Search

Clofazimine has been in clinical use for almost 40 years, but little is known of its mechanism of action. The primary indication for clofazimine is multibacillary leprosy, but it is useful in several infectious and noninfectious diseases, such as typical myocobacterial infections, rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe acne, pustular psoriasis, and discoid lupus erythematosus. Postulated mechanisms of action include intercalation of clofazimine with bacterial DNA and increasing levels of cellular phospholipase A2. Clinical experience, possible mechanisms of action, and side effects of clofazimine are summarized.

Skin biopsy specimens from two lepromatous leprosy patients with dark brown pigmentation who were receiving long-term clofazimine therapy were studied. Ceroid-lipofuscin pigment was demonstrated inside macrophages that contained numerous phagolysosomes. These contained lipids and clofazimine that appeared as electron-lucent vacuoles and a lipofuscin pigment that was electron dense, granular, and lamellated. Although the presence of the drug in tissues contributed to the skin pigmentation, the main cause was a drug-induced, reversible ceroid lipofuscinosis.

A 70-year-old woman developed dark reddish blue pigmentation in scarred areas of discoid lupus erythematosus after taking clofazimine intermittently over a period of 10 years. Although light microscopy of routinely processed tissue failed to define the cause of the pigment, fluorescent microscopy showed vivid red deposits concentrated around larger vessels within the dermis. These deposits were shown to correspond to birefringent red clofazimine crystals on fresh frozen sections. Although the hyperpigmentation may clinically resemble melanin, biopsy specimens from our patient revealed a loss of melanin pigment in lesional skin, suggesting a primary role for clofazimine in producing the color changes observed.

Several categories of chemical and pharmacologic agents can cause alterations in cutaneous pigmentation, although the mechanisms differ and in several instances may be unknown. Fixed drug eruptions appear to have alteration of the basement membrane zone with incontinence of epidermal pigment as the mechanism of hyperpigmentation. Heavy metals produce increased pigmentation in part from deposition of metal particles and in part from an increase in epidermal melanin production. The antimalarials may bind to melanin. The phenothiazines and minocycline produce pigmentation from deposition of the drug. The mechanism, site, and nature of the pigment occurring with antineoplastic agents is not well understood, but the location is most likely predominantly epidermal. Clofazimine (Lamprene) alteration in pigmentation appears to result from deposition of the drug in subcutaneous fat.