A 73-year-old Japanese man with chronic renal failure due to hypertension and a 9-month history of hemodialysis was admitted to our institution with non-healing painful digital ulcers on both hands. The digital ulcers had developed 2 months previously and the symptoms were more prominent on the right hand than the left. Ischemia of the legs and feet was not evident. Laboratory studies on admission revealed elevated serum creatinine levels, hypercholesterolemia, hyperphosphatemia, and mildly elevated parathyroid hormone levels. Partial calcification of radial, ulnar, and digital arteries was shown on hand roentgenograms. The arteriogram showed increased blood flow through an arteriovenous fistula on the right forearm and decreased blood flow in the digital arteries of both hands. From these findings, we supposed that the combination of atherosclerosis, tissue calcification due to secondary hyperparathyroidism, and vascular steal syndrome might have caused the development of the ischemic digital ulcers. Through treatment with intravenous prostaglandin E₁, oral phosphate-binding agents and lipid-lowering agents as well as local wound care with débridement, the digital ulcers healed.

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We describe a 55-year-old man with chronic recurrent ulceration in the right leg and foot of three years duration. The patient experienced prominent swelling and pain around the right ankle 10 years ago and thereafter noticed pigmented lesions around the right leg and foot. Intractable ulceration in the right lateral malleous first appeared three years ago. He visited us because ulceration recurred 11 months after surgical treatment using a myocutaneous flap performed in another hospital. Physical examination revealed ulcers with yellow bases with a maximum length of 10 cm on the long axis in both the right lateral and medial malleous around the grafted flap and dorsum pedis. Descending femoral phlebography revealed a reflux below the knee and a diagnosis of deep valve insufficiency was established. After external valvuloplasty, the ulcers of the right foot rapidly decreased in size and were completely epithelialized in about four months. Our case shows the value of descending femoral phlebography for the detection of underlying deep valve insufficiency and the effectiveness of valvuloplasty for recalcitrant ulceration due to deep valve insufficiency. We emphasize the importance of exploring the underlying cause of ulcers and appropriate causal treatment in venous ulceration.

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We have experienced three cases of venous thromboembolism (VTE) that occurred in patients with recalcitrant, autoimmune blistering disease. All had several risk factors for VTE. Case 1 was an 80-year-old male with paralysis of both legs. Case 2 was a 34-year-old male who was obese and a habitual smoker. He also had undergone long-term catheterization for plasmapheresis through the femoral vein, which had been complicated by bacterial infection. Case 3 was a 67-year-old female who had paraneoplastic pemphigus associated with B cell lymphoma. During hospitalization she had been treated with pulse therapy with methylprednisolone and also experienced dehydration. In all cases, administration of oral prednisolone and decrease of mobility after hospitalization were observed as common risk factors for VTE. During systemic therapy with corticosteroid, which promotes blood coagulation, such patients could easily develop VTE with additional risk factors such as advanced age, heart failure, respiratory distress, infection, dehydration or decrease of mobility. We must keep in mind that hospitalized patients with autoimmune blistering diseases, especially those treated with systemic corticosteroid, are prone to develop VTE and require active, proper preventive measures against VTE.

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The patient was a 76-year-old Japanese woman with severe rheumatoid arthritis (RA) who had developed a rheumatoid nodule on the occipital region. The onset of RA was at the age of 53 and the patient had been bedridden from the age of 71. Physical examination revealed a tender, firm, dark reddish and exophytic nodule on the occipital region. The nodule measured 28×22×12 mm. The nodule was totally excised under the clinical diagnosis of an adnexal tumor or metastatic skin carcinoma. On histopathological examination, within the deep dermis, there were several areas of fibrinoid degeneration of collagen surrounded by histiocytes in a palisaded arrangement. The number of reports of a rheumatoid nodule on the occipital region are few, but in fact there may be many cases that have not been reported.

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A 70-year-old man developed erythemas and erosions on the axilla, groin, navel and anal region over a period of 6 years. The lesions were non-responsive to topical steroid therapy. A diagnosis of Hailey-Hailey disease was made and topical tacrolimus therapy was initiated. The skin lesions dramatically improved within three weeks after the application of topical tacrolimus ointment. Topical tacrolimus is effective in controlling recalcitrant Hailey-Hailey disease.

