Successful treatment with hydroxychloroquine for systemic lupus erythematosus with cutaneous involvement accompanied by a xanthomatous reaction.

Antimalarials are usually recommended for the first-line systemic treatment of cutaneous lupus erythematosus. Alopecia in patients with discoid lupus erythematosus (DLE) is sometimes a refractory condition in spite of topical therapies. We herein described a case of DLE on the scalp with a pathological change of a xanthomatous reaction, which was successfully treated with hydroxychloroquine (HCQ). A 34-year-old woman presented with hair loss to the parietal region. She had been diagnosed with systemic lupus erythematosus (SLE) four years previously. Treatment with 30 mg/day of prednisolone (PSL) had been initiated, and the dose was gradually reduced. At 10 mg/day of PSL, she had noticed her hair loss. Physical examination revealed some small erythematous lesions to the parietal region with accompanying hair loss. Pathological findings of the erythematous lesion on her head revealed thickening of the basement membrane zone, the interface dermatitis with vacuolar degeneration, and both superficial perivascular and perifollicular infiltration of inflammatory cells in the dermis. In addition, there was an infiltrate of xanthomatous cells detected in the papillary dermis, which were positive for CD68 and CD163. The patient started treatment with HCQ at a dose of 200 mg/day. The skin lesions completely resolved within five months after initiation of HCQ without increase in the dose of PSL. Xanthomatous reactions are rarely recognized in lupus erythematosus. The chronic epithelial injury in DLE could be implicated in triggering the secondary reactive process of a xanthomatous reaction. We believe that the reaction seen in our patient was a secondary change to pathological alteration due to SLE. However, as yet unrecognized factors may play a role in the development of a xanthomatous reaction in DLE.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.

Palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus: possible involvement of CD163+ M2 macrophages in two cases, and a review of published works.

BACKGROUND: Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a commonly occurring condition related to systemic autoimmune disease. It is characterized histopathologically by a distinct pattern of granulomatous inflammation in the presence or absence of leukocytoclastic vasculitis. The properties of granulomatous cells in PNGD are still uncertain. OBJECTIVE: We sought further investigation on the phenotype of the infiltrated cells in PNGD from two patients with systemic lupus erythematosus (SLE) and reviewed the previous published reports in order to provide a comprehensive summary on the clinical features of PNGD in SLE. METHODS: The immunohistochemical features of granulomatous cells in PNGD associated with SLE were analyzed. Immunohistochemical studies were performed on sections from our two cases using antibodies against CD68, CD163, CD15, Factor XIIIa, myeloperoxidase and neutrophil elastase. The clinical characteristics of the SLE patients who developed PNGD were also evaluated. We included all cases retrieved through a PubMed search with the key words PNGD and SLE. RESULTS: Cutaneous lesions consisted of erythematous plaques distributed on the face and upper limbs in both cases. The infiltrated cells were mainly positive for CD68 and CD163, a phenotype suggestive of M2 macrophages. Some mature neutrophils and lymphocytes were also present. A review of the literature of PNGD associated with SLE revealed a predominance in females, high prevalence of lupus nephritis and a good response to systemic steroids, with frequent skin lesions relapses during tapering of the treatment. LIMITATIONS: This study examined only two cases; the pathogenesis of the disease remains to be clarified. CONCLUSION: PNGD lesions were abundantly infiltrated by M2 macrophages, suggesting that they may have a role in this condition. SLE accompanied by PNGD might be associated with lupus nephritis and frequent relapses of skin lesions.

The influence of glucose load on metabolism during minor surgery using remifentanil-induced anesthesia.

BACKGROUND: During perioperative fasting, lipid metabolism gradually increases, resulting in free fatty acids (FFA) and/or ketone bodies. Suppression of surgical stress by remifentanil may allow the safe administration of glucose infusions, avoiding both hyperglycemia and ketogenesis. The effects of glucose infusion on glucose and lipid metabolism were therefore investigated in patients undergoing minor surgery with remifentanil anesthesia. METHODS: Thirty-four patients were randomized 1 : 1 to receive no glucose (0G group) or low-dose glucose (0.1 g/kg/h for 1 h followed by 0.05 g/kg/h for 1 h; LG group). The concentrations of glucose, adrenocorticotropic hormone (ACTH), 3-methylhistidine (3-MH), insulin, cortisol, FFA, creatinine (Cr), and ketone bodies were measured before anesthetic induction, 1 and 2 h after glucose infusion, at the end of surgery, and the next morning. RESULTS: The concentrations of cortisol and ACTH decreased during surgery in both groups when compared with the concentrations before anesthesia and at the end of surgery (P < 0.05). Glucose and insulin concentrations were significantly higher in the LG than in the 0G group at 1 and 2 h after infusion. No patient experienced hyperglycemia. The concentrations of FFA and ketone bodies were lower in the LG than in the 0G group during surgery, but there were no significant between group differences in 3-MH/Cr. CONCLUSION: Infusion of low-dose glucose attenuated fat catabolism without causing hyperglycemia, indicating that infusion of low-dose glucose during remifentanil-induced anesthesia may be safe for patients.

