How does scleroderma progress

Attack on the skin and organs


Attack on the skin and organs

By Bettina Sauer, Berlin


Scleroderma leads to tissue hardening and usually affects the skin. But the autoimmune disease often affects internal organs as well. That is why patients need early diagnosis, close monitoring and complex therapy, emphasized experts at the rheumatology congress in Berlin.


In 1987 Emma Margarete Reil (then 40) from Heilbronn experienced the first symptoms of a rare disease that specialists only diagnosed a few years later and which hardly anyone in Germany knew at the time: scleroderma (Greek for "hard skin"). It is one of the rheumatic diseases, more precisely one of the collagenoses, manifests itself in an increase, thickening and hardening of the connective tissue and usually affects the skin. "However, I learned at the time that scleroderma can hardly be treated and often affects the internal organs," said Reil in an interview with the PZ. “It was said at the time that the mortality rate after five years was 70 percent. That made me angry and I thought: Not with me! ”So she joined the“ Scleroderma Self-Help ”program that had been founded a few years earlier. "In this way I wanted to do something about the disease myself and help ensure that those affected receive better care."


The former business economist has been chairwoman of the scleroderma self-help program since 1997. In her opinion, a lot has changed in the meantime through her organization and the associated foundation founded in 1994 for the benefit of those affected: »The disease is no longer unknown. Rather, numerous medical specialists and new drugs are available to patients. In addition, intensive research is being carried out to further improve the therapies. ”In 2002, the European rheumatologists association Eular (European League Against Rheumatism) founded its own research network called Eustar), and the“ German Network for Systemic Scleroderma ”has existed since 2003 Among other things, to improve patient care and to set up a nationwide anonymized scleroderma register for the first time.


The dermatologist Professor Dr. Michael Sticherling from the Department of Dermatology at the University of Erlangen. At a satellite symposium of the Actelion company at the annual congress of the German Rheumatological Society (DGRh) in Berlin, he said: "The available epidemiological studies hardly provide reliable data on the frequency of the disease, the probability of organ complications and mortality." So far, only roughly can be derived that there are about 100 scleroderma patients out of a million people, women are about three times as likely to get the disease as men and the symptoms usually appear between the ages of 30 and 50 years.


Predisposition and Triggers


The causes are still largely in the dark. “The patients seem to be genetically predisposed. Obviously, however, certain environmental factors such as infections, drugs, dusts or organic solvents have to be added in order for scleroderma to break out. ”Then an autoimmune reaction starts, an attack by the immune system on targets in one's own body. Apparently, blood vessels that run through the connective tissue come under attack first. "There are increased levels of the messenger substance endothelin-1 in the patient's blood," said associate professor Dr. Christian Opitz, chief physician for cardiology at the DRK clinics in Berlin-Köpenick at the satellite symposium. "By binding to its receptors, it mediates a strong vasoconstriction and the activation of connective tissue cells." As a reaction to endothelin-1 and the reduced blood flow, these seem to divide increasingly and to produce more collagen fibers. Both contribute to the hardening of the tissue.


So-called circumscribed scleroderma with its various sub-forms is limited to the skin. Mostly isolated round foci develop with a waxy center and a blue-violet border (lilac ring). Although these hardly respond to therapies, they usually heal spontaneously. In addition, there is no organ involvement. If, on the other hand, the hardened tissue affects large areas of skin and internal organs, doctors speak of "systemic scleroderma" or "systemic sclerosis". Usually hardened skin occurs over a large area, which sometimes severely restrict mobility or freeze facial features like a mask. Depending on the skin involvement, doctors subdivide several variants of systemic sclerosis. In the »limited form«, the hardening is essentially limited to the face, forearms and lower legs. The »diffuse form«, on the other hand, covers almost the entire body, usually progresses quickly and spreads to internal organs at an early stage. There are also mixed forms with other rheumatic diseases, and some variants affect the organs but not the skin. Emma Reil says: "Because every disease progresses very differently and the therapies usually start with the symptoms, patients need an early diagnosis and close monitoring for possible consequential damage."


