Looking for:
Vitamin A Toxicity - StatPearls - NCBI Bookshelf.Vitamin A toxicity | DermNet |
Tretinoin vitamin a toxicity -
Skip navigation! Story from Skin Care. Kristin Booker. Photo: Courtesy of Sephora. Everywhere you look, there's another skin cream containing retinol, the purest form of natural vitamin A. We're big fans of it over here in the beauty department, which is why, when we heard a rumor that you can be poisoned by using too much of it, our first reaction was "Jigga WHAT?!?
Before we get started, a quick note on what hypervitaminosis A could do to you: liver damage, blurred vision, hair loss, and a whole bunch of other Things You Do Not Want. It's not okay. So, it was time to ask some questions. One call to Dr. Jeannette Graf, M. Nope, it's not possible to get toxic quantities of vitamin A from your beauty products.
Those rumors are "crazy," says Dr. Retinol is the most naturally abundant form of vitamin A within the skin, so there's a natural limitation to how much you retain at any given point. If you become saturated, it just passes right through.
It's certainly not being absorbed. What about pro-retinol forms like beta-carotene? There's no danger of toxicity. What about that old fear of eating so many carrots that you turn orange? But, again, it's totally harmless.
Last item: Can any one product contain too much vitamin A? Graf says. Graf advises using products with retinol at night for best results. It's the desert island ingredient most people should be using. In closing, rest easy: You can't OD on too much vitamin A from your skin-care products.
Slather them on as directed and you'll A-okay. Before retinol came along and stole its thunder, hyaluronic acid was considered the gold standard. Scientists, dermatologists, and skinfluencers alike rega. Gua sha is so much more than the vibe-y jade or rose quartz tools you see on Instagram. But you know that already.
While real-deal gua sha which loosely. For more insid.
❿DermNet provides Google Translate, a free machine translation service. Note that this may not provide an exact translation in all languages. Author: Brian Wu PhD. Vitamin A is a fat soluble retinoid. It also called retinol. Vitamin A is needed for immunity, visual and dermatological health as well as cell communication and growth. In excessive amounts, however, it can accumulate in the liver and cause a wide array of symptoms. Toxicity is classified as either acute or chronic.
The most common cause of acute vitamin A toxicity is the ingestion generally accidental of overIU of vitamin A. The most common cause of chronic vitamin A toxicity is the regular ingestion of overIU daily, which is sometimes prescribed for dermatological conditions such as acne. It is also important to note that vitamin A is highly teratogenic if taken during pregnancy especially in the first 8 weeks if intake exceeds 10, IU daily. Birth defects can also be caused by isotretinoin or other oral retinoidsif taken while pregnant.
Excessive intake of Vitamin A during pregnancy has been associated with the following birth defects, collectively known as retinoic acid syndrome :. Diagnosis of vitamin A toxicity is based on signs and symptoms, patient history, lifestyle habits and use of supplements.
There is sometimes a poor correspondence between toxicity and serum retinol levels. The blood sample must be protected from light. Vitamin a toxicity is treated by stopping the use of vitamin A supplements.
Generally, signs and symptoms will resolve on their own with 1—4 weeks, depending on their severity. Birth defects caused by vitamin A toxicity during pregnancy are irreversible. Books about skin diseases Books about the skin Dermatology Made Easy book. DermNet does not provide an online consultation service.
If you have any concerns with your skin or its treatment, see a dermatologist for advice. Home arrow-right-small-blue Topics A—Z arrow-right-small-blue Vitamin A toxicity info-icon print-icon. Vitamin A toxicity — codes and concepts. Vitamin A poisoning, Hypervitaminosis A. Reaction to external agent, Systemic disorder. Table of contents arrow-right-small. What is vitamin A toxicity? What causes vitamin A toxicity? What are the signs and symptoms of vitamin A toxicity?
Vitamin A and teratogenicity How is vitamin A toxicity diagnosed? How is vitamin A toxicity treated? Vitamin A toxicity is also known as hypervitaminosis A. Acute toxicity The most common cause of acute vitamin A toxicity is the ingestion generally accidental of overIU of vitamin A. Chronic toxicity The most common cause of chronic vitamin A toxicity is the regular ingestion of overIU daily, which is sometimes prescribed for dermatological conditions such as acne. References Vitamin A — Johnson, L.
