Protoporphyria, also known as erythropoietic protoporphyria (EPP), is a rare inherited disorder that affects the production of heme, a crucial component of hemoglobin. Hemoglobin is responsible for carrying oxygen in red blood cells throughout the body.
Protoporphyria is classified as a type of porphyria, a group of genetic disorders that result from abnormalities in the heme biosynthesis pathway.
A genetic disorder called erythropoietic protoporphyria causes red blood cells to accumulate protoporphyrin’s, which can lead to non-blistering photosensitivity, acute, painful, and even liver illness.
When exposed to intense sunshine, it often first manifests in young children with instant pain and weeping. It has a seasonal aspect, with symptoms primarily manifesting in the spring and summer.
Epidemiology
Protoporphyria, specifically erythropoietic protoporphyria (EPP), is a rare disorder. The prevalence of EPP varies among different populations.
In the general population, it is estimated to affect approximately 1 in 75,000 to 200,000 individuals. In certain populations with a higher incidence of porphyria’s, such as individuals of European, African, and Asian descent, the prevalence may be slightly higher.
The most prevalent porphyria in children and the third most common in adults, respectively, is known as this condition. Both men and women are equally impacted by EPP.
Anatomy
Pathophysiology
The pathophysiology of protoporphyria is related to abnormalities in the heme biosynthesis pathway, particularly the deficiency or dysfunction of the enzyme ferrochelatase (FECH).
Heme is a critical molecule involved in various biological processes, including oxygen transport, energy production, and the function of numerous enzymes. The synthesis of heme occurs in several steps, primarily in the liver and bone marrow.
The largest concentrations of excess protoporphyrin are seen in reticulocytes and immature erythrocytes, which are produced during the development of erythroid cells in the bone marrow.
Red blood cells release metal-free protoporphyrin into the plasma, where it is removed by the liver and released into bile.
Etiology
The most common form of EPP is inherited in an autosomal dominant pattern, which means that a person needs to inherit a single abnormal gene from either parent to develop the condition. The specific gene implicated in most cases of EPP is the FECH gene, which provides instructions for producing the enzyme ferrochelatase.
EPP is an inherited disorder caused by mutations in the genes involved in the heme biosynthesis pathway. Most symptomatic people have FECH genotypes that are made up of either two mutant alleles or one mutation and a variant allele with a particular intronic single nucleotide polymorphism (IVS3-48C).
This polymorphism accelerates FECH mRNA’s rapid degradation and incorrect splicing, resulting in low expression.
The frequency of polymorphism varies widely in diverse populations studied, as follows:
Southeast Asian: – 31%
United Kingdom: – 6.5%
Black West African: – < 1%
United States: – 3.5%
White French: – 11.3%
North African: – 2.7%
Genetics
Prognostic Factors
The specific genetic mutation involved in protoporphyria can impact the severity of symptoms and the overall prognosis. Different mutations in genes such as FECH or ALAS2 can result in variable enzyme activity and protoporphyrin accumulation, leading to differences in symptom severity and disease progression.
The age at which symptoms first appear can influence the prognosis. EPP symptoms often manifest in childhood, and individuals who experience an early onset of symptoms may have a higher likelihood of more pronounced and persistent symptoms throughout their lives.
The residual activity of the affected enzyme, such as ferrochelatase in EPP, can affect the severity of symptoms. Individuals with higher residual enzyme activity may have milder symptoms compared to those with lower or absent enzyme activity.
Clinical History
Age Group:
In many cases, Protoporphyria is present from birth, but it may go undiagnosed or misdiagnosed for several years due to the variable nature of symptoms and their association with sunlight exposure.
During childhood, the symptoms of Protoporphyria may become more apparent and cause significant discomfort. Children with EPP may exhibit skin sensitivity to sunlight, with symptoms such as severe burning and pain, itching, swelling, redness, and blistering.
The individuals who develop EPP during childhood may continue to experience symptoms and require ongoing management throughout their lives.
Physical Examination
The affected areas may be palpated to assess for tenderness, texture changes such as thickening, and signs of edema.
The examination of skin may include checking for redness, swelling, blistering, scarring, thickening, and abnormal pigmentation in sun-exposed areas.
The examination of skin in areas that are typically exposed to sunlight, such as the face, neck, hands, and arms, to check for any specific signs of protoporphyria-related damage.
