Retinoic acid syndrome
Encyclopedia
Retinoic acid syndrome is a potentially life threatening complication observed in patients with acute promyelocytic leukemia
(APML) and first thought to be specifically associated with all-trans retinoic acid
(ATRA) (also known as tretinoin) treatment. Subsequently it was recognized that so-called RAS appeared in APML patients who had been treated with another highly efficacious drug, arsenic trioxide
, and yet did not appear in patents treated with tretinoin
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.
and holding ATRA (or arsenic trioxide) in severe cases. An elevated white count is sometimes associated with this syndrome, but is not a prerequisite.
Once RAS has resolved, pro-differentiation chemotherapy can be ali resumed.
from cytokine
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
has been suggested.
Acute promyelocytic leukemia
Acute promyelocytic leukemia is a subtype of acute myelogenous leukemia , a cancer of the blood and bone marrow. It is also known as acute progranulocytic leukemia; APL; AML with t, PML-RARA and variants; FAB subtype M3 and M3 variant.In APL, there is an abnormal accumulation of immature...
(APML) and first thought to be specifically associated with all-trans retinoic acid
Tretinoin
Tretinoin is the acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel...
(ATRA) (also known as tretinoin) treatment. Subsequently it was recognized that so-called RAS appeared in APML patients who had been treated with another highly efficacious drug, arsenic trioxide
Arsenic trioxide
Arsenic trioxide is the inorganic compound with the formula As2O3. This commercially important oxide of arsenic is the main precursor to other arsenic compounds, including organoarsenic compounds. Approximately 50,000 tonnes are produced annually...
, and yet did not appear in patents treated with tretinoin
Tretinoin
Tretinoin is the acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a drug commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel...
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.
Presentation
The syndrome is characterized by dyspnea, fever, weight gain, hypotension, and pulmonary infiltrates. This is effectively treated by giving dexamethasoneDexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
and holding ATRA (or arsenic trioxide) in severe cases. An elevated white count is sometimes associated with this syndrome, but is not a prerequisite.
Once RAS has resolved, pro-differentiation chemotherapy can be ali resumed.
Etiology
The etiology of RAS is not clear cut. Several causes have been speculated including a capillary leak syndromeCapillary leak syndrome
Capillary leak syndrome is a rare medical conditioncharacterized by self-reversing episodes during which the endothelial cells which line the capillaries are thought to separate for a few days, allowing for a leakage of fluid from the circulatory system to the interstitial space, resulting in a...
from cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
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
Cathepsin G is an enzymatic protein belonging to the peptidase or protease families. In humans, it is coded by the CTSG gene.The protein encoded by this gene, a member of the peptidase S1 protein family, is found in azurophil granules of neutrophilic polymorphonuclear leukocytes...
has been suggested.