Materiały źródłowe

• #1 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder with variable clinical presentations, that affects both adults and children. […] While the etiology is still unknown, many factors may contribute to disease development, including genetic predisposition, vascular dysregulation, TH1/TH2 imbalance with chemokines and cytokines associated with interferon- and profibrotic pathways as well as certain environmental factors. […] While the exact cause of the disease is still not known, certain stimuli (infection, drugs and/or trauma) may trigger vascular and immune dysregulations in genetically predisposed individuals. […] A variety of factors, including genetics, environmental factors, such as infections, skin trauma, autoimmune dysregulation with abnormal cytokine production, and/or vascular dysfunction may play a role in the development of morphea.

• #2 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #3 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Morphea, also known as localized scleroderma, is an autoimmune chronic connective tissue disease. It is characterized by excessive collagen deposition in the dermis and/or subcutaneous tissue. The etiopathogenesis of this disease is not fully understood, with endothelial cell damage, immunological disorders, extracellular matrix disorders and factors such as infection, trauma and other autoimmune diseases being considered. […] As medicine advances, there is increasing evidence that genetic factors play a significant role in disease risk and progression. In addition to environmental factors and genetic predisposition, epigenetic factors may be potential triggers for morphea. […] The exact cause that initiates the disease process is still unknown. Certain stimuli such as drugs/infection or trauma lead to dysregulation of angiogenesis and the immune system in genetically predisposed individuals.

• #4 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #5 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #6 Morphea – MD Searchlight

  https://mdsearchlight.com/skin-problems-and-treatments/morphea/

  The cause of morphea, a skin condition that causes hard, discolored patches on the skin, is still largely unknown. However, experts believe that it may be linked to genetic factors, issues with the immune system, and exposure to certain environmental factors. […] Strong associations have been found between morphea and two specific genetic markers, known as DRB1*04:04 in the HLA class II allele, and HLA-B*37 in the class I allele. In simpler terms, if you have these particular markers in your DNA, you might be more likely to develop morphea. […] Additionally, the presence of certain auto-antibodies (proteins that the immune system mistakenly produces to target its own cells) could suggest that the immune system is not functioning properly. These include the antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies. These irregularities in the immune system could also play a role in the development of morphea.

• #7 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #8 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #9 Frequently Asked Questions about Morphea: Department of Dermatology – UT Southwestern, Dallas, Texas

  https://www.utsouthwestern.edu/education/medical-school/departments/dermatology/research/morphea-registry/disease-faq.html

  Morphea, also known as localized scleroderma, is a condition which causes hardening and discoloration of the skin. It is thought to be isolated to the skin without internal organ involvement as seen in systemic sclerosis (commonly known as scleroderma). […] The cause of morphea is unknown, but it is thought that the collagen-producing cells become overactive and overproduce collagen. This can result in areas of sclerosis or skin hardening. Researchers are trying to determine what triggers the disease and whether it is genetic in origin. […] Data from our registry indicates that other autoimmune diseases are more common in patients with morphea and possibly their relatives as well.

• #10 Morphea – Wikipedia

  https://en.wikipedia.org/wiki/Morphea

  Morphea is a form of scleroderma that mainly involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, usually with no internal organ involvement. […] Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea. […] Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease. […] Borrelia burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called „Borrelia-associated early onset morphea” and is characterized by the combination of disease onset at younger age, infection with B. burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies.

• #11 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #12 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #13 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  The main regulator of the fibrosis process is TGF-β. An increase in its concentration causes an increase in the expression of collagen types I, III, VI, X, fibronectin and proteoglycans. […] Understanding the genetic basis of morphea is critical to uncovering the mechanisms underlying this disease and identifying potential treatment targets. […] Human leukocyte antigen (HLA) has been implicated as the most promising target in the pathogenesis of morphea, suggesting a genetic predisposition to the disease. […] Recent studies have highlighted the involvement of cutaneous mosaicism as a possible factor in morphea’s pathogenesis. […] Epigenetic factors are considered to be triggers of the morphea, next to environmental factors and genetic predisposition. […] Infectious factors include the occurrence of morphea-like lesions following infections with measles, varicella, Epstein–Barr, hepatitis B and C viruses.

• #14 Morphea Information for Patients | RDS

  https://www.rheumaderm-society.org/morphea-information-for-patients/

  Morphea (syn. localized scleroderma) occurs as a result of autoimmune fibrosing (leather-like) injury to the skin and sometimes the underlying fat, muscle and bone. […] The cause of morphea is unknown at this time. We know that patients with family histories of autoimmune diseases are more likely to get morphea, so there is probably a genetic link. Morphea has been reported to occur after injuries and radiation therapy, which may play a role as a disease trigger.

• #15 Morphea: Symptoms, causes, and treatment

  https://www.medicalnewstoday.com/articles/320708

  Most health professionals consider morphea to be an unusual autoimmune condition in which immune system dysfunction occurs and causes characteristic skin symptoms. […] However, the exact cause of the condition is unclear and remains unknown. When morphea occurs, the collagen-producing cells overproduce collagen, causing it to build up and the skin to harden. There is much to learn about morphea, but its onset could be related to: repeated trauma to the skin, aggressive treatments, such as radiation therapy, an infection, skin damage caused by environmental exposure. […] Morphea is not a contagious condition and cannot spread from person to person.