Age group
Associated comorbidity
Protoporphyria accumulation in the gallbladder can increase the risk of developing gallstones. These are solid deposits that form in the gallbladder and can cause symptoms such as abdominal pain, nausea, and vomiting.
EPP can be associated with an increased risk of other photosensitivity disorders, such as polymorphic light eruption (PLE) or solar urticaria. These conditions involve abnormal skin reactions to sunlight and can cause symptoms like EPP, including skin rash, itching, and swelling.
Prolonged protoporphyrin accumulation in the liver can lead to liver damage, cholestasis (impaired bile flow), and hepatotoxicity.
Associated activity
Acuity of presentation
The primary symptom of EPP is photosensitivity, which means that individuals with EPP experience an abnormal sensitivity to sunlight and other sources of visible light. The symptoms typically begin in early childhood and may persist throughout life.
Exposure to sunlight can cause severe pain and burning sensation within minutes to hours. The affected areas may become red, swollen, and blistered.
People with EPP have a deficiency of the enzyme ferrochelatase, which leads to the accumulation of protoporphyrin IX in the blood, skin, and other tissues.
Differential Diagnoses
Solar urticaria: This condition results in urticaria when exposed to sunlight. Like EPP, symptoms frequently appear within minutes.
Polymorphic light eruption: It is also known as sun allergy or sun poisoning. The first three decades of life are usually when this prevalent photo dermatosis occurs. Patients typically present with isolated lesions, such as vesicles, plaques, or pruritic papules in sun-exposed areas.
Lupus erythematosus: Systemic lupus erythematosus (SLE) and cutaneous lupus can both present photosensitivity and skin manifestations.
Contact dermatitis: Exposure to certain substances can cause an allergic reaction or irritation of the skin, resulting in redness, swelling, and blistering.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Photoprotection: The management of protoporphyria is based on avoidance of sunlight and other sources of triggering light, such as fluorescent lights.
This involves taking measures to protect the skin from exposure, including: Avoiding direct sunlight, especially during peak hours, usually 10 am to 4 pm. Wearing protective clothing, such as wide-brimmed hats, long-sleeved shirts, and long pants made from tightly woven fabrics.
Pain management: Individuals with protoporphyria may experience pain and discomfort due to photosensitivity. Over-the-counter pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may provide some relief.
Intake of Beta-carotene supplements: In some cases, oral beta-carotene supplements may be prescribed. Beta-carotene is a pigment found in fruits and vegetables that can provide some degree of photoprotection.
Protection from Sunlight: Install UV-protective films or tinted windows in your home to reduce the entry of sunlight. Utilize curtains, blinds, or shutters to block out direct sunlight. Consider using UV-protective window screens or window films in sun-exposed areas.
Modifications in Lighting: Replace fluorescent lights with alternative lighting options that emit less triggering light, such as LED lights.
External modifications: Create shaded areas in your outdoor spaces using umbrellas, canopies, or pergolas. Utilize portable sun shelters or pop-up tents when spending time outdoors. Consider installing UV-protective films or fabrics on car windows to reduce sun exposure during travel.
Planning Activities: Schedule outdoor activities during non-peak hours when sunlight is less intense, such as early morning or late afternoon. Seek shaded areas or use protective measures like hats, clothing, and sunscreen during unavoidable sun exposure.
Use of Alpha stimulating hormones
Alpha-Melanocyte Stimulating Hormone (α-MSH) is a hormone that plays a crucial role in regulating skin pigmentation, inflammation, and various physiological processes.
Analogs of the alpha melanocyte stimulating hormone boost the skin’s ability to produce eumelanin, the most prevalent type of melanin, without the need for exposure to natural or artificial light.
Afamelanotide: It is a melanocortin-1 receptor (MC1-R) agonist that stimulates eumelanin (the most prevalent kind of melanin) production in the skin without the need for exposure to natural or artificial light.
For adults with a history of phototoxic responses from erythropoietic protoporphyria (EPP), it is recommended to increase painless light exposure.
Use of Beta-carotene as Photo-protectants
Beta-Carotene: It is an oral supplement that is often prescribed to individuals with EPP. It acts as an antioxidant and can increase the skin’s tolerance to sunlight. By absorbing excess light energy, beta-carotene can reduce the production of Protoporphyria and minimize the risk of phototoxic reactions.
A minimal amount of photoprotection might be offered by this agent. Carotenoderma, the yellowing of the skin, is caused by it. After starting medication therapy, any provided photoprotection gradually increases over a 4- to 6-week period.
