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Basophils in incontinentia pigmenti
Basophils in incontinentia pigmenti Frank C, Schmalstieg, M.D., Ph.D.,* Joseph L. Jorizzo, M.D.,** Jaime Tschen, M.D.,*** and Paul Subrt, M.D.** Galveston and Houston, TX Incontinentia pigmenti is a rare genodermatosis of unknown etiology. A female infant with features typical of this disease was found to have basophils in early vesicular lesions. Mediators from these cells may be responsible for the accumulation of eosinophils in these lesions. (J AM ACAD DERMATO5 10:362-364, 1984.)
Incontinenfia pigmenti (Bloch-Sulzberger syndrome) is an unusual congenital disease characterized by linear, erythematous, or vesicular lesions that are present perinatally.) In addition to the dermatologic findings, these individuals often have anomalies of the eyes, central nervous system, and teeth, as well as other structural defects? Two recent reports of families with this disorder provide strong evidence that the syndrome is inherited as an X-linked dominant gene that is often lethal in utero for affected males ),4 The biochemical basis for the disease is unknown. The skin lesions characteristically exhibit three stages: (1) vesicular stage at birth, (2) lichenoid or verrucous stage, and (3) hyperpigmented stage. Histopathologically, the vesicular stage is characterized by an intraepidermal spongiotic blister with infiltration by lymphocytes, eosinophils, and polymorphonuclear cells, 5 and large dyskeratotic epidermal cells are found between vesicles; the verrucous stage is characterized by acanthosis, irregular papillomatosis, and hyperkeratosis with dyskeratotic ceils, as in the first stage. '~ The third stage, hyperpigmentation, histopathologically reveals pronounced pigmentary incontinence. 7 From the Departments of Pediatrics* and Dermatology,** The University of Texas Medical Branch at Galveston, and the Department of Dermatology,*** Baylor College of Medicine, Houston. Reprint requests to: Dr. Frank C. Schmalstieg, Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77550.
362
Fig. 1. Leg when patient was 4 days old. Note linear, whorled arrangement of tense vesicles and bullae on leg. Despite numerous histologic studies, the pathogenesis of the inflammatory lesions remains obscure. No infectious agent has been convincingly implicated in the evolution of these lesions. In this report the presence of basophils in the affected skin of an infant with the vesicular stage of incontinentia pigmenti is documented and the possible significance of this finding assessed. CASE REPORT A 2,900-gram female infant was noted to have vesiculobullous lesions over both extremities at 15 minutes after birth. The umbilical cord was wound tightly about the neck, and the Apgar score at 1 minute was 1. The child was resuscitated but appeared very depressed. At 24 hours of age the infant had several episodes of seizures that were controlled with phenobarbital. An electroencephalogram had grossly abnormal results. Exam-
Volume 10 Number 2, Part 2 February, 1984
Basophils in i~wontinentia pigmenti
363
Fig, 2. Skin biopsy showing multiloculated, spongiform pustules containing a mixed infiltrate with primarily eosinophils and an upper dermal perivascular, primarily mononuclear cell infiltrate. (Hematoxylin-eosin stain; original magnification, x 120.)
Fig. 3. Skin biopsy showing intraepidermal vesiculopustules containing three basophils
(arrows) and many eosinophils with rare mononuclear cells. (Giemsa stain; original magnification, x480.) ination for viral, bacterial, or protozoal infections was negative. She had a white blood cell count of 20,000/ mm a without peripheral eosinophilia. A slit-lamp examination of the eyes demonstrated atrophy of the right optic disc. At 31/z months of age the child had increased tone and abnormal posturing. The dermatosis progressed to hyperpigmentation, and a verrucous lesion remained on the right leg.
