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Eruptive keratoacanthomas associated with immunosuppressive therapy in a patient with systemic lupus erythematosus
BRIEF COMMUNICATIONS Eruptive keratoacanthomas associated with immunosuppressive therapy in a patient with systemic lupus erythematosus M. Wagdy Dessoukey, MD, Mohamed E Omar, MD, and Hussein Abdel-Dayem, MD Abu Dhabi, United Arab Emirates
Although the cause and pathogenesis of eruptive keratoacanthomas (EKs) are unknown, altered immunity has been implicated. We describe EK in a young woman with systemic lupus erythematosus (SLE) who was receiving immunosuppressive therapy. CASE REPORT
A 23-year-old white woman had a 4-month history of a progressive, generalized, pruritic eruption involving mainly the upper half of the body. The lesions began on her head, extended onto her neck and trunk, and were associated with painful intraoral lesions. There was no family history of similar skin lesions. She had a 6-year history of SLE with neurologic and renal involvement, for which she was receiving prednisolone, 30 mg/day, and cyclophosphamide, 100 mg/day. Examination disclosed a papular eruption on the face, neck, upper trunk, tongue, hard and soft palates,
From the Department of Dermatology, A1-Jazeera Hospital. Reprint requests: M. Wag@ Dessoukey, MD, Department of Dermatology, A1-Jazeera Hospital, EO. Box 2427, Abu Dhabi, United Arab Emirates. J Am Acad Dermatol 1997;37:478-80. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/82796
and nasal mucosa. The individual papules were 2 to 6 mm in diameter, flesh-colored, and firm. Some appeared to be follicular, and some contained a central keratinous crater. The face was severely affected (Fig. 1) with lesions tending to coalesce, resulting in ectropion. Multiple skin biopsy specimens showed domeshaped epidermal hyperplasia with a central crater filled with a hyperkeratotic and parakeratotic stratum corneum, epidermal lip, and well-differentiated epidermal strands composed of keratinocytes with a glassy appearance invading into the dermis (Fig. 2). Eight weeks after a regimen of isotretinoin, 1 mg/kg per day, all skin and mucosal lesions cleared with no recurrence for more than 3 years. DISCUSSION
Keratoacanthoma can occur as solitary or multiple lesions. Variants of multiple keratoacanthoma include the Ferguson Smith typO and EK of Grzybowski. 2 The age of our patient is more in keeping with multiple keratoacanthoma of Ferguson Smith, but the other features are less so. Generalized pruritic eruption of thousands of tiny disseminated 2 to 6 mm keratoacanthomas, ectropion, and involvement of the oral mucosa are more in favor of the generalized EK of Grzybowski. EK is an extremely rare condition. Since the
Fig. 1. Extensive, multiple, flesh-colored, 2 to 6 mm papules. Some appear follicular; some show central keratinous plugging. Lesions tend to coalesce, resulting in masked face and mild ectropion. 478
Journal of the American Academy of Dermatoiogy Volume 37, Number 3, Part 1
Brief communications 479
Fig. 2. Photomicrograph shows dome-shaped epidermal hyperplasia with central keratinous crater, epidermal lip, well-differentiated epidermal strands composed of keratinocytes with glassy appearance invading into dermis.
first description by Grzybowski 2 in 1950, only 27 additional cases (including the present case) have been reported. 324 This type of keratoacanthoma most c o m m o n l y affects patients in the fifth to seventh decades of life. The present patient is the youngest reported. Immunosuppression predisposes the patient to the development of a variety of neoplasms. Although the cause and pathogenesis of E K are unknown, altered immunity has been implicated. Multiple keratoacanthoma has a higher incidence in immunosuppressed patients and has been associated with leukemiaY leprosy, 26 kidney transplantation,27, 28 photochemotherapy,29 thermal bum, 30 and radiation therapy. 31 Of the 26 reported patients with EK, three had an associated internal malignancy, 7, 10, 16 two had latent syphilis, 4, 11 one had hemolytic anemia, 16 and one had a kidney transplantation.15 To our knowledge ours is the first case of E K in a patient with SLE who was receiving immunosuppressive therapy. REFERENCES
1. Ferguson Smith J. A case of multiple primary squamouscelled carcinomata of the skin in a young man, with spontaneous healing. Br J Dermatol 1934;46:267-72. 2. Grzybowski M. A case of peculiar generalized epithelial tumours of the skin. Br J Dermatol 1950;62:310-3. 3. Witten VH, Zak FG. Multiple, primary, self-healing prickle-cell epithelioma of the skin. Cancer 1952;5:53959. 4. Rossman RE, Freeman RG, Knox JM. Multiple kerato-
5. 6. 7.
