Significant increase in the prevalence of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, particularly the USA300 variant ΨUSA300, in the Japanese community.

IMPORTANCE: USA300 is an MRSA clone producing PVL, a toxin associated with SSTIs. ΨUSA300 is a USA300 variant recently identified in Japan by Takadama et al. (15). Here, we found that the prevalence rate of PVL-positive MRSA in S. aureus was elevated in the Japanese community, and ΨUSA300 accounted for most of them. ΨUSA300 strains have been isolated from several areas in Japan and were associated with deep-seated SSTIs. This study highlighted the emerging threat posed by ΨUSA300 in Japan.

Disseminated extrafacial rosacea with papulonecrotic lesions.

BACKGROUND: Rosacea is a common skin disease and predominantly affects on the face of middle-aged women. It exceptionally occurs on the extrafacial areas such as ear, neck, axilla, and upper extremities, and has been reported as disseminated rosacea. MAIN OBSERVATION: A 40-year-old Japanese female presented with one-month history of erythematous skin eruption with burning sensation on the face, neck, and upper limbs. Physical examination showed rosacea-like eruption on the face as well as multiple papules disseminated on the neck, forearms, and hands. These extrafacial lesions demonstrated papulonecrotic appearance. Bilateral conjunctiva showed marked hyperemic which was consistent with ocular rosacea. Corneal opacity was also seen. Histology of the umbilicated papule on the neck revealed necrobiotic granulomas around the hair follicle with transepidermal elimination. Another tiny solid papule on the forearm suggesting early lesion also demonstrated necrobiosis with palisading granuloma but no transepidermal elimination. Systemic administration of minocycline and topical tacrolimus therapy promptly improved the skin lesions. Topical application of fluorometholone in temporary addition with levofloxacin improved ocular involvement 12 weeks after her 1st visit. The clinical course of the skin lesion and ocular symptoms mostly correlated. Then, the skin lesion and ocular symptoms often relapsed. Rosacea uncommonly associates with the extrafacial involvement as disseminated rosacea. The present case is characterized by the disseminated papulonecrotic lesions of the extrafacial areas histologically showing transepidermal elimination of necrobiotic granulomas. CONCLUSIONS: Dermatologists should recognize that papulonecrotic lesions of the neck and upper extremities might be extrafacial rosacea when the patient has rosacea on the face.

Antiphospholipid IgM antibody response in acute and chronic Mycobacterium tuberculosis mouse infection model.

BACKGROUND AND AIMS: The clinical management of tuberculosis (TB) could be greatly improved by an affordable biomarker test to monitor treatment response. Here, we examined changes in immunoglobulin M (IgM) antibody response to lipids as a potential biomarker for monitoring TB treatment in an experimental mouse model. METHODS: We performed enzyme-linked immunosorbent assay to investigate changes in IgM antibody response against cardiolipin (CL), phosphatidylcholine (PTC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and sphingolipid (SL) in BALB/c mice that were treated after being infected with Mycobacterium tuberculosis for 4 weeks (acute infection) and 20 weeks (chronic infection). Cytokine levels [interleukin (IL)-5, IL-10, interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)] in lung and spleen homogenates as well as in blood were also compared. RESULTS: In both acutely and chronically infected mice, lungs were sterilised of M. tuberculosis infection after 8 weeks of treatment. The IgM response to CL, PTC, PE, PI and SL were consistently elevated throughout the course of infection in chronically infected mice compared with acutely infected mice. In acutely infected mice, the IgM antibody response against CL significantly decreased after 8 weeks of treatment, but not against other lipids. In chronically infected mice, the IgM response showed no significant changes against any of the lipids after 8 weeks of treatment. Of the cytokines examined, only MCP-1 levels in lungs decreased significantly after treatment. CONCLUSION: These findings demonstrate that antilipid IgM antibody can remain elevated in chronically infected mice, but with treatment, only anti-CL IgM antibody levels decreased together with M. tuberculosis bacterial burden in acutely infected mice. Treatment did not affect antilipid IgM levels in chronically infected mice.

Bullous pyoderma gangrenosum of the bilateral dorsal hands.

