Hitomi Tsuji

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.

Increased plasma resistin and decreased omentin levels in Japanese patients with psoriasis

Psoriasis is associated with obesity accompanied by insulin resistance. A recent study disclosed increased plasma resistin and decreased plasma omentin levels in obesity. Few studies of plasma levels of resistin and omentin are available in psoriasis. We analyzed plasma levels of resistin and omentin in psoriasis and compared them with those of healthy controls. Evaluation of plasma levels of resistin and omentin was performed by enzyme-linked immunosorbent assay (ELISA) for 62 psoriasis patients and 58 healthy controls. The severity of psoriasis was evaluated by psoriasis area and severity index (PASI) score. Plasma levels of resistin were significantly increased in psoriasis as compared with those of healthy controls. In contrast, plasma levels of omentin were significantly decreased in psoriasis patients. Plasma levels of resistin and omentin were positively and negatively correlated with PASI scores, respectively. After the treatment of psoriasis, resistin levels were decreased and omentin levels were increased, respectively, compared with those of pretreated. Plasma levels of resistin and omentin might be useful for evaluating the disease activity of psoriasis.

Defective barrier function accompanied by structural changes of psoriatic stratum corneum

Although barrier function of psoriatic skin is shown to be decreased by measuring transepidermal water loss (TEWL), few reports exist examining other physical skin properties and components including stratum corneum hydration, natural moisturizing factor (NMF), free fatty acids (FFA), β‐sheet and α‐helix ratio of structural protein(s), and sebum content. We compared the skin properties and components of normal, involved and uninvolved skin of psoriasis. Using a corneometer and attenuated total reflection‐infrared spectrometer, we measured TEWL, stratum corneum hydration, NMF, FFA, β/α ratio and sebum in psoriasis vulgaris patients and healthy controls. TEWL and β/α ratio of involved psoriatic skin were significantly increased compared with uninvolved skin and normal control skin. In contrast, stratum corneum hydration, NMF and FFA, but not sebum, are significantly decreased in the involved skin compared with uninvolved skin and normal skin. TEWL and stratum corneum hydration returned to the normal levels following clinical improvement of the lesion. Barrier function and hydration of psoriatic skin are defective and secondary structure in stratum corneum protein is altered in the involved psoriatic skin.

Serum level of adiponectin increases and those of leptin and resistin decrease following the treatment of psoriasis

Dear Editor, Serum level of adiponectin is increased in rheumatoid arthritis (RA) and inflammatory bowel disease during infliximab treatment. In the present study, we examined the serum levels of adipokines during various treatments of psoriasis. Psoriatic severity was determined by Psoriasis Area and Severity Index (PASI) score. A total of 37 plaque-type psoriasis patients, including 25 men and 12 women aged 35–71 years (mean age, 46.3), with PASI scores ranging 12.3–22.3 (mean 14.5) and body surface area of 9–45 (mean, 14.3) were enrolled. The patients were treated with infliximab, adalimumab, ustekinumab and narrowband ultraviolet B (NB-UVB) irradiation in addition to topical glucocorticoids or active vitamin D3 treatment. Signed informed consent was taken from all the patients and controls according to the guideline of the Asahikawa Medical School Ethics Committee. Serum levels of adiponectin, leptin and resistin were measured by enzymelinked immunosorbent assay kits (R&D System, Oxon, UK). The serum levels of cytokines were presented as an arithmetic mean standard deviation. Mann–Whitney U-test was used for statistical analysis. A total of 37 psoriatic patients were treated with infliximab (seven cases), adalimumab (10 cases), ustekinumab (seven cases) and NB-UVB (13 cases). All treatments significantly decreased PASI scores (Table 1). There was no significant difference in patients’ body mass index between before (26.2 2.5) and after the treatments (26.3 3.3). At 12 weeks, serum levels of adiponectin, leptin and resistin were not significantly different compared with the pretreatment levels. At 24 week, however, serum levels of adiponectin were significantly increased in all the treatment groups (Table 1). In contrast, serum levels of leptin and resistin were significantly decreased in the treatment groups at 24 weeks (Table 1). There was no significant difference in serum levels of adiponectin, leptin and resistin among the psoriasis treatments groups at 0, 12 and 24 weeks (Table 1). Although serum levels of adiponectin and leptin were not affected at 12 weeks, significant improvements were observed at 24 weeks. Shibata et al. showed increased serum levels of adiponectin in psoriatic patients at 8 weeks following antitumor necrosis factor (TNF)-a treatment. In their study, the patients responded well to the treatment and the PASI clearance rate at 8 weeks was 72%. In contrast, the PASI clearance rate of our patients at 12 weeks was 53% and that at 24 weeks was 74%, which is close to the value of Shibata et al. at 8 weeks. In contrast, Peters et al. showed lack of the effect of onercept, an antibody against human soluble p55 TNF receptor on the serum levels of adiponectin in psoriatic arthritis patients despite the significant improvement of 28-item Disease Activity Index score. The difference in the treatment target and clinical type of psoriasis may explain the difference in adiponectin serum levels. The present study demonstrated that serum levels of adipokines alter during ustekinumab and NB-UVB irradiation treatments. Previously, we reported that serum levels of adiponectin are inversely related with serum TNF-a levels in psoriatic patients, which is compatible with the present results. Because adiponectin does not directly bind with anti-