Use of Antihistamines in treatment of Protoporphyria
Antihistamines may be prescribed to help alleviate certain symptoms associated with the condition, such as itching, redness, and hives.
Fexofenadine: It is an antihistamine that provides relief from itching and helps manage allergic reactions. It is available both over the counter and in prescription strength.
Hydroxyzine: It is an antihistamine that can help relieve itching, hives, and other allergic skin reactions. It is available in both oral and topical form.
Use of Enteric adsorbents in treatment of Protoporphyria
Enteric adsorbents are substances that are used to bind and remove toxins, chemicals, or other substances from the gastrointestinal tract. In the context of Protoporphyria, enteric adsorbents may be utilized to help reduce the absorption of Protoporphyria from the diet, thereby potentially minimizing their accumulation in the body.
Activated Charcoal: Activated charcoal is a highly porous substance that has adsorptive properties. It can bind to various substances in the gastrointestinal tract, including toxins and chemicals.
Cholestyramine:Cholestyramine is a bile acid sequestrant commonly used to lower cholesterol levels. It binds to bile acids in the intestine, promoting their elimination from the body.
Use of Heme analogues in treatment of Protoporphyria
In the treatment of Protoporphyria, heme analogues can be administered to help reduce the overproduction of protoporphyrins and alleviate symptoms. They work by providing the body with a controlled source of heme, which can regulate the activity of the enzymes involved in heme synthesis.
Hemin:Hemin is a heme analogue that has been used as a treatment option for Protoporphyria, specifically Erythropoietic Protoporphyria (EPP). It is administered intravenously and acts as a negative feedback regulator of the enzyme responsible for the excessive production of protoporphyrin.
Dermatological treatments: Dermatological interventions can be employed to manage skin symptoms and complications associated with protoporphyria.
Topical corticosteroids: These medications can help reduce inflammation, itching, and redness of the skin.
Topical emollients: Moisturizers and emollients can help soothe and hydrate the skin, reducing dryness and preventing skin damage.
Wound care: For individuals with skin lesions, blisters, or secondary infections, proper wound care is essential. This may include cleaning the affected area with mild antiseptic solutions, applying sterile dressings.
Management of severe pain: Individuals with protoporphyria may experience significant pain and discomfort due to photosensitivity and skin symptoms. Pain management techniques, such as nonsteroidal anti-inflammatory drugs (NSAIDs), topical anesthetics, or other analgesic medications.
use-of-phases-in-managing-protoporphyria
Diagnosis and Evaluation: The initial phase involves obtaining a definitive diagnosis of protoporphyria through clinical evaluation, biochemical testing, and genetic testing.
Modifications in Photoprotection: The mainstay of management for protoporphyria is photoprotection. This phase involves implementing comprehensive sun protection strategies, including avoiding direct sunlight, using protective clothing, applying broad-spectrum sunscreen, and modifying the environment to minimize exposure to triggering light sources.
Current monitoring and support: Managing protoporphyria is an ongoing process that requires regular monitoring, follow-up appointments, and support from healthcare professionals.
Protoporphyria, also known as erythropoietic protoporphyria (EPP), is a rare inherited disorder that affects the production of heme, a crucial component of hemoglobin. Hemoglobin is responsible for carrying oxygen in red blood cells throughout the body.
Protoporphyria is classified as a type of porphyria, a group of genetic disorders that result from abnormalities in the heme biosynthesis pathway.
A genetic disorder called erythropoietic protoporphyria causes red blood cells to accumulate protoporphyrin’s, which can lead to non-blistering photosensitivity, acute, painful, and even liver illness.
When exposed to intense sunshine, it often first manifests in young children with instant pain and weeping. It has a seasonal aspect, with symptoms primarily manifesting in the spring and summer.
Protoporphyria, specifically erythropoietic protoporphyria (EPP), is a rare disorder. The prevalence of EPP varies among different populations.
In the general population, it is estimated to affect approximately 1 in 75,000 to 200,000 individuals. In certain populations with a higher incidence of porphyria’s, such as individuals of European, African, and Asian descent, the prevalence may be slightly higher.
The most prevalent porphyria in children and the third most common in adults, respectively, is known as this condition. Both men and women are equally impacted by EPP.
