REPORT
.
,
.
••
TINEA VERSICOLOR: HISTOLOGIC AND ULTRASTRUCTURAL INVESTIGATION OF PIGMENTARY CHANGES IBRAHIM GALADARI, M.D., MEDHAT EL KOMY, M.D., AHMED MOUSA, M.D., KEN HASHIMOTO, M.D., AND AMIR H. MEHREGAN, M.D.
Abstract A comparative histopathologic study is made between the hypopigmented and hyperpigmented skin lesions of pityriasis versicolor and normal skin areas utilizing histochemical stains and electron microscopy. There were no differences found between the population of Dopa-positive melanocytes within the hypopigmented and hyperpigmented lesions and the normal skin areas. The total epidermal pigmentation was diminished in hypopigmented lesions. The keratin layer was found to be significantly thicker in hyperpigmented lesions and contained more organisms. In hypopigmented lesions, melanocytes contained fewer and smaller melanosomes and exhibited signs of degenerative cellular changes.
clinical appearance, distribution pattern of the eruption, positive examination under Wood's lamp, and the microscopic findings of spores and mycelia in scraping material. Excisional biopsy specimens taken from the hypopigmented, hyperpigmented, and normal skin areas were divided equally into three parts. One part was fixed in 70% ethyl alcohol and was processed for paraffin embedding and routine histologic examination. The sections were stained by hematoxylin-eosin, acid-orcein-Giemsa, and a combination of alcian blue-PAS techniques. The second portion of the tissue specimens were fixed in 10% formalin at pH 7.4 containing 0.44 molar sucrose, incubated with Dopaoxidase, and processed for paraffin embedding. Tissue sections were counterstained with hematoxylin. The third portion of the tissue specimens were fixed in 5% glutaraldehyde, buffered to pH 7.4 with 0.1 M sodium cacodylate buffer. The specimens were postosmicated with 1% osmic acid and buffer for 1 hour, then dehydrated in 50% ethanol, and stained with 1% uranil acetate for 30 minutes. Following complete dehydration, the specimens were embedded in Araldite capsules and incubated for at least 2 days at 37°C, and at 60°C for an additional 2 days. Ultrathin sections were cut on a Packer-Blum MT 2 ultramicrotome, staining was done in a solution of uranyl acetate followed by Reynold's lead citrate, and finally the sections were examined by Hitachi, HU-12 electron microscope.
Tinea versicolor is a superficial infection caused by the lipophilic yeast Malassezia furfur.''^ This is the pathogenic form of a common skin flora, Fityrosporon orbiculare.^''^ The color of skin lesions in tinea versicolor varies widely, ranging from brown to pink and whitish hypopigmentation in different individuals. The pathogenesis of hyper- and hypopigmentation in tinea versicolor lesions is not yet fully understood. Among many ideas proposed are racial factors,^'^ light exposure,^'** cutaneous inflammatory reaction,'''" thickness of the stratum corneum,^'''^ and direct effect of Fityrosporon on melanocytes.'^''^ We report the results of histologic, histochemical, and ultrastructural investigation in a large series of patients with hypopigmented and hyperpigmented lesions of tinea versicolor and their normal skin areas.
RESULTS
- -
\
:
- :
/
- • •
Thickness of the surface keratin layer was measured in micrometers in all tissue specimens. Measurement was made in five different fields, and a mean thickness for each lesion was established (Table 1). A comparative study of the hyperpigmented, hypopigmented, and normal skin areas revealed a definite increase in the thickness of tbe keratin layer in hyperpigmented lesions. The thickness of the keratin layer was also slightly inTable 1. Thickness Measurements of Keratin Layer
Material and Methods Skin biopsy specimens from 30 patients with hypopigmented skin lesions, five with hyperpigmented lesions, and 30 specimens from normal skin areas of patients with tinea versicolor were utilized in this investigation. Diagnosis of tinea versicolor was established on a combination of the From the Departments of Dermatology, United Arab Emirates University, Dubai, United Arab Emirates, Cairo University, Cairo, Egypt, and Wayne State University School of Medicine, Detroit, Michigan.
