Porphyrias

Cells require the supply of oxygen for their proper functioning. Those responsible for carrying oxygen to the tissues are the red blood cells, also called erythrocytes or red blood cells. Inside it is a complex protein, hemoglobin, which is the one that carries oxygen and carbon dioxide that are exchanged in the pulmonary alveoli. Part of this protein is the heme group, formed by an iron nucleus, which has the ability to reversibly bind oxygen. The heme group, in addition to being part of hemoglobin, is a constituent of a series of liver enzymes, so that its synthesis occurs mainly at the liver and bone marrow level.

The heme group is formed through a complex chain of enzymatic reactions that gives rise to a series of intermediates called porphyrins, from the Greek porphyria, which means dark red. If there is a deficit of any of the enzymes that participate in the formation of the heme group, these intermediate substances accumulate and have repercussions on the body. The set of pathologies derived from the accumulation of these substances is what is known as porphyrias.

How is it produced?

Porphyrias are a group of rare diseases and are largely inherited. Depending on their origin, a difference is made between erythropoietic porphyrias, if they originate in the bone marrow, or hepatic porphyrias, if they are due to alterations generated in the liver.

The main ways are:

• Erythropoietic porphyrias:

Congenital erythropoietic porphyria (PEC), also called Günther's disease, is an autosomal recessive inherited disease.

Erythropoietic protoporphyria (EPP), it is an autosomal dominant inherited disease

• Hepatic porphyrias:

Porphyria cutanea Larva (PCT), the most common type, there is an acquired form (caused by alcohol, iron, estrogens, toxic chemicals, and other drugs) and a form that is inherited autosomal dominant.

Hepatoerythrocytic porphyria (PHE) is an autosomal recessive hereditary disease.

Porphyria variegata (PV), an autosomal dominant inherited disease.

Hereditary coproporphyria (HPC), also an autosomal dominant inherited disease.

Acute intermittent porphyria (AIP) is the most common acute form and is an autosomal dominant hereditary disease.

The age of onset is highly variable, being in childhood in the case of PEC and PEP, between 15 and 40 years of PAI, PV and CPH, and between 30 and 40 years in the case of PCT, the most common form.

Symptoms

The accumulation of porphyrins in different organs and systems of the body is responsible for the clinical manifestations, which are mainly cutaneous, digestive, neurological and psychiatric. In general, the enzymatic deficits are well compensated, but when there is a situation in which the synthesis of the heme group is increased, the balance is unbalanced and that is when the accumulation of porphyrins generates clinical manifestations.

At the skin level, episodes of photosensitivity occur, with itching and skin pain shortly after exposure to sunlight, followed by a lesion similar to a burn and disproportionate to the time of exposure to sunlight. It occurs especially in PPE.

Another skin manifestation is skin hyperfragility, in which blisters appear on the skin in the area exposed to the sun, especially on the back of the hands. These wounds heal causing an alteration in pigmentation, either by excess or by default. It is associated with excess facial hair in adults and generalized in children. As the skin undergoes these episodes, it atrophies. This skin alteration is seen in PCT, PHE, PV and CPH, the most aggressive form being that of PEC. The PAI does not present cutaneous alterations.

Some of the forms of porphyria present with acute outbreaks, characterized by abdominal pain, neurological symptoms, and psychiatric manifestations. It is the form of presentation characteristic of the PAI. Abdominal pain associated with nausea, vomiting and constipation appear. At the neurological level, polyneuropathies, muscle pain and sometimes paralysis of the extremities occur. The most common psychiatric manifestations are anxiety and psychosis attacks.

In the case of PEC, which appears in childhood, a dark urine that stains the diaper red and skin lesions can be seen from the first exposure to the sun. Over time these injuries can lead to mutilation of the fingers of the hands. The teeth usually have a brown color due to the accumulation of porphyrins. Likewise, it is associated with hemolytic anemia (due to ruptured red blood cells) and secondary splenomegaly, something that does not occur in PHE.

In PCT, the most common form, it is common for patients to present increased facial and hand pigmentation, with increased hair on the cheeks and scars and cysts on the back of the hands. Most have skin lesions on the back of the hands with the least trauma.

PV and CPH are so-called mixed forms, since they present identical skin lesions to those of PCT, but patients also suffer from episodes of acute attacks as occurs in IAP.

Diagnosis

The initial diagnosis will be clinical, in the presence of a patient with skin alterations such as those described or episodes of seizures with abdominal, neurological and psychiatric manifestations. It is essential to determine with the patient if there is a family history of symptoms similar to yours.

Given the clinical suspicion, the confirmatory diagnosis will be provided by analytical methods, determining the porphyrins and their derivatives and precursors in blood, urine and feces, in order to be able to assess which excess accumulates and be able to identify the type of porphyria.

In the ECP, a decrease in hemoglobin will be seen in the analysis due to the hemolytic anemia that occurs, so that an anemia with normal size red cells (normocytic) and with a normal hemoglobin concentration (normochromia) will be seen, as well such as an increase in the enzyme lactate dehydrogenase (LDH) and reticulocytes, the young forms of red blood cells, as the bone marrow will try to make up for the shortage of red blood cells.

Treatment

Cutaneous manifestations are caused by photosensitivity, so that treatment will be based on providing good sun protection and preventing the accumulation of porphyrins, suppressing the consumption of alcohol and certain drugs, and giving treatment with chloroquine diphosphate until achieving the remission, which is usually achieved in 12-18 months. To reinforce photoprotection, carotenes will be administered orally, especially in the case of PPE.

Abdominal pain crises in porphyria attacks in PAI, PV, or CPH are treated by administering intravenous carbohydrates in large doses.

Precautionary measures

The essential preventive measures will be aimed at avoiding crises, therefore, unprotected sun exposure should be avoided in those patients who present porphyrias with skin manifestations, and avoid substances that trigger outbreaks, such as alcohol and drugs with hepatic metabolism, such as estrogens, sulfa drugs, antimalarials, or morphine.