Scleroderma

Source: Wikipedia, the free encyclopedia.
This article is about the disease. For the mushroom, see Scleroderma (fungus).
Not to be confused with scleredema.
Scleroderma
non-steroidal anti-inflammatory drugs (NSAIDs)[2]
PrognosisLocalized: Normal life expectancy[7]
Systemic: Decreased life expectancy[3]
Frequency3 per 100,000 per year (systemic)[3]

Scleroderma is a group of

Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels.[1]

The cause is unknown, but it may be due to an abnormal immune response.

silica.[3][4][5] The underlying mechanism involves the abnormal growth of connective tissue, which is believed to be the result of the immune system attacking healthy tissues.[6] Diagnosis is based on symptoms, supported by a skin biopsy or blood tests.[6]

While no cure is known, treatment may improve symptoms.

non-steroidal anti-inflammatory drugs (NSAIDs).[2] Outcome depends on the extent of disease.[3] Those with localized disease generally have a normal life expectancy.[7] In those with systemic disease, life expectancy can be affected, and this varies based on subtype.[3] Death is often due to lung, gastrointestinal, or heart complications.[3]

About three per 100,000 people per year develop the systemic form.[3] The condition most often begins in middle age.[1] Women are more often affected than men.[1] Scleroderma symptoms were first described in 1753 by Carlo Curzio[9] and then well documented in 1842.[10] The term is from the Greek skleros meaning "hard" and derma meaning "skin".[11][12]

Signs and symptoms

Arm of a person with scleroderma showing skin lesions
Dark, shiny skin on distal phalanges of both hands in systemic sclerosis

Potential signs and symptoms include:[13][14][15]

Cause

Scleroderma is caused by genetic and environmental factors.

white spirits exposure seems to contribute to the condition in a small proportion of affected persons.[4][5][16][17][18]

Pathophysiology

Scleroderma is characterised by increased

T lymphocytes, and production of altered connective tissue.[19] Its proposed pathogenesis is the following:[20][21][22][23][24]

Vitamin D 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.[26]

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

antinuclear antibodies. 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.[27]

Laboratory testing can show

anti-scl70 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.[28]
Antidouble-stranded DNA autoantibodies are likely to be present in serum.[citation needed]

Differential

Diseases that are often in the differential include:[29]

  • eosinophils
    (a type of immune cell that attacks parasites and is involved in certain allergic reactions) are present in the blood.
  • L-tryptophan
    supplements.
  • Eosinophilic fasciitis affects the connective tissue surrounding skeletal muscles, bones, blood vessels, and nerves in the arms and legs.
  • Graft-versus-host disease 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.
  • cutaneous T cell lymphoma
    , a rare cancer that causes rashes all over the body.
  • Nephrogenic systemic fibrosis is a condition usually caused by kidney failure that results in fibrosis (thickening) of the tissues.
  • Primary biliary cirrhosis
    is an autoimmune disease of the liver.
  • Primary pulmonary hypertension
  • Complex regional pain syndrome

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:[30]

  • Localised scleroderma
    • Localised morphea
    • Morphea-lichen sclerosus et atrophicus overlap
    • Generalised morphea
    • Atrophoderma of Pasini and Pierini
    • Pansclerotic morphea
    • Morphea profunda
    • Linear scleroderma
  • Systemic scleroderma

Treatment

No cure for scleroderma is known, although relief of symptoms is often achieved; these include treatment of:[13][31]

Systemic

immunoglobulin, rituximab, sirolimus, alefacept, and the tyrosine kinase inhibitors, imatinib, nilotinib, and dasatinib.[16][31][32][33][34][35][36][37]

Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides,

haematopoietic stem cell transplantation.[38][39]

Immunomodulatory agents in the treatment of scleroderma
INN
 Mechanism of action[40][41] Route of administration[40] Pregnancy category[40][42] Major toxicities[40]
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)
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,
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.
Imatinib As above PO D (Au) As above and rarely: GI perforation, avascular necrosis and rhabdomyolysis
Immunoglobulin
 Immunoglobulin, modulates the immune system. IV N/A Varies
Methotrexate Antifolate; inhibits dihydrofolate reductase. PO, IV, IM, SC, IT D (Au) Myeosuppression, 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
aplastic anaemia and pure red cell aplasia
.
Nilotinib As per dasatinib PO D (Au) As per imatinib
Rituximab Monoclonal antibody against CD20, which is expressed on B lymphocytes IV C (Au) Infusion-related reactions, infection,
progressive multifocal leucoencephalopathy
.
Sirolimus
mTOR
inhibitor, thereby reducing cytokine-induced lymphocyte proliferation.		 PO C (Au)
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.

Prognosis

As of 2012[update], the five-year survival rate for systemic scleroderma was about 85%, whereas the 10-year survival rate was just under 70%.[43] 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: pulmonary hypertension, pulmonary fibrosis, and scleroderma renal crisis.[28] People with scleroderma are also at a heightened risk for developing osteoporosis and for contracting cancer (especially liver, lung, haematologic, and bladder cancers).[44] Scleroderma is also associated with an increased risk of cardiovascular disease.[45]

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 (around 8 years less than the average Australian life expectancy of 82 years).[46]

Epidemiology

Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected.[13][28] Women are four to nine times more likely to develop scleroderma than men.[28]

This disease is found worldwide.

