Masahiro Aoshima

The Burden and Etiology of Community- Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

Background The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. Methods A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. Results A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). Conclusions A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.

Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study

BACKGROUND The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population. METHODS For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design. FINDINGS 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia. INTERPRETATION PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated. FUNDING Pfizer and Nagasaki University.

Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma

Recently, an unexpected outbreak of patients with leukoderma occurred in Japan with the use of brightening/lightening cosmetics containing rhododendrol (RD). Patients developed leukoderma mostly on the skin sites repeatedly applied with RD, but some patients also had vitiligo-like lesions on the non-applied sites. RD is a tyrosinase-competitive inhibiting substance, thereby serving as an inhibitor of melanin synthesis. Upon inhibition of tyrosinase, RD is converted to new products such as tyrosinase-catalyzed hydroxyl-metabolite, which damage melanocytes. The melanocyte cell lysates seem to induce T-cell response. The frequencies of CD8+ T cells in both lesional skin and peripheral blood are significantly higher in the RD leukoderma as well as non-segmental vitiligo patients than in normal controls. In HLA-A*02:01 positive cases, circulating Melan-A-specific cytotoxic T cells can be detected at a high frequency. It is thus suggested that RD-induced leukoderma is induced by not only cytolysis of melanocytes but also subsequent immune reactions toward melanocytes.

Proteome analysis of stratum corneum from atopic dermatitis patients by hybrid quadrupole-orbitrap mass spectrometer

may also be anti-inflammatory by reducing nuclear factor kappa B gene expression. Similarly, in addition to their inflammatory role, Langerhans cells are thought to have immunoregulatory functions. Indeed, we see that langerin cells are largely reduced in lesional than in nonlesional AD skin at baseline, and significantly increase on clinical reversal after 12 weeks of CsA treatment (Fig 1, E, and Table E3). In addition to the RDGP, other possible mechanisms for disease recurrence in the same areas need to be considered, including (1) regional differences (increased humidity/friction, transepidermal water loss, pH, and lipids) that allow increased antigen penetration, (2) epigenetic modifications, and (3) microbiome differences. In summary, we have demonstrated that although the CsA RDGP is much smaller than the NB-UVB RDGP, important structural defects and residual inflammation remain and the overall size of the RDGP does not predict relapse kinetics. Given that NB-UVB and CsA have different courses of disease maintenance on discontinuing therapy, some elements in the RDGP of each treatment might explain relevant treatmentand disease-specific mechanisms. Mariya Rozenblit, BA Mayte Suarez-Farinas, PhD Avner Shemer, MD Saakshi Khattri, MD Patricia Gilleaudeau, NP Mary Sullivan-Whalen, NP Xiuzhong Zheng, MSc Hui Xu, MSc Irma Cardinale, MSc James G. Krueger, MD, PhD Emma Guttman-Yassky, MD, PhD

Emergence of circulating monomyeloid precursors predicts reactivation of human herpesvirus-6 in drug-induced hypersensitivity syndrome.

1999; 24:341–5. 5 de Onis M, Blössner M. Prevalence and trends of overweight among preschool children in developing countries. Am J Clin Nutr 2000; 72:1032–9. 6 Janssen I, Katzmarzyk PT, Boyce WF et al. Health Behaviour in School-Aged Children Obesity Working Group. Comparison of overweight and obesity prevalence in school-aged youth from 34 countries and their relationships with physical activity and dietary patterns. Obes Rev 2005; 6:123–32. 7 Griffiths CE, Christophers E, Barker JN et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol 2007; 156:258–62. 8 Poskitt EM, Cole TJ. Do fat babies stay fat? Br Med J 1977; 1:7–9. 9 Herron MD, Hinckley M, Hoffman MS et al. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol 2005; 141:1527–34. 10 Naldi L, Parazzini F, Peli L et al. Dietary factors and the risk of psoriasis. Results of an Italian case–control study. Br J Dermatol 1996; 134:101–6.

Erosive pustular dermatosis of the scalp arising concomitantly with elevation of serum matrix metalloproteinase-3 in a patient with rheumatoid arthritis.

tinoin, can be applied to GR treatment. However, our patient had wide resistance to conventional remedies other than topical corticosteroids. Recent reports have indicated that thalidomide has been introduced in the treatment of granulomatous disorders. Thalidomide can prevent formation of multinucleated giant cells from cultured monocytes, which may inhibit granulomatous formation. As a non-steroid calcineurin inhibitor, pimecrolimus has been confirmed to be well tolerated, safe and effective in atopic dermatitis, especially on facial areas. Although the first three-week therapy of pimecrolimus was ineffective in our patient, no recurrence was received after stopping pimecrolimus. In conclusion, oral thalidomide protocol combined with pimecrolimus cream 1% may be an ideal choice in recalcitrant and recurrent GR patients.

