Porphyria

　　1. Etiology

　　1. Acute intermittent type:Acute intermittent porphyria is more common, an autosomal dominant genetic disease caused by a deficiency of PBG deaminase (uroporphyrinogen synthase). This defect reduces the conversion of PBG to uroporphyrinogen III in the liver, leading to a hemoglobin synthesis disorder that enhances the activity of ALA synthesis enzyme. As a result, the synthesis of ALA and PBG increases, and they are excreted more in urine.

　　2. Delayed skin type:Delayed onset cutaneous porphyria is the most common type of porphyria, caused by a deficiency of urinary porphyrinogen decarboxylase within the liver. It is inherited in an autosomal dominant manner. Cases are sporadic, with more male patients than female, and most patients do not have a family history. Some individuals may have a biochemical defect with reduced enzyme activity of porphyrinogen decarboxylase, but the excretion of porphyrin in urine may not necessarily increase, and there may not be obvious symptoms in clinical practice. The synergistic effect of acquired factors such as alcoholism, excessive iron burden in the liver, liver damage, and female hormones further reduces the activity of porphyrinogen decarboxylase or stimulates the formation of ALA, resulting in a significant increase in the formation of porphyrin, leading to the onset of delayed onset cutaneous porphyria.

　　3. Mixed or variant type:Mixed porphyria is a disease caused by a decrease in protoporphyrinogen oxidase and heme synthase, which is inherited in an autosomal dominant manner and can affect both males and females.

　　4. Hereditary coproporphyria type:Hereditary coproporphyria is a rare type of porphyria. It is an autosomal dominant genetic disease caused by a lack of coproporphyrinogen oxidase. Some patients have photosensitive skin damage, and their clinical manifestations are similar to those of acute intermittent porphyria. Although patients with this disease also excrete a large amount of coproporphyrin in their feces, the content of protoporphyrin is generally low. During an acute attack, a large amount of uroporphyrin, coproporphyrin, ALA, and PBG can also be found in the urine. During the recovery period, it can return to normal.

　　Second, pathogenesis

　　1. Pathological factors

　　(1) Genetic factors: Porphyrin is an intermediate product in the synthesis process of hemoglobin, myoglobin, catalase, peroxidase, and cytochrome in animals. In humans, the common ones include coproporphyrin I, III, uroporphyrin I, III, and protoporphyrin IX. There is also coproporphyrin, which is a porphyrin precursor and is excreted in large quantities in the urine of some porphyria patients. The urine color is normal, but after the urine is placed in sunlight for a few hours, the urine color deepens and turns brownish, which is the result of coproporphyrin transforming into uroporphyrin. Various porphyrins are colored substances that exhibit red fluorescence under the ultraviolet light of a special filter plate, so they can be quantified by fluorescence spectrophotometry. Coproporphyrin dissolves in ether while uroporphyrin does not, which is convenient for separation. Various porphyrins have different absorption bands in the spectrum of a spectroscope.

　　The following conditions can increase porphyrin and porphyrin precursors (-aminolevulinic acid, coproporphyrin) and lead to porphyria cutanea tarda.

　　① Impaired heme synthesis.

　　② Mutation of the repressor or operator gene.

　　③ Enzyme defects: such as the lack of uroporphyrinogen I synthase, which prevents uroporphyrinogen from further cyclizing into uroporphyrinogen, leading to the accumulation of uroporphyrinogen; or insufficient uroporphyrinogen III co-synthase, which prevents coproporphyrin from transforming into uroporphyrinogen III but can only transform into uroporphyrinogen I type.

　　(2) Other factors: Certain drugs, such as sulfonamides, barbiturates, chloroquine, anesthetics, and chemicals, as well as poisoning, infection, alcohol consumption, fatigue, mental stimulation, menstruation, and pregnancy, and other diseases such as liver tumors can induce the onset of the disease.

