When a Blueberry Muffin Rash Isn’t Infectious- a Lesson on Differentials from a Rare Presentation
Introduction: Rashes are a common complaint in the neonatal and infantile periods, and recognizing those which may be a sign of more malignant conditions is undoubtedly important for pediatric providers. Here, we present the case of a purple to blue hued rash in a two month old infant, and discuss differentials for a “blueberry muffin” rash in this age category.
Case Description: A 2 month old infant presented for evaluation of a purple to blue colored rash. She reportedly had an uncomplicated pregnancy and delivery, was developing appropriately, and gaining weight well.
On initial presentation, the patient has multiple scattered subcutaneous nodules over large areas of her body including scalp, right nape of neck, right thigh, abdomen, back, and bilateral legs (see Figure 1). A skin biopsy revealed pathology consistent with metastatic neuroblastoma.
Discussion: Neuroblastomas are a primarily pediatric embryonal tumor arising from primitive sympathetic ganglion cells; approximately two-thirds of primary tumors arise in the abdomen. Metastasis to the skin can occur in disseminated disease, though this is a rarer finding (although more common in the neonatal period), and rarer still to be the initial presentation of disease.
Classically, a "blueberry muffin" rash is characterised by blue to red macules or dome shaped non-blanching papules, usually generalized.
The differentials for this type of rash are summarized in table 1. The rash in rubella and CMV infections are caused by dermal erythropoiesis. Clues to this diagnosis include prematurity, SGA, and associated hepatosplenomegaly, failed hearing screen, chorioretinitis, and developmental delay.
Dermal erythropoiesis can also occur in response to hemolytic disease of the newborn or hereditary spherocytosis, leading to a blueberry muffin type appearance. This patient in particular presented with subcutaneous nodules. An important differential for infants with firm subcutaneous nodules include subcutaneous fat necrosis, which is associated with birth asphyxia, hypoglycaemia, and therapeutic hypothermia.
Langerhans Cell Histiocytosis (LCH) and cutaneous leukemia should also be considered in these cases. Skin involvement occurs in approximately half of patients with LCH, and classically appear as small papules or nodules which often develop central ulceration. Involvement of the dermis in leukemia is usually concomitant with the development of the malignancy, and therefore the purpuric rash accompanies systemic signs of illness.
A notable characteristic of the blue-purple nodules of disseminated neuroblastoma is that these lesions blanch on palpation, then exhibit a halo of erythema which persists for approximately 30-60 minutes due to catecholamine release. Blueberry-muffin lesions due to other neoplastic causes tend to be fewer in number, larger, and firmer than those of infectious causes.
Conclusion: This case highlights the importance of considering differentials beyond TORCH infections in a patient presenting with a blueberry muffin type rash.