Merck Manual. National Institute of Health. Vitamin A Retinol — Mayo Clinic. Sign up to the newsletter. Full name. Email address.
❾-50%}- StatPearls [Internet].
The consumer who measures his or her daily intake of vitamin A by the DV percentage appearing on food labels could easily consume more than the RDA, and possibly come close to the UL. The RDA value used on the food label for vitamin A is overly generous for older adults. In the RDA tables, values for only a few nutrients differed between persons age years and those age 51 years or older. The data examined by the RDA Committee for the most part were not derived from studies on older adults but were data extrapolated from younger adult values.
Some foods have long been vitamin A—fortified, including milk, some margarine, instant oats, and ready-to-consume breakfast cereals. Recently, however, other foods have been fortified with relatively high amounts of vitamin A, as well as with other vitamins. These include cereal bars, energy bars, and candy. The decision regarding which foods are fortified, the amount of fortification, and the form of vitamin A that is used is not regulated; rather, individual manufacturers are free to make these decisions.
Some vitamin D supplements include preformed vitamin A. Consumers seeking a vitamin D supplement might not examine the labels of these supplements closely and could unwittingly choose one that also contains vitamin A. Fish liver oil and fish liver oil capsules, such as those from cod or halibut liver, also contain appreciable amounts of preformed vitamin A. The IOM encourages consumption of all carotenoid-rich fruits and vegetables for health-promoting benefits.
Recent research indicates that supplements in the form of whole food extracts rich in antioxidants may possibly have benefit in humans.
Clinical application of oral retinoids include the use of megadose vitamin A for the treatment of age-related macular degeneration ARMD. Isotretinoin is a retinoid that is Food and Drug Administration FDA —approved to be given orally for recalcitrant severe nodular acne. Incidentally, it is prescribed more and more frequently for less severe acne.
In addition, although there have not been significant numbers of older adults in clinical trials evaluating the use of isotretinoin, it has been used in this age range. There are several topical retinoids available. Topical retinoids are prescribed widely both for diseases that have been FDA—approved, as well as for evidence-based off-label uses.
A popular prescription is tretinoin, which is commonly used for the treatment of acne. All-trans retinol is a parent form of vitamin A, which is a weaker form of the prescription tretinoin and is added to many over-the-counter topical beauty products. The therapeutic window for medicinal benefit is narrow, particularly when addressing the comorbidities of many older adults and the combined effect of all medications, both prescribed and over-the-counter, as well as dietary intake.
There is a tendency in the older population for overuse of supplements. Supplement use in general is associated with high intakes of vitamin A. Most multivitamins specify the type and amount of vitamin A contained in the product. A widely referenced article published in the Journal of the American Medical Association advocated that all adults take a multivitamin daily and suggested a daily dose of two multivitamins for older adults.
This practice places the older adult at even greater risk of hypervitaminosis A, given that the DV on supplements is based on an RDA, which is higher than current recommendations; hence, this approach should be discontinued. Furthermore, chronic renal disease may also result in significantly elevated serum retinol levels and should be taken into consideration.
Synthetic retinoids, derivatives of vitamin A, are manufactured into a cream or gel such as isotretinoin and tretinoin. Any additional intake of vitamin A retinol should be avoided when using these products due to some systemic absorption.
It is known that serum levels are minimally affected by topical application of tretinoin, and case reports do exist describing topical tretinoin-induced teratogenesis. Research suggests that those of advancing age may require less vitamin A than younger adults because of higher circulating levels. With advancing age, both mean and median liver values for vitamin A do not decrease despite indication that dietary intake of vitamin A decreases. Animal studies indicate that uptake and absorption of vitamin A by the intestine increase with age.
Russell 8 compared blood response curves after feeding physiologic doses of vitamin A to young and older adults, and found that the latter had significantly higher blood responses than did the former. This could be due to either increased absorption or decreased clearance by peripheral tissue. Additional studies indicated that young adults were able to clear reinfused vitamin A twice as quickly as the older adults.
The significance of the decreased clearance is that when retinyl esters remain in serum associated with chylomicron remnants for any length of time, they begin to transfer to low-density lipoproteins and gradually become transformed to retinol, a nonspecific delivery system for vitamin A that is toxic to cell membranes. Patients with vitamin A toxicity can present with variable signs and symptoms, and the manifestation of acute and chronic toxicities may overlap.
