Is Common Neonatal Cephalic Pustulosis (Neonatal Acne) Triggered by Malassezia sympodialis? FREE

MALASSEZIA IS a lipophilic yeast linked to the Basidiomycetes class and a saprophyte that grows on the skin of healthy human adults and children.^{1 - 3} Its possible etiologic role in neonates with cephalic pustulosis was first suggested by Aractingi et al⁴ and subsequently by others.^{5 - 8}

To confirm a link between this type of eruption and Malassezia infection and to precisely determine the species of Malassezia associated with this disorder, we prospectively studied a newborn population at our hospital from February to April 1997.

We included 19 patients younger than 6 weeks with pustules on the head and neck and 19 age-matched and site-matched controls without lesions. The patients were seen consecutively in a 3-month period from February to April 1997 in the neonatology wards where all 161 infants admitted during the same period were systematically examined. Patients and controls were hospitalized for common conditions such as prematurity, dysmaturity, and neonatal sepsis. The infants' skin was routinely treated with a foaming gel without perfume (Rivadouce, Paris, France).

In the case group, smears were obtained with a microlance from pustules after disinfection with 0.1% hexamidine isethionate solution and then seeded in modified Dixon agar culture medium (3.6% malt extract, 0.6% peptone, 2% desiccated ox bile [oxoid], 1% polysorbate 40, 0.2% glycerol, 0.2% oleic acid, 0.05% chloramphenicol, 0.05% cycloheximide, and 1.2% agar; pH 6). Colonies were counted after 7 days. A glass slide was applied directly to the site of the pustule and used for direct microscopic examination after May-Grünwald staining. On the contralateral site of the pustule, a skin swab was used for culture without prior disinfection on a skin surface of 1 cm.² A similar swab was used in controls on a matched site without prior disinfection for culture. The yeasts were identified based on microscopic criteria (after May-Grünwald staining) and physiologic criteria (the polysorbate assimilation test of Guillot et al⁹ and Mayser et al¹⁰ ).

Table 1 and Table 2 summarize the clinical, mycological, and cytologic data of patients and controls. Three patients with generalized pustulosis were not included because of their diagnoses (listeriosis, transient pustular melanosis, and staphylococcal bullous impetigo). In the rest of the patients, there was no evidence of a correlation between clinical status on admission, especially related to sepsis, and the presence of pustules. Pustules were present 1 to 5 days before sampling.

Among 14 patients from whom adequate samples of pustules were taken, 4 had positive results from direct examinations and cultures for Malassezia . Cultures from 6 of 16 contralateral swabs were also positive. Among 19 controls, 6 had positive cultures. The number of patients sampled was not sufficient to make a statistical analysis, but the 2 groups positive for Malassezia were approximately the same size, which indicates that skin is normally colonized by yeasts of the genus Malassezia. Because the patient and control groups were separated by age, we were able to determine that the prevalence of Malassezia increased with age: the incidence was 7% in patients between birth and 15 days, 42% in patients between 16 and 30 days, and 71% in patients between 31 and 45 days. Among 11 infants who were from 28 to 33 weeks premature at birth, 4 had positive swab cultures. Two were diagnosed as having a minor form of papulopustulosis based on a blank sampling of their pustules. The time at onset of inflammatory lesions in the premature infants was the same as that for term infants.

We distinguished 3 clinical categories according to the severity of the cephalic pustulosis: minor forms with fewer than 3 papules and/or pustules (6 cases), moderate forms with between 4 and 10 pustules (4 cases), and severe forms with extensive erythema and pustules on most of the face (6 cases). A correlation between isolation of Malassezia and severity was found (Table 2).

Whenever results from microscopic examinations were positive, Malassezia was also found in culture. In all patients, when cultures were positive we identified Malassezia sympodialis. In the control group, when cultures were positive we identified Malassezia furfur in 4 cases and M sympodialis in 2 cases.

On direct examination, inflammatory cells were found in all positive cases. In most cases, the cells were polymorphonuclear neutrophils, and in rare cases, eosinophils, basophils, or lymphocytes mixed with some epithelial cells.

First described by Aractingi et al⁴ in 1991, this type of cephalic pustulosis associated with Malassezia is frequently identified in neonates (approximately 3% in our sample of hospitalized infants). The diagnostic criteria suggested by Rapelanoro et al⁶ are age at onset, cephalic location, direct microscopic examination positive for Malassezia, elimination of other causes of neonatal pustuloses, and response to topical ketoconazole therapy.

However, further criteria were needed to confirm the pathogenic role of Malassezia in cephalic pustulosis.

