CREST syndrome is a subtype of systemic sclerosis (scleroderma), which is an autoimmune connective tissue disorder. The name “CREST” is an acronym that stands for the five main features associated with this syndrome as:
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
In 1910, Thibierge and Weissenbach documented the initial instance report of what was subsequently identified as CRST (calcinosis cutis, Raynaud phenomenon, sclerodactyly, and telangiectasia) syndrome in English by Winterbauer who, in 1964, outlined a set of 8 patients with the characteristics that constitute the acronym CRST.
While he observed esophageal dysfunction in 4 out of 8 patients, he did not incorporate this characteristic in his initial portrayal of CRST syndrome. Frayha et al observed the common incidence of esophageal dysfunction and proposed that the abbreviation CREST might be more fitting. Velayos et al examined 13 patients with CREST and CRST syndromes and discovered that the syndromes were identical.
CREST syndrome is considered a milder form of systemic sclerosis and tends to progress more slowly than the diffuse cutaneous form. It predominantly affects the skin, and the internal organ involvement is typically limited compared to the diffuse form.
Epidemiology
Prevalence: Systemic sclerosis, including CREST syndrome, has an estimated prevalence of around 0.02% to 0.22% of the general population. However, CREST syndrome represents a smaller subset of systemic sclerosis cases.
Sex Distribution: CREST syndrome is more commonly diagnosed in women than in men. The female-to-male ratio can be as high as 3:1.
Age: CREST syndrome can affect individuals of all ages, but it is most commonly presents in individuals between the ages of 30 and 60 years.
Geographic variation: CREST syndrome occurs worldwide, but its prevalence can vary among different ethnic groups and geographic regions.
Anatomy
Pathophysiology
Progressive fibrosis, or the excessive deposition of collagen and other extracellular matrix proteins, is a hallmark of CREST syndrome. This fibrosis affects the skin and various internal organs, causing the characteristic thickening and tightening of the skin and potential complications in organs such as the lungs, heart, gastrointestinal tract, and kidneys.
Fibroblasts are cells responsible for producing collagen and other components of the extracellular matrix. In CREST syndrome, these fibroblasts become activated and overproduce collagen, leading to the development of fibrosis in affected tissues.
One of the early features of CREST syndrome is Raynaud’s phenomenon, which involves abnormal vasospasm of small blood vessels in response to cold or emotional stress. This phenomenon causes characteristic color changes in the skin of the fingers and toes in white, blue, and red colors.
Abnormal immune responses can lead to the formation of autoantibodies, particularly antinuclear antibodies (ANAs), which are present in most individuals with CREST syndrome. In autoimmune diseases like CREST syndrome, the immune system becomes dysregulated, and immune cells, particularly T cells and B cells, start attacking the body’s own tissues.
Etiology
Environmental factors may also play a role in the development of CREST syndrome. These triggers could include exposure to certain chemicals, infections, or other external factors that can initiate or exacerbate the autoimmune response in susceptible individuals.
Certain genes may be involved in regulating the immune system, collagen production, and the function of blood vessels, making some individuals more prone to developing the condition.
Contact with silica, man-made glues, chemicals such as chlorinated chemicals, fragrant chemicals, colorless liquid, toluene, trichloroethylene, formaldehyde, vinyl chloride, and cleaning items have been linked to an increased possibility of developing systemic sclerosis.
Genetics
Prognostic Factors
CREST syndrome is considered a milder form of systemic sclerosis, internal organ involvement can still occur. The specific organs affected, and the severity of organ involvement can significantly impact the prognosis. Commonly affected organs include the esophagus, lungs, heart, gastrointestinal tract, and kidneys.
Pulmonary hypertension i.e., high blood pressure in the arteries of the lungs is a potentially serious complication of CREST syndrome. It can lead to heart failure and significantly impact quality of life.
In research conducted by Mayes et al, the percentage of patients who survived after being diagnosed was calculated to be 77.9% at 5 years, 55.1% at 10 years, 37.4% at 15 years, and 26.8% at 20 years.
The degree of skin participation is a reliable indicator of the chances of survival in individuals with scleroderma.
Clinical History
Age Group:
CREST syndrome can affect individuals of all ages. The typical age group at which CREST syndrome is most diagnosed is between 30 and 60 years old.
Some people may experience the first symptoms and signs of CREST syndrome during their teenage years or early adulthood, while others may not develop the condition until their 50s or 60s.
Physical Examination
Calcinosis: This refers to the formation of calcium deposits under the skin, which can cause painful lumps or nodules.
Raynaud’s phenomenon: Raynaud’s phenomenon is characterized by the narrowing of blood vessels in response to cold temperatures or emotional stress, leading to color changes in the extremities like fingers and toes and causing them to become white, then blue, and finally red when blood flow returns.
Esophageal dysfunction: People with CREST syndrome may experience problems with the smooth muscle of the esophagus, leading to difficulty swallowing and sometimes acid reflux.
Sclerodactyly: Sclerodactyly refers to thickening and tightening of the skin on the fingers and toes, which can cause difficulty in moving the digits.
Telangiectasia: Telangiectasias are small, dilated blood vessels near the surface of the skin, which appear as red spots or lines, especially on the face, hands, and mouth.
Age group
Associated comorbidity
CREST syndrome can affect the smooth muscles of the gastrointestinal tract, leading to complications such as difficulty swallowing (dysphagia), gastroesophageal reflux disease (GERD).
Raynaud’s phenomenon, a common feature of CREST syndrome, can cause severe constriction of blood vessels in response to cold or stress, leading to reduced blood flow to the extremities and potential tissue damage.
Telangiectasias are small, dilated blood vessels near the skin’s surface, particularly in the face, hands, and mouth. While generally harmless, they can sometimes cause bleeding and cosmetic concerns.