Musculoskeletal and generalized complaints such as weakness, malaise, weight loss, myalgia, arthralgia, and bone pain may be present. Neurologic symptoms such as headache, drowsiness, blurred vision, and signs of increased intracranial pressure may occur. Skin manifestations are numerous and can include desquamation, pruritis, alopecia, and brittle nails. Gastrointestinal findings could encompass anorexia, abdominal pain, diarrhea, and hepatotoxicity, which can lead to cirrhosis if vitamin A toxicity is prolonged.
Acute toxic events may occur with ingestion of more than times the RDA over a period of hours or a few days. Resuscitative and supportive care as needed should be provided for any sequalae such as dehydration, altered mental status, hypercalcemia, and hepatotoxicity.
In general, it appears that monitoring serum vitamin A retinol level has little predictive value of toxicity, and one may need to rely on clinical suspicion, especially when following patients at risk. DermNet does not provide an online consultation service. If you have any concerns with your skin or its treatment, see a dermatologist for advice. Home arrow-right-small-blue Topics A—Z arrow-right-small-blue Vitamin A toxicity info-icon print-icon. Vitamin A toxicity — codes and concepts.
Vitamin A poisoning, Hypervitaminosis A. Reaction to external agent, Systemic disorder. Table of contents arrow-right-small. What is vitamin A toxicity? What causes vitamin A toxicity? What are the signs and symptoms of vitamin A toxicity? Vitamin A and teratogenicity How is vitamin A toxicity diagnosed? How is vitamin A toxicity treated? Vitamin A toxicity is also known as hypervitaminosis A. Acute toxicity The most common cause of acute vitamin A toxicity is the ingestion generally accidental of over , IU of vitamin A.
Chronic toxicity The most common cause of chronic vitamin A toxicity is the regular ingestion of over , IU daily, which is sometimes prescribed for dermatological conditions such as acne. References Vitamin A — Johnson, L. Merck Manual. National Institute of Health. Vitamin A Retinol — Mayo Clinic. Sign up to the newsletter. Full name.
Deficiency of vitamin A is rare in the United States, yet many people take supplemental vitamins that contain vitamin A to prophylactically manage what potentially may ail them. Vitamin A has received much attention, both in the scientific and lay press, that is established in fact, assumption, misinformation, as well as hype.
Recent findings on the nutritional and metabolic differences between young and old persons have raised the concern of vitamin A toxicity. Therefore, healthcare professionals should be cognizant of the physiology of retinol, and the benefits and risks of supplementation.
Vitamin A and its natural and synthetic analogs are referred to as retinoids. There are several forms of retinoids: retinal aldehyde ; retinoic acid, which is also known as tretinoin acid ; and retinol alcohol. Vitamin A is acquired through the diet and is ingested through animal sources as retinyl esters and through plant sources as carotenoids, and converted to retinol Figure.
Vitamin A is a group of compounds that plays an important role in vision, bone growth, reproduction, cell division, and cell differentiation. It helps regulate the immune system and may help lymphocytes. Vitamin A is found commonly in many animal and plant food sources and is a common component of fortified foods. In addition to foods, vitamin A is a common component of vitamin and mineral supplements. Consumption of vitamin and mineral supplements is a common behavior in the United States, especially in older adults.
Vitamin A found in foods that come from animals is called preformed vitamin A Table I. Retinol, one of the most usable active forms and the most reduced form of the vitamin, satisfies requirements for all known functions of vitamin A. Sources include liver, whole milk, and some fortified food products. The body can convert retinol into the other active forms, retinal and retinoic acid. Vitamin A that is found in colorful fruits and vegetables is called provitamin A carotenoid.
Among these, beta-carotene is most efficiently made into retinol. Alpha-carotene and beta-cryptoxanthin are also converted to vitamin A, but only half as efficiently as beta-carotene. However, these carotenoids are powerful antioxidants with greater protective effects against free radical damage than beta-carotene. Lycopene, lutein, and zeaxanthin are carotenoids that do not have vitamin A activity but have other health-promoting properties.
Vitamin A activity is measured relative to retinol as retinol equivalents RE. One RE is equal to 1 microgram mcg of retinol. International unit IU is a measurement of vitamin A commonly used for vitamin A supplement products. One RE of vitamin A in mcg equals:. The consumer who measures his or her daily intake of vitamin A by the DV percentage appearing on food labels could easily consume more than the RDA, and possibly come close to the UL.