Cutaneous examination 2 days after birth revealed a thin female neonate with a disseminated eruption characterized by a linear, whorled arrangement of tense vesicles and bullae on the trunk and extremities (Fig. 1). Nikolsky's sign was negative. No mucous membrane lesions were noted. A shave biopsy of a vesicular lesion from the lower left leg showed the following changes: The epidermis was mildly acanthotic and contained multiloculated
364
Journal of the American Academy of Dermatology
Schmalstieg et al
spongiform pustules with multiple eosinophils and less frequent polymorphonuclear and mononuclear leukocytes. The upper dermis showed a primarily mononuclear cell infiltrate, mainly around blood vessels, with scattered eosinophils (Fig. 2). Examination of Giemsastained serial sections from the skin biopsy was also performed. Each high-power field re,Jealed two or three basophils within the vesicuIopustules and in the adjacent epidermis (Fig. 3). Electron microscopy was performed in order to better examine the intraepidermal inflammatory ceils. Numerous cells with large cytoplasmic granules with a characteristic crystalloid inner structure compatible with eosinophils and basophils were seen. No epidermal mast cells were identified after extensive scanning. COMMENT T o our knowledge, this is the first report of the presence o f basophils in the lesions o f incontinentia pigmenti. Transmission electron micrography clearly distinguishes these cells from mast cells by the characteristics o f their granules, s T h e participation of basophils in a variety o f inflammatory lesions is well d o c u m e n t e d 2 These lesions include those associated with allergic reactions of the i m m e d i a t e type in which IgE bound to the basophil surface is cross-linked by antigen and results in the release o f a variety o f inflammatory mediators. T w o o f these mediators, particularly histamine and eosinophi! chemotactic factor of anaphylaxis, are chemotactic for eosinophils. '~ In addition, cutaneous basophil hypersensitivity reactions induced b y contact agents such as urushiol are well k n o w n 2 Although the histopathologic a p p e a r a n c e and the gross appearance o f neither i m m e d i a t e nor cutaneous basophil
hypersensitivity lesions closely resemble the lesions of incontinentia pigmenti, the presence of the basophils provides a possible mechanism for the recruitment of eosinophils through histamine and eosinophil chemotactic factor release. The finding of basophils in the areas of very early lesions of incontinentia pigmenti is consistent with this notion. REFERENCES
1. Carney RG: incontinentia pigmenti: A report of five cases and review of the literature. Arch Dermatol 64: I26-135, 1951. 2. Carney RG: Incontinentia pigmenti: A world statistical analysis. Arch Dermatol 112:535-542, 1976. 3. Wiklund DA, Weston WL: Incontinentia pigmenfi: A four-generation study. Arch Dermatol 116:701-703, 1980. 4. Bjellerup M: Incontinentia pigmenti with dental anomalies: A three-generation study. Acta Derm Venereol (Stockh) 62:262-264, 1982. 5. Asboe-Hansen G: Bullous keratogenous and pigmentary dermatitis with blood eosinophilia in newborn girls: Report of four cases. Arch Dermatol 67:152-157, 1953. 6. Lever WF: Histopatholgy of the skin, ed, 4. Philadelphia, 1967, JB Lippincott Co., pp. 86-88, 7. Schaumburg-Lever G, Lever WF: Electron microscopy of incontinentia pigmenti: J Invest Dermatol 61:151 - 158, 1973. 8. Asboe-Hansen G: The mast cell in health and disease. Acta Derm Venereol [Suppl] (Stockh) 73:139-148, 1973. 9. Dvorak AM, Mihm MC, Dvorak HF: Degranulation of basophilic leukocytes in allergic contact dermatitis in man. J Immunol 116:687-695, 1976. I0. Clark RAF, Gallin JI, Kaplan AP: The selective eosinophil chemotactic activity of histamine. J Exp Med 142: 1462-1476, 1975. 11. TurnbulI LW, Evans DP, Kay AB: Human eosinophils, acidic tetrapeptides (ECF-A) and histamine: Interactions in vitro and in vivo. Immunology 32:57-63, 1977.
Incontinenfia pigmenti (Bloch-Sulzberger syndrome) is an unusual congenital disease characterized by linear, erythematous, or vesicular lesions that are present perinatally.) In addition to the dermatologic findings, these individuals often have anomalies of the eyes, central nervous system, and teeth, as well as other structural defects? Two recent reports of families with this disorder provide strong evidence that the syndrome is inherited as an X-linked dominant gene that is often lethal in utero for affected males ),4 The biochemical basis for the disease is unknown. The skin lesions characteristically exhibit three stages: (1) vesicular stage at birth, (2) lichenoid or verrucous stage, and (3) hyperpigmented stage. Histopathologically, the vesicular stage is characterized by an intraepidermal spongiotic blister with infiltration by lymphocytes, eosinophils, and polymorphonuclear cells, 5 and large dyskeratotic epidermal cells are found between vesicles; the verrucous stage is characterized by acanthosis, irregular papillomatosis, and hyperkeratosis with dyskeratotic ceils, as in the first stage. '~ The third stage, hyperpigmentation, histopathologically reveals pronounced pigmentary incontinence. 7 From the Departments of Pediatrics* and Dermatology,** The University of Texas Medical Branch at Galveston, and the Department of Dermatology,*** Baylor College of Medicine, Houston. Reprint requests to: Dr. Frank C. Schmalstieg, Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77550.
362
Fig. 1. Leg when patient was 4 days old. Note linear, whorled arrangement of tense vesicles and bullae on leg. Despite numerous histologic studies, the pathogenesis of the inflammatory lesions remains obscure. No infectious agent has been convincingly implicated in the evolution of these lesions. In this report the presence of basophils in the affected skin of an infant with the vesicular stage of incontinentia pigmenti is documented and the possible significance of this finding assessed. CASE REPORT A 2,900-gram female infant was noted to have vesiculobullous lesions over both extremities at 15 minutes after birth. The umbilical cord was wound tightly about the neck, and the Apgar score at 1 minute was 1. The child was resuscitated but appeared very depressed. At 24 hours of age the infant had several episodes of seizures that were controlled with phenobarbital. An electroencephalogram had grossly abnormal results. Exam-
Volume 10 Number 2, Part 2 February, 1984
Basophils in i~wontinentia pigmenti
363
Fig, 2. Skin biopsy showing multiloculated, spongiform pustules containing a mixed infiltrate with primarily eosinophils and an upper dermal perivascular, primarily mononuclear cell infiltrate. (Hematoxylin-eosin stain; original magnification, x 120.)