The pathophysiology of protoporphyria is related to abnormalities in the heme biosynthesis pathway, particularly the deficiency or dysfunction of the enzyme ferrochelatase (FECH).
Heme is a critical molecule involved in various biological processes, including oxygen transport, energy production, and the function of numerous enzymes. The synthesis of heme occurs in several steps, primarily in the liver and bone marrow.
The largest concentrations of excess protoporphyrin are seen in reticulocytes and immature erythrocytes, which are produced during the development of erythroid cells in the bone marrow.
Red blood cells release metal-free protoporphyrin into the plasma, where it is removed by the liver and released into bile.
The most common form of EPP is inherited in an autosomal dominant pattern, which means that a person needs to inherit a single abnormal gene from either parent to develop the condition. The specific gene implicated in most cases of EPP is the FECH gene, which provides instructions for producing the enzyme ferrochelatase.
EPP is an inherited disorder caused by mutations in the genes involved in the heme biosynthesis pathway. Most symptomatic people have FECH genotypes that are made up of either two mutant alleles or one mutation and a variant allele with a particular intronic single nucleotide polymorphism (IVS3-48C).
This polymorphism accelerates FECH mRNA’s rapid degradation and incorrect splicing, resulting in low expression.
The frequency of polymorphism varies widely in diverse populations studied, as follows:
Southeast Asian: – 31%
United Kingdom: – 6.5%
Black West African: – < 1%
United States: – 3.5%
White French: – 11.3%
North African: – 2.7%
The specific genetic mutation involved in protoporphyria can impact the severity of symptoms and the overall prognosis. Different mutations in genes such as FECH or ALAS2 can result in variable enzyme activity and protoporphyrin accumulation, leading to differences in symptom severity and disease progression.
The age at which symptoms first appear can influence the prognosis. EPP symptoms often manifest in childhood, and individuals who experience an early onset of symptoms may have a higher likelihood of more pronounced and persistent symptoms throughout their lives.
The residual activity of the affected enzyme, such as ferrochelatase in EPP, can affect the severity of symptoms. Individuals with higher residual enzyme activity may have milder symptoms compared to those with lower or absent enzyme activity.
Age Group:
In many cases, Protoporphyria is present from birth, but it may go undiagnosed or misdiagnosed for several years due to the variable nature of symptoms and their association with sunlight exposure.
During childhood, the symptoms of Protoporphyria may become more apparent and cause significant discomfort. Children with EPP may exhibit skin sensitivity to sunlight, with symptoms such as severe burning and pain, itching, swelling, redness, and blistering.
The individuals who develop EPP during childhood may continue to experience symptoms and require ongoing management throughout their lives.
The affected areas may be palpated to assess for tenderness, texture changes such as thickening, and signs of edema.
The examination of skin may include checking for redness, swelling, blistering, scarring, thickening, and abnormal pigmentation in sun-exposed areas.
The examination of skin in areas that are typically exposed to sunlight, such as the face, neck, hands, and arms, to check for any specific signs of protoporphyria-related damage.
Protoporphyria accumulation in the gallbladder can increase the risk of developing gallstones. These are solid deposits that form in the gallbladder and can cause symptoms such as abdominal pain, nausea, and vomiting.
EPP can be associated with an increased risk of other photosensitivity disorders, such as polymorphic light eruption (PLE) or solar urticaria. These conditions involve abnormal skin reactions to sunlight and can cause symptoms like EPP, including skin rash, itching, and swelling.
Prolonged protoporphyrin accumulation in the liver can lead to liver damage, cholestasis (impaired bile flow), and hepatotoxicity.
The primary symptom of EPP is photosensitivity, which means that individuals with EPP experience an abnormal sensitivity to sunlight and other sources of visible light. The symptoms typically begin in early childhood and may persist throughout life.
Exposure to sunlight can cause severe pain and burning sensation within minutes to hours. The affected areas may become red, swollen, and blistered.
People with EPP have a deficiency of the enzyme ferrochelatase, which leads to the accumulation of protoporphyrin IX in the blood, skin, and other tissues.
Solar urticaria: This condition results in urticaria when exposed to sunlight. Like EPP, symptoms frequently appear within minutes.
Polymorphic light eruption: It is also known as sun allergy or sun poisoning. The first three decades of life are usually when this prevalent photo dermatosis occurs. Patients typically present with isolated lesions, such as vesicles, plaques, or pruritic papules in sun-exposed areas.
