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Scleroderma

Scleroderma is a chronic disease that affects the skin along with many organ systems.


Presentation

Scleroderma involves multiple systems. Limited cutaneous systemic sclerosis was earlier described as the CREST syndrome which included calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly and telangiectasis.

Scleroderma leads to tightening and hardening of the skin with beaklike facial feature and lack of wrinkles. It also leads to digital ulceration, loss of skin creases and contractures. Hypopigmented or hyperpigmented patches are seen on the skin.

It affects the vascular system and Raynaud’s phenomenon is seen as the first presenting symptom. Other symptoms include healed pitting ulcers in the fingers tips and telangiectasis. It also affects the gastrointestinal system and causes gastroesophageal reflux.

Respiratory affections are presented in the form of increasing dyspnea, pulmonary hypertension leading to chest pain and dry persistent cough suggestive of restricted lung disease. It also causes weakness and pains in the joints and muscles with contractures which restricts the range of movement of the joints [17].

The cardiovascular system presents with dyspnea caused by pericardial effusion or congestive heart failure or myocardial fibrosis. The other symptoms include sicca syndrome with poor dentition.

It also causes renal complaints like renal hypertension, renal crisis or renal insufficiency. Neurologic affections include facial pain and reduced sensations due to trigeminal neuralgia. One can suffer from carpel tunnel sensory neuropathy causing paresthesia and weakness of the hand.

Patients with diffuse systemic sclerosis may suffer from oropharyngeal and oesophageal cancers [18] [19] [20].

Raynaud Phenomenon
  • Raynaud’s phenomenon is a common condition. Most people with Raynaud’s phenomenon will NOT develop scleroderma. There are two types of Raynaud’s phenomenon: 1.[hopkinsscleroderma.org]
  • To avoid raynaud’s phenomenon one must avoid exposure to cold. Wounds or injuries must be protected from contamination.[symptoma.com]
  • Other treatments for specific symptoms may include: Treatments to improve Raynaud phenomenon. Medicines for heartburn or swallowing problems, such as omeprazole.[nlm.nih.gov]
  • OBJECTIVE: There are disorders that can cause hardening and tightening of skin and mimic scleroderma but are rarely associated with Raynaud phenomenon, sclerodactyly, and autoantibodies in the serum, features specific to scleroderma/systemic sclerosis[ncbi.nlm.nih.gov]
Food Intolerance
  • By RONI CARYN RABIN Ask Well Photo Credit Can You Get Over a Food Intolerance? Foods most often associated with intolerances were chocolate, food additives, citrus fruits, fish, shellfish, milk, cheese, eggs and nuts.[nytimes.com]
Periodontitis
  • Abstract Systemic Scleroderma (SSc) is an autoimmune disease that affects connective tissue, resulting in hardening skin, reduced vascular perfusion, gingival fibrosis, enlarged periodontal ligament, xerostomia, and trigeminal neuralgia.[ncbi.nlm.nih.gov]
  • […] fibrosis Eyes, ears, nose, and throat manifestations Patients may present with the following: Sicca syndrome Poor dentition secondary to sicca syndrome Loosening of dentition caused by alterations in the tooth suspensory ligament and thickening of the periodontal[emedicine.medscape.com]
Insomnia
  • By ANAHAD O’CONNOR Photo Credit Gracia Lam Personal Health Insomnia Can Kill You Chronic insomnia is linked to an increased risk of developing hypertension, Type 2 diabetes, heart attack, depression, anxiety and premature death. By JANE E.[nytimes.com]

Workup

Classical scleroderma manifests as thickening of the skin, Raynaud’s phenomenon, changes in nail-fold capillaries and anti-nuclear antibodies with a speckled or centromere pattern and nucleolar pattern which though uncommon are specific for scleroderma.

Atypical scleroderma may show any of the above changes without any skin symptoms or only with finger swelling.

Pulmonary function test helps detect early fibrotic changes, alveolitis and pulmonary hypertension. Active lung inflammation can be assessed by bronchoscopy with bronchoalveolar lavage.
HRCT scan is performed to check pulmonary involvement.