• #16 Morphea (Scleroderma): Treatment, Causes, and More

  https://www.verywellhealth.com/morphea-5179411

  Morphea seems to be a kind of autoimmune disease. In this case, dysregulation of part of the immune system drives the symptoms. […] Certain inflammatory cytokines (immune signaling molecules) can be overproduced. Certain immune cells like B cells and T cells may become unnaturally activated. The area gets inflamed, and certain cells help trigger fibrosis—the secretion of certain compounds usually used to make scar tissue. […] This fibrosis accounts for the rigid, tense areas seen in morphea. This fibrosis is part of why affected areas never get completely back to normal. Even after the initial inflammation has subsided, some scar-like tissue remains. […] Other factors may also play a role in triggering the disease in some people. Some of these might include having variations of certain genes (particularly ones important for the immune system), underlying damage to blood vessels in the area, certain kinds of infections, and previous trauma to the area (e.g., through radiation exposure). […] Morphea is not an infectious disease. It’s not contagious, so you can’t spread it to someone else. It is also not a sign of cancer.

• #17 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #18 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #19 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #20 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  The cause of morphea is unknown. An autoimmune mechanism is suggested by an increased frequency of autoantibody formation and a higher prevalence of personal and familial autoimmune disease in affected patients. […] Patients with generalized morphea are more likely to have a concomitant autoimmune disease, positive serology for autoantibodies, particularly ANA, and systemic symptoms. […] To date, investigations have not described any consistent etiologic factors. Different morphea subtypes often coexist in the same patient, suggesting that the underlying processes are similar. Note the following causes and associations: […] Radiation therapy: Morphea can occur at the site of previous radiation therapy for breast cancer and other malignancies, developing from 1 month up to more than 20 years after irradiation.

• #21 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #22 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #23 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  The cause of morphea is unknown. An autoimmune mechanism is suggested by an increased frequency of autoantibody formation and a higher prevalence of personal and familial autoimmune disease in affected patients. […] Patients with generalized morphea are more likely to have a concomitant autoimmune disease, positive serology for autoantibodies, particularly ANA, and systemic symptoms. […] To date, investigations have not described any consistent etiologic factors. Different morphea subtypes often coexist in the same patient, suggesting that the underlying processes are similar. Note the following causes and associations: […] Radiation therapy: Morphea can occur at the site of previous radiation therapy for breast cancer and other malignancies, developing from 1 month up to more than 20 years after irradiation.

• #24 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #25 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Damage to the endothelial cells is thought to be of primary importance in the pathogenesis of the disease and may initiate the disease process. The following insults are mentioned: trauma, infection, radiation or drugs (β-blockers, bleomycin, bromocriptine, D-penicillamine). […] Studies have confirmed that transforming growth factor β (TGF-β), interleukin IL-1β, IL-4, IL-6, IL-10, IL-27, interferon gamma (INF-γ) and, more recently, IL-17A are essential for inflammation and fibrosis. […] The most likely earliest phenomenon underlying the pathogenesis of morphea is thought to be endothelial cell activation resulting from endothelial damage. […] An important component in the pathogenesis of morphea is the activation of the immune system. Increased production of adhesion molecules such as ICAM-1, VCAM-1, E-selectin and P-selectin leads to increased recruitment of inflammatory cells, including T lymphocytes, monocytes and other immune cells.

• #26 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder with variable clinical presentations, that affects both adults and children. […] While the etiology is still unknown, many factors may contribute to disease development, including genetic predisposition, vascular dysregulation, TH1/TH2 imbalance with chemokines and cytokines associated with interferon- and profibrotic pathways as well as certain environmental factors. […] While the exact cause of the disease is still not known, certain stimuli (infection, drugs and/or trauma) may trigger vascular and immune dysregulations in genetically predisposed individuals. […] A variety of factors, including genetics, environmental factors, such as infections, skin trauma, autoimmune dysregulation with abnormal cytokine production, and/or vascular dysfunction may play a role in the development of morphea.

• #27 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Damage to the endothelial cells is thought to be of primary importance in the pathogenesis of the disease and may initiate the disease process. The following insults are mentioned: trauma, infection, radiation or drugs (β-blockers, bleomycin, bromocriptine, D-penicillamine). […] Studies have confirmed that transforming growth factor β (TGF-β), interleukin IL-1β, IL-4, IL-6, IL-10, IL-27, interferon gamma (INF-γ) and, more recently, IL-17A are essential for inflammation and fibrosis. […] The most likely earliest phenomenon underlying the pathogenesis of morphea is thought to be endothelial cell activation resulting from endothelial damage. […] An important component in the pathogenesis of morphea is the activation of the immune system. Increased production of adhesion molecules such as ICAM-1, VCAM-1, E-selectin and P-selectin leads to increased recruitment of inflammatory cells, including T lymphocytes, monocytes and other immune cells.

• #28 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  The main regulator of the fibrosis process is TGF-β. An increase in its concentration causes an increase in the expression of collagen types I, III, VI, X, fibronectin and proteoglycans. […] Understanding the genetic basis of morphea is critical to uncovering the mechanisms underlying this disease and identifying potential treatment targets. […] Human leukocyte antigen (HLA) has been implicated as the most promising target in the pathogenesis of morphea, suggesting a genetic predisposition to the disease. […] Recent studies have highlighted the involvement of cutaneous mosaicism as a possible factor in morphea’s pathogenesis. […] Epigenetic factors are considered to be triggers of the morphea, next to environmental factors and genetic predisposition. […] Infectious factors include the occurrence of morphea-like lesions following infections with measles, varicella, Epstein–Barr, hepatitis B and C viruses.

• #29 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #30 Morphea | Plastic Surgery Key

  https://plasticsurgerykey.com/morphea-3/

  This is likely the result of autoimmunity, as there is widespread autoimmune reactivity in morphea patients (elevated ANAs, cytokines, and adhesion molecules). […] Vessel damage and upregulation of adhesion molecules (ICAM-1, VCAM 1, and E-selectin) occur related to the inflammatory cell infiltrate which facilitates local monocyte recruitment. […] These cytokines and growth factors inhibit interferon- (a suppressor of collagen synthesis and Th1-related cytokine). Chimerism or nonself cells may play a role in the pathogenesis of morphea by initiating a local inflammatory reaction.

