Hidemitsu Orito

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction

Immune complex (IC)‐induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules. The roles and interactions of ICAM‐1 and VCAM‐1, the major regulators of leukocyte firm adhesion, were examined in the cutaneous reverse‐passive Arthus reaction using ICAM‐1‐deficient (ICAM‐1−/−) mice and blocking mAb against VCAM‐1. Within 8 h, IC challenge of wild‐type mice induced edema, hemorrhage, interstitial accumulation of neutrophils and mast cells, as well as production of TNF‐α and IL‐6. All of these inflammatory parameters were reduced significantly in ICAM‐1−/− mice. The blockade of VCAM‐1 in wild‐type mice did not affect any inflammatory parameters. In contrast, ICAM‐1−/− mice treated with anti‐VCAM‐1 mAb had significantly reduced edema, hemorrhage, and neutrophil infiltration. Furthermore, VCAM‐1 blockade in ICAM‐1−/− mice suppressed cutaneous TNF‐α and IL‐6 production. Thus, VCAM‐1 plays a complementary role to ICAM‐1 in the cutaneous Arthus reaction by regulating leukocyte accumulation and proinflammatory cytokine production.

Two cases of livedo vasculopathy with non‐criteria antiphospholipid antibodies

Livedo vasculopathy is characterized by reticular distribution of purpuric macules and papules of the lower legs, caused by intraluminal thrombosis of small vessels. Antiphospholipid antibodies are detected in a subset of these patients. We treated two cases (a 34‐year‐old man and a 46‐year‐old woman) with livedo vasculopathy. In both cases, thrombosis was seen only in the skin. The presence of immunoglobulin (Ig)G or IgM anticardiolipin antibody (Ab), IgG or IgM anti‐β2‐glycoprotein I Ab, or lupus anticoagulant are necessary for criteria‐based diagnosis of antiphospholipid syndrome. However, our patients were negative for these Ab, and instead had either IgG antiphosphatidylethanolamine Ab or IgA anticardiolipin Ab. These Ab are suggestive of antiphospholipid syndrome but are not considered “criteria” Ab. This report demonstrates the existence of antiphosphatidylethanolamine Ab or IgA anticardiolipin Ab in patients with livedo vasculopathy. However, the frequency and significance of these Ab in livedo vasculopathy should be confirmed in larger longitudinal studies.

Antigen specificity of antihistone antibodies in connective tissue disease patients with anti-U1RNP antibodies

To determine the prevalence of antibodies to individual histone components in collagen disease patients with anti-U1RNP antibodies. Serum samples were examined by enzyme-linked immunosorbent assay. Patients with mixed connective tissue disease (MCTD) and systemic sclerosis (SSc) showed similar levels and patterns of antihistone antibody (AHA) reactivities to individual histones: IgG responses to H2B or H3 and IgM responses to H2B were highest. However, both IgG and IgM AHAs against outer portion of chromatin (H1, H2A, or H2B) were generally higher in SLE compared with other diseases. SLE or SSc patients with anti-U1RNP antibodies showed generally higher AHA levels than in those without them. Thus, the pattern of reactivities to each histone component was dependent on the disease, while the intensity was dependent on both the disease and anti-U1RNP antibodies. The antigenic stimulus in SLE may be different from other connective tissue diseases and is more likely to be native chromatin.

Skin sclerosis as a manifestation of POEMS syndrome.

We report a case of a 64‐year‐old man with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome that had been previously misdiagnosed as systemic sclerosis. He had typical symptoms of POEMS syndrome, however, the existence of skin sclerosis, contracture of fingers and pigmentation were similar to that of systemic sclerosis. Ten patients, including the patient discussed in this case, visited our department between 1990 and 2011. Among them, five patients had skin sclerosis. Therefore, we compared skin lesions and clinical/laboratory features of POEMS syndrome and systemic sclerosis in an attempt to distinguish these disorders. Regarding the cutaneous and laboratory findings, the existence of hemangioma or hypertrichosis is indicative of POEMS syndrome. By contrast, the existence of systemic sclerosis‐specific autoantibodies, nail fold bleeding, digital ulcer/digital pitting scar or telangiectasia is highly suggestive of systemic sclerosis. To our knowledge, this is the first report to discuss in detail the differentiation between POEMS syndrome and systemic sclerosis.