Dramatic Clinical Response of Relapsed Metastatic Extramammary Paget's Disease to Trastuzumab Monotherapy.

We report the first case of 68-year-old Japanese woman with metastatic HER2-positive extramammary Paget's disease that showed the validity of trastuzumab monotherapy. We administered trastuzumab at a loading dose of 8 mg/kg i.v., followed by a 6 mg/kg maintenance dose every three weeks according to a protocol for HER2-positive metastatic breast cancers and a near-complete response was achieved after the tenth infusion. The patient experienced a moderate headache and flushing during the first infusion, but had no advanced effects during subsequent infusions with ibuprofen and d-chlorpheniramine maleate. Given the dramatic response, the patient has had 17 infusions of trastuzumab with no disease progression. Thus, trastuzumab has few side effects and is well tolerated for elderly patients. It may become a new choice of the adjubant therapy of this disease.

Melanoma in association with acquired melanocytic nevus in Japan: a review of cases in the literature.

BACKGROUND: Malignant melanomas clinically and/or histologically associated with melanocytic nevi have been reported worldwide. Approximately 20% of malignant melanomas in Caucasians, most of which are found on the trunk and proximal extremities, develop in association with pre-existing melanocytic nevi. In Japan, however, over half of all melanomas are acral lentiginous melanomas (ALMs) on the hands and feet; melanomas on sun-exposed areas are seen less frequently in Japanese people than in Caucasians. As ALMs are not usually accompanied by melanocytic nevi and there have been no reviews of the literature or statistical data regarding Japanese cases of melanomas with melanocytic nevi, dermatologists in Japan have few opportunities to see melanomas associated with pre-existing melanocytic nevi. METHODS: Here we report a case of a superficial spreading melanoma that was formed on a melanocytic nevus on the trunk, and we review for the first time the case reports from the Japanese literature. RESULTS AND CONCLUSIONS: With regard to the reported cases, melanomas associated with melanocytic nevi were mainly superficial spreading melanomas and nodular melanomas on the trunk or extremities; ALMs were rarely associated with nevi, indicating a trend similar to that observed in Caucasians. These findings suggest that the low frequency of associations between melanomas and melanocytic nevi in Japan reflects racial differences in the frequencies of each type of melanoma.

IL-6 attenuates apoptosis, while neither IL-6 nor IL-10 affect the numbers or protease phenotype of fetal liver-derived human mast cells.

BACKGROUND: The combination of recombinant human stem cell factor (rhSCF), rh interleukin (IL)-6 and rhIL-10 was reported to be optimal for mast cell development from cord blood progenitors and to induce chymase expression in all such mast cells earlier in their development than tryptase. OBJECTIVE: The effects of rhIL-6 and rhIL-10 in various combinations on the rhSCF-dependent development of human mast cells from fetal liver progenitors were examined in serum-free media. METHODS: Dispersed fetal liver cells were cultured in serum-free AIM-V medium with rhSCF alone, or with combinations of rhIL-6 and rhIL-10. Tryptase and chymase expression, surface Kit expression, metachromasia with toluidine blue and apoptosis were measured. RESULTS: Neither rhIL-6 nor rhIL-10 nor the two interleukins together, when included from day 0 of culture, affected the number or protease phenotype of mast cells at 1 or 3 weeks. Expression of tryptase paralleled the appearance of metachromasia and surface Kit, both of which preceded chymase expression, regardless whether a rabbit polyclonal or mouse monoclonal anti-chymase antibody preparation was used. On the other hand, rhIL-6 markedly attenuated baseline levels of apoptosis in the presence of rhSCF as well as apoptosis occurring after withdrawal of rhSCF, whereas rhIL-10 had no effect. CONCLUSION: RhIL-6 protected fetal liver-derived mast cells from apoptosis, particularly after withdrawal of rhSCF, but neither rhIL-6 nor rhIL-10 nor the combination of these interleukins affected the numbers or protease phenotype of these mast cells.