Fig. 3. Skin biopsy showing intraepidermal vesiculopustules containing three basophils
(arrows) and many eosinophils with rare mononuclear cells. (Giemsa stain; original magnification, x480.) ination for viral, bacterial, or protozoal infections was negative. She had a white blood cell count of 20,000/ mm a without peripheral eosinophilia. A slit-lamp examination of the eyes demonstrated atrophy of the right optic disc. At 31/z months of age the child had increased tone and abnormal posturing. The dermatosis progressed to hyperpigmentation, and a verrucous lesion remained on the right leg.
Cutaneous examination 2 days after birth revealed a thin female neonate with a disseminated eruption characterized by a linear, whorled arrangement of tense vesicles and bullae on the trunk and extremities (Fig. 1). Nikolsky's sign was negative. No mucous membrane lesions were noted. A shave biopsy of a vesicular lesion from the lower left leg showed the following changes: The epidermis was mildly acanthotic and contained multiloculated
364
Journal of the American Academy of Dermatology
Schmalstieg et al
spongiform pustules with multiple eosinophils and less frequent polymorphonuclear and mononuclear leukocytes. The upper dermis showed a primarily mononuclear cell infiltrate, mainly around blood vessels, with scattered eosinophils (Fig. 2). Examination of Giemsastained serial sections from the skin biopsy was also performed. Each high-power field re,Jealed two or three basophils within the vesicuIopustules and in the adjacent epidermis (Fig. 3). Electron microscopy was performed in order to better examine the intraepidermal inflammatory ceils. Numerous cells with large cytoplasmic granules with a characteristic crystalloid inner structure compatible with eosinophils and basophils were seen. No epidermal mast cells were identified after extensive scanning. COMMENT T o our knowledge, this is the first report of the presence o f basophils in the lesions o f incontinentia pigmenti. Transmission electron micrography clearly distinguishes these cells from mast cells by the characteristics o f their granules, s T h e participation of basophils in a variety o f inflammatory lesions is well d o c u m e n t e d 2 These lesions include those associated with allergic reactions of the i m m e d i a t e type in which IgE bound to the basophil surface is cross-linked by antigen and results in the release o f a variety o f inflammatory mediators. T w o o f these mediators, particularly histamine and eosinophi! chemotactic factor of anaphylaxis, are chemotactic for eosinophils. '~ In addition, cutaneous basophil hypersensitivity reactions induced b y contact agents such as urushiol are well k n o w n 2 Although the histopathologic a p p e a r a n c e and the gross appearance o f neither i m m e d i a t e nor cutaneous basophil
hypersensitivity lesions closely resemble the lesions of incontinentia pigmenti, the presence of the basophils provides a possible mechanism for the recruitment of eosinophils through histamine and eosinophil chemotactic factor release. The finding of basophils in the areas of very early lesions of incontinentia pigmenti is consistent with this notion. REFERENCES
1. Carney RG: incontinentia pigmenti: A report of five cases and review of the literature. Arch Dermatol 64: I26-135, 1951. 2. Carney RG: Incontinentia pigmenti: A world statistical analysis. Arch Dermatol 112:535-542, 1976. 3. Wiklund DA, Weston WL: Incontinentia pigmenfi: A four-generation study. Arch Dermatol 116:701-703, 1980. 4. Bjellerup M: Incontinentia pigmenti with dental anomalies: A three-generation study. Acta Derm Venereol (Stockh) 62:262-264, 1982. 5. Asboe-Hansen G: Bullous keratogenous and pigmentary dermatitis with blood eosinophilia in newborn girls: Report of four cases. Arch Dermatol 67:152-157, 1953. 6. Lever WF: Histopatholgy of the skin, ed, 4. Philadelphia, 1967, JB Lippincott Co., pp. 86-88, 7. Schaumburg-Lever G, Lever WF: Electron microscopy of incontinentia pigmenti: J Invest Dermatol 61:151 - 158, 1973. 8. Asboe-Hansen G: The mast cell in health and disease. Acta Derm Venereol [Suppl] (Stockh) 73:139-148, 1973. 9. Dvorak AM, Mihm MC, Dvorak HF: Degranulation of basophilic leukocytes in allergic contact dermatitis in man. J Immunol 116:687-695, 1976. I0. Clark RAF, Gallin JI, Kaplan AP: The selective eosinophil chemotactic activity of histamine. J Exp Med 142: 1462-1476, 1975. 11. TurnbulI LW, Evans DP, Kay AB: Human eosinophils, acidic tetrapeptides (ECF-A) and histamine: Interactions in vitro and in vivo. Immunology 32:57-63, 1977.