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Clobetasol-induced milia
Clobetasol-induced mifia Davide IacobeUi, MD, Ken Hashimoto, MD, Ichiro Kato, MD, Masaaki Ito, MD, and Yuhsuke Suzuki, M D Detroit and Allen Park, Michigan Milia developed in two patients with different chronic dermatoses after 2 weeks of treatment with clobetasol propionate ointment. Routine histologic and immunohistochemical analysis showed the cysts to be of ecerine gland origin (J AM ACAD DERMATOL 1989;21:215-7.)
New, more efficacious topical steroid preparations are available, but care must be taken in the use of these products because they may be associ-
ated with an increased incidence of adverse reactions. We report two patients with different skin conditions in whom milia developed after 2 weeks of treatment with clobetasol propionate ointment, a highly potent topical steroid.
From the Department of Dermatology, Wayne State University School of Medicine, Detroit, and the Veterans Administration Medical Center, Allen Park. Accepted for publication Aug. 15, 1988. Reprint requests: Ken Hashimoto, MD, Gordon H. Hall of Basic Medical Sciences, 540 E. Canfield Ave., Detroit, MI 48201.
CASE REPORTS Case 1 A 56-year-old white man had a 2-year l~story of lichen simplex chronicus on the left leg. The patient was treated with clobetasol propionate ointment twice daily. Two weeks later, multiple white, shiny, globoid milia measuring 2 to 4 mm in diameter were seen within the treated lesion (Fig. 1). Case 2 A 67-year-old white woman had a 20-year history of lichen planus that involved mainly the dorsa of the hands, the wrists, and forearms. The patient was treated with clobetasol propionate ointment twice daily. Two weeks later, multiple milia were noted in the treated areas (Fig. 2).
Fig. 1. Case 1. Multiple whitish, shiny, globoid, milia located in area of lichen simplex chronicus treated with clobetasol propionate ointment.
Fig. 2. Case 2. Multiple small milia located within lichen planus lesions treated with clobetasol propionate ointment. 215
216
Journal of the American Academy of Dermatology
Iacobelli et al.
Fig. 3. A, Thin-walled epidermal and papillary dermal cyst contains soft and laminated keratotic material. Small foci of lymphocitic infiltrate are present within surrounding areas. (• B, Higher magnification showing wall of cystic inclusion composed of several layers of squamous and granular cells. Laminated keratotic material is contained within cyst. (•
Fig. 4. A, Strong reaction of SKH1 to eecrine secretory coils. Antigen reacted less intensely to duct leading into milium. Laminated keratin in cyst is partially labeled. (• B, Reaction of EKH6 to eccrine duct, cyst wall, and keratin contents of milium. (•
Histologic examination A biopsy specimen from the first patient revealed a well-formed cystic inclusion located in the mid dermis. The cyst wall was composed of several layers of squamous and granular cells containing laminated keratotic material. A biopsy specimen from the second patient revealed a thin-waUed cyst containing soft and laminated keratotic material in the papillary dermis. The top of the cyst
pressed against the epidermis and may have been intraepidermal (Fig. 3, ,4 and B),
Immunohistoehemistry The absence of hair follicles suggested that these milia were related to the eccrine sweat duct. Immunohistochemical analysis was performed with the use of several monoclonal antibodies against the hair follicle and eccrine gland (Table I). The hair-structure anti-
Volume 21 Number 2, Part 1 August 1989
Clobetasol-induced milia 217
Table I. Reaction pattern of various monoclonal antibodies against eccrine and hair structures Antibody
Milium cyst
Eccrine duct
Eccrlne gland
Hair follicle (outer root sheath)
Epidermis
HKN2 HKN6 HKN7 EKH5 EKH6 SKH1
+ + ++ + (partial)
+ + -
+++ +++ +++
4+ + -
+ -
- , Negative; +_, positive,sometimes negative; +, weakly positive;++, moderately positive; +++, strongly positive.