Source of Skin Normal skin Hypopigmented lesions Hyperpigmented lesions
Address for correspondence: Ibrahim Galadari, M.D., U.A.E. University, P.O. Box 8716, Dubai, United Arab Emirates. 253
No. of Cases 30 30 5
Range of Average Thickness Thickness (\lm) (\Jim)
9-11 10-14 16-22
9.8 12.4 19.0
International Journal of Dermatology Vol. 31,No. 4, April 1992
creased in hypopigmented areas when compared with the normal skin of the same patient. Fityrosporon spores and hyphae were more numerous and more easily identified in the hyperpigmented lesions. Hypopigmented lesions showed fewer spores, which often required examination of PAS-stained sections for identification. The superficial perivascular lymphocytic inflammatory cell infiltrate was more pronounced in the hyperpigmented areas. Hypopigmented lesions showed only a low grade inflammatory cell infiltrate. Differences between the amount of epidermal pigmentation in hyperpigmented lesions and the normal skin areas was not appreciable. Tbere was, bowever, a definite diminution in the amount of epidermal pigmentation in the hypopigmented areas (Fig. 1). The results of Dopa-positive melanocyte counts are listed in Table 2. Dopa-positive melanocytes were counted in ten different high-power fields. There were no significant variations in the population of melanocytes in the hyperpigmented, hypopigmented, and normal skin areas. In several specimens of hypopigmented and hyperpigmented lesions, scattered within the stratum malpighii were degenerated cells with pyknotic nuclei and contracted cytoplasms. These cells showed desmosomal connections with the surrounding keratinocytes.
DISCUSSION
Tinea versicolor is a superficial infection caused by lipophilic yeast, Malassezia furfur. The color of skin lesions varies from brown to pink or hypopigmented whitish areas. The mechanism for the variation in pigmentation is not yet fully understood. Several theories have been proposed: (1) Malassezia furfur may filter ultraviolet light and consequently prevent tanning of the infected areas;^-** however, depigmented skin lesions also occur over the light-protected genital region.'''''^ (2) Racial factors have been incriminated. Hypopigmented lesions have been reported occurring predominantly in deeply pigmented skin individuals.^'^ (3) Another factor is increase in thickness of keratin
Number and sizes of melanosomes in junctional melanocytes were measured by examination of three different fields in electron micrographs. The results are summarized in Table 3. Ultrastructural studies of hypopigmented lesions revealed a definite reduction in the number, size, and in aggregation of melanosomes in junctional melanocytes and in the surrounding keratinocytes (Figs. 2 and 3). Some melanocytes exhibited degenerative changes in the form of mitochondrial and cytoplasmic vacuoles (Fig. 4). The number and sizes of melanosomes were approximately the same in hyperpigmented lesions of tinea versicolor and the normal skin areas. The melanocytes appeared morphologically intact (Fig. 5). Table 2. Dopa-Positive Melanocyte Counts in High Power Fields Source of Skin
No. of Cases
Normal skin , . Hypopigmented lesions Hyperpigmented lesions
30 30 5
Range
Average
9-12.3 8-13.3 11-12
10.05 11.04 11.2
Table 3. Average Number of Sizes and Melanosomes Source of Skin Normal skin Hypopigmented lesions Hyperpigmented lesions
No. of Cases
No. of Melanosomes
Size of Melanosomes
25
21.9
0.2x0.1
25
3.5
0.1 xO.6
5
22.8
0.17x0.1
Figure 1. Upper panel: normal skin stained by Dopa and counter stained with hematoxylin (original magnification X 125). Lower panel: hypopigmented lesion of tinea versicolor stained with Dopa and counterstained with hematoxylin show reduction in the amount of epidermal pigmentation (original magnification x 125). 254
Tinea Versicolor Galadari et al.
layer and larger n u m b e r of organisms in hyperpigmented compared with the hypopigmented and normal skin areas. (4) The inflammatory cell infiltrate was found to be more pronounced in the hyperpigmented lesions. The inflammatory responses have been report-
ed to act as stimulus to the melanocytes resulting in production of more pigment.'** (5) Degenerated keratinocytes have been observed in both hypopigmented
Figure 2. Dermo-epidemial junction in hypopigmented lesion shows normal melanocytes (Ml) in one area and partial degenerative melanocytes (M2) in another area. Melanosomes are smaller and less numerous when compared with normal skin (see Fig. 3). Keratinocytes indicated by (K) (original magnification x 9000). Figure 4. Electron micrograph of hypopigmented lesion show melanocyte (M) with mitochondrial and cytoplasmic vacuoles (V) (original magnification X 21,000). , .