Associated activity
Acuity of presentation
Esophageal dysfunction is common in CREST syndrome and may cause difficulty swallowing and acid reflux. These symptoms can develop over time and may be intermittent or progressive.
Skin involvement in CREST syndrome, such as thickening and tightening of the skin on the fingers or dilated blood vessels, may occur gradually over time. These changes are usually limited to the fingers, hands, face, and mouth.
The formation of calcium deposits under the skin also known as calcinosis can occur in some individuals with CREST syndrome. These deposits may develop gradually and cause painful lumps or nodules.
Differential Diagnoses
Systemic Lupus Erythematosus (SLE): It is another autoimmune connective tissue disease that can present with skin changes, Raynaud’s phenomenon, and other systemic symptoms.
Sjogren’s Syndrome: It is an autoimmune disorder characterized by dry eyes and dry mouth. It can also be associated with Raynaud’s phenomenon and specific autoantibodies.
Eosinophilic Fasciitis: This is a rare disorder characterized by inflammation and thickening of the skin and connective tissues, resembling early stages of systemic sclerosis.
Cutaneous Systemic Sclerosis: CREST syndrome is a subset of systemic sclerosis. Diffuse cutaneous systemic sclerosis is another form of the disease, characterized by widespread skin involvement.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Symptomatic Management:
Gastrointestinal Symptoms: Lifestyle modifications, such as avoiding large meals, elevating the head of the bed, and dietary changes, can help manage acid reflux and difficulty swallowing. Proton pump inhibitors (PPIs) or other medications may be prescribed for acid reflux.
Raynaud’s Phenomenon: Keeping warm and avoiding cold exposure is essential. Calcium channel blockers, such as nifedipine, can be prescribed to improve blood flow and reduce the frequency and severity of Raynaud’s attacks.
Physical and Occupational Therapies:
Physical therapy can help improve joint function and mobility and address muscle weakness.
Occupational therapy can help individuals adapt to limitations and maintain independence in daily activities.
Regular Monitoring and Lifestyle changes:
Regular medical check-ups are essential for monitoring disease progression, managing symptoms, and detecting potential complications early.
Smoking cessation is crucial, as smoking can exacerbate symptoms and worsen lung involvement.
Maintaining a healthy diet and exercise routine can promote overall well-being and help manage complications like gastroesophageal reflux.
Avoid cold: CREST syndrome causes fingers and toes to become sensitive to cold temperatures, leading to color changes and pain. To minimize symptoms, avoid exposure to cold environments and cold objects.
Protection of skin: CREST syndrome can cause skin sensitivity and the formation of painful calcium deposits. Apply moisturizing creams to keep the skin hydrated and reduce skin irritation.
Protection of hands: Protect hands from injury and trauma to minimize the risk of developing calcinosis, which involves calcium deposits under the skin.
Dietary supplements: A healthy and balanced diet is essential for overall well-being. In some individuals it may be found that certain foods trigger gastrointestinal symptoms hence dietary adjustments may be required.
Physical activity: Engage in regular, low-impact exercise as recommended by a healthcare provider. Exercise can help improve joint and muscle function and overall well-being.
Use of calcium channel blockers
These medications help relax and dilate blood vessels, reducing the frequency and severity of Raynaud’s attacks and improving blood flow to the extremities.
Calcium channel blockers work by blocking the entry of calcium ions into smooth muscle cells, leading to relaxation of the blood vessels and increased blood flow.
Nifedipine: Nifedipine is available in immediate-release and extended-release formulations. It works by blocking calcium channels in smooth muscle cells, causing relaxation and dilation of blood vessels, which helps to improve peripheral blood circulation.
Nicardipine: Nicardipine is another calcium channel blocker that can be used to manage Raynaud’s phenomenon in CREST syndrome. It is available in both oral and intravenous forms. It blocks calcium channels in blood vessel walls, leading to vasodilation and improved blood flow. Intravenous nicardipine may be used in severe cases of Raynaud’s phenomenon when rapid control of symptoms is required.
Use of Prostaglandins
CREST syndrome, prostaglandins are primarily used for the treatment of digital ulcers, a common complication of the condition. Prostaglandins help to promote blood vessel dilation, enhance blood flow, and accelerate the healing process.
Alprostadil: Alprostadil is a synthetic prostaglandin E1 analog. It is available in various formulations, including topical creams, injections, and intraurethral suppositories. In CREST syndrome, topical alprostadil cream or ointment can be applied to the affected areas to enhance blood flow and promote healing of digital ulcers.
Iloprost: It is a synthetic prostacyclin (prostaglandin I2) analog. It can be administered intravenously or inhaled. Intravenous iloprost is often used as a treatment for severe Raynaud’s phenomenon and digital ulcers in CREST syndrome.
It helps to dilate blood vessels, reduce platelet aggregation, and has anti-inflammatory effects.
Use of Phosphodiesterase (PDE) enzyme inhibitors
Phosphodiesterase (PDE) enzyme inhibitors are a class of medications that work by blocking the activity of phosphodiesterase enzymes. These molecules play a role in regulating various cellular processes, including smooth muscle relaxation, inflammation, and immune response.
Cilostazol: It is a medication that belongs to a class of drugs called phosphodiesterase 3 (PDE-3) inhibitors. In CREST syndrome, cilostazol may be considered as a treatment option for improving peripheral circulation and reducing the symptoms of Raynaud’s phenomenon. Raynaud’s phenomenon involves vasospasm of small arteries, resulting in reduced blood flow to the fingers and toes.
Cilostazol and its metabolites are suppressors of phosphodiesterase III and, consequently, cyclic AMP is elevated, which causes suppression of platelet aggregation and widening of blood vessels.