Pyoderma gangrenosum (PG) shows characteristic non-infectious ulcers that are commonly associated with systemic diseases such as inflammatory bowel diseases, myeloproliferative disorders or aortitis syndrome. The typical clinical appearance is undermining ulcers with reddish and irregular borders on the legs. As PG has these notable signs, the diagnosis is relatively easy and its treatment depends on the severity of underlying complications. We report a case of a 60-year-old Japanese man, diagnosed with bullous PG, who also had been suffering from myeloperoxidase antineutrophil cytoplasmic antibody-positive microscopic polyangiitis and pulmonary aspergillosis. This case displayed soft whitish ulcers that existed on the rough ulcer base, with irregular borders, on his bilateral dorsal hands. Initially, it seemed to be cutaneous secondary aspergillosis because the host was already infected with pulmonary aspergillosis in both lungs. The differential diagnosis of PG from aspergillosis was from the sterile bullae or neutrophilic bullae on his right forearm, which evolved into ulcers in a few days. This case was finally diagnosed as bullous PG and a topical glucocorticoid was very effective to epithelize the ulcers in 2-3 weeks.

An adjunctive therapeutic vaccine against reactivation and post-treatment relapse tuberculosis.

Preventing latently infected or inadequately treated individuals from progressing to active disease could make a major impact on tuberculosis (TB) control worldwide. The purpose of this study was to evaluate a new approach to prevent reactivation and TB relapse that combines drug treatment and vaccination. Mycobacterium tuberculosis harbors a gene called mce1R that, in vivo, negatively regulates a 13-gene cluster called the mce1 operon. In a Cornell mouse model, BALB/c mice infected with M. tuberculosis H37Rv disrupted in mce1R consistently develop latent infection and reactivation disease. We used this new mouse model to test a recombinant M. tuberculosis cell wall protein (Mce1A), encoded by a gene in the mce1 operon, for its ability to prevent post-treatment TB. At 32 weeks of follow-up, a complete sterilizing protection was observed in lungs of the vaccinated mice. Mce1A but not phosphate-buffered saline administered intraperitoneally during the period of latent infection prevented disease progression and proliferation of M. tuberculosis mce1R mutant. The only visible lung lesions in vaccinated mice included small clusters of lymphocytes, while the unvaccinated mice showed progressively enlarging granulomas comprised of foamy macrophages surrounded by lymphocytes. The combination of anti-TB drugs and a vaccine may serve as a powerful treatment modality against TB reactivation and relapse.

Mce2 operon mutant strain of Mycobacterium tuberculosis is attenuated in C57BL/6 mice.

Mycobacterium tuberculosis genome contains four related sets of an operon called mce (mce1-4). The disruption of one of these operons, mce1, causes M. tuberculosis to become hypervirulent, whereas the mce3 and mce4 operon mutants are attenuated in mice. This study examined the phenotype of the mce2 operon mutant. The deletion of mce2 operon in M. tuberculosis H37Rv had no effect on bacterial growth in 7H9 liquid broth or survival within macrophages. However, RAW macrophage-like cells infected with the mutant strain were reduced in their ability to produce TNF-alpha, IL-6 and MCP-1. In C57BL/6 mouse lungs, the mce2 operon mutant and wild type H37Rv replicated similarly up to 20 weeks of infection. However, by 56 weeks of infection, all mice infected with the wild type H37Rv had died, while 80% of those infected with the mutant remained alive (P<0.0001). The proportion of affected lung parenchyma in mice infected with the mutant was substantially less than that of mice infected with the wild type for the same time periods of infection. These observations suggest that the mce2 operon mutant is attenuated, and that this attenuation is related not to the bacterial burden but to the mutant's decreased ability to elicit a type of immune response and lung pathology detrimental to the survival of the animal.

Cutaneous extramedullary hematopoiesis in a patient with idiopathic myelofibrosis.

Idiopathic myelofibrosis (IM) is a chronic myeloproliferative disorder and some cases of IM have extramedullary hematopoiesis. Extramedullary hematopoiesis is commonly seen in the liver, spleen and lymph nodes, but cutaneous extramedullary hematopoiesis (CEH) is very rare in cases of IM. We report a case of CEH in a 65-year-old Japanese woman with IM. This patient had many hard brownish nodules on her chest, abdomen and scalp. Histopathological examination of the nodule on her chest showed the existence of various stages of immature erythrocytes, leukocytes and megakaryocytes indicating that these hard nodules showed extramedullary hematopoiesis in the dermis. The proliferation of these immature cells in the dermis plays an important role in the pathogenesis of CEH. CEH is a very rare manifestation of IM and progresses slowly.