Burkitt Lymphoma Virus

 

Burkitt-Lymphoma Virus 

Now known as Epstein - Barr Virus

P.K.Ghatak,MD.

Epstein-Barr Virus (EBV) was originally known as Burkitt Lymphoma Virus.     Dr. Denis P. Burkitt ( from Ireland) a surgeon working in Uganda reported a highly aggressive Head and Neck lymphoma of children in 1958. He send biopsy specimens to Dr. Epstein, a Pathologist in UK. Dr. Epstein, Barr- a virologist from Ireland and Dr. Achlonga, a Pathologist with interest in electron microscopy from Trinidad, worked together and identified a virus in the biopsy tissue. They reported their finding in 1964 and named the virus - Burkitt lymphoma virus. This is the first virus identified as the cause of human malignancy – the first human oncogene. The virus is known today as Epstein-Barr virus - EBV in short.

This articles on EBV is the 3rd and last of a series virus after producing the primary illness, enter in a latent period. In certain circumstances the virus is reactivated and produce different illnesses. The EBV infects B-lymphocytes and B-memory cells and remains dormant in these cells. EBV is known to produce a number malignancies and other medical illnesses when reactivates.

In a previous blog, many aspects of the EBV was discussed, this article is a supplement to - 

https://humihealth.blogspot.com/search?q=Epstein+Barr+virus.

EBV infects children and young adults worldwide. Saliva of the infected people contains EBV and kissing is the common mode of spread of EBV. Contaminated utensils, food and drinks are additional modes of spread. Blood transfusion, organ transplants and sexual activity also spread EBV.

Infectious Mononucleosis is the primary illness.

Incubation period is long, 4 to 6 weeks. The symptoms are that of an URI but distinctive features of EB virus infection are enlarged and edematous tonsils. Posterior cervical lymph node enlargement in addition to enlarged circular and longitudinal chains of cervical nodes and occasionally intrathoracic and axillary lymph nodes enlargement. Spleen is enlarged and may rupture with minor trauma. Liver enlargement is also seen

Another distinguishing feature is salmon colored morbilliform eruptions on the trunk in about 10% cases; those who do not have skin lesions will develop itchy but similar skin eruptions if they receive Ampicillin. Peripheral blood examination shows lymphocytosis and large atypical lymphocytes - resembling monocytes and that was the basis calling the illness as Infectious mononucleosis. IgM antibody appear early and persists for 6 weeks, the IgG antibody appears later and remains positive for the life of the patient.

Latent period:

The latency is divided into 3 stages.

In the 1^st stage of latency the virus remains totally inactive, except in Burkitt lymphoma. The initial adenopathy progress to lymphoma in a short time.

In the 2^nd stage the virus is only partly active and interferes with nucleic acid synthesis of the host cells, this results in gene mutation and subsequently chromosome breakage and fusion of genes.

In the final 3^rd stage the EBV is fully active and produces a number of malignancy and illnesses as listed below.

Illness produced after the virus is reactivated:

A. Malignancy-

Evidence points directly to EBV.

1. Burkitt lymphoma.

2. Undifferentiated Nasopharyngeal carcinoma.

3. Hodgkin lymphoma and perhaps non-Hodgkin lymphoma.

4. Lymphomas - designate as 1. Diffuse Large. 2. B-cell. 3. Extranodal T/NK. 4. Plasmablastic.5. Primary diffuse.

5. Hairy cell leukemia.

Evidence of EBV is strong but question remains -

1. Epithelial cell cancer of stomach.

2. Epithelial cells cancers of Tonsils, Thymus, Breasts, Skin, Uterine cervix,

3. Lymphoepithelial cancer of salivary glands.

Questionable association with EBV -

1. Renal cell cancer

2. Thyroid gland

3. Urinary bladder.

4. Leiomyoma / Leiomyosarcoma.

B. Non-Malignant Diseases.

Autoimmune diseases like 1.Sjorgen's syndrome 2. Rheumatoid arthritis. 3. SLE, 4.Type 1 Diabetes mellitus. 5. Hashimoto thyroiditis. 6.Graves' disease. 7. Multiple Sclerosis. 8. Hairy Leukoplakia.

Chronic illness.

    1.Long COVID-19

2. Chronic Mononucleosis. Symptoms are fatigue, fever, lymph node enlargement, Hepatosplenomegaly, headaches, joint pain and muscle pain.

3. Parkinson's disease and Acute cerebellar ataxia.

4. Irritable Bowl syndrome.

5. Chronic fatigue syndrome.

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Chickenpox

                                Chickenpox ( varicella)

                               P.K.Ghtak,MD.

Varicella virus causes Chickenpox when a person contact the virus for the first time. After recovery, the virus remains dormant in the nerve cells of the cranial nerve ganglia,  dorsal root ganglions of the spinal cord and autonomic ganglions for the entire life of the individual. In opportune moment, the virus re-emerges and produce Zoster (Shingles) and occasionally produce more serious neurological complications. The virus called Varicella Zoster Virus (VZV)

VZV is a alpha herpesvirus. It is human herpesvirus 3 and has almost identical genomes of Simian Pox virus (SPV). Some of the pathophysiological features of VZV are similar to Cytomegalovirus.

VZV has a double stranded DNA genome, surrounded by a nucleocapsid followed by a protein tegument and a lipid envelop.

