FETAL AND NEONATAL M E D I C I N E RichardE. Behrman, Editor
Transient neonatal pustular melanosis Newborn infants were observed with vesicopustular and pigmented macular skin lesions, which occurred more commonly in black and mature infants and which were distinct clinically and histopathological@ from erythema toxicum. Histopathology of skin biopsies of the vesicopustules is characterized by polymorphonuclear infiltration. The lesions often present as, or evolve into, a pigmented macule and persist from three weeks to three months. There ate no associated systemic symptoms.
Rajam S. Ramamurthy, M.D., Mridula Reveri, M.D., Nancy B. Esterly, M.D., David F. Fretzin, M.D,, and Rosita S. Pildes, M.D., Chicago, Ill.
THE FREQUENT OCCURRENCE of a distinct skin eruption consisting of vesicopustules and pigmented macules in newborn infants in our nursery stimulated an attempt to delineate the disorder more completely. The clinical manifestations and course of the dermatosis appeared to be different from that of the more commonly observed erythema toxicum. 1-~ To our knowledge, this condition has not been included in dermatology or neonat01ogy textbooks, nor has it been fully described in the medical literature. ~ This report presents the clinical manifestations, histopathology, and course of this not uncommon dermatosis of the neonate for which we propose the name "transient neonatal pustular melanosis." CLINICAL
STUDY
During a six-week period, 666 babies born at Cook Co,unty Hospital were evaluated within 24 hours of birth for the presence of one or more of the following types of cutaneous lesions: (1) Vesicopustules (Fig. 1); (2) Ruptured vesicopustules identifiable by the characteristic collarette of scale often surrounding a central pigmented macule (Fig. 2); and (3) Pigmented macules (Fig. 2). One or more types of lesions were seen in 23 of 515 black (4.4%) and one of 145 (0.6%) white consecutive neonates, an overall incidence of 2.2%. The sex ratio for affected infants was 1:1. Except for one infant of 34 weeks' gestation, the infants Were term and appropriate The Department of Pediatrics, Cook County Hospital, Division of Pediatric Dermatology and the Department of Pathology, Michael Reese Hospital.
for gestational age. None had a history of exposure to maternal infection or intake of drugs other than the usual vitamin and iron preparations. No other skin lesions were observed apart from insignificant flat hemangiomas (salmon patches and nuchal nevi) and mongolian spots. All infants were bathed routinely with a mild antiseptic soap (Babysan) and triple dye or alcohol was applied to the umbilical cord. Abbreviation used ET: erythema toxicum Biopsies were performed on 13 affected infants using a 3 mm skin biopsy punch. There was minimal bleeding following the procedure, and the biopsy site healed in three to four days. Seven vesicopustules and seven pigmented macules were obtained for histologic study. The specimens were fixed immediately in 10% buffered formalin. An additional three blisters were biopsied and fixed in 2.5% buffered glutaraldehyde for electron microscopic examination. Bacterial cultures were obtained from intact pustules from 13 infants. The study was approved by the Scientific and Human Experimentation Committees of Cook County Hospital and informed consent was obtained from the parents. NATURE
OF LESIONS
The lesions were observed at birth in every affected infant. The most common type of lesion was the pigmented macule. When vesicopustular lesions were present, they were superficial and ruptured easily during The Journal of P E D I A T R I C S Vol. 88, No. 5, pp. 831-835
831
83 2
Ramamurthy et al.
The Journal of Pediatrics May 1976
Fig. 1. Lower face and neck of an infant, 2 hours old, showing multiple vesicopustules desquamating lesions and pigmented macules.
