- Email: [email protected]
Incontinentia pigmenti: Three cases with unusual features
Sahn and Davidson
10.
11. 12. 13. 14.
normal embryonic development on microinjection into postimplantation mouse embryos. Nature 1985;318:182. Katz M, Weinrauch L. Differentiating vesicular linear lichen planus and lichen striatus. Cutis 1987;40:151-3. Kalter DC, Griffiths WA, AthertonDJ. Linear and whorled nevoid hypermelanosis. J AM ACAD DERMATOL 1988; 19:1037-44. Richarz U, Hubner J, Schmeel A, et al. StrHirer Lupus erythematodes im Verlauf der Blaschko-Linien. Hautarzt 1986;37:335-7. Heid E, Bekkali A, Lazrak B, et a!. Neurofibromes, poliose et vitiligo. Ann Dermatol Venereal 1978;105:645-6. Crovato F, Desirello G, Nazzari G, et a1. Linear pemphigus after x-ray irradiation. Dermatologica 1989; 179:135-6.
Journal of the American Academy of Dermatology November 1994 15. Atherton DJ, Kahana M, Russel-Jones R. Naevoid psoriasis. Br J Dermato11989;120:837-41. 16. Prigent F, Cavelier-Balloy B, Lemarchand-Venencie F, et a!. Lichen nitidus !ineare. Ann Dermatol Venereol1989; 116:814-5. 17. Taieb A, EI Youbi A, Grosshans E, et a1. Lichen striatus: a Blaschko linear acquired inflammatory skin eruption. J AM ACAD DERMATOL 1991;25:637-42. 18. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J AM ACAD DERMATOL 1987;16:899-906.
Incontinentia pigmenti: Three cases with unusual features Eleanor E. Sahn, MD,a and Lesly S. Davidson, MDb Charleston, South Carolina, and Norfolk, Virginia Three patients with incontinentia pigmenti are described who illustrate some of the unusual features of this uncommon genodermatosis. One child with skin, ophthalmologic, and dental findings had atrophic, hypopigmented streaks on her legs by the age of 2V2 years that were consistent with the fourth stage of incontinentia pigmenti. This child's mother, who also had incontinentia pigmenti, had identical atrophic streaks on the legs, as well as irregular axillary pigmentation, scarring alopecia, and dental abnormalities. A second child is described who had annular blisters, persistent verrucous plaques, whorled hyperpigmentation, and dental abnormalities. (J AM ACAD DERMATOL 1994;31:852-7.) Incontinentia pigmenti (IP) (Bloch-Sulzberger syndrome) is an uncommon genodermatosis characterized by four cutaneous stages and frequent association with dental, ocular, and central nervous system anomalies. We describe three patients: a white child and her mother, whose disease represents the familial aspect of IP, and a black child, whose disease was the result of a new mutation. Some unusual clinical features were noted in each patient.
From the Departments of Dermatology and Pediatrics, Medical University of South Carolina,a and the Department of Pediatrics, Eastern Virginia Medical School. b Reprint requests: Eleanor E. Sahn, MD, Departments of Dermatology and Pediatrics, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425-2215. Copyright © 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55290
852
CASE REPORTS
Case 1 A white newborn girl had erythematous papules and vesicles in a linear pattern on the extremities. These progressed to crusted and verrucous papules during the first few weeks oflue. The child was born at term by cesarean section without further complications, and had no siblings. Examination at 3 weeks of age revealed numerous vesicles and crusted papules with an erythematous base on the extremities with rare scattered lesions on the upper portion of the back, trunk, and pinna. The mucous membranes, hair, and nails were normal. One week later vesicles appeared on the abdomen and a linear, verrucous plaque developed at the base of one fingernail (Fig. 1). Ophthalmologic examination at 6 weeks of age revealed unilateral retinal vascular telangiectases with dot hemorrhages and a nonpatent lacrimal duct. The hemorrhages did not progress. The nonpatent lacrimal duct was
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2
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Fig. 1. Case 1. Linear, verrucous papule on finger at age 7 weeks.
Fig. 3. Case 2. Linear hyperpigrnentation in axilla at age 21 years. pegged tooth, the left central lower incisor, developed. The remainder of the dental examination at age 1Y2 years was normal. At 2Y2 years of age the child had no cutaneous findings other than the hypopigmented atrophic streaks on the legs (Fig. 2).