　　2. Pathology:The pathological changes are mainly in the liver, where there is a large deposition of coproporphyrin. When skin lesions occur, in addition to coproporphyrin, porphyrin can also be seen. The kidneys also have coproporphyrin, but the bone marrow has very little. The nervous system can have demyelination of nerve fibers, cell swelling, and degenerative changes. Skin lesions include erythema, vesicles, scar formation, and hyperpigmentation.

　　Patients may have constipation, abdominal distension, vomiting, low fever, increased white blood cells, and an increased heart rate.

　　Constipation is a common complex symptom in clinical practice, but it is not a disease itself. It mainly refers to a decrease in defecation frequency, a decrease in fecal volume, dry and hard stools, and difficult defecation.

　　1. Acute intermittent type

　　Clinical cases are common. According to incomplete statistics from the First Affiliated Hospital of Sun Yat-sen University over the past 10 years, among 17 cases of hepatic porphyria, this type accounts for 15 cases. The age of onset ranges from 23 to 58 years, with 8 cases between 20 and 30 years old, 7 males and 8 females. It is reported that very few cases occur before puberty or after 60 years of age. Abdominal pain and (or) nervous and mental symptoms are characteristic of the disease. Since porphyrin in the body does not increase, there is no photosensitive skin damage.

　　Abdominal pain occurs suddenly, with varying degrees of severity, usually moderate to severe colic pain or only a feeling of heavy pressure. The pain is either paroxysmal or persistent and may spread throughout the abdomen, or it may be localized but without a fixed position. The abdomen is soft, without a fixed tender point, and is often accompanied by nausea, vomiting, and constipation. Sometimes, the intestine loop can be palpated in the abdomen, and the intestinal peristalsis sound is normal or decreased. X-ray abdominal flat film shows an expanded intestine loop; barium meal gastrointestinal examination shows small bowel spasm, and an expanded intestine loop can be seen at the proximal end of the small bowel spasm. There may be fever and an increase in white blood cell count. There have been reports of misdiagnosis as acute abdomen and laparotomy. Sometimes, abdominal pain radiates to the back and bladder, external genitalia, and is similar to renal colic. The duration of abdominal pain attacks varies, as does the frequency. During the remission period, it can be long or short, and some patients may have only 1-2 attacks and never have another attack, but some may have attacks once or even several times a year. It is generally believed that the cause of abdominal pain is due to autonomic nervous system lesions that cause unbalanced nerve supply to the small intestine muscles, or the toxic effect of porphyrin precursors, leading to intestinal spasm.

　　The neurological and psychiatric symptoms are varied and often appear after or simultaneously with abdominal pain, or may precede abdominal pain or appear alone. The involvement of peripheral nerves is manifested as ascending paralysis of the limbs, abnormal sensation, disappearance of tendon reflexes, and sometimes positive ankle clonus with disappearance of the Achilles tendon reflex. All 12 pairs of cranial nerves can be affected, with facial nerve palsy being the most common. Autonomic nervous system involvement can cause excessive sweating, tachycardia, fluctuation of blood pressure, and even orthostatic hypotension. Sinus tachycardia often appears during an attack and disappears during remission, which can be a sign of disease activity. Brainstem involvement can cause swallowing disorders, laryngeal palsy, and respiratory center paralysis, and hoarseness or even aphonia are often a sign of respiratory center paralysis. Damage to the hypothalamus can cause a syndrome of abnormal secretion of diuretic hormones; and thereby causing convulsions, delirium, and even coma. The main psychiatric symptoms are similar to those of schizophrenia, hysteria, and neurasthenia, and after the appearance of neurological and psychiatric symptoms, the prognosis is generally poor, and late stages often show liver cirrhosis, liver dysfunction, and even jaundice, ascites, and hepatic encephalopathy and other serious conditions.

　　During an attack, the urine appears red, like wine, and sometimes the urine is normal in color when just excreted, but turns red after exposure to sunlight, addition of acid, or heating. This is helpful for the diagnosis of the disease. The excretion of aminolevulinic acid and porphyrinogen increases (normally 07-32mg of aminolevulinic acid is excreted from the urine daily in healthy individuals), and the porphyrinogen test is positive, which is an important laboratory basis for the diagnosis of the disease.