• #31 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #32 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #33 Morphea | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20375265/

  Morphea is a rare skin condition characterized by small red or purple patches that develop firm white or ivory centers. The affected skin becomes tight and less flexible. […] The cause of morphea is unknown. It may be caused by an unusual reaction of your immune system. In people at increased risk of morphea, it could be triggered by injury to the affected area, medications, chemical toxins, an infection or radiation therapy. […] The condition isn’t contagious.

• #34 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #35 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #36 Morphea (Localized Scleroderma) – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/morphea-localized-scleroderma/

  Morphea may present at any age. […] Morphea is not the same as scleroderma (systemic sclerosis), and it does not become scleroderma. […] Development of lesions has been associated with local tissue trauma such as insect bites, intramuscular injections, radiation, surgery. […] Uncertain; likely a complex genetic disease resulting in immune dysregulation producing excessive dermal (or deeper) deposition of collagen and extracellular matrix. […] Autoimmune-mediated inflammation is likely the initial event in the formation of morphea lesions.

• #37 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #38 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #39 Morphoea (Localised Scleroderma) | Doctor

  https://patient.info/doctor/localised-scleroderma-morphoea-pro

  What causes localised scleroderma? (Aetiology) The cause of localised scleroderma is unknown. It is thought that a genetic predisposition may lead to an immunologically mediated cytokine release, causing inflammation, dysfunction of the connective tissue metabolism and subsequent fibrosis. It appears to be debatable whether there is any risk of progression to systemic sclerosis; however, although the pathogenesis is similar, it is probably a completely separate disease. […] In some cases it has been thought to follow: Tick bites – it has been associated with Lyme disease. Measles and other viral infections. Localised injury. Pregnancy. Autoimmune diseases, including vitiligo, diabetes, lichen sclerosus and lichen planus. Radiotherapy. It may be as common as 2 in every 1,000 patients treated with radiotherapy. A few familial cases have been reported. People with localised scleroderma tend to have a family history of autoimmune disease.

• #40 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #41 Morphea | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816329/all/Morphea

  Sclerosis is limited to the skin and systemic sclerosis is absent. […] Causation thought to be from vascular damage and enhanced collagen production, although likely with underlying autoimmune etiology. […] Drug-induced morphea primarily identified in association with TNF- inhibitors. […] Some association with past trauma, including surgery and vaccination administration, or radiation to the area.

• #42 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #43 What Is Morphea?

  https://www.icliniq.com/articles/skin-care/morphoea

  Morphea, or localized scleroderma, is a rare fibrous disease characterized by inflamed fibrous skin due to increased collagen deposition. […] The exact cause of morphea is unknown. However, localized genetic factors and other external triggers could contribute to morphea. […] The exact cause of morphea is not known. However, it is found that certain genetic factors and autoimmune diseases can cause morphea. Severe forms of morphea are familial cases. Morphea seems to occur after external factors. […] The external triggers of morphea are, repeated friction, which also includes minor friction along the waistband and inguinal area, injection site, vaccination site, bite of an insect, surgery, radiotherapy, trauma, deep wound.

• #44 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #45 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #46 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  The cause of morphea is unknown. An autoimmune mechanism is suggested by an increased frequency of autoantibody formation and a higher prevalence of personal and familial autoimmune disease in affected patients. […] Patients with generalized morphea are more likely to have a concomitant autoimmune disease, positive serology for autoantibodies, particularly ANA, and systemic symptoms. […] To date, investigations have not described any consistent etiologic factors. Different morphea subtypes often coexist in the same patient, suggesting that the underlying processes are similar. Note the following causes and associations: […] Radiation therapy: Morphea can occur at the site of previous radiation therapy for breast cancer and other malignancies, developing from 1 month up to more than 20 years after irradiation.

• #47 Morphea – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK559010/

  The etiology of morphea is unclear, but genetic predisposition, autoimmune dysregulation, and environmental factors play a role in the pathogenesis of morphea. The strongest genetic associations with morphea were found with the HLA class II allele DRB1*04:04 and class I allele HLAB*37. The presence of auto-antibodies like antinuclear antibody (ANA), anti-single-stranded DNA (SS DNA), and anti-histone antibodies supports the role of autoimmune dysregulation. […] There is evidence from cohort studies that family members of morphea patients have an increased incidence of other autoimmune diseases, which also suggests the role of autoimmune dysregulation. […] Multiple environmental factors like trauma, radiation, and friction have been reported to play a role in morphea. Radiation can cause localized secretion of interleukin 4 and 5, which induce TGF-B mediated fibrogenesis.

• #48 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Other possible aetiological factors include infection with Borrelia burgdorferi (B. burgdorferi), the role of which remains controversial and debated. […] The association of morphea with other autoimmune diseases has been described in the medical literature for years. […] The pathogenesis of this phenomenon remains unclear. Data to date suggest that ionizing radiation activates fibroblasts to increase secretion of cytokines with profibrotic effects (IL-4, IL-5, TGF-β). […] Trauma has also been mentioned as a possible factor in the pathogenesis of morphea. Some authors postulate the occurrence of the Koebnerization phenomenon as an important factor in the pathogenesis of morphea.

