Biomedical subjects
Publications and source records attributed to J M Bonnetblanc.
A 25-year-old woman who was 20 weeks pregnant developed systemic lupus erythematosus with acquired ichthyosis and pyoderma gangrenosum. The course of these dermatoses suggests that an immunopathological mechanism was implicated in their pathogenesis.
Some types of hypersensitivity to drugs are defined either by the generic name of the drug or descriptive terms. They are sometimes assimilated to pseudolymphoma because the causative drugs are often the same, although the eruption lacks clinical and histopathological criteria of pseudolymphoma. It is then suggested to use 'idiosyncratic drug hypersensitivity syndrome' to define this type of drug reaction. As the skin and other organs may be involved, a generic name would help to determine a better definition and a surveillance program.
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We report a case of distal finger hypoplasia associated with foetal hydantoin syndrome (FHS). The occurrence of this syndrome is thought to be due to abnormalities of collagen, cytochrome P 450 and arachidonic acid metabolism. The risk of developing FHS could be evaluated by counting the glucocorticoid receptors of lymphocytes or by measuring epoxide hydrolase activity through amniocentesis. FHS can be prevented by taking folates during pregnancy.
A 64 year-old man was admitted for congestive heart failure induced by an acute renal failure due to obstruction. Retroperitoneal periaortic-aneurysmal fibrosis was the etiology of the obstruction. Type IV Ehlers-Danlos syndrome was diagnosed based upon clinical and histological cutaneous signs.
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A 69-year-old man with a history of relapsing polychondritis developed a widespread cutaneous eruption that was clinically and histologically typical of erythema elevatum diutinum. This eruption was accompanied by a recurrence of arthralgias. The significance of this association between relapsing polychondritis and erythema elevatum diutinum, which has not been previously reported, is discussed.
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Several components of the dermal-epidermal junction (DEJ) bear the name of the autoimmune bullous disease in which they are involved. The epidermolysis bullosa acquisita (EBA) antigen, a component of anchoring fibrils, and the bullous pemphigoid (BP) antigen, a component of hemidesmosomes (HD) with a molecular weight of 220-240 kD, have been well characterized. In contrast, there is little data known about the cicatricial pemphigoid (CP) antigen. No differences between CP and BP have been reported when sera of patients were studied by Western immunoblotting. Findings of a study of sera from 8 patients with CP by indirect immunoelectron microscopy (IEM) on normal human skin are reported. Saponin (0.1% 10 mn) was used as a permeabilizing agent of cytomembranes and saponin-treated skin samples were compared to saponin-untreated skin samples. Four sera from patients with BP, one from a patient with EBA, and three from healthy donors served as controls. The CP sera produced a similar staining of DEJ on both saponin-treated and saponin-untreated skin samples: immune deposits were localized over the lamina densa and the lower part of the lamina lucida clearly separated from the cytoplasmic membrane of keratinocytes, in regularly spaced clumps. The BP sera produced an intense staining of DEJ only on saponin-treated skin samples: immune deposits were observed on the cytoplasmic attachment plaque of the HD; on saponin-untreated skin samples, BP sera produced only a faint staining of the extracellular part of HD. Finally, as expected the EBA serum appeared on the lower part of the lamina densa and anchoring fibrils, and no DAB deposits were observed with the serum of healthy donors. This data indicated that CP antigen is different than BP antigen by its exclusive extracellular localization. It may be a component of anchoring filaments.
To study the subclass distribution of autoantibodies and their complement-fixing capacity in cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) we studied the sera from 23 patients by both indirect immunofluorescence (IIF) on 4-microns cryostat sections of normal human skin and immunoblotting of epidermal or dermal extracts. Monoclonal antibodies of strict specificity for human IgG subclasses were used. Sera from 20 patients with BP served as controls. In addition, total IgG subclass levels were determined by indirect competitive ELISA in all sera. Complement binding capacity was studied by IIF using antibodies to C3 after incubation of skin section with autoantibodies and source of fresh complement. CP autoantibodies reacting with the 230-240 kD and/or the 180-kD epidermal bands showed an IgG4/IgG1 subclass restriction, with a predominance of IgG4 in 10 cases, of IgG1 in four. In BP sera, IgG4 and IgG1 autoantibodies were detected with a similar frequency (100% and 83%, respectively). In EBA sera, autoantibodies reacting with the 290 kD and 145 kD dermal bands also showed an IgG1/IgG4 restriction. Concordant results were obtained by IIF. However, the IIF method had a lower sensitivity for the detection of IgG4 CP antibodies and IgG1 EBA antibodies than immunoblotting. Finally, when CP antibodies were analyzed for their complement-binding activity, it was found that sera containing IgG4 autoantibodies alone never fixed complement whereas all complement-fixing CP sera had IgG1 autoantibodies, suggesting that only this subclass of antibodies is capable of fixing complement.
