Kiyoshi Nishioka

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

SummaryPsoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1α was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.

Significance of Elevated Serum LDH (Lactate Dehydrogenase) Activity in Atopic Dermatitis

Serum lactate dehydrogenase activity (LDH) was elevated in most cases with the severe type of atopic dermatitis (AD). We examined whether LDH correlated specifically with the clinical courses and the severity of AD skin eruptions. Blood eosinophil numbers (Eo), LDH and its isoenzymes, and serum IgE (IgE) levels in eighty patients with AD were measured before and after treatment.

Drug‐induced Chronic Pigmented Purpura

A close correlation between purpuric reaction and drugs was observed in seven cases of chronic pigmented purpura. The patients developed purpuric lesions after taking certain drugs for more than 3 years, were thiamine propyldisulfide in 2 cases, and chlordiazepoxide in 1 case. The purpuric lesions stopped recurring after removal of the drugs in the rest of the cases. It is suggested that drugs are among the etiological factors in chronic pigmented purpura.

Anticardiolipin antibody in Henoch-Schönlein purpura and related vascular disorders

To clarify the exact role of these phospholipid antibodies in vascular injury, ACL titers were examined in 24 patients with Henoch-Schonlein purpura (HSP) and other forms of cutaneous vasculitis. ACL titers for HSP were lower than for cutaneous polyarteritis nodosa (PNC) or Takayasus arteritis, but were significantly higher than for normal controls, as is shown in Fig. 1. The patients with erythema nodosum or hypergammaglobulinemic purpura showed normal ACL titers. ACL titers for allergic vasculitis could not be determined in this study because of the difficulty to obtain the serum. Next, clinical analysis was performed on five HSP cases who showed elevated ACL titers (three elderly cases and two younger ones)

Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic sclerosis

Anticardiolipin antibody-positive patients with progressive systemic sclerosis were analyzed. Elevated anticardiolipin antibody titers were observed in 13 of 40 cases (33%). Anticardiolipin antibody titer was significantly higher in patients with progressive systemic sclerosis type 1 than in those with type 2 or type 3. Occurrence of anticardiolipin antibody was significantly more frequent in patients positive for anti-nRNP antibodies, rheumatoid factor, or thrombocytopenia. In contrast, patients with proximal scleroderma, scarring, or esophageal hypomotility were positive for anticardiolipin antibody less frequently. These results suggest that anticardiolipin antibody might be closely associated with lupuslike clinical manifestations in a subset of progressive systemic sclerosis or definite progressive systemic sclerosis with thrombocytopenia, rheumatoid factor, or anti-nRNP antibodies.

Annular erythema associated with primary Sjögren syndrome: Analysis of T cell subsets in cutaneous infiltrates

Immunohistochemical analysis was performed on the annular erythema associated with Sjögren syndrome. This type of annular erythema is characterized by a doughnutlike appearance with an elevated border and central pallor; it is distinct from subacute cutaneous lupus erythematosus. Histologically this erythema is characterized by coat sleeve-like infiltration of lymphocytes around blood vessels and by nuclear debris in the connective tissue. Vasculitis or epidermal changes suggestive of lupus erythematosus were not observed in any of the cases, although immunoglobulin or complement deposition along the basement membrane zone and focal liquefaction degeneration of the basal layer in involved skin were seen in some cases. Major dermal infiltrates consisted primarily of CD4+ and 4B4+ lymphocytes.

A Possible Pathogenesis for Blackfoot Disease

Blackfoot disease (BFD) is an endemic peripheral vascular occlusive disease found among the inhabitants of the southwest coast of Taiwan. The clinical features of BFD are similar to those of Buergers disease. Pathology shows arteriosclerosis obliterans and thromboangiitis obliterans. The high arsenic content of artesian well water in the area is regarded as the main causal factor of this disease. Therefore, the purpose of this study was to observe the toxic effects of various arsenic concentrations on cultured human umbilical vein endothelial cells (HUV‐EC). The methods of this study included cell growth assay, 51Cr‐release assay, and staining of Factor VIII related antigen (FVIII‐RAg) and Ulex europaeus agglutinin I (UEA‐I) binding sites of HUV‐EC. The following data were obtained: 1) no obvious cytotoxicity in 51Cr‐release assay; 2) inhibition of the synthesis of both FVIII‐RAg and UEA‐I binding sites when the arsenic concentration was above 100 ng/ml; 3) dose‐dependent inhibition of growth of HUV‐EC by any concentration of arsenic. At a higher concentration of more than 100 ng/ml, arsenic inhibited endothelial cell proliferation and glycoprotein synthesis, whereas it only inhibited the proliferation at a lower concentration of less than 50 ng/ml. It is suggested that arsenic, at both higher and lower concentrations, may damage endothelial cells. Such damage may play an important role in the pathogenesis of BFD.

Poikiloderma-like Lesions on the Neck in Atopic Dermatitis: A Histopathological Study

Reticulate pigmentation with or without skin atrophy, depigmentation and telangiectasia is frequently encountered on the neck of severe cases of adult type atopic dermatitis. These skin changes were graded clinically into 3 stages. Based on histological features, hyperplasia of the sebaceous gland, dilated tortuous capillaries, and mild degeneration of elastic fibers were noted in stage I lesions. Lesions of both stages II and III contained increased melanin in the basal cell layer with incontinence of pigment, remarkable destruction and degeneration of elastic fibers, proliferated and dilated capillaries, and deposition of mucinous substances. The numbers of mast cells in papillary dermis were significantly increased in late stage I and stage II lesions. Poikiloderma‐like lesions on the neck could be attributable to chronic inflammation and delay of wound healing process, possibly caused by long‐standing topical corticosteroid therapy.

In situ Expression of Interleukin-6 in Psoriatic Epidermis during Treatment

Interleukin‐6 (IL‐6) is a multipotential cytokine which may act as a growth factor for keratinocytes. The epidermal hyperplasia of psoriasis may be explained in part by an overproduction of this cytokine. We have previously shown by in situ hybridization that IL‐6 mRNA is most strongly expressed in the peripheral lesion of an advancing psoriatic plaque. In the present study, we investigated whether there were differences between the expression of IL‐6 in untreated psoriatic epidermis and the lesion during the course of clinical improvement. In the untreated psoriatic lesion, the weak expression of IL‐6 mRNA was localized in the lower epidermis. However, IL‐6 mRNA was not detected in the clearly improved lesion. In the improving lesion, with clinically less scaling, less induration, and histologically thinner epidermis, IL‐6 mRNA‐expressing keratinocytes were detectable in a greater proportion of the total epidermal components than in the untreated, fully developed lesion. These results showed that IL‐6 mRNA was strongly expressed in lesions with moderate epidermal hyperproliferation, indicating that this cytokine may play a role in the transitional phase during the course of improvement as well as in the lesions formation.

Neonatal lupus erythematosus with a high anticardiolipin antibody titer. Unusual variant of neonatal lupus erythematosus or early-onset systemic lupus erythematosus?

A malar rash associated with severe gastrointestinal manifestations developed in a 4-month-old baby 3 months after a normal delivery. Serum complement and IgA levels were low during the active phase of the illness. An increased anticardiolipin antibody titer was demonstrated at the onset of disease and persisted for more than 6 months, at which time the skin and gastrointestinal manifestations subsided. The babys mother, who had no symptoms, had an elevated Ro (SS-A) antibody titer and a moderately elevated anticardiolipin antibody titer.