Blueberry muffin baby | |
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A newborn baby with typical lesions of a blueberry muffin baby. | |
Specialty | Pediatrics, dermatology |
Symptoms | Reddish-blue purpura localized mainly to the face, neck, and trunk [1] |
Causes | Congenital rubella, congenital CMV, other TORCH infections, blood disorders, and malignancies [1] |
Diagnostic method | Blood tests for complete blood count, TORCH infections, haemoglobin, viral cultures and Coombs test, skin biopsy [1] |
Differential diagnosis | Hemangiopericytoma, blue rubber bleb nevus, hemangioma, glomangioma [1] |
Prevention | MMR vaccine covers for congenital rubella |
Frequency | Uncommon [2] |
Blueberry muffin baby, also known as extramedullary hematopoiesis, describes a newborn baby with multiple purpura, associated with several non-cancerous and cancerous conditions in which extra blood is produced in the skin. [1] The bumps range from 1-7 mm, do not blanch and have a tendency to occur on the head, neck and trunk. [1] They often fade by three to six weeks after birth, leaving brownish marks. [3] When due to a cancer, the bumps tend to be fewer, firmer and larger. [2]
The condition can occur following infection of an unborn baby with rubella, cytomegalovirus, toxoplasmosis, or coxsackie virus. [4] Other viral causes include parvovirus B19 and herpes simplex. [1] Non-infectious causes include haemolytic disease of the newborn, hereditary spherocytosis, twin-to-twin transfusion syndrome and recombinant erythropoietin administration. [1] Some types of cancers can cause it such as rhabdomyosarcoma, extrosseal Ewing sarcoma, Langerhans cell histiocytosis, congenital leukaemia and neuroblastoma. [1] During normal development of an unborn baby, blood production can occur in the skin until the fifth month of pregnancy. [3] Blueberry muffin lesions in the newborn indicate the prolongation of skin blood production after birth. [3]
Diagnosis involves a combination of appearance and laboratory studies, including blood tests for complete blood count, TORCH infections, haemoglobin, viral cultures and Coombs test. [1] A skin biopsy may be useful. [1] Conditions that may appear similar include hemangiopericytoma, blue rubber bleb nevus, hemangioma and glomangioma. [1]
Prognosis is variable based upon the cause of the characteristic rash. Treatment may include supportive care, anti-viral medication, transfusion, or chemotherapy depending on the underlying cause.
It is not common. [2] The term was coined in the 1960s to describe the skin changes in babies with congenital rubella. [2] Since then, it has been realised that blueberry muffin marks occur in several conditions. [2]
These lesions are typically non-blanching macules or papules that present as a generalized rash in the newborn. [3]
During normal embryologic development, hematopoiesis can occur in the dermis until the fifth month of gestation. [3] Blueberry muffin lesions in the neonate indicate the prolongation of dermal extramedullary hematopoiesis outside of the gestational period. [3]
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. [3] Other TORCH infections that can cause this rash include cytomegalovirus, [5] 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. [6] Listed below are a few known conditions [3] [7] that can cause a blueberry muffin baby.
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. [6] 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. [8] 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. [8] Laboratory studies for congential rubella infection should be done prior to 1 year of age as diagnosis becomes more challenging afterwards. [9]
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. [3]
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. [3]
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. [3]
Prognosis is variable based on underlying cause. Usually the lesions should resolve within three to six weeks post-delivery. [3] There has been a documented case of the rash completely resolving following a blood transfusion to treat severe anemia in a neonate. [7] The rash is usually transient and will resolve once the underlying cause is treated.
Treatment is variable based on underlying cause. If significant anemia is present, blood transfusion may be indicated. [7] 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. [10] 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. [11] If the cause is a malignancy, the patient should receive cancer treatment such as chemotherapy. [6] Overall, treatment of the blueberry muffin baby is centered around the underlying cause.
Rubella, also known as German measles or three-day measles, is an infection caused by the rubella virus. This disease is often mild, with half of people not realizing that they are infected. A rash may start around two weeks after exposure and last for three days. It usually starts on the face and spreads to the rest of the body. The rash is sometimes itchy and is not as bright as that of measles. Swollen lymph nodes are common and may last a few weeks. A fever, sore throat, and fatigue may also occur. Joint pain is common in adults. Complications may include bleeding problems, testicular swelling, encephalitis, and inflammation of nerves. Infection during early pregnancy may result in a miscarriage or a child born with congenital rubella syndrome (CRS). Symptoms of CRS manifest as problems with the eyes such as cataracts, deafness, as well as affecting the heart and brain. Problems are rare after the 20th week of pregnancy.
Congenital rubella syndrome (CRS) occurs when a human fetus is infected with the rubella virus via maternal-fetal transmission and develops birth defects. The most common congenital defects affect the ophthalmologic, cardiac, auditory, and neurologic systems.
Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening.
Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the normal biconcave disk shape. This abnormal shape interferes with the cells' ability to flex during blood circulation, and also makes them more prone to rupture under osmotic stress, mechanical stress, or both. Cells with the dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes and results in hemolytic anemia.
Neonatal jaundice is a yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels. Other symptoms may include excess sleepiness or poor feeding. Complications may include seizures, cerebral palsy, or kernicterus.
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, 15-40% of those with AIDS.
A vertically transmitted infection is an infection caused by pathogenic bacteria or viruses that use mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother has a pre-existing disease or becomes infected during pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infections. Vertical transmission is important for the mathematical modelling of infectious diseases, especially for diseases of animals with large litter sizes, as it causes a wave of new infectious individuals.
Dukes' disease, named after Clement Dukes (1845–1925), also known as fourth disease, Filatov-Dukes' disease, Staphylococcal Scalded Skin Syndrome (SSSS), or Ritter's disease is an exanthem (rash-causing) illness primarily affecting children and historically described as a distinct bacterial infection, though its existence as a separate disease entity is now debated.
Extramedullary hematopoiesis refers to hematopoiesis occurring outside of the medulla of the bone. It can be physiologic or pathologic.
Erythema toxicum neonatorum is a common, non-threatening rash in newborns. It appears in 4-70% of newborns within the first week of life, and it typically improves within 1–2 weeks. It only occurs during the newborn period, but may appear slightly later in premature babies. The rash has a variable appearance. It typically includes blotchy red spots, often with overlying firm, yellow-white bumps or pus-filled boils. There may be only a few or many lesions. The lesions can appear almost anywhere on the body, and individual lesions may appear and disappear within hours. There are no other symptoms associated with erythema toxicum neonatorum, and the rash does not have any long-term effects on the skin. Erythema toxicum neonatorum is not harmful and does not require any treatment.
Reticulocytopenia is the medical term for an abnormal decrease in circulating red blood cell precursors (reticulocytes) that can lead to anemia due to resulting low red blood cell (erythrocyte) production. Reticulocytopenia may be an isolated finding or it may not be associated with abnormalities in other hematopoietic cell lineages such as those that produce white blood cells (leukocytes) or platelets (thrombocytes), a decrease in all three of these lineages is referred to as pancytopenia.
Betaherpesvirinae is a subfamily of viruses in the order Herpesvirales and in the family Herpesviridae. Mammals serve as natural hosts. There are 26 species in this subfamily, divided among 5 genera. Diseases associated with this subfamily include: human cytomegalovirus (HHV-5): congenital CMV infection; HHV-6: 'sixth disease' ; HHV-7: symptoms analogous to the 'sixth disease'.
Myelophthisic anemia is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue by fibrosis, tumors, or granulomas. The word comes from the roots myelo-, which refers to bone marrow, and phthysis, shrinkage or atrophy.
Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.
Human betaherpesvirus 5, also called human cytomegalovirus (HCMV,HHV-5), is a species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.
A Cytomegalovirus vaccine is a vaccine to prevent cytomegalovirus (CMV) infection or curb virus re-activation in persons already infected. Challenges in developing a vaccine include adeptness of CMV in evading the immune system and limited animal models. As of 2018 no such vaccine exists, although a number of vaccine candidates are under investigation. They include recombinant protein, live attenuated, DNA and other vaccines.
Neonatal herpes simplex, or simply neonatal herpes, is a herpes infection in a newborn baby, caused by the herpes simplex virus (HSV). It occurs mostly as a result of vertical transmission of the HSV from an affected mother to her baby. Types include skin, eye, and mouth herpes (SEM), disseminated herpes (DIS), and central nervous system herpes (CNS). Depending on the type, symptoms vary from a fever to small blisters, irritability, low body temperature, lethargy, breathing difficulty, and a large abdomen due to ascites or large liver. There may be red streaming eyes or no symptoms.
Cytomegalovirus esophagitis is a form of esophagitis associated with cytomegalovirus. Symptoms include dysphagia, upper abdominal pain, diarrhea, nausea, vomiting, and sometimes hematemesis. This condition occurs in the setting of patients with a weakened immune system who are susceptible to both infections by CMV and the manifestation of symptoms. A large majority of patient that have CMV Esophagitis are diagnosed with HIV. Another significant segment of the population have weakened immune systems through transplant surgery, diabetes, or due to medication. Diagnosis is done primarily by endoscopy with biopsy, as CMV Esophagitis has a distinctive pathology pattern of linear ulcers.
Congenital cytomegalovirus (cCMV) is cytomegalovirus (CMV) infection in a newborn baby. Most have no symptoms. Some affected babies are small. Other signs and symptoms include a rash, jaundice, hepatomegaly, retinitis, and seizures. It may lead to loss of hearing or vision, developmental disability, or a small head.
Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.