Use of Proton pump inhibitors (PPI’s)
Proton pump inhibitors (PPIs) are a class of medications commonly used to reduce stomach acid production.
Omeprazole: Omeprazole is a widely prescribed PPI used to treat conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
By reducing stomach acid production, omeprazole can help relieve acid reflux, heartburn, and discomfort caused by esophageal involvement in CREST syndrome.
Pantoprazole: Pantoprazole is another PPI commonly used for managing conditions related to excess stomach acid, such as GERD and gastric ulcers. It works by inhibiting the action of proton pumps in the stomach lining, thus reducing acid production.
Use of combination of Antihypertensive agents with Angiotensin-converting enzyme (ACE) inhibitors
Antihypertensive agents are medications used to treat high blood pressure. In CREST syndrome, ACE inhibitors may be used to control hypertension if present, as well as to improve blood flow and protect the kidneys. They work by blocking the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that narrows blood vessels and increases blood pressure.
Losartan: It is a nonpeptide angiotensin II receptor antagonist that inhibits the narrowing of blood vessels and the secretion of aldosterone caused by angiotensin II. It may result in a more thorough suppression of the renin-angiotensin system compared to ACE inhibitors.
It is utilized for patients who cannot tolerate ACE inhibitors. Losartan is not as potent in patients with scleroderma as it is in individuals with primary Raynaud phenomenon.
Use of Histamine H2 antagonists/blockers
Histamine H2 antagonists, also known as H2 blockers, are a class of medications used to reduce the production of stomach acid. While their primary indication is for the treatment of conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
Ranitidine: Ranitidine is an H2 antagonist that works by blocking histamine receptors in the stomach, leading to a reduction in the production of stomach acid.
In CREST syndrome, ranitidine or other H2 blockers may be prescribed to alleviate symptoms of esophageal dysfunction, such as acid reflux and heartburn.
Use of combination of Antidepressants with Selective serotonin reuptake inhibitors (SSRIs)
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medications commonly prescribed to treat depression, anxiety, and other mood disorders. SSRIs are a commonly prescribed class of antidepressants that work by increasing the levels of serotonin, a neurotransmitter involved in regulating mood.
Fluoxetine: Fluoxetine is one of the most well-known SSRIs and is used to treat various mental health conditions, including depression, anxiety disorders, and obsessive-compulsive disorder (OCD). In individuals with CREST syndrome, fluoxetine may be prescribed to help manage symptoms of depression or anxiety.
Fluoxetine can be administered in both liquid and capsule form. It can be administered as a single dose or divided into multiple doses.
The consumption of food does not significantly change the levels. Due to its extended half-life of 72 hours, it may require 4 to 6 weeks to reach stable levels.
Digital Sympathectomy: For severe cases of Raynaud’s phenomenon that do not respond well to medications or other conservative measures, digital sympathectomy may be considered. This surgical procedure involves cutting or clamping the sympathetic nerves that control blood vessel constriction in the fingers and toes.
Debridement of Calcium: In cases of calcinosis, where calcium deposits cause painful lumps under the skin, surgical debridement or removal of the deposits may be performed to alleviate pain and reduce the risk of infection.
Gastrointestinal (GI) Procedure: If CREST syndrome leads to significant esophageal dysfunction, procedures such as esophageal dilation or endoscopic interventions may be performed to widen narrowed areas of the esophagus and improve swallowing.
use-of-phases-in-managing-crest-syndrome
Initial Phase: This phase begins with the early presentation of symptoms and the diagnosis of CREST syndrome.
The primary goals of this phase are to confirm the diagnosis, assess disease severity, and start appropriate treatments to manage symptoms and prevent complications.
The focus is on controlling Raynaud’s phenomenon, managing gastrointestinal symptoms, and addressing skin changes and other initial symptoms.
Immunosuppressive medications may be initiated in cases of active inflammation or organ involvement.
Maintenance Phase: The primary goal during this phase is to maintain disease stability, prevent disease progression, and manage complications and comorbidities.
Regular follow-up visits with healthcare providers are scheduled to monitor disease activity, assess treatment efficacy, and adjust medications as needed.
Physical therapy and occupational therapy may be continued to maintain joint function and improve mobility.
CREST syndrome is a subtype of systemic sclerosis (scleroderma), which is an autoimmune connective tissue disorder. The name “CREST” is an acronym that stands for the five main features associated with this syndrome as:
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
In 1910, Thibierge and Weissenbach documented the initial instance report of what was subsequently identified as CRST (calcinosis cutis, Raynaud phenomenon, sclerodactyly, and telangiectasia) syndrome in English by Winterbauer who, in 1964, outlined a set of 8 patients with the characteristics that constitute the acronym CRST.
While he observed esophageal dysfunction in 4 out of 8 patients, he did not incorporate this characteristic in his initial portrayal of CRST syndrome. Frayha et al observed the common incidence of esophageal dysfunction and proposed that the abbreviation CREST might be more fitting. Velayos et al examined 13 patients with CREST and CRST syndromes and discovered that the syndromes were identical.
CREST syndrome is considered a milder form of systemic sclerosis and tends to progress more slowly than the diffuse cutaneous form. It predominantly affects the skin, and the internal organ involvement is typically limited compared to the diffuse form.
Prevalence: Systemic sclerosis, including CREST syndrome, has an estimated prevalence of around 0.02% to 0.22% of the general population. However, CREST syndrome represents a smaller subset of systemic sclerosis cases.
Sex Distribution: CREST syndrome is more commonly diagnosed in women than in men. The female-to-male ratio can be as high as 3:1.
Age: CREST syndrome can affect individuals of all ages, but it is most commonly presents in individuals between the ages of 30 and 60 years.
Geographic variation: CREST syndrome occurs worldwide, but its prevalence can vary among different ethnic groups and geographic regions.