The RDA value used on the food label for vitamin A is overly generous for older adults. In the RDA tables, values for only a few nutrients differed between persons age years and those age 51 years or older.
The data examined by the RDA Committee for the most part were not derived from studies on older adults but were data extrapolated from younger adult values. Some foods have long been vitamin A—fortified, including milk, some margarine, instant oats, and ready-to-consume breakfast cereals.
Recently, however, other foods have been fortified with relatively high amounts of vitamin A, as well as with other vitamins. These include cereal bars, energy bars, and candy.
The decision regarding which foods are fortified, the amount of fortification, and the form of vitamin A that is used is not regulated; rather, individual manufacturers are free to make these decisions. Some vitamin D supplements include preformed vitamin A. Consumers seeking a vitamin D supplement might not examine the labels of these supplements closely and could unwittingly choose one that also contains vitamin A.
Fish liver oil and fish liver oil capsules, such as those from cod or halibut liver, also contain appreciable amounts of preformed vitamin A. The IOM encourages consumption of all carotenoid-rich fruits and vegetables for health-promoting benefits.
Recent research indicates that supplements in the form of whole food extracts rich in antioxidants may possibly have benefit in humans. Clinical application of oral retinoids include the use of megadose vitamin A for the treatment of age-related macular degeneration ARMD. Isotretinoin is a retinoid that is Food and Drug Administration FDA —approved to be given orally for recalcitrant severe nodular acne.
Incidentally, it is prescribed more and more frequently for less severe acne. In addition, although there have not been significant numbers of older adults in clinical trials evaluating the use of isotretinoin, it has been used in this age range. There are several topical retinoids available. Topical retinoids are prescribed widely both for diseases that have been FDA—approved, as well as for evidence-based off-label uses.
A popular prescription is tretinoin, which is commonly used for the treatment of acne. All-trans retinol is a parent form of vitamin A, which is a weaker form of the prescription tretinoin and is added to many over-the-counter topical beauty products.
The therapeutic window for medicinal benefit is narrow, particularly when addressing the comorbidities of many older adults and the combined effect of all medications, both prescribed and over-the-counter, as well as dietary intake.
There is a tendency in the older population for overuse of supplements. Supplement use in general is associated with high intakes of vitamin A. Most multivitamins specify the type and amount of vitamin A contained in the product.
A widely referenced article published in the Journal of the American Medical Association advocated that all adults take a multivitamin daily and suggested a daily dose of two multivitamins for older adults. This practice places the older adult at even greater risk of hypervitaminosis A, given that the DV on supplements is based on an RDA, which is higher than current recommendations; hence, this approach should be discontinued. Furthermore, chronic renal disease may also result in significantly elevated serum retinol levels and should be taken into consideration.
Synthetic retinoids, derivatives of vitamin A, are manufactured into a cream or gel such as isotretinoin and tretinoin. Any additional intake of vitamin A retinol should be avoided when using these products due to some systemic absorption.
It is known that serum levels are minimally affected by topical application of tretinoin, and case reports do exist describing topical tretinoin-induced teratogenesis. Research suggests that those of advancing age may require less vitamin A than younger adults because of higher circulating levels. With advancing age, both mean and median liver values for vitamin A do not decrease despite indication that dietary intake of vitamin A decreases.
Animal studies indicate that uptake and absorption of vitamin A by the intestine increase with age. Russell 8 compared blood response curves after feeding physiologic doses of vitamin A to young and older adults, and found that the latter had significantly higher blood responses than did the former.
This could be due to either increased absorption or decreased clearance by peripheral tissue. Additional studies indicated that young adults were able to clear reinfused vitamin A twice as quickly as the older adults. The significance of the decreased clearance is that when retinyl esters remain in serum associated with chylomicron remnants for any length of time, they begin to transfer to low-density lipoproteins and gradually become transformed to retinol, a nonspecific delivery system for vitamin A that is toxic to cell membranes.
Patients with vitamin A toxicity can present with variable signs and symptoms, and the manifestation of acute and chronic toxicities may overlap. Musculoskeletal and generalized complaints such as weakness, malaise, weight loss, myalgia, arthralgia, and bone pain may be present. Neurologic symptoms such as headache, drowsiness, blurred vision, and signs of increased intracranial pressure may occur. Skin manifestations are numerous and can include desquamation, pruritis, alopecia, and brittle nails.
