image of silk fabric and dry skin

A. K. Gupta MD, PhD, FRCPCa,b, R. Bluhm BSc (Hons), BA, MAb,c

aDivision of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Science Center (Sunnybrook site) and the University of Toronto, Toronto, Canada.
bMediprobe Laboratories Inc., Toronto, Ontario, Canada.
cUniversity of Western Ontario, London, Ontario, Canada.

ABSTRACT

Seborrheic dermatitis is a common superficial dermatosis, characterized by red, flaking areas of the skin, which may in some cases be covered with yellowish flakes. The most commonly affected areas are the nasolabial folds, ears, eyebrows, scalp and chest. While seborrheic dermatitis may be easy to recognize clinically, the variability of the lesions in both appearance and location may complicate the diagnosis. Seborrheic dermatitis has been described as resembling psoriasis (in which case, the condition may be called “sebopsoriasis”) and, when affecting the eyes or ears, has also been described as blepharitis and otitis, respectively. Seborrheic dermatitis tends to be chronic, though seasonal variation is common, with lesions worsening in the dry, winter months.

Key Words:
itraconazole, seborrheic dermatitis

Seborrheic dermatitis is relatively common, affecting between 1 and 3% of immunocompetent individuals. While the precise etiology of seborrheic dermatitis is not known, endogenous host factors are thought to predispose some people to develop this dermatosis. In particular, yeasts of the genus Malassezia (formerly Pityrosporum orbiculare/ovale) have been implicated. These yeasts are normal skin commensals, though in some individuals they may cause pityriasis versicolor and Malassezia folliculitis. While some investigators have reported that individuals with seborrheic dermatitis have higher Malassezia counts on their skin than healthy controls,1 others have found no difference in Malassezia counts between seborrheic dermatitis patients and controls2. These authors emphasize instead the importance of host reaction to the yeasts. Much of the evidence for the role of Malassezia yeasts is derived partly from treatment studies.

Ketoconazole, an imidazole, is effective against seborrheic dermatitis.3,4 The clinical improvement of the lesions is paralleled by a reduction in the number of Malassezia yeasts on the skin.3,4

Mechanism of Action

Itraconazole, (Sporanox®, Janssen Pharmaceuticals) a triazole, is highly keratinophilic and lipophilic, and tissue levels of the triazole are several times higher than peak plasma levels.5 As a result, itraconazole tends to reach high concentrations in the epidermis and may persist in the skin for 3-4 weeks depending upon the site of infection, thus creating a therapeutic reservoir.6 Furthermore, itraconazole does not redistribute into the systemic circulation.6 Itraconazole is active against Malassezia species in vitro7 and on excised human stratum corneum.8 This triazole may also demonstrate anti-inflammatory activity with inhibition of 5-lipooxygenase metabolites involved in allergic, inflammatory and immunoreactive processes.9-11

Clinical Trials

The data obtained from open trials9,12,13 (Table 1) suggest that itraconazole may be effective in the treatment of seborrheic dermatitis.

In one study,12 30 patients with seborrheic dermatitis of the head (n=10), face (n=10), head and face (n=8), head and extremities (n=1), and chest and thigh (n=1) were treated with itraconazole 150mg or 200mg once per week for 2-3 months. Moisturizers were applied topically. The efficacy of treatment was rated as: markedly effective (3 cases), effective (17), slightly effective (6), not effective (3) and aggravated (1). The efficacy rate was determined by adding cases in which the clinical response was graded as markedly effective or effective (67% of patients). Mycological samples were taken from these patients, but there was no apparent relationship between the presence of P. ovale and the clinical course of the disease.