• #49

  https://journals.lww.com/10.4103/0019-5154.190132

  Morphea postradiotherapy is a rare complication, with an estimated incidence of 1 in 500 patients, in contrast to that of morphea (of any etiology), which is 2.7/100,000 in the general population. […] Radiation and surgery are important causative factors for the development of morphea and patients receiving radiotherapy should be followed up for years to detect morphea. […] Radiation is an important trigger factor of morphea. It not only can induce localized morphea, but also generalized progressive morphea with severe disability. Presence of ANA in a patient increases the susceptibility for developing morphea. Regular monitoring of the patients receiving radiotherapy is recommended.

• #50 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #51 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Other possible aetiological factors include infection with Borrelia burgdorferi (B. burgdorferi), the role of which remains controversial and debated. […] The association of morphea with other autoimmune diseases has been described in the medical literature for years. […] The pathogenesis of this phenomenon remains unclear. Data to date suggest that ionizing radiation activates fibroblasts to increase secretion of cytokines with profibrotic effects (IL-4, IL-5, TGF-β). […] Trauma has also been mentioned as a possible factor in the pathogenesis of morphea. Some authors postulate the occurrence of the Koebnerization phenomenon as an important factor in the pathogenesis of morphea.

• #52 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #53 Morphea – Wikipedia

  https://en.wikipedia.org/wiki/Morphea

  Morphea is a form of scleroderma that mainly involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, usually with no internal organ involvement. […] Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea. […] Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease. […] Borrelia burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called „Borrelia-associated early onset morphea” and is characterized by the combination of disease onset at younger age, infection with B. burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies.

• #54 The role of infection in morphea disease

  https://rcm.mums.ac.ir/article_4762.html

  Morphea is a multifactorial process that its main underlying cause is not completely known but the most common causes related to the genesis of morphea including trauma, radiation, medications, infection, autoimmunity and microchimerism. […] Morphea is a multifactorial process that its underlying cause is not completely known. The most common causes are summarized in Table 1. […] The most likely disease cause is the Infection and according to the previous articles. Borrelia spp. and CMV are the most common infectious agents; however, newer molecular and genetic research are needed to confirm these results.

• #55 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #56 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #57 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #58 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #59 The role of infection in morphea disease

  https://rcm.mums.ac.ir/article_4762.html

  Morphea is a multifactorial process that its main underlying cause is not completely known but the most common causes related to the genesis of morphea including trauma, radiation, medications, infection, autoimmunity and microchimerism. […] Morphea is a multifactorial process that its underlying cause is not completely known. The most common causes are summarized in Table 1. […] The most likely disease cause is the Infection and according to the previous articles. Borrelia spp. and CMV are the most common infectious agents; however, newer molecular and genetic research are needed to confirm these results.

• #60 Pathology Outlines – Morphea and systemic sclerosis

  https://www.pathologyoutlines.com/topic/skinnontumorscleroderma.html

  Postulated etiologic stimuli (J Am Acad Dermatol 2011;64:217): Lyme disease […] Trauma […] Radiation (most frequently described) […] Medications (bisoprolol, D-penicillamine, bromocriptine and bleomycin) […] Infections (borrelia has been implied; cytomegalovirus) […] Postulated environmental factors in systemic sclerosis (Clin Dermatol 2013;31:432, Neth J Med 2010;68:348, J Dtsch Dermatol Ges 2012;10:705): Occupational and industrial exposures (vinyl chloride, silica dust and organic solvents) […] Chemotherapy drugs (taxanes and gemcitabine) (Lancet 2017;390:1685) […] Virus (parvovirus, cytomegalovirus)

• #61 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  The main regulator of the fibrosis process is TGF-β. An increase in its concentration causes an increase in the expression of collagen types I, III, VI, X, fibronectin and proteoglycans. […] Understanding the genetic basis of morphea is critical to uncovering the mechanisms underlying this disease and identifying potential treatment targets. […] Human leukocyte antigen (HLA) has been implicated as the most promising target in the pathogenesis of morphea, suggesting a genetic predisposition to the disease. […] Recent studies have highlighted the involvement of cutaneous mosaicism as a possible factor in morphea’s pathogenesis. […] Epigenetic factors are considered to be triggers of the morphea, next to environmental factors and genetic predisposition. […] Infectious factors include the occurrence of morphea-like lesions following infections with measles, varicella, Epstein–Barr, hepatitis B and C viruses.

• #62 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #63 Morphoea (Localised Scleroderma) | Doctor

  https://patient.info/doctor/localised-scleroderma-morphoea-pro

  What causes localised scleroderma? (Aetiology) The cause of localised scleroderma is unknown. It is thought that a genetic predisposition may lead to an immunologically mediated cytokine release, causing inflammation, dysfunction of the connective tissue metabolism and subsequent fibrosis. It appears to be debatable whether there is any risk of progression to systemic sclerosis; however, although the pathogenesis is similar, it is probably a completely separate disease. […] In some cases it has been thought to follow: Tick bites – it has been associated with Lyme disease. Measles and other viral infections. Localised injury. Pregnancy. Autoimmune diseases, including vitiligo, diabetes, lichen sclerosus and lichen planus. Radiotherapy. It may be as common as 2 in every 1,000 patients treated with radiotherapy. A few familial cases have been reported. People with localised scleroderma tend to have a family history of autoimmune disease.

