Tetsuya Tsuchida

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells.

We studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nm, increased dose‐dependently, and reached a plateau at 100 nm. At doses <1000 nm, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59.0% and that of IgM by 61.3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone‐induced decrease of IgG production compared with control was 26.9% and that of IgM was 24.9%. Exogenous IL‐6 partially restored the impaired immunoglobulin production of testosterone‐treated PBMC; IgG production in testosterone culture was increased by IL‐6 from 35.6% to 66.5% of control and that of IgM was also increased from 38.9% to 71.2%, respectively. Testosterone treatment reduced IL‐6 production of monocytes by 78.4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL‐6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases.

Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma.

Background:  Recent investigations have demonstrated the utility of the monoclonal antibody D2‐40 as a marker for lymphatic endothelium. D2‐40 can be used on formalin‐fixed and paraffin‐embedded materials. Our objective was to elucidate, using D2‐40 immunohistochemistry, the differences among capillary hemangiomas, and especially between kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). We studied four cases of KHE, nine cases of TA, and 31 cases of other vascular tumors. Antibodies against CD31, CD34, factor VIII‐related antigen, and GLUT1 were also applied.

Classification of lupus erythematosus based upon cutaneous manifestations : dermatological, systemic and laboratory findings in 191 patients

BACKGROUND Lupus erythematosus (LE) is a multi-organ-system disease, the characteristics of which are reflected in the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). From a dermatological point of view, only the presence of LE-specific histopathology is necessary and sufficient for the diagnosis of LE. The association between the type of LE-specific skin lesion and the severity of extracutaneous manifestations of LE has not yet been investigated systematically. OBJECTIVE The aim of this study was to evaluate, according to the type of LE skin lesions, the prevalence of the 1982 criteria for SLE. METHODS We selected 191 patients whose skin lesions were histologically diagnosed as LE specific. Patients were classified on the basis of skin disease, and their clinical and laboratory data were analyzed. RESULTS Of 191 patients, 130 (68%) exhibited only one type of LE-specific skin lesion (monomorphic), 55 (29%) had two types (bimorphic) and the remaining 6 (3%) displayed three types (trimorphic). Nineteen of 22 (86%) patients who presented discoid lupus skin lesions above the neck without other eruptions were classified in the cutaneous-limited LE spectrum. Of 116 patients with acute lupus skin lesions (malar rash), 83 (72%) clearly fulfilled the 1982 ARA criteria for SLE. In skin lesions of LE profundus, chilblain lupus, subacute lupus (annular-polycyclic erythema and the papulosquamous variant), there were no significant correlations between the type of eruption and the severity of extracutaneous manifestations. CONCLUSION Patients with acute lupus skin lesions could usually be classified as suffering from SLE, whereas monomorphic patients with localized discoid lesions rarely exhibited extracutaneous manifestations. This tendency was less distinct in bimorphic patients. Almost all patients with subacute skin lesions were bimorphic or trimorphic, which might be due to genetic or racial differences between Japanese and other populations.

Prevalence of dermatological disorders in Japan: A nationwide, cross‐sectional, seasonal, multicenter, hospital‐based study

To clarify the prevalence of skin disorders among dermatology patients in Japan, a nationwide, cross‐sectional, seasonal, multicenter study was conducted in 69 university hospitals, 45 district‐based pivotal hospitals, and 56 private clinics (170 clinics in total). In each clinic, information was collected on the diagnosis, age, and gender of all outpatients and inpatients who visited the clinic on any one day of the second week in each of May, August, and November 2007 and February 2008. Among 67 448 cases, the top twenty skin disorders were, in descending order of incidence, miscellaneous eczema, atopic dermatitis, tinea pedis, urticaria/angioedema, tinea unguium, viral warts, psoriasis, contact dermatitis, acne, seborrheic dermatitis, hand eczema, miscellaneous benign skin tumors, alopecia areata, herpes zoster/postherpetic neuralgia, skin ulcers (nondiabetic), prurigo, epidermal cysts, vitiligo vulgaris, seborrheic keratosis, and drug eruption/toxicoderma. Atopic dermatitis, impetigo, molluscum, warts, acne, and miscellaneous eczema shared their top‐ranking position in the pediatric population, whereas the most common disorders among the geriatric population were tinea pedis, tinea unguium, psoriasis, seborrheic dermatitis, and miscellaneous eczema. For some disorders, such as atopic dermatitis, contact dermatitis, urticaria/angioedema, prurigo, insect bites, and tinea pedis, the number of patients correlated with the average high and low monthly temperatures. Males showed a greater susceptibility to some diseases (psoriasis, erythroderma, diabetic dermatoses, inter alia), whereas females were more susceptible to others (erythema nodosum, collagen diseases, livedo reticularis/racemosa, hand eczema, inter alia). In conclusion, this hospital‐based study highlights the present situation regarding dermatological patients in the early 21st century in Japan.

