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`!Scleroderma`! is a group of `F33f`_`[autoimmune diseases`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Autoimmune_disease]`_`f that may result in changes to the `F33f`_`[skin`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Human_skin]`_`f, `F33f`_`[blood vessels`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Blood_vessels]`_`f, `F33f`_`[muscles`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Muscles]`_`f, and `F33f`_`[internal organs`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Internal_organ]`_`f.`:cite-ref-gard2017-2-3[`F5bf`_`[2`#cite-note-gard2017-2]`_`f]`:cite-ref-nih2016-6-1[`F5bf`_`[6`#cite-note-nih2016-6]`_`f]`:cite-ref-8[`F5bf`_`[8`#cite-note-8]`_`f] The disease can be either localized to the skin or involve other organs, as well.`:cite-ref-gard2017-2-4[`F5bf`_`[2`#cite-note-gard2017-2]`_`f] Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure.`:cite-ref-nord2007-1-3[`F5bf`_`[1`#cite-note-nord2007-1]`_`f] One form of the condition, known as `F33f`_`[CREST syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=CREST_syndrome]`_`f, classically results in `F33f`_`[calcium deposits`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Calcinosis]`_`f, `F33f`_`[Raynaud's syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Raynaud's_syndrome]`_`f, `F33f`_`[esophageal`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Esophagus]`_`f problems, `F33f`_`[thickening of the skin of the fingers and toes`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Sclerodactyly]`_`f, and `F33f`_`[areas of small, dilated blood vessels`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Telangiectasia]`_`f.`:cite-ref-nord2007-1-4[`F5bf`_`[1`#cite-note-nord2007-1]`_`f]

The cause is unknown, but it may be due to an abnormal immune response.`:cite-ref-gard2017-2-5[`F5bf`_`[2`#cite-note-gard2017-2]`_`f] Risk factors include family history, certain `F33f`_`[genetic`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Genetics]`_`f factors, and exposure to `F33f`_`[silica`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Silica]`_`f.`:cite-ref-har2018-3-3[`F5bf`_`[3`#cite-note-har2018-3]`_`f]`:cite-ref-bar2012-4-1[`F5bf`_`[4`#cite-note-bar2012-4]`_`f]`:cite-ref-gre2013-5-1[`F5bf`_`[5`#cite-note-gre2013-5]`_`f] The underlying mechanism involves the abnormal growth of `F33f`_`[connective tissue`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Connective_tissue]`_`f, which is believed to be the result of the immune system attacking healthy tissues.`:cite-ref-nih2016-6-2[`F5bf`_`[6`#cite-note-nih2016-6]`_`f] Diagnosis is based on symptoms, supported by a `F33f`_`[skin biopsy`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Skin_biopsy]`_`f or blood tests.`:cite-ref-nih2016-6-3[`F5bf`_`[6`#cite-note-nih2016-6]`_`f]

While no cure is known, treatment may improve symptoms.`:cite-ref-gard2017-2-6[`F5bf`_`[2`#cite-note-gard2017-2]`_`f] Medications used include `F33f`_`[corticosteroids`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Corticosteroids]`_`f, `F33f`_`[methotrexate`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Methotrexate]`_`f, and `F33f`_`[non-steroidal anti-inflammatory drugs`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Non-steroidal_anti-inflammatory_drugs]`_`f (NSAIDs).`:cite-ref-gard2017-2-7[`F5bf`_`[2`#cite-note-gard2017-2]`_`f] Outcome depends on the extent of disease.`:cite-ref-har2018-3-4[`F5bf`_`[3`#cite-note-har2018-3]`_`f] Those with localized disease generally have a normal `F33f`_`[life expectancy`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Life_expectancy]`_`f.`:cite-ref-un2006-7-1[`F5bf`_`[7`#cite-note-un2006-7]`_`f] In those with systemic disease, life expectancy can be affected, and this varies based on subtype.`:cite-ref-har2018-3-5[`F5bf`_`[3`#cite-note-har2018-3]`_`f] Death is often due to lung, gastrointestinal, or heart complications.`:cite-ref-har2018-3-6[`F5bf`_`[3`#cite-note-har2018-3]`_`f]

