Porphyria cutanea tarda is a chronic disease characterized by increased formation of porphyrins and their accumulation in the skin. In this form, the skin exposed to sunlight (photosensitization) is affected. Pathology is manifested by hyperpigmentation of skin areas, increased vulnerability, hypertrichosis, the formation of blisters, erosions and ulcers. The diagnosis is made on the basis of the clinical picture, anamnesis, high porphyrin content in plasma, urine and feces. As a treatment, plasmapheresis and bloodletting sessions are carried out, aminoquinoline and complexing drugs, sunscreens are prescribed.
ICD 10
E80.1 Slow Porphyria of the skin
General information
Porphyria cutanea tarda (PCT, urocoproporphyria, chronic hepatic porphyria) belongs to a group of diseases with a violation of porphyrin metabolism (porphyria) and is the most common of them. The average frequency of occurrence of urocoproporphyria is 1:10000 people, and in Western Europe and South Africa ‒ 1:1000 and 1:800 people, respectively. The manifestation of porphyria cutanea tarda occurs at the age of 40-50 years. Mostly men are ill, who account for 90-93% of all clinical cases. This pathology is characterized by a chronic course with relapses in the spring-summer period, which is associated with an increase in the length of the day and solar activity.
Causes
The development of the disease is based on the insufficient activity of uroporphyrinogen-decarboxylase, which leads to the accumulation of porphyrins in high concentrations that have a toxic effect. Porphyrins are organic tetrapyrrole compounds that are synthesized mainly in the liver and bone marrow and are necessary for the formation of hemoglobin, myoglobin, catalases, peroxidases, cytochrome P-450 and vitamin B12. Reduced function of uroporphyrinogen decarboxylase leads to inhibition of porphyrin synthesis at the level of uroporphyrin and coproporphyrin.
This can happen due to two mechanisms. The first is a mutation of the A1B18 gene encoding the enzyme, the second is the effect of various factors that have an inhibitory effect on the enzyme. Such factors include hepatitis C, alcoholism, chronic intoxication with heavy metals (arsenic, lead, mercury), taking oral contraceptives, prolonged contact with petroleum products. The most common cause of PCT in men is alcoholism and hepatitis C, in women – hormonal contraceptives. More rare causes are HIV infection, sarcoidosis, malignant liver tumor and end-stage chronic renal failure. The presence of hereditary and acquired forms is the main distinguishing feature of PCT from other disorders of porphyrin metabolism, which are only hereditary pathologies.
Pathogenesis
As a result of the reduced function of uroporphyrinogen decarboxylase, the concentration of coproporphyrin and uroporphyrin increases. These substances, accumulating in the skin, under the influence of the long-wavelength spectrum of sunlight, induce the formation of free radicals, which triggers the processes of lipid peroxidation and the release of proteolytic enzymes from mast cells. This leads to cellular damage to the basement membrane of the epidermis and the vessels of the dermis, which causes the detachment of the outer layer of the skin and the appearance of symptoms of photosensitization (slight vulnerability, blisters, erosion, ulcers).
The deposition of porphyrins in the skin, as well as the stimulation of melanin formation by melanocytes, contributes to increased pigmentation. Hyperpigmentation and phototoxic reactions are also associated with high iron content in the blood. Violation of iron metabolism is a frequent concomitant pathology of PCT, as it develops due to chronic liver diseases. The mechanism of accelerated facial hair growth (hypertrichosis) is still unknown. The damage to the nervous system is limited by the dysfunction of its autonomic department and neurotrophic disorders. Histopathological examination of the skin of patients with PCT reveals its subepidermal detachment, loosening of the stratum corneum of the epidermis, separation of the epidermis from the connective tissue part, characteristic scalloped papillae of the dermis and thickening of the endothelium of the superficial skin vessels.
