Cutaneous porphyria

Introduction to skin porphyria Dermatoporphyria is a group of photosensitized products produced by the accumulation of porphyrin and/or porphyrin precursors due to genetic defects or acquired factors during the biosynthesis of heme. Diseases characterized by cutaneous lesions, including erythropoietic protoporphyria (EPP), delayed porphyria (PCT), congenital erythropoietic porphyria (CEP), mixed porphyria ( VP) and hereditary fecal porphyria (HC). basic knowledge The proportion of illness: 0.035% Susceptible people: the incidence is mostly in childhood, mostly 4 to 10 years old Mode of infection: non-infectious Complications: gallstones, anemia, systemic lupus erythematosus

Cause of skin porphyria

(1) Causes of the disease

The intermediate product of the porphyrin heme synthesis process, the synthesis of heme begins in the mitochondria of bone marrow and hepatocytes, and the mitochondria are rich in glycine and succinate in the -aminolevulinic acid (ALA) synthase Catalytic synthesis of ALA, followed by dehydration of the biliary protoplast (PBG) synthetase to form PBG, a monopyrrole precursor of porphyrin, PBG deaminated to form hydroxymethylcholnetium, a small part of which is converted into uroporphyrin I, and most of them produce uroporphyrinogen III under the action of uroporphyrinogen III synthetase, further decarboxylation to produce coproporphyrinogen III, and then continuously oxidize to protoporphyrinogen IX and protoporphyrin IX, and then Complexation with iron under the action of ferrous chelatase produces heme.

(two) pathogenesis

The pathogenesis of porphyria is still not fully understood, but the genetic defects of certain enzymes in the process of porphyrin-heme biosynthesis are often the main cause of various skin porphyria diseases, in which the incidence of PCT is heterozygous. In addition, all of them are monogenic diseases. EPP, HC, VP and a small part of PCT are all autosomal dominant, but due to the low clinical penetrance, patients often complain of no family history, and CEF is autosomal recessive.

Due to the defects of specific enzymes, the accumulation of substrate is closely related to the clinical features of porphyria. In general, the episodes of acute neuropsychiatric disorders are always accompanied by the formation of porphyrin precursors (PBG or ALA). The occurrence of damage is directly related to the excessive production of various porphyrins. For example, urinary porphyrin, coproporphyrin and protoporphyrin have significant photo-sensitization in the excessive deposition of skin, especially urinary porphyrin. Water-soluble, light sensitivity is stronger, the protoporphyrin in the blood has affinity for erythrocyte membrane lipids, and is prone to photolylolytic reaction. In fact, porphyrin itself is not pathogenic, it is only a human body source. Photosensitive material, which has photodynamic action and has the ability to absorb a specific wavelength spectrum (peak is about 405 nm), thereby forming an excited state of porphyrin, or losing energy to emit red fluorescence, or transferring energy to other molecules in oxygen. In the presence of light toxicity, singlet oxygen is formed, free radicals such as peroxides cause cell lysosomal destruction, or membrane permeability increases due to release of inflammatory mediators such as histamine and bradykinin, resulting in tissue Damage; or Acting on the erythrocyte membrane, causing the formation of lipid peroxides to cause erythrocyte membrane damage and hemolysis. Recently, it has been found in experimental animal models that if porphyrin is injected and then irradiated with 405 nm light, complement is consumed, suggesting that complement activation is in some Some porphyria lesions may also play a role in the production of lesions. In short, the production of porphyria must have two conditions: First, there are too many porphyrins and/or porphyrin precursors in the organs of human tissues. Second, it is excited by light of a specific wavelength, and the spectrum of action of porphyria is 405 nm.

Skin porphyria prevention

Avoid sun and light as much as possible, and use sunscreen preparations that have good protection against visible light and long-wave ultraviolet rays.

Complications of porphyria Complications gallstone anemia systemic lupus erythematosus

Erythropoiogenic protoporphyria (EPP), an increase in protoporphyrin in the blood can lead to deposition and excessive accumulation in hepatocytes and gallbladder, resulting in gallstones and varying degrees of liver damage and sclerosis, and 2 cases of recurrent disease 3 to 4 years of biliary colic attacks, some patients with mild anemia, delayed skin porphyria (PCT), with systemic lupus erythematosus, non-insulin dependent diabetes, chronic lymphocytic leukemia and AIDS Reported, congenital erythropoietic porphyria (CEP), multiple attacks can occur extremity contracture, ear and nose finger defects, cheek scars, eyelid valgus, eye adhesions, scarring alopecia and other serious damage.

Symptoms of skin porphyria Common symptoms Depression scar Abdominal pain Gallbladder pimples Gallbladder stones Gallstones Crusts Edema Spot light allergy

Skin porphyria is reported in China less. According to our statistics, there were only 145 cases from 1953 to 1996, of which EPP accounted for 75.2% (109 cases), PCT had 28 cases, CEP had 3 cases, PV had 1 case, and untyped. 1 case, no HC reported.

