British Journal of Dermatology (1986) 115, 217-225.

Itraconazole therapy in pityriasis versicolor

A.DEL PALACIO HERNANZ, J.FRIAS-INIESTA*, O. GONZALEZ-
VALLE*, M.BORGERSt, J.VAN CUTSEMf AND CCAUWENBERGHf
Department of Microbiology, C.S. 'i°de Octubre', Madrid, *Departinent of Dermatology, Hospital Provincial,
Madrid, Spain and fjanssen Research Laboratories, Janssen Pharmaceutica, Beerse, Belgium

Accepted for publication 22 January 1986

SUMMARY
The efficacy of itraconazole was assessed in an open trial in 30 patients with disseminated lesions
of pityriasis versicolor confirmed by direct microscopy. The patients were allocated randomly to
one of two treatment regimens, 200 mg once daily for 5 days or 100 mg once daily for 10 days. On
assessment 3 weeks after the end of the treatment, 25 patients were healed, two patients had mild
residual lesions, two had considerable residual lesions and one patient had relapsed. One patient
reported dyspepsia and one patient reported stomach ache. One patient had asymptomatic
elevation of serum transaminase (GOT and GPT) but this had returned to normal 3 weeks after
the end of therapy.

Pityriasis versicolor is the most common superficial mycotic disease world-wide and is caused
by Malassezia furfur (Roberts, 1969a). Pityrosporum orbiculare and P. ovale, are both lipophilic
members of the normal human cutaneous flora, and are probably identical (Faergemann &
Frediksson, 1982). M. furfur is thought to be thefilamentousform of P. orbiculare (P. ovale) and
this is now considered the correct name under which P. ovale and P. orbiculare are combined
(Salkin & Gordon, 1977). Pityrosporum sp. develops from the saprophytic yeast form to the
pathogenic mycelial form under the influence of several factors, including seborrheic dermatitis
(Faergemann & Frediksson, 1979), hyperhidrosis (Burke, 1961; Roberts, 1969a, b), genetic
factors (Burke, 1961; Faergemann & Frediksson, 1982; Roberts, 1969a, b) systemic corticoster-
oid therapy, malnutrition and immunosuppressive treatment (Burke, 1961; Roberts, 1969b).
Sonhle and Collins-Lech (1978) found a defect in the production of lymphokines in patients
with pityriasis versicolor.
Spontaneous improvement is uncommon in pityriasis versicolor, and left untreated it tends to
persist for many years. Although a few cases clear spontaneously in cool weather, the majority of
patients require therapy. Treatment of pityriasis versicolor is simple, but relapse is common, as
well as depigmentation of infection sites. Pityriasis versicolor used to be treated with a wide
range of topical compounds (Ive, 1973; Hay, 1981), including selenium sulphide, thiosulphate.
Correspondence: Dr del Palacio Hernanz, Servicio de Microbiologia, C.S. 1° de Octubre', Crtra. Andalucia, Km.
5'4OO, 28041 Madrid, Spain.
217
2i8 A.del Palacio Hernanz et al.
keratolytic agents, propylene glycol and topical antifungals. Patients can experience difficulty in
applying topical preparations, especially on large areas of the body and often the treatment is
inadequate. In many instances, the choice of treatment is made on the basis of simplificity of
usage and patient acceptability.
Ketoconazole was the first oral antifungal effective in the treatment of pityriasis versicolor
(Borelli, 1980; Palacio-Hernanz and Merino, 1981) and clinical trials have confirmed that
treatment periods of between 5 and 28 days give satisfactory results (JoUiffe & Ngai, 1981;
Urcuyo & Zaias, 1982; Savin, 1984; Meisel, 1983; Hay & Midgeley, 1984). The majority of
patients find this treatment acceptable; its main disadvantage is the risk, albeit low, of liver
toxicity and the possibility of endocrine affects (Hanifin, 1983; Janssen & Symoens, 1983;
Schuermeyer & Nieschlag, 1982).
Itraconazole is a triazole derivative which has been shown to be highly active in vitro against a
wide range of fungi including Pityrosporum sp. (van Cutsem, van Gerven & Janssen, 1985;
Faergemann, 1984). Animal studies have indicated that this drug, when administered orally is
5-10 times more potent than ketoconazole (van Cutsem, 1983; van Cutsem et al., 1983), and
these animal data have been confirmed in clinical pilot studies (Janssen Pharmaceutica,
unpublished data). Toxicity studies have revealed no significant toxicity even at high doses in
dogs and rats (Janssen Pharmaceutica, unpublished data), nor any effect on steroidogenesis in
animals and human volunteers (R. de Coster, personal communication). Teratogenicity studies
were positive in rats receiving high doses of itraconazole (40 mg/kg and above), indicating that
this drug should not be used during pregnancy (Janssen Pharmaceutica, unpublished data).
We report here the results of a radomized open study of two treatment regimens with
itraconazole in patients with extensive pityriasis versicolor.