Japanese patients with psoriasis and atopic dermatitis show distinct personality profiles

Personality and emotional factors are supposed to influence the course of skin diseases, such as psoriasis and atopic dermatitis. Few reports exist, however, showing distinct personality traits among patients with psoriasis, atopic dermatitis patients and healthy controls. The aim of the present study was to examine personality differences among psoriasis patients, atopic dermatitis patients and healthy controls in Japan. A total number of 51 psoriasis patients, 97 atopic dermatitis patients and 48 healthy individuals were enrolled in the study. Questionnaires of Yatabe–Guilford Personality Inventory were administered individually. These groups were evaluated by 12 dimensions of temperaments. According to the dimension scores, personality was defined as five groups. Atopic dermatitis patients showed significantly higher scores regarding temperaments of depression, feelings of inferiority, nervousness and lack of objectivity than psoriasis patients. Regarding a temperament of cyclic tendency and lack of cooperativeness, female atopic dermatitis patients showed significantly higher scores than female psoriasis patients. Regarding general activity, female atopic dermatitis patients showed significantly lower scores than those of female psoriasis patients. No significant difference in scores of temperaments of lack of agreeableness, rhathymia, thinking extraversion, ascendance and social extraversion were detected among psoriasis patients, atopic dermatitis patients and healthy controls. The personalities of male psoriasis patients were significantly different from those of atopic dermatitis patients and healthy controls. Female psoriasis patients showed a significantly different personality profile from that of atopic dermatitis patients, but not from healthy controls. Japanese psoriasis and atopic dermatitis patients show distinct personality profiles suggesting that specific a psychosomatic approach may be required during the treatment.

Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as “erysipelas‐like erythema”, urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF.

Patients with psoriasis and atopic dermatitis show distinct anxiety profiles.

improved by both the direct anti-inflammatory effect of methotrexate and its inhibitory effect on anti-infliximab antibody production; therefore, the administration of methotrexate may be a reasonable option to treat patients with refractory PsA. At present, however, we cannot exclude the possibility that the high-dose methotrexate used in our case may have an anti-inflammatory effect on psoriatic arthritis in this patient. On the other hand, the risk of serious infections and malignancies should be considered more carefully in combination therapy. Further studies will be needed to establish the long-term efficacy and safety of combination therapy consisting of infliximab and methotrexate.

Olanzapine‐induced limb edema simulating episodic angioedema with eosinophilia

fragments on and around the left orbital region (Fig. 1a). The fragments had slightly injured the left cornea. Dermoscopy revealed tiny dust and metal particles (arrows) mostly on or partly inside the skin (Fig. 1b), which we removed through careful and intensive brushing with a toothbrush. The brushing was performed after wiping off the gels. The left cornea was carefully washed and the particles were removed. On 22 July, we used dermoscopy to evaluate the treatment (Fig. 1c) and confirmed that most of the particles had been eliminated (Fig. 1d). A second dermoscopic evaluation on 3 August showed similar results, with the remaining particles forming a traumatic tattoo (Fig. 1e,f). Dermoscopy was useful for evaluating the precise appearance of particles on and within the skin. It could be used as a guide for brushing with a toothbrush before treatment, because the distribution of metal particles is the most important point of treatment. It was also a useful tool for assessment after treatment. Using dermoscopy, we were able to brush the affected lesion sufficiently and eliminate almost all of the metal particles, even though some particles remained as a tattoo. Qswitched ruby laser, Q-switched alexandrite laser and Qswitched 1064-nm neodymium:yttrium–aluminum–garnet laser would be useful for the residual fragments. Future victims may benefit from dermoscopic evaluation of their treatments.

Femoral head osteonecrosis after long‐term topical corticosteroid treatment in a psoriasis patient

with such devices as the SDS and Strengths and Difficulties Questionnaire. In a preliminary study, we utilized the Dermatology Life Quality Index (DLQI) but the HD patients answered ‘‘not relevant’’ to most questions, thus resulting in invalid scores. However, because previously it has been reported that pruritus intensity was significantly related to poor scores for HD patients on all three subscales of Skindex-29 (symptoms, social function and emotions), the Skindex-16 or Skindex-29 would be better than the DLQI to evaluate their quality of life. In conclusion, our results indicate that reduction of pruritus can favorably influence the mental condition of HD patients.

Three cases of psoriasis vulgaris associated with myasthenia gravis

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