Progressive fibrosis, or the excessive deposition of collagen and other extracellular matrix proteins, is a hallmark of CREST syndrome. This fibrosis affects the skin and various internal organs, causing the characteristic thickening and tightening of the skin and potential complications in organs such as the lungs, heart, gastrointestinal tract, and kidneys.
Fibroblasts are cells responsible for producing collagen and other components of the extracellular matrix. In CREST syndrome, these fibroblasts become activated and overproduce collagen, leading to the development of fibrosis in affected tissues.
One of the early features of CREST syndrome is Raynaud’s phenomenon, which involves abnormal vasospasm of small blood vessels in response to cold or emotional stress. This phenomenon causes characteristic color changes in the skin of the fingers and toes in white, blue, and red colors.
Abnormal immune responses can lead to the formation of autoantibodies, particularly antinuclear antibodies (ANAs), which are present in most individuals with CREST syndrome. In autoimmune diseases like CREST syndrome, the immune system becomes dysregulated, and immune cells, particularly T cells and B cells, start attacking the body’s own tissues.
Environmental factors may also play a role in the development of CREST syndrome. These triggers could include exposure to certain chemicals, infections, or other external factors that can initiate or exacerbate the autoimmune response in susceptible individuals.
Certain genes may be involved in regulating the immune system, collagen production, and the function of blood vessels, making some individuals more prone to developing the condition.
Contact with silica, man-made glues, chemicals such as chlorinated chemicals, fragrant chemicals, colorless liquid, toluene, trichloroethylene, formaldehyde, vinyl chloride, and cleaning items have been linked to an increased possibility of developing systemic sclerosis.
CREST syndrome is considered a milder form of systemic sclerosis, internal organ involvement can still occur. The specific organs affected, and the severity of organ involvement can significantly impact the prognosis. Commonly affected organs include the esophagus, lungs, heart, gastrointestinal tract, and kidneys.
Pulmonary hypertension i.e., high blood pressure in the arteries of the lungs is a potentially serious complication of CREST syndrome. It can lead to heart failure and significantly impact quality of life.
In research conducted by Mayes et al, the percentage of patients who survived after being diagnosed was calculated to be 77.9% at 5 years, 55.1% at 10 years, 37.4% at 15 years, and 26.8% at 20 years.
The degree of skin participation is a reliable indicator of the chances of survival in individuals with scleroderma.
Age Group:
CREST syndrome can affect individuals of all ages. The typical age group at which CREST syndrome is most diagnosed is between 30 and 60 years old.
Some people may experience the first symptoms and signs of CREST syndrome during their teenage years or early adulthood, while others may not develop the condition until their 50s or 60s.
Calcinosis: This refers to the formation of calcium deposits under the skin, which can cause painful lumps or nodules.
Raynaud’s phenomenon: Raynaud’s phenomenon is characterized by the narrowing of blood vessels in response to cold temperatures or emotional stress, leading to color changes in the extremities like fingers and toes and causing them to become white, then blue, and finally red when blood flow returns.
Esophageal dysfunction: People with CREST syndrome may experience problems with the smooth muscle of the esophagus, leading to difficulty swallowing and sometimes acid reflux.
Sclerodactyly: Sclerodactyly refers to thickening and tightening of the skin on the fingers and toes, which can cause difficulty in moving the digits.
Telangiectasia: Telangiectasias are small, dilated blood vessels near the surface of the skin, which appear as red spots or lines, especially on the face, hands, and mouth.
CREST syndrome can affect the smooth muscles of the gastrointestinal tract, leading to complications such as difficulty swallowing (dysphagia), gastroesophageal reflux disease (GERD).
Raynaud’s phenomenon, a common feature of CREST syndrome, can cause severe constriction of blood vessels in response to cold or stress, leading to reduced blood flow to the extremities and potential tissue damage.
Telangiectasias are small, dilated blood vessels near the skin’s surface, particularly in the face, hands, and mouth. While generally harmless, they can sometimes cause bleeding and cosmetic concerns.
Esophageal dysfunction is common in CREST syndrome and may cause difficulty swallowing and acid reflux. These symptoms can develop over time and may be intermittent or progressive.
Skin involvement in CREST syndrome, such as thickening and tightening of the skin on the fingers or dilated blood vessels, may occur gradually over time. These changes are usually limited to the fingers, hands, face, and mouth.
The formation of calcium deposits under the skin also known as calcinosis can occur in some individuals with CREST syndrome. These deposits may develop gradually and cause painful lumps or nodules.
Systemic Lupus Erythematosus (SLE): It is another autoimmune connective tissue disease that can present with skin changes, Raynaud’s phenomenon, and other systemic symptoms.
Sjogren’s Syndrome: It is an autoimmune disorder characterized by dry eyes and dry mouth. It can also be associated with Raynaud’s phenomenon and specific autoantibodies.
Eosinophilic Fasciitis: This is a rare disorder characterized by inflammation and thickening of the skin and connective tissues, resembling early stages of systemic sclerosis.
Cutaneous Systemic Sclerosis: CREST syndrome is a subset of systemic sclerosis. Diffuse cutaneous systemic sclerosis is another form of the disease, characterized by widespread skin involvement.
Symptomatic Management:
Gastrointestinal Symptoms: Lifestyle modifications, such as avoiding large meals, elevating the head of the bed, and dietary changes, can help manage acid reflux and difficulty swallowing. Proton pump inhibitors (PPIs) or other medications may be prescribed for acid reflux.
Raynaud’s Phenomenon: Keeping warm and avoiding cold exposure is essential. Calcium channel blockers, such as nifedipine, can be prescribed to improve blood flow and reduce the frequency and severity of Raynaud’s attacks.
Physical and Occupational Therapies:
Physical therapy can help improve joint function and mobility and address muscle weakness.
