THALIDOMIDE IN THE TREATMENT OF CUTANEOUS LUPUS ERYTHEMATOSUS
Thalidomide has found favour in dermatological practice due to its successful use in several in inflammatory dermatoses. Their mechanism of action is not known, but their anti-inflammatory and immunomodulatory properties offer multiple sites where they may act.
Systemic lupus erythematosus. 2007 (SLE, or simply lupus) is a chronic autoimmune disease that can affect different organs and tissues of the body. In this case, the immune system produces antibodies that can attack the cells of the heart, skin, lung, vascular endothelium, joints (it is classified as a rheumatic disease), liver, kidneys and nervous system, causing inflammation and tissue damage.
It affects more females than males (9:1), of childbearing age. SLE is prevalent in all geographic areas, with a prevalence that is influenced by climatic conditions and racial. The disease appears to be more frequent in Mediterranean countries and in parts of South-East Asia and most striking blacks and whites oriental not.
70-80% of patients present with cutaneous signs (cutaneous lupus erythematosus - CLE). The CLE includes various specific skin lesions that are divided into three categories, depending on the clinical morphology, the average duration of lesions and histopathological examination routine: CLE chronic discoid lesions where the skin symptoms are the most frequent (DLE) subacute CLE (SCLE) and acute CLE (ACLE).
SLE is treatable with immunosuppressive therapy, especially by the administration of cyclophosphamide, corticosteroids and other immunosuppressive drugs; however, a cure does not exist.
The use of thalidomide, because of its anti-inflammatory properties, has been suggested as a possible drug in patients who do not respond to other medicines. The mechanisms that lead, after administration of thalidomide, an improvement of clinical conditions are not yet clear, but over the years the evidence of its possible utility in the treatment of cutaneous lupus erythematosus have multiplied.
In 1993 a study was done on 23 patients with systemic lupus erythematosus skin lesions that did not respond to chloroquine, photoprotectors and corticosteroid. They were treated with thalidomide 300 mg / day: eighteen of the 20 patients (90%) had complete remission of the cutaneous lesions and two had partial improvement.
Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide. 1993
In 2001, another study of 27 patients subjected to lower doses of thalidomide and found a general improvement in the clinical condition. The thalidomide induces an inhibition in the production of TNFa and a reduction of the ratio of CD4 to CD8 T-lynphocytes. In this study we have analyzed the responses of 27 patients with the administration of low doses (starting dose of 50 mg twice daily) of thalidomide: response was favorable, with 77% of patients showing some improvement in disease and initial complete clearing in 37%. No patient had symptoms of peripheral neuropathy.
Low-dose thalidomide is an effective second-line treatment in cutaneous lupus erythematosus. 2001
Trying to figure out if there was a dose-dependent relationship in the treatment with thalidomide, in 2005, forty-eight patients were subjected to different doses of thalidomide to assess whether there is a real difference in the treatment of high or low doses of the drug. The study, while confirming the efficacy of thalidomide in the treatment of severe cutaneous lupus, indicates that it is not yet clear the relationship between the dose of medication taken and the improvement of conditions.
Thalidomide for the treatment of resistant cutaneous lupus: Efficacy and safety of different therapeutic regimens. 2005
One possible explanation of its effectiveness can be traced in a study of 2012 which highlights the ability of thalidomide and its analogues to modulate monocyte, lymphocyte, and natural killer cell functions; was noted its ability to suppress the synthesis of immunoglobulins. B cells secreting antibodies stop producing immunoglobulins IgM and IgG after administration of lenalidone.
Lenalidomide alone or lenalidomide plus dexamethasone significantly inhibit IgG and IgM in vitro... A possible explanation for their mechanism of action in treating multiple myeloma. 2012
THALIDOMIDE AND ERYTHEMA NODOSUM IN THE COURSE OF LEPROSY
Erythema nodosum (EN) is an inflammatory condition characterised by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins. It may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes.
A series of controlled observations showed that thalidomide is effective in controlling erythema nodosum in the course of leprosy. It was observed that the Thalidomide provides better symptom control and fewer side effects than corticosteroids. It was also noticed a great effect on the fever. TNFa, IL-1 and IL-6 are three independently inflammatory cytokines that activate the hypothalamus-pituitary-adrenal axis and act synergistically when used in combination. The efficacy of thalidomide sull'eritema nodosum being leprosy is probably due to its inhibition of TNFa, with subsequent improvement in inflammation. In addition to its effects on cellular immune mechanisms, thalidomide also has an effect on immunity humoral immunity. It significantly inhibit the formation of antibodies of the IgM class; it is also likely to reduce the concentration of antigen-antibody complexes, which contribute to the genesis of the phenomena vasculitis and painful subcutaneous nodules.
The use of thalidomide in the treatment of severe erythema nodosum leprosum is found to be more effective than that of prednisolone, providing longer periods of remission. Comparative efficacy of thalidomide and prednisolone in the treatment of moderate to severe erythema nodosum leprosum: a randomized study. 2009
On the other hand during treatment with thalidomide was increased by thrombosis in the deep veins, especially when the drug is associated with corticosteroids or chemotherapy agents. Deep vein thrombosis in a patient with lepromatous leprosy receiving thalidomide to treat leprosy reaction. 2013
Thalidomide is used today, especially in Brazil, where the incidence of leprosy is very high. To discover the healing effects of thalidomide was a russian biologist australian, Jacob Sheskin, who experimented with the effects on the skin of laboratory animals. Recently there has been a spike in births of children with deformed limbs, which were transferred to the use of thalidomide in women affected by leprosy.