About three per 100,000 people per year develop the systemic form.`:cite-ref-har2018-3-7[`F5bf`_`[3`#cite-note-har2018-3]`_`f] The condition most often begins in middle age.`:cite-ref-nord2007-1-5[`F5bf`_`[1`#cite-note-nord2007-1]`_`f] Women are more often affected than men.`:cite-ref-nord2007-1-6[`F5bf`_`[1`#cite-note-nord2007-1]`_`f] Scleroderma symptoms were first described in 1753 by Carlo Curzio`:cite-ref-9[`F5bf`_`[9`#cite-note-9]`_`f] and then well documented in 1842.`:cite-ref-10[`F5bf`_`[10`#cite-note-10]`_`f] The term is from the `F33f`_`[Greek`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Ancient_Greek]`_`f `*skleros`* meaning "hard" and `*derma`* meaning "skin".`:cite-ref-11[`F5bf`_`[11`#cite-note-11]`_`f]`:cite-ref-12[`F5bf`_`[12`#cite-note-12]`_`f]

>>Contents

• `F0af`_`[Signs and symptoms`#signs-and-symptoms]`_`f

• `F0af`_`[Cause`#cause]`_`f

• `F0af`_`[Pathophysiology`#pathophysiology]`_`f

• `F0af`_`[Diagnosis`#diagnosis]`_`f

• `F0af`_`[Differential`#differential]`_`f

• `F0af`_`[Classification`#classification]`_`f

• `F0af`_`[Treatment`#treatment]`_`f

• `F0af`_`[Prognosis`#prognosis]`_`f

• `F0af`_`[Epidemiology`#epidemiology]`_`f

• `F0af`_`[Pregnancy`#pregnancy]`_`f

• `F0af`_`[See also`#see-also]`_`f

• `F0af`_`[References`#references]`_`f

• `F0af`_`[External links`#external-links]`_`f

-─

>>Signs and symptoms

Potential signs and symptoms include:`:cite-ref-mm-13-0[`F5bf`_`[13`#cite-note-mm-13]`_`f]`:cite-ref-pmsr-14-0[`F5bf`_`[14`#cite-note-pmsr-14]`_`f]`:cite-ref-harrison-15-0[`F5bf`_`[15`#cite-note-harrison-15]`_`f]`:cite-ref-16[`F5bf`_`[16`#cite-note-16]`_`f]

• Cardiovascular: `F33f`_`[Raynaud's phenomenon`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Raynaud's_phenomenon]`_`f (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting `F33f`_`[ulcers`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Ulcers]`_`f on the fingertips; skin and mucosal `F33f`_`[telangiectasis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Telangiectasis]`_`f; `F33f`_`[palpitations`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Palpitations]`_`f, irregular heart rate and `F33f`_`[fainting`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Syncope_(medicine)]`_`f due to `F33f`_`[conduction`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Electrical_conduction_system_of_the_heart]`_`f abnormalities, `F33f`_`[hypertension`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Hypertension]`_`f, and `F33f`_`[congestive heart failure`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Congestive_heart_failure]`_`f

• Digestive: `F33f`_`[gastroesophageal reflux disease`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Gastroesophageal_reflux_disease]`_`f, bloating, `F33f`_`[indigestion`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Dyspepsia]`_`f, loss of appetite, `F33f`_`[diarrhoea`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Diarrhoea]`_`f alternating with `F33f`_`[constipation`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Constipation]`_`f, `F33f`_`[sicca syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Sicca_syndrome]`_`f and its complications, `F33f`_`[gastric antral vascular ectasia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Gastric_antral_vascular_ectasia]`_`f, loosening of teeth, and hoarseness (due to acid reflux).

