1st International Meeting on Degos Disease March 18-19 2005

Event Poster Event Poster (PDF)

The 1st International Meeting on Degos Disease was held at Department of Dermatology, Venereology and Allergology, Charité-Universitätsmedizin Berlin on March 18-19 2005.

A DVD of the meeting is available from Matt Schuller at matschu@comcast.net if you are in the USA. Please let me know at judith@degosdisease.com if you are in Europe or elsewhere and I will send you one. See details on the Patients’ Forum.

The 1st International Meeting on Malignant Atrophic Papulosis (Degos disease) is supported by the Charity German Registry of Adamantiades-Behcet’s disease

Event Leaflet Event Leaflet (PDF)

Professor Zouboulis presented a clinical synopsis in which he introduced the setting up of a Biobank, beginning with anonymous samples from the patients and close relatives of those present. This will be full when it has 20 samples, as is the one set up originally by Professor Constantine Stratakis in the USA. These Biobanks will be used by international researchers studying the Human Genome Project.

More centres locally to patients need urgently to be found for taking, storing and examining of samples by medical researchers.

Professor Zouboulis asks in his study whether special proteins or molecules behave in a different way in the lesion than in a normal sample of tissue. He will concentrate on the attack by the disease on the endothelium.

He points out the close relationship or similarity between Degos disease and Behcet’s disease (Morbus Adamantiades-Behcet or MAB) and also Lupus Erythematosus (SLE). He will be examining similarities and differences between the three diseases.

In describing the historical perspective on Degos disease, the professor showed how Köhlmeier in Austria in 1941 took a structural view of the disease (ie the vascular involvement) and how Degos in France in 1942 described the look of the disease (ie the skin lesions). In 1979 Degos, Delort and Tricot acknowledged that the cutaneous disease can lead to intestinal involvement.

It was described by both as a unique disease and not a variant of another condition. It had been thought originally that it was a form of thromboangiitis obliterans.

The OMIM (Online Mendelian Inheritance in Man) number of Degos disease is 602248. This is important in case genetic information comes in to be added.

About 150 publications have appeared in all, with 200 cases described.

There is a so-called “grey number” of cases – ie those whose diagnosis has not been recognised or who have not consulted doctors about their symptoms. In Degos disease this is probably very high. (In MAB the grey number is 10 unknown patients for every one who has been diagnosed – ie 10:1)
When a disease begins to be more widely recognised, it tends to be over-diagnosed, but diagnosis can be readily corrected with biopsy examination.

As with MAB and SLE, there is no age or racial prevalence in Degos disease, and the most active age is between 20 and 40 years. There is a normal distribution curve across the ages for Degos patients. It is found worldwide, including in Africa and Japan, not just among Europeans or those whose ancestors moved from Europe.

It is extremely rare that a disease can be so easily recognised simply from the skin lesions, as they are so characteristic; however, a doctor has to have seen a patient before if he is to recognise it.

Its aetiology (cause) is unclear, in common with other vasculitides.

Professor Zouboulis describes two forms of Degos disease – a benign form, where only the skin is involved, and a malignant form where systemic involvement occurs.

There are two modes of thought about what is happening:

The study needs to look at the lesions to find out if there is inflammation, and whether there is something circulating in the blood.

Degos is a micro-arterial disease, where the tissue is starved of nutrition and so dies quickly; it is localised to the areas where the smallest blood vessels have been closed and so cannot feed the vessels they serve. All organs, even the nerves, are fed by these tiny blood vessels.

Diagnosis

1. Dermatologists are involved because most often the skin lesions are the first symptoms to be recognised. When there is gastrointestinal (GI) involvement, there is usually bleeding, constipation, diarrhoea and pain; however sometimes a patient with GI involvement has no symptoms. There is a secure diagnosis only if there are skin lesions. This is because of recognition but is confirmed with biopsy, otherwise the diagnosis is lost. This increases the grey number as possibly patients have the disease without the skin lesions.

2. Histology confirms the diagnosis.

In MAB, intestinal perforations occurred after medical investigation for ulceration after pain; could this manifestation be a reaction?

Eye involvement is a neurological involvement of the fundus (back of the eye) where the optic nerve is affected.
Heart involvement is often pericarditis.
Brain involvement shows as many micro-thromboses.

It may be that Degos disease is either an acute or a delayed reaction to a viral infection – a so-called type 3 reaction. The paromyxovirus has been mentioned.
It is speculated that there may be an “ancient virus” which has integrated with our genome.

If this is to be investigated, the RNA expressive of the virus (its activity) needs to be found locally in the body (ie where the virus is). It is well known that approximately 21 days after a virus infection in young people, there can be a vasculitis reaction. This is an immune reaction induced by the virus. Could this be a similar but delayed reaction?

Where the disease appears in families, it is always benign (ie there is no lethal outcome).
It is more dangerous to have a sporadic case than a familial one.
Does this mean that there is some protective factor at work within a family group?