Lupus erythematosus: Systemic lupus erythematosus (SLE) and cutaneous lupus can both present photosensitivity and skin manifestations.
Contact dermatitis: Exposure to certain substances can cause an allergic reaction or irritation of the skin, resulting in redness, swelling, and blistering.
Photoprotection: The management of protoporphyria is based on avoidance of sunlight and other sources of triggering light, such as fluorescent lights.
This involves taking measures to protect the skin from exposure, including: Avoiding direct sunlight, especially during peak hours, usually 10 am to 4 pm. Wearing protective clothing, such as wide-brimmed hats, long-sleeved shirts, and long pants made from tightly woven fabrics.
Pain management: Individuals with protoporphyria may experience pain and discomfort due to photosensitivity. Over-the-counter pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may provide some relief.
Intake of Beta-carotene supplements: In some cases, oral beta-carotene supplements may be prescribed. Beta-carotene is a pigment found in fruits and vegetables that can provide some degree of photoprotection.
Dermatology, General
Protection from Sunlight: Install UV-protective films or tinted windows in your home to reduce the entry of sunlight. Utilize curtains, blinds, or shutters to block out direct sunlight. Consider using UV-protective window screens or window films in sun-exposed areas.
Modifications in Lighting: Replace fluorescent lights with alternative lighting options that emit less triggering light, such as LED lights.
External modifications: Create shaded areas in your outdoor spaces using umbrellas, canopies, or pergolas. Utilize portable sun shelters or pop-up tents when spending time outdoors. Consider installing UV-protective films or fabrics on car windows to reduce sun exposure during travel.
Planning Activities: Schedule outdoor activities during non-peak hours when sunlight is less intense, such as early morning or late afternoon. Seek shaded areas or use protective measures like hats, clothing, and sunscreen during unavoidable sun exposure.
Dermatology, General
Gastroenterology
Alpha-Melanocyte Stimulating Hormone (α-MSH) is a hormone that plays a crucial role in regulating skin pigmentation, inflammation, and various physiological processes.
Analogs of the alpha melanocyte stimulating hormone boost the skin’s ability to produce eumelanin, the most prevalent type of melanin, without the need for exposure to natural or artificial light.
Afamelanotide: It is a melanocortin-1 receptor (MC1-R) agonist that stimulates eumelanin (the most prevalent kind of melanin) production in the skin without the need for exposure to natural or artificial light.
For adults with a history of phototoxic responses from erythropoietic protoporphyria (EPP), it is recommended to increase painless light exposure.
Dermatology, General
Beta-Carotene: It is an oral supplement that is often prescribed to individuals with EPP. It acts as an antioxidant and can increase the skin’s tolerance to sunlight. By absorbing excess light energy, beta-carotene can reduce the production of Protoporphyria and minimize the risk of phototoxic reactions.
A minimal amount of photoprotection might be offered by this agent. Carotenoderma, the yellowing of the skin, is caused by it. After starting medication therapy, any provided photoprotection gradually increases over a 4- to 6-week period.
Dermatology, General
Antihistamines may be prescribed to help alleviate certain symptoms associated with the condition, such as itching, redness, and hives.
Fexofenadine: It is an antihistamine that provides relief from itching and helps manage allergic reactions. It is available both over the counter and in prescription strength.
Hydroxyzine: It is an antihistamine that can help relieve itching, hives, and other allergic skin reactions. It is available in both oral and topical form.
Dermatology, General
Gastroenterology
Enteric adsorbents are substances that are used to bind and remove toxins, chemicals, or other substances from the gastrointestinal tract. In the context of Protoporphyria, enteric adsorbents may be utilized to help reduce the absorption of Protoporphyria from the diet, thereby potentially minimizing their accumulation in the body.
Activated Charcoal: Activated charcoal is a highly porous substance that has adsorptive properties. It can bind to various substances in the gastrointestinal tract, including toxins and chemicals.
Cholestyramine:Cholestyramine is a bile acid sequestrant commonly used to lower cholesterol levels. It binds to bile acids in the intestine, promoting their elimination from the body.
Dermatology, General
Hematology
In the treatment of Protoporphyria, heme analogues can be administered to help reduce the overproduction of protoporphyrins and alleviate symptoms. They work by providing the body with a controlled source of heme, which can regulate the activity of the enzymes involved in heme synthesis.