• Pulmonary: progressive worsening of shortness of breath, chest pain (due to `F33f`_`[pulmonary artery hypertension`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pulmonary_artery_hypertension]`_`f), and dry, persistent cough due to `F33f`_`[interstitial lung disease`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Interstitial_lung_disease]`_`f

• Musculoskeletal: `F33f`_`[joint`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Arthralgia]`_`f, `F33f`_`[muscle aches`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Myalgia]`_`f, loss of joint range of motion, `F33f`_`[carpal tunnel syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Carpal_tunnel_syndrome]`_`f, and `F33f`_`[muscle weakness`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Asthenia]`_`f

• Genitourinary: `F33f`_`[erectile dysfunction`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Erectile_dysfunction]`_`f, `F33f`_`[dyspareunia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Dyspareunia]`_`f, kidney problems, or `F33f`_`[kidney failure`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Kidney_failure]`_`f

• Other: facial pain due to `F33f`_`[trigeminal neuralgia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Trigeminal_neuralgia]`_`f, hand `F33f`_`[paresthesias`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Paresthesias]`_`f, headache, `F33f`_`[stroke`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Stroke]`_`f, fatigue, `F33f`_`[calcinosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Calcinosis]`_`f, and weight loss

>>Cause

Scleroderma is caused by genetic and environmental factors.`:cite-ref-bar2012-4-2[`F5bf`_`[4`#cite-note-bar2012-4]`_`f]`:cite-ref-gre2013-5-2[`F5bf`_`[5`#cite-note-gre2013-5]`_`f]`:cite-ref-path12-17-0[`F5bf`_`[17`#cite-note-path12-17]`_`f]`:cite-ref-env13-18-0[`F5bf`_`[18`#cite-note-env13-18]`_`f] Mutations in `F33f`_`[HLA`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Human_leukocyte_antigen]`_`f genes seem to play a crucial role in the `F33f`_`[pathogenesis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pathogenesis]`_`f of some cases; likewise `F33f`_`[silica`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Silica]`_`f, `F33f`_`[aromatic`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Aromatic_hydrocarbon]`_`f and `F33f`_`[chlorinated`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Chlorinated_hydrocarbon]`_`f solvents, `F33f`_`[ketones`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Ketones]`_`f, `F33f`_`[trichloroethylene`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Trichloroethylene]`_`f, `F33f`_`[welding`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Welding]`_`f fumes, and `F33f`_`[white spirits`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Mineral_spirits]`_`f exposure seems to contribute to the condition in a small proportion of affected persons.`:cite-ref-bar2012-4-3[`F5bf`_`[4`#cite-note-bar2012-4]`_`f]`:cite-ref-gre2013-5-3[`F5bf`_`[5`#cite-note-gre2013-5]`_`f]`:cite-ref-path12-17-1[`F5bf`_`[17`#cite-note-path12-17]`_`f]`:cite-ref-env13-18-1[`F5bf`_`[18`#cite-note-env13-18]`_`f]`:cite-ref-19[`F5bf`_`[19`#cite-note-19]`_`f]

>>Pathophysiology

Scleroderma is characterised by increased `F33f`_`[synthesis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Biosynthesis]`_`f of `F33f`_`[collagen`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Collagen]`_`f (leading to the `F33f`_`[sclerosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Sclerosis_(medicine)]`_`f), damage to small blood vessels, activation of `F33f`_`[T lymphocytes`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=T_lymphocytes]`_`f, and production of altered `F33f`_`[connective tissue`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Connective_tissue]`_`f.`:cite-ref-20[`F5bf`_`[20`#cite-note-20]`_`f] Its proposed pathogenesis is the following:`:cite-ref-path11-21-0[`F5bf`_`[21`#cite-note-path11-21]`_`f]`:cite-ref-22[`F5bf`_`[22`#cite-note-22]`_`f]`:cite-ref-23[`F5bf`_`[23`#cite-note-23]`_`f]`:cite-ref-24[`F5bf`_`[24`#cite-note-24]`_`f]`:cite-ref-25[`F5bf`_`[25`#cite-note-25]`_`f]

• It begins with an inciting event at the level of the `F33f`_`[vasculature`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Vasculature]`_`f, probably the `F33f`_`[endothelium`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Endothelium]`_`f. The inciting event is yet to be elucidated, but may be a viral agent, `F33f`_`[oxidative stress`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Oxidative_stress]`_`f, or autoimmune. `F33f`_`[Endothelial cell`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Endothelial_cell]`_`f damage and `F33f`_`[apoptosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Apoptosis]`_`f ensue, leading to the vascular leakiness that manifests in early clinical stages as tissue `F33f`_`[oedema`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Oedema]`_`f. At this stage, it is predominantly a `F33f`_`[Th1`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Th1_cell]`_`f- and `F33f`_`[Th17`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Th17]`_`f-mediated disease.