METHODS
Patient selection
Thirty patients with disseminated skin lesions consistent with pityriasis versicolor, who were
seen in our department over a 2-month period, were included in the trial. The criteria for
inclusion were skin lesions typical of this condition (erythema, scaling, hyper- and hypo-
pigmentation), fluorescence in Wood's light and positive microscopic diagnosis with potassium
hydroxide (KOH).
All patients were assessed prior to treatment with a detailed history and clinical examination.
Four parameters of clinical disease activity (itching, scaling, erythema and hypo- or
hyperpigmentation) were assessed and scored as: o = none; i = mild; 2 = moderate; 3 = severe.
Patients in any of the following categories were excluded: less than 17 years of age; presence of
systemic mycotic disease; women who were pregnant or breast-feeding, or those who were not
on reliable contraceptives; systemic or topical antimycotic treatment within one month prior to
the trial; serious concurrent disease that might prevent completion of therapy. Written consent
was obtained from all patients.
At the initial visit a blood sample was taken for haematology (packed cell volume,
haemoglobin, red cell count, leukocyte count with differential count, and platelets) and
biochemistry (glucose, creatinine, alkaline phosphatase, yGT, bilirubin, SGOT, SGPT, LDH,
cholesterol and triglycerides).

Medication
Thirty patients were allocated randomly, on an open basis, to either regimen I (15 patients).
 Itraconazole therapy in pityriasis versicolor 219
which consisted of 200 mg o.d. of itraconazole taken at breakfast for 5 consecutive days, or
regimen II (15 patients), which consisted of 100 mg o.d. of itraconazole for 10 consecutive days.
No other medication was allowed during the study.

Follow-up
The patients were asked to return one day after the end of therapy and again 3 weeks later. At
these visits, the patients were assessed in the same way as at the pre-treatment visit. All the
clinical evaluations were carried out by the same person.
At the end of the trial, the patient's condition was rated as healed, mild residual lesions,
considerable residual lesions, unchanged, deteriorated and unevaluable. Patients with complete
healing or residual lesions were considered responders. Adverse effects were recorded and rated
according to severity. Haematological and biochemical evaluations were repeated.

Mycological examination
At the first visit, scrapings were taken from the lesions for mycological assessment: light
microscopy with potassium hydroxide, culture of Pityrisporum sp., electron microscopy and
study of MIC of intraconazole. The culture medium was Sabouraud dextrose agar (Difco) with
0 5 g/1 cycloheximide and 0-05 g/1 of cloramphenicol, and olive oil overlay. Tubes with scrapings
were incubated at 37°C and maintained on a slope to keep the agar slant covered with oil. In all
patients Pityrosporum sp. was grown before starting treatment. Scales for electron microscopy
were fixed in glutaraldehyde and processed routinely for ultrastructural examination. Before
treatment, scanning electron microscopy showed normal size Pityrisporum yeasts as well as
short hyphae in all patients. Transmission electron microscopy revealed yeasts with thick cell
walls and short mycelia with a normal intracellular structure. In some patients a small
percentage of dead yeasts was observed before therapy.

