Keijiro Kitamura

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.

Carcinosarcoma of the skin: Immunohistochemical and electron microscopic observations

A rapidly growing, hemorrhagic, exophytic tumor on the upper back of a 44‐year‐old male patient was investigated. Histological, immunohistochemical, and electron microscopic studies revealed both basal cell carcinoma‐like and spindle cell sarcoma‐like structures intermingled in the same tumor. Clinical consequences to this patient were mainly dependent on the sarcomatous element.

A CASE OF PLASMACYTOSIS WITH MULTIPLE PECULIAR ERUPTIONS

A 32‐year‐old man had been in good health until he noticed painful swelling of the lymph nodes in the left occipital region in spring of 1975. Half a year later, multiple, infiltrating erythematous or nodular lesions appeared on the anterior chest and then spread over almost his entire body except for the lower extremities. These skin lesions were reddish brown to purplish brown in color, and irregular in shape and size. All of his superficial lymph nodes were palpable, and pain was felt on pressure. No other systemic symptoms were noted.

Platelet-activating factor and arachidonic acid metabolites in psoriatic inflammation

Platelet‐activating factor (PAF). as wel as PAF acetylhydrolase (PAF‐AH) activity in the peripheral blood plasma of patients with psoriasis and palmoplantar pustolosis, was measured with a radio‐immunoassay technique, and compared with leukotriene (LT) B4. LTC4. LTD4, and E4, (LTD4/E4). thromboxane (TX) B2 and prostaglandin (PG) E2 levels. In a normal healthy group (n= 1 2) PAF level was 25.9 ± 6.5 pg/0.1 ml plasma (mean ± standard error of the mean: SEM). and this was elevated in patients with psoriasis (68.1 ± 11.8, n= 25. P<0.01), without a change in the PAF‐AH level. LTB4 showed a similar increase (115.0 ± 21.6 pg/ml vs. 68.2 ± 11.8 pg/ml. P < 0.05), while TXB2, and PGE2 showed insignificant (P > 0.05) changes. LTC4 and LTE4/E4 were around the level of the limit of detection. Patients with palmoplantar pustulosis (n= 33) demonstrated similar, but milder and statistically insignificant, increases in PAF. LTB4. TXB2 and PGF2 levels. Modulation of the mediator levels before and after treatment was compared in 16 patients with psoriasis and 11 with palmoplantar pustulosis. PAF in psoriasis significantly decreased after treatment (70.9 ± 17.1 to 25.1 ± 5.5, P < 0.05) and this was moderately correlated (r= 0.298) with clinical improvement as indicated by the psoriasis area and severity index (38.5 ± 7.5 to 10.9 ± 4.2. P < 0.01). TXB2. (180.2 + 100.4 to 34.1 ± 13.5). PGF2 (3.7 ± 0.7 to 2.9 ± 0.5) and LTB4 (120.1 + 31.1 to 84.2 + 8.2). in psoriasis, mildly decreased without statistical significance. Patients with palmoplantar pustulosis demonstrated a similar decrease in all mediators without statistical significance. The results obtained suggest a role of PAF in psoriasis. As the priming effects of PAF have been shown, for leucocytes and endothelial cells, to enhance their inflammatory response, we assume that PAF has roles in the acute phase of osoriatic and leucotactic inflammation.

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.

Neonatal Lupus erythematosus: Dissolution of Atrioventricular Block after Administration of Corticosteroid to the Pregnant Mother

Histopathologic and immunofluorescence findings of facial annular erythema on a 3-month-old female child, as well as serological detection of anti-SS-A (Ro) and anti-SS-B (La) antibodies, led to the diagnosis of neonatal lupus erythematosus (LE), while no sign of abnormality in the conducting system of the heart was found. During the pregnancy of the present child her mother, with positive anti-SS-A and anti-SS-B antibodies, had a history of Sweets syndrome. She was treated with corticosteroid, resulting in a gradual diminution of the existing complete atrioventricular block of the fetus. This history may implicate a potential therapeutic effect for the congenital heart block associated with neonatal LE of corticosteroid given to the pregnant mother.

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.

Management of Congenital Melanocytie Nevi: A Decade Later

Twelve years ago we published a symposium entitled “The management of congenital melanocytie nevi.” This subject was addressed because of its controversial nature and because of the tremendous uncertainty as to how these lesions should be handled. In the interim between that symposium and this, considerable numbers of publications have dealt with various aspects of this dilemma. We wondered what impact these data might have on current practices. The responses of several colleagues are printed below.

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.

Leukocytoclasis: ultrastructural in situ nick end labeling study in anaphylactoid purpura

In order to characterize leukocytoclasis of polymorphonuclear neutrophils (PMNs), the method of in situ nick end labeling for DNA breakdown was applied on tissue samples from 36 patients with anaphylactoid purpura at ultrastructural, as well as light microscopic, level. Light microscopic immuno-peroxidase technique showed positively labeled PMNs infiltrating in the dermis of 24 cases in which leukocytoclastic vasculitis was fully developed, suggesting that breakdown of DNA strands is triggered in the PMNs. Electron microscopic immuno-gold technique employed in six patients with the fully developed stage of inflammation identified the DNA breaks in the nuclei of PMNs. Ultrastructure of these cells, however, showed that only a minor population ( approximately 1/60) of PMNs showed the condensed and marginated nuclei, being compatible with typical apoptotic change. However, the majority of immuno-gold-labeled cells showed relatively intact nuclei without margination of condensed heterochromatin and with disintegrated cytoplasmic organelles and plasma membrane, suggesting that apoptotic cell removal mechanism may be incomplete. The immuno-gold-positive nuclear debris scattering in the tissue is most likely the remnants of unsatisfactory disposal by apoptosis of potentially injurious PMNs, resulting in the vascular and perivascular damage in leukocytoclastic vasculitis in anaphylactoid purpura.