Figure 5. Electron micrograph showing dermo—epidermal junction in hyperpigmented lesion. Note the normal size, number, and distribution of melanosomes (original magnification X 12,000).
Figure 3. Electron micrograph of normal skin showing part of dendrite of melanocyte (M) with aggregation of melanosomes (original magnification x 21,000). 25.5
International Journal of Dermatology Vol. 31,No. 4, April 1992
and hyperpigmented lesions, but not in normal skin areas.'''•^'' Contribution of these cells to the etiology of pigmentary disturbances is unlikely. (6) Disturbances in the pigmentary system have been reported in a number of publications.'^"'•^'^' Our investigation revealed no difference in the population of Dopa-positive melanocytes in hypopigmented, hyperpigmented, and normal skin areas. There was, however, a definite diminution in the amount of epidermal pigmentation in hypopigmented areas compared with the normal skin and hyperpigmented lesions. Hypopigmentation of the epidermis was in part secondary to block in pigment transfer. There also appeared to be a definite disturbance in melanogenesis with formation of fewer and smaller melanosomes, reduced aggregation of melanosomes in melanocytes and in keratinocytes, and partial degeneration of melanocytes with formation of mitochondrial and cytoplasmic vacuoles. These changes are most likely due to the cytotoxic effect of dicarboxylic acids (azelic acid, oleic acid, and vaccinic acid) on melanogenesis. The dicarboxylic acids have been found to be cytotoxic to melanocytes.^^'^"'^''^^ There may be two modes of action for the effect of dicarboxylic acids. One possibility is that they may interfere with mitochondrial enzymes, as we have found vacuolization and degeneration in the mitrochondria. Another possibility is that dicarboxylic acids may be closely related to the pathway of melanin synthesis, leading to formation of fewer and smaller melanosomes and partial degeneration of melanocytes. • ; • Hyperpigmentation, on the other hand, is most likely secondary to multiple factors including the increased thickness of the keratin layer, the presence of larger number of organisms, and the more prevalent superficial perivascular lymphocytic infiltrate.
5. 6. 7. 8.
9.
10.
11.
12.
13.
14.
15.
16. 17. 18. 19.
REFERENCES
1.
2.
3.
4.
Gordon AM. Lipophilic yeast-like organisms associated with tinea versicolor. J Invest Dermatol 1951; 17: 267-270. Bruke RC. Tinea versicolor: susceptibility factors and experimental infection in human beings. J Invest Dermatol 1961; 36:389-392. Keddie F, Shadomy S. Etiological significance of Pityrosporum orbiculare in tinea versicolor. Sabouraudia 1963; 3:21-22. Dorn M, Roehnert K. Dimorphism of Pityrosporum or-
20.
21.
22.
23.