Occupational therapy can help individuals adapt to limitations and maintain independence in daily activities.
Regular Monitoring and Lifestyle changes:
Regular medical check-ups are essential for monitoring disease progression, managing symptoms, and detecting potential complications early.
Smoking cessation is crucial, as smoking can exacerbate symptoms and worsen lung involvement.
Maintaining a healthy diet and exercise routine can promote overall well-being and help manage complications like gastroesophageal reflux.
Dermatology, General
Body maintenance and hygiene:
Avoid cold: CREST syndrome causes fingers and toes to become sensitive to cold temperatures, leading to color changes and pain. To minimize symptoms, avoid exposure to cold environments and cold objects.
Protection of skin: CREST syndrome can cause skin sensitivity and the formation of painful calcium deposits. Apply moisturizing creams to keep the skin hydrated and reduce skin irritation.
Protection of hands: Protect hands from injury and trauma to minimize the risk of developing calcinosis, which involves calcium deposits under the skin.
Dietary supplements: A healthy and balanced diet is essential for overall well-being. In some individuals it may be found that certain foods trigger gastrointestinal symptoms hence dietary adjustments may be required.
Physical activity: Engage in regular, low-impact exercise as recommended by a healthcare provider. Exercise can help improve joint and muscle function and overall well-being.
Dermatology, General
These medications help relax and dilate blood vessels, reducing the frequency and severity of Raynaud’s attacks and improving blood flow to the extremities.
Calcium channel blockers work by blocking the entry of calcium ions into smooth muscle cells, leading to relaxation of the blood vessels and increased blood flow.
Nifedipine: Nifedipine is available in immediate-release and extended-release formulations. It works by blocking calcium channels in smooth muscle cells, causing relaxation and dilation of blood vessels, which helps to improve peripheral blood circulation.
Nicardipine: Nicardipine is another calcium channel blocker that can be used to manage Raynaud’s phenomenon in CREST syndrome. It is available in both oral and intravenous forms. It blocks calcium channels in blood vessel walls, leading to vasodilation and improved blood flow. Intravenous nicardipine may be used in severe cases of Raynaud’s phenomenon when rapid control of symptoms is required.
Dermatology, General
CREST syndrome, prostaglandins are primarily used for the treatment of digital ulcers, a common complication of the condition. Prostaglandins help to promote blood vessel dilation, enhance blood flow, and accelerate the healing process.
Alprostadil: Alprostadil is a synthetic prostaglandin E1 analog. It is available in various formulations, including topical creams, injections, and intraurethral suppositories. In CREST syndrome, topical alprostadil cream or ointment can be applied to the affected areas to enhance blood flow and promote healing of digital ulcers.
Iloprost: It is a synthetic prostacyclin (prostaglandin I2) analog. It can be administered intravenously or inhaled. Intravenous iloprost is often used as a treatment for severe Raynaud’s phenomenon and digital ulcers in CREST syndrome.
It helps to dilate blood vessels, reduce platelet aggregation, and has anti-inflammatory effects.
Dermatology, General
Phosphodiesterase (PDE) enzyme inhibitors are a class of medications that work by blocking the activity of phosphodiesterase enzymes. These molecules play a role in regulating various cellular processes, including smooth muscle relaxation, inflammation, and immune response.
Cilostazol: It is a medication that belongs to a class of drugs called phosphodiesterase 3 (PDE-3) inhibitors. In CREST syndrome, cilostazol may be considered as a treatment option for improving peripheral circulation and reducing the symptoms of Raynaud’s phenomenon. Raynaud’s phenomenon involves vasospasm of small arteries, resulting in reduced blood flow to the fingers and toes.
Cilostazol and its metabolites are suppressors of phosphodiesterase III and, consequently, cyclic AMP is elevated, which causes suppression of platelet aggregation and widening of blood vessels.
Dermatology, General
Proton pump inhibitors (PPIs) are a class of medications commonly used to reduce stomach acid production.
Omeprazole: Omeprazole is a widely prescribed PPI used to treat conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
By reducing stomach acid production, omeprazole can help relieve acid reflux, heartburn, and discomfort caused by esophageal involvement in CREST syndrome.
Pantoprazole: Pantoprazole is another PPI commonly used for managing conditions related to excess stomach acid, such as GERD and gastric ulcers. It works by inhibiting the action of proton pumps in the stomach lining, thus reducing acid production.
Dermatology, General
Antihypertensive agents are medications used to treat high blood pressure. In CREST syndrome, ACE inhibitors may be used to control hypertension if present, as well as to improve blood flow and protect the kidneys. They work by blocking the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that narrows blood vessels and increases blood pressure.
Losartan: It is a nonpeptide angiotensin II receptor antagonist that inhibits the narrowing of blood vessels and the secretion of aldosterone caused by angiotensin II. It may result in a more thorough suppression of the renin-angiotensin system compared to ACE inhibitors.
It is utilized for patients who cannot tolerate ACE inhibitors. Losartan is not as potent in patients with scleroderma as it is in individuals with primary Raynaud phenomenon.
Histamine H2 antagonists, also known as H2 blockers, are a class of medications used to reduce the production of stomach acid. While their primary indication is for the treatment of conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
Ranitidine: Ranitidine is an H2 antagonist that works by blocking histamine receptors in the stomach, leading to a reduction in the production of stomach acid.
In CREST syndrome, ranitidine or other H2 blockers may be prescribed to alleviate symptoms of esophageal dysfunction, such as acid reflux and heartburn.
Dermatology, General
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medications commonly prescribed to treat depression, anxiety, and other mood disorders. SSRIs are a commonly prescribed class of antidepressants that work by increasing the levels of serotonin, a neurotransmitter involved in regulating mood.
