VIGNETTES

Transient myeloproliferative disorder (TMD) is an exceptional cause of noninfectious neonatal pustules.¹ It is indistinguishable from congenital leukemia; the main difference is its spontaneous remission. However, 20% of patients with TMD develop acute megakaryoblastic leukemia during the first 4 years. Transient myeloproliferative disorder affects up to 10% of patients with Down syndrome, who also have an increased risk of developing congenital leukemia.² This disorder has also been described in 46,XX karyotype individuals with trisomy 21 mosaicism.³ Recent studies show that acquired mutations in the transcription factor GATA1, found initially in acute megakaryoblastic leukemia in patients with Down syndrome, also cause TMD. A second genetic hit is necessary to develop leukemia.^{2 ,4}

We present 2 monochorial female twins with a 46,XX karyotype. Obstetric history revealed a twin-to-twin transfusion syndrome, which was treated with intrauterine laser coagulation. The twins’ mother experienced preterm labor at 30 weeks’ gestation, and a cesarean delivery was undertaken. A third healthy triplet was born of an independent chorion.

On the second day of life, the monochorial twins had a vesiculopustular skin eruption and hepatosplenomegaly. A predominant blast cell population, anemia, and low platelet count were present in blood and bone marrow samples. The vesicles and pustules clustered over erythematous, mildly infiltrated plaques predominantly at sites of previous trauma or pressure. The lesions evolved into superficial ulcerations (Figure 1). Testing the lesions using gram stain, potassium hydroxide, Tzanck smears, and repeated culture gave negative findings. Cytologic findings revealed neutrophils, some eosinophils, and rare blast cells. A skin biopsy specimen showed a subcorneal pustule with multiple neutrophils and some eosinophils and several immature histiocytoid-appearing cells (Figure 2). Immunohistochemical studies showed isolated positivity for hematopoietic stem cells.

Cytogenetic studies of the bone marrow blast cells in both twins were trisomic for chromosome 21 of an undifferentiated cellular lineage.

Transient myeloproliferative disorder with sterile vesicles and pustules in normal karyotype twins and a trisomy 21 (47,XX, +21) in blast cells was diagnosed, and no specific treatment was given. Skin lesions followed a course parallel to hematological findings, resolving spontaneously when the twins were 3 months of age.

Obstetric history of twin-to-twin transfusion syndrome suggests a fetal origin and an in utero transmission of the hematological disorder.

Sterile vesicles and pustules are a typical manifestation of TMD, and, as far as we know, there are no cases of such lesions associated with true congenital leukemia, where skin findings are described as firm nodules.⁵ A sterile pustular rash in a neonate with trisomy 21 mosaicism or Down syndrome with leukocytosis and blast cells is a probable sign of the transitory nature of this hematological disorder, although it does not exclude the possibility of acute megakaryoblastic leukemia developing in subsequent years.

This clinical entity resembles neutrophilic dermatosis associated with myeloproliferative disorders, in which pronounced epidermal changes are more common. Immature myeloid precursors and histiocytoid-appearing cells that contain myeloperoxidase may be found in biopsy specimens of these skin lesions, suggesting an immature neutrophilic lineage. The polymorphous inflammatory infiltrate therefore could be a reactive phenomenon; the rare blast cells may have been recruited with the general inflammatory cell response. The existence of similar cellular infiltrates in the skin lesions of both twins suggests a blast cell tropism to the skin.

Correspondence: Dr Viros, Department of Dermatology, N461 Comprehensive Cancer Center at University of California–San Francisco, 2340 Sutter St, San Francisco, CA 94115-3024 (aviros@cc.ucsf.edu).

Financial Disclosure: None.

Acknowledgment: We thank Luís Requena, MD, from the Fundación Jiménez Díaz, Madrid, Spain, for his helpful comments.