Hemin:Hemin is a heme analogue that has been used as a treatment option for Protoporphyria, specifically Erythropoietic Protoporphyria (EPP). It is administered intravenously and acts as a negative feedback regulator of the enzyme responsible for the excessive production of protoporphyrin.
Dermatology, General
Pain Management
Dermatological treatments: Dermatological interventions can be employed to manage skin symptoms and complications associated with protoporphyria.
Topical corticosteroids: These medications can help reduce inflammation, itching, and redness of the skin.
Topical emollients: Moisturizers and emollients can help soothe and hydrate the skin, reducing dryness and preventing skin damage.
Wound care: For individuals with skin lesions, blisters, or secondary infections, proper wound care is essential. This may include cleaning the affected area with mild antiseptic solutions, applying sterile dressings.
Management of severe pain: Individuals with protoporphyria may experience significant pain and discomfort due to photosensitivity and skin symptoms. Pain management techniques, such as nonsteroidal anti-inflammatory drugs (NSAIDs), topical anesthetics, or other analgesic medications.
Pain Management
Diagnosis and Evaluation: The initial phase involves obtaining a definitive diagnosis of protoporphyria through clinical evaluation, biochemical testing, and genetic testing.
Modifications in Photoprotection: The mainstay of management for protoporphyria is photoprotection. This phase involves implementing comprehensive sun protection strategies, including avoiding direct sunlight, using protective clothing, applying broad-spectrum sunscreen, and modifying the environment to minimize exposure to triggering light sources.
Current monitoring and support: Managing protoporphyria is an ongoing process that requires regular monitoring, follow-up appointments, and support from healthcare professionals.
Protoporphyria, also known as erythropoietic protoporphyria (EPP), is a rare inherited disorder that affects the production of heme, a crucial component of hemoglobin. Hemoglobin is responsible for carrying oxygen in red blood cells throughout the body.
Protoporphyria is classified as a type of porphyria, a group of genetic disorders that result from abnormalities in the heme biosynthesis pathway.
A genetic disorder called erythropoietic protoporphyria causes red blood cells to accumulate protoporphyrin’s, which can lead to non-blistering photosensitivity, acute, painful, and even liver illness.
When exposed to intense sunshine, it often first manifests in young children with instant pain and weeping. It has a seasonal aspect, with symptoms primarily manifesting in the spring and summer.
Protoporphyria, specifically erythropoietic protoporphyria (EPP), is a rare disorder. The prevalence of EPP varies among different populations.
In the general population, it is estimated to affect approximately 1 in 75,000 to 200,000 individuals. In certain populations with a higher incidence of porphyria’s, such as individuals of European, African, and Asian descent, the prevalence may be slightly higher.
The most prevalent porphyria in children and the third most common in adults, respectively, is known as this condition. Both men and women are equally impacted by EPP.
The pathophysiology of protoporphyria is related to abnormalities in the heme biosynthesis pathway, particularly the deficiency or dysfunction of the enzyme ferrochelatase (FECH).
Heme is a critical molecule involved in various biological processes, including oxygen transport, energy production, and the function of numerous enzymes. The synthesis of heme occurs in several steps, primarily in the liver and bone marrow.
The largest concentrations of excess protoporphyrin are seen in reticulocytes and immature erythrocytes, which are produced during the development of erythroid cells in the bone marrow.
Red blood cells release metal-free protoporphyrin into the plasma, where it is removed by the liver and released into bile.
The most common form of EPP is inherited in an autosomal dominant pattern, which means that a person needs to inherit a single abnormal gene from either parent to develop the condition. The specific gene implicated in most cases of EPP is the FECH gene, which provides instructions for producing the enzyme ferrochelatase.
EPP is an inherited disorder caused by mutations in the genes involved in the heme biosynthesis pathway. Most symptomatic people have FECH genotypes that are made up of either two mutant alleles or one mutation and a variant allele with a particular intronic single nucleotide polymorphism (IVS3-48C).
This polymorphism accelerates FECH mRNA’s rapid degradation and incorrect splicing, resulting in low expression.
The frequency of polymorphism varies widely in diverse populations studied, as follows:
Southeast Asian: – 31%
United Kingdom: – 6.5%
Black West African: – < 1%
United States: – 3.5%
White French: – 11.3%
North African: – 2.7%
The specific genetic mutation involved in protoporphyria can impact the severity of symptoms and the overall prognosis. Different mutations in genes such as FECH or ALAS2 can result in variable enzyme activity and protoporphyrin accumulation, leading to differences in symptom severity and disease progression.