Fluoxetine: Fluoxetine is one of the most well-known SSRIs and is used to treat various mental health conditions, including depression, anxiety disorders, and obsessive-compulsive disorder (OCD). In individuals with CREST syndrome, fluoxetine may be prescribed to help manage symptoms of depression or anxiety.
Fluoxetine can be administered in both liquid and capsule form. It can be administered as a single dose or divided into multiple doses.
The consumption of food does not significantly change the levels. Due to its extended half-life of 72 hours, it may require 4 to 6 weeks to reach stable levels.
Dermatology, General
Digital Sympathectomy: For severe cases of Raynaud’s phenomenon that do not respond well to medications or other conservative measures, digital sympathectomy may be considered. This surgical procedure involves cutting or clamping the sympathetic nerves that control blood vessel constriction in the fingers and toes.
Debridement of Calcium: In cases of calcinosis, where calcium deposits cause painful lumps under the skin, surgical debridement or removal of the deposits may be performed to alleviate pain and reduce the risk of infection.
Gastrointestinal (GI) Procedure: If CREST syndrome leads to significant esophageal dysfunction, procedures such as esophageal dilation or endoscopic interventions may be performed to widen narrowed areas of the esophagus and improve swallowing.
Dermatology, General
Initial Phase: This phase begins with the early presentation of symptoms and the diagnosis of CREST syndrome.
The primary goals of this phase are to confirm the diagnosis, assess disease severity, and start appropriate treatments to manage symptoms and prevent complications.
The focus is on controlling Raynaud’s phenomenon, managing gastrointestinal symptoms, and addressing skin changes and other initial symptoms.
Immunosuppressive medications may be initiated in cases of active inflammation or organ involvement.
Maintenance Phase: The primary goal during this phase is to maintain disease stability, prevent disease progression, and manage complications and comorbidities.
Regular follow-up visits with healthcare providers are scheduled to monitor disease activity, assess treatment efficacy, and adjust medications as needed.
Physical therapy and occupational therapy may be continued to maintain joint function and improve mobility.
CREST syndrome is a subtype of systemic sclerosis (scleroderma), which is an autoimmune connective tissue disorder. The name “CREST” is an acronym that stands for the five main features associated with this syndrome as:
Calcinosis
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasia
In 1910, Thibierge and Weissenbach documented the initial instance report of what was subsequently identified as CRST (calcinosis cutis, Raynaud phenomenon, sclerodactyly, and telangiectasia) syndrome in English by Winterbauer who, in 1964, outlined a set of 8 patients with the characteristics that constitute the acronym CRST.
While he observed esophageal dysfunction in 4 out of 8 patients, he did not incorporate this characteristic in his initial portrayal of CRST syndrome. Frayha et al observed the common incidence of esophageal dysfunction and proposed that the abbreviation CREST might be more fitting. Velayos et al examined 13 patients with CREST and CRST syndromes and discovered that the syndromes were identical.
CREST syndrome is considered a milder form of systemic sclerosis and tends to progress more slowly than the diffuse cutaneous form. It predominantly affects the skin, and the internal organ involvement is typically limited compared to the diffuse form.
Prevalence: Systemic sclerosis, including CREST syndrome, has an estimated prevalence of around 0.02% to 0.22% of the general population. However, CREST syndrome represents a smaller subset of systemic sclerosis cases.
Sex Distribution: CREST syndrome is more commonly diagnosed in women than in men. The female-to-male ratio can be as high as 3:1.
Age: CREST syndrome can affect individuals of all ages, but it is most commonly presents in individuals between the ages of 30 and 60 years.
Geographic variation: CREST syndrome occurs worldwide, but its prevalence can vary among different ethnic groups and geographic regions.
Progressive fibrosis, or the excessive deposition of collagen and other extracellular matrix proteins, is a hallmark of CREST syndrome. This fibrosis affects the skin and various internal organs, causing the characteristic thickening and tightening of the skin and potential complications in organs such as the lungs, heart, gastrointestinal tract, and kidneys.
Fibroblasts are cells responsible for producing collagen and other components of the extracellular matrix. In CREST syndrome, these fibroblasts become activated and overproduce collagen, leading to the development of fibrosis in affected tissues.
One of the early features of CREST syndrome is Raynaud’s phenomenon, which involves abnormal vasospasm of small blood vessels in response to cold or emotional stress. This phenomenon causes characteristic color changes in the skin of the fingers and toes in white, blue, and red colors.
Abnormal immune responses can lead to the formation of autoantibodies, particularly antinuclear antibodies (ANAs), which are present in most individuals with CREST syndrome. In autoimmune diseases like CREST syndrome, the immune system becomes dysregulated, and immune cells, particularly T cells and B cells, start attacking the body’s own tissues.
Environmental factors may also play a role in the development of CREST syndrome. These triggers could include exposure to certain chemicals, infections, or other external factors that can initiate or exacerbate the autoimmune response in susceptible individuals.
Certain genes may be involved in regulating the immune system, collagen production, and the function of blood vessels, making some individuals more prone to developing the condition.
Contact with silica, man-made glues, chemicals such as chlorinated chemicals, fragrant chemicals, colorless liquid, toluene, trichloroethylene, formaldehyde, vinyl chloride, and cleaning items have been linked to an increased possibility of developing systemic sclerosis.
CREST syndrome is considered a milder form of systemic sclerosis, internal organ involvement can still occur. The specific organs affected, and the severity of organ involvement can significantly impact the prognosis. Commonly affected organs include the esophagus, lungs, heart, gastrointestinal tract, and kidneys.
Pulmonary hypertension i.e., high blood pressure in the arteries of the lungs is a potentially serious complication of CREST syndrome. It can lead to heart failure and significantly impact quality of life.
