A patient with necrobiotic xanthogranuloma (NXG) and paraproteinaemia, who was followed-up for several years, and treated with low-dose chlorambucil, died as a result of a respiratory illness. The significant findings at autopsy were a xanthogranuloma of the spleen and giant cell myocarditis. The myocardial lesions were composed of macrophages, giant cells and lymphocytes. This finding is important because four of five known autopsied patients with NXG have had giant cell myocardial disease, and an effort at antemortem diagnosis should be made.
Calcineurin is constitutively expressed in bone marrow-derived macrophages. However, macrophage response to macrophage colony-stimulating factor (M-CSF) was not impaired by the use of either calcineurin inhibitors (W-13, chlorpromazine and trifluoperazine), calcium chelators (BAPTA-AM) or Ca 2+ channel antagonists (verapamil, nifedipine and diltiazem). Inhibition of calcineurin expression by inhibitory antisense RNA treatment did not result in an inhibition of M-CSF-dependent proliferation. Only very high doses of cyclosporin A and FK506 inhibited macrophage proliferation induced by growth factors, such as M-CSF, granulocyte-macrophage (GM)-CSF or IL-3. This inhibitory action is mediated by the peptidylprolyl isomerase activity of the immunophilins, as demonstrated by the use of specific inhibitors (rapamycin and sanglifehrin A). These isomerase inhibitors exerted a negative effect on a key element involved in macrophage proliferation, namely the M-CSF-dependent activation of the extracellular signal-regulated kinases (ERK). In summary, the data presented here provide new insights in the mechanism of macrophage proliferation, which may have relevant consequences. First, we showed that in M-CSF-dependent proliferation calcineurin is not involved, and second, that immunophilins play a key role and their activation blocks ERK activation.
Background Erosive pustular dermatosis of the scalp (EPDS) is characterized by crusted erosions or superficial ulcerations that lead to scarring alopecia. Objectives and Methods We performed a multicentre retrospective clinical study including 56 patients (29 females and 27 males, mean age 62.7) with a confirmed EPDS in order to describe epidemiology, clinical findings and therapeutic choices of this disease. Results Mechanical/chemical trauma was reported in 28.6%, a previous infection in 10.7%, a previous cryotherapy in 5.4% androgenetic alopecia in 48.2% and severe actinic damage in 25%. Trichoscopy showed absence of follicular ostia, tufted and broken hair, crusts, serous exudate, dilated vessels, pustules and hyperkeratosis. Histopathology revealed three different features, depending on the disease duration. The most prescribed therapy was topical steroids (62.5%), followed by the combination of topical steroids and topical tacrolimus (8.9%), systemic steroids (7.1%) and topical tacrolimus (5.4%). A reduction of inflammatory signs was observed in 28 patients (50%) treated with topical steroids and in all three patients treated with topical tacrolimus. Conclusion The relatively high number of patients collected allowed us to identify a better diagnostic approach, using trichoscopy and a more effective therapeutic strategy, with high-potency steroids or tacrolimus, which should be considered as first-line treatment.
Among 14 patients (11 female and three male) with cutaneous and subcutaneous leiomyosarcomas, metastatic spread occurred in six of the 13 patients with adequate follow-up. The tumours were classified with regard to tumour grade, number of mitotic figures per 10 high-power fields, reactivity to antidesmin antibodies, and DNA pattern as assessed by flow cytometry. Antidesmin antibody staining was present in only six cases and seemed to be less common in the higher-grade tumours. The DNA pattern was aneuploid in five cases and non-classifiable in one case; all of these cases had metastatic spread. None of the eight remaining diploid cases had metastatic spread. DNA content was a strong predictor of metastatic potential.
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