The age at which symptoms first appear can influence the prognosis. EPP symptoms often manifest in childhood, and individuals who experience an early onset of symptoms may have a higher likelihood of more pronounced and persistent symptoms throughout their lives.
The residual activity of the affected enzyme, such as ferrochelatase in EPP, can affect the severity of symptoms. Individuals with higher residual enzyme activity may have milder symptoms compared to those with lower or absent enzyme activity.
Age Group:
In many cases, Protoporphyria is present from birth, but it may go undiagnosed or misdiagnosed for several years due to the variable nature of symptoms and their association with sunlight exposure.
During childhood, the symptoms of Protoporphyria may become more apparent and cause significant discomfort. Children with EPP may exhibit skin sensitivity to sunlight, with symptoms such as severe burning and pain, itching, swelling, redness, and blistering.
The individuals who develop EPP during childhood may continue to experience symptoms and require ongoing management throughout their lives.
The affected areas may be palpated to assess for tenderness, texture changes such as thickening, and signs of edema.
The examination of skin may include checking for redness, swelling, blistering, scarring, thickening, and abnormal pigmentation in sun-exposed areas.
The examination of skin in areas that are typically exposed to sunlight, such as the face, neck, hands, and arms, to check for any specific signs of protoporphyria-related damage.
Protoporphyria accumulation in the gallbladder can increase the risk of developing gallstones. These are solid deposits that form in the gallbladder and can cause symptoms such as abdominal pain, nausea, and vomiting.
EPP can be associated with an increased risk of other photosensitivity disorders, such as polymorphic light eruption (PLE) or solar urticaria. These conditions involve abnormal skin reactions to sunlight and can cause symptoms like EPP, including skin rash, itching, and swelling.
Prolonged protoporphyrin accumulation in the liver can lead to liver damage, cholestasis (impaired bile flow), and hepatotoxicity.
The primary symptom of EPP is photosensitivity, which means that individuals with EPP experience an abnormal sensitivity to sunlight and other sources of visible light. The symptoms typically begin in early childhood and may persist throughout life.
Exposure to sunlight can cause severe pain and burning sensation within minutes to hours. The affected areas may become red, swollen, and blistered.
People with EPP have a deficiency of the enzyme ferrochelatase, which leads to the accumulation of protoporphyrin IX in the blood, skin, and other tissues.
Solar urticaria: This condition results in urticaria when exposed to sunlight. Like EPP, symptoms frequently appear within minutes.
Polymorphic light eruption: It is also known as sun allergy or sun poisoning. The first three decades of life are usually when this prevalent photo dermatosis occurs. Patients typically present with isolated lesions, such as vesicles, plaques, or pruritic papules in sun-exposed areas.
Lupus erythematosus: Systemic lupus erythematosus (SLE) and cutaneous lupus can both present photosensitivity and skin manifestations.
Contact dermatitis: Exposure to certain substances can cause an allergic reaction or irritation of the skin, resulting in redness, swelling, and blistering.
Photoprotection: The management of protoporphyria is based on avoidance of sunlight and other sources of triggering light, such as fluorescent lights.
This involves taking measures to protect the skin from exposure, including: Avoiding direct sunlight, especially during peak hours, usually 10 am to 4 pm. Wearing protective clothing, such as wide-brimmed hats, long-sleeved shirts, and long pants made from tightly woven fabrics.
Pain management: Individuals with protoporphyria may experience pain and discomfort due to photosensitivity. Over-the-counter pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may provide some relief.
Intake of Beta-carotene supplements: In some cases, oral beta-carotene supplements may be prescribed. Beta-carotene is a pigment found in fruits and vegetables that can provide some degree of photoprotection.
Dermatology, General
Protection from Sunlight: Install UV-protective films or tinted windows in your home to reduce the entry of sunlight. Utilize curtains, blinds, or shutters to block out direct sunlight. Consider using UV-protective window screens or window films in sun-exposed areas.
Modifications in Lighting: Replace fluorescent lights with alternative lighting options that emit less triggering light, such as LED lights.
External modifications: Create shaded areas in your outdoor spaces using umbrellas, canopies, or pergolas. Utilize portable sun shelters or pop-up tents when spending time outdoors. Consider installing UV-protective films or fabrics on car windows to reduce sun exposure during travel.
