Blueberry muffin baby

Causes

During normal embryologic development, hematopoiesis can occur in the dermis until the fifth month of gestation. Blueberry muffin lesions in the neonate indicate the prolongation of dermal extramedullary hematopoiesis outside of the gestational period.

The blueberry muffin rash was originally considered pathognomonic of congenital rubella, but it is now considered to be potentially associated with many other intrauterine infections, hematologic diseases, and malignancies. Other TORCH infections that can cause this rash include cytomegalovirus, herpes virus, and toxoplasma. Blood disorders, such as hereditary spherocytosis and hemolytic disease of the newborn, that increase extramedullary hemotopoeisis can also cause a blueberry muffin baby. It is also possible that a neonate with the blueberry muffin rash can have an underlying malignancy such as metastatic neuroblastoma and congenital leukemia. Listed below are a few known conditions that can cause a blueberry muffin baby.

Infectious

• Toxoplasmosis: TORCH infection due to Toxoplasma gondii parasite. Condition is commonly associated with undercooked meat or contact with cat feces. Symptoms of this disease include seizures, hydrocephalus, and chorioretinitis.
• Cytomegalovirus: viral TORCH infection associated with sensorineural hearing loss, hepatomegaly, and jaundice.
• Rubella: viral TORCH infection associated with post-auricular and occipital lymphadenopathy in addition to a maculopapular rash that starts on the face and spreads to the trunk.
• Herpes virus: viral TORCH infection associated with painful vesicular lesions and meningitis.
• Syphilis: bacterial TORCH infection due to Treponema pallidum. Congenital syphilis can present with saber shins, saddle-shaped nose, Hutchinson's teeth, and deafness.
• Epstein Barr virus: viral infection that causes infectious mononucleosis. Condition is associated with lymphadenopathy, splenomegaly, and various lymphomas

Hematologic

• Hereditary spherocytosis: autosomal dominant disease that results in formation of aberrant erythrocyte membrane protein. This condition results in structural change of red blood cells (RBCs), shearing of RBCs, and anemia.
• Hemolytic disease of the newborn (ABO or Rh incompatibility): Condition is due to maternal and fetal red blood cell mismatch. Maternal antibodies destroy fetal RBCs which results in anemia.

Neoplastic

• Neuroblastoma: pediatric cancer due to malignancy in neuroblast cells. Tumor is usually localized to the adrenal glands.
• Congenital leukemia: pediatric cancer due to malignancy of white blood cells.
• Congenital rhabdomyosarcoma: pediatric cancer due to malignancy of mesenchymal cells that have failed to fully differentiate into muscle cells

Systemic

• Langerhans cell histiocytosis (LCH): Condition due to excess build-up of Langerhans cells.
• Lupus: autoimmune disease

Diagnosis

Diagnosis of the medical condition is based on a combination of clinical presentation, physical exam, and laboratory studies. When this characteristic rash is found in a neonate, laboratory workup is prompted.

Initial workup usually includes a complete blood count (CBC) with differential to evaluate for underlying blood disorders. Laboratory confirmation of the cause of the blueberry muffin rash depends on the underlying illness.

For example, serology positive for rubella specific antibodies, viral culture with isolated rubella, or isolation of rubella virus RNA through polymerase chain reaction can all confirm that congenital rubella infection is the underlying cause of the blueberry muffin rash. Other manifestations of congenital rubella disease can also appear in conjunction with the characteristic rash. These include congenital glaucoma, jaundice, hepatosplenomegaly, microcephaly, cataracts, or sensorineural hearing loss. The presence of these features can further bolster the diagnosis of congenital rubella as the cause of the blueberry muffin baby. Laboratory studies for congenital rubella infection should be done prior to 1 year of age as diagnosis becomes more challenging afterwards.

In the case of infection with cytomegalovirus (CMV), patients can present with associated symptoms such as deafness and chorioretinitis. On lab studies, there may be a high anti-cytomegalovirus antibody titer, positive CMV urine culture, and thrombocytopenia.

If the cause is due to hemolytic disease of the newborn or hereditary spherocytosis, the neonate will have a positive Coomb's test and unconjugated hyperbilirubinemia.

Malignancies such as neuroblastoma and acute myeloid leukemia are all rare but possible causes of a blueberry muffin baby. Most of the time, these conditions are diagnosed using immunohistochemistry and biopsy.

Prognosis

Prognosis is variable based on underlying cause. Usually the lesions should resolve within three to six weeks post-delivery. There has been a documented case of the rash completely resolving following a blood transfusion to treat severe anemia in a neonate. The rash is usually transient and will resolve once the underlying cause is treated.

Treatment

Treatment is variable based on underlying cause. If significant anemia is present, blood transfusion may be indicated. In the case of congenital rubella infection, there is no known cure. Therefore, the focus of treatment is disease prevention. The MMR vaccine is highly efficacious in preventing congenital rubella and is given routinely as a part of the pediatric vaccine schedule. For neonates with congenital CMV infection, antiviral medication is given. Most commonly, valganciclovir or ganciclovir are used as first-line antiviral therapy for congenital CMV. If the cause is a malignancy, the patient should receive cancer treatment such as chemotherapy. Overall, treatment of the blueberry muffin baby is centered around the underlying cause.