Extremity radiography might reveal calcinosis and/or resorption of the distal tufts of fingers and toes.

Echocardiography evaluates pulmonary artery pressure and checks for septal fibrosis or pericardial effusions. If the pulmonary artery pressure is high, then right-heart catheterization is performed to diagnose pulmonary hypertension.

Arrythmias and conduction defects are detected by performing 24-hour ambulatory Holter monitoring.

The gastrointestinal system is evaluated by performing esophago-gastro-duodenoscopy, esophageal manometry and pH monitoring studies.

Polyps
  • Examination revealed cervicitis with a benign endometric polyp, cholecystolithiasis, borderline pulmonary hypertension, and a hormonally inactive suprarenal adenoma. She was given prednisone 40 mg/day and penicillamine with effect.[ncbi.nlm.nih.gov]

Treatment

There is no cure for scleroderma because as of now there is no technique to stop collagen overproduction. One can obtain some measure of relief by various treatments.

Numerous experimental drugs or interventions like interferon-gamma, cyclophosphamide, mycophenolate mofetil, D-penicillamine, photopheresis, allogeneic bone marrow transplantation [21] are used to treat skin thickening. Proteinuria is commonly seen in patients who are receiving D-penicillamine as treatment for scleroderma.

Raynaud’s phenomenon is treated with vasodilators like alpha blockers, calcium channel blockers, local nitrates, angiotensin II receptor inhibitors, serotonin receptor antagonists, statins, etc.

Digital ulcers are treated with phosphodieterase 5 inhibitors or iloprost or with bosentan. Sildenafil is effective and well tolerated by patients with primary Raynaud’s phenomenon and it is also approved to treat pulmonary hypertension [22] [23]. Endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostanoids are used to treat pulmonary arterial hypertension.

Gatrointestinal symptoms are treated with H2 blockers, proton pump inhibitors, reflux and aspiration precautions, octreotide, prokinetic agents, and laxatives. Patients are advised to take smaller meals.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonist are used for treating renal diseases.

Immunosuppressants used in the treatment like cyclophosphamide, azathioprine, mycophenolate, methotrexate, intravenous immunoglobulin, sirolimus, alefacept, rituximab, and tyrosine kinase inhibitors like imatinib, dasatinib and nilotinib.
Pruritus can be managed with moisturizers, tricyclic antidepressants (TCAs), histamine 1 (H1) and histamine 2 (H2) blockers, and trazodone.

Arthralgias are controlled with acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs). Severe flexion contractures may need correction surgery.

Prognosis

In patients with scleroderma, the 5 year survival rate is about 85% while the 10 year survival rate is about 70% [11]. Patients with limited affections will have an approximate 60–70% of 10 year survival rate. In patients with widespread affections, the 10 year survival rate reduces to about 20%. The prognosis is not favourable in patients who are younger at age or suffer from anemia or have a high erythrocyte sedimentation rate (ESR). In cases where there is rapid progress of the disease or widespread extent, the prognosis is not favorable.

Patients with scleroderma can experience complications like pulmonary hypertension, pulmonary fibrosis or renal crisis which can be fatal [2]. Cancer of lungs, liver or bladder and cardiovascular diseases are commonly seen among those suffering from scleroderma [12] [13] [14] [15] [16].

Etiology

The exact cause of scleroderma is not known [2]. It is considered as an autoimmune disorder [2]. Studies suggest the role of genetic and environmental factors in causing scleroderma. Certain mutations in the HLA gene are said to be related to scleroderma [3] [4]. Environmental factors like silica, aromatic and chlorinated solvents, benzene, ketones, epoxy resins, radiations are factors known to contribute to increasing scleroderma [3] [4] [5] [6] [7].

Certain pathologic mechanisms like fibroblast activation, cellular and humoral immunologic derangement and endothelial cell injury are involved. Drugs like bleomycin and pentazocine may contribute to scleroderma.

Epidemiology

Scleroderma is found to affect women more than men, the ratio being 4 to 9: 1 [2]. It manifests mainly between the age group of 20 to 50 years, though it can affect any age group. Asians are less affected comparatively [2] [8] [9].