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We reported a 58-year-old woman with chronic renal failure who had been treated by hemodialysis since 1992. Painful skin lesions with black necrosis suddenly developed on her left arm, right femur and right thigh on Jan. 2003. We observed these dark red skin lesions with surrounding necrosis on her first visit to our hospital on 14 May, 2003. The skin biopsy showed degeneration and necrosis in the epidermis, and calcium-phosphate deposition on the arterial vessels in the dermis and subcutaneous fat, and the condition was diagnosed as calciphylaxis. The calcium and parathyroid hormone levels in the serum were normal but there was a high level of phosphate in the serum. The infection of the skin lesions could not be controlled well by antibiotics and skin ulcers enlarged. Sevelamer hydrochloride was effective to stop the progress of the skin lesions. She died suddenly after vomiting with no apparent cause.

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A 68-year-old male patient noticed black papules on the areola of the left mamma on July of 1988, and visited our department on August 2, 1999 after the papules had increased in number and size. The clinical features of the lesion included clustered black papules and erythema on the left areola and a thumb sized subcutaneous mass in the upper quadrant. After temporal diagnosis of breast cancer by imaging analyses, a modified radical mastectomy was performed. The pathological examination confirmed the diagnosis of scirrhous carcinoma (T4cN2M0, stage III B). Histologically, 100% of the cancer cells and 20% of them were stained with the antibody against the estrogen receptors and the progesterone receptors respectively. As part of a chemotherapy regimen, tamoxifen citrate, cyclophosphamide and doxifluridine were administered. However, two months later, the patient developed papulo-erythematous lesions on the sun light-exposed areas of the body. Administration of doxifluridine was continued for 4 years because of the high priority of chemotherapy. The skin eruptions disappeared with discontinuation of the drug. No recurrence or metastasis of the carcinoma has been observed for five years after the surgery.

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A 7-month-old girl presented with a red nodule that was located on the upper left arm. Her mother had first noticed it 3 months previously, and since that time it had gradually increased in size. At the first medical examination, a 30×40mm erythematous plaque composed of several red nodules was found to have formed on the upper left arm. A diagnosis of tufted angioma was made histopathologically. Oral administration of 40 mg (5mg/kg) of tranilast was begun at 9 months of age. The nodule began to show a reduction in size after 2 months of the tranilast treatment. At 7 months after presentation, the tufted angioma of the upper left arm appeared to have completely disappeared. Various therapies have been reported for tufted angioma, but no standard therapeutic regimen has been established. This report discribes a case of tufted angioma that was successfully treated with tranilast. Presented is an evaluation of the effectiveness of oral tranilast treatment and comparison of findings of treatment with oral tranilast with other cases that regressed spontaneously.

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We report a 72-year-old woman with metastatic malignant melanomas who also had widespread vitiligo and spontaneous complete regression of the primary lesion. She was referred to us by a surgeon after lymphoadenectomy in her right axilla with the tentative diagnosis by histopathology of a metastatic malignant tumor. The patient had a brown-gray “veiled” spot surrounded by a white halo of 24 mm in diameter on her right forearm. Histopathological examinations of this lesion demonstrated a prominent incontinence and marked hypopigmentation of the epidermis. A melanoma cell nest was not seen in any part of the excised specimen examined. Immunohistocheminal examinations of metastatic cells of the lymph node revealed both S-100 and HMB-45 positivity. We finally concluded that the patient had metastatic melanoma on the lymph node and that the primary lesion on the forearm had spontaneously and completely regressed. Because distant metastatic lesions were newly found in the pelvis in spite of periodic chemotherapy with DTIC and local injection of IFN-β, we started immunotherapy by infusion of autologous dendritic cells pulsed with HLA-A24 restricted melanoma specific peptide MAGE-3. However, multiple distant metastatic lesions continuously developed and the patient died after 4 courses of immunotherapy.

