Cytokines in Blister Fluids of Bullous Pemphigoid (BP)

Completed

• Conditions: Pemphigoid, Bullous

• Registration Number: NCT03856840
• Lead Sponsor: Mahmut Can Koska

Brief Summary

This study investigates the differences of Eosinophil Cationic Protein, Tumor Necrosis Factor-alpha and Anti-BP180-NC16A IgG levels of blister fluids in Bullous Pemphigoid patients which appeared before and under treatment subsequently. These molecules will also be measured in blood serum before and under treatment. Changes of titers in serum and differences between blister fluids will be compared to observe whether correlation exists between them. These measures will also be compared between groups of responders and non-responders to the first-line treatment options to analyze correlation with treatment success.

Detailed Description

Bullous Pemphigoid is an auto-immune bullous disorder in which auto-antibodies to hemidesmosomes, complement pathway, inflammatory cells and mediators play a crucial roles for disease pathogenesis.

Anti-BP180-NC16A IgG is an antibody that it primarily triggers inflammatory reactions and complement cascade in bullae development and plays major roles in disease pathogenesis. It is secreted by plasma cells which is induced by T-helper 2 cells and their cytokines in serum and lesional tissue. Anti-BP180 antibody detection in serum is very important in diagnosis and titers correlate with disease activity. Anti-BP180 antibody can also be detected in blister fluids and it may aid diagnosis.

Eosinophil cationic Protein is a cytokine and secreted by Eosinophil which is found in abundant numbers and correlated with tissue damage in Bullous Pemphigoid lesions. Serum titers of Eosinophil Cationic Protein has a correlation with disease activity and it is higher in blister fluid than serum. Tumor Necrosis Factor-alpha is an another cytokine which is secreted from inflammatory cells initially after inflammatory cascade is triggered. It is also found increased in serum blister fluids. Tumor necrosis factor-alpha is associated with clinical severity in bullous pemphigoid.

In Bullous Pemphigoid, development of bulla is required to be stopped if treatment will be considered as successful. Nevertheless smaller, more rapidly healing vesicles and bullae appear under treatment which are not regarded as findings of treatment failure. In this study we will measure Eosinophil Cationic Protein, Tumor Necrosis Factor-alpha and Anti-BP180-NC16A IgG levels with E.L.I.S.A. technique in these subsequently appeared blisters if they will appear and compare them with pretreatment blisters. We will also measure levels of these molecules in blood serum before and under treatment. We will analyze corralation between blood serum and blister fluids. Also we will compare responder patients and non-responder patients to first-line treatment options to observe correlation of changes and differences in these body fluids with treatment success.

Study Timeline

• Study Start: 2018-01-29
• Study First Submitted: 2019-02-19
• Study First Submitted QC: 2019-02-26
• Study First Posted: 2019-02-27
• Primary Completion: 2019-05-23
• Study Completion: 2019-08-27
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-02
• Last Update Posted: 2019-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• All patiens presented to clinics who is diagnosed with Bullous Pemphigoid by findings of clinical, histopathological, Direct Immunoflorescent evaluation.
• All relapsed/flared Bullous Pemphigoid patients.
• Patients who accept the terms and conditions and sign consent form.

Exclusion Criteria

• Patients who are received treatment before presenting clinics where the study is conducted.
• Patients who reject to join to study and the terms and condition
• Patients who leave the study by own decision

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Titers of Eosinophil Cationic Protein in blister fluid and blood serum	14 Days	Calculated of measurements of Eosinophil Cationic Protein (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.
Titers of Tumor Necrosis Factor-alpha in blister fluid and blood serum	14 Days	Calculated of measurements of Tumor Necrosis Factor-alpha (pg/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.
Titers of Anti-BP180-NC18A IgG in blister fluid and blood serum	14 Days	Calculated of measurements of Anti-BP180-NC18A IgG (U/ml) by ELISA technique in blister fluids and serums that obtained before treatment and under first and second weeks of treatment.

Secondary Outcome Measures

Name	Time	Method
Consolidation phase of Outcome Measures for Bullous Pemphigoid	14 days	Time interval between control of disease activity and end of consolidation phase.
Bullous Pemphigoid Disease Area Index (B.P.D.A.I.)-Pruritus score	Up to one year	Visual analogue score of pruritus is also part of this index. Minimum score is 0 and maximum score is 10. This score will be assessed for last 24 hours, last one week, last one month one by one; thus maximum score will be 30.; This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.
Time to control of disease activity	Up to 4 weeks	Time interval between initiation of treatment and control of disease activity/beginning of consolidation phase
Bullous Pemphigoid Disease Area Index (B.P.D.A.I.)	Up to one year	BPDAI is an index to assess disease area and severity depending on involvement of mucosa and skin region, lesion number and size. Minimum score is 0 and maximum score is 360.; This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.
Bullous Pemphigoid Disease Area Index (B.P.D.A.I.)-Damage score	Up to one year	Scars of previous lesions are also included to this index, minimum score is 0 and maximum score is 12.; This index will be calculated at before treatment, second week and fourth week of treatment. After first month it will be calculated in each follow-up visit.
Treatment Failure	4 week	Development of nontransient lesions that heal in more than one week, continued extension of old lesions, failure of established lesions to begin to heal or continued pruritus despite of Treatment of one month.
Relapse/Flare	Up to one year	Appearance of more than three lesions per month or at least one large eczematous lesion or urticarial plaques that do not heal within one week, or extension of established lesions or daily pruritus in patient who was achieved disease control
Bullous Pemphigoid disease severity assessment	One day	This assessment will depend on multiple factors according to more than one classification. Patients will be separated to mild, moderate, severe conditions according to their clinical findings.; Mild: Involvement of less than %10 of skin surface area and appearance of less than 10 bullae in each day. Both feature will be necessary to regard individual patient's disease as mild.; Moderate: Involvement of %10-30 of skin surface area and appearance of less than 10 bullae in each day. Both feature will be necessary to regard individual patient's disease as moderate.; Severe: Involvement of more than %30 of skin surface area or appearance of more than 10 bullae in each day or B.P.D.A.I. score more than 56 (without Visual analogue score of pruritus). Existence of even one of this findings will ve sufficient to regard individual patient's disease as severe.

Trial Locations

Locations (2)

Istanbul Training and Research Hospital; 🇹🇷 İstanbul, Samatya, Turkey

Istanbul Medeniyet University Goztepe Training and Research Hospital; 🇹🇷 Istanbul, Kadikoy, Turkey