Yusuke Yoshizawa

Serum cytokine levels in atopic dermatitis

Summary Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T‐helper (Th2) cytokines with a concomitant decrease in interferon‐gamma (IFN‐γ) production. However, the cross‐regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)‐18, IL‐12, IL‐10, IL‐2 and IFN‐γ] in patients with AD to assess their possible relationships to the severity of disease. Serum IL‐18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172–242 pg/mL vs. 144 pg/mL; 95% CI, 116–178 pg/mL; P = 0.026]. Those IL‐18 levels significantly correlated with eosinophil counts and serum soluble IL‐2 receptor (sIL‐2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL‐2 levels showed a significantly inverse correlation with serum IgE levels, and IL‐12 levels clearly correlated with IL‐10 levels. These results suggest the value of serum IL‐18 levels as a parameter of AD activity and may support a possible role for IL‐18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL‐2 levels suggests that IgE production may be inhibited by IL‐2 in patients with AD. Furthermore, the correlation of IL‐12 levels with IL‐10 levels may support the previous reports that show the induction of IL‐10 production by human natural killer cells and/or T cells stimulated with IL‐12 in vitro.

Sea water or its components alter experimental irritant dermatitis in man

Background/aims: Ocean bathing has been considered “healthy” for skin, but its efficacy remains testimonial in nature. Our aim was to evaluate the effects of sea water and its main components on experimental irritant contact dermatitis induced by sodium lauryl sulphate (SLS) cumulative irritation.

Topical dinitrochlorobenzene therapy in the treatment of refractory atopic dermatitis: Systemic immunotherapy

BACKGROUND Repeated dinitrochlorobenzene (DNCB) application has been proposed as a systemic immunotherapy on the basis of its ability to stimulate T helper 1 (T(H)1) responses, such as those for systemic lupus erythematosus and HIV infection. OBJECTIVE We report the effect of topical DNCB therapy in an open trial in patients with refractory atopic dermatitis (AD). METHODS Eight patients with refractory AD received weekly application of 0.2% to 1% DNCB to a 2. 5-cm(2) area on the upper arm after sensitization with 5% DNCB; the position was rotated at each application. Disease activity was monitored by pruritus score, percentage of body involvement, clinical severity score, eosinophil counts, serum IgE levels, and serum soluble interleukin 2 receptor levels. RESULTS Six of 8 patients (patients 1-6) showed apparent improvement both on clinical scores and laboratory data until 16 weeks after DNCB therapy (week 16). The clinical severity scores of patients 1 to 6 were significantly correlated with eosinophil counts, IgE levels, and serum soluble interleukin 2 receptor levels. One patient did not show clear improvement, and another (patient 8) showed deterioration. DNCB therapy was discontinued at week 12 for patient 8. CONCLUSION Topical DNCB may systemically stimulate T(H)1 cell responses of patients with AD, resulting in restoration of the T(H)1/T(H)2 imbalance and possible clinical improvement. These results, however, should be interpreted with caution until additional documentation is obtained.

Identification of the mouse calcium-binding proteins, MRP 8 and MRP 14, in Schistosoma mansoni-induced granulomas: biochemical and functional characterization.

Granuloma Initiation factor (GIF), which elicits a granulomatous reaction in naive murine skin, contains low‐molecular‐weight proteins partially purified from organized granulomas developed in livers of mice with schistosomiasis. In this study, we found that 10‐ and 14‐kDa proteins in the GIF are highly homologous to mouse migration inhibitory factor‐related protein (MRP) 8 and MRP 14. Compared with the N‐terminal amino acid sequence deduced from each corresponding cDNA, the 10‐kDa protein from the granuloma lacks the first methionine, whereas the 14 kDa misses methionine, alanine, and asparagine. Immunohistochemically, cells expressing MRP 8 and MRP 14 considerably increased in different murine tissues after Schistosoma mansoni infection and concentrated in liver around the dilated bloodvessels and at the edge of granulomas. The staining of differentiated macrophages and epithelioid cells located in the center of the granulomas was negative. Immunoreactivity of peritoneal exudate cells also was found to gradually disappear with time in cell culture. Furthermore, in vivo effects of the recombinant proteins in murine skin were described histologically. Both MRPs caused severe infiltration of neutrophils and monocytes during 7–14 days. The reaction resulting from individual MRP implantation became minimal after 50 days but inoculation of the Ca2+‐dependent heterodimers showed an extensive eosinophil accumulation. J. Leukoc. Biol. 61: 258–266; 1997.

