Successful treatment of complex aphthosis with colchicine and dapsone.

OBJECTIVE: To investigate the effectiveness of colchicine and dapsone, 2 corticosteroid-sparing anti-inflammatory agents, in the treatment of patients with complex aphthosis (recurrent oral and genital aphthous ulcers or severe, almost constant, multiple oral aphthae in the absence of Behçet syndrome). DESIGN: Retrospective review of medical records. SETTING: Tertiary care medical clinic. PATIENTS: Fifty-five patients with complex aphthosis evaluated and treated at Mayo Clinic between January 1, 1998, and July 31, 2007. All the patients were treated according to a therapeutic ladder, starting with colchicine and adding dapsone to treatment of patients who did not have a substantial response (>75% improvement) to colchicine or who discontinued colchicine use because of adverse effects. MAIN OUTCOME MEASURES: A substantial response to therapy with colchicine alone, dapsone alone, or colchicine and dapsone combined. RESULTS: Most patients (44 [80%]) had a substantial response to therapy and had no serious adverse effects. CONCLUSIONS: Colchicine and dapsone are effective, safe therapies for the treatment of complex aphthosis. Colchicine and dapsone, 2 established drugs also used for gout and leprosy, respectively, and for other dermatologic disorders, should be considered efficacious in the treatment of complex aphthosis.

Current role of thalidomide in HIV-positive patients with recurrent aphthous ulcerations.

Among patients with HIV/AIDS, mucosal lesions of unknown etiology such as recurrent aphthous ulcerations (RAUs) often are unresponsive to standard therapies, resulting in substantial morbidity. The literature regarding RAUs suggests that the inflammatory response contributes to its pathogenesis; however, the role of cytokines in this mucosal immune response remains largely unknown. Thalidomide first was marketed as a sedative in the 1950s and withdrawn from the market in 1961 following reports of teratogenicity. Later, it was used as an investigational agent for the treatment of Hansen's disease, Kaposi's sarcoma, myelofibrosis, RAUs, and wasting associated with HIV. Thalidomide's mechanism of action in RAUs still is not understood completely, but it appears to be mediated by inhibition of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). This article discusses the current status of thalidomide for treating RAUs in HIV-positive patients. Suggestions regarding the safe and effective prescribing of thalidomide have been included so that dental professionals will be able to treat these patients safely.

Thalidomide: an experience in therapeutic outcome and adverse reactions.

BACKGROUND: The US FDA-approved thalidomide for the treatment of chronic recurrent/severe erythema nodosum leprosum. Thalidomide is also useful in many other inflammatory dermatological conditions where patients have exhausted other treatment options. METHODS: The beneficial and adverse clinical effects of thalidomide were studied in 25 patients suffering from different inflammatory dermatological conditions that were poorly controlled with conventional therapies. RESULTS: Thalidomide was found to be effective in various inflammatory dermatological diseases other than chronic recurrent erythema nodosum leprosum such as Behçet's disease, disseminated and hypertrophic discoid lupus erythematosus, erosive lichen planus, discoid lupus erythematosus-lichen planus overlap, recurrent aphthous stomatitis and prurigo nodularis. Deep vein thrombosis due to thalidomide occurred in 20% of these patients and appears to be a significant side effect. CONCLUSION: Thalidomide appears promising in a number of inflammatory dermatological conditions and will probably find new usages in future. The treating physicians need to be wary of the thrombo-embolic complications due to thalidomide especially when glucocorticoids or other chemotherapeutic agents such as doxorubicin, gemcitabine, 5-fluorouracil or dexamethasone-cyclophosphamide pulse therapy are being used concomitantly, and in patients of metastatic renal carcinoma, myelodysplastic syndrome or multiple myeloma receiving thalidomide/chemotherapy. Antiphospholipid or anticardiolipin antibodies appear to be other possible risk factors for this complication.

Thalidomide: dermatological indications, mechanisms of action and side-effects.

Thalidomide was first introduced in the 1950s as a sedative but was quickly removed from the market after it was linked to cases of severe birth defects. However, it has since made a remarkable comeback for the U.S. Food and Drug Administration-approved use in the treatment of erythema nodosum leprosum. Further, it has shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell histiocytosis, aphthous stomatitis, Behçet's syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and uraemic pruritus. This article reviews the history, pharmacology, mechanism of action, clinical uses and adverse effects of thalidomide.

Thalidomide: an antineoplastic agent.

It has been more than three decades since the withdrawal of thalidomide from the marketplace. Thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor-alpha by accelerating the degradation of its messenger RNA. Thalidomide inhibits angiogenesis. Recently, thalidomide was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. Thalidomide has been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behcet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with HIV infection, in which this drug is an efficacious agent against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. Only in the last several years has thalidomide been aggressively investigated for its antiangiogenic potential and immunomodulatory properties in various tumor types. Current research on thalidomide in oncology covers investigation in a wide range of both solid tumors and hematologic malignancies.

Thalidomide: current and potential clinical applications.

More than three decades after its withdrawal from the world marketplace, thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. However, it has long been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behçet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with human immunodeficiency virus (HIV) infection; the drug is efficacious against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. To prevent teratogenicity, a comprehensive program has been established to control access to the drug, including registration of prescribing physicians, dispensing pharmacies, and patients; mandatory informed consent and education procedures; and limitation of the quantity of drug dispensed. Clinical and, in some patients, electrophysiologic monitoring for peripheral neuropathy is indicated with thalidomide therapy. Other adverse effects include sedation and constipation. With appropriate safeguards, thalidomide may benefit patients with a broad variety of disorders for which existing treatments are inadequate.

