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We evaluated the efficacy and safety of upadacitinib, janus kinase 1 inhibitor for atopic dermatitis (AD) in real-world practice. From September 2021 to March 2022, 31 patients with moderate-to-severe AD, aged ≥12 years were treated with oral upadacitinib 15 mg/day plus topical corticosteroids. Upadacitinib reduced clinical indexes compared to baseline levels: percent reduction at week 4 and 12 (median) was 73.6% and 85.6% in eczema area and severity index (EASI); 81.3% and 81.3% in AD control tool (ADCT); and 70% and 75% in peak pruritus numerical rating score (PP-NRS), respectively. The achievement rate of EASI 75 was 51.6% and 67.7% at week 4 and 12, respectively. Upadacitinib reduced serum lactate dehydrogenase and total eosinophil count (TEC) at week 4 and 12, and thymus and activation-regulated chemokine and immunoglobulin E at week 4, compared to baseline levels. Percent reduction of TEC was correlated with that of EASI at week 4 and 12. Baseline TEC was positively correlated with the percent reduction of EASI at week 4. Percent reduction of EASI in female patients was higher than that in male patients at week 4 and 12. Linear multivariate regression analyses revealed that high percent reduction of EASI at week 4 or 12 was associated with high baseline TEC or female gender, respectively. There were no serious treatment-emergent adverse events. Adverse events include acne (5%), elevation of creatine phosphokinase (9.7%), herpes zoster (1%), and AD (1%). Upadacitinib plus topical corticosteroids for patients with AD in the real-world practice was well tolerated and gave therapeutic effects comparable with those in previous clinical trials. The ADCT and PP-NRS rapidly reduced at week 4 while EASI gradually reduced until week 12. The TEC might act both as a predictive factor of response at week 4 and as a biomarker reflecting therapeutic effects in upadacitinib treatment for AD.

