Monthly Archives: February 2014

Related Articles

The possible association of hidradenitis suppurativa and Down syndrome: is increased APP expression resulting in impaired Notch signaling the missing link?

Br J Dermatol. 2014 Feb 7;

Authors: Blok JL, Jonkman MF, Horváth B

Abstract
Recently, mutations in genes encoding for ү-secretase (GS) have been demonstrated in familial hidradenitis suppurativa (HS), including presenilin-1 (PSEN1), that probably contribute to the pathogenesis of HS by impairing the Notch signaling pathway. Mutations in PSEN1 are also associated with Alzheimer’s disease (AD), a condition that is strongly related to Down syndrome (DS). Here we describe five cases where HS occurred in DS patients. An association between HS and DS is reasonable since trisomy of chromosome 21 probably leads to overexpression of the amyloid precursor protein (APP) resulting in a change of the substrate pool for GS processing at the expense of the Notch receptors. Consequently, Notch signaling is impaired which predisposes DS individuals to HS. Additionally, the relatively high prevalence of obesity in DS patients as well as alterations in their immune system could underlie the possible association between both conditions. To confirm our hypothesis, further studies are needed investigating the expression of Notch receptors and APP in the epidermis of DS patients. This article is protected by copyright. All rights reserved.

PMID: 24506173 [PubMed – as supplied by publisher]

Continue reading →

Related Articles

Low sensitivity of type VII collagen enzyme-linked immunosorbent assay in epidermolysis bullosa acquisita: serration pattern analysis on skin biopsy is required for diagnosis.

Br J Dermatol. 2013 Jul;169(1):164-7

Authors: Terra JB, Jonkman MF, Diercks GF, Pas HH

Abstract
BACKGROUND: The type VII collagen (coll VII) enzyme-linked immunosorbent assay (ELISA) has been reported to have high sensitivity (> 93%) and specificity (> 96%) for diagnosing epidermolysis bullosa acquisita (EBA) in patients who are seropositive on indirect immunofluorescence on salt-split skin (SSS).
OBJECTIVES: To investigate the added value of the coll VII ELISA in the laboratory diagnosis of SSS-positive and SSS-negative EBA and to correlate the ELISA index with disease episode.
METHODS: The coll VII ELISA was performed on banked sera of 28 patients with EBA: 15 SSS positive and 13 SSS negative. Sera from healthy blood donors (n = 17) and patients with other autoimmune blistering diseases (n = 29) served as controls. In four patients, the ELISA index was measured longitudinally. Serration pattern analysis by direct immunofluorescence has been prospectively performed since 2000 in 19 patients.
RESULTS: The sensitivity in the SSS-positive group was 80% whereas it was 23% in the SSS-negative group. In the prospective EBA subset it was 45%. The sensitivity of u-serration pattern analysis on skin biopsy was 89%. Ten (53%) of these cases were seronegative with both ELISA and SSS, and would have been missed by serum analysis alone. Of the 46 control sera, one serum tested positive (specificity 97·8%). The coll VII ELISA correlated with disease activity over time in individual patients.
CONCLUSIONS: The coll VII ELISA has limited added value in SSS-negative EBA cases. The ELISA test is valuable in differentiating EBA from antilaminin-332 mucous membrane pemphigoid and anti-p200 pemphigoid and in its ability to monitor patients with EBA serologically. U-serration pattern analysis on immunofluorescence skin biopsy is the gold standard for the diagnosis of EBA.

PMID: 23480491 [PubMed – indexed for MEDLINE]

Continue reading →

Related Articles

The n- vs. u-serration is a learnable criterion to differentiate pemphigoid from epidermolysis bullosa acquisita in direct immunofluorescence serration pattern analysis.

Br J Dermatol. 2013 Jul;169(1):100-5

Authors: Terra JB, Meijer JM, Jonkman MF, Diercks GF

Abstract
BACKGROUND: Serration pattern analysis of direct immunofluorescence (DIF) allows the differentiation of epidermolysis bullosa acquisita from other subtypes of pemphigoid. In daily practice its use is limited due to lack of experience and unfamiliarity.
OBJECTIVES: To test the learnability of DIF serrated-pattern recognition in groups with various a priori levels of competence.
METHODS: An online nversusu-test (www.nversusu.umcg.nl) was created, which contained 26 DIF images of the epidermal basement membrane zone, IgG stained and photographed with a magnification of × 40 and × 63. All images represented patients with a form of subepidermal autoimmune bullous disease. Thirteen DIF images were presented before and 13 DIF images after an instruction video about n- and u-serrated patterns. There were three options to choose from: n-serrated, u-serrated or undetermined. The test was completed by three groups of professionals: dermatology residents in training at the University Medical Center Groningen (UMCG), international experts on bullous diseases, and dermatologists and pathologists who had participated in the Groningen blistering course during the past 10 years.
RESULTS: The overall number of correct answers of serration patterns was significantly higher after instruction than before instruction (median 9.0 correct answers vs. 11.0 correct answers, P < 0.001). Participants showed a mean improvement after instruction of 15.4% in the UMCG group (66.7% vs. 82.1%), 16.2% in the international expert group (67.2% vs. 83.4%) and 12.1% in the blistering course group (60.7% vs. 72.8%). The u-serrated pattern was better recognized than the n-serrated pattern.
CONCLUSIONS: Serration pattern analysis by DIF can be learned irrespective of background of expertise.

PMID: 23489262 [PubMed – indexed for MEDLINE]

Continue reading →