African Americans 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.[28] In Germany, the prevalence is between 10 and 150 per million people, and the annual incidence is between three and 28 per million people.[43] In South Australia, the annual incidence is 23 per million people, and the prevalence 233 per million people.[47]

Pregnancy

Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child.

mycophenolate, etc., so careful avoidance of such drugs during pregnancy is advised.[48] In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.[48]

See also

References

  1. ^ a b c d e f g "Scleroderma". NORD (National Organization for Rare Disorders). 2007. Archived from the original on 8 September 2016. Retrieved 14 July 2017.
  2. ^ a b c d e f g h "Scleroderma". GARD. 2017. Archived from the original on 25 January 2017. Retrieved 14 July 2017.
  3. ^ a b c d e f g h Jameson L (2018). "Chapter 353". Harrison's Principles of Internal Medicine (20th ed.). McGraw Hill.
  4. ^
    S2CID 24050211
    .
  5. ^
    PMID 23288576
    .
  6. ^ a b c d "Handout on Health: Scleroderma". NIAMS. August 2016. Archived from the original on 4 July 2017. Retrieved 15 July 2017.
  7. ^
    ISBN 9781594548710. Archived
    from the original on 2017-09-06.
  8. S2CID 22247432
    .
  9. ISBN 9780080454740
    .
  10. ISBN 978-1437717389. Archived
    from the original on 2017-08-04.
  11. ^ Harper D. "scleroderma". Online Etymology Dictionary.
  12. Perseus Project
    .
  13. ^ a b c Hajj-ali, RA (June 2013). "Systemic Sclerosis". Merck Manual Professional. Merck Sharp & Dohme Corp. Archived from the original on 6 March 2014. Retrieved 5 March 2014.
  14. ^ Jimenez, SA, Cronin, PM, Koenig, AS, O'Brien, MS, Castro, SV (15 February 2012). Varga, J, Talavera, F, Goldberg, E, Mechaber, AJ, Diamond, HS (eds.). "Scleroderma Clinical Presentation". Medscape Reference. WebMD. Archived from the original on 6 March 2014. Retrieved 5 March 2014.
  15. ISBN 978-0-07174889-6.[page needed
    ]
  16. ^
    PMID 22424190
    .
  17. ^
    S2CID 37543720
    .
  18. PMID 24129037
    .
  19. PMID 21393982. Archived
    (PDF) from the original on 2014-03-06.
  20. PMID 21090968
    .
  21. PMID 21549861
    .
  22. PMID 21549220
    .
  23. PMID 21545850
    .
  24. S2CID 40400573
    .
  25. PMID 21315153
    .
  26. PMID 21320645
    .
  27. ^ Jimenez, SA, Cronin, PM, Koenig, AS, O'Brien, MS, Castro, SV (15 February 2012). Varga, J, Talavera, F, Goldberg, E, Mechaber, AJ, Diamond, HS (eds.). "Scleroderma Workup". Medscape Reference. WebMD. Archived from the original on 6 March 2014. Retrieved 6 March 2014.
  28. ^ a b c d e f g Jimenez, SA, Cronin, PM, Koenig, AS, O'Brien, MS, Castro, SV (15 February 2012). Varga, J, Talavera, F, Goldberg, E, Mechaber, AJ, Diamond, HS (eds.). "Scleroderma". Medscape Reference. WebMD. Archived from the original on 6 March 2014. Retrieved 5 March 2014.
  29. ^ Jimenez, SA, Cronin, PM, Koenig, AS, O'Brien, MS, Castro, SV (15 February 2012). Varga, J, Talavera, F, Goldberg, E, Mechaber, AJ, Diamond, HS (eds.). "Scleroderma Differential Diagnoses". Medscape Reference. WebMD. Archived from the original on 6 March 2014. Retrieved 6 March 2014.
  30. ISBN 978-0808923510
    .
  31. ^
    PMID 22464314
    .
  32. ^
    PMID 23806160
    .
  33. ^
    PMID 23541012
    .
  34. ^
    PMID 23344666. Archived
    (PDF) from the original on 2014-03-06.
  35. ^
    S2CID 25073736
    .
  36. ^
    S2CID 29026417
    .
  37. PMID 21091117
    .
  38. PMID 20210685
    .
  39. S2CID 24631979
    .
  40. ^
    ISBN 978-0-9805790-9-3.[page needed
    ]
  41. ISBN 978-0-07-162442-8.[page needed
    ]
  42. ^ "Medscape Multispecialty – Home page". WebMD. Archived from the original on 13 November 2013. Retrieved 27 November 2013.[full citation needed]
  43. ^
    S2CID 7422759
    .
  44. PMID 37028844
    .
  45. PMID 33217802
    .
  46. S2CID 4230441
    .
  47. PMID 21665131
    .
  48. ^
    PMID 22155199
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Scleroderma&oldid=1220653421"