Kei Hosoya,1 Taro Komachi,2,* Katsunori Masaki,3,* Isao Suzaki,4 Hidehisa Saeki,5 Naoko Kanda,6 Makoto Nozaki,7 Yosuke Kamide,8 Yoshinori Matsuwaki,9 Yoshiki Kobayashi,10 Eriko Ogino,11 Shin-Ichi Osada,12 Norihiro Usukura,13 Toshikazu Kurumagawa,14 Junya Ninomia,15 Mikiya Asako,16 Keitaro Nakamoto,17 Hidenori Yokoi,18 Manabu Ohyama,19 Keiji Tanese,3 Sho Kanzaki,3 Koichi Fukunaga,3 Motohiro Ebisawa,8 Kimihiro Okubo13 1Nippon Medical School, Musashi Kosugi Hospital, Kanagawa, Japan; 2Department of Otolaryngology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 3Keio Allergy Center, Keio University Hospital, Tokyo, Japan; 4Department of Otorhinolaryngology, Head and Neck Surgery, Showa University, School of Medicine, Tokyo, Japan; 5Department of Dermatology, Nihon Medical School, Tokyo, Japan; 6Department of Dermatology, Nippon Medical School, Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 7Wakaba-Hifuka Clinic, Tokyo, Japan; 8National Hospital Organization Sagamihara National Hospital, Clinical Research Center for Allergy and Rheumatology, Kanagawa, Japan; 9Matsuwaki Clinic Shinagawa, Tokyo, Japan; 10Allergy Center, Kansai Medical University, Hirakata, Japan; 11Kyoto Nose and Allergy Clinic, Kyoto, Japan; 12Department of Dermatology, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan; 13Department of Otolaryngology, Head and Neck Surgery, Nippon Medical School Hospital, Tokyo, Japan; 14Minamiosawa Medical Plaza, Tokyo, Japan; 15Nagase Clinic of Dermatology, Tokyo, Japan; 16Department of Otolaryngology, Head and Neck Surgery, Kansai Medical University, Osaka, Japan; 17Department of Respiratory Medicine, Kyorin University Faculty of Medicine, Tokyo, Japan; 18Department of Otolaryngology, Head and Neck Surgery, Kyorin University Faculty of Medicine, Tokyo, Japan; 19Department of Dermatology, Kyorin University Faculty of Medicine, Tokyo, Japan*These authors contributed equally to this workCorrespondence: Kei Hosoya, Nippon Medical School, Musashi Kosugi Hospital, 1-383 Kosugimachi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan, Tel +81-44-733-5181, Fax +81-44-711-8713, Email s00-073@nms.ac.jpPurpose: The status of dupilumab self-injection at home is not well understood. We therefore aimed to identify the barriers to adherence to dupilumab self-injection.Patients and Methods: This non-interventional open-label study was conducted between March 2021 and July 2021. Patients with atopic dermatitis, bronchial asthma, and chronic rhinosinusitis with nasal polyps receiving dupilumab, from 15 sites, were requested to complete a self-administered questionnaire regarding the frequency and effectiveness of dosing as well as their use and satisfaction with dupilumab. Barriers to adherence were assessed using the Adherence Starts with Knowledge-12.Results: We included 331 patients who used dupilumab for atopic dermatitis (n = 164), chronic rhinosinusitis with nasal polyps (n = 102), and bronchial asthma (n = 65). The median efficacy of dupilumab scored 9.3 on the visual analog scale. Overall, 85.5% of the patients self-injected dupilumab, and 70.7% perfectly complied with the established injection dates. The pre-filled pen was significantly superior to the conventional syringe in terms of usability, operability, ease of pushing the plunger, and patient satisfaction. However, the pre-filled pen caused more pain during self-injection than did the syringe. Multivariate logistic regression analysis showed that adherence decreased with longer dupilumab treatment duration (p = 0.017) and was not associated with age, sex, underlying disease, or device type. There was a difference in responses related to “inconvenience/forgetfulness” between the good and poor adherence groups.Conclusion: The pre-filled dupilumab pen was superior to the syringe in terms of usability, operability, ease of pushing the plunger, and satisfaction. Repetitive instructions are recommended for preventing poor adherence to dupilumab self-injection.Keywords: atopic dermatitis, biologics, bronchial asthma, chronic rhinosinusitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease with severe itch. The eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are reported to reflect itch or the severity of AD. We examined if these parameters may act as indicators for therapeutic effects of the Janus kinase 1 inhibitor upadacitinib for patients with AD in real-world clinical practice. Between August 2021 and September 2023, 65 Japanese patients (aged ≥ 12 years) with moderate to severe AD were treated with 15 mg/day of oral upadacitinib, plus twice daily topical corticosteroids. Before treatment, the baseline ELR, NLR, MLR, and PLR levels positively correlated with the eczema area and severity index (EASI), while the baseline NLR and PLR levels positively correlated with the peak pruritus-numerical rating scale (PP-NRS). After upadacitinib treatment, ELR and NLR remarkably decreased at week 4 and the reduced levels were maintained until week 24, in parallel with EASI and PP-NRS, while MLR and PLR transiently reduced at week 4, but returned to baseline levels after week 12. The percent reduction of ELR significantly correlated with the percent reductions of EASI and PP-NRS at weeks 4, 12, and 24 of upadacitinib treatment. ELR may act as an indicator for the improvement of clinical signs and itch by upadacitinib treatment in AD.

Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis and the defective gene in HHD is ATP2C1, which encodes secretory pathway Ca

Teppei Hagino,1,2 Shizuka Okazaki,1 Naotaka Serizawa,1 Kaori Suzuki,1 Mio Kaga,2 Yohei Otsuka,2 Erina Mikami,2 Toshihiko Hoashi,2 Hidehisa Saeki,2 Hiroki Matsuda,3 Hiroshi Mitsui,3 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Department of Dermatology, Tokyo Teishin Hospital, Tokyo, JapanCorrespondence: Naoko KandaDepartment of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694 JapanTel +81 476 99 1111Fax +81 476 99 1909Email n-kanda@nms.ac.jpPurpose: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls.Patients and Methods: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls.Results: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score > 25) was higher than that in patients with mild AA (a SALT score ≤ 25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age.Conclusion: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.Keywords: retinol, vitamin C, body mass index, atopic dermatitis

The pathomechanisms of various skin diseases have recently been elucidated progressively [...]