Thalidomide: a re-look.

Thalidomide was synthesized in 1954 in erstwhile West Germany and marketed as a sedative in over 46 countries until the early 1960s. Owing to serious teratogenic effects, the drug was withdrawn from the market in 1961. A chance observation suggested the utility of thalidomide in erythema nodosum leprosum (ENL). After many controlled and uncontrolled trials were published, the World Health Organization recommended its use in ENL. The Food and Drug Administration, USA approved it for use in ENL in July 1998. Only established and well-defined studies conducted to substantiate the efficacy of thalidomide have been included in this review. Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered. Once the anti-inflammatory, immuno-modulatory, anti-TNF-alpha and anti-angiogenic properties of thalidomide were discovered, it was also tried in AIDS and related wasting, apthous ulcers, microsporidiosis and Kaposi's sarcoma. Thalidomide has no clinical place as an immunosuppressant in solid organ transplantation. However, it has a therapeutic role in graft-verus-host-disease. Among the dermatological conditions, thalidomide has been found to be effective in systemic lupus erythematosus, discoid lupus erythematosus, actinic prurigo and prurigo nodularis. Used correctly, it is a safe and effective medicine (except for its teratogenic potential and delayed neuropathy) in a variety of disease conditions.

[Thalidomide once more in the spotlight]. / Thalidomide opnieuw in de belangstelling.

Thalidomide was withdrawn from the market in the early sixties because of major teratogenic effects such as reduction defects of the limbs. Since, however, it has been found to be an effective drug in erythema nodosum leprosum. In the United States it was decided in September 1997 to admit thalidomide to the market for this indication, and in South America it has been available for this indication all the time. Thalidomide is also efficacious in other major disorders (e.g. aphtae and ulcers in aids) or its efficacy is being investigated in clinical trials (e.g. autoimmune diseases, other complications in aids). The American Food and Drug Administration has imposed conditions for the use of thalidomide. Users have to sign an informed consent and to take adequate contraceptive measures. Physicians should inform the patients and monitor side effects. Pharmacists should record and control the use.

Thalidomide: new preparation. For well-defined indications.

(1) Thalidomide is highly teratogenic. It can also cause irreversible neuropathy. (2) In type II lepra reactions evidence of efficacy at a dose of 400 mg/day is based on a few relatively old comparative trials and above all a review of more than 4,500 cases. Most patients feel a benefit within 24-48 hours after beginning the treatment, but most also require lengthy treatment at a reduced dose (25-100 mg/day) to avoid relapses. (3) Two placebo-controlled trials involving a total of 130 patients have shown the efficacy of thalidomide in the treatment of severe recurrent aphthous disease. (4) In Jessner-Kanoff disease, a mild condition, the efficacy of thalidomide has been shown in a single placebo-controlled trial. (5) In chronic lupus erythematosus, non comparative trials have shown remission from skin lesions in patients resistant to previous treatments. (6) In the curative treatment of chronic graft-versus-host disease in bone marrow graft recipients, thalidomide has been assessed only in non comparative trials involving a few dozens of patients.

Thalidomide--the story goes on....

AIDS: The FDA has approved Thalidomide under the brand name THALOMID. The manufacturer, Celgene Corporation, has developed a distribution and training program for THALOMID, to minimize the possibility of the potentially devastating side effects associated with the drug. The program requires doctors and pharmacies to register with the FDA before they can dispense the drug. Clinical trials of Thalidomide will still continue, even though approval has been granted. Contact information is included for information on trials and expanded access programs.^ieng

Thalidomide's long and winding road.

AIDS: Thalidomide is a drug associated with devastating side effects. First prescribed in the late 1950s as a sedative, thalidomide caused more than 12,000 disfiguring birth defects, most commonly truncated arms and legs in infants, referred to as seal flipper limbs. Most alarming was that no link was made between the drug and birth defects in animal studies. The drug vanished from the market, except for use in treating leprosy. The history of the drug's use is outlined, along with its effects in treating progressive diseases such as HIV. The drug has never received marketing approval from the Food and Drug Administration (FDA), however, it was imported illegally by buyers' clubs in the United States. Results of several trials, including a Mexican study, showed the effectiveness of the drug. Side effects include sedation, rash, and neurotoxicity; some preliminary results suggest use of thalidomide can increase viral loads. Two expanded access programs exist today, and the manufacturer, Celgene, estimates that fewer than 10,000 patients will take the drug in its first year on the market due to safety concerns. Toratogenic drug concerns and preventing birth defects are critically important. The drug appears to be effective in non-pregnant patients and those suffering from diverse immune system and infectious disorders.^ieng

Thalidomide trial to begin.

AIDS: Celgene Corporation is enrolling 84 patients living with AIDS, including children, in a trial of thalidomide (Synovir). Thalidomide caused severe birth defects decades ago, however, it has been shown to be effective in treating AIDS-related aphthous ulcers and wasting syndrome.^ieng

Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations.

The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects. The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy. This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity. The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients. This article reviews the most important chemical and pharmacokinetic properties of thalidomide. The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed. Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded. Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy. Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups. Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age. Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded. Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy. In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy.