Katarzyna Wozniak

Definitions and outcome measures for mucous membrane pemphigoid: Recommendations of an international panel of experts

Mucous membrane pemphigoid encompasses a group of autoimmune bullous diseases with a similar phenotype characterized by subepithelial blisters, erosions, and scarring of mucous membranes, skin, or both. Although knowledge about autoimmune bullous disease is increasing, there is often a lack of clear definitions of disease, outcome measures, and therapeutic end points. With clearer definitions and outcome measures, it is possible to directly compare the results and data from various studies using meta-analyses. This consensus statement provides accurate and reproducible definitions for disease extent, activity, outcome measures, end points, and therapeutic response for mucous membrane pemphigoid and proposes a disease extent score, the Mucous Membrane Pemphigoid Disease Area Index.

Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients: coincidental phenomenon with a risk of disease development?

Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was to assess the frequency of circulating IgG pemphigus autoantibodies in the healthy relatives of pemphigus patients and of their ability to bind in vivo in the epidermis. We also analyzed IgG subclasses distribution, both in the serum-positive relatives and in the patients. Our study included 67 healthy relatives, 50 healthy normal controls and 33 patients (25 at an active stage of the disease, 8 in clinical remission). To detect circulating pemphigus antibodies we applied indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The frequency of circulating pemphigus autoantibodies in the relatives, detected by IIF (30/67) was statistically higher (Pxa0<xa00.001) than in the control group (0/50). ELISA revealed anti-desmoglein 1 and/or 3 antibodies in 13 out of 67 relatives. Direct immunofluorescence performed in 25 out of 32 seropositive relatives did not show intercellular bound in vivo IgG and/or C3 in the epidermis in any cases. Circulating IgG2 subclass was observed in 60% of the examined relatives and IgG4 was detected in 23.3% of them. In the patients at an active stage of pemphigus IgG4 and IgG1 were the dominant subclasses (96 and 76% relatively) while in clinical remission antibodies predominantly belonged to the IgG2 (75%) and IgG4 (37.5%) subclass. The obtained results confirmed polyclonal production of pemphigus autoantibodies and their different distributions dependent on the disease activity. Statistical analysis showed that the frequency of IgG1 and IgG4 subclasses was significantly higher in the patients at an active stage of the disease when compared to the patients in clinical remission (Pxa0<xa00.001) or with seropositive healthy relatives (Pxa0<xa00.001). The relevance of the presence of IgG4 autoantibodies in the healthy relatives’ sera requires further studies that focus on their potential pathogenicity.

Penicillin-induced anti-p200 pemphigoid: an unusual morphology.

We report here a case of a 52-year-old woman with erythema gyratum repens-like lesions appearing during anti-p200 pemphigoid, probably induced by oral penicillin. The diagnosis of anti-p200 pemphigoid was made by the presence of in vivo bound and circulating IgG anti-basement membrane zone auto-antibody reactive with the dermal side of salt-split skin and with 200 kDa protein in dermal extract on Western immunoblot. Laser scanning confocal microscopic study disclosed the localization of IgG at the lamina lucida-lamina densa border. Skin lesions responded poorly to high dose of prednisone and the combination of prednisone and dapsone. When methotrexate was added, skin lesions healed within 3 weeks. To our knowledge, erythema gyratum repens-like lesions have not been described previously in this disorder. Thus, we have expanded the clinical morphological spectrum of patients with anti-p200 pemphigoid and first described a patient whose disorder was probably drug-induced.

Novel keratin 5 and 14 gene mutations in patients with epidermolysis bullosa simplex from Poland.