Human skin-derived mast cells can proliferate while retaining their characteristic functional and protease phenotypes.

Human mast cells in adult tissues have been thought to have limited, if any, proliferative potential. The current study examined mast cells obtained from adult skin and cultured in serum-free medium with recombinant human stem cell factor. During the first 4 weeks of culture, the percentages of mast cells increased from 10 to almost 100. After 8 weeks, a 150-fold increase in the number of mast cells was observed. When freshly dispersed mast cells were individually sorted onto human fibroblast monolayers and cultured for 3 weeks, one or more mast cells were detected in about two thirds of the wells, and in about two thirds of these wells the surviving mast cells showed evidence of proliferation, indicating most mast cells in skin can proliferate. Such mast cells all expressed high surface levels of Kit and Fc epsilon RI, each of which were functional, indicating IgE was not required for Fc epsilon RI expression on mast cells. Such mast cells also retained the MC(TC) protease phenotype of mast cells that normally reside in the dermis. After 4 to 8 weeks of culture these mast cells degranulated in response to substance P and compound 48/80, characteristics of skin-derived mast cells that persist outside of the cutaneous microenvironment. (Blood. 2001;97:2045-2052)

Disialoganglioside GD3 is selectively expressed by developing and mature human mast cells.

BACKGROUND: Disialoganglioside GD3 is expressed on the surface of selected cell types. Anti-GD3 mAb administered to human subjects with malignant melanoma produces signs and symptoms of immediate hypersensitivity reactions. OBJECTIVE: The expression of GD3 by human mast cells was assessed during mast cell development in vitro and in samples of lung and skin. METHODS: GD3 on tissue- and in vitro-derived mast cells was analyzed after double labeling of cells for tryptase (G3 mAb) or Kit (YB5.B8 mAb) and GD3 (R24 mAb). Glycolipids in extracts of fetal liver-derived mast cells were examined by using high-performance thin-layer chromatography. RESULTS: Flow cytometry showed that the percentage of GD3+ cells increased in parallel to Kit+ cells during the recombinant human stem cell factor-dependent development of fetal liver-derived mast cells. Double-labeling experiments showed that GD3+ cells were also surface Kit+ and granule tryptase positive, identifying them as mast cells in preparations of lung-, skin-, fetal liver-, and cord blood-derived cells. The major acidic glycolipid detected was NeuAcalpha2-8NeuAcalpha2-3Galbeta1-4Glcbeta1-1'Cer (GD3). Among peripheral blood leukocytes, only basophils and about 10% of the T cells were labeled with anti-GD3 mAb. Anti-GD3 mAb-conjugated magnetic beads were used to purify mast cells to greater than 90% purity from dispersed skin cells enriched to approximately 12% purity by means of density-dependent sedimentation but were less proficient for dispersed human lung mast cells, most likely because of other cell types that express GD3. CONCLUSION: GD3 is expressed on the surface of developing human mast cells in parallel to tryptase in secretory granules and, like Kit, can serve as a target for their enrichment by immunoaffinity techniques.

Microcystic adnexal carcinoma. Electron microscopic and immunohistochemical study.

We present a patient with microcystic adnexal carcinoma. The lesion was an indurated plaque on the skin of the right upper lip of a 58-year-old woman which was slowly growing during 27 years. Carcinoembryonic antigen was immunoreactive in the luminal contents of the tumor ducts and in the cytoplasm of cells surrounding ducts. S-100 protein was positive in the cytoplasm of a few cells at the lower dermis. These observations suggested that this tumor was related to sweat glands. Furthermore, electron microscopy revealed that tumor cells had features of eccrine ductal cells. These observations confirm that this tumor appeared at least capable of eccrine duct differentiation.

Cutaneous sarcoidosis showing multiple papular eruptions with keratotic plugs.

A 26-year-old woman developed 249 discrete papules on her lower extremities. Twenty-three of them had keratotic plugs. Histologic examination demonstrated granulomatous foci consisting of epithelioid cells and a epidermal invagination which was disrupted at the base and lateral sites. This invagination was considered to represent transepithelial elimination.