Fig. 2. Multiple pigmented macules, some with a collarette of scales (arrow) distributed over the lower back and buttocks.
the first bathing of the infant, immediately leaving a collarette of fine white scales. Frequently, central to the scale, a pinhead-sized brown macule was observed. Clusters of lesions were seen most often under the chin, and on the forehead, nape, lower back, and shin. Occasionally, lesions were seen also on the cheek and on the trunk and extremities. Rarely, blisters appeared on the scalp, palms, and soles; these did not progress to pigmented macules. The pigmented macules (freckles) persisted for several weeks to several months. There were no associated systemic symptoms nor evidence of discomfort. Some of the infants with pustular melanosis also developed typical lesions of erythema toxicum on the third or fourth day of life.
feature of five lesions, and both subcorneal and intraepidermal separation was present in one lesion. The vesicles contained primarily polymorphonuclear leukocytes, some scattered eosinophils, keratinous debris, serous fluid, and fragmented hair shafts. The dermis appeared uninvolved in three lesions, but two lesions were noted to have some eosinophils a n d / o r polymorphonuclear leukocytes in the cerium, especially around small vessels and about the upper portion of hair follicles. There was modest capillary proliferation and dilatation in the dermis in three lesions (Fig. 3). Serial and/or multiple hematoxylin and eosin sections were examined from seven pigmented macules. Two macules had no appreciable histopathologic change. In the other five macules, moderate basketweave hyperkeratosis was found. These macules had focal areas of increased melanin in the basal and suprabasal layers of the epidermis. Melanin in macrophages was not observed in the papillary dermis. A Fontana-Masson preparation confirmed and enhanced the focal basilar hyperpigmentation seen on the hematoxylin and eosin sections (Fig. 4). The orcein elastic stain, colloidal iron stain for mucopolysaccharides, and the Brown-Brenn preparation for bacteria were unrevealing. Special stains for elastic tissue, mucosubstances, mast cells, glycogen, and melanin were not remarkable. No evidence for viral infection of epidermaI cells was discerned on examination of electron microscopic sections. Smears of vesicle fluid obtained from infants and
HISTOPATHOLOGY The skin biopsy specimens were sectioned at 5 /~ and prepared with hematoxylin and eosin, tuluidine blue, Brown-Brenn stain, orecein elastic stain, periodic acid-Shift, colloidal iron, and Fontana-Masson stain for melanin. Seven biopsies from six patients with vesicopustular lesions were examined microscopically. One lesion was indistinguishable from those seen in erythema toxicum and was therefore excluded from the study. On hematoxylin and eosin preparations, all six biopsies showed hyperkeratosis of the stratum corneum. Moderate acanthosis was noted in two lesions and mild acanthosis in a third lesion. Intracorneal separation was a prominent
Volume 88 Number 5
Transient neonatal pustular melanosis
Fig. 3. Vesicopustule showing an intracorneal separation containing polymorphonuclear leukocytes, sparse eosir/ophils, and keratinous debris with mild acanthosis and edema of the epidermis. (H & e; • 200.)
Fig. 4. Macule showing hyperpigmented central area involving only epidermal cells. Arrows point to junction between normal and abnormally pigmented epidermis. (Fontana-Masson; x 85.)
833
834
Ramamurthy et al.