Mutation analysis in keratins 5/14 (K5/14) had been performed in five Polish families with epidermolysis bullosa simplex (EBS) to extend genotype-phenotype correlation and to add to the mutation database. All the patients had been clinically classified into two subtypes of EBS; Weber-Cockayne (EBS-WC) and Dowling-Meara (EBS-DM) as well as one case of EBS with mottled pigmentation (EBS-MP). DNA from patients and their family members was assessed for mutations in K5 or 14 using polymerase chain reaction amplification and subsequent direct sequencing. We identified four different missense mutations in K5 and one missense mutation in K14. Three of these are novel. Mutations associated EBS-DM resided in the highly conserved 20 amino acids end of the 1A domain in K5. Direct nucleotide sequencing of a case of EBS-MP revealed a heterozygous P25L mutation in K5. However, no genotype-phenotype correlation was identified in families with EBS-WC. The present study demonstrates the first series of molecular genetic data in EBS from Poland.

IgA Anti-p200 Pemphigoid

BACKGROUNDnAnti-p200 pemphigoid is a rare autoimmune subepidermal blistering disorder. Clinically, it may resemble bullous pemphigoid, linear IgA bullous dermatosis, or dermatitis herpetiformis. Immunologically, anti-p200 pemphigoid is characterized by the development of IgG antibodies directed against a basement membrane zone protein with a molecular weight of 200 kDa.nnnOBSERVATIONSnWe report the first case, to our knowledge, of anti-p200 pemphigoid associated with IgA antibodies and having clinical features resembling pemphigus herpetiformis or dermatitis herpetiformis localized on traumatized areas. Histopathological examination of lesional skin showed dermal-epidermal separation and microabscesses composed of neutrophils in the dermal papillae. Direct immunofluorescence disclosed the presence exclusively of linear in vivo-bound IgA along the basement membrane zone. With the use of laser scanning confocal microscopy, in vivo-bound IgA was localized above collagen type IV and colocalized with laminin 332. Indirect immunofluorescence showed circulating IgA antibodies against basement membrane zone at a titer of 1:160 that reacted with the floor of an artificial blister of salt-split skin. Western immunoblot analysis using dermal extract confirmed the reactivity of circulating IgA antibodies with the 200-kDa antigen corresponding to laminin γ1; however, immunoblotting using recombinant protein of 107 amino acid C-terminus of laminin γ1 was negative for circulating IgA antibodies. Immunoelectron microscopy disclosed the reactivity of circulating IgA autoantibodies within the lower lamina lucida.nnnCONCLUSIONnTo the best of our knowledge, this is the first case fulfilling the immunopathological criteria for anti-p200 pemphigoid associated with IgA antibodies and having unusual clinical features.

Enzyme-linked Immunoassay Index for Anti-NC16a IgG and IgE Auto- antibodies Correlates with Severity and Activity of Bullous Pemphigoid

Bullous pemphigoid (BP) is characterized by IgG and IgE autoantibodies to the NC16a domain of BP180. This study evaluated the correlation between body surface area (BSA), total serum IgE and enzyme-linked immunoassay (ELISA) for IgG and IgE anti-NC16a in 77 patients with BP in the active stage, and the degree of conversion to negative of the studied parameters in clinical remission. Statistically positive correlations were observed between BSA and examined parameters (correlation index 0.2548, 0.2491, 0.311, respectively). Originally, patients with BP with positive ELISAs for both IgG and IgE autoantibodies presented twice as extensive skin lesions as those with positive IgG and negative IgE ELISAs. Conversion of ELISAs for IgG and IgE to negative in clinical remission occurred in 9.3% and 81% of patients with BP, respectively. This confirmed that ELISA for IgE anti-NC16a is a helpful parameter in the modification of current treatment and the assessment of risk of relapse in BP.

Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts

BACKGROUNDnSeveral European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management, OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of recommendations.nnnMETHODSnA preliminary survey, based on the European Dermatology Forum (EDF) and the European Academy of Dermatology and Venereology (EADV) guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology (AAD) conference. A second survey was sent following the meeting to more experts to achieve greater international consensus.nnnRESULTSnThe 39 experts participated in the first round of the Delphi-survey while 54 from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II based on Delphi results and meeting discussion.nnnLIMITATIONSnEach recommendation represents the majority opinion and therefore may not reflect all possible treatment options available.nnnCONCLUSIONSnWe present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first line therapy option for moderate to severe pemphigus.