Case 2
Fig. 2. Case 1. Atrophic, hyperpigmented streaks on legs at age 3 years. corrected surgically. The result of a complete neurologic examination at 7 weeks of age was normal. Vesicle formation continued until 7 weeks of age. Erythematous streaks persisted and progressed to linear, hypopigmented, atrophic depressions by 3Y2 months of age. The verrucous plaque resolved by 3 months of age. The patient had delayed dentition but eventually one
The 21-year-old mother of patient 1 had been born with vesicles on both arms and legs, and a diagnosis of IP had been made. The patient had a congenital area of scarring alopecia on the vertex of the scalp. As her teeth erupted, she had partial anodontia (missing two upper incisors) and pegged deformity of three teeth. Cosmetic dentistry was performed during childhood. The patient had a history of one spontaneous abortion of a male fetus at 5 months' gestation before the birth of her daughter with IP (patient 1). Her mother (the maternal grandmother of patient 1) was normal and had never had blistering but had had one spontaneous abortion of a fetus whose sex was unknown. Examination revealed a patch oflinear and reticulated hyperpigmentation in the left axilla (Fig. 3), and atrophic, hypopigmented, linear streaks on the legs resembling
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Journal of the American Academy of Dermatology November 1994
Fig. 4. Case 3. Annular vesicles and hyperpigmentation of extremity at age 9 weeks.
inal delivery at term without complications. Her parents
Fig. 5. Case 3. Whorls and streaks of hyperpigmentation follow Blaschko's lines at age 23 months.
those of her daughter, shown in Fig. 2. The vertex of the scalp contained an area of scarring alopecia.
Case 3 A black newborn girl had a diffuse vesicular eruption with crusting. The infant was born by spontaneous vag-
and two sisters were in good health without skin, dental, or neurologic problems. Her mother had had one spontaneous abortion ofa conceptus reported to have been a boy. Examination of the infant at 5 days of age revealed vesicles on the face, trunk, and extremities, some in an annular configuration (Fig. 4). There were linear streaks and whorls of hyperpigmentation on the trunk and extremities (Fig. 5). The mucous membranes, hair, and nails were normal. Examination of her mother and sisters revealed no stigmata of IP. New crops ofvesicles and blisters continued to develop for several months. The result of an ophthalmologic examination was normal but a neurologic examination revealed mild proximal hypotonia. An electroencephalographic examination showed no abnormalities. At 5 months of age, the patient's skin had features of three stages of IP: vesicles were present on the dorsa ofthe toes; verrucous papules were present on the dorsa of the hands, feet, and one knee; and hyperpigmented, reticulated macules in a swirled pattern were present over the abdomen, back, and proximal extremities. Blistering persisted until the end of the first year. The verrucous papules and plaques gradually resolved, with only a 1 cm verrucous plaque remaining on the knee by age 2 years. At that time, the streaks and swirls of hyperpigmentation were unchanged on the trunk and proximal extremities. Dentition was delayed and at 2 years of age, the patient had one pegged central incisor and partial anodontia (Fig. 6).
Histopathologic findings Examination of multiple skin biopsy specimens from patients 1 and 3 revealed the typical histopathologic findings of the various stages of IP.l The inflammatory, ve-
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2
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Fig. 6. Case 3. Pegged central incisor with partial anodontia at age 23 months.
siculobullous first stage of IP showed eosinophilic spongiosis, dyskeratotic keratinocytes, and a dense dermal infiltrate composed of eosinophils and mononuclear cells. The Tzanck preparation performed on a vesicle from patient 3 showed sheets of eosinophils with no multinucleated giant cells. Extracellular deposition of granular major basic protein has been demonstrated in vesicles OfIP,2 suggesting a pathogenic role for eosinophils in the disease. The verrucous second stage of IP typically shows acanthosis, irregular papillomatosis, and hyperkeratosis. I Dyskeratotic cells may be more pronounced than in the first stage. Basal cells may have vacuolization with decreased melanin. A mild chronic inflammatory infiltrate with melanophages may extend from the dermis into the epidermis. The hyperpigmented third stage of IP shows melanophages in the dermis and corresponding diminution of pigment in the basal layer with vacuolization and degeneration.! The atrophic fourth stage of IP characteristically shows scarring with loss of melanocytes and cutaneous appendages.! There may be round, eosinophilic colloid bodies in the papillary dermis 3 and abnormal cutaneous nerves extending into the epidermis. 4,5
DISCUSSION
IP is an uncommon genodermatosis characterized by four overlapping cutaneous stages and frequent neuroectodermal defects. Vesicular, verrucous, hyperpigmented, and atrophic manifestations may be seen. IP is presumed to result from an X-linked dominant mutation that is usually lethal in utero in
malefetuese. A female/male predominance of greater than 35:1 has been estimated from large statistical analyses. 6 The gene has been mapped to the Xpll band of the X chromosome.? There are rare reports of IP in twin girls. s The few cases reported in male patients were hypothesized to have occurred by spontaneous half-chromatid mutation. Several recent cases ofmale infants born with IP and family histories of IP have challenged this explanation. 9 Several cases of IP have been reported in male infants with Klinefelter's syndrome (47,XXYkaryotype).lo-t2Thedistribution onp by race is unknown. In Carney's series, 13 at least 24 black patients of 65 3 patients with IP were documented. The four stages ofIP may be concurrent (as in our patient 3) or some of the stages may occur in utero. The first stage usually begins within 2 weeks of birth but in rare cases may appear after the first year of life. 13 Itconsists oflinear erythema and vesicles that are most often located on the extremities. Crops of vesicles may be recurrent, as in our third case, and may persist until 6 years of age. 14 Stage 2 most often begins between the second and sixth weeks of life l3 and consists of verrucous papules that are often arranged linearly and found predominantly on the extremities. The lesions persist for 6 to 12 months 6 and then resolve spontaneously. However, in one recent report, a patient with IP had continuing development of new verrucous lesions, one of which resulted in squamous cell carcinoma in situ at the age of 25 years. IS