biculare in a defined culture medium. J Invest Dermatol 1977; 69:244-248. Lewis GH, Hopper ME. Pseudo-achromia of tinea versicolor. Arch Dermatol Syphilol 1936; 34:850-861. Pardo-Castello V. Achromia parasitica. Arch Dermatol Syphilol 1932; 25:785. Allen HB, Charles CR, Johnson BL. Hyperpigmented tinea versicolor. Arch Dermatol 1976; 112:110. Findlay GH. Superficial fungus infection. In: Fitzpatrick TB, Eisen AZ, Woolf K, et al., eds. Dermatology in general medicine. 2nd Ed. New York: McGraw Hill Book Co., 1979:1516. Pierard J, Dockx P. The ultrastructural study of tinea versicolor and Malassezia furfur. Int J Dermatol 1972; 11:116-120. Dotz WI, Hendrikson DM, Yu GS, et al. Tinea versicolor: a light and electron microscopic study of hyperpigmented skin. J Am Acad Dermatol 1985; 12:37-40. Karaoui R, Bou-Resli M, Al-Zaid NS, Mousa A. Ultrastructural studies of hypopigmented skin. Dermatologica 1981; 162:6973. Kamel M, Abdel-Fattah A, Nassar AM. Ultrastructural study of the epidermal changes in vitiligo and some hypopigmented skin diseases. Bull Egyp Soc Derm Ven 1982; 3:3640. Nazzaro-Porro M, Passi S, Bolus H. Fatty acids of human surface lipids and their relation to skin melanogenesis. BrJ Dermatol 1977; 97:16-18. El-Gothamy Z. Tinea versicolor hypopigmentation, histochemical and therapeutic studies. Int J Dermatol 1975; 14:510-517. Hattori M, Ogawa H, Takamori K, et al. De (hypo) pigmentation mechanism of affected area of pityriasis versicolor. J Dermatol 1984; 11:63-66. Smith EL. Pityriasis versicolor of the penis. Br J Venereol 1978; 54:441. Nia AK, Smith EL. Pityriasis versicolor of the glans penis. BrJ Venereol 1979; 55:230. Papa GM, Kligman AM. The behaviour of melanocytes in inflammation. J Invest Dermatol 1965; 45:465-468. Keddie FM. Electron microscopy of Malassezia furfur in tinea versicolor. Sabouraudia 1966; 5:134-136. Gharles CR, Sire DJ, Johnson BL, et al. Hypopigmentation in tinea versicolor: a histochemical and electron microscopy study. Int J Dermatol 1973; 12:48-52. Nazzaro-Porro M, Passi S, Morpurgo G, et al. Identification of tyrosinase inhibitors in cultures of Pityrosporum. Pigment Cell 1979; 4:234. Leible H, Stingl G, Pehamberger J, et al. Inhibition of DNA synthesis of melanoma cells by azelaic acid. J Invest Dermatol 1985; 85:417. Nazzaro-Porro M, Passi S, Breathnach A, Zina G. 10 years observations on the effect of azelaic acid on lentigo maligna. J Invest Dermatol 1986; 87:438.
.
,
.
••
TINEA VERSICOLOR: HISTOLOGIC AND ULTRASTRUCTURAL INVESTIGATION OF PIGMENTARY CHANGES IBRAHIM GALADARI, M.D., MEDHAT EL KOMY, M.D., AHMED MOUSA, M.D., KEN HASHIMOTO, M.D., AND AMIR H. MEHREGAN, M.D.
Abstract A comparative histopathologic study is made between the hypopigmented and hyperpigmented skin lesions of pityriasis versicolor and normal skin areas utilizing histochemical stains and electron microscopy. There were no differences found between the population of Dopa-positive melanocytes within the hypopigmented and hyperpigmented lesions and the normal skin areas. The total epidermal pigmentation was diminished in hypopigmented lesions. The keratin layer was found to be significantly thicker in hyperpigmented lesions and contained more organisms. In hypopigmented lesions, melanocytes contained fewer and smaller melanosomes and exhibited signs of degenerative cellular changes.
clinical appearance, distribution pattern of the eruption, positive examination under Wood's lamp, and the microscopic findings of spores and mycelia in scraping material. Excisional biopsy specimens taken from the hypopigmented, hyperpigmented, and normal skin areas were divided equally into three parts. One part was fixed in 70% ethyl alcohol and was processed for paraffin embedding and routine histologic examination. The sections were stained by hematoxylin-eosin, acid-orcein-Giemsa, and a combination of alcian blue-PAS techniques. The second portion of the tissue specimens were fixed in 10% formalin at pH 7.4 containing 0.44 molar sucrose, incubated with Dopaoxidase, and processed for paraffin embedding. Tissue sections were counterstained with hematoxylin. The third portion of the tissue specimens were fixed in 5% glutaraldehyde, buffered to pH 7.4 with 0.1 M sodium cacodylate buffer. The specimens were postosmicated with 1% osmic acid and buffer for 1 hour, then dehydrated in 50% ethanol, and stained with 1% uranil acetate for 30 minutes. Following complete dehydration, the specimens were embedded in Araldite capsules and incubated for at least 2 days at 37°C, and at 60°C for an additional 2 days. Ultrathin sections were cut on a Packer-Blum MT 2 ultramicrotome, staining was done in a solution of uranyl acetate followed by Reynold's lead citrate, and finally the sections were examined by Hitachi, HU-12 electron microscope.