Sensitivity testing
When growth was visible on the isolation medium, single colonies were sub-cultured onto
Dixon agar. For sensitivity testing, cultures in 5 ml Dixon broth were incubated at 37°C for 4
days and dilutions made in Dixon broth to give final concentrations in the test medium of
between 25 000 and 30 000 colony forming units per ml. Stock solutions (2 mg/ml) of miconazole
and ketoconazole were prepared in 50° ethanol and of itraconazole in DMSO. Drugs were added
to the test medium to give final concentrations from 100 ^g/ml to 0001 /ig/ml. Controls with and
without the solvents were included and all experiments were performed in duplicate.
Tubes were observed for visible growth after 7 and 14 days incubation at 37°C. After 14 days,
the tubes without macroscopically visible growth were subcultured to distinguish fungistatic
from fungicidal activity.

RESULTS

The patients' characteristics and history are shown in Table i. In seven patients in each group
pityriasis versicolor was present for the first time and these patients had not had previous
treatment. The mean duration of this episode was 24 months in Group I and 64 months in
Group II.
Eight patients in each group had recurrent pityriasis versicolor and they had had different
treatments with a variety of topical compounds (selenium sulphide, zince pyrithione, propylene
glycol and topical imidazoles). The majority of these patients had had several relapses.
220 A.del Palacio Hernanz et al.
TABLE I. Clinical details of patients in the trial

Group 1(15 patients) Group II (15 patients)

Sex: male 5 11
female 10 4
Age (years): mean (range) 30-1 (18-71) 26-2 (17-54)
Weight (kg): mean (range) 616 (44-82) 67 8 (54-90)
1st episode of pityriasis versicolor:
no. of patients 7 7
Duration of first episode (months)
mean (range) 24 (1-96) 63 5(1-360)
Recurrent pityriasis versicolor:
no. of patients 8 8
Recurrent pityriasis vesicolor:
duration (months) mean (range) 57 (6-72) 36(12-120)
Duration of last episode of
recurrent pityriasis versicolor (months)
mean (range) 2(1-7) 2-5 (2-7)

All patients in both groups had numular lesions but 12 also had confluent lesions. The lesions
were located on the trunk, neck and upper arms. Three patients also had lesions on their thighs,
two on the groin and three on the face. The lesions were erythematous or hypopigmented,
except for 13 patients who had hyperpigmented lesions. Thirteen patients noted mild to
moderate itching. All patients had scaling (10 mild, 14 moderate and 6 severe).

Assessment one day after the end of therapy

Table 2 shows the results of the treatment one day after the end of therapy. Itching and
erythema had disappeared in both groups of patients. Seven patients in Group I and 10 patients
in Group II had mild scaling. Six patients in Group I and one patient in Group II had
hyperpigmentation and four patients in Group II had both hyper- and hypopigmentation. Nine
patients in Group I and 10 patients in Group II had moderate hypopigmentation.
TABLE 2. Assessment one day after end of therapy

No. of patients (mean clinical score) No. of patients (mean clinical score)
Parameter Group I (15 patients) Group II (15 patients)

Pruritus o (o) o (o)

Scaling 7 (1) and 10 (i) and
8 (o) 5 (o)
Erythema o (o) o (o)
Hyperpigmentation 6 (i) 5 (i)*
Hypopigmentation 9 (2) 14 (2)**
KOH light microscopy-f ve 15 13
Wood's light-I-ve 14 13
Culture of PiOTOjporwm sp. -l-ve 3 6

Clinical scores: o = none, i = mild, 2 = moderate, 3 = severe.