In research conducted by Mayes et al, the percentage of patients who survived after being diagnosed was calculated to be 77.9% at 5 years, 55.1% at 10 years, 37.4% at 15 years, and 26.8% at 20 years.
The degree of skin participation is a reliable indicator of the chances of survival in individuals with scleroderma.
Age Group:
CREST syndrome can affect individuals of all ages. The typical age group at which CREST syndrome is most diagnosed is between 30 and 60 years old.
Some people may experience the first symptoms and signs of CREST syndrome during their teenage years or early adulthood, while others may not develop the condition until their 50s or 60s.
Calcinosis: This refers to the formation of calcium deposits under the skin, which can cause painful lumps or nodules.
Raynaud’s phenomenon: Raynaud’s phenomenon is characterized by the narrowing of blood vessels in response to cold temperatures or emotional stress, leading to color changes in the extremities like fingers and toes and causing them to become white, then blue, and finally red when blood flow returns.
Esophageal dysfunction: People with CREST syndrome may experience problems with the smooth muscle of the esophagus, leading to difficulty swallowing and sometimes acid reflux.
Sclerodactyly: Sclerodactyly refers to thickening and tightening of the skin on the fingers and toes, which can cause difficulty in moving the digits.
Telangiectasia: Telangiectasias are small, dilated blood vessels near the surface of the skin, which appear as red spots or lines, especially on the face, hands, and mouth.
CREST syndrome can affect the smooth muscles of the gastrointestinal tract, leading to complications such as difficulty swallowing (dysphagia), gastroesophageal reflux disease (GERD).
Raynaud’s phenomenon, a common feature of CREST syndrome, can cause severe constriction of blood vessels in response to cold or stress, leading to reduced blood flow to the extremities and potential tissue damage.
Telangiectasias are small, dilated blood vessels near the skin’s surface, particularly in the face, hands, and mouth. While generally harmless, they can sometimes cause bleeding and cosmetic concerns.
Esophageal dysfunction is common in CREST syndrome and may cause difficulty swallowing and acid reflux. These symptoms can develop over time and may be intermittent or progressive.
Skin involvement in CREST syndrome, such as thickening and tightening of the skin on the fingers or dilated blood vessels, may occur gradually over time. These changes are usually limited to the fingers, hands, face, and mouth.
The formation of calcium deposits under the skin also known as calcinosis can occur in some individuals with CREST syndrome. These deposits may develop gradually and cause painful lumps or nodules.
Systemic Lupus Erythematosus (SLE): It is another autoimmune connective tissue disease that can present with skin changes, Raynaud’s phenomenon, and other systemic symptoms.
Sjogren’s Syndrome: It is an autoimmune disorder characterized by dry eyes and dry mouth. It can also be associated with Raynaud’s phenomenon and specific autoantibodies.
Eosinophilic Fasciitis: This is a rare disorder characterized by inflammation and thickening of the skin and connective tissues, resembling early stages of systemic sclerosis.
Cutaneous Systemic Sclerosis: CREST syndrome is a subset of systemic sclerosis. Diffuse cutaneous systemic sclerosis is another form of the disease, characterized by widespread skin involvement.
Symptomatic Management:
Gastrointestinal Symptoms: Lifestyle modifications, such as avoiding large meals, elevating the head of the bed, and dietary changes, can help manage acid reflux and difficulty swallowing. Proton pump inhibitors (PPIs) or other medications may be prescribed for acid reflux.
Raynaud’s Phenomenon: Keeping warm and avoiding cold exposure is essential. Calcium channel blockers, such as nifedipine, can be prescribed to improve blood flow and reduce the frequency and severity of Raynaud’s attacks.
Physical and Occupational Therapies:
Physical therapy can help improve joint function and mobility and address muscle weakness.
Occupational therapy can help individuals adapt to limitations and maintain independence in daily activities.
Regular Monitoring and Lifestyle changes:
Regular medical check-ups are essential for monitoring disease progression, managing symptoms, and detecting potential complications early.
Smoking cessation is crucial, as smoking can exacerbate symptoms and worsen lung involvement.
Maintaining a healthy diet and exercise routine can promote overall well-being and help manage complications like gastroesophageal reflux.
Dermatology, General
Body maintenance and hygiene:
Avoid cold: CREST syndrome causes fingers and toes to become sensitive to cold temperatures, leading to color changes and pain. To minimize symptoms, avoid exposure to cold environments and cold objects.
Protection of skin: CREST syndrome can cause skin sensitivity and the formation of painful calcium deposits. Apply moisturizing creams to keep the skin hydrated and reduce skin irritation.
Protection of hands: Protect hands from injury and trauma to minimize the risk of developing calcinosis, which involves calcium deposits under the skin.
Dietary supplements: A healthy and balanced diet is essential for overall well-being. In some individuals it may be found that certain foods trigger gastrointestinal symptoms hence dietary adjustments may be required.
Physical activity: Engage in regular, low-impact exercise as recommended by a healthcare provider. Exercise can help improve joint and muscle function and overall well-being.
Dermatology, General
These medications help relax and dilate blood vessels, reducing the frequency and severity of Raynaud’s attacks and improving blood flow to the extremities.
Calcium channel blockers work by blocking the entry of calcium ions into smooth muscle cells, leading to relaxation of the blood vessels and increased blood flow.
Nifedipine: Nifedipine is available in immediate-release and extended-release formulations. It works by blocking calcium channels in smooth muscle cells, causing relaxation and dilation of blood vessels, which helps to improve peripheral blood circulation.
Nicardipine: Nicardipine is another calcium channel blocker that can be used to manage Raynaud’s phenomenon in CREST syndrome. It is available in both oral and intravenous forms. It blocks calcium channels in blood vessel walls, leading to vasodilation and improved blood flow. Intravenous nicardipine may be used in severe cases of Raynaud’s phenomenon when rapid control of symptoms is required.
