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].

• Anemia

  He underwent laser ablation of his gastral ectasias and was started on iron supplementation for anemia due to his chronic gastrointestinal bleeding. Acknowledgement Thank you to Dr. [stanfordmedicine25.stanford.edu]

  If the condition affects the internal organs, it is called systemic sclerosis (SSc) and can lead to serious complications such as trouble breathing, chest pain, bleeding and anemia. [hss.edu]

  Anemia can also develop with scleroderma, which may contribute to the severity of these symptoms. [verywellhealth.com]

  Anemia in scleroderma can be due to various causes such as chronic disease, iron deficiency by gastrointestinal bleeding, B12 deficiency and folic acid deficiency. ANA test (IIF Hep-2) is positive in 60 –90%. [indonesianjournalofclinicalpathology.org]

  These include dysphagia, odynophagia (painful swallowing), nausea and vomiting, anemia, weight loss and blood in the stool. [uclahealth.org]

• Raynaud Syndrome

  Systemic scleroderma can manifest itself in pulmonary fibrosis, raynaud's syndrome, digestive system telangiectasias, renal hypertension and/or pulmonary hypertension. A chronic multi-system disorder of connective tissue. [icd10data.com]

  People with limited systemic sclerosis have often lived with Raynaud's syndrome for a long time. [sruk.co.uk]

  […] phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome (disorder) Calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia syndrome (disorder) Crest syndrome Lipodermatosclerosis Lung [icd9data.com]

  Systemic scleroderma can manifest itself in pulmonary fibrosis, Raynaud's syndrome, digestive system telangiectasias, renal hypertension and/or pulmonary hypertension. Definition (MSH) A chronic multi-system disorder of CONNECTIVE TISSUE. [fpnotebook.com]

  Puffy fingers in Raynaud's syndrome patients. Differential diagnosis [ 5 ] Several other diseases can present in a similar way to SSc, including: Raynaud's phenomenon from other causes. Vibration injury. [patient.co.uk]

• Turkish

  Turkish Journal of Hematology, vol. 30, no. 1, 2013, p. 32+. Accessed 21 Apr. 2020. Gale Document Number: GALE|A345620963 [go.gale.com]

  […] delivery worldwide Order Status Wishlist Sign in/Join 0 Advanced Search Free delivery worldwide Free delivery worldwide Shop by category Categories Children's Age Ranges Bestsellers Coming Soon New Releases Bargain Shop English 0,00 € 0 Home Paperback Turkish [bookdepository.com]

• Vascular Disease

  English If you have collagen vascular disease such as scleroderma or systemic lupus erythematosus Last Update: 2012-04-12 Usage Frequency: 1 Quality: Reference: Wikipedia Slovak artritída, systémový lupus erythematosus, sklerodermia, Sjögrenov syndróm [mymemory.translated.net]

  Systemic sclerosis (SSc) is classified as a collagen vascular disease, but its most catastrophic involvement is in the lungs. [bumc.bu.edu]

  Clinical cardiovascular disease Peripheral vascular disease Peripheral vascular disease in patients with SSc has been reported in uncontrolled observational studies that used techniques such as the ankle brachial pressure index (ABPI), lower-limb Doppler [doi.org]

  Telangiectasias tend to be more numerous in people with other scleroderma related vascular disease (i.e., pulmonary arterial hypertension). [en.wikipedia.org]

• Heart Disease

  After establishing the diagnosis of ssSSc and starting immunosuppression, the ocular disease improved, while the lung and heart diseases remained stable. [ncbi.nlm.nih.gov]

  However, like diabetes, high blood pressure, heart disease, and psoriasis, scleroderma can be treated and the symptoms managed. [hopkinsscleroderma.org]

  Twenty-eight per cent of deaths were due to causes unrelated to systemic sclerosis, most commonly cancer and ischaemic heart disease, and in older patients This content is only available as a PDF. © Oxford University Press Related articles in PubMed [qjmed.oxfordjournals.org]

  Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation 131, e29–e322 (2015). 23. Ferdinand, K. C. Coronary artery disease in minority racial and ethnic groups in the United States. Am. J. [doi.org]

• Skin Disease

  SCLERO.ORG Overview of Autoimmune and Skin Diseases Scleroderma is a rare autoimmune disease that often affects the skin. It is also a form of arthritis and a connective tissue disease. Autoimmune Directory. [sclero.org]

  The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out [web.archive.org]

  Skin No one agent has proven effective in the treatment of scleroderma skin disease. When the patient has mild skin disease limited to the face and fingers, there is no indication to use systemic therapy. [mayoclinicproceedings.org]

  […] and Musculoskeletal and Skin Diseases) [medlineplus.gov]