• After this, the vasculature is further compromised by impaired `F33f`_`[angiogenesis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Angiogenesis]`_`f and impaired `F33f`_`[vasculogenesis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Vasculogenesis]`_`f (fewer endothelial progenitor cells), likely related to the presence of antiendothelial cell antibodies (AECA). Despite this impaired `F33f`_`[angiogenesis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Angiogenesis]`_`f, elevated levels of pro-angiogenic growth factors such as `F33f`_`[PDGF`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Platelet_derived_growth_factor]`_`f and `F33f`_`[VEGF`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Vascular_endothelial_growth_factor]`_`f are often seen in persons with the condition. The balance of `F33f`_`[vasodilation`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Vasodilation]`_`f and vasoconstriction becomes askew, and the net result is vasoconstriction. The damaged endothelium then serves as a point of origin for blood-clot formation and further contributes to `F33f`_`[ischaemia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Ischaemia]`_`f-`F33f`_`[reperfusion injury`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Reperfusion_injury]`_`f and the generation of `F33f`_`[reactive oxygen species`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Reactive_oxygen_species]`_`f. These later stages are characterised by `F33f`_`[Th2`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Th2]`_`f polarity.

• The damaged endothelium upregulates `F33f`_`[adhesion molecules`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Adhesion_molecules]`_`f and `F33f`_`[chemokines`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Chemokine]`_`f to attract `F33f`_`[leucocytes`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Leucocyte]`_`f, which enables the development of innate and adaptive immune responses, including loss of tolerance to various oxidised `F33f`_`[antigens`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Antigens]`_`f, which includes `F33f`_`[topoisomerase I`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Topoisomerase_I]`_`f. `F33f`_`[B cells`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=B_cells]`_`f mature into `F33f`_`[plasma cells`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Plasma_cells]`_`f, which furthers the autoimmune component of the condition. T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue `F33f`_`[fibrosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Fibrosis]`_`f. `F33f`_`[Anti–topoisomerase 1`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Topoisomerase_1]`_`f `F33f`_`[antibodies`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Antibodies]`_`f, in turn, stimulate `F33f`_`[type I interferon`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Type_I_interferon]`_`f production.

• `F33f`_`[Fibroblasts`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Fibroblast]`_`f are recruited and activated by multiple `F33f`_`[cytokines`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Cytokine]`_`f and growth factors to generate `F33f`_`[myofibroblasts`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Myofibroblasts]`_`f. Dysregulated `F33f`_`[transforming growth factor β`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Transforming_growth_factor_β]`_`f (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, `F33f`_`[IL-6`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Interleukin_6]`_`f and TGF-β produced by the B cells decrease collagen degradation and increase `F33f`_`[extracellular matrix`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Extracellular_matrix]`_`f production. `F33f`_`[Endothelin signalling`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Endothelin]`_`f is implicated in the pathophysiology of fibrosis.`:cite-ref-26[`F5bf`_`[26`#cite-note-26]`_`f]

`F33f`_`[Vitamin D`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Vitamin_D]`_`f is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted, and vitamin D is known to play a crucial role in regulating (usually suppressing) the actions of the immune system.`:cite-ref-27[`F5bf`_`[27`#cite-note-27]`_`f]

>>Diagnosis

Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynaud's phenomenon, nail-fold capillary changes, and `F33f`_`[antinuclear antibodies`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Anti-nuclear_antibody]`_`f. Affected individuals may experience systemic organ involvement. No single test for scleroderma works all of the time; hence, diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.`:cite-ref-wmsr-28-0[`F5bf`_`[28`#cite-note-wmsr-28]`_`f]

Laboratory testing can show `F33f`_`[antitopoisomerase antibodies`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Anti-topoisomerase_antibodies]`_`f, like `F33f`_`[anti-scl70`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Anti-scl70]`_`f (causing a diffuse systemic form), or `F33f`_`[anticentromere antibodies`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Anti-centromere_antibodies]`_`f (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.`:cite-ref-msr-29-0[`F5bf`_`[29`#cite-note-msr-29]`_`f] Antidouble-stranded DNA autoantibodies are likely to be present in serum.

