Thursday 28 February 2013

TORCH group of infections - Herpes simplex virus




Depending on immunological and clinical differences two types of herpes simplex viruses can be distinguished.

Type 1(HSV 1):
It is responsible for most nongenital herpetic infections.
But up to half of new cases of adult genital herpes are caused by HSV 1.

Type 2(HSV 2):
It is recovered almost exclusively from the genital tract.
Sexual contact is the main mode of transmission.

Maternal infection:
HSV 2 infections can be categorized into 3 types:
-Primary infection: No presence prior antibodies to HSV 1 or HSV 2.
-Nonprimary first episode: Newly acquired HSV 2 infection with preexisting HSV 1 cross-reacting antibodies.
-Recurrent infection: Reactivation of prior HSV 2 infection in the presence of HSV2 2 antibodies.


Primary infection:
-Among newly acquired primary HSV 2 genital infections only one third are symptomatic.
-Incubation period: 3 to 6 days.
-Clinical features: Papular eruption follows with itching and tingling.
-The eruption then becomes painful and vesicular with multiple vulvar and perineal lesions that may coalesce.
-Severe inguinal adenopathy may occur.
-Transient systemic influenza like symptoms caused by viremia.
-Hepatitis, encephalitis, pneumonia etc may develop.
-Usually by 2 to 4 weeks all signs and symptoms of infection will disappear.
-Cervical involvement can occur but may not cause clinical symptoms.
-Some cases may require hospitalization.

Nonprimary first infection:
-Previously existing HSV 1 antibody can give partial protection.
-They may present as first clinical infection but symptoms will be less severe.
-They will have fewer lesions, less systemic manifestations, less pain, briefer duration of lesion and viral shedding.
-Sometimes difficult to distinguish with primary infection.

Recurrent infection:
-In latency period viral particles recide in nerve ganglia. They can get reactivated.
-It is called recurrent infection and virus shedding occurs during this.
-The lesions will be fever in number, less painful and shedding of the virus will be for shorter periods (2 to 5 days).
-Usually recurrence will be at the same site.

Sub clinical shedding occurs in around 60% of women with history of genital herpes infection.
Many sexually transmitted cases occur due to sub clinical shedding. Its effect on pregnancy has yet to be determined.


Neonatal infection:
-Vertical transmission through placenta or membranes is rare.
-Usually the fetus will get infection by contact with virus shed from cervix or lower genital tract during birth.
Newborn infection presents as:
-Disseminated wit involvement of major viscera.
-Localized with involvement confined to central nervous system, eyes, skin, mucosa etc.
-Asymptomatic.

With primary maternal infection 50% risk of neonatal infection is there.
With recurrent infection the risk decreases to 0 to 5%.
This could be due to smaller viral load in maternal secretions and transplacentally   acquired antibody, which will decrease the severity and incidence of the disease.
Localized infection will be usually associated with good outcome.
But disseminated infection, even when treated with acyclovir or vidarabine can result in around 50% mortality rate.
In at least half of the survivors serious ophthalmic and central nervous system damage can occur.


Diagnosis:
-Tissue culture is optimal to confirm apparent infection and asymptomatic recurrences.
-The tissue should be taken from lesions before they undergo crusting, then it will give 95% of sensitivity.
-Tzanck smear: cytological examination after alcohol fixation and papanicolaou staining. It is having 70% sensitivity.
-Using PCR increases HSV detection by four to eight fold compared to culture.

Management:
-Antiviral therapy with acyclovir, fansciclovir and velacyclovir are used to treat first episode of genital herpes in non pregnant and pregnant women.
-In recurrent infections and to reduce heterosexual transmission the drugs can be used as suppressive therapy.
-Intense discomfort can treated with analgesics and topical anesthetics.
-Severe urinary retention may need catheterization.
-Trails are going on to keep acyclovir or valacyclovir as suppressive therapy during last month of pregnancy to prevent recurrence nears term.
-It reduces signs and symptoms of recurrent infection but does not completely eliminate asymptomatic viral shedding.
-Cesarean delivery is indicated to those with active genital lesions or in those with a typical prodrome of an impending outbreak.
 -So if primary or recurrent lesions visualized near the time of labor cesarean to be done irrespective of the time of rupture of the membranes.




