Phenotype and functional identity of GM-CSF-independent dendritic cells generated by long-term propagation of DC progenitor cells in bone marrow cells and skin Langerhans cells.

Evidence is provided that dendritic cells (DC) generated by either long-term bone marrow cell (BMC) culture with Flt3L and interleukin-6 (IL-6), or after short-term BMC culture with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), contain heterogeneous cell populations of admixed DC and Mphi, regardless of the cytokine source. By employing GM-CSF-independent culture systems with the aid of Flt3/Flk-2 ligand and IL-6 and phenotypic characterization of BMC-derived DC and skin Langerhans cells (LC), revealed similar phenotypes. Furthermore, CD103 (OX62), which is widely used for rat DC separation, was found to be insufficient to enrich DC, due to downregulation of the marker. In this regard, the most efficient selection of rat DC, was obtained by CD161a (NKR-P1A), a member of the C-type lectin family. Despite the phenotypic similarity with BMC-derived DC, the nucleus of LC showed a distinct morphology. A large population of DC generated by Flt3L/IL-6 from GM-CSF receptor-deficient mice by do not express NK1.1 (NKR-P1B and NKR-P1C). The profiles for BMC-derived DC were the same as for skin Langerhans cells.

A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Use of a wrist activity monitor for the measurement of nocturnal scratching in patients with atopic dermatitis.

BACKGROUND: The amount of nocturnal scratching can be an indirect correlate of itch in pruritic dermatoses. We have previously used an infrared video camera to measure nocturnal scratching in atopic dermatitis (AD). Although this is a reliable method of measuring nocturnal scratching, it is not suitable for routine monitoring in clinical use. OBJECTIVES: To find a simplified way of monitoring itch. METHODS: We tried using a wrist activity monitor (ActiTrac) for the measurement of nocturnal scratching in patients with AD. ActiTrac is a wristwatch-shaped device that contains a piezoceramic sensor to measure and record limb movement over a pre-set time interval. The acceleration signal produced by motion of the hands is stored and downloaded into a personal computer. The average value of acceleration (AVA, 10(-3) g min(-1)) was calculated and compared with total scratching time as a percentage of total recording time (TST%) measured with the use of an infrared video camera in 63 recordings of 21 patients with AD. For 261 recordings in 29 patients with AD, the AVA was measured and correlated with disease severity, and compared with the AVA of five non-itchy controls. RESULTS: There was a significant correlation between the AVA and TST% (r = 0.91, P < 0.001), and a regression equation of y = 0.44x - 2.5 was obtained. The AVA correlated well with the severity of AD and definitely differed from the results observed in normal controls. The AVA (mean +/- SD) was 44.4 +/- 19.1 for 115 recordings in patients with severe AD, 23.2 +/- 10.9 for 89 recordings in patients with moderate AD, 8.9 +/- 6.0 for 57 recordings in patients with mild AD and 4.1 +/- 1.9 for 25 recordings in five normal controls. The units used here are arbitrary units min-1 with a range of 0--250, which corresponds to 0-75 x 10(-6) g min(-1). CONCLUSIONS: A wrist activity monitor is able to measure nocturnal scratching. However, further methods of analysis should be sought to select scratching activity exclusively.

Five cases of photocontact dermatitis due to topical ketoprofen: photopatch testing and cross-reaction study.

BACKGROUND: In parallel with the popular usage of topical ketoprofen, the number of reported cases of ketoprofen-induced photoallergic contact dermatitis has been increasing. It is clinically important to know the cross-reactivity of ketoprofen in order to avoid cross-sensitization caused by several structurally similar non-steroidal anti-inflammatory drugs (NSAID) on the market. METHODS: To evaluate the spectrum of cross sensitization, photopatch testing was performed on five patients with ketoprofen-induced photoallergic contact dermatitis using ketoprofen and other structurally similar chemicals, such as oxybenzone, tiaprofenic acid and suprofen. RESULTS: All five patients reacted positively to ketoprofen or ketoprofen plaster on photopatch testing. All four patients photopatch tested with related chemicals showed cross-photosensitization with tiaprofenic acid and suprofen. However, none of the patients reacted positively to oxybenzone. CONCLUSION: Either the diphenylketone moiety or a structurally similar tiophene-phenylketone moiety is important as the antigenic determinants of ketoprofen photoallergy. The arylpropionic acid side chain would not be involved.