>>>Differential

Diseases that are often in the differential include:`:cite-ref-dmsr-30-0[`F5bf`_`[30`#cite-note-dmsr-30]`_`f]

• `F33f`_`[Eosinophilia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Eosinophilia]`_`f is a condition in which too many `F33f`_`[eosinophils`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Eosinophils]`_`f (a type of immune cell that attacks parasites and is involved in certain allergic reactions) are present in the blood.

• `F33f`_`[Eosinophilia-myalgia syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Eosinophilia-myalgia_syndrome]`_`f is a form of eosinophilia caused by `F33f`_`[L-tryptophan`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=L-tryptophan]`_`f supplements.

• `F33f`_`[Eosinophilic fasciitis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Eosinophilic_fasciitis]`_`f affects the connective tissue surrounding skeletal muscles, bones, blood vessels, and nerves in the arms and legs.

• `F33f`_`[Graft-versus-host disease`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Graft-versus-host_disease]`_`f is an autoimmune condition that occurs as a result of bone-marrow transplants in which the immune cells from the transplanted bone marrow attack the host's body.

• `F33f`_`[Mycosis fungoides`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Mycosis_fungoides]`_`f is a type of `F33f`_`[cutaneous T cell lymphoma`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Cutaneous_T_cell_lymphoma]`_`f, a rare cancer that causes rashes all over the body.

• `F33f`_`[Nephrogenic systemic fibrosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Nephrogenic_systemic_fibrosis]`_`f is a condition usually caused by `F33f`_`[kidney failure`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Kidney_failure]`_`f that results in fibrosis (thickening) of the tissues.

• `F33f`_`[Primary biliary cirrhosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Primary_biliary_cirrhosis]`_`f is an autoimmune disease of the liver.

• `F33f`_`[Primary pulmonary hypertension`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Primary_pulmonary_hypertension]`_`f

• `F33f`_`[Complex regional pain syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Complex_regional_pain_syndrome]`_`f

>>>Classification

Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:`:cite-ref-31[`F5bf`_`[31`#cite-note-31]`_`f]

• `F33f`_`[Localised scleroderma`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Localised_scleroderma]`_`f

• `F33f`_`[Localised morphea`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Localised_morphea]`_`f

• `F33f`_`[Morphea-lichen sclerosus et atrophicus overlap`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Morphea-lichen_sclerosus_et_atrophicus_overlap]`_`f

• `F33f`_`[Generalised morphea`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Generalised_morphea]`_`f

• `F33f`_`[Atrophoderma of Pasini and Pierini`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Atrophoderma_of_Pasini_and_Pierini]`_`f

• `F33f`_`[Pansclerotic morphea`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pansclerotic_morphea]`_`f

• `F33f`_`[Morphea profunda`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Morphea_profunda]`_`f

• `F33f`_`[Linear scleroderma`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Linear_scleroderma]`_`f

• `F33f`_`[Systemic scleroderma`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Systemic_scleroderma]`_`f

• `F33f`_`[CREST syndrome`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=CREST_syndrome]`_`f

• `F33f`_`[Progressive systemic sclerosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Progressive_systemic_sclerosis]`_`f

>>Treatment

No cure for scleroderma is known, although relief of symptoms is often achieved; these include treatment of:`:cite-ref-mm-13-1[`F5bf`_`[13`#cite-note-mm-13]`_`f]`:cite-ref-sem-32-0[`F5bf`_`[32`#cite-note-sem-32]`_`f]