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in the cranial nerve or dorsal root ganglia, with spread of the virus along the sensory nerve to the dermatome. Postherpetic neuralgia is a feared complication of HZ and impairs patients' quality of life enormously. However, there is no predictor of the duration of neuralgia. Our objective was to investigate whether there are correlations between the duration of neuralgia and serum levels of potential biomarkers in order to find practical predictors of the duration of neuralgia. Patients who were diagnosed with HZ at our hospital from April 2013 to January 2014 were included in this study. Serum levels of cytokines and other biomarkers were measured using commercial enzyme-linked immunosorbent assay kits. Thirty patients (15 men and 15 women) with HZ were enrolled in this study. The mean age was 66.1 ± 9.2 (standard deviation) years (range, 51-84 years). Four patients were evaluated as having mild, 19 as having moderate, and seven as having severe HZ. Patients with severe HZ suffered from neuralgia for a significantly longer period of time than patients with mild-to-moderate HZ (9.86 ± 8.25 months vs. 2.01 ± 2.68 months, severe vs. mild-to-moderate, p = 0.0021). The serum interleukin (IL)-10 level was significantly higher in patients with severe HZ than in those with mild-to-moderate HZ (12.93 ± 3.27 pg/mL vs. 6.74 ± 3.72 pg/mL; severe vs. mild-to-moderate; p = 0.0487). Furthermore, the serum IL-10 level was significantly correlated with the duration of neuralgia (r = 0.5193, p = 0.0111). Lastly, the serum IL-10 level significantly decreased after treatment in comparison with that before treatment (from 8.15 ± 4.46 pg/mL to 4.32 ± 11.83 pg/mL, p < 0.0001). In conclusion, these results suggest that the serum IL-10 level is an objective biomarker of the severity of HZ, and that the serum IL-10 level can be a practical predictor of the duration of neuralgia.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α (TNF-α) /interleukin (IL) -23/IL-17 axis, epidermal hyperproliferation, and dysregulated differentiation. Psoriasis is occasionally associated with autoimmune liver diseases such as autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), caused by autoimmunity against hepatocyte- or cholangiocyte-specific autoantigens, respectively. Overlap syndrome is a condition in which patients have features of both AIH and PBC. It has been reported that AIH, PBC, or the overlap syndrome can be triggered by certain drug therapies. A 65-year-old Japanese man developed increased serum levels of aspartate and alanine aminotransferases, and positive anti-nuclear and anti-mitochondrial M2 antibodies, along with neutropenia, at 4 weeks of treatment with an anti-IL-17 receptor A antibody brodalumab for generalized pustular psoriasis. Histological evaluation of the liver revealed interface hepatitis and non-suppurative destructive cholangitis, which is compatible with the overlap syndrome of AIH and PBC. This is the first case of AIH/PBC overlap syndrome during treatment with brodalumab for generalized pustular psoriasis. The relationship between brodalumab and AIH/PBC overlap syndrome should be further elucidated. The risk of autoimmune liver diseases in patients with psoriasis treated with brodalumab should be carefully considered.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by hyperproliferation of epidermal keratinocytes. Biologics have been available for the treatment of patients with refractory psoriasis since 2010 in Japan, and as of December 2021, 10 biologics were available. The Biologics Review Committee of the Japanese Dermatological Association for Psoriasis recommends blood examination tests for antinuclear antibodies (ANA), Krebs von den Lugen (KL)-6, hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBsAb), hepatitis B core antibodies (HBcAb), hepatitis C virus (HCV) antibodies, HIV antibodies, human T-cell leukemia virus (HTLV)-1 antibodies, β-D-glucan, and the T-cell spot (T-SPOT) test before initiation of biologics at screening. In this study, we evaluated the use of biologics for 127 psoriasis patients and the blood examination screening data before initiation of biologics in the real-world setting. Tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors were initiated for 54 (42.5%), 36 (28.3%), and 37 (29.1%) patients, respectively. The numbers of patients positive for ANA, HBsAg, HBsAb, HBcAb, HCV antibody, HIV antibody, HTLV-1 antibody, and T-SPOT were 27 (21.3%), 0 (0%), 22 (17.3%), 20 (15.7%), three (2.4%), zero (0%), one (0.8%), and 4 (3.1%), respectively. The numbers of patients whose KL-6 and β-D-glucan levels were higher than the reference values were seven (5.5%) and seven (5.5%), respectively. In the real-world setting, it is sometimes unavoidable to use biologics for those patients with abnormal data although careful monitoring is necessary.

