Retinoic acid syndrome (RAS) is a potentially life-threatening complication observed in people with acute promyelocytic leukemia (APML) and first thought to be specifically associated with all-''trans'' retinoic acid (ATRA) (also known as tretinoin) treatment. Subsequently, so-called RAS was recognized in APML patients who had been treated with another highly efficacious drug,

arsenic trioxide Arsenic trioxide, sold under the brand name Trisenox among others, is an inorganic compound and medication. As an industrial chemical, whose major uses include in the manufacture of wood preservatives, pesticides, and glass. As a medication, it ...

, and yet did not appear in patients treated with

tretinoin Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth ...

for other disorders. These facts and others support the notion that RAS depends on the presence of the malignant promyelocytes. This has led to the growing deprecation of the term 'retinoic acid syndrome' and to an increasing use of the term differentiation syndrome to signify this APML treatment complication.

Signs and symptoms

The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates. This is effectively treated by giving

dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...

and withholding ATRA (or arsenic trioxide) in severe cases. An elevated white count is sometimes associated with this syndrome, but is not always pathognomonic. Once RAS has resolved, pro-differentiation chemotherapy can be resumed.

Causes

The cause of RAS is not clear. Several causes have been speculated, including a

capillary leak syndrome Capillary leak syndrome, or vascular leak syndrome, is characterized by the escape of blood plasma through capillary walls, from the blood circulatory system to surrounding tissues, muscle compartments, organs or body cavities. It is a phenomenon ...

from

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

release from the differentiating myeloid cells. Alternatively, ATRA may cause the maturing myeloid cells to acquire the ability to infiltrate organs such as the lung. Mediation by

cathepsin G Cathepsin G is a protein that in humans is encoded by the ''CTSG'' gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin ...

has been suggested.

Diagnosis

Treatment

The treatment of RAS usually involves administering dexamethasone IV, with the dosage usually 10 mg twice a day for 10 days. It is important for patients to discontinue the use of tretinoin due to the elevation of white blood cells and possible low blood oxygen.

References

{{reflist Paraneoplastic syndromes

Signs and symptoms

Causes

Diagnosis

Treatment

See also

References