• `F33f`_`[Raynaud's phenomenon`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Raynaud's_phenomenon]`_`f with vasodilators such as `F33f`_`[calcium channel blockers`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Calcium_channel_blockers]`_`f, `F33f`_`[alpha blockers`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Alpha_blocker]`_`f, `F33f`_`[serotonin receptor antagonists`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Serotonin_receptor_antagonist]`_`f, `F33f`_`[angiotensin II receptor`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Angiotensin_II_receptor]`_`f inhibitors, `F33f`_`[statins`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Statins]`_`f, local nitrates or `F33f`_`[iloprost`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Iloprost]`_`f

• Digital ulcers with `F33f`_`[phosphodiesterase 5`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Phosphodiesterase_5]`_`f inhibitors (e.g., `F33f`_`[sildenafil`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Sildenafil]`_`f) or `F33f`_`[iloprost`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Iloprost]`_`f

• Prevention of new digital ulcers with `F33f`_`[bosentan`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Bosentan]`_`f

• Malnutrition, secondary to intestinal flora overgrowth with `F33f`_`[tetracycline antibiotics`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Tetracycline_antibiotic]`_`f such as `F33f`_`[tetracycline`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Tetracycline]`_`f

• `F33f`_`[Interstitial lung disease`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Interstitial_lung_disease]`_`f with `F33f`_`[cyclophosphamide`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Cyclophosphamide]`_`f, `F33f`_`[azathioprine`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Azathioprine]`_`f with or without corticosteroids

• `F33f`_`[Pulmonary arterial hypertension`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pulmonary_arterial_hypertension]`_`f with endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostanoids

• Gastrooesophageal reflux disease with antacids or prokinetics

• Kidney crises with `F33f`_`[angiotensin converting enzyme inhibitors`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Angiotensin_converting_enzyme_inhibitor]`_`f and `F33f`_`[angiotensin II receptor antagonists`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Angiotensin_II_receptor_antagonist]`_`f

Systemic `F33f`_`[disease-modifying treatment`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Disease-modifying_treatment]`_`f with immunosuppressants is often used.`:cite-ref-path12-17-2[`F5bf`_`[17`#cite-note-path12-17]`_`f]`:cite-ref-clin13-33-0[`F5bf`_`[33`#cite-note-clin13-33]`_`f]`:cite-ref-mayo-34-0[`F5bf`_`[34`#cite-note-mayo-34]`_`f]`:cite-ref-pol-35-0[`F5bf`_`[35`#cite-note-pol-35]`_`f]`:cite-ref-arch-36-0[`F5bf`_`[36`#cite-note-arch-36]`_`f]`:cite-ref-exp-37-0[`F5bf`_`[37`#cite-note-exp-37]`_`f] Immunosuppressants used in its treatment include `F33f`_`[azathioprine`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Azathioprine]`_`f, `F33f`_`[methotrexate`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Methotrexate]`_`f, `F33f`_`[cyclophosphamide`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Cyclophosphamide]`_`f, `F33f`_`[mycophenolate`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Mycophenolate]`_`f, intravenous `F33f`_`[immunoglobulin`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Immunoglobulin]`_`f, `F33f`_`[rituximab`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Rituximab]`_`f, `F33f`_`[sirolimus`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Sirolimus]`_`f, `F33f`_`[alefacept`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Alefacept]`_`f, and the tyrosine kinase inhibitors, `F33f`_`[imatinib`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Imatinib]`_`f, `F33f`_`[nilotinib`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Nilotinib]`_`f, and `F33f`_`[dasatinib`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Dasatinib]`_`f.`:cite-ref-path12-17-3[`F5bf`_`[17`#cite-note-path12-17]`_`f]`:cite-ref-sem-32-1[`F5bf`_`[32`#cite-note-sem-32]`_`f]`:cite-ref-clin13-33-1[`F5bf`_`[33`#cite-note-clin13-33]`_`f]`:cite-ref-mayo-34-1[`F5bf`_`[34`#cite-note-mayo-34]`_`f]`:cite-ref-pol-35-1[`F5bf`_`[35`#cite-note-pol-35]`_`f]`:cite-ref-arch-36-1[`F5bf`_`[36`#cite-note-arch-36]`_`f]`:cite-ref-exp-37-1[`F5bf`_`[37`#cite-note-exp-37]`_`f]`:cite-ref-38[`F5bf`_`[38`#cite-note-38]`_`f]

Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, `F33f`_`[halofuginone`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Halofuginone]`_`f, `F33f`_`[basiliximab`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Basiliximab]`_`f, `F33f`_`[alemtuzumab`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Alemtuzumab]`_`f, `F33f`_`[abatacept`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Abatacept]`_`f, and `F33f`_`[haematopoietic stem cell transplantation`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Haematopoietic_stem_cell_transplantation]`_`f.`:cite-ref-39[`F5bf`_`[39`#cite-note-39]`_`f]`:cite-ref-40[`F5bf`_`[40`#cite-note-40]`_`f]

| Immunomodulatory agents in the treatment of scleroderma | Immunomodulatory agents in the treatment of scleroderma | Immunomodulatory agents in the treatment of scleroderma | Immunomodulatory agents in the treatment of scleroderma | Immunomodulatory agents in the treatment of scleroderma |

|---|---|---|---|---|

| Alefacept | Monoclonal antibody to inhibit T lymphocyte activation by binding to CD2 portion of human leukocyte function antigen-3 . | IM | B (US) | Malignancies, injection site reactions, blood clots, lymphopenia , hepatotoxicity and infections. |

| Azathioprine | Purine analogue that inhibits lymphocyte proliferation via conversion to mercaptopurine | PO, IV | D (Au) | Myelosuppression and rarely malignancy, hepatitis, infection, hepatic sinusoidal obstruction syndrome and hypersensitivity reactions. |

| Cyclophosphamide | Nitrogen mustard that cross-links DNA base pairs, leading to breakages and triggering apoptosis in haematopoietic cells. | PO, IV | D (Au) | Vomiting, myelosuppression, haemorrhagic cystitis and rarely heart failure, pulmonary fibrosis, hepatic sinusoidal obstruction syndrome , malignancy and SIADH |

| Dasatinib | Tyrosine kinase inhibitor against various proangiogenic growth factors (including PDGF and VEGF). | PO | D (Au) | Fluid retention, myelosuppression, haemorrhage, infections, pulmonary hypertension, electrolyte anomalies and uncommonly hepatotoxicity, heart dysfunction/failure, myocardial infarction, QT interval prolongation, renal failure and hypersensitivity. |

| Methotrexate | Antifolate; inhibits dihydrofolate reductase . | PO, IV, IM, SC, IT | D (Au) | Myelosuppression, pulmonary toxicity, hepatotoxicity, neurotoxicity, and rarely kidney failure, hypersensitivity reactions, skin and bone necrosis, and osteoporosis |

| Mycophenolate | Inosine monophosphate dehydrogenase inhibitor, leading to reduced purine biosynthesis in lymphocytes. | PO, IV | D (Au) | Myelosuppression, blood clots, less commonly GI perforation/haemorrhage and rarely pancreatitis , hepatitis , aplastic anaemia and pure red cell aplasia . |

| Rituximab | Monoclonal antibody against CD20 , which is expressed on B lymphocytes | IV | C (Au) | Infusion-related reactions, infection, neutropenia , reduced immunoglobulin levels, arrhythmias, less commonly anaemia, thrombocytopenia, angina, myocardial infarction, heart failure, and rarely haemolytic anaemia , aplastic anaemia , serum sickness, severe skin conditions, pulmonary infiltrates, pneumonitis , cranial neuropathy (vision or hearing loss) and progressive multifocal leucoencephalopathy . |

| Sirolimus | mTOR inhibitor, thereby reducing cytokine-induced lymphocyte proliferation. | PO | C (Au) | Neutropenia , hypokalaemia , interstitial lung disease, pericardial effusion , pleural effusion , less commonly pulmonary haemorrhage, nephrotic syndrome, and rarely hepatotoxicity and lymphoedema . |

| PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted. | PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted. | PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted. | PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted. | PO = Oral. IV = Intravenous. IM = Intramuscular. SC = Subcutaneous. IT = Intrathecal. The preferred pregnancy category, above, is Australian, if available. If unavailable, an American one is substituted. |