856 Sahn and Davidson Stage 3, with age of onset most frequently between 12 and 26 weeks,!3 is characterized by whorled, browntoslate-brownhyperpigmentedmacules and patches on the trunk; the extremities are less often affected. These streaky macules tend to follow Blaschko's lines, as seen clearlyin our third case. The hyperpigmentation may occur in previously unaffected areas and may last many years. 13, 15 Residual axillary hyperpigmentation, as seen in our case 2, has been reported as a subtle marker oflP in otherwise normal patients.l 6 Stage 4 disease, if present, is characterized by streaky hypopigmentation and atrophy on the lower extremities, as seen in cases 1 and 2. 5,8, 17 This stage may be underreported because it was not originally described. Clinicians should search for atrophic, hypopigmented streaks in mothers of infants in whom a diagnosis of IP is suspected because these streaks may be difficult to see. 9 Hair abnormalities seen with IP include vertex alopecia, hair loss from other body sites, and woolly haired nevus. 16 Nail changes in IP include longitudinal and transverse striations, and subungual hyperkeratotic tumors,18 often in association with scalloped bone deformities of the distal phalanges. 19 Partial sweat gland aplasia also has been noted. 6 Major dental abnormalities occur in 65% of patients; the majority of these are identifiable by the age of 2 years,13 The most common are partial anodontia (43%) and pegged teeth (30%), as were seen in each of our patients. Eye anomalies have been reported in 25% to 35% of patients6; strabismus is the most common (18%).20 Retinal detachment and a fibrovascular retrolental membrane are the most frequently reported intraocular abnormalities. 2o Early diagnosis of the retinopathy of IP may allow successful treatment by photocoagulation or cryotherapy to prevent retinal detachment and blindness. 21 ,22 Cataracts, nystagmus, and optic atrophy have also been reported. 13, 23 Asymmetric eye involvement is usual; the affected eye often shows microphthalmia. 24 The central nervous system is affected in up to 33% ofpatients. 6The most commonly reported central nervous system abnormalities are seizures (13%), mental retardation (12%), spastic paralysis (11%), microcephaly, and motor retardation. 13, 23 A variety ofstructural anomalies have also been reported, but their incidences may be no greater than that in the general population. 6 There may be an increased incidence of certain childhood malignancies in IP, perhaps from chromosomal in-
Journal of the American Academy of Dermatology November 1994
stability.25 In one study a cellular defect was noted in polymorphonuclear chemotaxis in six of eight patients with IP.26 , The differential diagnosis of infants with IP has been thoroughly discussed in recent publications. 6,27 Management ofthe newborn infant with IP includes neurologic examination with additional testing on the basis of initial findings. Ophthahnologic examination should be done within 1 month of birth and should be repeated at 3-month intervals until 1 year of age. Mothers and sisters of patients with IP should have careful examinations for cutaneous lesions and for ophthalmologic and dental abnormalities. All patients with IP should have dental examinations by the age of 2 years to evaluate partial anodontia and tooth spacing. Acid-etched restorations of pegged teeth are possible. 6 REFERENCES 1. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:93-95. 2. Thyresson NH, Goldberg NC, Tye MJ, et al. Localization of eosinophil granule major basic protein in incontinentia pigmenti. POOiatr Dermatol 1991;8:102-6. 3. Zillikens D, Mehringer A, Lechner W, et al. Hypo- and hyperpigmentOO areas in incontinentia pigmenti: light and electron microscopic studies. Am J Dermatopathol 1991; 13:57-62. 4. Worret WI, Nordquist RE, Burgdorf WHo Abnormal cutaneous nerves inincontinentia pigmenti. UltrastructPathol 1988;12:449-54. 5. Worret WI. Hypo- and hyperpigmentOO areas in incontinentia pigmenti. Am J DermatopathoI1991;13:629-30. 6. Cohen BA. Incontinentia pigmenti. Neurol Clin 1987; 5:361-77. 7. Cannizzaro LA, Heckt F. Gene for incontinentia pigmenti maps to band Xp11 with an (X: 10) (P 112) translocation. Clin Genet 1987;32:66-9. 8. Tanaka K, Kambe N, Fujita M. Incontinentia pigmenti in identical twins with separate skin and neurological disorders. Acta Derm Venereol (Stockh) 1990;70:267-8. 9. Garcia-Dorado J, de Unamuno P, Fernandez-Uiez E, et al. Incontinentia pigmenti: XXV male with a family history. Clin Genet 1990;38:128-38. 10. Prendiville JS, Gorski JL, Stein CK, et al. Incontinentia pigmenti in a male infant with Klinefelter syndrome. JAM ACAD DERMATOL 1989;20:937-40. 11. Kunze J, Frenzel UH, Huttig E, et al. Klinefelter's syndrome and incontinentia pigmenti Bloch-Sulzberger. Hum Genet 1977;35:237-240. 12. Ormerod AD, White MI, McKay E, et al. Incontinentia pigmenti in a boy with Klinefelter's syndrome. J Moo Genet 1987;24:439-41. 13. Carney RG. Incontinentia pigmenti: a world statistical analysis. Arch DermatoI1976;1l2:535-542. 14. O'Brien JE, Feingold M. Incontinentia pigmenti: a longitudinal study. Am J Dis Child 1985;139:711-2. 15. Korstanje MJ, Bessems PJMJ. Incontinentia pigmenti with hyperkeratotic lesions in adulthood and possible squamous cell carcinoma. Dermatologica 1991;183:234-6.