Planning Activities: Schedule outdoor activities during non-peak hours when sunlight is less intense, such as early morning or late afternoon. Seek shaded areas or use protective measures like hats, clothing, and sunscreen during unavoidable sun exposure.
Dermatology, General
Gastroenterology
Alpha-Melanocyte Stimulating Hormone (α-MSH) is a hormone that plays a crucial role in regulating skin pigmentation, inflammation, and various physiological processes.
Analogs of the alpha melanocyte stimulating hormone boost the skin’s ability to produce eumelanin, the most prevalent type of melanin, without the need for exposure to natural or artificial light.
Afamelanotide: It is a melanocortin-1 receptor (MC1-R) agonist that stimulates eumelanin (the most prevalent kind of melanin) production in the skin without the need for exposure to natural or artificial light.
For adults with a history of phototoxic responses from erythropoietic protoporphyria (EPP), it is recommended to increase painless light exposure.
Dermatology, General
Beta-Carotene: It is an oral supplement that is often prescribed to individuals with EPP. It acts as an antioxidant and can increase the skin’s tolerance to sunlight. By absorbing excess light energy, beta-carotene can reduce the production of Protoporphyria and minimize the risk of phototoxic reactions.
A minimal amount of photoprotection might be offered by this agent. Carotenoderma, the yellowing of the skin, is caused by it. After starting medication therapy, any provided photoprotection gradually increases over a 4- to 6-week period.
Dermatology, General
Antihistamines may be prescribed to help alleviate certain symptoms associated with the condition, such as itching, redness, and hives.
Fexofenadine: It is an antihistamine that provides relief from itching and helps manage allergic reactions. It is available both over the counter and in prescription strength.
Hydroxyzine: It is an antihistamine that can help relieve itching, hives, and other allergic skin reactions. It is available in both oral and topical form.
Dermatology, General
Gastroenterology
Enteric adsorbents are substances that are used to bind and remove toxins, chemicals, or other substances from the gastrointestinal tract. In the context of Protoporphyria, enteric adsorbents may be utilized to help reduce the absorption of Protoporphyria from the diet, thereby potentially minimizing their accumulation in the body.
Activated Charcoal: Activated charcoal is a highly porous substance that has adsorptive properties. It can bind to various substances in the gastrointestinal tract, including toxins and chemicals.
Cholestyramine:Cholestyramine is a bile acid sequestrant commonly used to lower cholesterol levels. It binds to bile acids in the intestine, promoting their elimination from the body.
Dermatology, General
Hematology
In the treatment of Protoporphyria, heme analogues can be administered to help reduce the overproduction of protoporphyrins and alleviate symptoms. They work by providing the body with a controlled source of heme, which can regulate the activity of the enzymes involved in heme synthesis.
Hemin:Hemin is a heme analogue that has been used as a treatment option for Protoporphyria, specifically Erythropoietic Protoporphyria (EPP). It is administered intravenously and acts as a negative feedback regulator of the enzyme responsible for the excessive production of protoporphyrin.
Dermatology, General
Pain Management
Dermatological treatments: Dermatological interventions can be employed to manage skin symptoms and complications associated with protoporphyria.
Topical corticosteroids: These medications can help reduce inflammation, itching, and redness of the skin.
Topical emollients: Moisturizers and emollients can help soothe and hydrate the skin, reducing dryness and preventing skin damage.
Wound care: For individuals with skin lesions, blisters, or secondary infections, proper wound care is essential. This may include cleaning the affected area with mild antiseptic solutions, applying sterile dressings.
Management of severe pain: Individuals with protoporphyria may experience significant pain and discomfort due to photosensitivity and skin symptoms. Pain management techniques, such as nonsteroidal anti-inflammatory drugs (NSAIDs), topical anesthetics, or other analgesic medications.
Pain Management
Diagnosis and Evaluation: The initial phase involves obtaining a definitive diagnosis of protoporphyria through clinical evaluation, biochemical testing, and genetic testing.
Modifications in Photoprotection: The mainstay of management for protoporphyria is photoprotection. This phase involves implementing comprehensive sun protection strategies, including avoiding direct sunlight, using protective clothing, applying broad-spectrum sunscreen, and modifying the environment to minimize exposure to triggering light sources.
Current monitoring and support: Managing protoporphyria is an ongoing process that requires regular monitoring, follow-up appointments, and support from healthcare professionals.
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