Fluorescence overlay antigen mapping using laser scanning confocal microscopy differentiates linear IgA bullous dermatosis from epidermolysis bullosa acquisita mediated by IgA

Backgroundu2002 Linear IgA bullous dermatosis (LABD) and epidermolysis bullosa acquisita (EBA) mediated by IgA antibodies belong to the group of autoimmune subepidermal bullous diseases mediated by IgA autoantibodies. Early and correct diagnosis is crucial because the management and prognosis of the diseases are different.

Measuring of quality of life in autoimmune blistering disorders in Poland. Validation of disease – specific Autoimmune Bullous Disease Quality of Life (ABQOL) and the Treatment Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires

PURPOSEnAutoimmune bullous dermatoses (AIBD) are rare, severe diseases resulting from some antibodies activity against the different adhesion structures within the skin and/or mucosa. Few studies investigated quality of life (QOL) in AIBD by generic and dermatology-specific instruments, all reporting strong impact on QOL. Recently, disease-specific measurement tools have been developed: Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The aim of this study was to test the reliability and validity of ABQOL and TABQOL by developing the first foreign language versions and to evaluate ABQOL and TABQOL in Polish patients.nnnMATERIAL AND METHODSnThe study enrolled 80 patients from the tertiary referral center for AIBD at the outpatient clinic or on admission to the hospital. Sixty six patients completed the 17-item questionnaires of each ABQOL and TABQOL at day 0 and after 5-7 days. Both questionnaires were translated into Polish according to protocol.nnnRESULTSnThe internal consistency and test-retest reliability were high (Cronbach α=0.95 for ABQOL, α=0.87 for TABQOL), (R=0.98 for ABQOL, R=0.86 for TABQOL). In convergent validity, the correlation of ABQOL and TABQOL was strong (R=0.81), but low with objective disease activity scales. The strongest impact of AIBD on QOL has been observed in flares and in patients with the onset below 70 years of age. The patients with bullous pemphigoid had the highest QOL compared to other AIBD patients.nnnCONCLUSIONSnThe ABQOL and TABQOL are reliable and valid instruments for the assessment of QOL in AIBD.

Anti‐epiligrin cicatricial pemphigoid initially limited to the upper respiratory tract

The fact that the Turkish diet is based mainly on cereals such as wheat may explain the higher frequency of antigliadin antibodies in healthy individuals than in other populations with different diets. Our small number of controls may not represent the general population; however, other studies with larger groups had similar results. The presence of antibodies to gliadin had no influence on the disease characteristics. In order to form subgroups that may be correlated with the presence of antibodies, we selected patients that are claimed to have ‘severe disease’ with early age of onset (before 30 years), family history of psoriasis, generalized disease and arthropathy. Although only seven patients had generalized pustular or erythrodermic psoriasis, the frequency of antigliadin antibodies in this subgroup was 22Æ2%. However, we agree with Abenavoli et al. that coeliac disease-associated antibody positivity does not correlate with a greater psoriasis activity. Another interesting aspect of the results was that while all patients with coeliac disease had high positive antibody (>100 AU mL) results, psoriatic patients mostly had moderately positive (50–100 AU mL) results. Healthy controls had only weak positive (>25 AU mL) results. These may indicate that a possible gluten hypersensitivity in psoriasis is less than that of actual coeliac patients but more than that of the healthy individuals. Antigliadin antibody positivity is controversial in individuals without GI complaints. We did not perform a jejunal biopsy in this study; however, a ‘latent gluten enteropathy’ is thought to exist in some patients without any small intestinal pathology. The so-called ‘psoriatic enteropathy’ may be a secondary phenomenon as are other noncoeliac enteropathies, due to a possible common antigen that may affect both the GI system and the skin. However, the reports of patients that have undergone remission with only gluten-free diet argue against this hypothesis. Despite being insignificant, an increase in the presence of antibodies to gliadin was noted in patients with psoriasis. There seems to be a subgroup of patients with psoriasis with positive antibodies to gliadin but without GI symptoms. We agree with the authors that gluten-free diet deserves a trial in selected group of patients, especially those with severe disease.