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2 16. Wiklund DA, Weston WL. Incontinentia pigmenti: a fourgeneration study. Arch DermatoI1980;116:701-3. 17. Nazzaro V, Brusasco A, Gelmetti C, et al. Hypochromic reticulated streaks in incontinentia pigmenti: an immunohistochemical and ultrastructural study. Pediatr Dermatol 1990;7:174-8. 18. Mascaro JM, Palou J, Vives P. Painful subungual keratotic tumors in incontinentia pigmenti. JAM ACAD DERMATOL 1985;13:913-8. 19. Simmons DA, Kegel MF, Scher RK, et aL Subungual tumors in incontinentia pigmenti. Arch Dermatol 1986; 122: 1431-4. 20. Heathcote JG, Schoales BA, Willis NR. Incontinentia pigmenti (Bloch-Sulzberger syndrome): a case report and review of the ocular pathological features. Can J Ophthalmol 1991;26:229-37. 21. Rahi J, Hungerford J. Early diagnosis ofthe retinopathy of incontinentia pigmenti: successful treatment by cryotherapy. Br J Ophthalmol 1990;74:377-9.
Burden et al. 857 22. Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti. Am J OphthalmoI1990;110:701-2. 23. Damstra RJ, Van Duren JA, Van Ginkel CWJ. Incontinentia pigmenti (Bloch-Sulzberger). Br J Dermatol1991; 125:280-1. 24. Catalano, RA. Incontinentia pigmenti. Am J Ophthalmol 1990;110:696-9. 25. Roberts WM, Jenkins JJ, Moorhead EL, et aL Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer 1988;62:2370-2. 26. Menni S, Piccinno R, Biolchini A, et aL Immunologic investigations in eight patients with incontinentia pigmenti. Pediatr DermatoI1990;7:275-7. 27. Mallory SB, Krafchik BR. Incontinentia pigmenti: the syndrome page. Pediatr DermatoI1992;9:304-8.
IgA anticardiolipin antibodies associated with Henoch-Schonlein purpura A. David Burden, MRcp,a Ian W. Gibson, MBChB,b R. Stuart C. Rodger, FRCP,c and David M. Tillman, MRcpa Glasgow, Scotland Henoch-SchOnlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-SchOnlein purpura. A potential role for IgA autoantibodies in Henoch-SchOnlein purpura needs to be further explored. (J AM ACAD DERMATOL 1994;31:857-60.) Antiphospholipid antibodies are a heterogeneous group of immunoglobulins of the IgG, IgM, or IgA classes directed against a variety of phospholipid antigens. They are important risk factors for arterial and venous thrombosis and are also associated with recurrent fetal loss, thrombocytopenia, and an autoimmune postpartum syndrome. Various cutaneous manifestations have also been reported, such as
From the University of Glasgow Departments of Dennatology,' Pathology,b and Renal Medicine,c Western Infirmary. Reprint requests: A. David Burden, MRCP, University Department of Dermatology, Western Infirmary, Glasgow GIl 6NT, Scotland, United Kingdom. Copyright @ 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55289
livedo reticularis, 1 necrotizing purpura,2 and widespread cutaneous necrosis 3; these have recently been reviewed. 4 We report for the first time the finding of IgA anticardiolipin antibodies CACAs) in a patient with Henoch-Schonlein purpura CHSP). CASE REPORT A 51-year-old man had palpable purpura for 4 months on the legs (Fig. 1). Two years before he had a cerebrovascular accident that resulted in a right-sided hemiparesis. A computed tomographic scan at that time revealed infarction in the left middle cerebral artery territory. The patient had been taking low-dose aspirin since the cerebrovascular accident but was taking no other medication. His general health was otherwise good. In particular, he had no joint pains or abdominal symptoms and could recall no recent sore throat.
10.