An open trial13 evaluated 10 patients with sebopsoriasis of the scalp and face. Eight patients also had lesions of the trunk and extremities. The lesions of sebopsoriasis (lesions of the scalp, eyebrows, ears and seborrheic areas of the trunk) were more inflammatory and eczema-like than most psoriatic lesions. Patients were started on itraconazole 50mg/day for two weeks. If this dosage was well tolerated, the itraconazole was increased to 100mg/day for an additional 4 weeks. Patients were told not to wash their hair for 5 days prior to each assessment of the scalp, and lesions were evaluated using a quadrant-area-severity-scale of 1 (less than 10% involvement) to 5 (greater than 70% involvement). Severity was measured on a 0 – 3 scale, with 0 being “healed”. The total scalp score was obtained by multiplying the total area of the scalp involved by the severity score for the whole scalp. Non-scalp lesions were examined using a 0 – 4 scale. Samples were also taken from the vertex area of the scalp using a detergent scrub technique.14 Overall, the scalp lesions showed the best response: 4 patients were cured of scalp lesions and one patient was cured overall. The “classic” psoriatic plaques, particularly of the extremities, were often unchanged during treatment. In addition to the clinical improvement shown by these patients, there was a significant (P<0.01) reduction in the number of P. orbiculare per cm2. No side effects were noted in any patient.

The largest study to date9 was an open, single center study involving 160 patients with seborrheic dermatitis. Itraconazole 200mg/day was administered for 7 consecutive days. Patients were evaluated at baseline, day 7 and day 37 following the end of therapy. The parameters evaluated were itching, burning, erythema, desquamation, and each was rated as: absent (0), mild (1), moderate (2), and intense (3). An overall assessment of the degree of improvement was also made by both the physician and the patient at the end of the study. Mycological examination for Malassezia yeasts was also performed at baseline, and at days 7 and 37 following therapy.

Author Study Regimen (n) Outcome
Masataro (1995)12 Open

N=30 subjects, most with seborrheic dermatitis of the face and/or head

Itraconazole 150mg or 200mg once weekly for 2-3 months Clinical response was graded as “markedly effective” or “effective” in 67% of patients
Faergemann (1985)13 Open

N=10 patients with sebopsoriasis – defined as psoriasis of the scalp, eyebrows, ears and sebborheic areas of the trunk. Lesions appeared more inflammatory and eczema-like than most psoriasis lesions

Itraconazole 50mg/day for 2 weeks: if well tolerated, followed by 100mg/day for an additional 4 weeks 4 patients were cured of scalp lesions and one other patient cured overall. Scalp lesions in general showed the best response. Plaques that had the appearance of classical psoriasis were often unchanged during treatment.

Significant (P<0.01) decrease in the number of Malassezia yeasts.

Caputo, et al (2002)9 Open

N=160 patients with seborrheic dermatitis

Itraconazole 200mg/day for 7 consecutive days At follow-up 30 days after treatment, clinical improvement was evaluated as:
Excellent: 34.3%
Good: 40%
Moderate: 18.7%

Mycological tests positive for Malassezia in
68.7% of patients at baseline. Of these, 46.2%
were negative at follow-up

The clinical picture in sebopsoriasis patients is
intermediate between seborrheic dermatitis and
psoriasis. Based on the response to itraconazole
(both clinical and in terms of Malassezia
yeasts), at least some of the lesions appear to
be seborrheic dermatitis rather than psoriasis.

Table 1: Itraconazole in Seborrheic Dermatitis.

Two patients discontinued therapy for personal reasons. Improvement in itching was reported in 122 (76.2%) and 130 patients (81.2%) at days 7 and 37, respectively. Burning improved in 84 (52.5%) and 89 (55.6%) patients at days 7 and 37, respectively. There was an improvement in erythema in 112 (70.0%) and 118 (73.7%) patients at days 7 and 37, respectively. Desquamation improved in 128 patients (80%) at day 7, and in 147 patients (91.8%) at day 37. The treatment was judged to be effective by 148 patients (92.5%), with clinicians rating overall improvement as excellent in 55 patients (34.3%), good in 64 patients (40.0%), and moderate in 30 patients (18.7%). Mycological examination (presence of Malassezia spores) was positive at baseline in 110 patients (68.7%) and this became negative at day 37 in 74 patients (46.2%).

A maintenance regimen of itraconazole was 200mg/day for the first 2 days of each month. At month 9 following the start of therapy, 28 of 30 patients reported that they had not experienced a relapse. Tolerance and compliance was reported as being excellent. Itraconazole was well tolerated in these studies and this is consistent with previous experience.15-18

Conclusion

The data suggest that itraconazole may be effective and safe in the treatment of seborrheic dermatitis, particularly that present on the face and scalp. Further larger randomized, controlled trials will help confirm these observations.

References

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