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We report the results of a French multicentre study to evaluate the efficiency of psoralen plus ultraviolet A (PUVA) therapy in the prophylactic treatment of benign summer light eruption (BSLE) and to establish the optimal protocol of radiation. Nine photobiology centres took part in this study; 83 patients (76 of them women) were evaluated. The radiation protocols were as follows: oral psoralen (8-methoxypsoralen; 0.6 mg/kg) was taken at each session; the starting dose of UVA radiation was determined according to skin type, with increments of 0.5 J/cm2 every 2 sessions. The subjects were randomized to receive 10-20 sessions 3 times per week. PUVA therapy was very effective: 68 patients (82%) reported total protection from BSLE. Four patients (5%) showed progress. Only 13% showed no improvement. The satisfactory results were not correlated with either the number of sessions or the J/cm2 of UVA. The intensity of tanning after the PUVA sessions did not appear to predict cure. Thirty-six percent of the patients had adverse reactions to treatment, including erythema, pruritus and triggering of BSLE. However, these effects only required the treatment to be stopped in 2% of the cases (for severe pruritus). The results in the various centres were similar.
A 74-year-old woman developed a generalized pustular dermatosis with erythema-multiforme-like and vesiculobullous lesions 10 days after beginning a treatment by nadoxolol. Despite the clinical polymorphism of the eruption, histology constantly revealed the presence of subcorneal pustules, even within the epidermis overlying subepidermal bullae. The eruption spontaneously healed after discontinuation of nadoxolol.
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Sera from 20 patients with bullous pemphigoid (BP) were analyzed for the subclass distribution of IgG autoantibodies by Western immunoblotting of normal human heat-separated epidermal extracts. Strips were sequentially probed with patient sera, monoclonal antibodies (Mab) anti-human IgG1-4, and a labeled anti-mouse Ig. The relative dilutions of each subclass-specific Mab were determined in dot immunobinding experiments in order to give uniform reactivity to the corresponding human IgG subclass. Circulating BP autoantibodies reacting with the major BP antigen of 220 kDa and/or a 165-kDa band showed a stricking predominance of IgG4. Overall, IgG4 was the major subclass reactive with the 220-kDa band, whereas, in addition to IgG4, IgG1 and IgG2 were frequently represented in the response to the 165-kDa band. Complement fixation of circulating BP antibodies was studied by complement indirect immunofluorescence using human serum as source of complement and FITC goat anti-human C3, C1q, and C4, on normal human skin substrate. When circulating BP antibodies contained IgG1 or IgG2 in addition to IgG4, they fixed C3 and, in some cases, C1q and C4, suggesting complement activation by either the classical or the alternate pathway.
We studied 11 consecutive patients with classical cicatricial pemphigoid (CP) using direct immunoelectron microscopy (IEM) and Western immunoblotting analysis. Direct IEM performed in the skin or gingival mucosa revealed in all 11 CP patients that immunoglobulins and complement deposits were usually thick and discontinuous along the dermoepidermal junction, mostly localized on the lamina densa and occasionally in the lamina lucida. By direct IEM, the ultrastructural aspect in CP differs from the pattern observed in bullous pemphigoid (BP) and from that of chronic epidermolysis bullosa acquisita (EBA). Nine CP patients were studied by Western immunoblotting and, of these nine, only two had detectable anti-basement membrane zone (BMZ) antibodies by indirect immunofluorescence on salt-split skin. By immunoblotting performed on protein extracts of heat-separated epidermis, eight out of the nine CP sera specifically reacted with two protein bands of approximately 230-240 kD and 180 kD, similar to those recognized by BP sera in co-migration experiments. By immunoblotting on skin BMZ extracts, none of these nine CP sera recognized the 290-kD major polypeptide of EBA antigen. Taken together, these results suggest that, in CP, the target-antigen, as identified on immunoblots, is similar to BP antigen, but with an abnormal expression within the dermoepidermal junction of patients, which may in part explain the scarring course of the disease.