11. 12. 13. 14.
normal embryonic development on microinjection into postimplantation mouse embryos. Nature 1985;318:182. Katz M, Weinrauch L. Differentiating vesicular linear lichen planus and lichen striatus. Cutis 1987;40:151-3. Kalter DC, Griffiths WA, AthertonDJ. Linear and whorled nevoid hypermelanosis. J AM ACAD DERMATOL 1988; 19:1037-44. Richarz U, Hubner J, Schmeel A, et al. StrHirer Lupus erythematodes im Verlauf der Blaschko-Linien. Hautarzt 1986;37:335-7. Heid E, Bekkali A, Lazrak B, et a!. Neurofibromes, poliose et vitiligo. Ann Dermatol Venereal 1978;105:645-6. Crovato F, Desirello G, Nazzari G, et a1. Linear pemphigus after x-ray irradiation. Dermatologica 1989; 179:135-6.
Journal of the American Academy of Dermatology November 1994 15. Atherton DJ, Kahana M, Russel-Jones R. Naevoid psoriasis. Br J Dermato11989;120:837-41. 16. Prigent F, Cavelier-Balloy B, Lemarchand-Venencie F, et a!. Lichen nitidus !ineare. Ann Dermatol Venereol1989; 116:814-5. 17. Taieb A, EI Youbi A, Grosshans E, et a1. Lichen striatus: a Blaschko linear acquired inflammatory skin eruption. J AM ACAD DERMATOL 1991;25:637-42. 18. Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J AM ACAD DERMATOL 1987;16:899-906.
Incontinentia pigmenti: Three cases with unusual features Eleanor E. Sahn, MD,a and Lesly S. Davidson, MDb Charleston, South Carolina, and Norfolk, Virginia Three patients with incontinentia pigmenti are described who illustrate some of the unusual features of this uncommon genodermatosis. One child with skin, ophthalmologic, and dental findings had atrophic, hypopigmented streaks on her legs by the age of 2V2 years that were consistent with the fourth stage of incontinentia pigmenti. This child's mother, who also had incontinentia pigmenti, had identical atrophic streaks on the legs, as well as irregular axillary pigmentation, scarring alopecia, and dental abnormalities. A second child is described who had annular blisters, persistent verrucous plaques, whorled hyperpigmentation, and dental abnormalities. (J AM ACAD DERMATOL 1994;31:852-7.) Incontinentia pigmenti (IP) (Bloch-Sulzberger syndrome) is an uncommon genodermatosis characterized by four cutaneous stages and frequent association with dental, ocular, and central nervous system anomalies. We describe three patients: a white child and her mother, whose disease represents the familial aspect of IP, and a black child, whose disease was the result of a new mutation. Some unusual clinical features were noted in each patient.
From the Departments of Dermatology and Pediatrics, Medical University of South Carolina,a and the Department of Pediatrics, Eastern Virginia Medical School. b Reprint requests: Eleanor E. Sahn, MD, Departments of Dermatology and Pediatrics, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425-2215. Copyright © 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55290
852
CASE REPORTS
Case 1 A white newborn girl had erythematous papules and vesicles in a linear pattern on the extremities. These progressed to crusted and verrucous papules during the first few weeks oflue. The child was born at term by cesarean section without further complications, and had no siblings. Examination at 3 weeks of age revealed numerous vesicles and crusted papules with an erythematous base on the extremities with rare scattered lesions on the upper portion of the back, trunk, and pinna. The mucous membranes, hair, and nails were normal. One week later vesicles appeared on the abdomen and a linear, verrucous plaque developed at the base of one fingernail (Fig. 1). Ophthalmologic examination at 6 weeks of age revealed unilateral retinal vascular telangiectases with dot hemorrhages and a nonpatent lacrimal duct. The hemorrhages did not progress. The nonpatent lacrimal duct was
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2
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Fig. 1. Case 1. Linear, verrucous papule on finger at age 7 weeks.
Fig. 3. Case 2. Linear hyperpigrnentation in axilla at age 21 years. pegged tooth, the left central lower incisor, developed. The remainder of the dental examination at age 1Y2 years was normal. At 2Y2 years of age the child had no cutaneous findings other than the hypopigmented atrophic streaks on the legs (Fig. 2).
Case 2
Fig. 2. Case 1. Atrophic, hyperpigmented streaks on legs at age 3 years. corrected surgically. The result of a complete neurologic examination at 7 weeks of age was normal. Vesicle formation continued until 7 weeks of age. Erythematous streaks persisted and progressed to linear, hypopigmented, atrophic depressions by 3Y2 months of age. The verrucous plaque resolved by 3 months of age. The patient had delayed dentition but eventually one
The 21-year-old mother of patient 1 had been born with vesicles on both arms and legs, and a diagnosis of IP had been made. The patient had a congenital area of scarring alopecia on the vertex of the scalp. As her teeth erupted, she had partial anodontia (missing two upper incisors) and pegged deformity of three teeth. Cosmetic dentistry was performed during childhood. The patient had a history of one spontaneous abortion of a male fetus at 5 months' gestation before the birth of her daughter with IP (patient 1). Her mother (the maternal grandmother of patient 1) was normal and had never had blistering but had had one spontaneous abortion of a fetus whose sex was unknown. Examination revealed a patch oflinear and reticulated hyperpigmentation in the left axilla (Fig. 3), and atrophic, hypopigmented, linear streaks on the legs resembling
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Journal of the American Academy of Dermatology November 1994
Fig. 4. Case 3. Annular vesicles and hyperpigmentation of extremity at age 9 weeks.
inal delivery at term without complications. Her parents
Fig. 5. Case 3. Whorls and streaks of hyperpigmentation follow Blaschko's lines at age 23 months.
those of her daughter, shown in Fig. 2. The vertex of the scalp contained an area of scarring alopecia.