　　The remission period of this disease is asymptomatic, and it may be induced by mental stimulation, infection, trauma, alcohol consumption, hunger, and the use of barbiturates, librium, methaqualone (Nembutal), sulfonamide drugs, phenytoin sodium, griseofulvin, estrogens, and other medications; during the attack, the condition may worsen due to the aforementioned factors, and some female patients' attacks may be related to menstruation or pregnancy.

　　Other patients have a latent course without symptoms, with only an increase in the excretion of -aminoketone acid and porphobilinogen in urine, which is called the latent type. However, under the influence of the above various triggering factors, acute attacks may also occur sometimes.

　　2. Delayed skin type

　　The onset is mostly in middle age or later, with a higher prevalence in males. The skin may have eczematous, urticarial, summer itchy rash-like, and polymorphic erythema, which usually appear after a period of exposure. When the sun is bright, the skin exposed to the body often shows redness with blisters due to slight trauma or pressure after exposure. Subsequently, bleeding within the blisters, erosion, scab formation, and scar formation may occur. Chronic skin damage may have hypertrichosis, hyperpigmentation, papulosis, and manifestations similar to those of scleroderma and dermatitis. There are varying degrees of liver damage, which is caused by the deposition of porphyrin in the liver. Some patients are accompanied by alcoholic liver cirrhosis, and some have liver adenomas. Drinking, using estrogens or iron, and exposure to hexachlorocyclohexane are often triggers for the onset. During an attack, the excretion of urine porphyrin I increases, and -aminoketone acid and porphobilinogen are normal. During remission, the excretion of urine porphyrin I decreases, while the excretion of porphyrin in feces increases.

　　3. Mixed type or variant

　　The onset age is mostly between 10 to 30 years old, and the clinical manifestations are characterized by the features of the above two types. This type is a dominant hereditary porphyria in middle-aged whites in South Africa, which can be traced back to a white family that immigrated from the Netherlands. In addition to abdominal symptoms and neurological symptoms during adulthood, there are also photosensitive skin lesions. The photosensitivity of the skin is mild, and herpes may occasionally occur. The skin lesions are intermittent and sometimes the only clinical symptom of the disease. Some patients have acute attacks with abdominal pain and weakness, slight mechanical skin trauma, and sometimes induction of skin lesions. Skin lesions during pregnancy in women are more significant. During the intermission, drugs such as barbiturates, chloroquine, alcohol, and anesthetics can induce acute attacks, which should be considered as contraindications. In severe cases, symptoms of abdominal pain, neurological symptoms, and liver function damage are similar to those of acute intermittent type. The characteristic of porphyrin metabolism disorder is that during the intermission or latent period, porphyrins and porphyrin precursors such as -aminolevulinic acid and porphobilinogen in the urine are negative, while a large amount of coproporphyrin and protoporphyrin are excreted in the feces. During an acute attack, a large amount of coproporphyrin and protoporphyrin are excreted in the feces, and the levels of -aminolevulinic acid and porphobilinogen in the urine also increase significantly, which are key points for diagnosis.

　　4. Hereditary coproporphyrin type

　　It can occur at any age, with equal prevalence in males and females, and has a clear family history. The disease is latent and asymptomatic, with only an increase in coproporphyrin excreted in feces. However, under the induction of drugs such as barbiturate, methaqualone (Nembutal), phenytoin sodium, and others, acute intermittent clinical manifestations may occur. Skin lesions are rare, and some patients may experience photosensitive skin damage. Its biochemical diagnostic feature is the excretion of a large amount of coproporphyrin type III in the feces, but without protoporphyrin. The excretion of coproporphyrin type III in the urine may not increase, but during an acute attack, the levels of coproporphyrin type III and its precursor porphobilinogen and -aminolevulinic acid in the urine all increase, with an even greater amount of coproporphyrin type III in the feces.