stained with Wright stain demonstrated large numbers of polymorphonuclear cells, cellular debris, and few or no eos!nophils. Gram Stains of the fluid were negative in every instance. No macrophages were seen on a Giemsa stain of vesicle fluid from one infant. Bacterial cultures of blister fluid were negative in every instance. Serum IgM concentrations in cord blood of five infants were within normal limits. DISCUSSION Small pigmented macules, at times associated with vesicopustules, have bee n observed frequently, especially among black newborn infants in our nursery. The pustular eruption, when extensive, poses a considerable diagnostic dilemma. The lesion can be mistaken easily for a staphylococcal pustule an d result in extensive diagnostic studies and unnecessary therapy. Rarely, the appearance or configuration of lesions may suggest another type of vesicu!ar eruption. The most intriguing differential, however, is between this entity and the very common dermatosis, erythema toxicum. Several large series of infants with erythema toxicum have been reported during the past 20 years, 1-~ Speculation as to the etiology of the disease has ranged from the allergic theory of Mayerhofer and Lypolt-Kramjnovic~ to the more colorful suggestion of Dewes dating back to 1826.* Even today, the exact etiology of erythema toxicum is not known. The differences between erythema toxicum and pustular melanosis are summarized in Table I. The occurrence of pigmented macules Seems to be higher in black than in white infants. Although erythema toxicum has been reported to occur more frequently in white infants,4 further observations have n o t supported that impression. In our infants the pigmented macules often coexisted with the pustules. When the evolution of individual pustu!ar lesions was observed, many but not all developed pigmented macules following rupture. It is impossible to know whether the pigmented macules which were already present at birth in many infants represent end-stage lesions which were previously pustular. If so, it would suggest that the process is initiated in utero and completed *"This complaintis confinedto early infancy,and especiallyto 'the month,' as it is called.Very few childrenescape this complaint;and most nursesare fondof seeingit-so muchsoindeed,and so invitableand useful do theyconsiderits presence,that shouldanyindispositionbefallthe child, and this eruptionnot have possessionof the skin~it is at onceattributedto the absenceof the gum.Witha viewthento invit~its appearance,the child is kept unusuallywarm, and some stimulatingtea is givenit, such as of sweet marjoram, saffron, catmint, etc., and the poor child is but too frequen!ly loaded with a lieavy crop of 'Red Gum.' This eruption, however,seemsconnectedin somewayorother witha derangementof the stomach and bowels. . . . This disease, under ordinary circumstances, requires little or no medicaltreatment."Dewes, 18267
The Journal of Pediatrics May 1976
after birth, and that each lesion runs it course, with many pustules evolving into pigmented macules. Perrin and associates 7 described an eruption similar to pustular melanosis, which was present at birth and seen only in black infants, and gave it the name lentigines neonatorum? They suggested that the pigmented macules represented areas of hyperpigmentation which followed healing of an intrauterine skin eruption (postinflammatory hyperpigmentation). On examination of the placentas from these infants, a higher incidence of squamous metaplasia was found when compared to a control group. These authors ascribed both the cutaneous and placental lesions to an intrauterine infection. Although squamous metaplasia was found in the placentas of two infants in this study, we were unable to confirm the significance of this finding since only a small number of placentas were evaluated. Two infants with pustular ET, which was noticed at birth, have been reported2 ~~' Although o n e of these infants~appeared to have the typical eruption of erythema toxicum with eosinophils on smear of intralesional contents, the other infant may have had pustular melanosis? The latter infant, a black baby, not only had hyperpigmented macules but also had scaly-collared lesions and pustules with involvement of the soles. No bacteria were seen on Gram stain of pustules, but numerous eosinophils were said tO be present with Wright stain. However, as in the first infant, no peripheral eosinophila was noted. Hyperpigmented macules were Still apparent at two weeks of age. Although Harris and Schick 1alluded to the finely peppered appearance of the skin in their description of ET, we have never seen a typical ET eventuate in postinflammatory pigmentation. The pathologic changes in pustular melanosis appear distinctive from erythema toxicum, though some similarities may exist, possibly