Search

The T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is a co‐inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation‐regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway‐based therapeutic approach for AD. [ABSTRACT FROM AUTHOR]

Dear Editor, A case of bullous pemphigoid associated with interstitial pneumonia Bullous pemphigoid is an autoimmune subepidermal bullous disease caused by autoantibodies against adhesion molecules located in the epidermal basement membrane zone including bullous pemphigoid antigen 180 (BP180). Direct immunofluorescence testing of the bullous skin lesion showed weak linear deposition of IgG and strong linear deposition of C3 in the basement membrane zone (Fig d, e). Direct immunofluorescence testing of transbronchial lung biopsy revealed minimal deposition of IgG and some deposition of C3 in a part of basement membrane zone of the alveolar epithelia (Fig g, h). [Extracted from the article]

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double-blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open-label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end-points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index ( PASI75) and Physician's Global Assessment of 'clear' or 'almost clear' ( PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria ( ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty-seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies. [ABSTRACT FROM AUTHOR]

Psoriasis has been shown to accompany systemic inflammation. We aimed to examine serum C-reactive protein ( CRP) levels in Japanese psoriatic patients, and to elucidate their long-term as well as short-term changes by treatment with different biologics. A retrospective study was conducted in those who initiated and successfully continued the treatment for up to 24 months with either infliximab, adalimumab or ustekinumab, at the psoriasis special clinic of Jikei University School of Medicine. A total of 212 patients were included, 171 with plaque-type psoriasis (PsV) and 41 with psoriatic arthritis (PsA). A statistically significant elevation of CRP values was found in the group with a Psoriasis Area and Severity Index ( PASI) of 12 or more compared with the PASI of less than 12 for both PsV and PsA. The CRP-positive patients had a higher proportion of PsA compared with the CRP-negative patients, and they had significantly higher PASI scores. Serum CRP values declined as early as at 3 months after systemic treatment with biologics. Tumor necrosis factor ( TNF)-α antagonists did lead to a notable and sustained CRP decline up to 24 months. Infliximab showed rapid decline, while CRP decline by adalimumab treatment was time-dependent. The interleukin-12/23 p40 antagonist, ustekinumab, appeared to be less potent than TNF-α antagonists in stabilizing CRP values at low levels despite good control of cutaneous lesions. In conclusion, serum CRP levels can be used to assess disease severity in Japanese psoriatic patients as a marker of systemic inflammation. TNF-α antagonists may be more beneficial than ustekinumab in this regard. [ABSTRACT FROM AUTHOR]

The tumor necrosis factor-α inhibitor, adalimumab, is approved to treat moderate-to-severe plaque psoriasis (40 mg every-other-week or 80 mg every-other-week following inadequate response at 40 mg in Japan). This open-label extension (OLE) trial evaluated the optimal adalimumab dose for long-term efficacy and safety in Japanese patients with moderate-to-severe plaque psoriasis following a prior 24-week, phase 2/3, randomized, double-blind study. Of the 169 patients from the phase 2/3 trial, 147 entered the OLE on 40 mg ( n = 89) or 80 mg ( n = 58) adalimumab every-other-week. Patients on 40 mg with Psoriasis Area and Severity Index (PASI) of less than 50 could escalate to 80 mg. At week 52 (28 of OLE), patients entering the OLE on 80 mg were reduced to 40 mg, with the option to re-escalate. For patients entering the OLE on 40 mg, final PASI 50/75/90 response rates were 85.1%/73.3%/60.4%, respectively, including effects of dose escalation. Among patients whose dose was escalated, final PASI 50/75/90 response rates were 70.0%/53.3%/36.7%, respectively. For patients entering the OLE on 80 mg, final PASI 50/75/90 response rates were 92.5%/84.9%/73.6%, respectively, including effects of dose re-escalation. Overall incidence rates of adverse events (AE) and injection-site reaction AE declined over time; rates for serious AE and infections were generally stable. Clinically meaningful efficacy of adalimumab was sustained to 4 years. Dose escalation to 80 mg every-other-week for patients with suboptimal response to 40 mg every-other-week, and dose reduction to 40 mg every-other-week for patients satisfactorily controlled on 80 mg every-other-week, are viable strategies for adalimumab optimization. [ABSTRACT FROM AUTHOR]

Mycobacterium haemophilum is a slow-growing non-tuberculous mycobacterium that is rarely known to cause human skin infection, particularly in immunocompromised patients. We recently experienced a 69-year-old Japanese woman with this infection who had been under immunosuppressive treatment for recalcitrant rheumatoid arthritis. The patient showed disseminated erythematous plaques and subcutaneous nodules on the face and extremities, and interestingly, the face manifested with a striking 'facies leontina' appearance. Biopsy revealed abscess and granulomatous dermatitis with the involvement of peripheral nerve bundles and the presence of innumerable acid-fast bacilli, thus necessitating differentiation from lepromatous leprosy. M. haemophilum was identified by molecular characterization as well as by successful culture with iron supplements. Although drug susceptibility testing indicated responsiveness to multiple antibiotics administrated simultaneously for the treatment, it took over 6 months to achieve significant improvement, and we also employed concurrent oral potassium iodide administration and repeated surgical excision. This case highlights the importance of continuous combination therapy for successful outcome in this rare infection. Furthermore, application of potassium iodide for mycobacterial infection warrants further evaluation by accumulating more cases. [ABSTRACT FROM AUTHOR]

Patients with psoriasis undergoing hemodialysis have additional difficulties in treatment compared with general patients. Conventional treatments such as cyclosporin, retinoids and methotrexate are not widely administrated due to the chances of an increase in adverse effects and the possibility of risk to patient survival. Recently, biologic treatments have been recognized as having sufficient efficacy for severe psoriasis with low incidence of organ toxicities. For this reason, biologic treatments may be more preferable for patients on hemodialysis; however, there is not sufficient evidence. We have treated three patients with psoriasis with ustekinumab for 1 year, who had been undergoing hemodialysis. They were previously treated with conventional treatments before ustekinumab treatments; however, they did not respond to these treatments sufficiently. Following treatment with ustekinumab, rapid and maintained improvement in psoriasis was observed. Over the course of treatments, two of the three patients encountered no adverse events during their first year of treatment. The other patient discontinued ustekinumab due to elevated levels of C-reactive protein. These findings suggest that ustekinumab may be an appropriate treatment for patients undergoing hemodialysis who are suffering from psoriasis. However, the risk of developing infection remains higher than in general patients. [ABSTRACT FROM AUTHOR]