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to June 2022, 28, 15 and 12 patients with psoriasis were treated with infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP), respectively. The values of C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio decreased in parallel with psoriasis area and severity index (PASI) at weeks 12 and 52 of treatment. The percentage reduction of the CRP was correlated with that of the PASI at week 52 in all patients and subgroups treated with IFX. The percentage reduction of the PLR was correlated with that of the PASI at week 52 in all patients. Linear multivariate regression analyses revealed that the presence of scalp lesions was associated with a high percentage reduction of the PASI at week 52 in the ADA subgroup. The CRP and PLR might act as biomarkers reflecting the treatment response to TNF-α inhibitors in patients with psoriasis. The presence of scalp lesions might be a predictive factor for a high treatment response to ADA in patients with psoriasis.

Background Dupilumab, a fully human monoclonal antibody that blocks signalling pathways of interleukin (IL)-4 and IL-13, is effective in treating patients with atopic dermatitis (AD). We previously showed that transitions of serum thymus and activation-regulated chemokine (TARC) levels and eosinophil numbers were strongly associated with that of AD activity and that the transitions of serum lactate dehydrogenase (LDH) and immunoglobulin E (IgE) levels were weakly and not associated with that of AD activity, respectively, in patients treated without dupilumab. Objectives The purpose of this study was to elucidate whether the association of the transition of laboratory marker levels and transition of disease activity in dupilumab-treated AD patients (present study) was different from that in patients who are not treated with dupilumab (previous study). Methods Sixty AD outpatients treated with dupilumab were included in this study. Associations between the transition of the eczema area and severity index (EASI) score and those of above-mentioned laboratory marker levels were evaluated using a mixed effects model of EASI as the response variable, laboratory markers as fixed effects and patients as random effects. Results The transitions of serum TARC and LDH levels were associated strongly with that of AD activity, but the transitions of serum IgE level and eosinophil numbers were associated with that of AD activity intermediately and weakly, respectively. Conclusions Laboratory markers are useful for evaluating the effects of treatments for AD, but the meaning of each laboratory marker depends on the drugs used for treatment.

Among human cutaneous malignancies, basal cell carcinoma is the most common. Solid advances in unveiling the molecular mechanisms of basal cell carcinoma have emerged in recent years. In Gorlin syndrome, which shows basal cell carcinoma predisposition, identification of the patched 1 gene (PTCH1) mutation was a dramatic breakthrough in understanding the carcinogenesis of basal cell carcinoma. PTCH1 plays a role in the hedgehog pathway, and dysregulations of this pathway are known to be crucial for the carcinogenesis of many types of cancers including sporadic as well as hereditary basal cell carcinoma. In this review, we summarize the clinical features, pathological features and hedgehog pathway as applied in basal cell carcinoma. Other crucial molecules, such as p53 and melanocortin-1 receptor are also discussed. Due to recent advances, therapeutic strategies based on the precise molecular mechanisms of basal cell carcinoma are emerging. Target therapies and biomarkers are also discussed.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin (IL)-23/IL-17 axis. Patients with psoriasis manifest functional defects in CD4+CD25+ forkhead box protein 3 (Foxp3)+ regulatory T cells (Tregs), which suppress the excess immune response and mediate homeostasis. Defects in Tregs contribute to the pathogenesis of psoriasis and may attribute to enhanced inhibition and/or impaired stimulation of Tregs. IL-23 induces the conversion of Tregs into type 17 helper T (Th17) cells. IL-17A reduces transforming growth factor (TGF)-β1 production, Foxp3 expression, and suppresses Treg activity. Short-chain fatty acids (SCFAs), butyrate, propionate, and acetate are microbiota-derived fermentation products that promote Treg development and function by inducing Foxp3 expression or inducing dendritic cells or intestinal epithelial cells to produce retinoic acids or TGF-β1, respectively. The gut microbiome of patients with psoriasis revealed reduced SCFA-producing bacteria, Bacteroidetes, and Faecallibacterium, which may contribute to the defect in Tregs. Therapeutic agents currently used, viz., anti-IL-23p19 or anti-IL-17A antibodies, retinoids, vitamin D3, dimethyl fumarate, narrow-band ultraviolet B, or those under development for psoriasis, viz., signal transducer and activator of transcription 3 inhibitors, butyrate, histone deacetylase inhibitors, and probiotics/prebiotics restore the defected Tregs. Thus, restoration of Tregs is a promising therapeutic target for psoriasis.