Gastrointestinal findings could encompass anorexia, abdominal pain, diarrhea, and hepatotoxicity, which can lead to cirrhosis if vitamin A toxicity is prolonged. Acute toxic events may occur with ingestion of more than times the RDA over a period of hours or a few days. Resuscitative and supportive care as needed should be provided for any sequalae such as dehydration, altered mental status, hypercalcemia, and hepatotoxicity.
In general, it appears that monitoring serum vitamin A retinol level has little predictive value of toxicity, and one may need to rely on clinical suspicion, especially when following patients at risk. This ideology would be analogous to that of working up a disorder and finding a normal erythrocyte sedimentation rate, which may not be helpful in confirming a diagnosis, but yet an extremely high value would certainly prompt further evaluation. Consumption of large amounts of dietary carotenoids will not contribute to vitamin A toxicity since efficiency of absorption decreases with dosage, and conversion to the vitamin is not rapid enough to contribute to toxic levels; however, beta-carotene supplements are not without concern.
Although considered benign, carotenemia is manifested as a yellow-orange coloration of the skin, and in dark-complexion individuals this is particularly noticeable on the palms and soles.
This is not to be confused with jaundice and can be easily differentiated by physical examination of the sclera. The sclera tissue is rich in elastin, which has a high affinity to bilirubin; hence, the sclera will be icteric in those with jaundice and spared in carotenemia. Management of carotenemia involves reducing or eliminating carotene from the diet.
Disappearance of the discoloration may take a few months due to its accumulation in fat tissue. Monitoring vitamin A or carotene levels is not helpful. Adverse effects and toxicity of megadoses of beta-carotene for protracted periods of time ie, beyond a decade have not been fully determined. Vitamin A has several medicinal uses; however, many older adults also use vitamin A prophylactically. This article should not be taken as an endorsement of supplements.
Healthcare professionals should include questions about the use of dietary supplements as well as topical preparations when obtaining a medical history from their older adult patients. All dietary supplements should clearly list ingredients and known contraindications. Patients planning to use supplements and other preparations should first have their dietary practices and lifestyles evaluated by a healthcare professional.
Stephanie C. Volume 18 - Number 02 - February, Copied to clipboard. Introduction Deficiency of vitamin A is rare in the United States, yet many people take supplemental vitamins that contain vitamin A to prophylactically manage what potentially may ail them.
Clinical Application Clinical application of oral retinoids include the use of megadose vitamin A for the treatment of age-related macular degeneration ARMD. Precautions in Prescribing Vitamin A The therapeutic window for medicinal benefit is narrow, particularly when addressing the comorbidities of many older adults and the combined effect of all medications, both prescribed and over-the-counter, as well as dietary intake.
Summary Vitamin A has several medicinal uses; however, many older adults also use vitamin A prophylactically. The authors report no relevant financial relationships.
Any additional intake of vitamin A (retinol) should be avoided when using these products due to some systemic absorption. It is known that serum levels are. The clinical signs of vitamin A toxicity include nausea and vomiting, headache, dizziness, blurred vision, lack of muscular coordination, abnormal liver. (Retinol Toxicity) Vitamin A toxicity can be acute (usually due to accidental ingestion by children) or chronic. Both types usually cause headache and. Cosmetics can contribute to vitamin A toxicity. Addressing a separate issue, the German and Norwegian governments have cautioned that retinol and other vitamin. Oral vitamin A toxicity can be acute, due to the ingestion of a large amount of vitamin A over a short period of time, or chronic, due to oral. Alpha-carotene and beta-cryptoxanthin are also converted to vitamin A, but only half as efficiently as beta-carotene. Skin irritation in the form of peeling and erythema is the most common adverse effect from topical vitamin A use. Central nervous system effects include headache, nausea, and vomiting. The majority of other adverse effects, including skin irritation, dryness, and increased intracranial pressure, will resolve once ingestion or application of vitamin A is reduced or discontinued. But you know that already. Last item: Can any one product contain too much vitamin A?Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Jazmine M.
Authors Jazmine M. Vitamin A toxicity can due to either topical or oral vitamin A administration. Oral vitamin A toxicity can be acute, due to the ingestion of a large amount of vitamin A over a short period of time, or chronic, due to oral ingestion over a longer duration. The most severe adverse effect of systemic retinoids is teratogenicity.