• Muscle Weakness

  Arthritis and muscle weakness, including: Pain, stiffness and swelling General fatigue Muscle weakness, often in your upper arms or thighs Digestive problems including poor function of your esophagus and bowels. [ucsfhealth.org]

  RVLS freewall results were lower in the JSSc patients with interstitial lung fibrosis, arthritis, muscle weakness, weight loss, and anti-scl 70 antibodies than in the JSSc patients without these variables. We found that a GCS of [ncbi.nlm.nih.gov]

  Scleroderma can have inconvenient and dangerous side effects related to the autoimmune condition, such as high blood pressure, damage to blood vessels, shortness of breath and other breathing problems, difficulty swallowing, acid reflux, muscle weakness [house.wikia.com]

  weakness digestive problems kidney problems A Word From Verywell If you suspect or have been diagnosed with scleroderma or systemic sclerosis, getting a proper diagnosis and learning more about your condition can help you better manage it. [verywellhealth.com]

  After reduction of steroid doses, increased CPK-AST-LDH values and muscle weakness were observed. As a result of this intravenous immunoglobulin (400 mg / kg / day) was added. [causapedia.com]

• Tendon Friction Rub

  OBJECTIVE: Palpable tendon friction rubs (TFRs) in systemic sclerosis (SSc; scleroderma) have been associated with diffuse skin thickening, increased disability, and poor survival. [ncbi.nlm.nih.gov]

  friction rubs Nailfold capillary dilation and capillary drop-out Early and significant incidence of renal, interstitial lung, diffuse gastrointestinal,and myocardial disease Anti-Scl-70 (30 percent) and anti-RNA polymerase-I, II, or III (12 to 15 percent [uofmhealth.org]

  Tendon friction rubs are found almost exclusively in diffuse systemic sclerosis and may be detected as the tendon is moved actively or passively. [emedicine.medscape.com]

  Diffuse scleroderma has the following features: Onset of Raynaud’s within 1 year of onset of skin changes (puffy or hidebound skin) Truncal and acral skin involvement Presence of tendon friction rubs Early and significant incidence of interstitial lung [endocrinologyadvisor.com]

• Hand Stiffness

  Stiffness and swelling Many scleroderma patients have hand stiffness and swelling that is worse in the morning and improves with activity throughout their day. [creakyjoints.org]

  stiffness (81–59%), joint pain (81–64%), and sleep disorders (76–59%). [intechopen.com]

• Swelling of Hand

  Other early symptoms include: Fatigue Swelling of hands and feet Numbness of hands and feet Shiny skin and disappearance of skin folds Ulcers on the fingers Calcium deposits on the fingers Joint inflammation Joints tightening into bent position Muscle [dmso.org]

• Suggestibility

  News, syndicated NORD Opens COVID-19 Financial Aid Program for Rare Disease Community News Blocking CCR2 Protein May Ease Scleroderma Symptoms, Mouse Study Suggests News Horizon Plans to Advance Oral dcSSc Therapy in Trials, Having Acquired Curzion News [sclerodermanews.com]

  In general, the demographic and clinical characteristics of the ssSSc patients suggest that they are similar to those with diffuse or limited form of the disease. [ncbi.nlm.nih.gov]

  A unique nucleolar RNA polymerase III expression pattern has been identified in malignant tissue from these scleroderma patients suggesting that autoantigen expression in the cancer and the autoantibody response are associated. [doi.org]

• Dyspareunia

  Difficult or painful sexual intercourse (dyspareunia). Respiratory/lungs Progressive shortness of breath (dyspnea) and pain in the chest wall (precordial chest pain) and a persistent dry cough. Renal Hypertension or the kidneys not working well. [sclerodermasociety.co.uk]

  Women may have dyspareunia. Investigations General blood tests FBC. ESR and CRP. Baseline biochemistry and renal function. Autoantibodies [ 6, 7 ] These are now considered crucial for classification. [patient.co.uk]

  Genitourinary: erectile dysfunction, dyspareunia, kidney problems, or kidney failure. Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis and weight loss. [en.wikipedia.org]

  Genitourinary manifestations Patients with systemic sclerosis may present with the following: Bladder fibrosis Dyspareunia (if introitus is affected) Vaginal narrowing, dryness and pain caused by vaginal fibrosis Eyes, ears, nose, and throat manifestations [emedicine.medscape.com]

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.

• Pericardial Effusion

  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. [symptoma.com]

  effusion (excess fluid around the heart) that required pericardial window. [clinicaltrials.gov]

  Pericarditis or pericardial effusion ; these may cause cardiac impairment or congestive cardiac failure. Arrhythmias and conduction defects (including bradyarrhythmias and tachyarrhythmias). Endocarditis. [patient.co.uk]

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.

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].

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.

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.

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].

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.

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.

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.

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