Late skin porphyria: causes, symptoms, diagnosis, treatment

Late skin porphyria is a relatively common developing pathology, affecting mainly the skin. Iron ions play a key role in the pathogenesis of the development of this form of porphyria. Clinical symptoms include the appearance of fragility and brittleness of the skin and the appearance of blisters on exposed to sunlight areas of the skin or bruising. Among the population of patients with this form of porphyria, there is an increase in cases of liver pathology. The provoking factors include excessive exposure to the open sun, alcohol, estrogens, transferred hepatitis C and, possibly, HIV infection; However, medications that do not contain iron and estrogens are not dangerous. Diagnosis is based on plasma fluorescence or the detection of porphyrins in urinalysis and stools. Treatment is to reduce the iron content in the blood with phlebotomy, the appointment of chloroquine and increase the excretion of porphyrins, using hydrochloroquine. Prevention is that patients are advised to avoid direct sunlight on the skin, the use of alcohol and iron-containing drugs is prohibited.

[1], [2], [3], [4]

The causes of late cutaneous porphyria

Late skin porphyria (PCT) is the result of a genetically determined deficiency of uroporphyrinogen decarboxylase. Porphyrins accumulate in the liver and are transported to the skin, where they are the cause of increased photosensitivity. Reduction of UPGD activity by 50% in heterozygous patients is not sufficient for the appearance of clinical symptoms of late cutaneous porphyria. For their appearance other factors of disturbance of enzymatic activity should be present. Iron plays a key role, probably contributing to the generation of free oxygen radicals that inhibit UPGD through the oxygenation of their substrate; thus, hemochromatosis is a pronounced risk factor. The use of alcohol, estrogen and a chronic viral infection are also likely to affect the pathogenetic pathways of this porphyria, promoting an increase in the activity of iron ions in liver tissue. Various drugs capable of triggering the triggering mechanism of acute porphyria are not triggers for late cutaneous porphyria.

Liver diseases are often found in late porphyria and are a result of partial accumulation of porphyrin, the development of infectious hepatitis C, concomitant hemosiderosis or alcohol abuse. Cirrhosis occurs in less than 35% of patients, and hepatocellular carcinoma - in 7-24% (more typical for middle-aged men).

Two known forms of the disease, type 1 and type 2, have a similar beginning, rapid development, the same symptomatology and the same treatment. Other less common forms also take place. The frequency of their occurrence is about 1/10000.

In type 1 late cutaneous porphyria (sporadic), the developing deficit of decarboxylase is limited to the liver. Usually this type manifests clinically in middle age or later.

In type 2 of late cutaneous porphyria (familial), the developing deficit of decarboxylase is hereditary, transmitted by the pautosomal dominant type, with limited penetrance. Deficiency develops in all cells, including erythrocytes. Clinical manifestations of it are observed earlier than in type 1, sometimes from childhood.

Secondary PCT-like conditions (pseudoporphyria) may occur with the use of certain photosensitizing drugs (eg, furosemide, tetracyclines, pentanoic acid, sulfonamide drugs, certain NSAIDs). Because of the poor excretion of porphyrins by the kidneys, some patients fall into chronic hemodialysis and develop a skin pathology similar to late cutaneous porphyry (pseudoporphyria of the terminal stage of chronic renal failure).

Symptoms of late cutaneous porphyria

In patients, thinning and brittle skin develops mainly in unprotected areas from the sun. Increased photosensitivity of the skin decreases: patients do not always develop characteristic symptoms when they are in the sun.

Spontaneously or after a slight injury develops pemphigus. Associated erosion and skin ulceration can be complicated by a secondary infection; they slowly heal, leaving atrophic scars. Staying in the sun sometimes leads to the appearance of erythema, edema and itching. Conjunctivitis may develop, but other mucous membranes remain intact. There may be areas of hypopigmentation or hyperpigmentation, as well as facial hypertrichosis and pseudosclerodermoid changes.

Diagnosis of late cutaneous porphyria

In some cases, other healthy people develop thinning and brittle skin and a vesicular rash, which testify to the benefit of the PCT. Therefore, differential diagnosis of acute porphyria with skin symptoms [varigate porphyria (VP) and hereditary coproporphyria (NCP)] is extremely important, as the use of porphyrinogenic medications in patients with VP and NSR can cause the development of neurovisceral symptoms. Previously noted neurological, psychosomatic symptoms or transferred abdominal symptoms of unknown etiology may be indicative of acute porphyria. It should also be borne in mind the history of the use of chemicals by the patient, which can cause symptoms of pseudoporphyria.

Although all porphyria that causes skin lesions exhibit elevated plasma porphyrin levels, increased levels of uroporphyrin and heptacarboxylporphyrin in urine and isocoproporin in feces testify to PCT. The concentration in the urine of the porphyrin porphyrin precursor (PBG) and, as a rule, 5-aminolevulinic acid (ALA) with PCT is normal. The activity of UPGD erythrocytes in type 1 of the PCT is also normal, but increased in type 2.

Because the concomitant development of infectious hepatitis C is characteristic of this pathology and the clinical symptoms of hepatitis are thus smoothed or not determined, serum markers for hepatitis C should be determined (see page 292).

[5], [6], [7], [8], [9]

Treatment and prevention of late cutaneous porphyria

It is possible to use two different therapeutic approaches: reducing iron stores in the body and increasing the excretion of porphyrins. These two approaches to treatment can be combined.

Reducing the supply of iron by phlebotomy and bloodletting is usually effective. The patient gets rid of about 0.5 liters of blood every 2 weeks. When the serum iron level drops slightly below normal, the phlebotomy stops. Usually only 5-6 procedures are needed. The levels of porphyrin in urine and plasma decrease gradually, during the entire treatment period, followed by a parallel decrease in serum iron levels. The skin eventually becomes normal. After the onset of remission, further phlebotomy is necessary only in the case of recurrent disease.

Small doses of chloroquine and hydrochloroquine (100 to 125 mg orally twice a week) help get rid of the excess porphyrins in the liver by increasing excretion. High doses can cause transient liver damage and worsening of porphyria. When remission is achieved, therapy is stopped.

The use of chloroquine and hydrochloroquine is not effective in the case of pronounced renal pathology. Phlebotomy in this case is usually contraindicated, since the development of secondary anemia is observed. Nevertheless, recombinant erythropoietin mobilizes excess iron, reduces the severity of anemia, which is enough to still use phlebotomy as a method of treatment.

Patients should avoid exposure to the sun; headgear and clothes try to choose with the best sun protection properties and use zinc or titanium (from titanium oxide) sun screens. Conventional screens that retain only UV rays are ineffective, but UFO-absorbing protective screens containing dibenzylmethane may in part help protect patients. Categorically avoid drinking alcohol, but estrogen therapy can be successfully resumed after the onset of remission of the disease.