relating to the duration of the lesion at the time of biopsy, In ET, the major pathologic change is a severe eosinophilie inflammatory reaction about the superficial portion of the pilosebaceous unit. Additionally, eosinophils are present around vessels and diffusely in the upper and mid corium. Our cases differed in that the level of the bulla was intracorneal. The dermis appeared either uninvolved or showed a modest inflammatory reaction of polym0rphonuclear leukocytes and eosinophqls. The pigmented macules present another histologic dilemma. Since clinically some of these macules appear to follow a vesicopustule, one would consider them postinflammatory in nature, yet the absence of melanophages in the papillary dermis is unusal in post!nflammatory hyperpigmentation. Possibly, the minor degree of dermal inflammation and lack of exocytic invasion of the
Volume 88 Number 5
Transient neonatal pustular melanosis
835
Table I. Clinical and histopathologic differences between transient neonatal pustular melanosis and erythema toxicum
Incidence Age of onset Types of lesions
Sites of involvement Duration Smear of lesional contents Histopathology Pustule
Pigmented macule
Pustular melanosis
Erythema toxicum
More common in black infants Always present at birth Vesicopustules with no surrounding erythema; desquamated vesicopustule with collarette of scale; pigmented macule Chin, neck, nape, lower back, and shins; vesicles on palms and soles Vesicopustules disappear in 24-48 hr; pigmented macules fade in 3 wk to 3 mo Polymorphonuclear leukocytes, cellular debris, sparse eosinophils
Equal in black and white infants Rarely present at birth White papules with surrounding erythema; vesicopustule, usually with surrounding erythema
Intracorneal and subcorneal pustules with infiltrate mainly polymorphonuclear leukocytes, variable eosinophils Basketweave hyperkeratosis, focal basilar hyperpigmeritation
epidermis might account for the minimal stimulation of melanocytic activity and its distribution only in the basal and suprabasal epidermal cells. We were unable to discern the etiology of pustular melanosis. No correlation was found with maternal infection, drug intake, or use of contraceptive pills. There was no evidence of bacterial infection on Gram stain or culture of the pustule contents, nor were any bacterial organisms detected on Brown-Brenn stains of sections from skin biopsies. Ultrastructural studies of three vesicular lesions failed to demonstrate viral particles within epidermal cells. Clinically, the infants remained healthy and were discharged h o m e with their mothers. The extensive evaluation of sepsis and antibiotic therapy which was given some o f these infants in ou r nursery before the true nature of the vesicopustules was appreciated is n o longer routine since our residents have become familiar with this disorder. The transient nature of the pustular melanosis and the rare possibility of recurrence of pustules should be explained to the mother to avoid unnecessary anxiety. This is a self-limited condition which requires no therapy. The authors thank Drs. Suma P. Pyati and Ramasamy SethuPathY, fellows, Division of Neonatotogy, Cook County Hospital, for their help in collecting clinical data. They also wish to thank
Face, forehead, trunk, and extremities; no involvement of palms and soles Persists for up to 6 days, occasionally longer; no residual pigmentation Numerous eosinophils
Intraepidermal or subcorneal pustule involving superficial portion pilosebaceous unit, dense infiltrate of eosinophils
Dr. Eugene Perrin for looking at the placentas and Ms. Irene Goldberger for the technical help in the histopathological examination of skin biopsies. REFERENCES 1. Harris JH, and Schick B: Erythema neonatorum, Am J Dis Child 92:27, 1956. 2. Taylor WB, and Bondurant CP Jr: Erythema neonatorum allergicium, Arch Dermatol 76:591, 1957. 3. Keitel HG, and Yadav V: Etiology of toxic erythema, Am J Dis Child 106:306, 1963. 4. Carr JA, Hodgeman JE, Freedman RI, and Levan NE: Relationship between toxic erythema and infant maturity, Am J Dis Child 112i129, 1966. 5. Mayerhofer E, and Lypolt-Krajnovic M: Das erythema neonatorum to• ("Erythema papulatum" der alten Arzte) als Teilerscheinung einer allgemeinen Allergie des Neugeborenen, Z Kinderhl, 43:630, 1927. 6. Finlay HVL, and Bound JP: Urticaria neonatorum (erythema toxicum neonatorum), Arch Dis Child 28:404, 1953. 7. Perrin E, Sutherland J, and Baltazar S: Inquiry into the nature of lentigines neonatorum, demonstration of a statistical relationship with squamous metaplasia of the amnion, Abstract. No. 282, Soc Pediatr Res, Am J Dis Child 102:648, 1961. 8. Levy HL, and Cothran F: Erythema toxicum neonatorum present at birth, Am J Dis Child 103:125, 1962. 9. Marino LJ: Toxic erythema present at birth, Arch Derm 92:402, 1965.