Early signs of Raynaud's syndrome


Systemic sclerosis almost always begins on the hands and manifests itself as Raynaud's syndrome, a dysregulation of blood flow (see Raynaud's syndrome: When the cold becomes torture, PZ 39/2008). In response to cold, stress or other stimuli, small arteries cramp suddenly and cause the fingers to pale. Avoiding cold, wetness and nicotine and, if necessary, long-term therapy with vasodilating calcium antagonists help, according to a quality manual from the DGRh (; path: quality assurance, quality manual). It also regards Raynaud's syndrome as a key symptom for early diagnosis. However, further examinations are required to confirm the diagnosis, in particular the detection of antinuclear antibodies (ANA) in the blood. These autoantibodies are directed against various cell nucleus components, occur in around 90 percent of all scleroderma patients and even provide information about the subtypes.


Skin and organ symptoms usually appear at the earliest one year or much later after the onset of Raynaud's syndrome. The DGRh manual names hardening of the lungs, the so-called fibrosing alveolitis, as the "most common life-threatening manifestation" of systemic sclerosis. This leads to inflammation in the alveoli, in which more connective tissue is then deposited. This can also make blood flow more difficult and thus lead to arterial high blood pressure in the pulmonary circulation. Lung function can be effectively improved by immunosuppressive therapy with cyclophosphamide alone or in combination with the glucocorticoids prednisolone or methyl prednisolone, according to the DGRh manual. "Endothelin receptor antagonists such as bosentan, phosphodiesterase inhibitors such as sildenafil and prostanoids such as iloprost are available for treating pulmonary hypertension," said cardiologist Opitz. "Study results are available for all three vasodilating substance groups that show an improvement in symptoms and performance in patients with scleroderma-related pulmonary hypertension." In order to identify and counteract this dangerous complication as early as possible, all patients with systemic sclerosis required regular checks, among other things by x-rays of the lungs and electrocardiograms and ultrasound scans of the heart.


The latter can also be used to identify possible hardening of the heart itself. These occur only very rarely, are usually inconspicuous, but can lead to cardiac arrhythmias and reduced pumping performance, among other things. Kidney involvement occurs more frequently, which, according to the DGRh manual, can now be managed well with ACE inhibitors. These drugs prevent high blood pressure crises that can otherwise result from kidney strain and appear to improve kidney function at the same time. For early detection, patients with systemic scleroderma need regular blood pressure and kidney function checks using urine and blood tests.


"The other organic symptoms are very common, but usually do not pose a serious threat," said Sticherling. Up to 50 percent of patients with systemic sclerosis develop painful and infection-prone ulcers (digital ulcerations) on the tips of their fingers and toes, which may require analgesic or antibiotic therapy. For faster healing, the DGRh manual recommends infusions with the prostanoids iloprost or prostavasin, the effectiveness of which has been proven by several controlled clinical studies. The endothelin receptor antagonist bosentan is used to prevent the development of new ulcerations. Two clinical studies confirm this effect, whereupon the European approval authority EMEA granted approval for use in digital ulcerations in 2007.


"Many patients complain of swelling and pain in their joints, which doctors may try to treat with non-steroidal anti-inflammatory drugs," said Sticherling. Furthermore, there are very often complaints in the gastrointestinal tract, especially hardening of the esophagus. These express themselves as swallowing disorders or heartburn. In order to increase the mobility of the esophagus, the DGRh manual recommends the use of prokinetics such as metoclopramide. Patients who already have heartburn should take proton pump inhibitors such as omeprazole in addition to reducing stomach acid build-up. In addition, Reil recommends not to eat anything two hours before going to sleep and to keep your upper body high so that the acid stays in the stomach.


Throttle immune processes


In principle, according to the DGRh manual, doctors can try to reduce systemic scleroderma, especially in the early stages, by means of immunosuppressive therapy. Accordingly, cyclophosphamide, methotrexate, azathioprine, ciclosporine and systemic glucorticoids offer the advantage that they also alleviate skin symptoms. However, they show such strong side effects that doctors have to weigh up the costs and benefits on a patient-by-patient basis. The manual also recommends comprehensive patient training, which can best be achieved by referring to a self-help group. Emma Reil sees it the same way and asks every pharmacist who cares for those affected to refer them to a regional group or the federal office of scleroderma self-help (; phone: 07131 3902425, sklerodermie (at) . »There, patients receive an exchange with other affected persons, individual information, concrete tips for everyday life and psychological help. After all, despite all the progress, scleroderma remains a stressful, threatening and so far incurable disease.