User:Anewens/Diffuse neonatal hemangiomatosis

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Diffuse neonatal hemangiomatosis (DNH) is a potentially fatal disorder where multiple benign (non-cancerous) blood vessel tumors (hemangiomas) are present in the skin and other organs. The mortality rate of diffuse neonatal hemangiomatosis is 50-90%. This disease is normally found in female Caucasian infants. The most common site of internal organ damage, or lesions, is the liver, which can redirect blood away from the heart and cause arteriovenous shunting. This can cause high cardiac output, leading to further complications such as congestive heart failure. This condition affecting the liver is also known as infantile hepatic hemangioma (IHH). Other sites of internal organ damage can include the intestines, nervous system, lungs, and sometimes the skeletal system. Early detection and treatment with steroids results in most newborn babies with this disease remaining healthy, with serious problems developing for some individuals during the hemangioma's growth phase.

Differential Diagnosis

In the past, the diagnosis of "diffuse neonatal hemangiomatosis" included both infantile hemangioma (IH) and multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). With advances in medicine and vascular anomalies, there is now a differentiation between the diagnosis of IH, which is benign, and MLT, which has a high mortality rate. Because of this misdiagnosis of MLT as DNH, it is believed that DNH has lower mortality rate than the report 50-90% that it is currently believed to have.[citation needed]

In a literature review of 73 cases of DNH that have been reported, many of these reports classified diffuse neonatal hemangiomatosis as other multifocal vascular abnormalities such as multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT). It is important to have an accurate diagnosis and reference the correct data in order to administer adequate treatment for individuals.

Hepatic hemangiomas

Hepatic hemangiomas are the most common site for internal organ damage. It may be difficult to identify hepatic hemangiomas because it can be inaccurately diagnosed as a hyper-vascular malignancy. These malignancies can live alongside other liver tumors such as hepatic cysts, hepatic angiosarcoma, focal nodular hyperplasia, and a myriad of others. Hepatic hemangiomas are usually small and discovered by chance when looking at the liver with an ultrasound, MRI, or other medical scans. Normally, these hepatic hemangiomas are seen on the right lobe of the liver.

In many circumstances, infants with multiple marks on the skin have hepatic hemangiomas. One retrospective review followed 26 infants between 1996-2007 to evaluate the management of hepatic hemangiomas and whether the infants required more complex treatment methods. The infants were classified as having either focal (8), multiple (12), or diffuse (6) lesions, or injuries. All of the infants who had multiple or diffuse injuries were assessed and screened for congestive heart failure and hypothyroidism, in which 4 patients later developed congestive heart failure. During the review, 9 infants required treatment with steroids, and 3 infants received additional treatment with alpha-interferon after poor response to the steroids. The review concluded that individuals with multiple marks on the skin require screening for hepatic hemangiomas, and individuals with multifocal or diffuse liver hemangiomas require screening for heart failure and hypothyroidism to determine the most effective treatment method. In addition, the condition of an individual's injuries can indicate whether hepatic hemangiomas are present and if extensive treatment is needed.

Another retrospective review followed 25 infants over a span of 10 years with a serious case of hemangiomas, which could even be life threatening. 68% of the infants displayed an injury in the blood vessel to indicate a hemangioma. 23 out of 25 of the infants were given corticosteroids to treat their condition with a range of responses from complete failure to rapid improvement. 30% of the infants given corticosteroids failed the treatment while 30% of the infants saw dramatic improvement in their condition. Out of the 25 infants, 3 of the infants were diagnosed with hepatic hemangiomas and were associated with cardiac failure and a high mortality rate. In the end, the 3 infants with hepatic hemangiomas died due to the high mortality.

Intracranial Hemangiomas: Case Study

Case Report

The patient was suspected to have a fetal brain tumor found through a prenatal ultrasonography when the mother was at 39 weeks gestation. Three weeks later, the ultrasonography showed a light mass on the fetus' frontal lobe. This tumor had no blood flow going to it as seen by the color sonography. It is important to note that the mother had a normal medical history and no hereditary condition.

The infant was 3.1 kg and had normal movement. With a CT scan, it was found that there was cranial edema, and a round mass in the frontal lobe. At birth, there was no skin discoloration. However, six days later, the skin discoloration was found on the abdomen and right scrotum. Additionally, at day six, a four centimeter hepatic mass was found on the left lobe. On day thirteen and seventeen, a hepatic hemorrhage was found on the left lobe and the right lobe was damaged as well. The CT scan also found damage to the paraspinal muscles. Then, the provider decided to give the infant propranolol 3mg/kg/day.

The baby was not taken in for a second round of treatment until two months and twenty-two days later. The tumor noticeably shrank to cysts; however, the biggest cyst was at the frontal lobe. A myriad of lesions were still found on the thalamus, pons, cerebral hemispheres, cerebellum, and choroid plexus. It was then the radiologist diagnosed the patient with diffuse neonatal hemangiomatosis. At nine months, the patient experienced loss of brain tissue due to the shrunken tumor.

Discussion

Second to the liver, the brain is the most common place for diffuse neonatal hemangiomatosis. With that being said, there has only been only sixteen cases of cranial hemangioma. Nine out of the total sixteen cases undergo neurological manifestations. With damage to the brain, the skin red discolorations are usually half to one and half centimeters.

