], although the precise involvement of the high levels of MDC in AD has not yet been fully identified.We measured serum MDC levels in a large number of patients with AD, and compared them with levels in psoriasis vulgaris patients and healthy controls. We also examined the correlation between serum MDC levels, disease severity and the change in serum MDC levels in AD patients, before and after treatment. In addition, we compared serum MDC levels with laboratory data for AD disease markers such as serum soluble (s) SUMMARYAtopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophagederived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furt...

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Recent studies indicate the presence of systemic inflammation in psoriatic patients, and this inflammatory status is significantly associated with a range of comorbidities. The aim of this study was to evaluate the clinical significance of novel inflammatory biomarkers, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mean platelet volume (MPV) in Japanese patients with plaque-type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty-six patients with PsV and 50 patients with PsA treated with biologics, including infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and after treatment. At baseline, NLR and PLR, as well as C-reactive protein (CRP), were significantly higher in PsA patients than those in PsV patients, and a significant correlation was found between NLR and PLR. In PsV patients, the NLR-high and PLR-high subgroups exhibited significantly higher Psoriasis Area and Severity Index scores compared with the NLR-low and PLR-low subgroups, respectively, and the NLR-high subgroup also showed higher CRP levels. MPV value was negatively associated with the presence of arthritis, but its association with inflammation was less clear than that of NLR or PLR. After treatment of the patients with biologics for up to 12 months, NLR and PLR decreased promptly in parallel with a decrease of CRP, irrespective of the type of biologics used. Altogether, these results indicate that both NLR and PLR may be useful markers to evaluate systemic inflammation in psoriatic patients. They may serve as simple, convenient and cost-effective biomarkers to monitor the disease course after systemic therapy.

As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti‐tumor necrosis factor‐α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti‐interleukin (IL)‐12/IL‐23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL‐17 inhibitors of secukinumab and ixekizumab, anti‐IL‐17A antibodies, and brodalumab, an anti‐IL‐17 receptor antibody, and two anti‐IL‐23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration‐related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self‐injection, maintenance therapy at clinics, feasibility of drug discontinuation/re‐administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above‐mentioned factors.

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