>>Prognosis

As of 2012, the five-year survival rate for systemic scleroderma was about 85%, whereas the 10-year survival rate was just under 70%.`:cite-ref-germ-44-0[`F5bf`_`[44`#cite-note-germ-44]`_`f] This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: `F33f`_`[pulmonary hypertension`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pulmonary_hypertension]`_`f, `F33f`_`[pulmonary fibrosis`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Pulmonary_fibrosis]`_`f, and scleroderma renal crisis.`:cite-ref-msr-29-1[`F5bf`_`[29`#cite-note-msr-29]`_`f] People with scleroderma are also at a heightened risk for developing osteoporosis and for contracting cancer (especially liver, lung, haematologic, and bladder cancers).`:cite-ref-45[`F5bf`_`[45`#cite-note-45]`_`f] Scleroderma is also associated with an increased risk of cardiovascular disease.`:cite-ref-46[`F5bf`_`[46`#cite-note-46]`_`f]

According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years (the average Australian life expectancy increased from 76 to 82 years in the same period).`:cite-ref-47[`F5bf`_`[47`#cite-note-47]`_`f]

>>Epidemiology

Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected.`:cite-ref-mm-13-2[`F5bf`_`[13`#cite-note-mm-13]`_`f]`:cite-ref-msr-29-2[`F5bf`_`[29`#cite-note-msr-29]`_`f] Women are four to nine times more likely to develop scleroderma than men.`:cite-ref-msr-29-3[`F5bf`_`[29`#cite-note-msr-29]`_`f]

This disease is found worldwide.`:cite-ref-msr-29-4[`F5bf`_`[29`#cite-note-msr-29]`_`f] In the United States, prevalence is estimated at 240 per million, and the annual incidence of scleroderma is 19 per million people.`:cite-ref-msr-29-5[`F5bf`_`[29`#cite-note-msr-29]`_`f] Likewise, in the United States, it is slightly more common in `F33f`_`[African Americans`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=African_American]`_`f than in their white counterparts. Choctaw Native Americans are more likely than Americans of European descent to develop the type of scleroderma that affects internal organs.`:cite-ref-msr-29-6[`F5bf`_`[29`#cite-note-msr-29]`_`f] In `F33f`_`[Germany`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Germany]`_`f, the prevalence is between 10 and 150 per million people, and the annual incidence is between three and 28 per million people.`:cite-ref-germ-44-1[`F5bf`_`[44`#cite-note-germ-44]`_`f] In `F33f`_`[South Australia`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=South_Australia]`_`f, the annual incidence is 23 per million people, and the prevalence 233 per million people.`:cite-ref-48[`F5bf`_`[48`#cite-note-48]`_`f]

>>Pregnancy

Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child.`:cite-ref-preg-49-0[`F5bf`_`[49`#cite-note-preg-49]`_`f] Overall, scleroderma is associated with reduced fetal weight for gestational age.`:cite-ref-preg-49-1[`F5bf`_`[49`#cite-note-preg-49]`_`f] The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, `F33f`_`[mycophenolate`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Mycophenolate]`_`f, etc., so careful avoidance of such drugs during pregnancy is advised.`:cite-ref-preg-49-2[`F5bf`_`[49`#cite-note-preg-49]`_`f] In these cases `F33f`_`[hydroxychloroquine`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Hydroxychloroquine]`_`f and low-dose `F33f`_`[corticosteroids`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Corticosteroid]`_`f might be used for disease control.`:cite-ref-preg-49-3[`F5bf`_`[49`#cite-note-preg-49]`_`f]

>>See also

• `F33f`_`[Congenital fascial dystrophy`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Congenital_fascial_dystrophy]`_`f

• `F33f`_`[Chi Chi DeVayne`:/page/wikibook/entry.mu`zim=wikipedia_en_all_nopic_2025-08.zim|entry_path=Chi_Chi_DeVayne]`_`f, (developed scleroderma in the years leading up to her death)

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>>External links

• Handout on Health: Scleroderma – US National Institute of Arthritis and Musculoskeletal and Skin Diseases

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