Early Acral Melanoma In Situ: Correlation Between the Parallel Ridge Pattern on Dermoscopy and Microscopic Features

In non-white populations, acral skin is the most prevalent site of malignant melanoma. Early melanomas of this anatomic site are often misdiagnosed as melanocytic nevi, which are not uncommon on acral skin. In fact, clinical and/or histopathological features of melanocytic nevi occasionally mimic those of early acral melanoma and vice versa, and thus differentiation of early acral melanoma from melanocytic nevus is sometimes very difficult for clinicians as well as for histopathologists. Our dermoscopic investigation has revealed that the parallel ridge pattern, a band-like pigmentation on the ridges of the skin markings, is highly specific to malignant melanoma in situ on acral volar skin. In the present study, we reviewed 22 acral melanocytic lesions that showed the parallel ridge pattern on dermoscopy but had very subtle clinical and/or histopathological presentations. We diagnosed 20 of them as early melanoma in situ by careful histopathological examination, which revealed histopathological features very similar to those seen in macular portions of overt acral melanoma, but fundamentally different from features found in melanocytic nevi on acral skin. In correspondence with their dermoscopic pattern, in these early lesions of acral melanomas, proliferation of solitary arranged melanocytes was mainly detected in the crista profunda intermedia, the epidermal rete ridge underlying the ridge of the skin marking. The two remaining lesions were diagnosed as possible cases of acquired melanocytic nevus because of the formation of well-demarcated nests of melanocytes in the epidermal rete ridges. We propose that a finding of preferential proliferation of solitary arranged melanocytes in the crista profunda intermedia is an important clue for the histopathological diagnosis of early phases of acral melanoma.

Clinical evaluation of scleroderma spectrum disorders using a points system

We have established a new diagnostic method using a points system to evaluate patients with early scleroderma and those with scleroderma spectrum disorders (SSD). To examine the clinical usefulness of this method, it was applied to a total of 215 cases including 97 patients with scleroderma, 32 with SSD, 28 with presumed primary Raynauds phenomenon (RP) and 58 with other connective tissue disorders (CTD). A total score was obtained for each patient as the sum of the following five factors: (1) extent of skin sclerosis (maximum, 10 points); (2) pulmonary changes (maximum, 4 points); (3) antinuclear antibodies (maximum, 5 points); (4) pattern of Raynauds phenomenon (maximum, 3 points); and (5) nailfold bleeding (maximum, 2 points). Of the 97 scleroderma patients, 86 (89%) had 9 or more points, and of the 32 SSD patients, 28 (88%) had 5 to 8 points. In contrast, all patients with presumed primary RP and 54 of 58 (93%) patients with other CTD had 0 to 4 points. These data suggest that this diagnostic method is very useful not only for clinical evaluation of SSD, but also for the differentiation of scleroderma and SSD from other CTD and primary RP.

Epidermolysis bullosa acquisita: clinical response to plasma exchange therapy and circulating anti-basement membrane zone antibody titer

Epidermolysis bullosa acquisita has been recognized as a rare autoimmune mechanobullous disorder since the detection of immunoglobulin and complement deposits along the basement membrane zone. A circulating anti-basement membrane zone antibody has also been detected in some cases. We are reporting a case of epidermolysis bullosa acquisita in which clinical symptoms were well correlated with the circulating anti-basement membrane zone antibody titers. Although the patient initially responded very well to corticosteroid therapy, remission could not be maintained without increasing the dosage. Other therapies, including azathioprine, dapsone, vitamin E, and gold sodium thiomalate, produced no beneficial effects. Although a high dose of oral corticosteroid and cyclophosphamide decreased the antibody titer and blister formation, this therapy had to be terminated because of side effects. Plasma exchange therapy in combination with corticosteroid and low-dose cyclophosphamide resulted in a marked decrease of the anti-basement membrane zone antibody titer and clinical improvement. Thus plasma exchange therapy may be a useful adjunct to conventional treatments for patients with epidermolysis bullosa acquisita.

Lupus erythematosus profundus: a cutaneous marker for a distinct clinical subset?

Summary Sixteen patients with histologically confirmed lupus erythematosus profundus were followed for a decade (on average). At the initial examination. two of 16 (12%) patients fulfilled the 1982 American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE). During the period of observation. SLE developed in another two (12%) patients, both of whom developed a malar rash. The remaining 12 (75%) patients never met the criteria for SLE. Four of the 16 (25%) had no extracutaneous manifestation. In conclusion, most patients with lupus erythematosus profundus have a relatively mild disease course, although a few develop systemic abnormalities and have abnormal laboratory findings.

Cutaneous lupus mucinosis: a review of our cases and the possible pathogenesis

Cutaneous lupus mucinosis (CLM) is a rare variant of lupus erythematosus eruptions. Our 5 cases with CLM were reviewed. All were men with systemic lupus erythematosus (SLE). CLM occurred as asymptomatic cutaneous papules, nodules, or plaques on the trunk, upper and lower extremities, and face. Histopathology of CLM mainly revealed abundant mucin deposits among splayed collagen bundles throughout the dermis. However, some CLM lesions showed discoid lupus erythematosus‐like epidermal and dermal changes and/or lupus profundus. Vasculitis was also revealed in the CLM lesions of 2 cases. The pathogenesis of CLM may be closely related to its two important features, the male preponderance and the association with SLE. Vasculopathy may also be involved in the development of CLM.

Vesicle formation in dermatomyositis associated with gynecologic malignancies

Vesicle formation in dermatomyositis is rare. We describe two women with dermatomyositis and vesicle formation on their extremities. Both had an ovarian cancer and histologic examinations revealing subepidermal vesicles. In both patients, direct immunofluorescence did not reveal deposition of immunoglobulin in the basement membrane zone. Of our two patients and the 17 previously reported to have dermatomyositis with vesicle formation, 10 had an internal malignant disease. Of these 10 patients, eight women had gynecologic malignant disease and two men had gastric cancer and lung cancer, respectively. Vesicle formation in dermatomyositis is strongly related to the presence of an internal malignant process, especially gynecologic malignant disease in female patients.