Behçet's disease in India: a dermatological perspective.

BACKGROUND: Behcet's disease (BD) is a chronic, recurrent, multi-system inflammatory disorder involving mucocutaneous (MC), ocular, intestinal, articular, vascular, urogenital and neurologic systems. BD occurs with a high prevalence in the Mediterranean population. There is scarcity of clinical data on BD from India with only three case series in the last two decades. AIMS: To study demographic profile, clinical manifestations and treatment outcome of patients with BD presenting to the dermatologic clinic in a tertiary hospital in north India. METHODS: Prospective analysis of all patients diagnosed to have BD between 1997 to 2011. RESULT: Twenty nine patients were diagnosed to have BD. The disease had a female preponderance (M:F = 1:3.8) with a mean age of disease onset of 27.4 (range 16-61) years. The prevalence of various MC and systemic manifestations are as follows: oral aphthae (100%), genital aphthae (93.1%), erythema nodosum (62%), papulopustular and acneiform lesions (31%), articular involvement (68.9%), ocular involvement (31%) and gastrointestinal (GI) involvement (3.4%) . Pathergy test positivity was observed in 31%. The treatment comprised of colchicine (16/29 patients), dapsone (7/29), dapsone with pentoxiphylline (3/29), systemic steroid (2/29), systemic steroid with methotrexate (1/29). Colchicine was effective and well tolerated in all patients. CONCLUSION: The disease occurs in a much milder form in India and is primarily mucocutaneous and arthritic. A high index of suspicion in patients with MC lesions may result in early diagnosis, management and prevention of complications of BD. We suggest colchicine as an effective and safe therapeutic option for MC and joint involvement.

[Thalidomide as immunomodulatory drug: pharmacological actions and its indications].

Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases. The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-κB may explain these effects of thalidomide. NF-κB is retained in the cytoplasm with IκBα, and is activated by a wide variety of inflammatory stimuli including TNF, IL-1 and endotoxin followed by its translocation to the nucleus. Angiogenesis and organogenesis also require gene transcription and signal translocation. The findings shed new light on the anti-inflammatory properties of thalidomide and suggest pharmaceutical actions of thalidomide via interference of transcription mechanism. I reviewed the effects of thalidomide on auto-inflammatory diseases of childhood.

Thalidomide and analogues: potential for immunomodulation of inflammatory and neoplastic dermatologic disorders.

Thalidomide and analogues are a class of immunomodulatory drugs or IMiDS. Thalidomide was initially approved by the U.S. Food and Drug Administation for treatment of erythema nodosum in leprosy and is now approved for multiple myeloma as well. A second generation IMiD, lenalidomide, is also approved for multiple myeloma and refractory myelodysplastic syndrome. Discovery of this class of drugs has been serendipitous and empirical, as the drug targets have been unknown. In this review, the authors integrate recent identification of drug targets of IMiDS, which include the inducible form of nitric oxide synthase (iNOS), Rho GTPase and caspase-1, with the developments in the understanding of the molecular biology of human inflammatory, infectious and neoplastic skin disorders. Because thalidomide reemerged through leprosy, the original disease classified by the T cell, the authors have also emphasized advances in the understanding of T-cell subsets in human skin disorders.

Pentoxifylline: a drug with wide spectrum applications in dermatology.

Pentoxifylline (PTX) is a methylxanthine derivative with a variety of anti-inflammatory effects. Currently, PTX is approved by the Food and Drug Administration for the treatment of intermittent claudication, but studies have shown that it has a variety of physiological effects at the cellular level, which may be important in treating a diverse group of diseases.

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.

Talidomida y análogos de talidomida / Thalidomide and analogous

La talidomida se introdujo en la década del '50 como droga hipnótica, sedante y antiemética, especialmente indicada en mujeres gestantes durante el primer trimestre del embarazo. Se asociaron al uso del fármaco graves anormalidades congénitas y polineuropatías, por lo que se la retiró del mercadoen los años '60. Posteriormente se comprobaron propiedades inmunomoduladoras en pacientes con eritema nudoso lepromatoso, así como también efectos antiinflamatorios como lupus eritematoso discoide, enfermedad de Behcet, úlceras aftosas en pacientes con SIDA, enfermedad crónica injerto contra huésped, mieloma múltiple y neoplasia de órganos sólidos. Actualmente, con el desarrollo de nuevos fármacos análogos de la talidomida, que conservan sus propiedades terapéuticas sin presentar teratogenicidad, su aplicación futura es más promisoria

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: 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.

Recurrent aphthous stomatitis of the Behçet's type: successful treatment with thalidomide.

A 48-year-old man with a 27-year history of debilitating recurrent aphthous stomatitis major and pustular skin lesions was treated successfully with thalidomide. Side effects have not been encountered during a 6-month symptom-free period, while he has taken 25 mg per day. The drug is currently unavailable in this country except for the treatment of leprosy. It is hoped that publication of the dramatic response to thalidomide in this one instance will encourage greater interest in this potentially useful drug.

Thalidomide--effect on T cell subsets as a possible mechanism of action.

Thalidomide is the drug of choice in the erythema nodosum leprosum (ENL) type of lepra reaction. Lately it has been used successfully in other diseases, such as discoid lupus erythematosus, actinic prurigo, Behcet's disease, etc. However, its mechanism of action remains unknown. In patients for whom thalidomide provided relief in their disorder, the proportions of T lymphocytes and their subsets in peripheral blood were assessed by means of monoclonal antibodies. Three lepromatous leprosy patients with ENL had their T helper populations significantly increased after thalidomide therapy. A 14-year-old girl with Behcet's syndrome showed a consistent decrease in Ia+ cells throughout her three-month course of thalidomide therapy. The same findings were observed in two patients with the actinic prurigo type of polymorphous light eruption. From these results, we conclude that thalidomide may act as an immunomodulating agent on T cell subsets.