• #64 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #65 Pathology Outlines – Morphea and systemic sclerosis

  https://www.pathologyoutlines.com/topic/skinnontumorscleroderma.html

  Postulated etiologic stimuli (J Am Acad Dermatol 2011;64:217): Lyme disease […] Trauma […] Radiation (most frequently described) […] Medications (bisoprolol, D-penicillamine, bromocriptine and bleomycin) […] Infections (borrelia has been implied; cytomegalovirus) […] Postulated environmental factors in systemic sclerosis (Clin Dermatol 2013;31:432, Neth J Med 2010;68:348, J Dtsch Dermatol Ges 2012;10:705): Occupational and industrial exposures (vinyl chloride, silica dust and organic solvents) […] Chemotherapy drugs (taxanes and gemcitabine) (Lancet 2017;390:1685) […] Virus (parvovirus, cytomegalovirus)

• #66 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #67 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #68 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #69 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #70 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #71 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #72 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #73 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #74 RF – Generalized Morphea: Definition and Associations | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/en-rf-generalized-morphea-definition-articulo-S1578219021000810

  Morphea, also known as localized scleroderma, encompasses a set of cutaneous sclerotic disorders of unknown etiology, with a wide range of manifestations and symptoms that range from mild local discomfort to severe complications. […] The literature contains several cases of patients with generalized morphea and various types of malignancy, such as lung cancer and breast cancer, although while systemic sclerosis has been reported to be a paraneoplastic phenomenon, the association between morphea and cancer is not so consolidated. Nevertheless, given the potential association, it seems advisable to take a targeted clinical history and appropriate work-up to rule out malignancy, especially in older patients with acute onset morphea and extensive involvement. Morphea has also been reported to be induced by various medications, with the most commonly reported in the literature being tumor necrosis factor drugs (although, paradoxically, infliximab has led to a good response in some cases of morphea). Given the recent report of a case of morphea induced by nivolumab, this possibility should be taken into account when there is a temporal relationship with the introduction of a new drug.

• #75 Morphea | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/816329/all/Morphea

  Sclerosis is limited to the skin and systemic sclerosis is absent. […] Causation thought to be from vascular damage and enhanced collagen production, although likely with underlying autoimmune etiology. […] Drug-induced morphea primarily identified in association with TNF- inhibitors. […] Some association with past trauma, including surgery and vaccination administration, or radiation to the area.

• #76 Pathology Outlines – Morphea and systemic sclerosis

  https://www.pathologyoutlines.com/topic/skinnontumorscleroderma.html

  Postulated etiologic stimuli (J Am Acad Dermatol 2011;64:217): Lyme disease […] Trauma […] Radiation (most frequently described) […] Medications (bisoprolol, D-penicillamine, bromocriptine and bleomycin) […] Infections (borrelia has been implied; cytomegalovirus) […] Postulated environmental factors in systemic sclerosis (Clin Dermatol 2013;31:432, Neth J Med 2010;68:348, J Dtsch Dermatol Ges 2012;10:705): Occupational and industrial exposures (vinyl chloride, silica dust and organic solvents) […] Chemotherapy drugs (taxanes and gemcitabine) (Lancet 2017;390:1685) […] Virus (parvovirus, cytomegalovirus)

• #77 Morphea – DoveMed

  https://www.dovemed.com/diseases-conditions/morphea

  Morphea is a type of Localized Scleroderma of unknown cause. […] The exact cause of Morphea is presently unknown. It is thought to occur due to genetics. Research is being currently performed to identify the relevant causal factors. […] Many researchers believe that Scleroderma is an autoimmune disorder, where the body’s immune system mistakenly attacks healthy tissues resulting in damage of the tissues and organs. […] Some studies have revealed that there may be a higher risk for the condition, due to occupational exposure to chemicals such as silica dust and PVC.

• #78 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #79 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Putative genetic associations of morphea include HLA class I and II genes. […] The strongest associations were found with DRB1*04:04 and HLA-B*37. […] Individuals with morphea have a higher frequency of concomitant and familial autoimmunity. […] Alleles associated with morphea are in parallel strongly associated with rheumatoid arthritis (RA), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and type 1 diabetes mellitus. […] Interestingly, population-based studies observing the autoimmune profile of RA, MS, and AITD have identified an increased risk of morphea in these patients, suggesting a common genetic susceptibility. […] Furthermore, up to 50% of patients have elevated levels of three main autoantibodies: antinuclear (ANA), anti-histone (AHA), and anti-single-stranded DNA (ssDNA) antibodies, whereas other autoantibodies are observed at frequencies below 10%, indicating that morphea involves autoimmune abnormalities against an unknown self-antigen. […] Beside the genetic component, various exogenous triggers are suggested, including some infections as for SSc, Epstein-Barr virus, varicella zoster virus and Borrelia burgdorferi, as well as local trauma, surgical operations, radiation and BCG vaccinations or adjuvants.

• #80 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #81 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #82 Morphea: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1065782-overview

  Chimerism: Immature chimeric cells have been found in morphea lesions, suggesting that such nonself cells may lead to an autoimmune phenotype. […] Infection: Infections, such as Epstein-Barr virus infection, varicella, measles, hepatitis B, and borreliosis, have been reported to precede the onset of morphea and have been proposed as possible triggers. […] Vaccination: Morphealike lesions have also been reported to occur following vaccinations, including BCG, tetanus, and mumps-measles-rubella vaccinations. […] Drug-induced morphea: This is only rarely reported (ie, from bisoprolol, bleomycin, D-penicillamine, L-5-hydroxytryptophane, balicatib, pembrolizumab, interferon beta-1a, ustekinumab). […] Trauma: Some morphea patients report a history of local trauma directly preceding the onset of disease. […] Genetics: A few familial cases of morphea have been reported, most commonly the disabling pansclerotic subtype. […] Chemical exposure.

• #83 Morphea: Symptoms, Causes, and Effective Treatment Options – The Kingsley Clinic

  https://thekingsleyclinic.com/resources/morphea-symptoms-causes-and-effective-treatment-options/

  Morphea is a rare autoimmune skin condition that causes localized patches of hardened skin and, in some cases, affects the tissues beneath the skin. […] While the exact cause remains unclear, researchers believe it arises from a combination of genetic, environmental, and immune system factors. […] Autoimmune disorders are a significant risk factor for developing Morphea. Conditions such as lupus, rheumatoid arthritis, or Hashimoto’s thyroiditis may increase the likelihood of autoimmune-related skin changes, including Morphea. […] Some medications, including those used for chemotherapy or immune suppression, may indirectly contribute to Morphea by altering immune function. However, these cases are rare and require further research to establish a definitive connection. […] Genetics may play a role in the development of Morphea, although no specific gene has been identified. A family history of autoimmune diseases may increase susceptibility. […] Women are more likely than men to develop Morphea, suggesting that hormonal factors may influence its onset.

• #84 Limited Scleroderma (Morphea) – causes, symptoms • OT.CO Clinic

  https://otcoclinic.com/blog/scleroderma-limited-morphea-causes-symptoms/

  Limited Scleroderma (Morphea): A rare autoimmune disorder causing hardening and thickening of the skin, typically sparing internal organs. […] Causes: Autoimmune malfunction, genetic predisposition, infections (e.g., Borrelia burgdorferi), mechanical injuries, chemical exposure, and hormonal changes. […] The causes of scleroderma are not fully known, but there are several theories about what may trigger the disease. The main factors contributing to the development of the disease include autoimmune ones. It is believed that limited scleroderma is an autoimmune disease, meaning that the immune system begins to attack its own tissues, in this case the skin and subcutaneous tissues. This can lead to inflammation and excessive collagen production, resulting in hardening of the skin. Genetic predisposition can also play a role in the development of the condition. People who have a family history of autoimmune diseases may be at higher risk for scleroderma. In addition, some bacterial or viral infections trigger or exacerbate the symptoms of scleroderma limited. For example, infection with Borrelia burgdorferi, the bacterium responsible for Lyme disease, is one potential risk factor. Mechanical injuries, such as cuts, burns or other skin damage, can sometimes trigger a local inflammatory reaction that leads to the development of scleroderma at the site of injury. Also, exposure to certain chemicals or drugs can increase the risk of developing scleroderma. Although there is no conclusive evidence, some studies suggest a link between exposure to pesticides and the occurrence of this condition. Changes in hormone levels, especially in women, may also influence the development of the disease, although the exact mechanism is not well understood. […] The causes, though not fully understood, involve autoimmune responses and, possibly, external triggers.

• #85 Morphea: Symptoms, Causes, and Effective Treatment Options – The Kingsley Clinic

  https://thekingsleyclinic.com/resources/morphea-symptoms-causes-and-effective-treatment-options/

  Morphea is a rare autoimmune skin condition that causes localized patches of hardened skin and, in some cases, affects the tissues beneath the skin. […] While the exact cause remains unclear, researchers believe it arises from a combination of genetic, environmental, and immune system factors. […] Autoimmune disorders are a significant risk factor for developing Morphea. Conditions such as lupus, rheumatoid arthritis, or Hashimoto’s thyroiditis may increase the likelihood of autoimmune-related skin changes, including Morphea. […] Some medications, including those used for chemotherapy or immune suppression, may indirectly contribute to Morphea by altering immune function. However, these cases are rare and require further research to establish a definitive connection. […] Genetics may play a role in the development of Morphea, although no specific gene has been identified. A family history of autoimmune diseases may increase susceptibility. […] Women are more likely than men to develop Morphea, suggesting that hormonal factors may influence its onset.

• #86 Morphoea (localised scleroderma, morphea)

  https://dermnetnz.org/topics/morphoea

  Morphoea is rare and is estimated to have an incidence of 13 per 100,000 children. It is three times more common in females compared to males and often begins in childhood. Although not an inherited disorder, certain HLA subtypes (HLA-DRB1*04:04 and HLA-B*37) are associated with an increased risk of morphoea. […] The precise cause of morphoea is unknown. […] Localised genetic factors appear to play a role; for example, cutaneous mosaicism may important in linear morphoea, which follows Blaschko lines of epidermal development. […] Up to 40% of patients with severe forms of morphoea have a personal or family history of autoimmune disease (eg, thyroid disease, vitiligo) or rheumatologic disease (eg, rheumatoid arthritis). […] For unknown reasons, morphoea often develops after an external trigger such as: insect bite or tick bite (the role of Borellia burgdorferi, cause of Lyme disease is controversial), injection (eg, bleomycin, silicone) or vaccination, repeated friction, surgery, radiotherapy, penetrating wound, extreme exercise, repeated minor friction along the waistband, bra strap and inguinal region, in isomorphic disseminated plaque morphoea. […] Trauma-related morphoea may occur at the affected site, or at unrelated distant sites.

• #87 RF – Generalized Morphea: Definition and Associations | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/en-rf-generalized-morphea-definition-articulo-S1578219021000810

  Morphea, also known as localized scleroderma, encompasses a set of cutaneous sclerotic disorders of unknown etiology, with a wide range of manifestations and symptoms that range from mild local discomfort to severe complications. […] The literature contains several cases of patients with generalized morphea and various types of malignancy, such as lung cancer and breast cancer, although while systemic sclerosis has been reported to be a paraneoplastic phenomenon, the association between morphea and cancer is not so consolidated. Nevertheless, given the potential association, it seems advisable to take a targeted clinical history and appropriate work-up to rule out malignancy, especially in older patients with acute onset morphea and extensive involvement. Morphea has also been reported to be induced by various medications, with the most commonly reported in the literature being tumor necrosis factor drugs (although, paradoxically, infliximab has led to a good response in some cases of morphea). Given the recent report of a case of morphea induced by nivolumab, this possibility should be taken into account when there is a temporal relationship with the introduction of a new drug.