The most common adverse effect of topical vitamin A is skin irritation, erythema, and peeling. This activity describes the evaluation and management of vitamin A toxicity and highlights the role of the interprofessional team in improving care for affected patients. Objectives: Describe the pathophysiology of vitamin A toxicity. Review the presentation of a patient with vitamin A toxicity.
Describe the typical laboratory findings of a patient with vitamin A toxicity. Describe the importance of coordination among the interprofessional team to ensure safe prescribing practices for vitamin A supplements, in particular in women that are or may become pregnant. Access free multiple choice questions on this topic. Vitamin A toxicity can occur from either the topical or oral form of Vitamin A.
Each has its own set of adverse effects. Oral vitamin A toxicity can be acute or chronic. In acute toxicity, ingestion occurs because of the ingestion of a large amount of vitamin A over a short period of time.
In chronic toxicity, intake is over a longer duration. The most common adverse effect of topical retinoids is skin irritation, notably erythema and peeling. Each year, in the US alone over 60, cases of Vitamin toxicity are reported.
Unlike the water-soluble vitamins, the fat-soluble vitamins tend to accumulate in the body. As noted above, vitamin A toxicity can occur from either topical or oral use. Oral vitamin A delivery comes in two forms: provitamin A a prodrug that is metabolized to vitamin A and preformed vitamin A. Pre-formed vitamin A is obtained from animal food sources, including dairy products and liver, and in most supplements.
A list of other foods containing Vitamin A includes milk, cheese, margarine, butter, eggs, chicken, chicken liver, beef, beef liver, processed meats, pizza, fish, and cold breakfast cereals [1]. Provitamin A beta-carotene and other carotenoids , found in plants such as green leafy vegetables, sweet potatoes, and carrots, must be metabolized to vitamin A. As a result, it is less likely to cause toxicity. Many people in the United States take either isolated supplemental Vitamin A or other supplements that contain vitamin, A in addition to dietary intake.
The current recommended dietary allowance of vitamin A is retinol equivalents or international units IU for women [1]. Excessive intake of preformed vitamin A, but not precursors, has been linked to teratogenicity in both human and animals studies [1]. In women taking over 10, IUs of preformed vitamin A per day from supplements, it is estimated that 1 of 57 babies is born with a secondary congenital disability.
Reported incidences of vitamin A toxicity are quite rare, with fewer than 10 cases per year from to [2]. Epidermal irritation is the most common side effect of topical retinoids. Teratogenicity is the most severe side effect of oral retinoids, affecting 1 in 57 women ingesting over 10, IUs daily of preformed vitamin A [1].
Isotretinoin is estimated to increase the risk of malformation fold [2]. Skin irritation in the form of peeling and erythema is the most common adverse effect from topical vitamin A use.
The peeling from topical retinoids is secondary to the hyper-proliferation of the epidermis mediated by retinoic acid receptor stimulation [3]. Interestingly, the erythema may be mediated through a different mechanism. The risk of teratogenicity from the use of topical retinoids is extremely low given that systemic absorption has been inconsequential in animal and human studies [4].
Topical retinoid application has not been proven to cause congenital disorders when used during pregnancy. Other adverse effects include transient hypopigmentation and hyperpigmentation, Koebnerization of psoriasis, allergic contact dermatitis, and ectropion.
With regards to systemic retinoid usage, teratogenicity is the most worrisome adverse effect. Isotretinoin is estimated to increase the risk of these malformations fold.
The mechanism is thought to be through a toxic effect on neural crest cells, possibly affecting the regulation of axial patterning in the embryo via the expression of the homeobox gene Hoxb-1 [5]. Acute retinoid toxicity has resulted in mucocutaneous and laboratory abnormalities.
Mucocutaneous effects include dry lips, cheilitis, and dry oral, ophthalmic, and nasal mucosa. The putative mechanism is decreased sebum production, reduced epidermal thickness, and altered barrier function.
Other cutaneous effects seen include overall skin dryness and pruritus, peeling of palms and soles, and fingertip fissuring. Telogen effluvium may be seen with higher doses. Chronic retinoid toxicity can affect many organ systems. Bone effects include changes such as bone spurs, calcinosis, and bone resorption with resulting hypercalcemia [6].