Corticosteroid-Induced Pancreatitis in Patients with Autoimmune Bullous Disease: Case Report and Prospective Study

Corticosteroid pulse therapy using very high doses may produce corticosteroid-induced pancreatitis (CIP) that is unexpected during conventional oral corticosteroid therapy and may sometimes be fatal. Our goal was to evaluate the relation between pulse corticosteroid administration and pancreatitis. A case of CIP is reported, and a prospective study was performed. Corticosteroid pulse therapy followed by 30 mg prednisolone orally was utilized in 7 hospitalized patients with autoimmune bullous disease, and serum pancreatic enzymes were measured during therapy. The case report revealed reproducible pancreatitis in a dose-dependent manner after 2 corticosteroid regimens. In the prospective study, serum pancreatic enzyme levels increased significantly within several days after pulse therapy, then decreased with tapering of the dose of oral prednisolone. Laboratory pancreatic alterations appear to be induced within days after pulse corticosteroid administration in a dose-dependent manner: less than 25 mg of oral prednisolone may be below threshold to alter the pancreatic enzyme level.

Paraneoplastic Pemphigus: Report of a Case

A 56‐year‐old male with chronic lymphocytic leukemia developed extensive erosive mucocutaneous lesions with histologic acantholysis. Immunopathologic studies showed IgG deposition at the intercellular space, C3 deposition at both the intercellular space and the dermo‐epidermal junction, and reactivity of the serum to rat urinary bladder epithelium. Autoantibodies in the serum to human epidermal proteins of 210 kD and 190 kD were shown by Western blotting and to proteins of 250 kD, 210 kD, and 190 kD by immunoprecipitation. All these data suggest the diagnosis of paraneoplastic pemphigus. Repeated plasmapheresis resulted in re‐epithelialization of the mucocutaneous lesions and reduction in antibody titer from 1:1280 to 1:20. Although this mucocutaneous disease was established as a new autoimmune bullous disease by Anhalt et al. (1990), cases have rarely been reported from Japan. The present patient demonstrates the major characteristics of paraneoplastic pemphigus.

Toxic epidermal necrolysis complicated by multiple intestinal ulcers

On 11 November 2001, a 30‐year‐old woman was treated by an emergency doctor for cold symptoms, including pyrexia and pain in the pharynx. She was prescribed norfloxacin (NFLX), acetaminophen, and tranexamic acid, as well as additional supporting medicines that she chose not to use. On the following day, the patient went to the outpatient unit of the department of internal medicine of a general hospital; she was admitted because of continuing fever. She was prescribed a combination medication for Bifidus bacillus containing mefenamic acid and aluminum hydroxide gel/magnesium hydroxide, as well as NFLX and teprenone, but erosions of her face appeared on 15 November, followed by erosions of the trunk on 17 November. She was suffering from inflammation and blisters over her whole body. She was diagnosed with toxic epidermal necrolysis (TEN) by the department of dermatology of the same hospital. The patient underwent steroid pulse therapy for 3 days from 17 November, which was not effective, and was transferred to our hospital on 22 November.

A case of hypereosinophilic syndrome.

A 22‐year‐old man developed papules on his legs in November of 2001, which then spread to cover almost his entire body. He was treated with a topical steroid and PUVA therapy at another hospital. The symptoms showed no improvement, and, in February of 2002, he came to our hospital. Examination revealed hypereosinophilia, and, because he had symptoms of organ involvement by the heart, lung, and inguinal lymph nodes as well as the skin, we diagnosed him with idiopathic hypereosinophilic syndrome (HES). The patient was treated with oral prednisolone at a dose of 60 mg/day, and his cutaneous lesions and other organ symptoms improved.

Hemostatic and Fibrinolytic Changes in Herpes Zoster

When the patients with herpes zoster (HZ) have severe underlying diseases or being treated with immunosuppressive agents, they may occasionally develop severe complications such as disseminated intravascular coagulation (DIC) or encephalitis [1,2]. Histopathological examination of herpetic lesion revealed that endothelial cells are damaged, suggesting that some mechanism takes place to induce hypercoagulable condition in this disease [2,3]. However, effects of varicella zoster virus (VZV) infection to coagulation and fibrinolysis system have not been fully documented. This study investigates changes of platelet count and hemostatic and fibrinolytic molecular markers. Influencing factors to hemostatic and fibrinolytic conditions such as location and size of lesions, dissemination, and pleocytosis of cerebrospinal fluid were analyzed. The age of the patient was found to be crucial factor to modify hemostatic and fibrinolytic changes in HZ.

A case of primary lesion indistinctness malignant melanoma.A summary of exerienced cases after opening of hospital.

A rare case of metastatic malignant melanoma of unknown primary origin to the right inguinal lymph nodes was reported. Although the melanoma was largely developed dimensioned 20×15×7cm, after extensive chemotherapy combined with radiotherapy and hyperthermia, we were able to excise the melanoma from the inguinal area. However, after 7 months it recurred. In addition 11 patients with malignant melanoma including the present case experienced by us in the Department of Dermatology, Saitama Medical Center, Saitama Medical School, between 1986 and 1991, were summarized and discussed.