• #88 Morphea – Therapeutics in Dermatology

  https://www.therapeutique-dermatologique.org/spip.php?article1641

  The cause of morphea is unknown. It is not contagious. Some patients with family history of autoimmune diseases are more likely to get morphea, so there may be a genetic link. […] Morphea can be triggered by skin injury such as an insect bite, a burn, radiation therapy, or viral infections. […] Morphea usually affects white skinned people and is rare in African-American people.

• #89 Morphea: progress to date and the road ahead

  https://atm.amegroups.org/article/view/61306/html

  Although it is generally accepted that immune dysfunction is the principal component in the development of morphea, other factors are also thought to contribute to pathogenesis, including genetic predisposition, traumatic or environmental factors, and vascular dysfunction. […] There are several aspects of morphea that point to the role of autoimmunity in pathogenesis. […] Recent observations have supported the role of dysregulated immune pathways, particularly IFN gamma, demonstrating that CXCL9 and CXCL10 levels are associated with increased clinical measures of disease activity. […] Beyond CXCR3 ligands, other upstream and downstream pathways have also been implicated in the pathogenesis of morphea. […] A variety of additional factors have been thought to play a role in morphea beyond immune dysregulation, including genetic predisposition, traumatic factors, and vascular dysregulation.

• #90 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Damage to the endothelial cells is thought to be of primary importance in the pathogenesis of the disease and may initiate the disease process. The following insults are mentioned: trauma, infection, radiation or drugs (β-blockers, bleomycin, bromocriptine, D-penicillamine). […] Studies have confirmed that transforming growth factor β (TGF-β), interleukin IL-1β, IL-4, IL-6, IL-10, IL-27, interferon gamma (INF-γ) and, more recently, IL-17A are essential for inflammation and fibrosis. […] The most likely earliest phenomenon underlying the pathogenesis of morphea is thought to be endothelial cell activation resulting from endothelial damage. […] An important component in the pathogenesis of morphea is the activation of the immune system. Increased production of adhesion molecules such as ICAM-1, VCAM-1, E-selectin and P-selectin leads to increased recruitment of inflammatory cells, including T lymphocytes, monocytes and other immune cells.

• #91 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Damage to the endothelial cells is thought to be of primary importance in the pathogenesis of the disease and may initiate the disease process. The following insults are mentioned: trauma, infection, radiation or drugs (β-blockers, bleomycin, bromocriptine, D-penicillamine). […] Studies have confirmed that transforming growth factor β (TGF-β), interleukin IL-1β, IL-4, IL-6, IL-10, IL-27, interferon gamma (INF-γ) and, more recently, IL-17A are essential for inflammation and fibrosis. […] The most likely earliest phenomenon underlying the pathogenesis of morphea is thought to be endothelial cell activation resulting from endothelial damage. […] An important component in the pathogenesis of morphea is the activation of the immune system. Increased production of adhesion molecules such as ICAM-1, VCAM-1, E-selectin and P-selectin leads to increased recruitment of inflammatory cells, including T lymphocytes, monocytes and other immune cells.

• #92 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  Damage to the endothelial cells is thought to be of primary importance in the pathogenesis of the disease and may initiate the disease process. The following insults are mentioned: trauma, infection, radiation or drugs (β-blockers, bleomycin, bromocriptine, D-penicillamine). […] Studies have confirmed that transforming growth factor β (TGF-β), interleukin IL-1β, IL-4, IL-6, IL-10, IL-27, interferon gamma (INF-γ) and, more recently, IL-17A are essential for inflammation and fibrosis. […] The most likely earliest phenomenon underlying the pathogenesis of morphea is thought to be endothelial cell activation resulting from endothelial damage. […] An important component in the pathogenesis of morphea is the activation of the immune system. Increased production of adhesion molecules such as ICAM-1, VCAM-1, E-selectin and P-selectin leads to increased recruitment of inflammatory cells, including T lymphocytes, monocytes and other immune cells.

• #93 Morphea (Scleroderma): Treatment, Causes, and More

  https://www.verywellhealth.com/morphea-5179411

  Morphea seems to be a kind of autoimmune disease. In this case, dysregulation of part of the immune system drives the symptoms. […] Certain inflammatory cytokines (immune signaling molecules) can be overproduced. Certain immune cells like B cells and T cells may become unnaturally activated. The area gets inflamed, and certain cells help trigger fibrosis—the secretion of certain compounds usually used to make scar tissue. […] This fibrosis accounts for the rigid, tense areas seen in morphea. This fibrosis is part of why affected areas never get completely back to normal. Even after the initial inflammation has subsided, some scar-like tissue remains. […] Other factors may also play a role in triggering the disease in some people. Some of these might include having variations of certain genes (particularly ones important for the immune system), underlying damage to blood vessels in the area, certain kinds of infections, and previous trauma to the area (e.g., through radiation exposure). […] Morphea is not an infectious disease. It’s not contagious, so you can’t spread it to someone else. It is also not a sign of cancer.

• #94 Scleroderma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/scleroderma/symptoms-causes/syc-20351952

  Scleroderma happens when the body produces too much collagen and it builds up in body tissues. Collagen is a fibrous type of protein that makes up the body’s connective tissues, including the skin. […] Experts don’t know exactly what causes this process to begin, but the body’s immune system appears to play a role. Most likely, scleroderma is caused by a combination of factors, including immune system problems, genetics and environmental triggers.

