isotretinoin and Bone-Diseases

The acne conglobata (AC)-, acne fulminans (AF)-, and isotretinoin-associated musculoskeletal syndromes are three distinct clinical entities. The AC-associated musculoskeletal syndrome occurs primarily in black men over the age of 22, who develop sacroilitis with or without a peripheral arthropathy. In contrast, the AF-associated musculoskeletal syndrome is found almost exclusively in white male teenagers. Fever, weight loss, and arthralgias are prominent components of this syndrome. A unique feature of the AF-associated musculoskeletal syndrome is osteolytic lesions that occur most frequently in the clavicle, sternum, long bones, and ilium. The isotretinoin-associated musculoskeletal syndrome occurs with equal frequency in male and female acne patients. Mild, transient myalgias and arthralgias are very common and do not require discontinuation of isotretinoin therapy. Asymptomatic, small, hyperostotic lesions of the spine occur in approximately 10% of acne patients with the isotretinoin-associated musculoskeletal syndrome.

Topics: Acne Vulgaris; Adolescent; Adult; Bone Diseases; Female; Humans; Isotretinoin; Male; Middle Aged; Muscular Diseases; Syndrome

Topics: Administration, Oral; Animals; Bone Diseases; Etretinate; Humans; Hyperostosis, Diffuse Idiopathic Skeletal; Isotretinoin; Keratosis; Retinoids

The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively non-toxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited.

Topics: Acne Vulgaris; Bone Diseases; Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Isomerism; Isotretinoin; Keratosis; Kinetics; Psoriasis; Skin Diseases; Skin Neoplasms; Tretinoin; Triglycerides; Vitamin A

The synthetic retinoids are a new class of drugs which are highly effective in the treatment of a broad spectrum of dermatologic disease. In this report 15 patients with chronic disorders of keratinization and one patient with severe cystic acne were treated with oral isotretinoin. The degree of clinical response and duration of post-treatment remission varied with the different disorders. Acute side effects were predominantly limited to the skin and mucous membranes and were reversible after discontinuation of treatment in these patients. Acute retinoid toxicity and the potential for developing chronic toxicity are reviewed. In an attempt to facilitate the monitoring of dermatologic patients treated with oral synthetic retinoids, we present our current guidelines for the use of these agents.

Topics: Acne Vulgaris; Adolescent; Animals; Bone Diseases; Child; Child, Preschool; Etretinate; Humans; Isomerism; Isotretinoin; Joint Diseases; Keratosis; Mice; Psoriasis; Skin Diseases; Tretinoin

Isotretinoin is a vitamin A derivative, indicated for the treatment of patients with severe acne, which shows several side effects on bone metabolism.. This study analyzed the process of bone repair in rats receiving 7.5 mg/kg/day of oral isotretinoin.. Thirty-three male albino Wistar rats, at approximately 60 days of age, were randomly assigned to control (n = 15) and experimental (n = 18) groups. Only the experimental group underwent oral isotretinoin therapy. In both groups, a 2-mm cavity was established in the calvarium of each animal. The animals were euthanize 21, 28 and 90 days postoperatively. The parietal bone was removed and the surgical specimens underwent histological examination. Computed histomorphometry allowed the measurement of the total area of bone defects and the proportion of newly formed bone at the different observation time points.. In the experimental group, the results, expressed as mean percentage of newly formed bone, were: 25.37% (±9.14) at day 21; 41.78% (±7.00) at day 28; and 57.51% (±11.62) at day 90. In the control group, the results were: 17.10% (±9.23) at day 21; 34.42% (±7.70) at day 28; and 48.49% (±16.40) at day 90.. These results enabled us to conclude that isotretinoin promoted acceleration in the process of new bone formation in rat calvaria, although this increase was not statistically significant.