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Four months before visiting our department, an 88-year-old woman consulted a nearby ophthalmologist with swelling of the left internal canthal area. She received the diagnosis of dacryocystitis. Subsequently, when skin and bone defects began to appear in the same region, the patient visited our department. At the first examination, skin and bone defects 17 × 17 mm in size were observed in the left internal canthal area. Although a causative organism could not be identified, the patient was diagnosed with dacryocystitis because of the presence of pus discharge from the left lacrimal duct. Since the condition was intractable, we attempted surgical therapy. We performed debridement of the wound and skin grafting to inhibit the growth of granulation tissue and constructed a dermal flap with the aim of closing the cavity. Subsequently, the course has been favorable with no recurrence.

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A 53-year-old female developed repeated attacks of fixed drug eruption. The eruption resolved with residual hyperpigmentation on the mandibular region and without residual hyperpigmentation on the lower leg. Both patch testing (on affected and normal skin) and scratch-patch testing (on normal skin) were negative. Reactivation of the lesions occurred and a new lesion developed on the frontal region following oral administration of 5 mg of minocycline. Histological findings showed that the number of dermal melanophages was greater in the mandibular region than in the lower leg. Immunohistochemical staining revealed that tryptase-containing mast cells were significantly greater in number in the mandibular region compared with the lower leg, especially at the dermal papilla level. Mast cell-derived chemical mediators and cytokines promote melanin synthesis in melanocytes and melanin transfer from melanocytes to keratinocytes. These mechanisms contributed to the increase in the degree of pigmentation.

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Itching and sleep disturbance at night is known to lower the daily QOL of patients with atopic dermatitis (AD). The guidelines for therapy for AD of the Japanese Dermatological Association recommended the use of topical adrenal cortical steroids/humidifying agents for dermatitis according to the circumstances, immunomodulator external preparations, and administration of antihistamine/antiallergic medicine for itching as adjuvant therapy. Olopatadine hydrochloride is an antiallergic agent with antihistamine action (second generation antihistamine) and is expected to improve the QOL of AD patients by the reduction of itching and improvement of sleep disturbance. Olopatadine hydrochloride was administered to 22 AD patients and changes in objective symptoms, the number of eosinophils and itching/sleep disturbance with a visual analogue scale (VAS) for 10 weeks were monitored. Results showed 86.4% of patients showed improvement, including that related to objective symptoms, itching/sleep disturbance and the number of peripheral blood eosinophils, by use of olopatadine hydrochloride. Itching was significantly improved from that prior to administration after 2 weeks to 10 weeks. In addition, long-term administration was suggested to be useful by a significant difference between 2 weeks and 10 weeks, between 4 weeks and 6-/10-weeks and between 6 weeks and 10 weeks. As for sleep disturbance, a significant improvement was reported from 2 weeks to 10 weeks. Furthermore, there was a significant difference between 2 weeks and 8 weeks and between 4 weeks and 6-/8-/10-weeks. Although the number of eosinophils did not significantly change between the pre-administration and 8-week value, the average high pre-administration value, 662.3/mm³ eosinophils, declined to an average normal value of 558.83/mm³ at 8 weeks. No side effects in any patient were observed, nor did any patient discontinue use of the medication. Therefore, olopatadine hydrochloride was suggested to be a useful agent to improve itching/sleep disturbance and improve QOL in AD.

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We examined the effects of a novel H₁ receptor antagonist, olopatadine hydrochloride, on itching associated with psoriasis vulgaris. Both daytime and nighttime itching scores significantly improved within two weeks following the commencement of the study (p<0.01, Wilcoxon test). We also examined, by means of visual analogue scales (VAS), the intensity of daytime and nighttime itching, which patients recorded in their diaries. The daytime VAS score significantly decreased within two days following the commencement of the study (p<0.01, Wilcoxon Test). The nighttime VAS score significantly decreased within one day following the commencement of the study (p<0.01, Wilcoxon Test). Although the scores for skin conditions did not decrease greatly, patients in whom itching was alleviated to a greater extent had lower scores for skin conditions. No adverse drug reaction to olopatadine hydrochloride was observed during this study. It is considered that olopatadine hydrochloride, a fast-acting, effective antipruritic, improves patient's QOL and skin conditions by preventing scratching.