Transient neonatal pustular melanosis Newborn infants were observed with vesicopustular and pigmented macular skin lesions, which occurred more commonly in black and mature infants and which were distinct clinically and histopathological@ from erythema toxicum. Histopathology of skin biopsies of the vesicopustules is characterized by polymorphonuclear infiltration. The lesions often present as, or evolve into, a pigmented macule and persist from three weeks to three months. There ate no associated systemic symptoms.
Rajam S. Ramamurthy, M.D., Mridula Reveri, M.D., Nancy B. Esterly, M.D., David F. Fretzin, M.D,, and Rosita S. Pildes, M.D., Chicago, Ill.
THE FREQUENT OCCURRENCE of a distinct skin eruption consisting of vesicopustules and pigmented macules in newborn infants in our nursery stimulated an attempt to delineate the disorder more completely. The clinical manifestations and course of the dermatosis appeared to be different from that of the more commonly observed erythema toxicum. 1-~ To our knowledge, this condition has not been included in dermatology or neonat01ogy textbooks, nor has it been fully described in the medical literature. ~ This report presents the clinical manifestations, histopathology, and course of this not uncommon dermatosis of the neonate for which we propose the name "transient neonatal pustular melanosis." CLINICAL
STUDY
During a six-week period, 666 babies born at Cook Co,unty Hospital were evaluated within 24 hours of birth for the presence of one or more of the following types of cutaneous lesions: (1) Vesicopustules (Fig. 1); (2) Ruptured vesicopustules identifiable by the characteristic collarette of scale often surrounding a central pigmented macule (Fig. 2); and (3) Pigmented macules (Fig. 2). One or more types of lesions were seen in 23 of 515 black (4.4%) and one of 145 (0.6%) white consecutive neonates, an overall incidence of 2.2%. The sex ratio for affected infants was 1:1. Except for one infant of 34 weeks' gestation, the infants Were term and appropriate The Department of Pediatrics, Cook County Hospital, Division of Pediatric Dermatology and the Department of Pathology, Michael Reese Hospital.
for gestational age. None had a history of exposure to maternal infection or intake of drugs other than the usual vitamin and iron preparations. No other skin lesions were observed apart from insignificant flat hemangiomas (salmon patches and nuchal nevi) and mongolian spots. All infants were bathed routinely with a mild antiseptic soap (Babysan) and triple dye or alcohol was applied to the umbilical cord. Abbreviation used ET: erythema toxicum Biopsies were performed on 13 affected infants using a 3 mm skin biopsy punch. There was minimal bleeding following the procedure, and the biopsy site healed in three to four days. Seven vesicopustules and seven pigmented macules were obtained for histologic study. The specimens were fixed immediately in 10% buffered formalin. An additional three blisters were biopsied and fixed in 2.5% buffered glutaraldehyde for electron microscopic examination. Bacterial cultures were obtained from intact pustules from 13 infants. The study was approved by the Scientific and Human Experimentation Committees of Cook County Hospital and informed consent was obtained from the parents. NATURE
OF LESIONS
The lesions were observed at birth in every affected infant. The most common type of lesion was the pigmented macule. When vesicopustular lesions were present, they were superficial and ruptured easily during The Journal of P E D I A T R I C S Vol. 88, No. 5, pp. 831-835
831
83 2
Ramamurthy et al.
The Journal of Pediatrics May 1976
Fig. 1. Lower face and neck of an infant, 2 hours old, showing multiple vesicopustules desquamating lesions and pigmented macules.