Topics: Administration, Oral; Animals; Bone Diseases; Craniotomy; Image Processing, Computer-Assisted; Isotretinoin; Male; Osteogenesis; Parietal Bone; Random Allocation; Rats; Rats, Wistar; Time Factors; Wound Healing

An 18-year old male patients with tetracycline-resistant acne vulgaris was prescribed isotretinoin in daily doses of 0.5 mg/kg. Ten days later, he developed an acute episode of acne fulminans which was regressive. Subsequently, two attempts were made at reintroducing isotretinoin; the first one was followed by a new episode of acne fulminans and the second one, by ordinary myalgias, while the patient was still under corticosteroid therapy. A search in the literature yielded 14 cases of acne fulminans that had possibly been induced by isotretinoin. Doses and intervals between medication and acute manifestations varied, and the responsibility of isotretinoin was seldom demonstrated. Associations with erythema nodosum myalgias and arthralgias have been described. This rare adverse effect of isotretinoin therapy must be known. Its course and treatment are not different from those of ordinary acne fulminans.

Topics: Acne Vulgaris; Adolescent; Adrenal Cortex Hormones; Bone Diseases; Humans; Isotretinoin; Joint Diseases; Muscular Diseases; Recurrence; Suppuration

The case is presented of a 33-year-old man treated with Roaccutane for two years on account of severe acne conglobata. X-ray examination after two years showed pronounced hyperostoses with bridging in the thoracic spine and hyperostoses and beginning bridging in the cervical spine. Furthermore, small exostoses were found on the hands and feet. X-ray control of patients treated for more than six months with Roaccutane is recommended.

Topics: Adult; Bone Diseases; Exostoses; Humans; Isotretinoin; Male; Radiography; Time Factors

We evaluated the effects of long- and short-term isotretinoin therapy on the skeletons of patients. Eight patients who were treated with isotretinoin for disorders of keratinization received frequent radiographic evaluations for 4 to 9 years. Seven patients developed multiple hyperostoses at the spine and extremities. Hyperostoses increased in size and number over the course of therapy, although relatively few sites were symptomatic. Hyperostoses typically developed first in the spine and later in the extremities, where both bilaterally symmetric and asymmetric involvement was observed. After 5 years of therapy one patient did not develop hyperostosis. In a group of nine patients who received a relatively high dose of isotretinoin in 1982 for the treatment of acne, two patients developed tiny, asymptomatic hyperostoses. One patient had hyperostoses 1 year after isotretinoin therapy, which remained unchanged 3 years later, whereas the other patient had one hyperostosis 4 years after therapy had been stopped. Although we suspect that these hyperostoses were retinoid induced, they should not be of concern for the patient needing routine isotretinoin therapy for the treatment of cystic acne.

Topics: Acne Vulgaris; Adolescent; Adult; Bone Diseases; Child; Female; Follow-Up Studies; Humans; Ichthyosis; Isomerism; Isotretinoin; Male; Radiography; Skin Diseases; Spinal Diseases; Time Factors; Tretinoin

Skeletal toxicity is known to occur with high doses of isotretinoin (greater than 2 mg/kg/day). We have attempted to evaluate the clinical significance and document the extent of musculoskeletal toxicity associated with a relatively low dose of isotretinoin (0.5 mg/kg/day) used in the treatment of severe acne. Radiographs of 120 patients were examined. Twelve per cent showed minor changes (four patients had spinal hyperostoses and 10 had calcaneal hyperostoses). None of the musculoskeletal changes we observed was clinically significant. Comparison with matched control X-rays showed 8% of the controls to have similar non-significant changes. Follow-up of 11 of the patients with abnormal X-rays showed minor deterioration in one patient, no change in four and improvement in six. Thus, doses of 0.5 mg/kg/day isotretinoin in such patients did not produce any significant long-term musculoskeletal changes. With increasing use of this beneficial drug in acne, radiologists and dermatologists should be aware of its skeletal toxicity.

Topics: Acne Vulgaris; Adolescent; Adult; Bone and Bones; Bone Diseases; Female; Humans; Isotretinoin; Male; Middle Aged; Radiography; Spinal Osteophytosis