The incidence is about 10 times higher among African Americans as compared to Native Americans. In the United States, the incidence is 19 cases per million population annually, and the prevalence is approximately 240 cases per million population.

Sex distribution
Age distribution

Pathophysiology

Scleroderma affects many organ systems but mainly the skin, the gastrointestinal tract, respiratory, cardiovascular, renal and genitourinary systems and the vasculature. The pathophysiology of scleroderma involves alterations at the level of vasculature like endothelial cell damage and apoptosis causing vascular leakiness presenting initially as tissue oedema.

Anti-endothelin cell antibodies cause impaired angiogenesis and impaired vasculogenesis which increases the vascular damage.
Cytokines and growth factors help generate myofibroblasts from fibroblasts. Studies of patients with scleroderma show presence of dysregulated transforming growth factor β in fibroblasts and myo-fibroblasts. These lead to increased collagen and other protein deposition causing fibrosis. Extracellular matrix production is increased by IL-6 and TGF-β produced by B cells. Endothelin signalling has also been implicated in the pathophysiology of the fibrosis [10].

Prevention

Patients suffering from scleroderma are advised to maintain the core body temperature to minimize chances of Raynaud’s phenomenon. They must avoid large doses of vitamin C as it accelerates collagen formations and deposition. Skin wounds caused by ischemic lesions or calcinosis must be protected from contamination.

In order to avoid contractures or minimise them, one must undergo regular physiotherapy. Nicotine worsens scleroderma and hence, patients must stop smoking. Patients must avoid exposure to cold weather to prevent any circulatory problems. In cases of gastrointestinal tract symptoms, one must eat small but frequent meals.

Summary

Scleroderma is a word of Greek origin. ‘Skleros’ means hard or indurated and ‘derma’ means skin. It was originally defined by Hippocrates as thickened skin [1]. In 1945, Robert Goetz described it as progressive systemic sclerosis to indicate its systemic affections and defined it as a gradually progressing disease.

Scleroderma or systemic sclerosis is characterized by skin induration and thickening along with tissue fibrosis and chronic inflammatory penetration in various visceral organs, fibro-proliferative vasculopathy, and humoral and cellular immune alterations.

Patient Information

Systemic sclerosis is a multi-organ, chronic disease that affects almost all systems. It mainly affects the skin causing tightening and hardening of the skin. It also involves the gastrointestinal tract, the respiratory system, kidneys, the heart, genitourinary systems and the vasculature. It also causes pain, swelling and contractures of the musculoskeletal system.

It is supposed to be an autoimmune disorder where one’s own immune system harms the tissues of the body. Genetic and environmental factors are also considered to play a role in the same.

For patients with minimal spread, the 10-year survival rates are 60-70% and for those with widespread disease, the 10-year survival rates are only 20%.

At the level of the skin, it causes fingers to turn blue or white in cold temperature called as Raynaud’s phenomenon, thickening and hardening of the skin, ulcers on the tips of fingers and toes and facial mask-like look. It causes joint pains, stiffness, weakness of muscles, and contractures. It also affects the lungs causing breathlessness and high blood pressure in the lungs. In the gastric system it causes acid reflux, constipation or diarrhoea. It can lead to kidney damage and failure. It also causes affections of the nervous system.

There is no specific treatment. Treatment is aimed at controlling the symptoms and preventing further complications. Medicines normally used are immunosuppressants, corticosteroids, NSAIDs, Antacids, Anti-hypertensives etc. Surgeries may be required for contractures. Patients must avoid smoking as nicotine worsens scleroderma. To avoid raynaud’s phenomenon one must avoid exposure to cold. Wounds or injuries must be protected from contamination.