1. erythropoietic proto-porphyria (EPP): is the most common skin porphyria disease, often family history, autosomal dominant inheritance, the incidence is mostly in childhood, mostly 4 to 10 years old, adult onset Rarely, it is characterized by acute photosensitivity reaction. After 5-30 minutes of exposure to the sun, the exposed parts of the face and back of the hand are itchy or burning, followed by flaky swelling, erythema, depending on the intensity and time of the sun. The cheeks of the cheeks, the dorsal side of the fingers, the ventral side of the nails and the ventral side of the fingertips may have ecchymoses or even blistering and nail peeling. If the skin can be protected from light after the onset, the swelling can be eliminated within 2 to 5 days, and the skin fragility is increased. After the stimulation, the strip-like epidermis peeling and crusting and the worm-like depression of the needle to the sesame are generally shallow. After repeated attacks for several years, the skin gradually thickens and the face looks like wax. Skin-like nose, pale and thick lips, thick red mucous membrane texture, connected with perioral dermabrasion into characteristic radial cracks and scars, thickening of the back of the hand often begins at the metacarpophalangeal joint and the proximal interphalangeal joint. Behind the knuckles, followed by the back of the hand Tiger's mouth even more, gradually moss-like thickening, grooves obviously, was paving pebble-like appearance, mostly diamond-shaped neck, skin, occasionally skin pigmentation and temporal vellus hair thickening, the whole face was weather-beaten appearance of premature aging.

The porphyrin abnormalities in patients are mainly excessive protoporphyrin in plasma and red blood cells. The increase of protoporphyrin in blood can lead to deposition and excessive accumulation in hepatocytes and gallbladder, causing gallstones and varying degrees of liver damage and Hardening, we have seen 2 cases of 6-year-old children with recurrent episodes of this disease for 3 to 4 years caused by biliary colic, B-ultrasound showed gallstones, 1 case confirmed by surgery, some patients have mild anemia, small cell-like low blood red Anemia, the patient is not deficient in iron, and may be related to defects in the body's ferrous chelatase.

2. Delayed skin porphyria (PCT): The disease is divided into two types, type I is sporadic (or symptomatic, acquired), type II is familial, the former is more common, and the patient has no family inheritance. Background, can occur at any age after the age of 20; the latter is autosomal dominant, rare in the disease, mild symptoms, mostly within 20 years of age, has been confirmed in the patient's liver, red blood cells and other tissues There is a defect of uroporphyrinogen decarboxylase. In sporadic cases, this defect is only found in the liver. The defects of this enzyme are often related to hepatic iron deposition caused by overload of liver iron load. Patients often have some liver toxicity. The basis of the factor, such as found in alcoholics, long-term use of estrogens (treatment of prostate lesions, oral contraceptives, etc.), halogen hydrocarbon chemical poisoning (can be epidemic after consumption of crops sprayed with such pesticides) and Liver disease (various viral hepatitis, cirrhosis and hepatocellular carcinoma, etc.), in addition to reports of systemic lupus erythematosus, non-insulin-dependent diabetes mellitus, chronic lymphocytic leukemia and AIDS, in long-term hemodialysis Also visible in the incidence of this disease, these circumstances may be related to disturbed porphyrin metabolism.

The onset of the disease is slow and insidious. Patients often have no clear history of sun allergy. Skin lesions are mainly distributed in the light exposed areas of the face and hands. The most common manifestations are: increased skin fragility, blisters under the epidermis, hairy and pigmentation, and easy skin. It is rubbed into an irregularly-shaped ablative surface. The blisters can be small or large, or bloody, and scars and hemorrhoids are left behind. The hairy hair is two inches, especially the periorbital and forehead. The mane is dense, thick and long black; the pigmentation is diffuse. Distributed in the exposed area, especially in the periorbital and temporal regions, the latter two lesions are often overlooked in the early stage and are not easy to diagnose. In addition, there are scleroderma lesions, scarring alopecia and nail damage, such as periungual swelling and Freckles, nail peeling, missing and deformed.

The abnormality of porphyrin in patients is mainly due to excessive urinary porphyrin and coproporphyrin in urine. In some patients, due to the presence of a large amount of porphyrin, the urine color can be deepened like black tea, and the liver can have different degrees of damage and hardening. Corresponding symptoms, the patient's serum iron is often increased, saturated iron is reduced, generally no significant systemic symptoms.