Xeroderma pigmentosum variant heterozygotes show reduced levels of recovery of replicative DNA synthesis in the presence of caffeine after ultraviolet irradiation.

Patients with xeroderma pigmentosum variant show clinical photosensitivity, skin neoplasias induced by ultraviolet light, and defective postreplication repair, but normal nucleotide excision repair. We recently reported an alternative, simple method for the diagnosis of xeroderma pigmentosum variant that measures by autoradiography three cellular markers for DNA repair after ultraviolet irradiation: unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis. Among hereditary photosensitive disorders, including other xeroderma pigmentosum groups, Cockayne syndrome, and a newly established ultraviolet-sensitive syndrome, only xeroderma pigmentosum variant cells exhibited normal unscheduled DNA synthesis, normal recovery of RNA synthesis, but reduced recovery of replicative DNA synthesis (51 +/- 6% the rate relative to normal controls). This reduction of recovery of replicative DNA synthesis was enhanced in the presence of a nontoxic level of caffeine to 36 +/- 5%. In this study we assess the cellular markers in two independent families that included two photosensitive patients that were identified as xeroderma pigmentosum variant. Cells from heterozygotic parents showed normal levels of unscheduled DNA synthesis, recovery of RNA synthesis, and recovery of replicative DNA synthesis, but reduced rates of recovery of replicative DNA synthesis in the presence of 1 mM caffeine (53 +/- 8% relative to the normal control). Furthermore, with a colony-forming assay, the cells showed normal survival by ultraviolet without caffeine, but slightly reduced survival by ultraviolet with 1 mM caffeine present. In one family, we confirmed inheritance of two heterozygous mis-sense mutations. One mutation is an A-->G transition at nucleotide 1840 that generates a K535E mis-sense mutation. Another mutation is an A-->C transversion at nucleotide 2003 that generates a K589 mis-sense mutation. Each of these mutations were absent in 52 unrelated Japanese individuals. These results suggest that xeroderma pigmentosum variant heterozygotes can be identified by their sensitivity to ultraviolet irradiation in the presence of nontoxic levels of caffeine.

A case of pemphigus vulgaris successfully treated with single filtration plasmapheresis: a correlation of clinical disease activity with serum antibody levels.

We report a patient with pemphigus vulgaris (PV) successfully treated with single filtration plasmapheresis. A 40-year-old man with PV was started on therapy with prednisolone (PSL). Although the dosage of PSL was doubled, and both cyclosporin A (CyA) and pulse therapy were added, the disease was not controlled. After single filtration plasmapheresis began, most of the eroded lesions on the trunk reepithelialized. A switch to double filtration was followed by recurrence. Finally, additional treatments with single filtration plasmapheresis were required to obtain remission. To evaluate the efficacy of the treatment, circulating antibodies were measured by immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) using recombinant desmoglein (Dsg) 3. IIF titer and the ELISA scores correlated with the clinical disease activity. It is suggested that ELISA was more sensitive than IIF.

The characteristics of nocturnal scratching in adults with atopic dermatitis.

Patients with atopic dermatitis (AD) are known to suffer from nocturnal itch, and the resultant scratching may worsen the skin lesions. We observed nocturnal scratching for 112 nights in 35 adult patients with AD, using an infrared video camera system. To quantify the amount of scratching, we counted scratching bouts lasting more than 5 s and calculated the duration of all the scratching bouts (total scratching time, TST). The percentage of TST in the total recording time (TST%) was used as an index of nocturnal scratching. Mean +/- SD TST% was 14.3 +/- 13.9 for patients with severe AD, 6.2 +/- 3.7 for those with moderate AD and 0.7 +/- 0.4 for those with mild AD. The higher TST% in the severely affected group was attributed mainly to a longer duration rather than a higher frequency of bouts. Patients scratched more in the first third of the night than in the later two-thirds. Both the group of patients whose disease distribution pattern was generalized and those who showed a head-neck-shoulder type distribution scratched their heads, faces and necks for longer than other parts of the body. Repeated measurement performed on individual subjects resulted in a similar TST% when there was little change in skin lesions. TST% reduced by 15 +/- 21% when the patients showed marked improvement. The measurement of nocturnal scratching helps to evaluate the severity of itch in AD. In addition, the infrared video successfully detected the location and nature of nocturnal scratching in AD.