Seven patients with disorders of keratinization (ichthyosis in six and Darier disease in one) were treated with 13-cis-retinoic acid and followed with annual skeletal surveys for 4-6 years. Six of the seven patients developed hyperostoses attributable to the retinoid therapy, manifested as multifocal entheseal calcifications or ossifications in both the axial and appendicular skeletons. In general, the earliest appearing hyperostoses became the largest with time, although in some instances, growth ceased at some foci and progressed at others. The severity of skeletal involvement was seemingly independent of dose, and may have been related to the patient's age at time of therapy. Involvement of the spine was earlier and more pronounced than the appendicular involvement, consisting of tiny hyperostoses arising from the corners of the vertebral bodies, primarily in the cervical and thoracic spine; these later matured into either discrete ossific spurs, or focal or flowing ossification of the anterior longitudinal ligament. The most prominent appendicular hyperostoses were at the tendinous or aponeurotic insertions on the calcaneus, were often unilateral or asymmetric when small, and became bilateral with time. Appendicular hyperostoses occurring at locations besides the calcanei were much smaller, often unilateral, and occurred later (generally between the third and fifth years of therapy). Our findings indicate that the earliest hyperostoses occurring in patients with 13-cis-retinoic acid occur in the spine and feet, and become the most prominent with time. Most appendicular hyperostoses occur later, are smaller, and frequently are asymmetric or unilateral.

Topics: Adolescent; Adult; Bone Diseases; Child; Child, Preschool; Darier Disease; Female; Humans; Ichthyosis; Isotretinoin; Male

An update is presented of bone changes taking place in association with oral treatment with the two most relevant synthetic retinoids, 13-cis-retinoic acid (isotretinoin; Roaccutan, Accutane) and etretinate (aromatic retinoid; Tigason, Tegison). All of the important clinical studies are reviewed, including our own results concerning etretinate-associated bone changes. While there are no more doubts about the potential bone toxicity of 13-cis-retinoic acid, the possibility of etretinate-induced bone changes probably occurring within a longer latency period cannot be conclusively assessed at present. The available clinical data concerning the potential skeletal toxicity of 13-cis-retinoic acid and etretinate should be carefully taken into consideration when determining the risk/benefit ratio, especially for long-term oral retinoid treatment.

Topics: Administration, Oral; Bone and Bones; Bone Diseases; Dermatitis; Etretinate; Humans; Isotretinoin; Retinoids; Risk; Tretinoin

During the last 10 years we treated 39 children with severe keratinization disorders with the aromatic retinoid etretinate. Six of these children were followed-up for 8-9 years. Mucocutaneous serum enzymatic and lipid side effects of etretinate were mild, transient and well tolerated. Osseous side effects were present after 4-6 years in all our 6 patients on prolonged retinoid therapy. Asymptomatic osseous neoformation and osseous reabsorption in the absence of calcium, phosphate, and alkaline phosphatase serum alterations have been observed. The growth and development curves and the sexual development of our patients (with exception of a patient with Rud's syndrome) have been normal. Osteoporosis and slender diaphysis were often present at initiation of therapy. On the basis of our findings and recent reports of the literature we suggest restricting retinoid therapy of keratinizing disorders in children to conditions severe enough to be physically, psychologically or socially incapacitating. In an attempt to reduce the risk of chronic toxicity and possibly to allow regression of initial bone alterations, intermittent therapy and combination therapy are recommended.

Topics: Adolescent; Bone Diseases; Child; Drug Administration Schedule; Drug Therapy, Combination; Etretinate; Female; Humans; Isotretinoin; Keratosis; Male; Tretinoin

Topics: Bone Diseases; Dermatologic Agents; Humans; Isotretinoin; Tretinoin

Bilateral 2.5 and 3.0 mm nasal bone osteophytes developed five weeks following the initiation of oral isotretinoin therapy (50 mg daily) for severe cystic acne vulgaris in a healthy 30-year-old white woman who had undergone uneventful rhinoplasty 12 years earlier. Histologically mature bone fragments were removed at surgery. Vitamin A and its analogs have been reported to cause hyperostosis of the vertebrae and long bones, but no known reports link them to nasal bone changes. Clinically significant nasal bone osteophytosis may be another adverse reaction to oral isotretinoin therapy.

Topics: Acne Vulgaris; Adult; Bone Diseases; Female; Humans; Isotretinoin; Nasal Bone; Rhinoplasty; Risk; Tretinoin

A boy with epidermolytic hyperkeratosis was treated systemically for 4 1/2 years with 13-cis-retinoic acid. At the age of 10 1/2 years, he developed pain in his right knee and radiographic evidence of partial closure of the proximal epiphysis of the right tibia. Similar radiographic changes have been described in individuals ingesting excessive amounts of vitamin A.

Topics: Bone Diseases; Child; Epiphyses; Humans; Isotretinoin; Keratosis; Male; Tibia; Tretinoin