Clofazimine in the treatment of discoid lupus erythematosus

Mackey, J. P.; Barnes, J.

doi:10.1111/j.1365-2133.1974.tb06723.x

Cited by 69 publications

(21 citation statements)

References 5 publications

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“…In the past, only a few uncontrolled, open trials involving treatment of chronic CLE with CFZ produced good results (12)(13)(14)(15). One case report also described a good response to CFZ in the treatment of subacute CLE (16).…”

Section: Lupus Erythematosus (Le) Is An Autoimmune Disease That Can Ementioning

confidence: 99%

Double‐blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus

Bezerra¹,

Vilar²,

Neto³

et al. 2005

Arthritis & Rheumatism

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Objective. To evaluate the efficacy of clofazimine (CFZ) compared with chloroquine diphosphate (CDP) for the treatment of cutaneous involvement in systemic lupus erythematosus (SLE).Methods. A prospective, randomized, controlled, double-blind clinical trial was carried out in SLE patients with active cutaneous lesions, of whom 16 were randomized to receive CFZ at 100 mg/day and 17 received CDP at 250 mg/day for 6 months. All drugs had a similar appearance to avoid identification. Both groups received broad-spectrum sunscreens twice a day and the prednisone dose was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers at baseline and at months 1, 2, 4, and 6.Results. Thirty-three patients were randomized to a treatment group, of whom 27 completed 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ-treated patients and 1 CDP-treated patient (P ‫؍‬ 0.15) dropped out due to development of severe lupus flare. At the end of the study, 12 CFZtreated patients (75%) and 14 CDP-treated patients (82.4%) had complete or near-complete remission of skin lesions; intention-to-treat analysis showed no significant difference in the response rates between groups. Side effects, mainly skin and gastrointestinal events, were frequent in both groups, but no patients had to discontinue their treatment.Conclusion. These findings suggest that CFZ is equally as effective as CDP in controlling cutaneous lesions in SLE patients. However, we cannot exclude the possibility that the CFZ itself could be the cause of systemic lupus flare. Lupus erythematosus (LE) is an autoimmune disease that can exclusively affect the skin (cutaneous LE [CLE]) or can affect other systems as well (systemic LE [SLE]). Cutaneous lesions are classified as either specific or nonspecific. Lupus-specific cutaneous lesions are divided into acute, subacute, and chronic. Acute CLE includes malar and generalized maculopapular rashes. Subacute CLE includes the annular-polycyclic and papulosquamous (psoriasiform) variants. Chronic CLE includes discoid lupus erythematosus, lupus profundus, and LE tumidus, among others. Of the nonspecific LE cutaneous lesions, Raynaud's phenomenon, bullous LE, and vasculitic lesions are most common (1-3).In the literature, there are no reports of controlled, randomized clinical trials of a treatment strategy for SLE patients with cutaneous lesions. Based on clinical experience, antimalarial drugs are considered to be the first option for treatment of these patients (4). When a safe dosage of antimalarial drugs is used, the side effects are rare and include retinopathy, corneal deposition, disturbance of visual accommodation, nausea, vomiting, urticaria, hair discoloration, skin and mucosal hyperpigmentation, headache, tinnitus, dizziness, and myopathy, among others (5,6). Unfortunately, not all SLE patients with cutaneous lesions show a good response to antimalarial drugs. Treatment of the refractory cases includes use of thalidomide...

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Section: Lupus Erythematosus (Le) Is An Autoimmune Disease That Can Ementioning

confidence: 99%

Double‐blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus

Bezerra¹,

Vilar²,

Neto³

et al. 2005

Arthritis & Rheumatism

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“…In spite of its bioaccumulation, several clinical trials have established CFZ as a potentially useful therapeutic agent for treating a variety of chronic inflammatory diseases (17)(18)(19)(20)(21)(22). Furthermore, in vitro studies have shown that intracellular CFZ biocrystals dampen proinflammatory pathways while enhancing anti-inflammatory signals (23).…”

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confidence: 99%

Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State

Yoon

Keswani

Sud

et al. 2016

Antimicrob Agents Chemother

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Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ therapy is accompanied by the formation of drug biocrystals that accumulate within resident tissue macrophages, without obvious toxicological manifestations. Therefore, to specifically elucidate the off-target consequences of drug bioaccumulation in macrophages, we compared the level of inflammasome activation in CFZ-accumulating organs (spleen, liver and lung) in mice after 2 and 8 weeks of CFZ treatment when the drug exists in soluble and insoluble (biocrystalline) forms, respectively. Surprisingly, the results showed a drastic reduction in caspase 1 and interleukin-1␤ (IL-1␤) cleavage in the livers of mice treated with CFZ for 8 weeks (8-week-CFZ-treated mice) compared to 2-week-CFZ-treated and control mice, which was accompanied by a 3-fold increase in hepatic IL-1 receptor antagonist (IL-1RA) production and a 21-fold increase in serum IL-1RA levels. In the lung and spleen, IL-1␤ cleavage and tumor necrosis factor alpha expression were unaffected by soluble or biocrystal CFZ forms. Functionally, there was a drastic reduction of carrageenan-and lipopolysaccharide-induced inflammation in the footpads and lungs, respectively, of 8-week-CFZ-treated mice. This immunomodulatory activity of CFZ biocrystal accumulation was attributable to the upregulation of IL-1RA, since CFZ accumulation had minimal effect in IL-1RA knockout mice or 2-week-CFZ-treated mice. In conclusion, CFZ accumulation and biocrystal formation in resident tissue macrophages profoundly altered the host's immune system and prompted an IL-1RA-dependent, systemic anti-inflammatory response.

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“…Positive results of -as a rule -open studies using clofazimine were reported in cheilitis granulomatosa [7], pyoderma gan grenosum [8], lupus vulgaris [9], Buruli ul cer [10], granuloma facíale [11], lupus erythematodes discoides [12], psoriasis pustulosa [3,13] and atopic dermatitis [6], Dermatitis ulcerosa is a rare dermatologic disease, characterized by an extraordinary chronic course [14], The main localization is the head and trunk of older patients; women and men seem to be equally affected. The primary lesion is a sterile pustule, which dis integrates after a few days resulting in a ul ceration.…”

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confidence: 99%