• #95 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  The main regulator of the fibrosis process is TGF-β. An increase in its concentration causes an increase in the expression of collagen types I, III, VI, X, fibronectin and proteoglycans. […] Understanding the genetic basis of morphea is critical to uncovering the mechanisms underlying this disease and identifying potential treatment targets. […] Human leukocyte antigen (HLA) has been implicated as the most promising target in the pathogenesis of morphea, suggesting a genetic predisposition to the disease. […] Recent studies have highlighted the involvement of cutaneous mosaicism as a possible factor in morphea’s pathogenesis. […] Epigenetic factors are considered to be triggers of the morphea, next to environmental factors and genetic predisposition. […] Infectious factors include the occurrence of morphea-like lesions following infections with measles, varicella, Epstein–Barr, hepatitis B and C viruses.

• #96 Causes of Pediatric Localized Scleroderma – National Scleroderma Foundation

  https://scleroderma.org/what-causes-pediatric-localized-scleroderma/

  In localized scleroderma, also called morphea, the immune system doesnt work correctly. Inflammation doesnt go away. It keeps going, inflaming the skin and often, the tissues under the skin. This sets off fibrosis: scarring of skin and tissues. Localized scleroderma is called an autoimmune disease. […] Its unclear why this happens. Some people may be born with certain genes that make them more likely to develop an autoimmune disease. Others may be exposed to something in the environment, like an infection or smoking, that turn on the autoimmune reaction. Researchers are trying to find out why this happens in some people, but not others. […] In localized scleroderma, your immune system attacks the skin and tissue underneath as the foreign object. You may build up extra immune cells and inflammation in these areas of skin and tissue that shouldnt be there. Your skin changes. After some time, these skin changes may become like a scar.

• #97 Causes of Pediatric Localized Scleroderma – National Scleroderma Foundation

  https://scleroderma.org/what-causes-pediatric-localized-scleroderma/

  Inflammation that doesnt stop sets off a new chain of events. Skin cells make collagen, a normal repair protein. Normally, extra collagen is cleaned up when the repair is done, but in localized scleroderma, your skin keeps making more and more collagen. You may have a thick build-up of scar-like collagen. You may lose healthy cells in your skin, muscle, bone, and other tissues.

• #98 What Is New in Morphea—Narrative Review on Molecular Aspects and New Targeted Therapies

  https://www.mdpi.com/2077-0383/13/23/7134

  The main regulator of the fibrosis process is TGF-β. An increase in its concentration causes an increase in the expression of collagen types I, III, VI, X, fibronectin and proteoglycans. […] Understanding the genetic basis of morphea is critical to uncovering the mechanisms underlying this disease and identifying potential treatment targets. […] Human leukocyte antigen (HLA) has been implicated as the most promising target in the pathogenesis of morphea, suggesting a genetic predisposition to the disease. […] Recent studies have highlighted the involvement of cutaneous mosaicism as a possible factor in morphea’s pathogenesis. […] Epigenetic factors are considered to be triggers of the morphea, next to environmental factors and genetic predisposition. […] Infectious factors include the occurrence of morphea-like lesions following infections with measles, varicella, Epstein–Barr, hepatitis B and C viruses.

• #99 Morphea: The 2023 update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9969991/

  Morphea, also known as localized scleroderma, is a chronic inflammatory connective tissue disorder with variable clinical presentations, that affects both adults and children. […] While the etiology is still unknown, many factors may contribute to disease development, including genetic predisposition, vascular dysregulation, TH1/TH2 imbalance with chemokines and cytokines associated with interferon- and profibrotic pathways as well as certain environmental factors. […] While the exact cause of the disease is still not known, certain stimuli (infection, drugs and/or trauma) may trigger vascular and immune dysregulations in genetically predisposed individuals. […] A variety of factors, including genetics, environmental factors, such as infections, skin trauma, autoimmune dysregulation with abnormal cytokine production, and/or vascular dysfunction may play a role in the development of morphea.

• #100 Orphanet: Localized scleroderma

  https://www.orpha.net/en/disease/detail/90289

  The exact cause of localized scleroderma is unknown. The disease originates from a combination of genetic predisposition and environmental factors, implies vascular and autoimmune pathways which lead to localized overproduction of extracellular matrix (collagen).

• #101 Morphea | Health Library | Memorial Health System

  https://www.mhsystem.org/health-library/con-20375265/

  Morphea is a rare skin condition characterized by small red or purple patches that develop firm white or ivory centers. The affected skin becomes tight and less flexible. […] The cause of morphea is unknown. It may be caused by an unusual reaction of your immune system. In people at increased risk of morphea, it could be triggered by injury to the affected area, medications, chemical toxins, an infection or radiation therapy. […] The condition isn’t contagious.

• #102 Morphea: Symptoms, causes, and treatment

  https://www.medicalnewstoday.com/articles/320708

  Most health professionals consider morphea to be an unusual autoimmune condition in which immune system dysfunction occurs and causes characteristic skin symptoms. […] However, the exact cause of the condition is unclear and remains unknown. When morphea occurs, the collagen-producing cells overproduce collagen, causing it to build up and the skin to harden. There is much to learn about morphea, but its onset could be related to: repeated trauma to the skin, aggressive treatments, such as radiation therapy, an infection, skin damage caused by environmental exposure. […] Morphea is not a contagious condition and cannot spread from person to person.

• #103 Study Probes New Gene Therapy for Severe, Localized Scleroderma (Morphea) – The Rheumatologist

  https://www.the-rheumatologist.org/article/study-probes-new-gene-therapy-for-severe-localized-scleroderma-morphea/

  Morphea can be a devastating disease for patients for many reasons: the sclerosis, which can lead to loss of joint mobility and functional disability; the cosmetic disfiguration, caused by dyspigmentation or atrophy; pruritus; and pain. […] No available treatments directly address the underlying disease etiology. […] The majority of patients with localized scleroderma first experience symptoms in childhood. […] Pediatric morphea, in particular, represents a major unmet need, because these patients often have more sclerotic disease that can affect joint function and cause significant pain and disability.

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