Emergence of Photosensitivity with Decreased Treg Cells in a Patient with Mycosis Fungoides Treated with Anti-CC Chemokine Receptor 4 Antibody Mogamulizumab.

Mogamulizumab is a therapeutic monoclonal antibody that targets the CC chemokine receptor 4 (CCR4). The treatment exhibits strong cytotoxicity for adult T-cell leukaemia/lymphoma (ATLL) cells via antibody-dependent cellular cytotoxicity (ADCC), although it carries the risk of serious adverse reactions to the skin, such as StevensJohnson syndrome (1, 2). We report here a patient with mycosis fungoides (MF) at tumour stage treated with mogamulizumab, who developed a photosensitivity reaction during the course of treatment. At the onset of photosensitivity, a reduction in both circulating and skin infiltrating regulatory T cells (Tregs) was observed.

TGFβ/SMAD4 signalling is inhibited in tumour cells and infiltrating lymphocytes of a patient with colon cancer-associated dermatomyositis.

of the patients received one to no less than two treatments respectively. Our results suggest that QSNYL is effective to treat xanthelasma after one session of treatment, and multiple treatments will lead to greater response and excellent response rates. A high fluence (5–7 J cm ) and a small spot size (2 mm) might be necessary to achieve a clinically satisfying outcome. Pain without anaesthesia is considerable and making local anaesthesia necessary. Mild erythema and hyperpigmentation were all resolvable. Rarely, mild scar needs to be taken into account in those needs multiple treatments.

Pustular psoriasis‐like lesions associated with hereditary lactate dehydrogenase M subunit deficiency without interleukin‐36 receptor antagonist mutation: long‐term follow‐up of two cases

DEAR EDITOR, Lactate dehydrogenase (LDH) is a key enzyme involved in the catalysis of the interconversion of pyruvate and lactate in the final step of anaerobic glycolysis, and is present in almost all cells. It exists as five isozymes composed of tetramers with two different subunits: H (heart) and M (muscle). The isozymes composed mainly of the M subunit (LDH4 and LDH5) are predominant in tissues that undergo anaerobic metabolism, such as skin, liver and muscle. LDH M subunit deficiency, first reported in two Japanese families, is characterized by fatigability and myalgia with myoglobinuria and high creatine kinase after strenuous exercise. The diagnosis of LDH M subunit deficiency is usually based on the electrophoretic pattern of LDH, which shows a band for LDH1 only. Erythematosquamous skin lesions were documented first, and several types of eruptions have since been reported, for example desquamating erythematosquamous lesions and annular erythematous plaques with desquamating borders. Here, we report two patients with LDH M subunit deficiency with generalized pustular psoriasis (GPP)-like lesions, and include the immunological aspects of their longterm follow-up. Patient 2 is the same patient reported previously by Yoshikuni et al. in 1986. Patient 1, a 64-year-old man, was initially referred to us in October 2006 for evaluation of annular erythematous plaques (Fig. 1a), with pustules on the peripheries (Fig. 1b). He had suffered from asymptomatic scaly papules and erythematous patches on the elbows and knees since childhood, which were exacerbated in the summer. Laboratory tests revealed moderately elevated levels of aspartate transaminase (70 U L ; normal range 10–35 U L ) and alanine aminotransferase (79 U L ; normal range 5–40 U L ). The electrophoretic pattern of LDH showed 100% LDH1 and 0% LDH2–LDH5. A skin biopsy taken from abdominal skin showed a subcorneal infiltrate of neutrophils in the psoriasiform epidermis with spongiform pustules of a Kogoj-like pattern (Fig. 1c). The patient had been treated intermittently with oral ciclosporin 3 5 mg kg 1 daily, and with topical corticosteroid and calcipotriol for 3 years. In order to avoid the adverse effects of ciclosporin, the cessation period of ciclosporin treatment was taken into consideration during treatment. However, his pustular lesions worsened. Therefore, intravenous infliximab 5 mg kg 1 was started, and marked therapeutic effectiveness was seen. Patient 2, at the age of 50 years, had suffered from small follicular erythematous papules with scales and large desquamating erythematous plaques on the elbows and legs since early childhood, with myalgia after exercise (Fig. 1d). At the age of 56 years, pustules emerged on large desquamating ery-

Mogamulizumab‐induced photosensitivity in patients with mycosis fungoides and other T‐cell neoplasms

Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T‐cell leukaemia/lymphoma (ATLL), followed by cutaneous T‐cell lymphoma and peripheral T‐cell lymphoma.