8. 9. 10. 11. 12. 13.
14. 15. 16. 17.
acanthoma: a case study of the eruptive type with observations on pathogenesis. Arch Dermatol 1964;89:37481. Jolly HW, Carpenter CL. Multiple keratoacanthomata. Arch Dermatol 1966;93:348-53. Winkelmann RK, Brown J. Generalized eruptive keratoacanthoma. Arch Dermatol 1968;97:615-23. Weber G, Stetter H, Pliess G, et al. Assoziiertes Vorkommen von eruptiven keratoacanthomen, tubencarcinom und paramyeloblasten leukaemie. Arch Klin Exp Derm 1970;238:107-19. Tachi T, Kawashima Y, Eguchi K, et al. Eruptive keratoacanthoma. Hifu Rinsyo 1978;20:381-7. Balus L, Fazio M, Carducci M, et al. Une variet6 de kerato-acanthome multiple: le kerato-acanthome eruptif. Ann Dermatol Venereol 1981;108:995-1000. Snider BL, Benjamin DR. Eruptive keratoacanthoma with an internal malignant neoplasm. Arch Dermatol 1981;117:788-90. Sterry W, Steigleder GK, Pullmann H, et al. Eruptive keratoacanthoma. Hautarzt 1981;32:119-25. Yoshikawa K, Hirano S, Kato T, et al. A case of eruptive keratoacanthoma treated by oral etretinate. Br J Dermatol 1985;112:579-83. Blitstein-Willinger E, Haas N, Nurnberger F, et al. Immunological findings during treatment of multiple keratoacanthoma with etretinate. Br J Dermatol 1986; 114:109-16. Young SK, Larsen PE, Markowitz NR. Generalized eruptive keratoacanthoma. Oral Surg Oral Med Oral Pathol 1986;62:422-6. Washington CV, Mikhail GR. Eruptive keratoacanthoma en plaque in an immunosuppressed patient. J Dermatol Surg Oncol 1987;13:1357-60. Cabotin PR Vignon-Pennamen MD, Miclea JM, et al. Keratoacanthomes multiples eruptifs revelateurs d'un lymphome. Ann Dermatot Venereol 1989;116:860-2. Lloyd KM, Madsen DK, Lin PY. Grzybowski's eruptive
48t1
Journal of the American Academy of Dermatology September 1997
Brief communications
keratoacanthoma. J Am Acad Dermatol 1989; 16:1023-4. 18. Street ML, White JW, Gibson LE. Multiple keratoacanthomas treated with oral retinoids. J Am Acad Dermatol 1990;23:862-6. 19. Yell JA. Grzybowski's generalized eruptive keratoacanthoma. J R Soc Med 1991;84:170-1. 20. Laaff H, Mittelviejhans H, Wokalek H, et al. Eruptive keratoacanthome typ Grzybowski und ektropium. Hautarzt 1992;43:143-7. 21. Dangoisse C, Meyvisch K, Ledoux M. Multiple eruptive keratoacanthoma and immunity disorders. Dermatology 1993;186:313-6. 22. Kavanagh GM, Marshman G, Hanna MM. A case of Grzybowski's generalized eruptive keratoacanthomas. Australas J Dermatol 1995;36:83-5. 23. Jaber PW, Cooper PH, Greer KE. Generalized eruptive keratoacanthoma of Grzybowski. J Am Acad Dermatol 1993;29:299-304. 24. Czubak A, Kalbarczyk K, Maciejowska E, et al. Keratoacanthoma eruptivum varietas Grzybowski: coexistence with keratoacanthoma marginatum-centrifugum
25. 26. 27. 28. 29. 30. 31.
and typical solitary tumor [abstract]. J Am Acad Dermatol 1996;35:105. Degos R, Bernard J, Delort J, et al. Keratoacanthomes centrifuges dissemines. Bull Soc Fr Dermatol Syph 1967;74:417-9. Job CK. Keratoacanthoma associated with leprosy. Indian J Pathol Bacteriol 1963;6:160-2. Guillot B, Fesneau H, Mourad G, et al. Keratoacanthomes multiples sous ciclosporine [letter]. Presse Med 1990; 19:1286. Walder BK, Robertson MR, Jeremy D. Skin cancer and immunosuppression. Lancet 1971 ;2:1282-3. Sina B, Adrian RM. Multiple keratoacanthomas possibly induced by psoralens and ultraviolet A photochemotherapy. J Am Acad Dermatol 1983;9:686-8. Hendricks WM. Sudden appearance of multiple keratoacanthomas three weeks after thermal burn. Cutis 1991;17:110-2. Shaw JC, Storrs FJ, Everts E. Multiple keratoacanthomas after megavoltage radiation therapy. J Am Acad Dermatol 1990;23:1009-11.