* One patient had hyperpigmentation; four patients had hyper- and hypopigmentation.
** Ten patients had hypopigmentation; four patients had hyper- and hypopigmentation.
 Itraconazole therapy in pityriasis versicolor 221
Light microscopy with KOH was positive in all patients in Group I and 13 patients in Group
II. In some patients who still had mild scaling after treatment, the yeast and the mycelial form
could be observed. Transmission electron microscopy showed that the intracellular structure of
the cells had changed.
Electron microscopy showed a much smaller number of yeast cells and mycelium at the end of
treatment, and the proportion of cells with a completely necrotic interior was markedly
increased. However, cells with a completely degenerate cytoplasm, often loaded with lipid
globules, retained an intact cell wall. This was confirmed by scanning electron microscopy,
which showed that the surface of the cells remained as smooth as those in the pre-treatment
sample. Thus, itraconazole appears to have a 'mummifying' effect on P. ovale.
Wood's light was positive in 14 patients in Group I and in 13 patients in Group II.
Pityrosporum sp. was grown from three patients in Group I and from six patients in Group II.
The antifungal activity of miconazole, ketoconazole and itraconazole against seven strains of
Pityrosporum sp. isolated from the patients is given in Table 3. Miconazole was fimgicidal at 10
/ig/ml in six strains and at 100 /ig/ml for one. i /^g/ml gave more than 90% growth inhibition and
partial growth inhibition was obtained at lower concentrations. Ketoconazole was fungicidal at a
concentration of i /zg/ml; itraconazole, however, was fungicidal for six out of seven strains at o-1
/ig/ml and in one at i /ig/ml. Fungistatic activity was observed at lower concentrations of all
three drugs. None of the strains isolated after therapy was stopped was shown to have developed
in vitro resistance to itraconazole.

TABLE 3. Antifungal activity of azoles against Pityrosporum sp. in Dixon broth

(broth decimal test)

Concentration /Jg/ml

Miconazole Ketoconazole Itraconazole

P. ovale markedly markedly markedly

strains fungicidal fungistatic* fungicidal fungistatic fungicidal fungistatic

I. B 40689
(7.2826 no. 2) 10 I I 01 —
2. B 40690
(8 1496 no. 2) 10 I I 01 —
3.B 40691
(8.2946 no. 9) 10 I I 01 —
4. B 40830
(9.1855 no. 13) 10 I I o-i —
5.B 40831
(9.2013 no. 17) 100 I I 1 01
6. B 40832
(9.0179 no. 18) 10 I I 01 —
7. B 40836
(9.0763 no. 22) 10 I I

* Marked fungistatic activity: more than 90% versus controls.

— = endpoint not observed.
222 A.del Palacio Hernanz et al.
Assessment 3 weeks after therapy
Table 4 shows the results of the global assessment of treatment 3 weeks after finishing therapy.
Fourteen patients (93%) in Group I had responded to treatment; 13 patients were completely
healed and one had mild residual lesions. One patient had considerable residual lesions.
Thirteen patients (87%) in Group II had responded to the therapy; 12 patients were completely
healed and one had mild residual lesions; one patient had considerable residual lesions and one
patient had deteriorated.
Pityrosporum sp. was cultured from four patients in Group I (two patients who were healed,
one with mild residual lesions and one with considerable residual lesions), and from six patients
in Group II (three patients who were healed, one who had mild residual lesions, one who had
considerable residual lesions and one who had deteriorated). In Group I, KOH and Wood's
light were positive in two patients (one patient with considerable residual lesions and the other
with mild residual lesions).
At the second evaluation, only material from patients who were not cured was studied by
electron microscopy. In these few samples both the yeast form and the short mycelial form were
detected; transmission electron microscopy showed that these few organisms had a normal
intracellular structure.
In Group II, KOH and Wood's light were positive in three patients (one with considerable
residual lesions one who had deteriorated and one with mild residual lesions). Depigmentation
remained in seven patients in Group I and 10 patients in Group II (one of whom had
TABLE 4. Assessment 3 weeks after the end of therapy

No. of patients

Parameter Group I Group II Total

Responders: healed 13 12 25
mild residual lesions I i' 2
Total (%) 14 (93) 13 (87) 27 (90)
Considerable residual lesions I 2
Unchanged 0 0 0
Deteriorated or relapsed 0 I I
Positive culture of Pytirosporum sp. 4^ 6" 10
Positive KOH microscopy 3= 3-^ 6
No residual lesions 5 3 8
Residual hypopigmentation only 7 9 16
Residual hyperpigmentation only I 0 I