　　1. General measures

　　1. Prevention first:Avoid close relatives from getting married to prevent the occurrence of the disease; patients should strictly abstain from alcohol, and pregnant women should not deliver.

　　2. Emotional stability:Psychological care should be provided according to the different conditions of the patient, and confidence in overcoming the disease should be established. It is not advisable to be overly happy, sad, or angry, and to avoid emotional stimulation.

　　3. Avoid sun exposure:People with photosensitive dermatitis should avoid sunlight exposure.

　　4. Close monitoring:During the treatment process, attention should be paid to water and electrolyte balance. When complications such as hyponatremia, hypochloremia, hypomagnesemia, water deficiency or excess occur, appropriate treatment should be given after identifying the cause, and respiratory monitoring should be carried out. Special attention should be paid to patients with swallowing difficulties, hoarseness, or aphonia, and auxiliary respiration should be used in a timely manner to help patients with respiratory paralysis to pass the danger.

　　5. Caution in medication:Patients should use barbiturates, Librium, methaqualone (Miltown), sulfonamides, phenytoin sodium, griseofulvin, and estrogens with strict caution to prevent or exacerbate the disease.

　　2. Nutritional principles:Patients with this disease should consume soft foods that are easy to digest and non-irritating, rich in high sugar, high protein, various vitamins.

　　1. Carbohydrates:Patients with this disease should consume a high sugar diet, which is effective for both prevention and treatment. The daily intake should not be less than 300g, which can reach 500g or more, administered intravenously or orally.

　　2. Protein:Patients should consume high-quality protein rich in various amino acids, such as animal proteins such as eggs, fish, and milk.

　　3. Vitamin:Due to the large consumption of vitamin B6 in the tissues of patients with this disease by the porphyrin precursor synthesis enzyme, vitamin B6 deficiency can occur. Also, due to the damage to the liver and nervous system caused by the disease, vitamin B should be supplemented appropriately. In addition, vitamin E can block and reverse the induction synthesis of the porphyrin precursor synthesis enzyme (rate-limiting enzyme), so vitamin E should be given appropriately.

　　3. Drug treatment

　　1. Acute intermittent type:Acute phase requires rapid relief of symptoms. Glucose and ferric protoporphyrin can inhibit -ALAase, leading to rapid improvement of the condition. Approximately 400g of glucose is administered daily. If the patient cannot eat, 10% or 25% glucose solution can be administered intravenously at a rate of 10-20g per hour; insulin may be added if necessary. Ferric protoporphyrin can be administered at a dose of 3-4mg per kilogram of body weight, dissolved in normal saline and administered intravenously slowly: the duration should be no less than 10 minutes, repeated every 12 hours as needed: generally, symptoms can be relieved within 48 hours after the first injection; large doses used for a short period of time can cause renal damage and should be noted. Symptomatic treatment can use tranquility, chlorpromazine, prochlorperazine, tranquility dialdehyde, chloral hydrate, etc.; hypertension can use antihypertensive drugs, but methyldopa cannot be used. Propranolol (Propranolol) can inhibit -ALAase, and there have been reports of doses up to 100mg, 4 times a day, which can alleviate tachycardia, abdominal discomfort, and anxiety. During the treatment process, attention should also be paid to water and electrolyte balance. When complications such as hyponatremia, hypochloremia, hypomagnesemia, water deficiency or excess occur, appropriate treatment should be given after identifying the cause.

　　2. Delayed skin type:Venous bloodletting to reduce the iron content in liver blood can alleviate skin symptoms and improve liver function. Bloodletting can be performed once a week, with each session ranging from 300 to 500ml, until hemoglobin decreases to 110g/L and hematocrit decreases to 38ml%. If the excretion of porphyrin in urine does not decrease, wait until hemoglobin increases or returns to normal levels before performing bloodletting again.

　　3. Mixed type and hereditary coproporphyrin type:During acute intermittent attacks, the treatment is the same as that for acute intermittent attacks. The main treatment for skin symptoms is to prevent trauma and sunlight exposure. The effectiveness of beta-carotene is yet to be studied.