Paget's disease arising near a male areola without an underlying carcinoma.

We report a 56-year-old man with Paget's disease occurring near the left areola without any underlying breast carcinoma. Histologically, there was no evidence suggesting continuity with a lactiferous duct, accessory breast, or microscopic gynecomastia. We review previous case reports of Paget's disease occurring in unusual sites and discuss their nomenclature from the histogenetic point of view.

A variety of skin responses to ultraviolet irradiation in patients with atopic dermatitis.

Skin responses to ultraviolet irradiation in patients with atopic dermatitis were studied to evaluate the role of sunlight in the exacerbation of atopic dermatitis. A total of 15 patients, seven males and eight females, with atopic dermatitis who complained of exacerbation of their dermatitis after sun exposure were examined by photo testing with UVB and UVA irradiation and photopatch tests. Nine out of 15 patients showed abnormal skin reactions. Lowered minimal erythema doses (MEDs) to a single exposure of UVB, papular or erythematous responses after single or repeated exposures to UVB or UVA and positive photopatch test reactions to sunscreen ingredients and fragrances were found. There are apparently multiple mechanisms of photoexacerbation in patients with atopic dermatitis.

Effects of nitrazepam on nocturnal scratching in adults with atopic dermatitis: a double-blind placebo-controlled crossover study.

We investigated the effect of nitrazepam on nocturnal scratching in 10 adult out-patients with atopic dermatitis (AD) using a double-blind placebo-controlled crossover method. Patients were given either nitrazepam (Benzalin tablets containing 5 mg nitrazepam) or a placebo on 3 successive nights, with a washout interval of 4 days. We used an infrared video camera to identify bouts of scratching lasting more than 5 s. These were counted and the duration of all the bouts of scratching (total scratching time, TST) was calculated. The percentage of TST to total recording time (TST%) was used as an index of nocturnal scratching. The frequency with which bouts of scratching (bouts/h) occurred was reduced by 10 mg nitrazepam (7.7 +/- 3.6 with nitrazepam vs. 9.6 +/- 3.6 with placebo, P < 0.05). However, the mean duration (s/bout) of the bouts of scratching was longer with 10 mg nitrazepam (32.3 +/- 23.4 with nitrazepam vs. 19.1 +/- 10.0 with placebo, P < 0.05). As a result, there was no significant difference between TST% (6.5 +/- 4.2 with nitrazepam vs. 5.4 +/- 3.8 with placebo, not significant). All the above values are mean +/- SD. The degree of itching and the condition of the AD did not change during the 2 weeks of the study. We conclude that taking 10 mg nitrazepam is not an effective way of reducing the total duration of nocturnal scratching in AD patients, although it decreases the frequency with which bouts of nocturnal scratching occur.

Long-term follow-up in treatment of solar lentigo and café-au-lait macules with Q-switched ruby laser.

A Q-switched ruby laser was used for treatment of 10 patients with solar lentigo and 12 patients with café-au-lait macules. In this study, the lesions were treated with the laser at a rate of 6 J/cm2. The patients were observed for 10-21 months with an average of 13.8 months after the final session. Solar lentigos were treated once or twice, and the response rate was 70%. Café-au-lait macules were treated one to six times, and the response rate was 33%. Side effects, such as hyperpigmentation and scar formation, were rarely seen. Therefore, Q-switched ruby laser treatment is an effective treatment for epidermal pigmented lesions; however, in patients with café-au-lait macules, the responses to the treatment varied, and a repigmentation was seen in 50% of these patients. Thus, long-term follow-up is required for patients with café-au-lait macules.

[Histopathological diagnosis by skin biopsy].

As post-transfusion graft-vs-host disease (GVHD) has poor prognosis, early diagnosis by skin biopsy is essential. The histopathology of the skin lesion includes a lymphocytic infiltration to the dermo-epidermal junction associated with vacuolization of the basal layer. Dyskeratotic or necrotic epidermal cells are scattered through the epidermis. Some of these necrotic cells are surrounded by a few lymphocytes (satellite cell necrosis). These histopathological findings are referred to as a lichenoid tissue reaction, but is not specific to GVHD, and can be seen in some types of drug eruption (toxic epidermal necrolysis type and erythema multiforme type). Final diagnosis will be confirmed by the clinical symptoms, such as liver dysfunction, diarrhea and pancytopenia.