3. Congenital erythropoietic porphyria (CEP): also known as Gunther disease, this disease is rare, is autosomal recessive, the incidence is mostly in infancy, often severe photosensitive damage soon after birth: erythema, Edema, ecchymosis, blood blisters and bullae, the skin lesions are slower and slower, often causing ulcers, scars, limb contractures after multiple episodes, missing ear and nose fingers, cheek scars, eyelid valgus, eyeball adhesions, scarring baldness The hair is severely damaged, and the lighter skin is affected by pigmentation, increased hairiness and fragility. Since the porphyrin metabolism erupts before the deciduous teeth, the teeth of the child are brown and show bright red fluorescence, which is characteristic of this disease. Urinary dark red, diaper red staining is often the first symptom, the course progresses slowly, often hemolytic anemia and spleen enlargement, secondary bacterial infection and severe anemia, bleeding is the main cause of death, the late hair of this disease can be In the onset of puberty, the symptoms are significantly lighter, easily misdiagnosed as PCT, the patient's porphyrin abnormalities, mainly in the plasma, red blood cells and urine have an excess of urinary porphyrin.

4. Hereditary fecal porphyria (HC) and mixed porphyria (VP): These two porphyria are similar to acute intermittent porphyria (AIP), with acute symptoms of porphyria. More than puberty, mainly manifested as acute abdominal pain and a variety of neuropsychiatric symptoms, belonging to the scope of acute hepatic porphyria, AIP is a more common one, but no photosensitivity and skin damage, HC and VP are rare, There may be skin manifestations similar to PCT, which are often difficult to distinguish clinically, but the performance of HC is mainly caused by the acute porphyrin symptoms of AIP, while VP has more PCT skin lesions.

Examination of skin porphyria

Mainly to measure various porphyrins (urinary porphyrins, coproporphyrins and protoporphyrins) and porphyrin precursors (PBG and ALA) in plasma, red blood cells, urine and feces, clinically used for urine and red blood cells The simple screening method can basically diagnose and identify the three common skin porphyria diseases - EPP, PCT and CEP.

There are two screening methods: one is the extraction method: the urine is extracted with pentanol, the red blood cells are hemolyzed, extracted with ether, and then acidified to remove the sediment, and then checked for fluorescence under the filtered ultraviolet lamp, which is pink to bright red fluorescent. Positive, the second is the fluorescence method: mainly to measure the protoporphyrin in red blood cells, that is, the ratio of the number of red blood cells emitting bright red fluorescence under the fluorescence microscope, the normal value is <1%, if >5% has diagnostic significance for EPP, In patients with lead poisoning, pernicious anemia and hemolytic anemia, abnormal porphyrins can also be detected in red blood cells, urine and feces, which should be identified and quantified if necessary, such as urinary porphyrin and coproporphyrin in 24 hours. Quantitative determination, fluorescence spectrophotometric determination of free protoporphyrin in red blood cells, quantitative analysis of porphyrin by high performance liquid chromatography.

Histopathology: The lesions of all porphyria lesions in both types were accompanied by an increase in the concentration of porphyrin in the skin and plasma. The histopathological changes were approximately the same, characterized by a uniform eosinophilic red around the capillary wall in the upper part of the dermis. Dyed rings, these red-stained substances are the deposition of clear proteins, which can be more clearly shown by PAS staining. They are also found in the basement membrane band and may damage the adhesion between the dermis and the epidermis, forming subepidermal blisters, which are characterized by blister The dermal papilla protrudes into the blister cavity and is colored balls.

Diagnosis and diagnosis of porphyria

diagnosis

The clinical manifestations of porphyria are very varied. Therefore, the diagnosis relies mainly on the vigilance of doctors and the understanding of the clinical syndrome and various types of characteristics of the disease. Generally, according to the characteristics and distribution of light-sensitive skin lesions, combined with the age of onset of patients and Family genetic history can make a preliminary diagnosis. For example, CEP should be considered in severe photosensitivity damage in infancy, and EPP is mostly in childhood. Photosensitive damage and hairy at the same time in adulthood, pigmentation should be considered as PCT.

Differential diagnosis

What should be distinguished from CEP is dystrophic bullous epidermolysis, which is often destroyed, but its occurrence and lesions are related to trauma and collision without photosensitivity, and no red teeth and red urine. EPF must be differentiated from acne-like vesicular disease. The age of onset, light-sensitive history and family history are similar, but the onset and performance of skin lesions are significantly different from the phototoxic damage of EPP. The main pruritus is not burning. The lesions are mainly papules and blisters without obvious swelling and ecchymosis. The formed acne-like scars and EPP are superficial and have different depressions. The incidence is mostly relieved after puberty without repeated episodes of EPP. Characteristic skin thickening performance, early diagnosis of PCT is often difficult, because there is often no clear history of sun allergy, facial epidermal erosion needs to be differentiated from artificial dermatitis, blister, blood blister damage and niacin deficiency Identification, scar and millet rash damage should be differentiated from acquired bullous epidermolysis. When hirsutism or pigmentation damage is dominant, it needs to be differentiated from related endocrine diseases. The main point of diagnosis of PCT is to express these results. Do not Isolation from and should be considered.

For patients with suspected skin porphyria disease, porphyrin examination in urine and red blood cells must be performed. The positive detection of porphyrin analysis is decisive for the diagnosis and differential diagnosis of this disease.

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