Case 3 A black newborn girl had a diffuse vesicular eruption with crusting. The infant was born by spontaneous vag-
and two sisters were in good health without skin, dental, or neurologic problems. Her mother had had one spontaneous abortion ofa conceptus reported to have been a boy. Examination of the infant at 5 days of age revealed vesicles on the face, trunk, and extremities, some in an annular configuration (Fig. 4). There were linear streaks and whorls of hyperpigmentation on the trunk and extremities (Fig. 5). The mucous membranes, hair, and nails were normal. Examination of her mother and sisters revealed no stigmata of IP. New crops ofvesicles and blisters continued to develop for several months. The result of an ophthalmologic examination was normal but a neurologic examination revealed mild proximal hypotonia. An electroencephalographic examination showed no abnormalities. At 5 months of age, the patient's skin had features of three stages of IP: vesicles were present on the dorsa ofthe toes; verrucous papules were present on the dorsa of the hands, feet, and one knee; and hyperpigmented, reticulated macules in a swirled pattern were present over the abdomen, back, and proximal extremities. Blistering persisted until the end of the first year. The verrucous papules and plaques gradually resolved, with only a 1 cm verrucous plaque remaining on the knee by age 2 years. At that time, the streaks and swirls of hyperpigmentation were unchanged on the trunk and proximal extremities. Dentition was delayed and at 2 years of age, the patient had one pegged central incisor and partial anodontia (Fig. 6).
Histopathologic findings Examination of multiple skin biopsy specimens from patients 1 and 3 revealed the typical histopathologic findings of the various stages of IP.l The inflammatory, ve-
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855
Fig. 6. Case 3. Pegged central incisor with partial anodontia at age 23 months.
siculobullous first stage of IP showed eosinophilic spongiosis, dyskeratotic keratinocytes, and a dense dermal infiltrate composed of eosinophils and mononuclear cells. The Tzanck preparation performed on a vesicle from patient 3 showed sheets of eosinophils with no multinucleated giant cells. Extracellular deposition of granular major basic protein has been demonstrated in vesicles OfIP,2 suggesting a pathogenic role for eosinophils in the disease. The verrucous second stage of IP typically shows acanthosis, irregular papillomatosis, and hyperkeratosis. I Dyskeratotic cells may be more pronounced than in the first stage. Basal cells may have vacuolization with decreased melanin. A mild chronic inflammatory infiltrate with melanophages may extend from the dermis into the epidermis. The hyperpigmented third stage of IP shows melanophages in the dermis and corresponding diminution of pigment in the basal layer with vacuolization and degeneration.! The atrophic fourth stage of IP characteristically shows scarring with loss of melanocytes and cutaneous appendages.! There may be round, eosinophilic colloid bodies in the papillary dermis 3 and abnormal cutaneous nerves extending into the epidermis. 4,5
DISCUSSION
IP is an uncommon genodermatosis characterized by four overlapping cutaneous stages and frequent neuroectodermal defects. Vesicular, verrucous, hyperpigmented, and atrophic manifestations may be seen. IP is presumed to result from an X-linked dominant mutation that is usually lethal in utero in
malefetuese. A female/male predominance of greater than 35:1 has been estimated from large statistical analyses. 6 The gene has been mapped to the Xpll band of the X chromosome.? There are rare reports of IP in twin girls. s The few cases reported in male patients were hypothesized to have occurred by spontaneous half-chromatid mutation. Several recent cases ofmale infants born with IP and family histories of IP have challenged this explanation. 9 Several cases of IP have been reported in male infants with Klinefelter's syndrome (47,XXYkaryotype).lo-t2Thedistribution onp by race is unknown. In Carney's series, 13 at least 24 black patients of 65 3 patients with IP were documented. The four stages ofIP may be concurrent (as in our patient 3) or some of the stages may occur in utero. The first stage usually begins within 2 weeks of birth but in rare cases may appear after the first year of life. 13 Itconsists oflinear erythema and vesicles that are most often located on the extremities. Crops of vesicles may be recurrent, as in our third case, and may persist until 6 years of age. 14 Stage 2 most often begins between the second and sixth weeks of life l3 and consists of verrucous papules that are often arranged linearly and found predominantly on the extremities. The lesions persist for 6 to 12 months 6 and then resolve spontaneously. However, in one recent report, a patient with IP had continuing development of new verrucous lesions, one of which resulted in squamous cell carcinoma in situ at the age of 25 years. IS
