Research for more effective treatment – The world’s first research centre for chronic inflammatory skin diseases is being established on the Lübeck Campus
Stefanie Gärtner (87) from Hanover, Martin Romberger (53) from Kassel, and Dr Wilhelm Schütte (71) from Braunschweig: All of them suffer from different embodiments of the same rare disease, mucous membrane pemphigoid, a chronic inflammatory formation of lesions that affect the body’s mucous membranes. They had all spent a long time in search of an accurate diagnosis and appropriate treatment before finding what they sought at the University Dermatology Clinic in Lübeck.
Researching the causes of the disease and developing new treatment approaches is among the research focuses of Prof. Detlef Zillikens, the clinic's director, and his team. This means that they belong to the German Research Foundation’s Cluster of Excellence for Precision Health for chronic inflammatory diseases (Precision Health in Schleswig-Holstein, PHSH), alongside researchers from other clinics and university institutes in Lübeck, the Christian Albrecht University of Kiel, the Borstel Research Center of the Leibniz Association, and the Max Planck Institute for Evolutionary Biology in Plön.
New research building for the CRIS
Following the success of previous research, the world’s first research centre for chronic inflammatory skin diseases, the Center for Research on Inflammation of the Skin (CRIS), will be opened in Lübeck. In 2017, the creation of the centre was approved by the Council of Science and Humanities, Germany’s most important science policy advisory body. Set to be completed in 2022 and to the tune of almost 25 million euros, the CRIS’s new, five-storey research building encompassing 3,048 square metres of floor space is under construction at the heart of the Lübeck Campus. The groundbreaking ceremony was held on 15 July of this year.
140 researchers from six institutes and two hospitals of the university and University Medical Center in Lübeck will carry out interdisciplinary work at the CRIS. The scientific goal is to shed light on the mechanisms that lead to skin inflammation and to develop innovative and curative approaches to treatment. The working groups involved on the Lübeck Campus include those focused on immunology, rheumatology, biostatistics, system-based medicine, pharmacology, anatomy, and biomedical optics. There is close collaboration within the Cluster of Excellence, including with the dermatology clinic and the department of gastroenterology in Kiel and with the Max Plank Center in Plön.
Chronic inflammatory lesion formation on mucous membranes
Mucous membrane pemphigoid (greek “pemphix” for lesion) is among the chronically progressing, lesion-forming autoimmune diseases. Their foundational cause lies in the immune system’s dysfunctional tolerance of its own body. Typically, roughly five percent of the population of a country is affected by an autoimmune disease. The most common afflictions are psoriasis, rheumatoid arthritis, and autoimmune thyroid diseases. Autoimmune diseases are still insufficiently understood and their causes cannot be treated. They are often life-long diseases that are treated with anti-inflammatory or immunosuppressive therapy to reduce suffering or slow down the destruction of the affected organs.
The mucous membrane plays a decisive role in the different types of mucous membrane pemphigoid, and also gives the disorder its name. The extent of the skin changes and thus the severity of the illness vary widely from patient to patient. Due to the often painful changes to the oral mucous membrane, patients frequently experience difficulty eating, which may in turn lead to weight loss and general fatigue.
For most patients, the disease begins orally. The oral mucous membrane is also often the most severely affected mucous membrane region. However, in some patients the disease may begin in the nasal mucous membrane, with symptoms including nose bleeds, the formation of bloody scabs, and reduced nasal breathing. For some patients, in particular women, the genital mucous membranes are most severely affected. Mucous membranes of the throat, oesophagus, and anus can also be affected. Lesions that affect the mucous membranes tear easily, and painful wounds known as erosions occur.
The eye’s mucous membrane, known as the conjunctiva, can also be affected, leading to the formation of scars and, in the worst case scenario, blindness. Therefore, patients’ whose conjunctivas are affected require particularly urgent treatment. Precise diagnosis requires a tissue and a blood sample.
Rare diseases often involve a long journey
In Stefanie Gärtner’s case, bleeding gums were the first symptom, followed by eye pain. It is primarily Dr. Schütte’s larynx and vocal cords which are affected; his voice sounds hoarse. Along with Martin Romberger and, on average, around ten other patients, they come to the short-term unit at the university’s dermatological clinic in Lübeck for five days every four weeks. The disease’s progress and diagnostic values are checked, medication is adjusted as required, and, if necessary, doctors from other disciplines become involved. If the disease progresses in a satisfactory manner, treatment can later be purely out-patient.
”Above all, I am pleased that after a long journey through the countless doctors’ surgeries and clinics, my illness was finally properly recognised and stabilised in Lübeck,” says Dr. Wilhelm Schütte, a patient at the clinic. Martin Romberger was pointed in the direction of the Lübeck clinic by a self-help group.
For the clinic’s director Prof. Dr. Detlef Zillikens, it is essential that treatment begins as early as possible so as to prevent it spreading to other organs. “We are trying to make the medication even more specific in its effects, so that it only acts on those cells that are actually responsible for the disease,” he says.
New approaches to diagnosis and treatment
Due to the currently unsatisfactory and unspecific treatment options, approaches to possible future treatments are focusing, on the one hand, on reducing the formation of antibodies (afferent phase of the autoimmune reaction), and, on the other hand, influencing the inflammatory reaction induced by the autoantibodies binding to the skin and mucous membranes (efferent inflammatory phase).
Current specific results for new approaches to treatment exist for the inhibition of the complement system, which plays an essential role in the efferent phase, in other words after the antibodies bind to the skin. The researchers were able to show that in mice the disease could be fully eliminated by blocking certain components. A clinical study based on these pre-clinical results is currently in progress at the Lübeck clinic.
New approaches to therapy are expected with regard to both the reduction of antibody production and the tissue damage caused by the autoantibodies in the skin. There are also various new approaches regarding the diagnosis of cutaneous autoimmune diseases. In particular, ELISA- and biochip-based procedures involving the use of molecular forms of autoantigens are being deployed.
These new test procedures are suitable for both the improved diagnosis of the disease as well as assessing the need for treatment and the particular treatment required, as in many of these diseases the autoantibody levels in the serum correlate to the disease activity. Due to the particular characteristics of autoimmune bullous dermatoses, in which specific autoantibodies can be detected in both the patients’ skin and serum, it is easier to define subgroups of these diseases compared to other diseases, which can then be given specific treatments.
Support from the German Research Foundation’s Clinician Scientist Programme.
For Prof. Zillikens and his research group it is important that the support of the German Research Foundation’s Clinician Scientist Programme allows young doctors involved in this work to be relieved of their routine tasks and thus able to fully concentrate on research.