If the disease becomes systemic, it is not always malignant, but patients are always followed up very closely. Doctors find this difficult to discuss with patients, as they are not able to predict progression and outcome.

Professor Zouboulis proposes that a new name be considered for Degos disease, to reflect its nature as a vasculitis.
He suggests Atrophic Papulosis (Köhlmeier-) Degos. Any change would have to be approved.

His tests will ask
a) how to induce a reaction in endothelial cells of healthy and diseased tissue.
b) Can viral DNA/RNA be recognised?
c) Are there continuous levels of C reactive protein, or does its activity increase when new lesions appear?
d) Can a worsening of internal symptoms be predicted with a simple blood test?

The tests are not sophisticated or expensive. They are based on observations of similar testing in MAB.

We need
large numbers of patients; statistically our numbers are too small to make firm conclusions yet.
medical researchers prepared to set up local biobanks, using the same protocol as set up in Berlin.

At present, all those who have participated in the study have access to the internet. We have to find those patients who do not use computers or email. In some parts of the world doctors too distrust email (because letters are not signed by hand) and are not prepared to communicate via computer. Doctors need to be contacted to put forward the names of patients who can join the study.

Dr Matthias Steinhoff made a presentation entitled The Skin Biopsy: a major diagnostic tool.

He has studied the histological criteria in the literature. He has found that a variety of features may be connected with the clinical evolution of the disease.
He has looked at the different stages of the disease, and the lesions are described in 3 stages (new, fully developed, scar).

In the new lesion, slides showed an inflammatory infiltration around the vessels (very similar to SLE) and mucin, a material which lies between the collagen bands.
Intraneural and perineural inflammation were present but not specific to Degos.

In the developed lesion, the typical wedge-shaped necrosis was visible and the epidermis is flat and scaling.
There is sclerosis of the epidermis, similar to that in lichen sclerosis et atrophicans.
There is inflammation around the blood vessels; lymphocytes destroy the cells in the vessel walls.
Thrombosed vessels were clearly visible.

In the late lesions, the wedge shaped necrosis is visible with the thickening epidermis and an inflamed rim. The mucin is there (this is a marker or sign of disease, but not specific to Degos) but is diminished. The vessel walls are thickened and sclerotic.

This is not always classic histology for Degos:

The thrombotic vessels, V-shaped necrosis and lymphocytic infiltrate visible in the early lesions can be absent in the later ones.
It is the histology plus the clinical picture which lead to diagnosis.

Dr Steinhoff has a very clear picture for diagnosis, which will be published together with the findings from Professor Zouboulis and Dr Theodoridis in a consensus paper.

Dr Athanasios Theodoridis made a presentation entitled
Epidemiologic and first prognostic study on Malignant Atrophic Papulosis

He presented comparative studies of Degos patients and paid tribute to the work done by Dr Julia Turnbull, who started the research for Professor Zouboulis, and who now works in Hamburg.

In particular, a study by Burg in 1989 of 101 patients (1 of his own and 100 from the literature) was compared with the present study.
Dr Theodoridis has 76 patients in his study, made up of
- 4 patients seen in Berlin
- 16 patients from the patients’ support network
These 20 patients are group A for the summary below.
- 56 cases from the literature.
Group B for the summary below consists of all 76 patient cases.

Findings are more positive than those of Burg, and figures will be published soon. Some are summarised below.

(Although relatively low numbers have been studied, as more patients are found and their stats added to the study, the figures will become more statistically significant).

In group B 39% of men had systemic involvement
In group A 29% of men had systemic involvement

In group B 37% women had systemic involvement
In group A 46% women had systemic involvement

In group B 21% of men had a positive family history (ie someone in their family had Degos disease)
In group A 29% of men had a positive family history

In group B 27% of women had a positive family history
In group A 0% of women had a positive family history

Patients with positive family history had no systemic involvement (ie no lethal outcome from Degos).

In Burg’s study the mean age of Degos patients was 35 years.
In the current study the mean age is 35.4 years.

A graph showed that 85-90% of patients who develop systemic involvement will do that within the first 6 years after the skin lesions appear. (However one patient is known who developed systemic involvement after 13 years). Statistics from our group of 20 patients show the same distribution of probabilities.
Almost 85% of those with systemic involvement developed their symptoms within the first three years after the appearance of the skin lesions.

Question and Answer session (some observations)

The skin lesions seem to appear in waves. In some patients (and in common with all vascular diseases) the initial skin symptoms are very severe, but later ones seem to be milder.

There is no way of reliably measuring the severity or the number of the skin lesions.
Although lesions have been counted and different patterns of frequency have been observed in Degos and in MAB, systemic involvement is the only sign of the severity of the disease.