Tinea versicolor is a superficial infection caused by the lipophilic yeast Malassezia furfur.''^ This is the pathogenic form of a common skin flora, Fityrosporon orbiculare.^''^ The color of skin lesions in tinea versicolor varies widely, ranging from brown to pink and whitish hypopigmentation in different individuals. The pathogenesis of hyper- and hypopigmentation in tinea versicolor lesions is not yet fully understood. Among many ideas proposed are racial factors,^'^ light exposure,^'** cutaneous inflammatory reaction,'''" thickness of the stratum corneum,^'''^ and direct effect of Fityrosporon on melanocytes.'^''^ We report the results of histologic, histochemical, and ultrastructural investigation in a large series of patients with hypopigmented and hyperpigmented lesions of tinea versicolor and their normal skin areas.
RESULTS
- -
\
:
- :
/
- • •
Thickness of the surface keratin layer was measured in micrometers in all tissue specimens. Measurement was made in five different fields, and a mean thickness for each lesion was established (Table 1). A comparative study of the hyperpigmented, hypopigmented, and normal skin areas revealed a definite increase in the thickness of tbe keratin layer in hyperpigmented lesions. The thickness of the keratin layer was also slightly inTable 1. Thickness Measurements of Keratin Layer
Material and Methods Skin biopsy specimens from 30 patients with hypopigmented skin lesions, five with hyperpigmented lesions, and 30 specimens from normal skin areas of patients with tinea versicolor were utilized in this investigation. Diagnosis of tinea versicolor was established on a combination of the From the Departments of Dermatology, United Arab Emirates University, Dubai, United Arab Emirates, Cairo University, Cairo, Egypt, and Wayne State University School of Medicine, Detroit, Michigan.
Source of Skin Normal skin Hypopigmented lesions Hyperpigmented lesions
Address for correspondence: Ibrahim Galadari, M.D., U.A.E. University, P.O. Box 8716, Dubai, United Arab Emirates. 253
No. of Cases 30 30 5
Range of Average Thickness Thickness (\lm) (\Jim)
9-11 10-14 16-22
9.8 12.4 19.0
International Journal of Dermatology Vol. 31,No. 4, April 1992
creased in hypopigmented areas when compared with the normal skin of the same patient. Fityrosporon spores and hyphae were more numerous and more easily identified in the hyperpigmented lesions. Hypopigmented lesions showed fewer spores, which often required examination of PAS-stained sections for identification. The superficial perivascular lymphocytic inflammatory cell infiltrate was more pronounced in the hyperpigmented areas. Hypopigmented lesions showed only a low grade inflammatory cell infiltrate. Differences between the amount of epidermal pigmentation in hyperpigmented lesions and the normal skin areas was not appreciable. Tbere was, bowever, a definite diminution in the amount of epidermal pigmentation in the hypopigmented areas (Fig. 1). The results of Dopa-positive melanocyte counts are listed in Table 2. Dopa-positive melanocytes were counted in ten different high-power fields. There were no significant variations in the population of melanocytes in the hyperpigmented, hypopigmented, and normal skin areas. In several specimens of hypopigmented and hyperpigmented lesions, scattered within the stratum malpighii were degenerated cells with pyknotic nuclei and contracted cytoplasms. These cells showed desmosomal connections with the surrounding keratinocytes.
