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Biomedical subjects

O Chosidow

Publications and source records attributed to O Chosidow.

At least 109 records · Page 6Linked to original sources

CD23-mediated nitric oxide synthase pathway induction in human keratinocytes is inhibited by retinoic acid derivatives.

Retinoids exert various functions including anti-proliferative and anti-inflammatory effects on many cell types including keratinocytes and are widely used in skin diseases, such as psoriasis and acne. We have previously shown that human keratinocytes express low affinity immunoglobulin E receptor (FcepsilonRII/CD23) when stimulated with interleukin-4. Immunoglobulin E ligates CD23 and induces the production of nitrites (reflecting the mobilization of the nitric oxide [NO]-pathway) and tumor necrosis factor-alpha by human keratinocytes. Here, 13-cis and all-trans retinoic acid (RA) were shown to reduce the production of nitrites by immunoglobulin E-activated keratinocytes by 80% in a time- and concentration-dependent fashion. As a consequence, RA derivatives also reduced the production of tumor necrosis factor alpha by these cells by 70%. The level of inducible NO synthase activity in activated human keratinocytes was significantly decreased upon treatment of the cells with RA derivatives (inhibition by 60% of the mean inducible NO synthase activity with 13-cis RA, 2 microM). Treatment for 24 h with RA derivatives almost completely abolished transcription of inducible NO synthase-specific mRNA in activated keratinocytes. Therefore, RA derivatives downregulate tumor necrosis factor-alpha release and the NO-transduction pathway through the inhibition of inducible NO synthase transcription. Together, our data provide evidence for inhibition of the NO-pathway by 13-cis and all-trans retinoic acid on CD23-activated human keratinocytes. These data may clarify the mechanism of the anti-inflammatory activity of RA derivatives in skin diseases.

Cell Division↗

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous adverse drug reactions (ADRs) (Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN, 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug, and with a standard series of drugs. 2 patients among the 22 SJS/TEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS/TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AGEP, in which the proportion of positive patch tests was significantly higher (p < 0.02). Nevertheless, the difference of sensitivity of patch testing in SJS/ TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also to the different spectrum of culprit drugs in each type of eruption.

Adult↗

Cutaneous reactions after treatment with 2-chlorodeoxyadenosine.

2-chlorodeoxyadenosine (2-CdA) is a new purine analogue which has shown great efficacy in the treatment of hairy cell leukemia. Only one case of cutaneous reaction after this treatment has previously been reported. The data from 33 patients treated with 2-CdA were retrospectively reviewed. Seven of these (21%) developed a disseminated eruption during the month following 2-CdA. One had toxic epidermal necrolysis. A reaction to the associated antibiotic therapy seemed "likely" or "very likely" in 5 out of the 7 cases. The incidence of adverse drug reactions may be increased after 2-CdA, and the role of CD4+ lymphocytopenia in these reactions is discussed.

Adult↗

Specific mucosal erosions in hypereosinophilic syndrome. Evidence for eosinophil protein deposition.

BACKGROUND: Mucosal erosions can be a presenting feature of the hypereosinophilic syndrome. The aim of this study was to analyze in situ the presence of eosinophil proteins and the state of eosinophil activation. Biopsy specimens of mucosal lesions and normal skin were taken from two men with oral and genital erosions typical of hypereosinophilic syndrome. Tissue sections were immunohistochemically labeled with anti-major basic protein, anti-eosinophil-derived neurotoxin, and anti-eosinophil peroxidase antibodies. The same specimens were also subjected to electron microscope examination. OBSERVATIONS: Eroded specimens displayed areas of eosinophil spongiosis within which extracellular deposits of eosinophil peroxidase, major basic protein, and eosinophil-derived neurotoxin were present. In normal skin, only a few eosinophils were present within the capillary lumen, and no extracellular deposits of these proteins were seen. Under the electron microscope, the cytoplasmic membranes of eosinophils located around the erosion were disrupted. Remnants of necrotic keratinocytes were found near these lysed eosinophils. CONCLUSION: As with other involved organs in hypereosinophilic syndrome, mucosal erosions seem to be the consequence of eosinophil protein release.

Humans↗

Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities.