Dermatology, General
CREST syndrome, prostaglandins are primarily used for the treatment of digital ulcers, a common complication of the condition. Prostaglandins help to promote blood vessel dilation, enhance blood flow, and accelerate the healing process.
Alprostadil: Alprostadil is a synthetic prostaglandin E1 analog. It is available in various formulations, including topical creams, injections, and intraurethral suppositories. In CREST syndrome, topical alprostadil cream or ointment can be applied to the affected areas to enhance blood flow and promote healing of digital ulcers.
Iloprost: It is a synthetic prostacyclin (prostaglandin I2) analog. It can be administered intravenously or inhaled. Intravenous iloprost is often used as a treatment for severe Raynaud’s phenomenon and digital ulcers in CREST syndrome.
It helps to dilate blood vessels, reduce platelet aggregation, and has anti-inflammatory effects.
Dermatology, General
Phosphodiesterase (PDE) enzyme inhibitors are a class of medications that work by blocking the activity of phosphodiesterase enzymes. These molecules play a role in regulating various cellular processes, including smooth muscle relaxation, inflammation, and immune response.
Cilostazol: It is a medication that belongs to a class of drugs called phosphodiesterase 3 (PDE-3) inhibitors. In CREST syndrome, cilostazol may be considered as a treatment option for improving peripheral circulation and reducing the symptoms of Raynaud’s phenomenon. Raynaud’s phenomenon involves vasospasm of small arteries, resulting in reduced blood flow to the fingers and toes.
Cilostazol and its metabolites are suppressors of phosphodiesterase III and, consequently, cyclic AMP is elevated, which causes suppression of platelet aggregation and widening of blood vessels.
Dermatology, General
Proton pump inhibitors (PPIs) are a class of medications commonly used to reduce stomach acid production.
Omeprazole: Omeprazole is a widely prescribed PPI used to treat conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
By reducing stomach acid production, omeprazole can help relieve acid reflux, heartburn, and discomfort caused by esophageal involvement in CREST syndrome.
Pantoprazole: Pantoprazole is another PPI commonly used for managing conditions related to excess stomach acid, such as GERD and gastric ulcers. It works by inhibiting the action of proton pumps in the stomach lining, thus reducing acid production.
Dermatology, General
Antihypertensive agents are medications used to treat high blood pressure. In CREST syndrome, ACE inhibitors may be used to control hypertension if present, as well as to improve blood flow and protect the kidneys. They work by blocking the enzyme responsible for converting angiotensin I to angiotensin II, a hormone that narrows blood vessels and increases blood pressure.
Losartan: It is a nonpeptide angiotensin II receptor antagonist that inhibits the narrowing of blood vessels and the secretion of aldosterone caused by angiotensin II. It may result in a more thorough suppression of the renin-angiotensin system compared to ACE inhibitors.
It is utilized for patients who cannot tolerate ACE inhibitors. Losartan is not as potent in patients with scleroderma as it is in individuals with primary Raynaud phenomenon.
Histamine H2 antagonists, also known as H2 blockers, are a class of medications used to reduce the production of stomach acid. While their primary indication is for the treatment of conditions such as gastroesophageal reflux disease (GERD) and peptic ulcers.
Ranitidine: Ranitidine is an H2 antagonist that works by blocking histamine receptors in the stomach, leading to a reduction in the production of stomach acid.
In CREST syndrome, ranitidine or other H2 blockers may be prescribed to alleviate symptoms of esophageal dysfunction, such as acid reflux and heartburn.
Dermatology, General
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant medications commonly prescribed to treat depression, anxiety, and other mood disorders. SSRIs are a commonly prescribed class of antidepressants that work by increasing the levels of serotonin, a neurotransmitter involved in regulating mood.
Fluoxetine: Fluoxetine is one of the most well-known SSRIs and is used to treat various mental health conditions, including depression, anxiety disorders, and obsessive-compulsive disorder (OCD). In individuals with CREST syndrome, fluoxetine may be prescribed to help manage symptoms of depression or anxiety.
Fluoxetine can be administered in both liquid and capsule form. It can be administered as a single dose or divided into multiple doses.
The consumption of food does not significantly change the levels. Due to its extended half-life of 72 hours, it may require 4 to 6 weeks to reach stable levels.
Dermatology, General
Digital Sympathectomy: For severe cases of Raynaud’s phenomenon that do not respond well to medications or other conservative measures, digital sympathectomy may be considered. This surgical procedure involves cutting or clamping the sympathetic nerves that control blood vessel constriction in the fingers and toes.
Debridement of Calcium: In cases of calcinosis, where calcium deposits cause painful lumps under the skin, surgical debridement or removal of the deposits may be performed to alleviate pain and reduce the risk of infection.
Gastrointestinal (GI) Procedure: If CREST syndrome leads to significant esophageal dysfunction, procedures such as esophageal dilation or endoscopic interventions may be performed to widen narrowed areas of the esophagus and improve swallowing.
Dermatology, General
Initial Phase: This phase begins with the early presentation of symptoms and the diagnosis of CREST syndrome.
The primary goals of this phase are to confirm the diagnosis, assess disease severity, and start appropriate treatments to manage symptoms and prevent complications.
The focus is on controlling Raynaud’s phenomenon, managing gastrointestinal symptoms, and addressing skin changes and other initial symptoms.
Immunosuppressive medications may be initiated in cases of active inflammation or organ involvement.
Maintenance Phase: The primary goal during this phase is to maintain disease stability, prevent disease progression, and manage complications and comorbidities.
Regular follow-up visits with healthcare providers are scheduled to monitor disease activity, assess treatment efficacy, and adjust medications as needed.
Physical therapy and occupational therapy may be continued to maintain joint function and improve mobility.
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