　　1. Acute intermittent type

　　The color of freshly voided urine is mostly normal, but if the urine is placed in direct sunlight, it gradually turns dark red, even black, which is the result of PBG being converted into red uroporphyrin and porphyrin under the action of light. The uroporphyrin produced has a special spectrum, emitting red fluorescence under ultraviolet light. If the urine is made strongly acidic and boiled for 30 minutes, the urine color quickly turns dark red or brown red. The dimethylaminobenzaldehyde test (Watson-Schwartz test) is a simple and reliable method to check for PBG. PBG reacts with dimethylaminobenzaldehyde (Ehrlich's aldehyde reagent) to turn deep red, and urobilinogen or indole also produces red with this reagent. However, after adding chloroform or butanol and shaking, the red color is extracted by this solvent, while the red color of PBG remains in the water layer. During the acute attack of the disease, this test often shows a strong positive reaction; during the remission period, it is usually positive, but it may also be negative; the results of the test in latent cases are usually weakly positive or negative.

　　The most reliable diagnostic basis is the determination of the content of ALA and PBG in urine by chromatography, especially for the intercritical period and latent cases. During the acute attack period, the excretion of PBG is approximately 50-200mg/d (the normal range is 0-4mg/d), and the excretion of ALA is about 20-100mg/d (the normal range is 0-7mg/d). The measured values of ALA and PBG often decrease with the improvement of clinical symptoms. For patients in the acute attack period, if a positive result of the dimethylaminobenzaldehyde test can be obtained in clinical practice, the diagnosis can be established.

　　2. Delayed skin type

　　The excretion of ALA and PBG in urine does not increase, and coproporphyrin in feces is often significantly increased, while protoporphyrin is normal or moderately increased. Most patients do not have anemia, and a few patients may have mild erythrocytosis. Due to the common liver disease, urobilinogen may be positive, serum transaminases may be elevated, and the excretion of sodium bromosulfophthalein is often lower than normal.

　　3. Mixed or variant type

　　The most significant laboratory finding is the presence of a large amount of coproporphyrin and protoporphyrin in bile and feces during the onset and remission periods, as well as throughout the entire course of the disease. Even in cases with mild symptoms or in childhood, the same findings are present. During acute attacks, the levels of ALA and PBG in urine are significantly increased, and sometimes coproporphyrin and uroporphyrin in urine are also significantly increased.

　　4. Hereditary coproporphyrin type

　　Although a large amount of coproporphyrin is also excreted in the feces of patients with this disease, the content of protoporphyrin is generally low. During an acute attack, a large amount of uroporphyrin, coproporphyrin, ALA, and PBG can also be found in the urine, and they can become normal during the recovery period.

　　It is possible to choose to do B-ultrasound, X-ray, electrocardiogram, electroencephalogram, CT, and other examinations.

　　1. Suitable foods:It is advisable to consume high-sugar, high-protein, a variety of vitamins, easily digestible and non-irritating soft foods, such as eggs, fish, milk, and other animal proteins. Eat more fruits such as apples, pears, and more vegetables.

　　2. Unsuitable foods:Hard, fried, and various刺激性 foods, cold things, avoid drinking alcohol, leftovers, and deteriorated foods such as deteriorated eggs, meat, fish, etc.

　　3. Diet therapy:

　　1. Floating wheat 45g, Jujube 5 pieces, Liquorice 15g, Atractylodes 20g, Trichosanthes 9g, Codonopsis pilosula 30g, Prunella 30g, Angelica sinensis 15g, Pheretima 12g, Coptis 9g, Styrax 12g, Corydalis 1.8g (powdered), decocted in water.

　　2. Rhubarb (added later) 10g, Coptis 6g, Costus 10g, Tangerine peel 10g, Scutellaria baicalensis 10g, Pinellia ternata 10g, Magnolia officinalis 10g,竹茹12g, Alisma orientale 10g, decocted in water.