Classification
Depending on the predominance of certain clinical manifestations, cutaneous, cutaneous-nervous, cutaneous-visceral and mixed forms are distinguished. According to the severity of symptoms, manifest and latent PCT are divided. According to the etiological factor , the following types of urocoproporphyria are distinguished:
- Hereditary. It develops due to a genetic mutation. Inheritance occurs according to the autosomal dominant type. A decrease in the level of uroporphyrinogen-decarboxylase is observed in the liver, erythrocytes, plasma.
- Sporadic (acquired). The most common type of control panel. The main causes are alcoholism, hepatitis C, estrogen intake. Low content of uroporphyrinogen-decarboxylase is noted only in the liver.
- Paraneoplastic. It occurs as a result of the development of a hepatoma that produces excessive amounts of porphyrins. A distinctive feature is the late debut (60-70 years).
- Pseudo-PCT. It develops in patients with chronic renal insufficiency in the terminal stage, i.e. those on hemodialysis. The clinical picture arises not because of the increased production of porphyrins, but their reduced excretion. Features of this form – normal concentration of porphyrins in urine and very high in plasma, pronounced phototoxic reactions.
Symptoms
The main organ of the lesion is the skin. The most typical manifestations of the manifest form are hyperpigmentation, blistering, hypertrichosis. Increased pigmentation is observed in areas of the skin that are systematically exposed to insolation (face, ears, neck, upper chest, hands). The skin takes on various shades – from earthy gray to bronze. The intensity of pigmentation is more pronounced in brunettes. At the beginning of the disease, the change in skin color is temporary, disappearing in winter. As PCT progresses, hyperpigmentation becomes permanent. In some patients, this may be the only symptom for a long time.
Signs of photosensitivity include increased vulnerability of the skin. Detachment of the epidermis occurs even with minor mechanical influences. Dense bubbles up to 1 cm in size with liquid contents form on the skin, which may be serous, purulent or hemorrhagic in nature. After a while, the bubbles open, leaving behind painful erosions. After the erosion heals, scars form.
Latent PCT is characterized by hypertrichosis of the temporomandibular region of the face, thickening of the skin on the back of the neck with deep diamond-shaped folds. Patients look older than their years due to the appearance or strengthening of wrinkles on the face. Vegetative-trophic disorders include increased sweating, headache, sleep disorders, diarrhea or constipation, palpitations, increased vascular pattern on the skin of the upper chest due to paresis of the superficial capillaries (a symptom of “glow” or “lemon skin”), nail deformity, atrophy of the muscles of the hands, forearms, shoulder girdle.
There are atypical variants of cutaneous porphyria. Ulcerative necrotic form develops in people with weakened immunity (diabetes mellitus, HIV infection). With this type of PCT, deep ulcerative skin defects and purulent-necrotic decay of soft tissues occur. Infiltrative plaque, scleroderm-like and vitiliginous forms mimic skin changes in discoid lupus erythematosus (scaly erythema on the face in the form of a butterfly), diffuse scleroderma (compaction, calcification of the skin) and vitiligo (depigmented spots), which causes frequent diagnostic errors.
Cutaneous porphyria in women has some features of the course: an earlier onset of the disease (about 30 years), limited pigmentation on the face (chloasma), pronounced hypertrichosis, damage to atypical skin areas – back, hips, plantar surface of the feet. Among women, vitiliginous, scleroderm-like and infiltrative plaque forms of PCT are more common than among men.
Complications
Porphyria cutanea tarda worsens the course of cardiovascular diseases, increases the risk of developing diabetes mellitus. Permanent erosions and ulcerative defects of the skin are often complicated by bacterial infection. In rare cases, with ulcerative-necrotic form, a syndrome of systemic inflammatory reaction and sepsis develops. The main danger to life are diseases that cause PCT: viral hepatitis C and alcoholic hepatitis, which can lead to cirrhosis and liver failure, oncological diseases, chronic renal failure, HIV infection.