Responders = patients with complete healing or mild residual

lesions.
' With hyperpigmentation.
•'• With hypopigmentation.
' Two patients were healed, one had mild residual lesions and
one had considerable residual lesions.
* Three patients were healed, one had mild residual lesions, one
had considerable residual lesions and one had deteriorated.
' One patient was healed, one had mild residual lesions and one
had considerable residual lesions.
* One patient had mild residual lesions, one had relapsed and
one had considerable residual lesions.
 Itraconazole therapy in pityriasis versicolor 223
considerable residual lesions). Eight patients who sunbathed after treatment were evenly tanned
and had no residual lesions. One patient in Group I had mild hyperpigmentation without
scaling on a restricted area on the side of the neck, but was mycologically cured (Wood's light,
KOH direct microscopy and culture for Pityrosporum sp. were negative). The patient in Group
II who had mild hyperpigmentation and scaling was evaluated in the final assessment as having
mild residual lesions, and KOH, Wood's light and culture for Pityrosporum sp. were positive.

Three-month follow-up
All patients were questioned by telephone 3 months after the end of treatment. All patients who
had cleared 3 weeks after the end of therapy, were still clear 3 months later. In most patients
repigmentation had occurred.

Acceptability
All the patients found the treatment simple, easy and acceptable. Compliance was very good,
probably because the medication was given in a single daily dose and for a short period of time.

Adverse reactions
Two adverse reactions were reported in Group I. One patient experienced mild dyspeptic
symptoms with each dose, that lasted for 2-3 h after ingestion of the drug. Another patient
reported mild stomach ache for i h following each dose. Both patients were able to complete the
treatment schedule.

Haematology and biochemistry

One patient in Group II presented significantly abnormal GOT and GPT values at the end of
the treatment (GOT 121 IU/1, GPT 131 IU/1, normal range 0-45 IU/1. This increase was
asymptomatic and had completely normalized by the 3-week follow-up. No other significant
haematological or biochemical abnormalities were observed.