Based on epidemiological data, the saprophytic role of Malassezia yeast in the skin of healthy adults and children suggests that the causative role of Malassezia in neonatal pustulosis is debatable when found in cutaneous lesions, except if a primary colonization elicits in some individuals an inflammatory skin reaction. Malassezia is found in more than 90% of adults,^{5 - 6} and it is now admitted that the degree of Malassezia colonization increases with age. Nevertheless, authors do not agree on the age at which Malassezia develops on skin after birth. According to Faergemann and Fredriksson,¹¹ colonization starts after 5 years of age, but Koseki and Takahashi² found this yeast in 50% of healthy newborns and in 80% of infants after 7 days of life. Borderon et al³ found Malassezia in 13%, 30%, and 77% of most premature neonates younger than 15 days, 16 to 30 days, and 31 to 90 days, respectively. In both of our groups combined as well as in the control group only, progressive colonization was correlated with age, beginning primarily after 2 weeks of age, whatever the term of the infant at birth. The controversy is mainly due to differences in patients (premature vs term newborns), methods (smears vs scrapings or intravascular catheters), and settings (intensive care vs outpatient facilities) used by investigators. Based on our findings in a nonintensive care neonatal unit where the infants were treated with a skin hygiene regimen that is not supposed to support the growth of lipophilic yeasts, we believe that the colonization of Malassezia in neonates increases with age.

In our study, the mean age at onset of cephalic papulopustulosis was 12 days. Patients with the severe form of neonatal acnelike lesions in whom findings from direct examinations and cultures were positive for Malassezia were older than 3 weeks, and in the case group, Malassezia species were not detected before 16 days. Thus, other factors may contribute to the development of the common papulopustular facial eruptions commonly seen in newborns, or favor a secondary colonization or invasion by Malassezia species. The pathogenesis of cephalic papulopustulosis may involve neonatal sebum production, which allows for a better growth of lipophilic yeasts and the seeding of yeasts from the mother or other carriers in the child's environment. Furthermore, papulopustular facial lesions in neonates are difficult to interpret clinically; some may correspond to milia and sebaceous gland hyperplasia. As in our previous study,⁶ all infants with significant lesions were cured after the application of topical 2% ketoconazole cream twice per day for 1 week. The anti-inflammatory effect of ketoconazole may have had a nonspecific effect similar to that reported for infantile seborrheic dermatitis.¹² However, on direct microscopic examination, high cellularity was correlated with the detection of Malassezia, suggesting a pathogenic link. We recovered polymorphonuclear neutrophils, eosinophils, basophils, and lymphocytes in most of our positive cases. Our data suggest that increasing colonization leads to increasing clinical severity. We also noted a tendency toward an increased number of colonies of Malassezia in the contralateral nonpustular skin of patients with pustules positive for Malassezia. This contralateral skin was disinfected. The samples that were taken from a larger area by swabbing contralateral skin may explain the higher count of colonies on those sites (vs samples from pustules), as well as the inhibitory role of proteases released by polymorphonuclear cells in the pustules.

The recent taxonomic revision of the lipophilic yeast genus based on morphologic, ultrastructural, physiological, and molecular biologic analyses included 7 species of the 3 former taxa—M furfur, Malassezia pachydermatis, M sympodialis —and 4 new taxa—Malassezia globosa, Malassezia obtusa, Malassezia restricta, and Malassezia sloofiae.¹³ Malassezia sympodialis was first reported in humans in 1990 by Simmons and Guého,¹⁴ and more recently in the cat by Bond et al.¹⁵ If it is confirmed that M pachydermatis is adapted to animals (and occasionally encountered in humans), M sympodialis, along with M globosa and M restricta, appears to be a yeast that occurs frequently on human skin. This seems not to be the case with M furfur, which develops less frequently on human skin.¹³ However, currently it is only possible to speculate on the prevalence of M sympodialis, since the data concerning the collection of species came from several sources, not from a prospective study of young patients such as ours. In our study, we identified 2 species: M sympodialis and M furfur. In the case group, from all pustules or skin scrapings positive for Malassezia, we identified only M sympodialis (6 patients) in culture, and we always recovered this same species in both smears and contralateral swab cultures. In contrast, we never isolated M furfur in this group. However, in controls, M furfur was identified on 4 occasions, and M sympodialis was identified only twice.

Common neonatal cephalic pustulosis is now a well-recognized benign entity that was in the past improperly named neonatal acne. The hypothesis that it represents an inflammatory reaction against a colonization by yeasts of the genus Malassezia is strongly suggested by this study. Based on our findings, M sympodialis has a possible role in the severe form of common neonatal cephalic pustulosis. In contrast, the presence of M furfur in nonsymptomatic patients suggests that this species is a saprophytic inhabitant of normal human skin at birth. It is likely that colonization resulting from environmental factors could lead to cutaneous inflammation in predisposed children with more intense sebum production, which may be an initiating factor in follicular or poral occlusion.

Accepted for publication March 3, 1998.

Reprints: Alain Taïeb, MD, Pediatric Dermatology Unit, Hôpital Pellegrin-Enfants, Centre Hospitalier Universitaire de Bordeaux, Place Amélie Raba-Léon, 33076 Bordeaux, Cedex, France (e-mail: alain.taieb@u-bordeaux2.fr).