DISCUSSION
Tinea versicolor is a superficial infection caused by lipophilic yeast, Malassezia furfur. The color of skin lesions varies from brown to pink or hypopigmented whitish areas. The mechanism for the variation in pigmentation is not yet fully understood. Several theories have been proposed: (1) Malassezia furfur may filter ultraviolet light and consequently prevent tanning of the infected areas;^-** however, depigmented skin lesions also occur over the light-protected genital region.'''''^ (2) Racial factors have been incriminated. Hypopigmented lesions have been reported occurring predominantly in deeply pigmented skin individuals.^'^ (3) Another factor is increase in thickness of keratin
Number and sizes of melanosomes in junctional melanocytes were measured by examination of three different fields in electron micrographs. The results are summarized in Table 3. Ultrastructural studies of hypopigmented lesions revealed a definite reduction in the number, size, and in aggregation of melanosomes in junctional melanocytes and in the surrounding keratinocytes (Figs. 2 and 3). Some melanocytes exhibited degenerative changes in the form of mitochondrial and cytoplasmic vacuoles (Fig. 4). The number and sizes of melanosomes were approximately the same in hyperpigmented lesions of tinea versicolor and the normal skin areas. The melanocytes appeared morphologically intact (Fig. 5). Table 2. Dopa-Positive Melanocyte Counts in High Power Fields Source of Skin
No. of Cases
Normal skin , . Hypopigmented lesions Hyperpigmented lesions
30 30 5
Range
Average
9-12.3 8-13.3 11-12
10.05 11.04 11.2
Table 3. Average Number of Sizes and Melanosomes Source of Skin Normal skin Hypopigmented lesions Hyperpigmented lesions
No. of Cases
No. of Melanosomes
Size of Melanosomes
25
21.9
0.2x0.1
25
3.5
0.1 xO.6
5
22.8
0.17x0.1
Figure 1. Upper panel: normal skin stained by Dopa and counter stained with hematoxylin (original magnification X 125). Lower panel: hypopigmented lesion of tinea versicolor stained with Dopa and counterstained with hematoxylin show reduction in the amount of epidermal pigmentation (original magnification x 125). 254
Tinea Versicolor Galadari et al.
layer and larger n u m b e r of organisms in hyperpigmented compared with the hypopigmented and normal skin areas. (4) The inflammatory cell infiltrate was found to be more pronounced in the hyperpigmented lesions. The inflammatory responses have been report-
ed to act as stimulus to the melanocytes resulting in production of more pigment.'** (5) Degenerated keratinocytes have been observed in both hypopigmented
Figure 2. Dermo-epidemial junction in hypopigmented lesion shows normal melanocytes (Ml) in one area and partial degenerative melanocytes (M2) in another area. Melanosomes are smaller and less numerous when compared with normal skin (see Fig. 3). Keratinocytes indicated by (K) (original magnification x 9000). Figure 4. Electron micrograph of hypopigmented lesion show melanocyte (M) with mitochondrial and cytoplasmic vacuoles (V) (original magnification X 21,000). , .
Figure 5. Electron micrograph showing dermo—epidermal junction in hyperpigmented lesion. Note the normal size, number, and distribution of melanosomes (original magnification X 12,000).
Figure 3. Electron micrograph of normal skin showing part of dendrite of melanocyte (M) with aggregation of melanosomes (original magnification x 21,000). 25.5
International Journal of Dermatology Vol. 31,No. 4, April 1992
and hyperpigmented lesions, but not in normal skin areas.'''•^'' Contribution of these cells to the etiology of pigmentary disturbances is unlikely. (6) Disturbances in the pigmentary system have been reported in a number of publications.'^"'•^'^' Our investigation revealed no difference in the population of Dopa-positive melanocytes in hypopigmented, hyperpigmented, and normal skin areas. There was, however, a definite diminution in the amount of epidermal pigmentation in hypopigmented areas compared with the normal skin and hyperpigmented lesions. Hypopigmentation of the epidermis was in part secondary to block in pigment transfer. There also appeared to be a definite disturbance in melanogenesis with formation of fewer and smaller melanosomes, reduced aggregation of melanosomes in melanocytes and in keratinocytes, and partial degeneration of melanocytes with formation of mitochondrial and cytoplasmic vacuoles. These changes are most likely due to the cytotoxic effect of dicarboxylic acids (azelic acid, oleic acid, and vaccinic acid) on melanogenesis. The dicarboxylic acids have been found to be cytotoxic to melanocytes.^^'^"'^''^^ There may be two modes of action for the effect of dicarboxylic acids. One possibility is that they may interfere with mitochondrial enzymes, as we have found vacuolization and degeneration in the mitrochondria. Another possibility is that dicarboxylic acids may be closely related to the pathway of melanin synthesis, leading to formation of fewer and smaller melanosomes and partial degeneration of melanocytes. • ; • Hyperpigmentation, on the other hand, is most likely secondary to multiple factors including the increased thickness of the keratin layer, the presence of larger number of organisms, and the more prevalent superficial perivascular lymphocytic infiltrate.