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Wednesday 27 February 2013

TORCH group of infections - Cytomegalovirus




-          Causative organism: Cytomegalovirus, a ubiquitous DNA herpes virus.
-          Most common cause of perinatal infection.
-          Incidence: fetal infection found in 0.2 to 2% of all newborn infants.

Transmission:
-Horizontal transmission by droplet infection via saliva and urine.
- Vertical transmission by mother to fetus – infant.
- Sexual transmission.
- After primary infection the virus becomes latent. Periodic reactivation with viral shedding is possible despite of the presence of serum antibody.
Immunosuppressed states increase the propensity of serious cytomegalovirus infections.

Features of maternal infection:
-          No evidence that pregnancy increases the risk or severity of maternal CMV infection.
-          Most of the infections will remain asymptomatic. About 15% of the adults will have mononucleosis like syndrome.
With features like :
-          Fever
-          Pharyngitis
-          Lymphadenopathy
-          Polyarthritis.

-          The risk of sero-conversion among susceptible women during pregnancy is 1 to 4%.
-          In around 40% cases primary infection to the fetus is associated with severe morbidity.
-          Transmission is more common in first half of the pregnancy.
-          Maternal immunity to CMV does not prevent recurrence or reactivation or congenital infection.
-          Usually recurrent infections are more common cause of congenitally infected newborn.
-          Fortunately clinically apparent sequelae are less common with recurrent infections than primary infections.


Congenital infection:
-          Results in cytomegalic inclusion disease.
-          This syndrome presents with features like low birth weight, microcephaly, intracranial calcifications, chorioretinitis, mental and motor retardation, sensorineural deafness, hepatosplenomegaly, jaundice, hemolytic anemia and thrombocytopenic purpura.
-          Usually these findings are seen in 5 to 6% of infected neonates only.


Daignosis:
Infection is diagnosed by measuring IgG and IgM antibodies.
If patient results show :
-          IgG and IgM negative  - indicates Cytomegalovirus uninfected and no further evaluation is needed.
-          If abnormal Cytomegalovirus screening with IgG and IgM positives occur, following steps are needed, estimation of:
-          CMV specific IgG and IgM by EIA.
-          CMV specific IgG avidity by EIA.
-          CMV specific IgM by immunoblot.

Then if the results show:
-          CMV IgG positive, high IgG avidity index and IgM negative- latent CMV infection. And no further evaluation is needed.
-          CMV IgG positive or serocenversion, low IgG avidity index and IgM positive – primary CMV infection. Needs invasive follow-up.
-          Uncertain serologic results – undefined CMV infection. Needs invasive follow-up.
-          CMV IgG positive, high IgG avidity index and IgM positive – recurrent CMV infection. Needs non-invasive follow-up.

-Ultrasound to know the effects on the fetus. Sometimes defects like microcephaly, ventriculomegaly, cerebral calcifications, hyperechoic bowel, ascites, hepatosplenomegaly and hydrops etc. can be seen.
-Amniotic fluid analysis using viral culture and polymerase chain reaction.
-Fetal blood sampling- to detect anemia, thrombocytopenia, hepatic dysfunction etc.
-The fetal outcome depends on the stage of gestation during which primary infection documented.
-Usually the majority of infants develop normally even with being affected with primary infections in the first half of the pregnancy.


Treatment:
-No effective therapy for maternal infections. So routine serological screening is not recommended.
-Not possible to predict which fetuses are infected.
-Maternal reinfection with a different CMV strain can occur.
-No vaccine.
-Attempts to identify and isolate infants excreting  CMV are expensive and impractical.



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TORCH group of infections - Rubella



Rubella infection also called as German measles is caused by Rubella virus.
If this infection occurs in non-pregnant women, usually the severity will be minimal.
If infection occurs in pregnancy it will present with more severity and it can cause abortion, severe congenital malformations etc.