The initial infection activates cellular immune reactions followed by IgM, IgG, and IgA antibodies production. Cellular immunity provides life long lifelong protection.

In the USA a vaccine is routinely administered as a part of childhood vaccination, the vaccine is made from attenuated life VZV. Adults over 50 yrs of age are urged to take a second approved Zoster vaccine. This is a non-live recombinant zoster vaccine. It is given by intramuscular injection – two doses 2 to 6 months apart. It reduces the risk of herpes zoster by 92 %. The vaccine is named Shringrix and it protects vaccinated people for up to 9 years.

Clinical feature of Chickenpox.

Chickenpox infection is a common infection of childhood. It is a highly communicable disease. It is estimated that over 90 % of the world population had chickenpox. The mode of infection is by droplets and also the virus becomes airborne from raw wound of an open vesicles. The incubation period in 10 to 15 days may be delayed to 3 weeks. The initial symptoms are cold and cough, fever, and body aches followed by erythematous skin rashes follows by papular eruptions appears the next day. The papular lesions appear first on the chest, back and then on the face followed by outwards spread to arms and legs but no lesions appear on the palms and soles. In 2 to3 days vesicles become embellicated and crusted. Mixed rashes consisting of papules, vesicles and crusted lesions are present at anytime which is a distinguishing feature of chickenpox from small pox. The skin rashes are intensely itchy. In about one week the scabs begin to fall off. From the day of onset of respiratory symptoms to crusting all vesicles the patient remain infectious.

Venerable population are pregnant women who did not have chickenpox before. HIV infection, cancer chemotherapy, long term steroid therapy and organ transplant patients.

Complications:

Young adult male and adult males in some instances develop orchitis, epididymitis and testicular atrophy. In a few cases pancreatitis is reported. In rare cases viral pneumonia can occur.

Neurological complication from Chickenpox.

The common neurological complication is cerebellititis (infection of cerebellum). In rare cases central vein thrombosis and stokes are recorded.

Since childhood vaccination is introduced in the USA, hardly any new chickenpox is seen. Immune status is judged by serology. It is a mandatory test for all prenatal care in the USA.

Diagnosis and Treatment:

Clinical features are distinct and since most older adults had chickenpox that helps them in diagnosis. In doubtful cases viral DNA, specimen obtained from a vesicle, by PCR may be required.

The choice of antivirus drug is Acyclovir. The oral dose is 800 mg  given 5 times a day for 5 days.(200mg/Kg/day). Other antiviral used in Cytomegalovirus infection are also effective in chickenpox.

Varicella-Zoster Immune Globulin (VZIG):

VZIG is given as IM injection, never by IV. The therapy is a passive transfer of immunity in life threating situations.

Indication of VZIG.

Premature infants of immune-negative mothers. Pregnant women past 1 weeks of gestation with unvaccinated or negative history of previous VZV infection (seronegative). Bone marrow transplants in seronegative patents. Immune compromised patients.  Passive immunity is followed by vaccination. 

Reactivation of VZV.

Immunosuppressive conditions lead to the reactivation of VZV.  Nerve cells of all cranial nerve ganglions, Autonomic ganglion and sensory Dorsal Root Ganglion of spinal nerves are at risk of resurgence and Zoster lesions. The virus produces vasculopathy with loss of cells and focal migration of inflammatory cells and giant cell formation. This causes pain and paresthesia and loss of motor function of the dermatome the nerves supply. The pain is sharp and severe and localized to the dermatome involved and strictly limited to one side of the body. The motor fibers of the spinal are commonly effected producing palsy ( partial paralysis). The vesicles appear as bunches, like grapes are strictly limited to the side of the body and do not cross the mid line. Multiple dermatomes and contiguous dermatome and multiple dermatomes of different areas of the body may be involved. In some instances no skin lesions develop, only pain is experienced.

The common places herpes zoster appear are the chest wall followed by the face. Of the cranial nerve the 5^th cranial nerve zoster is most common. It produces pain and vesicular lesions of one half of the face, eyelids and forehead.

In rare circumstances the virus travels to the brain and meninges via the sensory nerve from the Geniculate ganglion (ganglion of the 5th cranial nerve) producing meningoencephalitis.

Ramsay Haunt Syndrome:

Ramsay-Hunt syndrome is a special case of herpes zoster involving multiple cranial nerves. The ganglia of the 7^th,8^th, 9^th and 10^th nerves are involved. this causes severe pain, vesicular eruptions on dermatomes and mouth, tongue and throat of the area supplied by the nerves.. Skin lesions appear on the external ear canal, pinna (supply by 10^th), one half of anterior 2/3rd of the tongue and soft palate and uvula. 7^th cranial nerve lesions produce lower motor neuron paralysis and stapedius muscle. 8^th cranial nerve lesion produces loss of hearing hearing, tinnitus, nausea, vomiting, vertigo and nystagmus. 9^th and 10^th cranial nerve lesions result in paralysis of tongue, muscles of deglutition. Chorda tympani nerve lesion causes loss of taste sensation.

Diagnosis and treatment:

Clinical feature is diagnostic and confirmation if required the PCR test for viral antigen is available. The choice of  antiviral agent is Acyclovir. Other antiviral agents used in  chickenpox are also effective in Zoster lesions.. In addition to viral therapy, prevention of secondary bacterial infection of the skin and mouth lesions and adequate management of pain by opioid derivates by mouth should be provided.

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