Fig. 2. Multiple pigmented macules, some with a collarette of scales (arrow) distributed over the lower back and buttocks.
the first bathing of the infant, immediately leaving a collarette of fine white scales. Frequently, central to the scale, a pinhead-sized brown macule was observed. Clusters of lesions were seen most often under the chin, and on the forehead, nape, lower back, and shin. Occasionally, lesions were seen also on the cheek and on the trunk and extremities. Rarely, blisters appeared on the scalp, palms, and soles; these did not progress to pigmented macules. The pigmented macules (freckles) persisted for several weeks to several months. There were no associated systemic symptoms nor evidence of discomfort. Some of the infants with pustular melanosis also developed typical lesions of erythema toxicum on the third or fourth day of life.
feature of five lesions, and both subcorneal and intraepidermal separation was present in one lesion. The vesicles contained primarily polymorphonuclear leukocytes, some scattered eosinophils, keratinous debris, serous fluid, and fragmented hair shafts. The dermis appeared uninvolved in three lesions, but two lesions were noted to have some eosinophils a n d / o r polymorphonuclear leukocytes in the cerium, especially around small vessels and about the upper portion of hair follicles. There was modest capillary proliferation and dilatation in the dermis in three lesions (Fig. 3). Serial and/or multiple hematoxylin and eosin sections were examined from seven pigmented macules. Two macules had no appreciable histopathologic change. In the other five macules, moderate basketweave hyperkeratosis was found. These macules had focal areas of increased melanin in the basal and suprabasal layers of the epidermis. Melanin in macrophages was not observed in the papillary dermis. A Fontana-Masson preparation confirmed and enhanced the focal basilar hyperpigmentation seen on the hematoxylin and eosin sections (Fig. 4). The orcein elastic stain, colloidal iron stain for mucopolysaccharides, and the Brown-Brenn preparation for bacteria were unrevealing. Special stains for elastic tissue, mucosubstances, mast cells, glycogen, and melanin were not remarkable. No evidence for viral infection of epidermaI cells was discerned on examination of electron microscopic sections. Smears of vesicle fluid obtained from infants and
HISTOPATHOLOGY The skin biopsy specimens were sectioned at 5 /~ and prepared with hematoxylin and eosin, tuluidine blue, Brown-Brenn stain, orecein elastic stain, periodic acid-Shift, colloidal iron, and Fontana-Masson stain for melanin. Seven biopsies from six patients with vesicopustular lesions were examined microscopically. One lesion was indistinguishable from those seen in erythema toxicum and was therefore excluded from the study. On hematoxylin and eosin preparations, all six biopsies showed hyperkeratosis of the stratum corneum. Moderate acanthosis was noted in two lesions and mild acanthosis in a third lesion. Intracorneal separation was a prominent
Volume 88 Number 5
Transient neonatal pustular melanosis
Fig. 3. Vesicopustule showing an intracorneal separation containing polymorphonuclear leukocytes, sparse eosir/ophils, and keratinous debris with mild acanthosis and edema of the epidermis. (H & e; • 200.)
Fig. 4. Macule showing hyperpigmented central area involving only epidermal cells. Arrows point to junction between normal and abnormally pigmented epidermis. (Fontana-Masson; x 85.)
833
834
Ramamurthy et al.