Malignant atrophic papulosis (Degos' disease) involving three generations of a family Sara K. Katz, MD, Leslie J. Mudd, BA, and H e n r y H. Roenigk, Jr., M D
Malignant atrophic papulosis or D e g o s ' disease is a rare m u l t i s y s t e m vasculopathy o f u n k n o w n cause that affects the skin, gastrointestinal tract, and central nervous system. The characteristic skin lesions are multiple a s y m p t o m a t i c papules with an atrophic white scarlike center surrounded b y a telangiectatic border. Within weeks to years m o s t patients develop infarctions mainly in the gastrointestinal and nervous systems. Systemic i n v o l v e m e n t portends a fatal prognosis. There have, however, been reports of cases with only cutaneous manifestations and a favorable prognosis. 1-7 Although D e g o s ' disease is not thought to be a genetic disorder, there h a v e been seven previously reported familial cases (Table I). 1-6 We describe a familial clustering of D e g o s ' disease
From the Department of Dermatology, Northwestern University Medical School, Chicago. Reprint requests: Henry H. Roenigk, Jr., MD, Professor of Dermatology, Department of Dermatology, Northwestern UniversityMedicalSchool,222 E. SuperiorSt., Chicago,IL 60611. J Am Acad Dermatol 1997;37:480-4. Copyright © 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00 + 0 16/54/83209
Chicago, Illinois
T a b l e I. Reported cases of familial Degos' disease
Author(s)
2
2
1 (M)
2
2
0
2
2
0
6
2
0
2
2
0
2
2
0
5
1
1
6
3
1 (M)
No. of patients affected
Hall-Smith I (1969) Newton & Black 2 (1984) Moulin et al. 3 (1984) Kisch & Bmynzeel 4 (1984) Habbema, Kisch, Starink 5 (1986) Beljaards, Starink, Meuwissen 6 (1988) Beljaards, Starink, Meuwissen 6 (1988) Current study wE With.
Generations
No. of patients w/ systemic involvement (Sex)
Although the cause and pathogenesis of eruptive keratoacanthomas (EKs) are unknown, altered immunity has been implicated. We describe EK in a young woman with systemic lupus erythematosus (SLE) who was receiving immunosuppressive therapy. CASE REPORT
A 23-year-old white woman had a 4-month history of a progressive, generalized, pruritic eruption involving mainly the upper half of the body. The lesions began on her head, extended onto her neck and trunk, and were associated with painful intraoral lesions. There was no family history of similar skin lesions. She had a 6-year history of SLE with neurologic and renal involvement, for which she was receiving prednisolone, 30 mg/day, and cyclophosphamide, 100 mg/day. Examination disclosed a papular eruption on the face, neck, upper trunk, tongue, hard and soft palates,
From the Department of Dermatology, A1-Jazeera Hospital. Reprint requests: M. Wag@ Dessoukey, MD, Department of Dermatology, A1-Jazeera Hospital, EO. Box 2427, Abu Dhabi, United Arab Emirates. J Am Acad Dermatol 1997;37:478-80. Copyright © 1997 by the American Academy of Dermatology, Inc. 0190-9622/97/$5.00 + 0 16/54/82796
and nasal mucosa. The individual papules were 2 to 6 mm in diameter, flesh-colored, and firm. Some appeared to be follicular, and some contained a central keratinous crater. The face was severely affected (Fig. 1) with lesions tending to coalesce, resulting in ectropion. Multiple skin biopsy specimens showed domeshaped epidermal hyperplasia with a central crater filled with a hyperkeratotic and parakeratotic stratum corneum, epidermal lip, and well-differentiated epidermal strands composed of keratinocytes with a glassy appearance invading into the dermis (Fig. 2). Eight weeks after a regimen of isotretinoin, 1 mg/kg per day, all skin and mucosal lesions cleared with no recurrence for more than 3 years. DISCUSSION
Keratoacanthoma can occur as solitary or multiple lesions. Variants of multiple keratoacanthoma include the Ferguson Smith typO and EK of Grzybowski. 2 The age of our patient is more in keeping with multiple keratoacanthoma of Ferguson Smith, but the other features are less so. Generalized pruritic eruption of thousands of tiny disseminated 2 to 6 mm keratoacanthomas, ectropion, and involvement of the oral mucosa are more in favor of the generalized EK of Grzybowski. EK is an extremely rare condition. Since the
Fig. 1. Extensive, multiple, flesh-colored, 2 to 6 mm papules. Some appear follicular; some show central keratinous plugging. Lesions tend to coalesce, resulting in masked face and mild ectropion. 478
Journal of the American Academy of Dermatoiogy Volume 37, Number 3, Part 1
Brief communications 479
Fig. 2. Photomicrograph shows dome-shaped epidermal hyperplasia with central keratinous crater, epidermal lip, well-differentiated epidermal strands composed of keratinocytes with glassy appearance invading into dermis.