856 Sahn and Davidson Stage 3, with age of onset most frequently between 12 and 26 weeks,!3 is characterized by whorled, browntoslate-brownhyperpigmentedmacules and patches on the trunk; the extremities are less often affected. These streaky macules tend to follow Blaschko's lines, as seen clearlyin our third case. The hyperpigmentation may occur in previously unaffected areas and may last many years. 13, 15 Residual axillary hyperpigmentation, as seen in our case 2, has been reported as a subtle marker oflP in otherwise normal patients.l 6 Stage 4 disease, if present, is characterized by streaky hypopigmentation and atrophy on the lower extremities, as seen in cases 1 and 2. 5,8, 17 This stage may be underreported because it was not originally described. Clinicians should search for atrophic, hypopigmented streaks in mothers of infants in whom a diagnosis of IP is suspected because these streaks may be difficult to see. 9 Hair abnormalities seen with IP include vertex alopecia, hair loss from other body sites, and woolly haired nevus. 16 Nail changes in IP include longitudinal and transverse striations, and subungual hyperkeratotic tumors,18 often in association with scalloped bone deformities of the distal phalanges. 19 Partial sweat gland aplasia also has been noted. 6 Major dental abnormalities occur in 65% of patients; the majority of these are identifiable by the age of 2 years,13 The most common are partial anodontia (43%) and pegged teeth (30%), as were seen in each of our patients. Eye anomalies have been reported in 25% to 35% of patients6; strabismus is the most common (18%).20 Retinal detachment and a fibrovascular retrolental membrane are the most frequently reported intraocular abnormalities. 2o Early diagnosis of the retinopathy of IP may allow successful treatment by photocoagulation or cryotherapy to prevent retinal detachment and blindness. 21 ,22 Cataracts, nystagmus, and optic atrophy have also been reported. 13, 23 Asymmetric eye involvement is usual; the affected eye often shows microphthalmia. 24 The central nervous system is affected in up to 33% ofpatients. 6The most commonly reported central nervous system abnormalities are seizures (13%), mental retardation (12%), spastic paralysis (11%), microcephaly, and motor retardation. 13, 23 A variety ofstructural anomalies have also been reported, but their incidences may be no greater than that in the general population. 6 There may be an increased incidence of certain childhood malignancies in IP, perhaps from chromosomal in-
Journal of the American Academy of Dermatology November 1994
stability.25 In one study a cellular defect was noted in polymorphonuclear chemotaxis in six of eight patients with IP.26 , The differential diagnosis of infants with IP has been thoroughly discussed in recent publications. 6,27 Management ofthe newborn infant with IP includes neurologic examination with additional testing on the basis of initial findings. Ophthahnologic examination should be done within 1 month of birth and should be repeated at 3-month intervals until 1 year of age. Mothers and sisters of patients with IP should have careful examinations for cutaneous lesions and for ophthalmologic and dental abnormalities. All patients with IP should have dental examinations by the age of 2 years to evaluate partial anodontia and tooth spacing. Acid-etched restorations of pegged teeth are possible. 6 REFERENCES 1. Lever WF, Schaumburg-Lever G. Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:93-95. 2. Thyresson NH, Goldberg NC, Tye MJ, et al. Localization of eosinophil granule major basic protein in incontinentia pigmenti. POOiatr Dermatol 1991;8:102-6. 3. Zillikens D, Mehringer A, Lechner W, et al. Hypo- and hyperpigmentOO areas in incontinentia pigmenti: light and electron microscopic studies. Am J Dermatopathol 1991; 13:57-62. 4. Worret WI, Nordquist RE, Burgdorf WHo Abnormal cutaneous nerves inincontinentia pigmenti. UltrastructPathol 1988;12:449-54. 5. Worret WI. Hypo- and hyperpigmentOO areas in incontinentia pigmenti. Am J DermatopathoI1991;13:629-30. 6. Cohen BA. Incontinentia pigmenti. Neurol Clin 1987; 5:361-77. 7. Cannizzaro LA, Heckt F. Gene for incontinentia pigmenti maps to band Xp11 with an (X: 10) (P 112) translocation. Clin Genet 1987;32:66-9. 8. Tanaka K, Kambe N, Fujita M. Incontinentia pigmenti in identical twins with separate skin and neurological disorders. Acta Derm Venereol (Stockh) 1990;70:267-8. 9. Garcia-Dorado J, de Unamuno P, Fernandez-Uiez E, et al. Incontinentia pigmenti: XXV male with a family history. Clin Genet 1990;38:128-38. 10. Prendiville JS, Gorski JL, Stein CK, et al. Incontinentia pigmenti in a male infant with Klinefelter syndrome. JAM ACAD DERMATOL 1989;20:937-40. 11. Kunze J, Frenzel UH, Huttig E, et al. Klinefelter's syndrome and incontinentia pigmenti Bloch-Sulzberger. Hum Genet 1977;35:237-240. 12. Ormerod AD, White MI, McKay E, et al. Incontinentia pigmenti in a boy with Klinefelter's syndrome. J Moo Genet 1987;24:439-41. 13. Carney RG. Incontinentia pigmenti: a world statistical analysis. Arch DermatoI1976;1l2:535-542. 14. O'Brien JE, Feingold M. Incontinentia pigmenti: a longitudinal study. Am J Dis Child 1985;139:711-2. 15. Korstanje MJ, Bessems PJMJ. Incontinentia pigmenti with hyperkeratotic lesions in adulthood and possible squamous cell carcinoma. Dermatologica 1991;183:234-6.