DISCUSSION
At the assessment one day after the end of therapy, itching and erythema had disappeared in all
patients in both groups. However, mild scaling persisted in seven patients in Group I and in 10
patients in Group II. Almost all patients had a positive KOH test. Wood's light was also still
positive in these patients, although the intensity of the fluorescence was reduced when
compared with that prior to treatment. Electron microscopy showed that in many of the patients
who still had some scaling with a positive KOH test, fungal elements had been altered or
destroyed, and it was observed that cells could become 'mummified' after treatment, with dead
cells retaining an intact surface structure.
Comparing the results immediately after the end of treatment and 3 weeks later, it is evident
that thefinalclinical and mycological evaluation of a treatment of pityriasis versicolor should be
performed at least 3 weeks after the end of treatment. The KOH test and Wood's light
examination are not relevant immediately after the end of the therapy.
Pityrosporum orbiculare (P. ovale) is considered to be the aetiological agent of tinea versicolor
(Roberts & Mackenzie, 1979; Faergemann & Fredriksson 1982; Salkin & Gordon, 1977). This
organism was cultured from all patients prior to therapy, from nine patients at the end of
treatment and from 10 patients 3 weeks later. At this time, five of the patients with a positive
culture were assessed as healed and no fungi were seen microscopically, which suggested that
224 A.del Palacio Hernanz et al.
they were carrying the yeast as a saprophyte on their skin. Faergemann and Djarv (1982)
reported a similar finding on the last day of treatment in 10 healed patients with pityriasis
versicolor, who had been treated with 200 mg oral ketoconazole o.d. for 3 weeks. In 20 patients
in our study, culture of Pityrisporum sp. 3 weeks after the end of treatment was negative; these
findings demonstrate the prolonged pityrosporicidal effect of itraconazole even when treatment
is ended. These findings make the evaluation of a treatment of pityriasis versicolor rather
difficult. Cultures give no definitive answer since Pityrosporum sp. lives on the skin of many
people in a saprophytic form. Microscopy and Wood's lamp are not valid criteria when the
assessment is done immediately after treatment with an orally active antifungal, since dead
fungal elements remain on the skin. Valid assessment of the efficacy of an oral treatment appears
to be possible only a minimum of 3 weeks after end of therapy. At this time, both microscopy and
clinical aspects should be evaluated. Hypopigmentation cannot be regarded as a primary
symptom of the infection since the melanocytes need some time to recover even after
disappearance of the fungus from the skin.
Clinically mild side-effects (mild dyspeptic symptoms and stomach ache) only appeared in
two patients in Group I and were probably related to the higher daily dose of the drug.
Sensitivity to the three azoles of the seven Pityriosporum strains tested was comparable to
those obtained in previous experiments (Faergemann, 1984; Faergemann & Djarv, 1982;
Faergemann 1979; Faergemann & Bernander, 1979). Miconazole possesses high activity in vitro
against Pityrosporum sp. and in vivo in pityriasis versicolor after topical application (Faerge-
mann & Djarv, 1982; Faergemann & Bernander, 1979). The most important problems with
topical imidazole treatment are the untreated lesions and the presence of the yeast as a
saprophyte in the follicles. Ketoconazole is more active in vitro, and is absorbed systemically
after oral intake and distributed as the active substance to the areas involved (van Cutsem, 1983).
The in vitro activity of itraconazole is about roo and about 10 times more potent than those of
miconazole and ketoconazole respectively (Janssen Pharmaceutica, 1984; Faergemann & Djarv,
1982). Most important is its superiority over ketoconazole, suggesting possible greater activity
in vivo.
Asymptomatic increases of liver enzymes have been observed during the first days of
treatment with all drugs that are extensively metabolized in the liver (Petersen, Ailing &
Kirkpatrick, 1980; Drouhet & Dupont, 1983). Although our finding with itraconazole in one
patient is not necessarily relevant to the general population, it remains necessary to monitor liver
function in patients who receive long-term therapy with this drug.
In our study, the response to therapy did not seem to be influenced significantly by the
existence of previous episodes of pityriasis versicolor or by the duration of the episode being
treated. The introduction of ketoconazole made oral treatment of pityriasis versicolor possible
(Borelli, 1980), an important advance since non-compliance with topical therapy is common,
and oral drugs, particularly given in a single dose or a short course, may produce better
compliance. Itraconazole seems to be an effective agent for the treatment of pityriasis versicolor;
however, optimum treatment schedules and more clinical experience with longer follow-up
periods are required to determine the efficacy and safety of the drug. Itraconazole should also be
compared under double-blind conditions with alternative agents.