Diagnostics
Porphyria cutanea tarda is an interdisciplinary problem. Doctors of various specialties take part in its diagnosis – dermatologists, hematologists, infectious diseases specialists, hepatologists, rheumatologists, oncologists. Since in most cases skin porphyria is acquired in nature, it is necessary to find out against what disease it has developed. The patient needs to learn about alcohol consumption, oral contraceptives, the presence of viral hepatitis C. To make a diagnosis, the following research methods are carried out:
- Routine laboratory tests. In the biochemical analysis of blood, there is an increase in hepatic transaminases, bilirubin, gamma-glutamyltranspeptidase (a specific indicator of alcoholic liver damage), ferritin, serum iron, creatinine (in renal failure), a decrease in albumin levels. With cirrhosis of the liver, signs of hypocoagulation are detected in the coagulogram. Many patients have positive markers of hepatitis C virus.
- Specific laboratory tests. There is an increase in the concentration of uroporphyrin in plasma and urine, coproporphyrin in feces. Under Wood’s lamp, urine takes on a red-orange or bright pink glow. With luminescent microscopy, plasma gives red fluorescence. A decrease in the activity of the enzyme uroporphyrinogen-decarboxylase in erythrocytes and the presence of a genetic mutation is characteristic only for the hereditary form of the disease.
- Instrumental research. Imaging methods (ultrasound and CT of the abdominal cavity) should be carried out to exclude malignant liver formation producing porphyrins. This primarily concerns patients who developed symptoms of the disease after the age of 60.
Cutaneous porphyria should be differentiated from other types of porphyria occurring with skin lesions (hereditary coproporphyria, congenital erythropoietic and variegate porphyria). Porphyria cutanea tarda is also differentiated with dermatological (photodermatoses, vulgar pemphigus, During’s herpetiform dermatitis), rheumatological diseases (discoid lupus erythematosus, diffuse scleroderma), hemochromatosis, adrenal insufficiency.
Treatment
Special attention in the treatment of PCT is paid to the elimination of factors and pathologies that led to the development of the disease. This implies complete abstinence from alcohol, discontinuation of oral contraceptives, treatment of hepatitis C, antiretroviral therapy, chemotherapy and surgical removal of a malignant liver tumor.
Pathogenetic treatment of PCT includes several measures. In order to remove excess porphyrins and iron from the blood, phlebotomy (bloodletting) and plasmapheresis sessions are performed. In addition to these procedures, as well as with contraindications to them, drugs that bind and remove porphyrins and iron are used. These include synthetic antimalarial drugs from the group of aminoquinolines (chloroquine, hydroxychloroquine) and complexing compounds (deferoxamine, D-penicillamine). When using aminoquinolines, it is very important to start taking them with small doses. This is due to the fact that the usual doses at the beginning of treatment cause a specific toxic reaction (porphyrin crisis), characterized by increased synthesis of porphyrins and a sharp deterioration in the patient’s condition (fever, nausea, vomiting, abdominal pain). Enterosorbents (activated charcoal) are prescribed to reduce the absorption of porphyrins in the gastrointestinal tract.
To protect the skin from sunlight, it is recommended to wear maximally closed clothing, use sunscreens and ointments containing parsol- 1789 or mexomil ‒ substances that do not transmit ultraviolet rays of the long-wavelength spectrum. Constant treatment of erosive skin surfaces with antiseptic solutions is mandatory in order to avoid infectious complications.
Prognosis and prevention
Among all pathologies with impaired porphyrin metabolism, cutaneous porphyria is the most favorable in terms of course and prognosis. Serious complications rarely occur, their cause is mainly diseases or pathologies that lead to the development of PCT. Prevention consists in avoiding factors contributing to the occurrence of skin porphyria (alcohol consumption, oral contraceptives, prolonged exposure to the sun, contact with heavy metals, petroleum products). People who have a patient with a hereditary form of PCT in their family are shown to determine the activity of uroporphyrinogen-decarboxylase and conduct molecular genetic diagnostics.