bodies were HKN2, HKN6, and HKN7.' EKH5, EKH6, z and SKHU were antibodies to the eccrine gland and duct. The results (Table I) and histologic specimens (Fig. 4) demonstrate that these cysts were dilated cccrine ducts in which keratinous material was retained. Some aberrations from the expected pattern, such as the weak reaction of the cyst contents to HKN6 and S K i l l (which are only a part of the cyst), may be due to modification of the keratin within the cyst and an acquisition of abnormal immunogenicity against these monoclonal antikeratin antibodies. DISCUSSION In 1986 Tsuji et al. 4 described nine elderly patients in whom milia developed after 1 to 11 years of using various topical steroids ranging from class VI to class I. Most of the milia (88%) were connected to a hair follicle, and they always occurred on atrophic and telangiectatic skin. Routine histologic and immunohistochemical analysis showed that the milia in our cases were not related to the hair follicle but represented dilated eccrine ducts. It is also noteworthy that these milia developed within 2 weeks of the initial treatment and only where clobetasol propionate ointment was
applied. Therefore we can assume that they were induced b y the use of this steroid preparation. The vehicle o f clobetasol propionate ointment consists of propylene glycol, sorbitan sesquioleate, and white petrolatum. It is unlikely that the mili.a were induced by one of the vehicle components, because these ingredients are widely used in other ointments and have not been implicated previously as the cause of milia. Both patients had pruritic eruptions, and one may argue that scratching alone induced the milia. The milia did not develop before clobetasol application, however, and lichen simplex chronicus and lichen planus are not known to be associated with milia. REFERENCES t. Ito M, Tazawa T, Shimizu N, ct al. Cell differentiation in human anagen hair and hair follicles studied with antihair keratin rnonoclonal antibodies. J Invest Dermatol 1986;86:563-9. 2. Hashimoto K, Eto H, Matsumoto M, et al. Anti-keratin monoclonal antibodies: production, spccificities and applications. J Cutan Pathol 1983;t0:529-39. 3. Suzuki Y, Hashimoto K, Kato 1, et al. A monoclonal antibody, SHKI, reacts with 40 Kd sweat gland-associated antigen J Cutan Pathol (In press.) 4. Tsuji T, Kadoja A, Tanaka R, et al. Milia induced by corticosteroids. Arch Dermatol 1986;122:139-40.
New, more efficacious topical steroid preparations are available, but care must be taken in the use of these products because they may be associ-
ated with an increased incidence of adverse reactions. We report two patients with different skin conditions in whom milia developed after 2 weeks of treatment with clobetasol propionate ointment, a highly potent topical steroid.
From the Department of Dermatology, Wayne State University School of Medicine, Detroit, and the Veterans Administration Medical Center, Allen Park. Accepted for publication Aug. 15, 1988. Reprint requests: Ken Hashimoto, MD, Gordon H. Hall of Basic Medical Sciences, 540 E. Canfield Ave., Detroit, MI 48201.
CASE REPORTS Case 1 A 56-year-old white man had a 2-year l~story of lichen simplex chronicus on the left leg. The patient was treated with clobetasol propionate ointment twice daily. Two weeks later, multiple white, shiny, globoid milia measuring 2 to 4 mm in diameter were seen within the treated lesion (Fig. 1). Case 2 A 67-year-old white woman had a 20-year history of lichen planus that involved mainly the dorsa of the hands, the wrists, and forearms. The patient was treated with clobetasol propionate ointment twice daily. Two weeks later, multiple milia were noted in the treated areas (Fig. 2).
Fig. 1. Case 1. Multiple whitish, shiny, globoid, milia located in area of lichen simplex chronicus treated with clobetasol propionate ointment.
Fig. 2. Case 2. Multiple small milia located within lichen planus lesions treated with clobetasol propionate ointment. 215
216
Journal of the American Academy of Dermatology
Iacobelli et al.