Autoimmune hepatitis (AIH) is a chronic inflammation of the liver caused by hepatocyte-specific autoantigens. Psoriasis is a chronic inflammatory skin disease characterized by a skewed interleukin-17 immune response and dysregulated epidermal hyperproliferation and differentiation. Patients with psoriasis have a higher risk of AIH. Some evidence indicates that AIH is triggered by treatment with certain drugs. Brodalumab is a human monoclonal antibody against interleukin-17 receptor A and is used to treat psoriasis. A 70-year-old Japanese man with psoriasis had elevated serum levels of transaminases and bilirubin, positive antinuclear antibodies, and high serum IgG levels after 11 months of brodalumab treatment. Histological analysis of liver tissue revealed interface hepatitis with lymphoplasmacytic infiltration. AIH was diagnosed and treated with prednisolone, which improved his symptoms. This is the first case of AIH during brodalumab treatment for psoriasis. The relationship between brodalumab and AIH should be further examined, and the risk of AIH in psoriatic patients treated with brodalumab should be carefully considered.

Psoriasis is characterized by T-helper 17 cell-dominant abnormal immunity, and hyperproliferation and abnormal differentiation of epidermal keratinocytes. Some patients are associated with arthritis. Dietary habits can modulate the pathogenesis of psoriasis. Previous studies in Western countries showed higher body mass indices, higher intake of fat and lower intake of fish or vegetables in psoriatic patients compared with the reference groups. We evaluated dietary habits in adult Japanese psoriatic patients, using a validated brief-type self-administered dietary history questionnaire, and compared the results to those of age- and sex-matched healthy controls. The results in psoriatic patients with arthritis were compared with those in the patients without. Japanese psoriatic patients showed higher body mass indices, higher intake of fish/shellfish, pulses, sugar/sweeteners, vitamin B12 and vitamin D, and lower intake of meat, compared with those of healthy controls. The logistic regression analysis showed that psoriasis was associated with high body mass index and low intake of meat. The intake of confection in patients with high Psoriasis Area and Severity Index was higher than that in those with low index. The intake of β-carotene, vitamin A and green/yellow vegetables in psoriatic patients with arthritis were higher than those in the patients without. The dietary habits in Japanese psoriatic patients are rather different from those in Western patients. This is the first study showing the differences in dietary habits between psoriatic patients with arthritis and those without. Further studies should elucidate the relationships of these results with skin and joint lesions in psoriatic patients.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that targets the low-density lipoprotein (LDL) receptor for lysosomal degradation. PCSK9 impedes the receptor-mediated clearance of LDL-cholesterol, thereby increasing serum LDL-cholesterol levels. Evolocumab, a human monoclonal antibody against PCSK9, effectively reduces serum LDL-cholesterol levels. We report the first known case of a patient who developed an atopic dermatitis (AD)-like rash during evolocumab therapy. A 43-year-old Japanese man with heterozygous familial hypercholesterolemia was treated with subcutaneous injection of 140 mg evolocumab biweekly, for 16 months. The therapy was then changed to subcutaneous injection of 420 mg evolocumab monthly. A few days after the first dose, the patient experienced pruritus and rash on his extremities. The rash worsened, while the pruritus subsided, then relapsed after the second and third doses. He had erythema and excoriation on his legs, lichenification over his popliteal fossa, xerosis on his forearms, an increased serum IgE level, and a family history of AD in his siblings. We made a provisional diagnosis of AD characterized by enhanced type 2 helper T (Th2) activity and treated him with topical corticosteroids and oral anti-histamines. His rash improved and did not relapse after the fifth dose; however, his LDL-cholesterol level increased. PCSK9 or oxidized LDL activates macrophages or dendritic cells, respectively, and enhances their activity to induce Th1 cells antagonizing Th2 cells. We hypothesized that high-dose evolocumab may suppress Th1 activity to antagonize Th2, and unmask Th2 disposition based on the patient's atopic diathesis, triggering the rash mimicking AD. Clinicians should be aware of rash development during evolocumab therapy.

