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New Discoveries of Significance to the Prevention, Control, and Treatment of Leprosy
Published in Max J. Miller, E. J. Love, Parasitic Diseases: Treatment and Control, 2020
In the last several years a number of findings have come to light which are of significance in the treatment of leprosy: Efforts have been made to improve on existing individual antileprosy drugs.Attempts to develop analogues of thalidomide which are not teratogenic and which are effective in erythema nodosum leprosum have been unsuccessful.Attempts to develop analogues of clofazimine which lack pigmenting and GI side effects and which are otherwise safe and effective against M. leprae and in reactions have been unsuccessful.The thioamides — ethionamide and prothionamide — seem optimal as to antibacterial activity and safety. They have been shown to act via the same mechanism as thiambutosine and thiacetazone.Rifampin analogues have been shown to have antileprosy activity.Dapsone seems to be optimal for activity against M. leprae. The extraordinary sensitivity of M. leprae to dapsone has been shown to be due to the high affinity of its dihydropteroate synthetase for dapsone.34
Minocycline
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
The potential efficacy of minocycline against M. leprae was highlighted by an interesting case of a 19 year-old Angolan woman, resident in Portugal for the previous 10 years, who was diagnosed with Hansen’s disease at the age of 12, but had received inadequate therapy and was lost to follow up. She presented with painful nodules and pustules on the upper limbs, and diffuse facial infiltration with pustules and fever, after initiating minocycline for the treatment of acne. The diagnosis of erythema nodosum leprosum was confirmed by the presence of acid-fast bacilli in the skin smear and also in skin biopsy. Minocycline was suspended and the patient was treated with systemic steroids, with prompt clinical improvement. The case highlights the unintended consequences of using minocycline for other purposes, when it is in fact effective in treating (partially in this case) Hansen’s disease (Travassos et al., 2012).
Clofazimine
Published in Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer, Handbook of Systemic Drug Treatment in Dermatology, 2015
Eglantine Lebas, Stephen L. Walker
Clofazimine is indicated for the treatment of leprosy. It is only available on a named patient basis in the UK and USA and is used as follows in leprosy: Multibacillary leprosy in combination with rifampicin and dapsone.Erythema nodosum leprosum (ENL). Due to its immunosuppressive actions, clofazimine has been used in the management of chronic discoid lupus erythematosus, granulomatous cheilitis, chronic graft-versus-host disease, necrobiosis lipoidica, pyoderma gangrenosum and other neutrophilic dermatoses such as Sweet’s syndrome. Although not a first-line treatment for these diseases, it can be considered in refractory cases.
Repurposing fluoxetine to treat lymphocytic leukemia: Apoptosis induction, sigma-1 receptor upregulation, inhibition of IL-2 cytokine production, and autophagy induction
Published in Expert Opinion on Therapeutic Targets, 2022
Chanichon Chomchoei, James Michael Brimson, Sirikalaya Brimson
One strategy for the fast production of more drugs with reduced cost is repurposing drugs that are already on the market for other conditions and have passed the critical step of phase 1 safety trials [9]. There has been a strong precedent set in the field of drug repurposing, with examples including the use of sildenafil, originally a failed cardiovascular drug that has become the market leader in the treatment of erectile dysfunction. Another example of a failed drug being repurposed is the much-maligned thalidomide. Thalidomide was initially used as an anti-emetic in women with morning sickness. However, the later discovery of congenital malformations caused thalidomide to be withdrawn from the market. Thalidomide has subsequently been repurposed for treating Erythema nodosum leprosum and multiple myeloma. Subsequently, Thalidomide is now on the WHO list of essential medicines [10].
Immunology of leprosy
Published in International Reviews of Immunology, 2022
Luis Alberto Ribeiro Froes, Maria Angela Bianconcini Trindade, Mirian Nacagami Sotto
Leprosy reactions are episodes of acute hypersensitivity presenting as aggravation of the previous lesions or the appearance of new ones, occurring before, during or after treatment [91,92]. Most commonly, leprosy reactions happen in disseminated presentations during the first three months of treatment and currently represent the main complication of the disease, requiring immediate treatment to prevent permanent neural damage [93]. They can be of two types: reverse reaction (RR) or erythema nodosum leprosum (ENL). RR occurs in approximately one-third of patients with the borderline presentation, whereas ENL occurs in around 50% of patients with lepromatous and 10% of patients with borderline leprosy [51], especially in those with a skin bacilloscopy index equal to, or greater than, 4 + [94].
Biologic and advanced immunomodulating therapeutic options for sarcoidosis: a clinical update
Published in Expert Review of Clinical Pharmacology, 2021
Ogugua Ndili Obi, Elyse E. Lower, Robert P. Baughman
Thalidomide was first introduced to the market in 1957 as a sedative-hypnotic and subsequently an antiemetic, but was quickly withdrawn in 1961 after it was linked to several cases of severe birth defects [335]. It has subsequently been approved by the FDA for the treatment of erythema nodosum leprosum with very strong recommendations to avoid use in pregnancy [335–337]. It is an immunomodulatory agent with potent activity against TNF and interferon-γ while paradoxically enhancing IL-2, IL4 and IL-5 [328,335]. It has been shown to reduce TNF production in human alveolar macrophages [338] and was postulated to support a switch from the TNF-driven Th1 response in sarcoidosis to a Th2 response [328]. Thalidomide was first used in a patient with chronic cutaneous sarcoidosis in 1983 [339] and subsequently also in the 1990s [340–342]. Its role in patients with chronic pulmonary and cutaneous sarcoidosis is unclear due to conflicting study results [325–329].