Fig. 3. A, Thin-walled epidermal and papillary dermal cyst contains soft and laminated keratotic material. Small foci of lymphocitic infiltrate are present within surrounding areas. (• B, Higher magnification showing wall of cystic inclusion composed of several layers of squamous and granular cells. Laminated keratotic material is contained within cyst. (•
Fig. 4. A, Strong reaction of SKH1 to eecrine secretory coils. Antigen reacted less intensely to duct leading into milium. Laminated keratin in cyst is partially labeled. (• B, Reaction of EKH6 to eccrine duct, cyst wall, and keratin contents of milium. (•
Histologic examination A biopsy specimen from the first patient revealed a well-formed cystic inclusion located in the mid dermis. The cyst wall was composed of several layers of squamous and granular cells containing laminated keratotic material. A biopsy specimen from the second patient revealed a thin-waUed cyst containing soft and laminated keratotic material in the papillary dermis. The top of the cyst
pressed against the epidermis and may have been intraepidermal (Fig. 3, ,4 and B),
Immunohistoehemistry The absence of hair follicles suggested that these milia were related to the eccrine sweat duct. Immunohistochemical analysis was performed with the use of several monoclonal antibodies against the hair follicle and eccrine gland (Table I). The hair-structure anti-
Volume 21 Number 2, Part 1 August 1989
Clobetasol-induced milia 217
Table I. Reaction pattern of various monoclonal antibodies against eccrine and hair structures Antibody
Milium cyst
Eccrine duct
Eccrlne gland
Hair follicle (outer root sheath)
Epidermis
HKN2 HKN6 HKN7 EKH5 EKH6 SKH1
+ + ++ + (partial)
+ + -
+++ +++ +++
4+ + -
+ -
- , Negative; +_, positive,sometimes negative; +, weakly positive;++, moderately positive; +++, strongly positive.
bodies were HKN2, HKN6, and HKN7.' EKH5, EKH6, z and SKHU were antibodies to the eccrine gland and duct. The results (Table I) and histologic specimens (Fig. 4) demonstrate that these cysts were dilated cccrine ducts in which keratinous material was retained. Some aberrations from the expected pattern, such as the weak reaction of the cyst contents to HKN6 and S K i l l (which are only a part of the cyst), may be due to modification of the keratin within the cyst and an acquisition of abnormal immunogenicity against these monoclonal antikeratin antibodies. DISCUSSION In 1986 Tsuji et al. 4 described nine elderly patients in whom milia developed after 1 to 11 years of using various topical steroids ranging from class VI to class I. Most of the milia (88%) were connected to a hair follicle, and they always occurred on atrophic and telangiectatic skin. Routine histologic and immunohistochemical analysis showed that the milia in our cases were not related to the hair follicle but represented dilated eccrine ducts. It is also noteworthy that these milia developed within 2 weeks of the initial treatment and only where clobetasol propionate ointment was
applied. Therefore we can assume that they were induced b y the use of this steroid preparation. The vehicle o f clobetasol propionate ointment consists of propylene glycol, sorbitan sesquioleate, and white petrolatum. It is unlikely that the mili.a were induced by one of the vehicle components, because these ingredients are widely used in other ointments and have not been implicated previously as the cause of milia. Both patients had pruritic eruptions, and one may argue that scratching alone induced the milia. The milia did not develop before clobetasol application, however, and lichen simplex chronicus and lichen planus are not known to be associated with milia. REFERENCES t. Ito M, Tazawa T, Shimizu N, ct al. Cell differentiation in human anagen hair and hair follicles studied with antihair keratin rnonoclonal antibodies. J Invest Dermatol 1986;86:563-9. 2. Hashimoto K, Eto H, Matsumoto M, et al. Anti-keratin monoclonal antibodies: production, spccificities and applications. J Cutan Pathol 1983;t0:529-39. 3. Suzuki Y, Hashimoto K, Kato 1, et al. A monoclonal antibody, SHKI, reacts with 40 Kd sweat gland-associated antigen J Cutan Pathol (In press.) 4. Tsuji T, Kadoja A, Tanaka R, et al. Milia induced by corticosteroids. Arch Dermatol 1986;122:139-40.