　　3. Broussonetia papyrifera 15g, Scutellaria baicalensis 10g, Pinellia ternata 10g, Zingiber officinale 3g, Angelica sinensis 10g, Ligusticum chuanxiong 6g, White peony 10g, Licorice 5g, Longnose 15g, Cynanchum otophyllum 15g, decocted in water.

　　4. Bupleurum 9g, White peony 12g, White peony 12g, Costus 9g, Curcuma 9g, Citrus aurantium 12g, Melia toosendan 12g, Corydalis 12g, Taraxacum mongolicum 30g, Rhubarb 9g (added later), decocted in water. (2) Bupleurum 9g, Scutellaria baicalensis 60g, Liquorice 12g, Cynanchum wilfordii 20g, Scolopendra 3 pieces, Poria 30g, Costus 15g, Atractylodes 12g, Cinnamomum cassia bark 9g, Taraxacum mongolicum 30g, Rhubarb 6g (added later), decocted in water.

　　5. Angelica sinensis 15g, Ligusticum chuanxiong 10g, Persica 10g, Carthamus 10g, White peony 15g, Corydalis 30g, Zingiber officinale 7.5g, Licorice 10g, taken before meals with water.

　　6. Persica 10g, Cinnamomum cassia bark 7g, Rhubarb 9g, Natrii sulfas 15g, White peony 15g, Licorice 3g, decocted in water.

　　1. Treatment

　　1. Acute intermittent type

　　(1) Chlorpromazine is effective in alleviating abdominal pain and relieving nervous and mental symptoms, with a general dose of 12.5 to 100mg per time, 3 to 4 times a day. Prochlorperazine (mepiperchlorpromazine) is more effective than chlorpromazine, with a dose of 5 to 10mg per time, 3 to 4 times a day; it can also be administered intramuscularly, and can be repeated every 3 to 4 hours if necessary. It can also be used in hibernation therapy. Aspirin can be used for cases with severe abdominal pain and pain in the limbs, waist, and back. Adenosine monophosphate is administered intramuscularly at 125mg every 12 hours, and 400ml of 0.1% procaine is administered intravenously (after a negative allergic test) for pain relief. Pethidine (Duelingding) 50 to 100mg, administered intramuscularly, can quickly and temporarily relieve pain, but due to its easy addiction, it should be used as little as possible or not at all.

　　(2) Ethylenediaminetetraacetic acid has the effect of inhibiting ALA synthase and accelerating the excretion of porphyrin zinc complexes. Oral calcium disodium EDTA is 1g per dose, 4 times a day; or 0.25 to 0.5g can be added to normal saline or glucose solution to be diluted into a 0.25% to 0.5% solution for intravenous infusion, 2 times a day. The course of treatment is 3 to 5 days. The next course should be started 2 to 4 days after discontinuation of the previous course, and generally 3 to 4 courses can be used.

　　(3) Ferric hemoglobin: Ferric hemoglobin can inhibit the synthesis of ALA synthase by negative feedback mechanism, reduce the levels of delta-ALA, PBG, and porphyrin, and is an effective means of treating severe acute porphyria. For patients with acute attacks who cannot stabilize within a day with other treatments such as glucose, ferric hemoglobin should be administered. Early use is recommended for severe patients. The general dose is 2 to 4 mg/kg, diluted with normal saline and administered intravenously at a speed of ≤40 mg/min, completed within 6 to 10 minutes; it can also be added to 500 ml of normal saline for intravenous infusion. There should be at least a 12-hour interval between two intravenous injections. It can also be administered intravenously once a day, with a total daily dose of ≤6 mg/kg within 24 hours. The course of treatment is 3 to 5 days. Symptoms usually improve quickly within 24 to 48 hours, with clinical and biochemical remission; it is generally well tolerated. Blood coagulation should be monitored before and during treatment to avoid concurrent use with other anticoagulants. There may be transient low fever and superficial thrombophlebitis, and there may be transient renal injury with high-dose intravenous injection.