stained with Wright stain demonstrated large numbers of polymorphonuclear cells, cellular debris, and few or no eos!nophils. Gram Stains of the fluid were negative in every instance. No macrophages were seen on a Giemsa stain of vesicle fluid from one infant. Bacterial cultures of blister fluid were negative in every instance. Serum IgM concentrations in cord blood of five infants were within normal limits. DISCUSSION Small pigmented macules, at times associated with vesicopustules, have bee n observed frequently, especially among black newborn infants in our nursery. The pustular eruption, when extensive, poses a considerable diagnostic dilemma. The lesion can be mistaken easily for a staphylococcal pustule an d result in extensive diagnostic studies and unnecessary therapy. Rarely, the appearance or configuration of lesions may suggest another type of vesicu!ar eruption. The most intriguing differential, however, is between this entity and the very common dermatosis, erythema toxicum. Several large series of infants with erythema toxicum have been reported during the past 20 years, 1-~ Speculation as to the etiology of the disease has ranged from the allergic theory of Mayerhofer and Lypolt-Kramjnovic~ to the more colorful suggestion of Dewes dating back to 1826.* Even today, the exact etiology of erythema toxicum is not known. The differences between erythema toxicum and pustular melanosis are summarized in Table I. The occurrence of pigmented macules Seems to be higher in black than in white infants. Although erythema toxicum has been reported to occur more frequently in white infants,4 further observations have n o t supported that impression. In our infants the pigmented macules often coexisted with the pustules. When the evolution of individual pustu!ar lesions was observed, many but not all developed pigmented macules following rupture. It is impossible to know whether the pigmented macules which were already present at birth in many infants represent end-stage lesions which were previously pustular. If so, it would suggest that the process is initiated in utero and completed *"This complaintis confinedto early infancy,and especiallyto 'the month,' as it is called.Very few childrenescape this complaint;and most nursesare fondof seeingit-so muchsoindeed,and so invitableand useful do theyconsiderits presence,that shouldanyindispositionbefallthe child, and this eruptionnot have possessionof the skin~it is at onceattributedto the absenceof the gum.Witha viewthento invit~its appearance,the child is kept unusuallywarm, and some stimulatingtea is givenit, such as of sweet marjoram, saffron, catmint, etc., and the poor child is but too frequen!ly loaded with a lieavy crop of 'Red Gum.' This eruption, however,seemsconnectedin somewayorother witha derangementof the stomach and bowels. . . . This disease, under ordinary circumstances, requires little or no medicaltreatment."Dewes, 18267
The Journal of Pediatrics May 1976
after birth, and that each lesion runs it course, with many pustules evolving into pigmented macules. Perrin and associates 7 described an eruption similar to pustular melanosis, which was present at birth and seen only in black infants, and gave it the name lentigines neonatorum? They suggested that the pigmented macules represented areas of hyperpigmentation which followed healing of an intrauterine skin eruption (postinflammatory hyperpigmentation). On examination of the placentas from these infants, a higher incidence of squamous metaplasia was found when compared to a control group. These authors ascribed both the cutaneous and placental lesions to an intrauterine infection. Although squamous metaplasia was found in the placentas of two infants in this study, we were unable to confirm the significance of this finding since only a small number of placentas were evaluated. Two infants with pustular ET, which was noticed at birth, have been reported2 ~~' Although o n e of these infants~appeared to have the typical eruption of erythema toxicum with eosinophils on smear of intralesional contents, the other infant may have had pustular melanosis? The latter infant, a black baby, not only had hyperpigmented macules but also had scaly-collared lesions and pustules with involvement of the soles. No bacteria were seen on Gram stain of pustules, but numerous eosinophils were said tO be present with Wright stain. However, as in the first infant, no peripheral eosinophila was noted. Hyperpigmented macules were Still apparent at two weeks of age. Although Harris and Schick 1alluded to the finely peppered appearance of the skin in their description of ET, we have never seen a typical ET eventuate in postinflammatory pigmentation. The pathologic changes in pustular melanosis appear distinctive from erythema toxicum, though some similarities may exist, possibly