As emphasized before, it is rare to have a fetal brain tumor. With intracranial hemangiomas, hemmorhages are seen frequently. Since shrinkage of organs, otherwise known as involution, is found with cutaneous hemangioma, it can be said that involution can be used to help diagnose diffuse neonatal hemangiomatosis.

Finally, there is no set therapy or treatment for intracranial hemangioma. For now, small damages are only observed due to the expectation of shrinkage. Oral steroids, vinscritine, thalidomide, temozolimide, propranolol, interferon, and bevacizumab can be used to combat intracranial hemangioma. Propranolol is the most common treatment for it, although it is not established as a standard treatment. It is essential to follow up three months after the diagnosis of intracranial hemangiomas.

Treatment with Cyclophosphamide

A case report involving a four month old girl that was diagnosed with heart failure and critical hemangiomas located on the skin, head, mouth, and liver that were resistant to steroid treatment, was given Cyclophosphamide. Cyclophosphamide is an anti-cancer agent that causes immune suppression. The course of therapy was IV Cyclophosphamide 10mg/kg/day with Mesna 10mg/kg/day for four days. The second course was given 10 days later. 12 days after that course of therapy, the hemangiomas on the liver decreased in size and the hemangiomas on the skin were drying out. The third and final course of therapy was given 2.5 weeks after the second course. 10 days after the cessation of therapy, the hepatic hemangiomas size remained stable and the girl was able to gain some weight and be physically active. The heart failure was found to have resolved four months later. One year later, the hepatic hemangioma was barely visible on imaging and the majority of the hemangiomas on the skin were gone. She was reassessed at six years old and was overall relatively healthy, had no cardiac issues, no signs of hemangiomas, and no signs or symptoms of liver disease.

Two other case reports found that after using Cyclophosphamide 10mg/kg/day after the lack of success of four days of corticosteroids, there was fast shrinkage of the tumors. There were no side effects found. Because of an effective response to the cyclophosphamide, the infants stopped the therapy after three and four doses. Those who were involved in the case reports suggest that it is a requirement to have assertive and forceful treatment. They concluded that cyclophosphamide is safe for diffuse neonatal hemangiomatosis

Treatment with Propranolol

One study looked at the use of propranolol, a beta-blocker medication, for treating infantile hepatic hemangiomas. The study followed 8 infants with infantile hepatic hemangiomas under three classifications: focal, multifocal, or diffuse. 4 infants had multifocal hepatic injuries (4 to 20 injuries) and 4 infants had diffuse injuries (more than 20 injuries).The diffuse IHH are life-threatening because they can induce heart failure. Systemic steroids were given as first-line treatment for the infants with heart failure, but were stopped due to inefficacy or lack of improvement of IHH. The infants were given propranolol and a majority saw improvement in their condition. The first three infants saw undetectable injuries after 1 month of propranolol, and the other infants saw a decrease in size of the injuries of 50% after 2 to 4 months. One infant also saw a reduction in overall liver size. Propranolol greatly improved symptoms for the 8 infants with infantile hepatic hemangiomas, with a range of responses from significant improvement to complete resolution of the injuries.

Another case report involving the use of propranolol was performed on a neonatal that had multiple hemangiomas on the skin, scalp, lips, brain, liver, lungs, kidney, and bones. The neonatal was also diagnosed with cerebral palsy. Initially, prednisolone was given as a first line treatment at 4mg/kg/day for four weeks from 27-55 postnatal days. This therapy was not effective, and the medical team switched to administering propranolol 2mg/kg/day for two weeks. After the two week treatment, the hemangiomas decreased in size and had no acute hemorrhage. The use of propranolol was also found not to be associated with any severe adverse effects. The newborn baby was discharged with a four month supply of propranolol to be administered at home. After the four month course, the newborn baby was examined, and the size of the hemangiomas on the scalp, neck, skin, bones, brain, and kidney had decreased in size and number. The hemangiomas on the liver persisted but the ones on the lungs disappeared. At 10 months of age, the cerebral palsy was found to have improved. Although corticosteroids are the first line treatment option, the success rates are only 30-60%. That is why there are alternative second line treatment options, like propranolol. There is no established dosing at this time due to lack of studies. But, it is recommended to be on Propranolol therapy for at least seven months post birth to minimize any further replication of the hemangiomas.

Consideration for Treatment with mTOR Inhibitors

Other medications are currently being considered as treatment for diffuse neonatal hemangiomatosis. mTOR inhibitors, an inhibitor that is normally used for post-organ transplantation, has previously been used for vascular anomalies. mTOR is controlled by phosphoinositide 3-kinase which is essential in cell function. Given its immunosuppressive, antiangiogenic, and antiproliferative characteristics, it could slow down disease progression. For example, the mTOR inhibitor, Sirolimus, can be used to treat diffuse neonatal hemangiomatosis. It is important to note that diffuse neonatal hemangiomatosis therapy requires a multidisciplinary team approach due to its perplexing, rare properties.

Other Therapies

Radiotherapy

Radiotherapy helps get rid of blood vessels that are not fully developed due to fast proliferation. However, getting rid of these types of blood vessels cells have negative effects. Thus, this is no longer an option for therapy.

Surgery

Surgery is an effective option, but has high mortality rates. The mortality rate is 20%.

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