Ciclopirox Shampoo for Treating Seborrheic Dermatitis

A. K. Gupta MD, PhD, FRCPC^1,2 and R. Bluhm BSc (Hons), BA, MA^2,3

¹Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Science Centre (Sunnybrook site) and the University of Toronto, Toronto, Canada
²Mediprobe Research, London, Ontario, Canada
³University of Western Ontario, London, Ontario, Canada

ABSTRACT

Seborrheic dermatitis is a common inflammatory skin disease, affecting between 1% and 3% of immunocompetent adults. While its cause is unknown, a number of predisposing factors have been reported, including the implications of Malassezia yeasts. Various treatment options are available, such as ciclopirox shampoo, which combines anti-Malassezia activity with an anti-inflammatory action. This agent has been shown to be an effective and safe treatment for seborrheic dermatitis of the scalp.
Key Words: ciclopirox, seborrheic dermatitis

Clinically, seborrheic dermatitis presents as red, flaking, slightly greasy-looking patches, which are located primarily on the scalp, nasolabial folds, ears, eyebrows and chest. The degree of flaking and erythema can vary markedly between patients.¹ The exact cause of seborrheic dermatitis is not known, however, a number of predisposing factors have been reported. Such endogenous host factors include nutritional,² environmental,^3,4 and immunological⁵ factors, as well as the presence of Malassezia yeast.⁶

While there is some controversy with regard to the relationship between seborrheic dermatitis of the scalp and dandruff, it has been argued that dandruff is a mild form of seborrheic dermatitis.^7,8 Furthermore, the relationship between Malassezia yeasts and the effective treatment of seborrheic dermatitis with antifungal agents helps to support the claim that these yeasts are the primary cause of seborrheic dermatitis.⁹

Due to the fact that there is an increased prevalence of seborrheic dermatitis in HIV-positive and AIDS patients,^10,11 it is thought that the disease may be caused by an abnormal immune response to Malassezia. However, it is unclear exactly what this immune response might be. Many individuals without seborrheic dermatitis have antibodies to Malassezia yeasts and while some authors have found that the level of IgG antibodies to the yeasts is increased in patients with seborrheic dermatitis,^5,12 others¹ have found no difference in the number of antibodies produced by patients with seborrheic dermatitis and controls.

It has recently been suggested that the reaction by seborrheic dermatitis patients to Malassezia is best characterized as an irritant response¹³ involving an inflammatory reaction and that reduction of Malassezia yeast on the skin reduces the clinical signs of seborrheic dermatitis.

Treating Seborrheic Dermatitis

The two main classes of treatment for seborrheic dermatitis are topical corticosteroids and antifungal agents. Corticosteroids reduce inflammation, thus resulting in clinical improvement of seborrheic dermatitis. However, prolonged treatment with topical steroids may result in adverse effects on the skin, such as atrophy, telangiectasia, or perioral dermatitis¹⁴ and, especially in the case of higher potency, fluorinated topical steroids, to dysfunction of the adrenal cortex.¹⁵ Because of the adverse effects associated with topical steroids, there has been a shift in treatment strategies for seborrheic dermatitis with an increased interest in antifungal agents. Several antifungal agents have been found to be effective in the treatment of seborrheic dermatitis. These include non-specific agents (e.g., zinc pyrithione, selenium sulfide, propylene glycol, lithium succinate), hydroxypyridones (e.g., ciclopirox), azoles (e.g., bifonazole, fluconazole, itraconazole, ketoconazole, miconazole, metronidazole), and the allylamines (e.g., terbinafine).

Ciclopirox

Ciclopirox is the ethanolamine salt of 6-cyclohexyl-I-hydroxy-4- methyl-2(IH)-pyridone.¹⁶ The empirical formula of ciclopirox is C12H17NO2, with a molecular weight of 207.27.17 Ciclopirox shampoo 1% is a colorless, translucent solution,¹⁷ which has been used in the treatment of seborrheic dermatitis. In addition to its effect on Malassezia yeasts, ciclopirox has been shown to decrease inflammation. Rosen et al.¹⁸ found that the anti-inflammatory activity of ciclopirox was greater than that of several azole agents or hydrocortisone. Ciclopirox appears to exert its anti-inflammatory effect via several pathways, including the inhibition of 5-lipoxygenase and cyclo-oxygenase.^19,20

Clinical Trials of Ciclopirox

Vardy et al.²¹ conducted a double-blind, randomized, placebocontrolled clinical study of ciclopirox olamine 1% shampoo to determine its effectiveness in the treatment of scalp seborrheic dermatitis. One hundred and two patients were randomly selected to apply either ciclopirox olamine 1% shampoo or the vehicle shampoo to the scalp for 5 minutes, twice per week for 4 weeks. Signs and symptoms of erythema, scaling, and pruritus were assessed at the end of the study, which revealed that 93% of the ciclopirox shampoo-treated patients had significantly improved or cleared compared to 41% in the placebo group (P<0.00001). Another double-blind, randomized, vehicle-controlled study was conducted to assess the efficacy of 1% ciclopirox shampoo in the treatment of seborrheic dermatitis of the scalp.²² Subjects were randomly selected to 5ml (10ml for shoulder-length hair or longer) of either 1% ciclopirox or vehicle shampoo twice per week for 4 weeks. Grading of erythema, scaling, and the overall status of seborrheic dermatitis was performed at week 4, using a 6-point rating scale (0=none, 1=slight, 2=mild, 3=moderate, 4=pronounced, and 5=severe). Effective treatment was defined as a score of 0 (or 1 if baseline score was ≥3) for the combined rating of global status, erythema, and scaling. It was reported that 26% of the ciclopirox-treated patients were effectively treated compared to 13% of the vehicle group (P=0.0001).²²

Adverse Effects

Ciclopirox shampoo 1% was used twice a week in 626 patients.¹⁷ Increased itching was the most frequent adverse event found in 1% of the subject population. Furthermore, application reactions, such as burning, erythema, and itching also occurred in 1% of the subjects.¹⁷

Dosage and Administration

After wetting hair, apply approximately 1 teaspoon (5ml) of ciclopirox shampoo 1% to the scalp.¹⁷ If the patient has long hair, it is recommended to use up to 2 teaspoons (10ml). Lather and leave on for 3 minutes before rinsing. Treatment should be repeated twiceper week for 4 weeks, with a minimum of 3 days between each application.¹⁷

Conclusion

Evidence suggests that an abnormal or inflammatory immune system reaction to Malassezia yeasts may be the cause of seborrheic dermatitis. An available treatment for this disease is ciclopirox shampoo, which is an antifungal agent that also has antibacterial and anti-inflammatory properties. The proven efficacy and safety of ciclopirox shampoo in the treatment of seborrheic dermatitis of the scalp makes it an important addition to the treatment options available.

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