Systemic sclerosis

from Wikipedia, the free encyclopedia
Classification according to ICD-10
M34 Systemic sclerosis
M34.0 Progressive systemic sclerosis
M34.1 CR (E) ST syndrome
M34.2 Systemic sclerosis, induced by drugs or chemical substances
ICD-10 online (WHO version 2019)

The systemic sclerosis (abbreviated SSc ) or systemic scleroderma (from ancient Greek σκληρός skleros , German , hard ' and ancient Greek δέρμα derma , German , skin' ), formerly progressive (systemic) scleroderma (abbreviated PSS ), is an autoimmune rheumatic disease from the group of connective tissue diseases ( collagenoses ). The main symptoms are the hardening of the skin, especially on the hands and face, and the attack-like reduced blood flow to the fingers or toes, the Raynaud's syndrome . The involvement of internal organs (digestive tract, lungs, heart and kidneys) is possible and largely determines the prognosis.

Systemic sclerosis is incurable, but the course of the disease can be slowed down or stopped with medication and specialized rehabilitation . The former name progressive systemic sclerosis is therefore used less and less. Diagnosis and therapy of scleroderma require special medical experience with these diseases. The research network on systemic sclerosis funded by the Federal Ministry of Education and Research (BMBF) has therefore named clinics and centers in its patient information that have sufficient experience with this disease in Germany (see under web links).

Clinical picture

Scleroderma spreads painlessly per se, but can be accompanied by joint and muscle pain ( arthralgia and myalgia ). The speed of the course of the disease is variable and includes rapid courses, courses over years and self-limiting forms that come to a standstill on their own. Because of the rarity of the disease and the very different course with variable organ involvement, the disease is particularly common in the absence of typical symptoms, e.g. B. difficult to diagnose in the early stages.

Early symptoms of systemic sclerosis are the shortening of the inferior frenulum and Raynaud's syndrome . This leads to edema formation on the hands ("puffy fingers") and feet. The skin becomes rigid (called sclerodactyly on the fingers ) and then atrophies . At this stage, it looks waxy and thin. Finally the hands deform: The fingers remain fixed in the bent position (claw hand) and are greatly narrowed (Madonna fingers). Sometimes open areas ( ulcerations ) occur on the skin, which can be extremely painful and in some cases heal so poorly that amputations on fingers or toes are necessary. The death of the skin on the fingertip is also known as rat bite necrosis . Characteristic symptoms in the further course are the mask face with rigid facial expressions, microstomy (the mouth can no longer be opened wide) and problems with the eyelid closure. Radially arranged folds around the mouth are known as the tobacco pouch mouth.

Due to nerve damage, the peristalsis of the gastrointestinal tract can be disturbed; many patients suffer from heartburn because zurückfließendem gastric juice ( reflux ) . By hardening of the lung itself can tidal volume decrease also is gas exchange disturbed. The loss of pulmonary vessels increases blood pressure in the pulmonary circulation ( pulmonary arterial hypertension ) , which puts stress on the right heart and damages it in the long term ( cor pulmonale ) . In addition, by exudation to pleural effusions come. The heart can also be directly affected by sclerosis. All of these processes limit physical performance. The risk of pneumonia and heart attack is increased. The kidney, which is responsible for half of all deaths, is also prognostically important.

to form

If the trunk, upper arms or thighs are affected, one speaks of diffuse , otherwise of limited systemic sclerosis . The so-called CREST syndrome ( calcium deposits in the skin , Raynaud's syndrome, esophageal involvement, sclerodactyly, telangiectasia ) is a prototypical form of limited systemic sclerosis and is equated with this by some authors. Thibièrge-Weissenbach syndrome is a less favorable form .

The diffuse form progresses faster and more frequently in a burst form and affects internal organs earlier. The limited form typically begins on the hands and spreads towards the trunk (centripetal) ; high blood pressure in the pulmonary circulation is more common.

The circumscribed scleroderma , also called morphea (morphea), must be clearly differentiated from systemic sclerosis . This is a dermatological clinical picture that never affects the hands or internal organs. In contrast to systemic sclerosis, the hardening of the skin is limited to circumscribed areas and life expectancy is not reduced.

causes

The cause of scleroderma is not exactly known. Genetic factors and pathological autoimmune processes have been proven. The diffuse form is associated with the genetic variant HLA- DR5, the limited with HLA-DR1, HLA-DR4 and HLA-DR8. Stimulating autoantibodies against the receptor of the growth factor platelet-derived growth factor (PDGF) may be the cause of the disease. An association with cancer has also been observed. About 2 to 50 out of 100,000 people fall ill, mostly between the ages of 50 and 60. Women are about three to four times more likely to be affected than men. One reckons with around 1 to 2 new cases per 100,000 people / year.