first description by Grzybowski 2 in 1950, only 27 additional cases (including the present case) have been reported. 324 This type of keratoacanthoma most c o m m o n l y affects patients in the fifth to seventh decades of life. The present patient is the youngest reported. Immunosuppression predisposes the patient to the development of a variety of neoplasms. Although the cause and pathogenesis of E K are unknown, altered immunity has been implicated. Multiple keratoacanthoma has a higher incidence in immunosuppressed patients and has been associated with leukemiaY leprosy, 26 kidney transplantation,27, 28 photochemotherapy,29 thermal bum, 30 and radiation therapy. 31 Of the 26 reported patients with EK, three had an associated internal malignancy, 7, 10, 16 two had latent syphilis, 4, 11 one had hemolytic anemia, 16 and one had a kidney transplantation.15 To our knowledge ours is the first case of E K in a patient with SLE who was receiving immunosuppressive therapy. REFERENCES
1. Ferguson Smith J. A case of multiple primary squamouscelled carcinomata of the skin in a young man, with spontaneous healing. Br J Dermatol 1934;46:267-72. 2. Grzybowski M. A case of peculiar generalized epithelial tumours of the skin. Br J Dermatol 1950;62:310-3. 3. Witten VH, Zak FG. Multiple, primary, self-healing prickle-cell epithelioma of the skin. Cancer 1952;5:53959. 4. Rossman RE, Freeman RG, Knox JM. Multiple kerato-
5. 6. 7.
8. 9. 10. 11. 12. 13.
14. 15. 16. 17.
acanthoma: a case study of the eruptive type with observations on pathogenesis. Arch Dermatol 1964;89:37481. Jolly HW, Carpenter CL. Multiple keratoacanthomata. Arch Dermatol 1966;93:348-53. Winkelmann RK, Brown J. Generalized eruptive keratoacanthoma. Arch Dermatol 1968;97:615-23. Weber G, Stetter H, Pliess G, et al. Assoziiertes Vorkommen von eruptiven keratoacanthomen, tubencarcinom und paramyeloblasten leukaemie. Arch Klin Exp Derm 1970;238:107-19. Tachi T, Kawashima Y, Eguchi K, et al. Eruptive keratoacanthoma. Hifu Rinsyo 1978;20:381-7. Balus L, Fazio M, Carducci M, et al. Une variet6 de kerato-acanthome multiple: le kerato-acanthome eruptif. Ann Dermatol Venereol 1981;108:995-1000. Snider BL, Benjamin DR. Eruptive keratoacanthoma with an internal malignant neoplasm. Arch Dermatol 1981;117:788-90. Sterry W, Steigleder GK, Pullmann H, et al. Eruptive keratoacanthoma. Hautarzt 1981;32:119-25. Yoshikawa K, Hirano S, Kato T, et al. A case of eruptive keratoacanthoma treated by oral etretinate. Br J Dermatol 1985;112:579-83. Blitstein-Willinger E, Haas N, Nurnberger F, et al. Immunological findings during treatment of multiple keratoacanthoma with etretinate. Br J Dermatol 1986; 114:109-16. Young SK, Larsen PE, Markowitz NR. Generalized eruptive keratoacanthoma. Oral Surg Oral Med Oral Pathol 1986;62:422-6. Washington CV, Mikhail GR. Eruptive keratoacanthoma en plaque in an immunosuppressed patient. J Dermatol Surg Oncol 1987;13:1357-60. Cabotin PR Vignon-Pennamen MD, Miclea JM, et al. Keratoacanthomes multiples eruptifs revelateurs d'un lymphome. Ann Dermatot Venereol 1989;116:860-2. Lloyd KM, Madsen DK, Lin PY. Grzybowski's eruptive
48t1
Journal of the American Academy of Dermatology September 1997
Brief communications
keratoacanthoma. J Am Acad Dermatol 1989; 16:1023-4. 18. Street ML, White JW, Gibson LE. Multiple keratoacanthomas treated with oral retinoids. J Am Acad Dermatol 1990;23:862-6. 19. Yell JA. Grzybowski's generalized eruptive keratoacanthoma. J R Soc Med 1991;84:170-1. 20. Laaff H, Mittelviejhans H, Wokalek H, et al. Eruptive keratoacanthome typ Grzybowski und ektropium. Hautarzt 1992;43:143-7. 21. Dangoisse C, Meyvisch K, Ledoux M. Multiple eruptive keratoacanthoma and immunity disorders. Dermatology 1993;186:313-6. 22. Kavanagh GM, Marshman G, Hanna MM. A case of Grzybowski's generalized eruptive keratoacanthomas. Australas J Dermatol 1995;36:83-5. 23. Jaber PW, Cooper PH, Greer KE. Generalized eruptive keratoacanthoma of Grzybowski. J Am Acad Dermatol 1993;29:299-304. 24. Czubak A, Kalbarczyk K, Maciejowska E, et al. Keratoacanthoma eruptivum varietas Grzybowski: coexistence with keratoacanthoma marginatum-centrifugum
25. 26. 27. 28. 29. 30. 31.