5. 6. 7. 8.
9.
10.
11.
12.
13.
14.
15.
16. 17. 18. 19.
REFERENCES
1.
2.
3.
4.
Gordon AM. Lipophilic yeast-like organisms associated with tinea versicolor. J Invest Dermatol 1951; 17: 267-270. Bruke RC. Tinea versicolor: susceptibility factors and experimental infection in human beings. J Invest Dermatol 1961; 36:389-392. Keddie F, Shadomy S. Etiological significance of Pityrosporum orbiculare in tinea versicolor. Sabouraudia 1963; 3:21-22. Dorn M, Roehnert K. Dimorphism of Pityrosporum or-
20.
21.
22.
23.
biculare in a defined culture medium. J Invest Dermatol 1977; 69:244-248. Lewis GH, Hopper ME. Pseudo-achromia of tinea versicolor. Arch Dermatol Syphilol 1936; 34:850-861. Pardo-Castello V. Achromia parasitica. Arch Dermatol Syphilol 1932; 25:785. Allen HB, Charles CR, Johnson BL. Hyperpigmented tinea versicolor. Arch Dermatol 1976; 112:110. Findlay GH. Superficial fungus infection. In: Fitzpatrick TB, Eisen AZ, Woolf K, et al., eds. Dermatology in general medicine. 2nd Ed. New York: McGraw Hill Book Co., 1979:1516. Pierard J, Dockx P. The ultrastructural study of tinea versicolor and Malassezia furfur. Int J Dermatol 1972; 11:116-120. Dotz WI, Hendrikson DM, Yu GS, et al. Tinea versicolor: a light and electron microscopic study of hyperpigmented skin. J Am Acad Dermatol 1985; 12:37-40. Karaoui R, Bou-Resli M, Al-Zaid NS, Mousa A. Ultrastructural studies of hypopigmented skin. Dermatologica 1981; 162:6973. Kamel M, Abdel-Fattah A, Nassar AM. Ultrastructural study of the epidermal changes in vitiligo and some hypopigmented skin diseases. Bull Egyp Soc Derm Ven 1982; 3:3640. Nazzaro-Porro M, Passi S, Bolus H. Fatty acids of human surface lipids and their relation to skin melanogenesis. BrJ Dermatol 1977; 97:16-18. El-Gothamy Z. Tinea versicolor hypopigmentation, histochemical and therapeutic studies. Int J Dermatol 1975; 14:510-517. Hattori M, Ogawa H, Takamori K, et al. De (hypo) pigmentation mechanism of affected area of pityriasis versicolor. J Dermatol 1984; 11:63-66. Smith EL. Pityriasis versicolor of the penis. Br J Venereol 1978; 54:441. Nia AK, Smith EL. Pityriasis versicolor of the glans penis. BrJ Venereol 1979; 55:230. Papa GM, Kligman AM. The behaviour of melanocytes in inflammation. J Invest Dermatol 1965; 45:465-468. Keddie FM. Electron microscopy of Malassezia furfur in tinea versicolor. Sabouraudia 1966; 5:134-136. Gharles CR, Sire DJ, Johnson BL, et al. Hypopigmentation in tinea versicolor: a histochemical and electron microscopy study. Int J Dermatol 1973; 12:48-52. Nazzaro-Porro M, Passi S, Morpurgo G, et al. Identification of tyrosinase inhibitors in cultures of Pityrosporum. Pigment Cell 1979; 4:234. Leible H, Stingl G, Pehamberger J, et al. Inhibition of DNA synthesis of melanoma cells by azelaic acid. J Invest Dermatol 1985; 85:417. Nazzaro-Porro M, Passi S, Breathnach A, Zina G. 10 years observations on the effect of azelaic acid on lentigo maligna. J Invest Dermatol 1986; 87:438.