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A comparative study was made on the therapeutic effect when maxacalcitol ointment 25 μg/g (Oxarole^® ointment) and clobetasol propionate ointment 0.5 mg/g (Dermovate^® ointment) were concomitantly applied in patients with psoriasis vulgaris. The 36 subjects were categorized into three groups. For those in Group I, maxacalcitol ointment 25 μg/g was used alone twice daily on weekdays and clobetasol propionate ointment 0.5 mg/g was concomitantly used twice daily on weekends; for those in Group II, clobetasol propionate ointment 0.5 mg/g was used once daily in the morning and maxacalcitol ointment 25 μg/g was used once daily in the evening; and for those in Group III, premixed ointment using maxacalcitol ointment 25 μg/g and clobetasol propionate ointment 0.5 mg/g (mix formulation=1:1) was used twice daily in the morning and evening. Clinical efficacy was determined in each group. Moderate improvement, marked improvement or clearance of psoriasis was greatest in Group III (mixture group), followed by Group II (morning/evening) and then Group I (weekdays/weekends) after 2-week and 4-week treatment periods. However, after a 6-week treatment period, a marked therapeutic effect was also achieved in Group I, and after 8 weeks of treatment, considerable improvement was seen in all groups. In conclusion, results of this study revealed that concomitant treatment with these external medicines is a useful therapy for psoriasis.

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A comparative study was made on the therapeutic effect when maxacalcitol ointment 25 μg/g (Oxarol^® ointment) and clobetasol propionate ointment 0.5 mg/g (Dermovate^® ointment) were used as monotherapy and as a mixture in the form of ointment for patients with psoriasis vulgaris. The 64 subjects were categorized into three groups. For subjects in Group I, maxacalcitol ointment 25 μg/g was used alone twice daily; for those in Group II, clobetasol propionate ointment 0.5 mg/g was used alone twice daily; and for those in Group III, a premixed ointment comprised of maxacalcitol ointment 25 μg/g and clobetasol propionate ointment 0.5 mg/g (mix formulation=1:1) was used twice daily to determine clinical efficacy in each group. Results indicated that concomitant external application of medication comprised of maxacalcitol ointment 25 μg/g and clobetasol propionate ointment 0.5 mg/g was more efficacious than each monotherapy after 2-4-weeks of treatment. Monotherapy with maxacalcitol ointment 25 μg/g showed a marked effect after 6 to 8 weeks of treatment; therefore, even monotherapy with maxacalcitol 25 μg/g ointment could be as effective as treatment with the premixed ointment.

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In patients treated at the Department of Dermatology of Fukuoka University Hospital and its affiliated centers, we investigated the efficacy, safety, and usefulness of once-daily application of a cream containing thiocarbamate antifungal liranaftate (Zefnart^®) for the treatment of tinea pedis. Twenty-eight patients (6 with vesicular, 19 with interdigital, and 3 with hyperkeratotic tinea pedis) were included in the analysis. After application of Zefnart^® for 4 weeks, the efficacy rate (defined as an evaluation of effective or better) in the overall efficacy evaluation, which included assessment of dermatological symptoms and results of mycological testing, were 60%, 64.7%, and 33.3% for vesicular, interdigital and hyperkeratotic tinea pedis, respectively. In addition, efficacy rates at the final evaluation for long-term use were 100%, 88.9%, and 100%, respectively. In patients with interdigital tinea pedis, the dermatological symptoms improved significantly after 1 week of treatment. However, the dermatological-symptom improvement rate and fungi-negative rate for interdigital tinea pedis after 4 weeks of treatment were somewhat divergent: i. e., 72% and 59.2%, respectively. The mean time required for elimination of the causal fungi in vesicular, interdigital and hyperkeratotic tinea pedis was 6.5 weeks, 4.4 weeks, and 3.9 weeks, respectively. Based on these results and the absence of adverse drug reactions, Zefnart^® cream appears to be useful for the treatment of tinea pedis.

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