Diagnosis

In the laboratory, antinuclear antibodies (ANA) can be detected in 90% of cases . If the antinuclear antibodies are differentiated more precisely, anti-SCL 70 is found in 40% of the diffuse courses and anti-centromere antibodies in 70% of the limited courses . The capillary microscopy of the nail fold can quickly and easily detect changes in the smallest vessels. If the skin findings are unclear, a biopsy can bring clarity. In the x-ray of the hands, calcium deposits may be visible in the skin or broken bones on the phalanges of the fingers.

Kidney involvement is monitored by measuring creatinine in the blood and protein excretion in the urine . Computed tomography and lung function testing with diffusion testing are suitable for detecting and observing pulmonary fibrosis . Pulmonary hypertension can be shown indirectly on echocardiography ; The right heart catheter is used to secure the diagnosis .

therapy

A cure is not yet possible; the therapy is individually oriented to the symptoms and organ involvement present. Non-drug measures to avoid contractures and vacancies include physiotherapy , occupational therapy , massage, and phototherapy (UVA-1, PUVA , photopheresis ). Avoiding the cold or wearing (heated) gloves reduces the frequency of Raynaud's symptoms . Beta blockers (blood pressure drugs that constrict blood vessels) should be avoided, whereas calcium antagonists of the nifedipine type (blood pressure drugs that dilate blood vessels ) are beneficial. It is imperative to quit smoking to improve blood flow and reduce cardiovascular risk. ACE inhibitors (also blood pressure drugs) protect the kidneys.

Against the pulmonary hypertension can, inter alia, endothelin receptor antagonists (. E.g., bosentan ), prostacyclin - analogues (eg. , Iloprost ), and PDE-5 inhibitors ( sildenafil , tadalafil ) are used. Bosentan is taken as a tablet and is also useful for preventing vacancies. Prostacyclin analogues and PDE-5 inhibitors are helpful against acute ulceration and are also used in severe Raynaud's symptoms.

Fibrosis of the skin and lungs can be favorably influenced by immunosuppressants . For example, MTX is used ; Mycophenolate mofetil or cyclophosphamide as shock therapy, especially when the disease is active in the lungs . In the past, high doses and long-term treatment with glucocorticoids were often used , but we now know that this can trigger life-threatening renal crises. Glucocorticoids are therefore only used briefly and in low doses in the early oedematous phase of the disease. The use of biologics such as rituximab or tocilizumab is not established.

In March 2018, the Food and Drug Administration (FDA) granted the active ingredient nintedanib for the treatment of scleroderma with interstitial lung disease an accelerated approval process ( i.e. Fast Track ).

An autologous stem cell transplant can significantly increase survival, but it is itself life-threatening, especially for patients in whom vital organs are already damaged. Patients at the onset of the disease who still have little organ damage, but who are expected to experience an unfavorable course of the disease, are therefore particularly suitable.

forecast

The overall prognosis is not primarily determined by the development of symptoms and findings in the individual affected body regions. The courses can be very difficult to assess. Fulminant courses can lead to death within a few months. In women, the course is more favorable than in men.

See also

literature

Web links

Individual evidence

  1. ↑ Berthold Jany, Tobias Welte: Pleural effusion in adults - causes, diagnosis and therapy. In: Deutsches Ärzteblatt. Volume 116, No. 21, (May) 2019, pp. 377-385, here: p. 379.
  2. ↑ a b c d e f Gerd Herold and colleagues: Internal Medicine 2019 . Self-published, Cologne 2018, ISBN 978-3-9814660-8-9 , p. 681-683 .
  3. ^ Theuma-online
  4. ↑ SS Baroni et al .: Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. In: N Engl J Med. Volume 354, 2006, pp. 2667-2676.
  5. ↑ J. Varga, D. Abraham: Systemic sclerosis: a prototypic multisystem fibrotic disorder. In: Journal of Investigative Dermatology . Volume 117, 2007, pp. 557-567.
  6. ^ Association of the autoimmune disease scleroderma with an immunologic response to cancer. In: Science 2013. doi: 10.1126 / science.1246886 .
  7. ↑ FDA grants Fast Track designation to nintedanib for the treatment of systemic sclerosis with associated interstitial lung disease , PM Boehringer Ingelheim, March 19, 2018, accessed on March 19, 2018