OBJECTIVE: To test the hypothesis that drug-induced pseudolymphoma and hypersensitivity syndrome are 2 distinct clinical entities. DESIGN: Retrospective study from 1980 to 1993. SETTING: Departments of dermatology and medicine of 5 referral universitary hospitals. PATIENTS: Twenty-four patients who met arbitrary criteria selected as being suggestive of lymphoma, with probable drug cause. Patients with other definite cutaneous drug-induced eruptions were excluded. INTERVENTION: None. MAIN OUTCOME MEASURES: Suspect drugs; clinical, biological, and pathological findings; and evolution of each case and of 110 published case reports. RESULTS: Two groups were separated according to their mode of onset and clinical aspect. Three patients (and 15 cases in the literature) had subacute papulonodular or infiltrated plaques, without visceral involvement. Skin biopsy specimens showed a dense lymphocytic infiltrate mimicking lymphoma. Healing was constant when the drug was stopped. The 21 remaining patients (and 95 published cases) had an acute widespread eruption, with fever, enlarged lymph nodes, and multivisceral involvement. Lymphocytosis, atypical lymphocytes, eosinophilia, hepatitis, and high levels of lactate dehydrogenase were frequent. Skin biopsy findings were usually not specific (lymphocytic infiltrate and keratinocyte necrosis) but sometimes mimicked lymphoma. Severe forms and relapses occurred, even after the drug was stopped. The inducing drugs were the same in the 2 groups. CONCLUSIONS: These 2 groups correspond to drug-induced pseudolymphoma and hypersensitivity syndrome. We think that they are 2 distinct entities with different clinical and biological features and outcome, even if the pathological findings are sometimes similar. Prospective studies are needed to confirm these facts, to evaluate the therapy, and to follow up patients.

Adolescent↗

[Cutaneous graft versus host disease].

Graft versus host disease is frequently encountered in patients with an allogenic bone marrow transplantation. The disease apparently results from the activity of the donor T lymphocytes which react against the recipient's cells. There are two categories of graft versus host disease: the acute form which occurs within 3 months of the graft and the chronic form which occurs thereafter. Skin is the predominant site of manifestations, although the liver, the gut and the eye may be involved. In acute graft versus host disease, there is a characteristic maculo-papular rash raising a difficult differential diagnosis which pathology examination of biopsy cannot always resolve. The chronic disease is easier to recognize on the basis of local or generalized lichenoid or sclerodermal skin lesions. Several risk factors have been identified including the degree of donor-recipient HLA mismatch, recipient age and the number of T cells grafted. Graft versus host disease leads to immune deficiency with lymphoid depletion and increased risk of infection. Treatment depends on the site of organ involvement and extension. Corticosteroids and immunosuppressors are used.

Acute Disease↗

Essential mixed cryoglobulinemia. A comparative study of dermatologic manifestations in patients infected or noninfected with hepatitis C virus.

BACKGROUND AND DESIGN: An association between essential mixed cryoglobulinemia and hepatitis C virus (HCV) infection has been reported. Dermatologic manifestations are a classic presenting complaint in essential mixed cryoglobulinemia. The aim of this study was to compare the frequency and the nature of dermatologic manifestations in essential mixed cryoglobulinemia according to the presence of anti-HCV antibodies. Sixty-two consecutive patients with essential mixed cryoglobulinemia were tested for anti-HCV antibodies. Dermatologic manifestations were systematically assessed. RESULTS: Anti-HCV antibodies were detected in 35 patients. Palpable purpura corresponding histologically to leukocytoclastic vasculitis was the more frequently observed dermatologic manifestation and occurred mainly in HCV-antibody-positive patients. The patients with purpura had significantly higher serum cryoglobulin levels than patients without purpura. CONCLUSIONS: The frequency of palpable purpura is higher in HCV-antibody-positive patients and is related to the serum cryoglobulin levels.

Cryoglobulinemia↗

Neutrophilic dermatoses during granulocytopenia.

BACKGROUND AND DESIGN: Noninfectious cutaneous neutrophilic lesions can occur during granulocytopenia, but their mechanism remains unknown. We undertook a retrospective study of the neutrophilic dermatoses that developed during granulocytopenia induced by chemotherapy for acute myelogenous leukemia. RESULTS: Seven men and one woman were included (2.6% of treated cases of acute myelogenous leukemia); half had acute myelogenous leukemia subtypes 4 and 5. The male-to-female ratio was 7:1. Neutrophilic eccrine hidradenitis was diagnosed in five cases, Sweet's syndrome in two cases, and difficult-to-classify neutrophilic dermatoses in one case. Cutaneous lesions appeared 12.5 days after the start of chemotherapy, and the mean leukocyte count was 0.426 x 10(9)/L. Three patients needed corticosteroids systemically. CONCLUSION: Neutrophilic dermatoses during chemotherapy-induced granulocytopenia seem to occur more frequently in men with acute myelogenous leukemia subtypes 4 and 5.

Adult↗