isotretinoin and Hypervitaminosis-A

Although neuromuscular adverse effects represent significant clinical manifestations of hypervitaminosis A syndrome, surprisingly little attention has been paid to the potential neuromuscular toxicity of vitamin A derivatives (retinoids). Since isotretinoin and acitretin are currently the two most commonly used oral retinoids in systemic dermatotherapy, this review focuses exclusively on their neuromuscular adverse effects and proposes a neuromuscular algorithm for appropriate monitoring of patients treated with these two compounds. The most frequent CNS adverse effect associated with oral isotretinoin is headache, either as an independent adverse effect or as part of benign intracranial hypertension, which is additionally characterized by nausea and visual changes. Isolated cases of stiff-person-like syndrome, epileptic seizures and generalized muscle stiffness syndrome, possibly or probably related to oral treatment with isotretinoin, have also been reported. In addition, oral isotretinoin has reportedly been associated with muscular adverse effects that most frequently manifest as myalgia and stiffness and, in rare cases, as true myopathy or rhabdomyolysis. Creatine phosphokinase, a specific marker of muscle destruction, has been found to be elevated, occasionally by up to 100 times the normal value (with or without muscular symptoms and signs), in a variable percentage of patients receiving isotretinoin treatment and particularly in those undergoing vigorous physical exercise. Oral acitretin has been found to cause peripheral nerve dysfunction, particularly of sensory fibres, which in rare cases leads to clinically evident sensory disturbances. Less clear is the causal relationship between acitretin and benign intracranial hypertension or myopathy, whereas an isolated case of cranial nerve IV (oculomotor) palsy and a further case of thrombotic stroke during treatment with oral acitretin have been reported. Systemic diseases with involvement of nervous and/or muscle tissue and neuromuscular disorders should be regarded as exclusion criteria for initiation of oral retinoid therapy. Additionally, intense physical exercise and concurrent treatment with neurotoxic or myotoxic drugs should be avoided during treatment with oral retinoids. In order to minimize the potential risk of neuromuscular adverse effects, a neuromuscular algorithm is suggested that may be useful for monitoring patients taking oral retinoids.

Topics: Acitretin; Administration, Oral; Biomarkers; Creatine Kinase; Dermatologic Agents; Drug Monitoring; Exercise; Humans; Hypervitaminosis A; Isotretinoin; Neuromuscular Diseases; Practice Guidelines as Topic; Skin Diseases

This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.

Topics: Abnormalities, Drug-Induced; Animals; Brain; Central Nervous System; Female; History, 20th Century; History, 21st Century; Humans; Hypervitaminosis A; Isotretinoin; Male; Pregnancy; Retinoids; Teratogens; Teratology; Tretinoin

Topics: Diagnosis, Differential; Humans; Hypervitaminosis A; Isotretinoin; Prognosis; Pseudotumor Cerebri; Retinol-Binding Proteins; Tretinoin; Vitamin A

Primary care physicians should be familiar with the effects and appropriate uses of retinoids. Topical tretinoin (Retin-A) can reverse photoaging of the skin, although some transient, undesirable side effects usually occur. In patients with acne vulgaris, topical tretinoin and systemic isotretinoin (Accutane) are the only agents that act upon the apparent underlying causes. Recurrence is unlikely after successful results are achieved. Chronic hypervitaminosis A presents insidiously, and physicians must maintain a high index of suspicion. Complete history taking should always include questions about the patient's use of vitamin supplements.

Topics: Acne Vulgaris; Administration, Topical; Animals; Drug Eruptions; Drug Therapy, Combination; Humans; Hypervitaminosis A; Isotretinoin; Medical History Taking; Physical Examination; Skin Aging; Skin Neoplasms; Tretinoin

A vitamin A derivative, 13-cis-retinoic acid (isotretinoin), has been administered to treat several types of pediatric cancer and has improved survival rates in patients despite being known to induce premature epiphyseal closure. As the number of patients treated by 13-cis-retinoic acid increases, demands for salvage treatment after systemic retinoid therapy are emerging. However, few studies have described the surgical treatment of this disease.. We report a case with bilateral varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin for neuroblastoma. The patient was successfully treated with correction osteotomy using a Taylor spatial frame in the right knee joint and femoral closed wedge osteotomy using a locking plate in left knee joint. Histopathological examination of the growth plate showed polar irregularity of chondrocytes and decreased cartilage matrix without apoptosis. In contrast, arthroscopic findings showed an intact joint surface. No recurrence of varus deformity was evident on follow-up at 1 year.. To the best of our knowledge, this represents the first report of correction osteotomy for varus knee deformity due to premature epiphyseal closure that occurred during treatment with isotretinoin.

Topics: Bone Plates; Child; Female; Femur; Growth Plate; Humans; Hypervitaminosis A; Isotretinoin; Knee Joint; Magnetic Resonance Imaging; Neuroblastoma; Osteoarthritis, Knee; Osteotomy; Tibia; Treatment Outcome

A case of hypervitaminosis A (HVA) as a complication of therapy for stage-IV neuroblastoma is presented. The patient was randomized to a trial of 13-cis -retinoic acid (a vitamin A-related compound) after completing routine chemotherapy. This acid was given as a means of maturing potential minimal residual disease. A routine follow-up bone scan revealed areas of increased activity, initially along the midshaft of the right ulna and subsequently bilaterally, which were ultimately found to be due to HVA. Hypervitaminosis A has not been previously reported in this setting, and awareness of the condition is important in centers where this treatment is contemplated.

Topics: Adrenal Gland Neoplasms; Bone and Bones; Child, Preschool; Humans; Hypervitaminosis A; Isotretinoin; Male; Neuroblastoma; Radiography

Topics: Acne Vulgaris; Administration, Topical; Adolescent; Adult; Depressive Disorder; Female; Humans; Hypervitaminosis A; Isotretinoin; Male; Patient Care Team

Vitamin A is essential for growth and development, reproduction and vision in humans. Chemical modification of vitamin A has yielded compounds showing therapeutic promise in skin and neoplastic diseases. The medicinal use of retinoids (vitamin A and its derivatives) is limited by the toxicity associated with this group of compounds. One retinoid, 13-cis-retinoic acid, has proved to be quite effective in the treatment of severe recalcitrant cystic acne under conditions in which toxicity is manageable.

Topics: Acne Vulgaris; Adolescent; Humans; Hypervitaminosis A; Isotretinoin; Male; Retinoids; Tretinoin; Vitamin A Deficiency