Psoriasis is a chronic inflammatory skin disease characterized by IL-17-dominant abnormal innate and acquired immunity, and the hyperproliferation and aberrant differentiation of epidermal keratinocytes, and comorbid arthritis or cardiometabolic diseases. This Special Issue presented updated information on pathogenesis, comorbidities, and therapy of psoriasis. The pathogenesis of psoriasis may involve the dysfunction of indoleamine 2,3-dioxygenase 2 or of UBA domain containing 1-mediated regulation of CARD14/CARMA2sh. The blood cells of psoriasis patients showed the enhanced oxidative stress/autophagy flux and decreased 20S proteasome activity. Elafin, clusterin, or selenoprotein P may act as biomarkers for psoriasis and comorbid metabolic diseases. The proteomic profile of psoriasis lesions showed the dysfunction of dermal fibroblasts; up-regulation of proinflammatory factors and signal transduction or down-regulation of structural molecules. The skin inflammation in psoriasis may populate certain gut bacteria, such as Staphylococcus aureus and Streptococcus danieliae, which worsen the skin inflammation in turn. The psoriasis-associated pruritus may be caused by immune, nervous, or vascular mechanisms. In addition to current oral treatments and biologics, a new treatment option for psoriasis is now being developed, such as retinoic-acid-receptor-related orphan nuclear receptor γt inhibitors, IL-36 receptor antagonist, or aryl hydrocarbon receptor agonist. Antimicrobial peptides and innate immune cells, involved in the pathogenesis of psoriasis, may be novel therapeutic targets. The pathomechanisms and responses to drugs in collagen diseases are partially shared with and partially different from those in psoriasis. Certain nutrients can exacerbate or regulate the progress of psoriasis. The articles in this Special Issue will encourage attractive approaches to psoriasis by future researchers.

Atopic dermatitis (AD) is a chronic eczematous disease characterized by T helper 2 (Th2) -shifted allergic immunity, skin barrier impairment, and pruritus. Oral intake of certain nutrients might help regulate AD. Serum 25-hydroxyvitamin D levels are often low in patients with AD, and oral vitamin D supplementation improves AD. Vitamin D increases regulatory T (Treg) cells, which promote tolerance to allergens and prevent allergic inflammation by inducing expression of filaggrin and cathelicidin in keratinocytes. Vitamin A strengthens Treg cells by inducing expression of forkhead box P3 and inhibits mediator release from mast cells and eosinophils. Serum levels of γ-linolenic acid and its metabolite, dihomo-γ-linolenic acid, are low in patients with AD, and oral γ-linolenic acid improves AD through anti-inflammatory prostaglandin D1 and E1 derived from dihomo-γ-linolenic acid. Eicosapentaenoic acid and docosahexaenoic acid ameliorate AD by suppressing production of leukotriene B4, increasing ceramides in the stratum corneum, and through their metabolites, resolvin E1 and D1, which resolve inflammation. The probiotics Lactobacillus and Bifidobacteria improve the intestinal permeability barrier and induce Treg cells. Zinc levels in serum, hair, and erythrocytes are diminished in patients with AD. Zinc induces forkhead box P3 expression and increases Treg cells, and zinc-finger protein A20 suppresses nuclear factor-κB-dependent expression of inflammatory cytokines and cell-adhesion molecules. Oral supplementation of the above nutrients might have therapeutic or preventive roles in AD.