References

Article

  1. David M. A case of scleroderma mentioned by Hippocrates in his aphorisms. Korot. 1981;8(1-2):61-3.
  2. Jimenez SA, Cronin PM, Koenig AS, O'Brien MS, Castro SV. Scleroderma. In Varga, J; Talavera, F; Goldberg, E; Mechaber, AJ; Diamond, HS. 15 February 2012. Medscape Reference. WebMD. Retrieved 5 March 2014.
  3. Balbir-Gurman A, Braun-Moscovici Y. Scleroderma – New aspects in pathogenesis and treatment. Best Pract Res Clin Rheumatol. 2012 Feb ;26 (1): 13–24.
  4. Greenblatt MB, Aliprantis AO. The immune pathogenesis of scleroderma: context is everything. Curr Rheumatol Rep. 2013 Jan;15 (1): 297.
  5. Barnes J, Mayes MD. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol. 2012 Mar ;24 (2): 165–70.
  6. Dospinescu P, Jones GT, Basu N. Environmental risk factors in systemic sclerosis. Curr Opin Rheumatol. 2013 March ;25 (2): 179–83.
  7. Marie I, Gehanno JF, Bubenheim M, Duval-Modeste AB, et al. Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature. Autoimmun Rev. 2014 Feb;13 (2): 151–6.
  8. Hajj-ali, RA. Systemic Sclerosis. Merck Manual Professional. Merck Sharp & Dohme Corp. 
  9. Gelber AC, Manno RL, Shah AA, Woods A, et al. Race and association with disease manifestations and mortality in scleroderma: a 20-year experience at the Johns Hopkins Scleroderma Center and review of the literature. Medicine (Baltimore). 2013 Jul;92 (4): 191–205.
  10. Leask A. The role of endothelin-1 signaling in the fibrosis observed in systemic sclerosis. Pharmacol Res. 2011 Jun ;63 (6): 502–3.
  11. Sticherling M. Systemic sclerosis-dermatological aspects. Part 1: Pathogenesis, epidemiology, clinical findings. J Dtsch Dermatol Ges. 2012 Oct;10 (10): 705–18; quiz 716.
  12. Ngian GS, Sahhar J, Wicks IP, Van Doornum S. Cardiovascular disease in systemic sclerosis--an emerging association? Arthritis Res Ther. 2011 Aug;13 (4): 237.
  13. Szekanecz É, Szamosi S, Horváth Á, Németh Á, et al. Malignancies associated with systemic sclerosis. Autoimmun Rev. 2012 Oct; 11 (12): 852–5.
  14. Shah AA, Rosen A. Cancer and systemic sclerosis: novel insights into pathogenesis and clinical implications. Curr Opin Rheumatol. 2011 Nov;23 (6): 530–5.
  15. Onishi A, Sugiyama D, Kumagai S, Morinobu A. Cancer incidence in systemic sclerosis: meta-analysis of population-based cohort studies. Arthritis Rheum. 2013 Jul;65 (7): 1913–21.
  16. Bonifazi M, Tramacere I, Pomponio G, Gabrielli B, et al. Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies. Rheumatology (oxford). 2013 Jan; 52 (1): 143–154.
  17. Pope JE. Musculoskeletal involvement in scleroderma. Rheum Dis Clin North Am. 2003 May;29(2):391-408.
  18. Derk CT, Rasheed M, Spiegel JR, et al. Increased incidence of carcinoma of the tongue in patients with systemic sclerosis. J Rheumatol. 2005 Apr;32(4):637-41.
  19. Derk CT, Rasheed M, Artlett CM, et al. A cohort study of cancer incidence in systemic sclerosis. J Rheumatol. 2006 Jun;33(6):1113-6.
  20. Wooten M. Systemic sclerosis and malignancy: a review of the literature. South Med J. 2008 Jan;101(1):59-62.
  21. Nash RA, McSweeney PA, Nelson JL, et al. Allogeneic marrow transplantation in patients with severe systemic sclerosis: resolution of dermal fibrosis. Arthritis Rheum. 2006 Jun;54(6):1982-6.
  22. Fries R, Shariat K, von Wilmowsky et al. Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005 Nov 8;112(19):2980-5.
  23. Badesch DB, Hill NS, Burgess G, et al. Sildenafil for pulmonary arterial hypertension associated with connective tissue disease. J Rheumatol. 2007 Dec;34(12):2417-22.

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Last updated: 2019-07-11 22:28