　　(4) Hormones: In some cases, especially in patients with orthostatic hypotension, the use of glucocorticoids such as prednisone (Prednisone) at a dose of 30 to 60 mg per day has a good therapeutic effect. However, it needs to be used for a long time and is not easy to discontinue. A few cases of acute porphyria with a clear relationship to the menstrual cycle may be effectively treated with androgens, estrogens, or oral contraceptives. Some patients' attacks may be related to this, so the use of estrogens or contraceptives must be individualized.

　　(5) Other symptomatic treatments: Low-dose reserpine has a certain effect on neurological and psychiatric symptoms. Patients with restlessness, anxiety, or convulsions can use paraffin (polyethylene oxide) or chloral hydrate. Tachycardia can be treated with propranolol (Propranolol). Hypertensive patients should use antihypertensive drugs (but not methyldopa, as it can worsen symptoms). Severe constipation can be treated with neostigmine. Attention should be paid to maintaining electrolyte balance.

　　Early diagnosis and prevention can lead to a favorable prognosis, not necessarily poor. Patients with recurrent episodes have a poor prognosis. Those with neurological symptoms have a poor prognosis, and patients often die during an acute attack due to ascending paralysis or respiratory paralysis, with a mortality rate of about 15% to 20%. Most death cases are young people under the age of 30. Early detection of patients, attention to avoiding various triggering factors, supportive therapy and care during the attack, especially respiratory care for patients with respiratory paralysis, and rational use of hemin for rescue treatment can greatly reduce the mortality rate. With the increase of age, the disease tends to ease, and the prognosis is better.

　　2. Delayed skin type

　　(1) Venous bloodletting: Venous bloodletting has definite therapeutic value for patients with delayed skin type of blood porphyrin disease. The theoretical basis of bloodletting therapy is not yet fully clear. It is generally believed that the accumulation of porphyrin in the liver and the increased excretion of porphyrin in the urine are caused by excessive synthesis of porphyrin within the liver. After bloodletting, the production of hemoglobin in the body increases, which makes the porphyrin and protoporphyrin that were produced in excess enter the normal channel of hemoglobin synthesis. In addition, it is also related to the reduction of iron load in the liver by bloodletting. About 400ml of blood is let out each time, and the amount of bloodletting for patients with old age, weakness, heart disease, and emphysema can be halved each time. Stop bloodletting when the excretion of urine porphyrin is significantly reduced to a urine total porphyrin content of 0.5mg/L or hemoglobin of 110g/L. Generally, bloodletting 2.4-3L (once a week or every other week, 0.47L) is effective. Skin damage can disappear within a few months, but there is a large individual difference.

　　(2) Chloroquine or hydroxychloroquine (hydroxychloroquine): After the drug combines with porphyrin and iron in liver cells, it is excreted from the urine. Chloroquine 125mg/d, twice a week, hydroxychloroquine 100mg/d, twice a week, the course can last for several months to several years. Patients with delayed skin type can achieve complete clinical and biochemical remission and have good tolerance. However, liver function should be closely observed during the treatment process. Stop taking the medicine when the urine porphyrin is below 100μg per day. The remission period should last at least 20 months. Repeated medication after recurrence is still effective. Venous bloodletting can reduce the dosage of chloroquine. Chloroquine or hydroxychloroquine (hydroxychloroquine) in conventional doses cannot be used because they can cause transient but sometimes severe liver damage, exacerbating photosensitive skin damage.

　　(3) Abstaining from alcohol can alleviate skin symptoms and improve liver function.

　　The prognosis of the delayed skin type is generally good.

　　3. Mixed type and hereditary coproporphyrin type:See acute intermittent type and delayed skin type.

　　Second, prognosis

　　1. Acute intermittent type:Rational application of hemin as rescue treatment can greatly reduce the mortality rate. With the increase of age, the disease tends to ease, and the prognosis is good.

　　2. Delayed skin type:The prognosis is generally good.