The study will concentrate on comparison of the histology of the lesions, new and old, and on their comparison with other diseases and see what will develop in the long term. The lesions in different people are not all the same, just as vascular reactions are not the same.

There is no standard prognosis for patients with systemic involvement; each patient has to be examined separately.
It is possible to have GI involvement and not have any symptoms.
To discover this, patients would need to be monitored regularly, and many patients’ symptoms and data examined.

It has not been able to examine patients not receiving any therapy, as there would be none left to study.
The usual therapy prescribed for Degos patients includes
Pentoxifylline (Trental)
Aspirin
Dipyridamole

Any other drugs specifically targeted at treating Degos disease would be so-called “orphan drugs”.
What is needed is a published paper positing a good idea for therapy, which would highlight Degos as a �marker disease� � ie one whose research and therapy would have a knock-on effect for other diseases in the same group. This is what makes the current research so important � finding out what group of vascular diseases to place Degos in will lead to clearer delineation of need for drug research.

Setups in different countries can lead to situations where , for instance, only one specialist can bill a medical insurance company when several have met to compare notes on a case. This makes it difficult to persuade doctors with different specialities to have a consensus meeting when diagnosis is unclear. In Degos, often haematologists, gastroenterologists, dermatologists, neurologists and more might be called in to be consulted about symptoms.

When there is a clearer picture from the data we have contributed during this conference weekend as to what kind of vasculitis group Degos may be related, we may be able to “attach” ourselves to that group for insurance purposes.

The use of nicotine patches in a case in Japan was because nicotine is an anti-inflammatory drug. It has been noted that in MAB patients, smokers have less lesions. However, tests would have to be made before this therapy could be recommended.

In 15 years of studying MAB (Behcet’s) and setting up its German Registry , Professor Zouboulis has developed an expertise which he can bring to bear on his study of Degos disease. For the first ten years he tried to persuade individual patients to form a self-help or support group. Once this was finally started, the research was enhanced and patients benefited.

Our own Degos Patients’ Support Network has been in existence since 1999 and although we have found more patients than originally expected, we now believe that there may be many more who could be contacted and maybe helped.
IF YOU OR YOUR DOCTORS KNOW OF ANY DEGOS PATIENTS OR THEIR FAMILIES, PLEASE ENCOURAGE THEM TO CONTACT US OR THE DOCTORS IN BERLIN. WE NEED MANY MORE FOR THE RESEARCH PROJECT IF WE ARE TO HAVE ANY CHANCE OF FINDING OUT MORE ABOUT THIS DISEASE.

He feels it is essential that we say not so much “Why me?” but that we should take a positive attitude and work hard to find out how we can advance the work which will help all of us. The disease is nobody’s fault – but we could see it as a sign to do something with our lives. We should ask what we can do with our lives – take a wholly unacceptable situation and develop something better, for ourselves and for others. We can do something about this disease if we understand what is happening and do everything we can to motivate researchers and medical doctors wherever we live to continue this work internationally, in co-operation with the doctors in berlin who have set up the study.
The protocols are simple; the tests are not expensive. Other tests can be added in later when this international network is set up.
Prof. Zouboulis and Dr Theodoridis want to share the study, have it for other doctors to consult.

This 1st meeting has been part-funded by the MAB registry in Berlin and we are grateful for this help.

Professor Zouboulis promises to attend the next meeting wherever it is.

The doctors’ consensus paper will be published – dates and other details to follow when we are informed.
We patients and relatives who attended the conference have been encouraged to write our own consensus paper to be published both on the website and also in a journal yet to be approached.

The study
Degos patients , family members, friends and medical professionals were present to hear the presentations by Professor Zouboulis, Dr Theodoridis and Dr Steinhoff.

All of the patients and one of the close relatives took part in the study being launched by the doctors. It involved taking a sample of venous blood, and two tissue extractions (from affected and clinically healthy skin) with punch biopsies. Each sample will be processed and encoded with a secret number. The connection between the trial number and the name of the patient is only known and available to the doctors involved in the study.

Its aims are
- the determination of the aetiology of the disease
- an attempt to determine whether a familial predisposition can be found, via a genetic examination
- verification of the vessel involvement.

No previous results or studies are available.

The study has the purpose of creating a biobank of samples for genetic examination, which will prove to be suitable in the near future to search for the origin and eventually for a treatment for this disease.

When the biobank in Berlin has its allotted number of samples then it must be closed by international law. It is essential to find more research institutions around the world which can begin to collect similar samples to widen the study, using the same protocols as have been started here in Berlin. The doctors will be using C-reactive protein, a test to measure the concentration of a protein in serum that indicates acute inflammation.

If you know of enthusiastic and committed medical researchers in the fields of dermatology, haematology, rheumatology or gastro-enterology particularly, please talk to them about this valuable work and ask them to contact Professor Zouboulis at christos.zouboulis@klinikum-dessau.de.

Page last modified on 5 October, 2005

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