Palmoplantar pustulosis (PPP) is a chronic dermatitis characterized by sterile intra-epidermal pustules associated with erythema and scales on the palms and soles. Tumor necrosis factor (TNF)-α/interleukin (IL)-23/IL-17 inflammatory pathway may be involved in the pathogenesis of PPP, and the skin lesions manifest the enhanced expression of IL-8 in keratinocytes and increased levels of antimicrobial peptide cathelicidin, leucine leucine-37 in vesicles/pustules. Some PPP patients are associated with arthro-osteitis, called pustulotic arthro-osteitis (PAO). Dietary habits may modulate the pathogenesis of PPP, however, have not been investigated in PPP patients. We evaluated dietary habits in adult Japanese PPP patients, using a validated, brief-type self-administered diet history questionnaire, and compared their results to those of age- and sex-matched healthy controls. The results in PPP patients with PAO were compared to those in the patients without. Japanese PPP patients showed higher body mass indices (BMIs), higher intakes of pulses and sugar/sweeteners, and lower intake of vitamin A, compared to those of healthy controls. The bivariate and multivariable logistic regression analysis showed that PPP was associated with high BMI, high intake of pulses, and low intake of vitamin A. The sodium intake and BMI were positively correlated with palmoplantar pustulosis area and severity index (PPPASI). The linear multivariate regression analysis revealed that sodium intake and BMI were predictors of PPPASI. The age and sodium intake in the patients with PAO were lower than those in the patients without. The bivariate and multivariable logistic regression analysis showed that PAO was negatively associated with age and sodium intake. This is the first study showing the dietary habits in patients with PPP. Further studies should clarify if the dietary intervention to correct the BMI and sodium intake will alter the progress of PPP.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α/interleukin-23/interleukin-17 axis, hyperproliferation and abnormal differentiation of epidermal keratinocytes. Psoriasis patients are frequently associated with obesity, diabetes, dyslipidemia, cardiovascular diseases, or inflammatory bowel diseases. Psoriasis patients often show unbalanced dietary habits such as higher intake of fat and lower intake of fish or dietary fibers, compared to controls. Such dietary habits might be related to the incidence and severity of psoriasis. Nutrition influences the development and progress of psoriasis and its comorbidities. Saturated fatty acids, simple sugars, red meat, or alcohol exacerbate psoriasis via the activation of nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 inflammasome, tumor necrosis factor-α/interleukin-23/interleukin-17 pathway, reactive oxygen species, prostanoids/leukotrienes, gut dysbiosis or suppression of regulatory T cells, while n-3 polyunsaturated fatty acids, vitamin D, vitamin B12, short chain fatty acids, selenium, genistein, dietary fibers or probiotics ameliorate psoriasis via the suppression of inflammatory pathways above or induction of regulatory T cells. Psoriasis patients are associated with dysbiosis of gut microbiota and the deficiency of vitamin D or selenium. We herein present the update information regarding the stimulatory or regulatory effects of nutrients or food on psoriasis and the possible alleviation of psoriasis by nutritional strategies.

A 39-year-old Japanese woman presented with a pruritic infiltrated erythematous plaque on the right cheek. Histopathologic analysis of the erythema showed dermal edema, separation of collagen bundles, and nodular perivascular and periadnexal infiltration of lymphocytes in the whole dermis, without epidermal changes. Alcian blue staining intensity was elevated between the collagen bundles, indicating dermal mucinosis. The nodular infiltrates consisted of CD3+ T cell clusters and CD20+ B cell clusters (ratio, approximately 3:1) and included numerous CD123+ cells, indicative of plasmacytoid dendritic cells. Blood analysis revealed serum antinuclear antibody at a titer of 1:160 (homogeneous, speckled pattern). Lupus erythematosus tumidus with pseudolymphomatous infiltrates was diagnosed. Hydroxychloroquine treatment partially improved symptoms; however, the addition of prednisolone was required for complete resolution. Lupus erythematosus tumidus is sometimes accompanied by pseudolymphomatous infiltrates. Dermal mucinosis and the presence of numerous plasmacytoid dendritic cells are useful in differentiating lupus erythematosus tumidus from pseudolymphoma.

Background Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. Methods We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. Results Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test ≦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. Conclusions Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.