relating to the duration of the lesion at the time of biopsy, In ET, the major pathologic change is a severe eosinophilie inflammatory reaction about the superficial portion of the pilosebaceous unit. Additionally, eosinophils are present around vessels and diffusely in the upper and mid corium. Our cases differed in that the level of the bulla was intracorneal. The dermis appeared either uninvolved or showed a modest inflammatory reaction of polym0rphonuclear leukocytes and eosinophqls. The pigmented macules present another histologic dilemma. Since clinically some of these macules appear to follow a vesicopustule, one would consider them postinflammatory in nature, yet the absence of melanophages in the papillary dermis is unusal in post!nflammatory hyperpigmentation. Possibly, the minor degree of dermal inflammation and lack of exocytic invasion of the
Volume 88 Number 5
Transient neonatal pustular melanosis
835
Table I. Clinical and histopathologic differences between transient neonatal pustular melanosis and erythema toxicum
Incidence Age of onset Types of lesions
Sites of involvement Duration Smear of lesional contents Histopathology Pustule
Pigmented macule
Pustular melanosis
Erythema toxicum
More common in black infants Always present at birth Vesicopustules with no surrounding erythema; desquamated vesicopustule with collarette of scale; pigmented macule Chin, neck, nape, lower back, and shins; vesicles on palms and soles Vesicopustules disappear in 24-48 hr; pigmented macules fade in 3 wk to 3 mo Polymorphonuclear leukocytes, cellular debris, sparse eosinophils
Equal in black and white infants Rarely present at birth White papules with surrounding erythema; vesicopustule, usually with surrounding erythema
Intracorneal and subcorneal pustules with infiltrate mainly polymorphonuclear leukocytes, variable eosinophils Basketweave hyperkeratosis, focal basilar hyperpigmeritation
epidermis might account for the minimal stimulation of melanocytic activity and its distribution only in the basal and suprabasal epidermal cells. We were unable to discern the etiology of pustular melanosis. No correlation was found with maternal infection, drug intake, or use of contraceptive pills. There was no evidence of bacterial infection on Gram stain or culture of the pustule contents, nor were any bacterial organisms detected on Brown-Brenn stains of sections from skin biopsies. Ultrastructural studies of three vesicular lesions failed to demonstrate viral particles within epidermal cells. Clinically, the infants remained healthy and were discharged h o m e with their mothers. The extensive evaluation of sepsis and antibiotic therapy which was given some o f these infants in ou r nursery before the true nature of the vesicopustules was appreciated is n o longer routine since our residents have become familiar with this disorder. The transient nature of the pustular melanosis and the rare possibility of recurrence of pustules should be explained to the mother to avoid unnecessary anxiety. This is a self-limited condition which requires no therapy. The authors thank Drs. Suma P. Pyati and Ramasamy SethuPathY, fellows, Division of Neonatotogy, Cook County Hospital, for their help in collecting clinical data. They also wish to thank
Face, forehead, trunk, and extremities; no involvement of palms and soles Persists for up to 6 days, occasionally longer; no residual pigmentation Numerous eosinophils
Intraepidermal or subcorneal pustule involving superficial portion pilosebaceous unit, dense infiltrate of eosinophils
Dr. Eugene Perrin for looking at the placentas and Ms. Irene Goldberger for the technical help in the histopathological examination of skin biopsies. REFERENCES 1. Harris JH, and Schick B: Erythema neonatorum, Am J Dis Child 92:27, 1956. 2. Taylor WB, and Bondurant CP Jr: Erythema neonatorum allergicium, Arch Dermatol 76:591, 1957. 3. Keitel HG, and Yadav V: Etiology of toxic erythema, Am J Dis Child 106:306, 1963. 4. Carr JA, Hodgeman JE, Freedman RI, and Levan NE: Relationship between toxic erythema and infant maturity, Am J Dis Child 112i129, 1966. 5. Mayerhofer E, and Lypolt-Krajnovic M: Das erythema neonatorum to• ("Erythema papulatum" der alten Arzte) als Teilerscheinung einer allgemeinen Allergie des Neugeborenen, Z Kinderhl, 43:630, 1927. 6. Finlay HVL, and Bound JP: Urticaria neonatorum (erythema toxicum neonatorum), Arch Dis Child 28:404, 1953. 7. Perrin E, Sutherland J, and Baltazar S: Inquiry into the nature of lentigines neonatorum, demonstration of a statistical relationship with squamous metaplasia of the amnion, Abstract. No. 282, Soc Pediatr Res, Am J Dis Child 102:648, 1961. 8. Levy HL, and Cothran F: Erythema toxicum neonatorum present at birth, Am J Dis Child 103:125, 1962. 9. Marino LJ: Toxic erythema present at birth, Arch Derm 92:402, 1965.