and typical solitary tumor [abstract]. J Am Acad Dermatol 1996;35:105. Degos R, Bernard J, Delort J, et al. Keratoacanthomes centrifuges dissemines. Bull Soc Fr Dermatol Syph 1967;74:417-9. Job CK. Keratoacanthoma associated with leprosy. Indian J Pathol Bacteriol 1963;6:160-2. Guillot B, Fesneau H, Mourad G, et al. Keratoacanthomes multiples sous ciclosporine [letter]. Presse Med 1990; 19:1286. Walder BK, Robertson MR, Jeremy D. Skin cancer and immunosuppression. Lancet 1971 ;2:1282-3. Sina B, Adrian RM. Multiple keratoacanthomas possibly induced by psoralens and ultraviolet A photochemotherapy. J Am Acad Dermatol 1983;9:686-8. Hendricks WM. Sudden appearance of multiple keratoacanthomas three weeks after thermal burn. Cutis 1991;17:110-2. Shaw JC, Storrs FJ, Everts E. Multiple keratoacanthomas after megavoltage radiation therapy. J Am Acad Dermatol 1990;23:1009-11.
Malignant atrophic papulosis (Degos' disease) involving three generations of a family Sara K. Katz, MD, Leslie J. Mudd, BA, and H e n r y H. Roenigk, Jr., M D
Malignant atrophic papulosis or D e g o s ' disease is a rare m u l t i s y s t e m vasculopathy o f u n k n o w n cause that affects the skin, gastrointestinal tract, and central nervous system. The characteristic skin lesions are multiple a s y m p t o m a t i c papules with an atrophic white scarlike center surrounded b y a telangiectatic border. Within weeks to years m o s t patients develop infarctions mainly in the gastrointestinal and nervous systems. Systemic i n v o l v e m e n t portends a fatal prognosis. There have, however, been reports of cases with only cutaneous manifestations and a favorable prognosis. 1-7 Although D e g o s ' disease is not thought to be a genetic disorder, there h a v e been seven previously reported familial cases (Table I). 1-6 We describe a familial clustering of D e g o s ' disease
From the Department of Dermatology, Northwestern University Medical School, Chicago. Reprint requests: Henry H. Roenigk, Jr., MD, Professor of Dermatology, Department of Dermatology, Northwestern UniversityMedicalSchool,222 E. SuperiorSt., Chicago,IL 60611. J Am Acad Dermatol 1997;37:480-4. Copyright © 1997 by the AmericanAcademyof Dermatology,Inc. 0190-9622/97/$5.00 + 0 16/54/83209
Chicago, Illinois
T a b l e I. Reported cases of familial Degos' disease
Author(s)
2
2
1 (M)
2
2
0
2
2
0
6
2
0
2
2
0
2
2
0
5
1
1
6
3
1 (M)
No. of patients affected
Hall-Smith I (1969) Newton & Black 2 (1984) Moulin et al. 3 (1984) Kisch & Bmynzeel 4 (1984) Habbema, Kisch, Starink 5 (1986) Beljaards, Starink, Meuwissen 6 (1988) Beljaards, Starink, Meuwissen 6 (1988) Current study wE With.
Generations
No. of patients w/ systemic involvement (Sex)