Journal of the American Academy of Dermatology Volume 31, Number 5, Part 2 16. Wiklund DA, Weston WL. Incontinentia pigmenti: a fourgeneration study. Arch DermatoI1980;116:701-3. 17. Nazzaro V, Brusasco A, Gelmetti C, et al. Hypochromic reticulated streaks in incontinentia pigmenti: an immunohistochemical and ultrastructural study. Pediatr Dermatol 1990;7:174-8. 18. Mascaro JM, Palou J, Vives P. Painful subungual keratotic tumors in incontinentia pigmenti. JAM ACAD DERMATOL 1985;13:913-8. 19. Simmons DA, Kegel MF, Scher RK, et aL Subungual tumors in incontinentia pigmenti. Arch Dermatol 1986; 122: 1431-4. 20. Heathcote JG, Schoales BA, Willis NR. Incontinentia pigmenti (Bloch-Sulzberger syndrome): a case report and review of the ocular pathological features. Can J Ophthalmol 1991;26:229-37. 21. Rahi J, Hungerford J. Early diagnosis ofthe retinopathy of incontinentia pigmenti: successful treatment by cryotherapy. Br J Ophthalmol 1990;74:377-9.
Burden et al. 857 22. Catalano RA, Lopatynsky M, Tasman WS. Treatment of proliferative retinopathy associated with incontinentia pigmenti. Am J OphthalmoI1990;110:701-2. 23. Damstra RJ, Van Duren JA, Van Ginkel CWJ. Incontinentia pigmenti (Bloch-Sulzberger). Br J Dermatol1991; 125:280-1. 24. Catalano, RA. Incontinentia pigmenti. Am J Ophthalmol 1990;110:696-9. 25. Roberts WM, Jenkins JJ, Moorhead EL, et aL Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer 1988;62:2370-2. 26. Menni S, Piccinno R, Biolchini A, et aL Immunologic investigations in eight patients with incontinentia pigmenti. Pediatr DermatoI1990;7:275-7. 27. Mallory SB, Krafchik BR. Incontinentia pigmenti: the syndrome page. Pediatr DermatoI1992;9:304-8.
IgA anticardiolipin antibodies associated with Henoch-Schonlein purpura A. David Burden, MRcp,a Ian W. Gibson, MBChB,b R. Stuart C. Rodger, FRCP,c and David M. Tillman, MRcpa Glasgow, Scotland Henoch-SchOnlein purpura is associated with the deposition of immune complexes containing IgA. The nature of the antigen in these immune complexes is uncertain but in some reported cases has included autoantigens such as IgA rheumatoid factor and IgA antineutrophil cytoplasmic antibody. We report the finding of an IgA class anticardiolipin antibody in a 51-year-old patient with Henoch-SchOnlein purpura. A potential role for IgA autoantibodies in Henoch-SchOnlein purpura needs to be further explored. (J AM ACAD DERMATOL 1994;31:857-60.) Antiphospholipid antibodies are a heterogeneous group of immunoglobulins of the IgG, IgM, or IgA classes directed against a variety of phospholipid antigens. They are important risk factors for arterial and venous thrombosis and are also associated with recurrent fetal loss, thrombocytopenia, and an autoimmune postpartum syndrome. Various cutaneous manifestations have also been reported, such as
From the University of Glasgow Departments of Dennatology,' Pathology,b and Renal Medicine,c Western Infirmary. Reprint requests: A. David Burden, MRCP, University Department of Dermatology, Western Infirmary, Glasgow GIl 6NT, Scotland, United Kingdom. Copyright @ 1994 by the American Academy of Dennatology, Inc. 0190-9622/94 $3.00 + 0 16/4/55289
livedo reticularis, 1 necrotizing purpura,2 and widespread cutaneous necrosis 3; these have recently been reviewed. 4 We report for the first time the finding of IgA anticardiolipin antibodies CACAs) in a patient with Henoch-Schonlein purpura CHSP). CASE REPORT A 51-year-old man had palpable purpura for 4 months on the legs (Fig. 1). Two years before he had a cerebrovascular accident that resulted in a right-sided hemiparesis. A computed tomographic scan at that time revealed infarction in the left middle cerebral artery territory. The patient had been taking low-dose aspirin since the cerebrovascular accident but was taking no other medication. His general health was otherwise good. In particular, he had no joint pains or abdominal symptoms and could recall no recent sore throat.