A major increase in the incidence of BP has been recently reported in the United Kingdom. In addition, there are some controversies about the over-mortality of BP patients. The primary objective was ...to reevaluate the incidence of BP in France as compared with that we estimated 15 years ago. The secondary objective was to assess mortality of BP patients. BP incidence was retrospectively estimated from all BP cases diagnosed between January 2000 and December 2005 in three French regions with a total population of 3.858 million inhabitants. BP mortality was assessed from a prospective cohort accrued during the same time period. A total of 502 incident BP patients (mean age: 82.6±8.8years) were identified. Overall estimated incidence was 21.7 cases per million persons per year (95%CI:19.8–23.7 cases per million persons per year), which is about 3-fold higher than the incidence that we estimated 15 years ago. In the population aged 70 years or above, BP incidence was 162 cases per million per year (95%CI:147–177 cases per million per year). The overall 1-year survival rate was 62% (95% CI: 56–67%). The risk of death for BP patients was more than six times greater than that for the general population (SMR:6.60; 95%CI:5.47–7.90). The incidence of BP in France has increased 3-fold in the last 15 years. BP is associated with high mortality.
To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma subtypes, we ...analyzed a total cohort of 20 PCLBCL-LT patients by using next-generation sequencing with a lymphoma panel designed for diffuse large B-cell lymphoma. We also analyzed 12 pairs of tumor and control DNA samples by whole-exome sequencing, which led us to perform resequencing of three selected genes not included in the lymphoma panel: TBL1XR1, KLHL6, and IKZF3. Our study clearly identifies an original mutational landscape of PCLBCL-LT with a very restricted set of highly recurrent mutations (>40%) involving MYD88 (p.L265P variant), PIM1, and CD79B. Other genes involved in B-cell signaling, NF-κB activation, or DNA modeling were found altered, notably TBL1XR1 (33%), MYC (26%) CREBBP (26%), and IRF4 (21%) or HIST1H1E (41%). MYD88L265P variant was associated with copy number variations or copy neutral loss of heterozygosity in 60% of patients. The most frequent genetic losses involved CDKN2A/2B, TNFAIP3/A20, PRDM1, TCF3, and CIITA. Together, these results show that PCLBCL-LT exhibits a unique mutational landscape, combining highly recurrent hotspot mutations in genes involved in NF-kB and B-cell signaling pathways, which provides a rationale for using selective inhibitors of the B-cell receptor.
We describe a series of patients whose auto-immune bullous skin disease (AIBD) of the dermal-epidermal junction (DEJ) was characterized by clinical, immunological and ultrastructural features ...intermediate between bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), and a recalcitrant course.
From the database of the French reference centre for AIBD, we screened all the patients who were referred for an AIBD of the DEJ with a mucosal involvement, who neither met the diagnostic criteria for the diagnosis of BP, nor were typical of MMP. Sera were analysed by NC16A-ELISA and immunobloting against the C-terminal and LAD-1 parts of BP180. Skin biopsies were studied by direct immunoelectron microscopy (IEM).
Fifteen patients (4 males, 11 females) of mean age 70.8 ± 11.8 years were included. The mucosal involvement was localized in oral cavity in all cases and in pharyngeal/laryngeal or genital area in 8 (53%), and 6 patients (40%), respectively. No patient had ocular involvement, nor atrophic or fibrosing scars. All patients had extensive skin lesions (mean BPDAI score =65.9 ± 24.4), which predominated on the upper body part. Direct IEM performed on 8 patients showed IgG deposits on the lamina lucida in all cases, and the lamina densa in 5 cases. All sera recognized NC16A, while none recognized BP-230 in ELISA. 10 out of the 13 tested sera (76.9%) contained IgG which recognized the C-terminal domain of BP180 and 10 sera (76.9%) the LAD-1 domain of BP180. Patients poorly responded to super potent topical corticosteroids and were treated with oral corticosteroids ± immunosuppressant in 13 cases (86.6%).
This mixed muco-cutaneous pemphigoid differs from BP by the younger age of patients, multiple mucosae involvement, circulating antibodies against both the C- and N-terminal part of BP180, and very poor response to topical CS. It differs from MMP by extensive inflammatory skin lesions, absence of ocular involvement and atrophic/fibrosing scars.
Abstract
Calcific uremic arteriolopathy (CUA) is a severely morbid disease, affecting mostly dialyzed end-stage renal disease (ESRD) patients, associated with calcium deposits in the skin. ...Calcifications have been identified in ESRD patients without CUA, indicating that their presence is not specific to the disease. The objective of this retrospective multicenter study was to compare elastic fiber structure and skin calcifications in ESRD patients with CUA to those without CUA using innovative structural techniques. Fourteen ESRD patients with CUA were compared to 12 ESRD patients without CUA. Analyses of elastic fiber structure and skin calcifications using multiphoton microscopy followed by machine-learning analysis and field-emission scanning electron microscopy coupled with energy dispersive X-ray were performed. Elastic fibers specifically appeared fragmented in CUA. Quantitative analyses of multiphoton images showed that they were significantly straighter in ESRD patients with CUA than without CUA. Interstitial and vascular calcifications were observed in both groups of ESRD patients, but vascular calcifications specifically appeared massive and circumferential in CUA. Unlike interstitial calcifications, massive circumferential vascular calcifications and elastic fibers straightening appeared specific to CUA. The origins of such specific elastic fiber’s alteration are still to be explored and may involve relationships with ischemic vascular or inflammatory processes.
Systemic lupus erythematosus is characterized by the production of autoantibodies directed against nuclear Ags, including nucleosome and DNA. TLR9 is thought to play a role in the production of these ...autoantibodies through the capacity of nuclear immunogenic particles to interact both with BCR and TLR9. To determine the role of TLR9 in SLE, C57BL/6-lpr/lpr-TLR9(-/-) and TLR9(+/+) mice were analyzed. The abrogation of TLR9 totally impaired the production of anti-nucleosome Abs, whereas no difference was observed in the frequency of anti-dsDNA autoantibodies whose titer was strikingly higher in TLR9(-/-) mice. In addition a higher rate of mesangial proliferation was observed in the kidney of TLR9-deficient animals. These results indicate that in C57BL/6-lpr/lpr mice, TLR9 is absolutely required for the anti-nucleosome Ab response but not for anti-dsDNA Ab production which is involved in mesangial proliferation.
Mucous membrane pemphigoid is a rare autoimmune blistering disease characterized by post-bullous erosion of mucous membranes. Herein, we present a case of a nonagenarian man who was referred to our ...department of dermatology presenting with painful erosion of the buccal mucosa. Physical examination revealed palate erosion associated with erosion of the buccal mucosa. A diagnosis of mucous membrane pemphigoid was confirmed, and the patient was successfully treated with topical corticosteroids.
Balloon cell nevus: Histologic and dermoscopic features Dhaille, Florie, MD; Courville, Philippe, MD; Joly, Pascal, MD, PhD ...
Journal of the American Academy of Dermatology,
02/2015, Volume:
72, Issue:
2
Journal Article
Primary cutaneous EBV‐positive diffuse large B‐cell lymphoma is an exceptional and aggressive neoplasia with a poorer prognosis than other cutaneous lymphoma. Our observation points out the rarity of ...the presentation and the dismal clinical course.
Primary cutaneous EBV‐positive diffuse large B‐cell lymphoma is an exceptional and aggressive neoplasia with a poorer prognosis than other cutaneous lymphoma. Our observation points out the rarity of the presentation and the dismal clinical course.
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