An infrared video camera system to observe nocturnal scratching in atopic dermatitis patients.

We used an infrared video camera and video tape recorder system to record and analyze nocturnal scratching in seven patients with atopic dermatitis (AD) and three non-itchy healthy controls. The patterns and the locations of scratching were successfully observed. Scratching bouts lasting more than 5 sec were counted, and the summation of the duration of all the scratching bouts (total scratching time, TST) was used as an index of nocturnal scratching. TST in patients with AD turned out to be some hundreds to ten thousands of seconds; the TST in controls was between zero and a hundred seconds. The infrared video camera system measured nocturnal scratching simply and reliably without disturbing the patients' sleep.

Chronic actinic dermatitis. An analysis of 51 patients evaluated in the United States and Japan.

BACKGROUND AND DESIGN: We studied the clinical and photobiologic features of 51 patients with chronic actinic dermatitis who were evaluated at three institutions. The following criteria for patient selection were used: (1) a persistent eczematous eruption in the sun-exposed areas of greater than 3 months' duration; (2) decreased phototest results; and (3) when available, histologic changes of a dermal infiltrate of lymphocytes and macrophages, with or without epidermal spongiosis and atypical mononuclear cells in the dermis and epidermis. RESULTS: The 51 patients had a mean age of 62.7 years, a male-to-female ratio of 2.6:1, and a mean duration of eruption of 5.8 years. The most common abnormal results of the phototests were decreased minimal erythema doses to both UV-A and UV-B, followed by decreased minimal erythema doses to UV-A alone. Patients with abnormally low responses to UV-A or visible light and normal minimal erythema doses to UV-B had the same clinical profile as the overall patient population. Aside from protection from sunlight, treatment modalities that have been used include PUVA (8-methoxypsoralen and UV-A) photochemotherapy, azathioprine, hydroxychloroquine sulfate, and, for recalcitrant cases, cyclosporine. CONCLUSIONS: Chronic actinic dermatitis is a persistent photodermatosis associated with abnormal phototest responses to UV-A, and/or UV-B, and/or increased sensitivity to visible light; histopathologic changes are consistent with photodermatitis. Treatment consists of combinations of topical and oral medications.

Photoleukomelanodermatitis (Kobori) induced by afloqualone.

We reported a case of photoleukomelanodermatitis (Kobori) type drug eruption due to afloqualone (Arofuto). The patient was given afloqualone and imipramine hydrochloride (Chrytemin) for cervical spondylosis from November of 1990. Edematous erythema with slight itching appeared on the sun-exposed areas in December of 1990. As drug eruption was suspected, drugs were ceased, and the cutaneous lesions almost disappeared but pigmentations and depigmentations developed in spots in sun-exposed areas in March of 1991. Photopatch and oral challenge tests were positive.

Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy group at the 8 position in mice irradiated with long-wavelength UV light.

A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was substituted at the 8 position of the quinoline nucleus, was very stable under irradiation with long-wave UV light (UVA). Derivatives, a fluoroquinolone with no substitution (the 8-H analog) and one in which a fluorine was substituted (the 8-F analog), were degraded in their solutions by the UVA irradiation. The phototoxic inducibility by these derivatives was further studied in a murine model. When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body weight, the maximum dose given, and exposed to the UVA light, no inflammatory lesions were observed in their ears. Ear redness was marked in mice given more than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg. Histopathological changes, edema, and infiltration of neutrophils were also observed microscopically in groups receiving the 8-H or 8-F analog but not in groups receiving Q-35 (8-OCH3). Similar inflammatory reactions were observed to occur in a dose-dependent manner with other available fluoroquinolone antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin and ofloxacin. These results suggest that the introduction of a methoxy group at the 8 position of the quinolone nucleus is important for the reduction of phototoxicity.

A case of temporal arteritis successfully treated with recombinant interleukin-2.

An 80-year-old Japanese woman with temporal arteritis was treated with systemic recombinant human interleukin-2 (IL-2) (1 x 10(6) unit/day for six weeks). The presenting symptoms of headache and skin necrosis and abnormal laboratory findings, such as an elevated erythrocyte sedimentation rate and CRP, promptly improved without any serious side effects. Although the pathogenesis of temporal arteritis and the mechanism(s) of the beneficial effect of IL-2 on it still remain unknown, this preliminary study highly encourages further investigations.