Long-term consumption of high levels of dietary vitamin A may stimulate bone resorption and inhibit formation, contributing to osteoporosis and hip fractures [7]. Central nervous system effects include headache, nausea, and vomiting. Pseudotumor cerebri syndrome rarely has been noted secondary to vitamin A toxicity [8].
Additionally, reversible renal dysfunction characterized by elevated creatinine was seen with etretinate but not isotretinoin [10]. Hypertriglyceridemia is the most common systemic effect of retinoids. Both triglyceride and cholesterol levels have been found to be elevated in patients using bexarotene, isotretinoin, etretinate, and acitretin.
Total and LDL elevations may occur [11] [12]. Accompanying cases of acute hemorrhagic pancreatitis and eruptive xanthomas can also be seen. Elevated serum transaminases may occur with oral retinoid usage. These elevations more often occur with etretinate or acitretin as compared to isotretinoin and bexarotene.
These elevations typically occur weeks after initiation of therapy with normalization over another weeks. Liver damage leading to fibrosis and hepatic stellate cell activation have both been seen in patients with hypervitaminosis A [13]. No causal association exists between isotretinoin and depression, psychosis, or suicide attempts, although a link had been previously suggested [14].
The dose used in the treatment of degenerative eye diseases is 15, IUs daily. LRAT lecithin retinol acyltransferase is the enzyme that catalyzes retinoid esterification and storage [16].
These two proteins are essential in the mechanism of retinoids and may also be responsible for their toxicity. With systemic use, the patient may exhibit overall xerosis of the skin, oral, ophthalmic, and nasal mucosa. Fissuring and redness of the lips cheilitis may also be seen, as well as peeling of the palms and soles and fissuring of the fingertips. Diffuse hair shedding may also occur.
Mental status changes are common following Vitamin A intoxication. In addition, there is a risk for seizures, headache, and blurred vision due to elevated intracranial pressure. Chronic toxicity can lead to alopecia, anorexia, pruritus, dryness of mucous membranes, muscle and bone pain and hyperlipidemia. Given that elevated triglyceride and cholesterol levels are the most common lab abnormality in patients taking isotretinoin, both of these levels should be checked periodically in a patient taking this medication [17].
Liver enzyme elevations are typically mild and reversible. However, alanine aminotransferase and aspartate aminotransferase monitoring are recommended based upon dosage and patient comorbidities. The patient must also have two negative urine or serum pregnancy tests beta-hCG 30 days apart prior to initiation of isotretinoin.
Beta-hCG should be checked monthly while on therapy as well as one month after cessation of treatment. A complete blood count may be considered before initiation although abnormalities are rare and idiosyncratic. Skeletal monitoring for hyperostosis is only recommended if the patient is receiving multiple courses of isotretinoin or is on the medication long-term. In a patient taking a vitamin A-containing medication who is complaining of a persistent headache, evaluation should be undertaken for increased intracranial pressure to rule out pseudotumor cerebri syndrome.
Free T4 should be monitored before and during treatment with bexarotene [18]. Baseline fasting serum lipids should also be monitored at initiation and every weeks during therapy until stable. If a patient on etretinate therapy has a history of kidney disease, monitor their renal function during treatment [10]. Management of skin irritation from topical retinoids is accomplished with reduced medication volume of application, reduced frequency, and increased emollient use.
Reassurance that this side effect will improve with continued use should also be provided. For ophthalmologic dryness, artificial tears and lubricating eye drops, such as methylcellulose containing eye drops, can be helpful. Milder elevations may be monitored or similarly treated. For bexarotene, concomitant use of a statin or fibrate may be considered to treat retinoid-induced hyperlipidemia and reduce pancreatitis risk [19].
Elevations higher than three times the upper limit of normal may necessitate cessation of therapy if the levels remain elevated despite intervention [19]. Acute retinoid toxicity is rare, but in the cases that have been documented, recovery is rapid upon cessation of medication [20].
In patients with pseudotumor cerebri syndrome, discontinuation of the medication containing vitamin A as well as treatment with acetazolamide has been effective in reducing intracranial pressure [8]. Acute cases may require admission with close monitoring. For most patients who discontinue the vitamin, the symptoms gradually reverse and complete recovery is the norm. However, if vitamin A ingestion is continued, then the adverse effects on the nerves and brain are not always reversible.
Teratogenicity is the most significant adverse effect of vitamin A toxicity.
No comments:
Post a Comment