Rare Disease Day

The aim of Rare Disease Day, celebrated throughout the world on 28 February, is to raise awareness of the concerns of those affected. At which point a disease can be classified as rare, how the diagnosis and treatment are handled in our Center for Rare Diseases (ZSE) at Hannover Medical School (MHH) and why this job is so exciting is explained in an interview by the pneumologist and BREATH scientist, PD Dr. Felix Ringshausen.

PD Dr. Ringshausen is Senior Physician at the Department of Pulmonary and Infectious Diseases (MHH) and heads the Bronchiectasis and Cystic Fibrosis Team. These two diseases are also the main focus of his research at BREATH, the Hannover site of the German Center for Lung Research (DZL). For several years, the Department of Pulmonary and Infectious Diseases has provided an outpatient clinic for those patients with bronchiectasis not caused by cystic fibrosis, primary ciliary dyskinesia (PCD, a congenital disorder of the cilia in the respiratory tract) or Kartagener‘s Syndrome (PCD with Situs inversus/laterally reversed  inner organs).

Dr. Ringshausen, at which point can a disease be classified as rare?

According to the definition set out by the EU Commission, a disease can be classified as rare if it affects less than 5 out of 10,000 inhabitants.

Why is there an outpatient clinic for bronchiectasis, PCD and Kartagener‘s Syndrome or rather the ZSE-B Center for PCD and Kartagener‘s Syndrome at the MHH?

Principally, our Bronchiectasis Outpatient Clinic and the ZSE-B Center should serve as a point of contact for those affected and their families, but also for their practitioners. Adequate medical treatment of the patients is hampered here by the fact that, up to now, no medications have as yet been approved for the treatment of bronchiectasis, PCD and Kartagener’s Syndrome. Whilst the prescription of approved medication is unproblematic and the costs in every case have to be paid by the statutory health insurance (GKV), all necessary drug prescriptions must be made „off-label“, which presents a huge problem, particularly for general practitioners, who treat the majority of patients. With the off-label prescriptions, there is a danger of medication regression, meaning that doctors are then personally responsible for the costs of therapy, which the statutory health insurance, unlike with approved medications, will cover only under certain circumstances such as a severe illness, absence of approved medication or chance of success. The medical risk of an off-label prescription is, when used appropriately, easily manageable. Our general practitioner colleagues are always on the defensive as the regression often only follows years later, so that the necessary regulations cease and the patients are treated at best like COPD patients if the lung function is impaired accordingly.

And what expertise distinguishes the Center from other centers?

In accordance with the main emphasis of the MHH, we have at our disposal exceptional expertise in treating patients with terminal lung manifestations, for example extensive bronchiectasis, transplant preparation and evaluation as well as complex and difficult-to- treat chronic infections, particularly through multiresistant gram-negative bacteria or non-tuberculous mycobacteria. This special expertise is particularly important if these infections lead to comparatively rare or severe complications, such as pulmonary hemorrhage, collapsed lungs or respiratory failure or require interdisciplinary management. Chronic rhinosinusitis with nasal polyps (continuous inflammation of the mucous membranes in the nose and the paranasal sinuses), chronic otitis media (durable and long-lasting middle ear infection) with conductive hearing loss,  the unfulfilled wish to have children or fertility counseling for those with PCD or Kartagener’s Syndrome as well as support during a high-risk pregnancy and delivery require the expertise of many different specialist departments.

Luckily, it is mostly the supposedly little things for which we use our expert knowledge in the sense of „navigating the jungle of loopholes and paragraphs“ in the Social Security Statute Book V or to strengthen self-management, for example by transferring the patient to a specialist physiotherapeutic respiratory therapist close to home. For this specialist expertise, our patients travel at least once or twice a year to the MHH  at an average distance of 105 km each way.

How do you approach the treatment and diagnosis of a rare disease?

We follow a totally patient-centered treatment approach. A large proportion of the patients have no causal diagnosis and are presented to us based on their bronchiectasis. For other affected persons, with an established diagnosis, whom we have been looking after for years or even decades, we continue to carry out regular controls in the sense of predictive disease management and always try to find the latest medical and scientific treatment that is most suitable for the patient.

New patients: To guarantee an efficient process with a high degree of effectiveness for the patients, getting to know those affected and their personal history begins already before the first appointment. For this, generally speaking, the already extensive findings and CT scans will be looked at and a diagnostic plan prepared for the day of the visit to the outpatient clinic. In the Center, however – it may sound trivial – the detailed anamnesis discussion, clinical examination and a therapeutic plan designed to suit the needs of the patient will be drawn up. In my experience, exact knowledge about one’s own diagnosis is a basic human need and right. There is something very satisfying in being able to make the diagnosis of a rare  congenital disease based on the anamnesis, clinic and, where applicable, according to a further screening test to correct a lifelong error – and confirm this then without a doubt here at the MHH within six to eight weeks by molecular genetic diagnostics. Ultimately, it is the knowledge of the exact diagnosis that allows a personalized therapy.

How is the treatment carried out?

Taking into consideration the fact that no medication is approved for this therapy, basic therapeutic measures like sociomedical counseling, infection prophylaxis through vaccination, sport, secretion-promoting respiratory therapy as well as rehabilitation and the prescription of adjuvants are available. The organization of a treatment infrastructure in the sense of helping people to help themselves in the patient’s vicinity is paramount. Part of this is also the establishment of contact with the disease-specific self-help organization Selbsthilfeverein Kartagener Syndrom und Primäre Ciliäre Dyskinesie e.V., for which we provide the voluntary Co-Speaker and a further member of the Medical Advisory Board. For some patients, we have to put in a little more effort and sometimes indicate very extensive, complex and cost-intensive therapeutic measures, such as an oral antibiotic long-term therapy, regular antibiotic intravenous therapy at home or a long-term suppression therapy with inhaled antibiotics.

What contribution to research is made in the Center?

Our research is closely interwoven at all levels: from epidemiological research and healthcare research within the framework of disease-specific national and international registry studies, via translational research at the German Center for Lung Research (DZL) e.g. with inducible pluripotent stem cells in the sense of a possible future cell therapy right up to clinical randomized controlled AMG (Medicinal Products Act) studies. The latter will in future be coordinated through a specific clinical study network (clinical trials network / PCD-CTN) via the European Reference Network for Rare Lung Diseases (ERN-LUNG). We, as one of the centers with the most patients in Europe, are the founder member of this network and as such make a significant contribution to the research. We are represented in the network with the largest number of adult patients after London. In ERN-LUNG, we represent one of the two centers for PCD alongside the Unikinderklinik Münster, whilst we are the only German center for bronchiectasis in this European reference network.

On the MHH YouTube channel, there is a video about the work of the Rare Disease Center.

Text: MHH/Lisa Marie Weigelt

Photo: privat

PD Dr. Felix Ringshausen, senior physician and head of the bronchiectasis-outpatient department at MHH