REFERENCES
BORELLI, D . (1980) Treatment of pityriasis versicolor with ketoconazole. Reviews of Infectious Diseases, 4, 592.
BURKE, R . C . (1961) Tinea versicolor: susceptibility factors and experimental infections in human beings. Journal of
Investigative Dermatology, 36, 389.
 Itraconazole therapy in pityriasis versicolor 225
DROUHET, E . & DUPOKT, B . (1983) Laboratory and clinical assessment of ketoconazole in deep-seated mycoses.
American Journal of Medicine, 74 (iB), 30.
FAERGEMANN, J . (1979) Tinea versicolor and Pityrisporum orbiculare: mycological investigations, experimental
infections and epidemiological surveys. Acta Dermato-Venereologica, 86 (Suppl.), 5.
FAERGEMANN, J . (1984) In vitro and in vivo activities of ketoconazole and itraconazole against Pityriosporum orbiculare.
Antimicrobial Agents and Chemotherapy, 26, 773.
FAERGEMANN, J. & BERNANDER, S . (1979) The activity of five different antimycotics against Pityriosporum orbiculare in
vitro. Acta Dermato-Venereologica, 59, 521.
FAERGEMANN, J. & DJARV, L . (1982) Tinea versicolor: treatment and prophylaxis with ketoconazole. Cutis, 30, 542.
FAGEMANN, J . & FREDIKSSON, T . (1979) Tinea versicolor with regard to seborrheic dermatitis. Archives of Dermatology,
IIS, 966-
FAERGEMANN, J. & FREDIKSSON, T . (1982) Tinea versicolor: some new aspects of etiology, pathogenesis and treatment.
International Journal of Dermatology, 21, 8.
HANIFIN, J . (1983) Adverse reactions. In: Ketoconazole in the Management of Fungal Disease, ADIS Press, Balgowlah,
Australia.
HAY, R . J . (1981) Treatment of superficial fungal infections. Clinical and Experimental Dermatology, 6, 509.
HAY, R.J. & MIDGELEY, G . (1984) Short course ketoconazole therapy in pityriasis versicolor. Clinical and Experimental
Dermatology, 9, 571.
IvE, F.A. (1973) Treatment of skin infections and infestations. British Medical Journal, 4, 475.
JANSSEN, P . A . J . & SYMOENS, J . E . (1983) Hepatic reactions during ketoconazole treatment. American Journal of
Medicine, 74, 80.
JANSSEN PHARMACEUTICA (1984) RS1211 Basic Medical Information Brochure, August 1984.
JOLLIFFE, D.S. & NGAI, Y . L . (1981) Systemic treatment of tinea versicolor with ketoconazole in forty four patients.
Clinical and Experimental Dermatology, 6, 625.
MEISEL, C . (1983) 10 Tage- therapie der pityriasis versicolor mit ketoconazol. Zeitschriftfur Hautkrankheiten, 58,1130.
PALACIO-HERNANZ, A . & MERINO, M . V . (1981) Treatment of pityriasis versicolor with ketoconazole. In: Abstracts 21st
Intersdence Conference on Antimicrobial Agents and Chemotherapy, p. 849. Chicago.
PETERSEN, E.A., ALLING, D . U . V . & KIRKPATRICK, C . H . (1980) Treatment of chronic cutaneous candidosis with
ketoconazole: a controlled clinical trial. Annals of Internal Medicine, 93, 791.
ROBERTS, S . O . B . (1969a) Pityrosporum orbiculare. incidence and distribution on clinically normal skin. British Journal of
Dermatology, 81, 264.
ROBERTS, S.O.B. (1969b) Pityriasis versicolor: a clinical and mycological investigation. British Journal of Dermatology,
81,315.
ROBERTS, S.O.B. & MACKENZIE, D . W . R . (1979) Pityriasis versicolor. In: Textbook of Dermatology, (ed. by A.J. Rook,
D.S. Wilkinson and F.J. Ebling). 3rd Edn. Vol. i, p. 825. Blackwell Scientific Publications, Oxford.
SALKIN, I . F . & GORDON, M . A . (1977) Polymorphism oiMalassezia furfur. Canadian Journal of Microbiology, 23, 471.
SAVIN, R.C. (1984) Systemic ketoconazole in tinea versicolor: a double-blind examination and i year follow-up. Journal
of the American Academy of Dermatology, 10, 824.
ScHUERMEYER, T. & NiESCHLAG, E. (1982) Ketoconazole induced drop in serum and saliva testosterone. Lancet, ii, 1098.
SOHNLE, P.G. & COLLINS-LECH, C . (1978) Cell-mediated immunity to Pityrosporum orbiculare in tinea versicolor.
Journal of Clinical Investigation, 62, 45.
URCUYO, G . & ZAIAS, N . (1982) Successful treatment of pityriasis versicolor by systemic ketoconazole. Journa/0/t/ie
American Academy of Dermatology, 6, 24.
VAN CUTSEM, J. (1983) T h e antifungal activity of ketoconazole. American Journal of Medicine, 74, 9.
VAN CUTSEM, J., VAN GERVEN, F . & JANSSEN, P.A.J. (1985) The antifungal activity of azoles: in vitro and in vivo activity.
ISHAM, ic)-24 May, p. 3-23. Atlanta, U.S.A.
VAN CUTSEM, J., VAN GERVEN, F . , ZAMAN, R . , HEERES, J. & HANSSEN, P.A.J. (1983) Pharmacological and preclinical
results with a new oral and topical broad-spectrum antifungal, R 51 211. 13th International Congress of
Chemotherapy, Vienna, August 28-September 2, Part 40: i - i i .