Blueberry muffin baby, also known as extramedullary hematopoiesis, describes a
newborn baby with multiple
purpura
Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...
, associated with several non-cancerous and cancerous conditions in which
extra blood is produced in the skin.
The bumps range from 1-7mm, do not blanche and have a tendency to occur on the head, neck and trunk.
[ They often fade by 3 to 6 weeks after birth, leaving brownish marks.] When due to a cancer, the bumps tend to be fewer, firmer and larger.
It can occur following infection of an unborn baby with rubella
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 ...
, cytomegalovirus
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
, toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
, or coxsackie virus
Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovirus and echoviru ...
. Other viral causes include parvovirus B19
Primate erythroparvovirus 1, generally referred to as B19 virus (B19V), parvovirus B19 or sometimes erythrovirus B19, is the first (and until 2005 the only) known human virus in the family ''Parvoviridae'', genus ''Erythroparvovirus''; it measur ...
and herpes simplex
Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected.
Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold ...
.[ Non-infectious causes include ]haemolytic disease of the newborn
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
, hereditary spherocytosis
Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (sp ...
, twin-to-twin transfusion syndrome
Twin-to-twin transfusion syndrome (TTTS), also known as feto-fetal transfusion syndrome (FFTS), twin oligohydramnios-polyhydramnios sequence (TOPS) and stuck twin syndrome, is a complication of monochorionic multiple pregnancies (the most common ...
and recombinant erythropoietin administration.[ Some types of cancers can cause it such as ]rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.
There are four subt ...
, extrosseal Ewing sarcoma
Ewing sarcoma is a type of cancer that forms in bone or soft tissue. Symptoms may include swelling and pain at the site of the tumor, fever, and a bone fracture. The most common areas where it begins are the legs, pelvis, and chest wall. In about ...
, Langerhans cell histiocytosis
Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes.
Symptoms range from isolated bone lesions to multisystem dise ...
, congenital leukaemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
and neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
.[ During normal development of an unborn baby, blood production can occur in the skin until the fifth month of pregnancy.][ Blueberry muffin lesions in the newborn indicate the prolongation of skin blood production after birth.][
Diagnosis involves a combination of appearance and laboratory studies, including blood tests for ]complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
, TORCH infections, haemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
, viral cultures and Coombs test.[ A skin biopsy may be useful.][ Conditions that may appear similar include ]hemangiopericytoma
A hemangiopericytoma is a type of soft-tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behavior ...
, blue rubber bleb nevus, hemangioma
A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the ski ...
and glomangioma.[
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.][ The term was coined in the 1960s to describe the skin changes in babies with congenital rubella.][ Since then, it has been realised that blueberry muffin marks occur in several conditions.][
]
Signs and symptoms
These lesions are typically non-blanching macules
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...
or papules
A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
that present as a generalized rash in the newborn.[
]
Causes
During normal embryologic development, hematopoiesis
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
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
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 ...
, 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
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
, herpes virus, and toxoplasma. Blood disorders, such as hereditary spherocytosis
Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (sp ...
and hemolytic disease of the newborn
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
, 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
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
and congenital leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
. Listed below are a few known conditions that can cause a blueberry muffin baby.
Infectious
* Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...
: 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
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
, and chorioretinitis
Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthalm ...
.
* Cytomegalovirus
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
: viral TORCH infection associated with sensorineural hearing loss
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of rep ...
, hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...
, and jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
.
* Rubella
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 ...
: 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
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
.
* Syphilis
Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
: bacterial TORCH infection due to Treponema pallidum
''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...
. Congenital syphilis can present with saber shin
Saber shin is a malformation of the tibia. It presents as a sharp anterior bowing, or convexity, of the tibia.
__TOC__
Causes
Periosteal reaction along the shaft of the tibia.
It can result from congenital syphilis, yaws, Paget's disease of bo ...
s, saddle-shaped nose, Hutchinson's teeth
Hutchinson's teeth is a sign of congenital syphilis. Affected people have teeth that are smaller and more widely spaced than normal and which have notches on their biting surfaces. It is named after Sir Jonathan Hutchinson, an English surgeon an ...
, and deafness.
* Epstein Barr virus The surname Epstein ( yi, עפּשטײן, Epshteyn) is one of the oldest Ashkenazi Jewish family names. It is probably derived from the German town of Eppstein, in Hesse; the place-name was probably derived from Gaulish ''apa'' ("water", in the se ...
: viral infection that causes infectious monocleosis. Condition is associated with lymphadenopathy
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
, splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulating ...
, and various lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
s
Hematologic
* Hereditary spherocytosis
Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (sp ...
: autosomal dominant
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
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
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
(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
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
: pediatric cancer due to malignancy in neuroblast cells. Tumor is usually localized to the adrenal gland
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
s.
* Congenital leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...
: pediatric cancer due to malignancy of white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s.
* Congenital rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.
There are four subt ...
: pediatric cancer due to malignancy of muscle cells.
Systemic
* Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
histiocytosis (LCH): Condition due to excess build-up of Langerhans cell
A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...
s.
* Lupus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
: 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
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cell ...
(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
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
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
Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...
, jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
, hepatosplenomegaly
Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and hist ...
, microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
, cataracts
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
, or sensorineural hearing loss
Sensorineural hearing loss (SNHL) is a type of hearing loss in which the root cause lies in the inner ear or sensory organ (cochlea and associated structures) or the vestibulocochlear nerve (cranial nerve VIII). SNHL accounts for about 90% of rep ...
. The presence of these features can further bolster the diagnosis of congenital rubella as the cause of the blueberry muffin baby. Laboratory studies for congential 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
Chorioretinitis is an inflammation of the choroid (thin pigmented vascular coat of the eye) and retina of the eye. It is a form of posterior uveitis. If only the choroid is inflamed, not the retina, the condition is termed choroiditis. The ophthalm ...
. On lab studies, there may be a high anti-cytomegalovirus antibody titer, positive CMV urine culture, and thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
.[
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
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
and acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...
are all rare but possible causes of a blueberry muffin baby. Most of the time, these conditions are diagnosed using immunohistochemistry
Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
and biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
.[
]
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
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
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
The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles), abbreviated as ''MMR''. The first dose is generally given to children around 9 months to 15 months of age, with a second dose at 15 months to 6 years of age, ...
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
Valganciclovir, sold under the brand name Valcyte among others, is an antiviral medication used to treat cytomegalovirus (CMV) infection in those with HIV/AIDS or following organ transplant. It is often used long term as it only suppresses rath ...
or ganciclovir
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.
Ganciclovir was patented in 1980 and approved for medical use in 1988.
Medical use
Ganciclovir is indicated f ...
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
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
. Overall, treatment of the blueberry muffin baby is centered around the underlying cause.
See also
* List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...
* Congenital rubella
Congenital rubella syndrome (CRS) can occur in a developing fetus of a pregnant woman who has contracted rubella, usually in the first trimester. If infection occurs 0–28 days before conception, the infant has a 43% risk of being affected. If t ...
References
External links
* {{DermAtlas, 1885510711
Vascular-related cutaneous conditions