Features of maternal infection:
-Usually viremia precedes 1 week to clinical disease.
-Generally 25% of infected women will be asymptomatic.
-Clinical features: lymphadenopathy, fever, malaise, arthralgia etc.
 Maculopapular rash can occur. It starts on the face and spreads to the trunk and     extremities.


Effects on fetus:
With progression of pregnancy the possibility of congenital malformations will decrease.
Usually most sequelae are seen before 20 weeks.

Congenital rubella syndrome:
 It can present with one or more of below findings:
-Eye lesions like cataracts, glaucoma, microphthalmia and other abnormalities.
-Heart diseases like patent ductus arteriosus, septal defects and pulmonary artery stenosis.
-Sensorineural deafness.
-Central nervous system defects including  meningoencephaliis.
-Fetal growth restriction.
-Thrombocytopenia, anemia
-Hepaitis, hepatosplenomegaly, jaundice
-Chronic diffuse interstitial pneumonitis.
-Osseous changes.
-Chromosomal abnormalities.

Infants born with congenital rubella syndrome may shed the virus, It can continue for months, other infants and susceptible adults who came in contact to these infants can get affected with this.

Extended rubella syndrome:
-Progressive panencephalitis.
-Type 1 diabetes mellitus – it may develop clinically in second and third decades of life.
-One third of asymptomatic infants at birth may manifest such developmental injury later in life.
-Other later sequalae are : thyroid disease, ocular damage, mental retardation etc.


Vaccination:
For complete eradication of the disease vaccination is recommended.
-Health education to all.
-Vaccination of susceptible women.
-Vaccination of unimmunized women immediately after child birth and abortion.
-Vaccination to unmarried teenage girls.
-Susceptible hospital personnel who might be exposed to patients with rubella or might have contact with pregnant women.
As vaccine contains attenuated live virus vaccination should be avoided shortly before or during pregnancy. But there is no evidence that the vaccine induced malformations.



Treatment:
No effective therapy for maternal infections. Symptomatic therapy with anti-viral drugs can be given.
Acyclovir 200mg, five times a day for five days can be given.




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Tuesday 26 February 2013

TORCH group of infections - Toxoplasmosis



Toxoplasmosis, rubella, cytomegalovirus and herpes simplex viruses are collective called as TORCH group of infections.
These are important infections that should be ruled out in pregnancy because they can cause congenital malformations.

Toxoplasmosis
Causative organism:  Toxoplasma gondii
Transmission :
-Through encysted organisms by eating infected raw or uncooked beef or  pork.
-Through contact with oocytes in infected cat feces.
-The fetus can get infected by transplacental route.
  Usually fetus will be protected by maternal immunity. So if the women get infection  during the pregnancy the fetus can get affected.

Incidence:
Incidence of new infection in pregnancy is 0.5 to 8.1/1000.

Symptoms of maternal infection:
-Usually the infection will remain sunclinical.
-Some women may present with features like:
  Fatigue
  Muscle pains
  Fever
  Chills
  Maculopapular rash
  Lymphadenopathy etc.
-Infection can result in abortion or live baby with evidence of disease.

Effect on the fetus:
-The possibility and severity of the congenital infection depends on the gestational age when the fetus acquired it.
-With progression of pregnancy the risk of fetal infection increases but severity decreases.
-Generally less than 25% of congenital toxoplasmosis infected newborns will have clinical illness at birth. But later most of the children can show some sequelae of infection. So follow-up is needed.
-Clinically affected infants at birth can present with:
   Evidence of generalized disease
   Low birth weight
   Hepatosplenomegaly
   Icterus
   Anemia
-Some infants can have neurological sequelae also, like:
  Convulsions
  Intracranial calcifications
 Mental retardation
 Hydrocephaly or microcephaly.
-All most all infected infants develop chorioretenitis.


Treatment:
-Routine screening is not recommended in general.
But in women with HIV infection screening should be done.
-In women with active toxoplasmosis (IgM positive) antimicrobial treatment should be given.
Spiramycin, a macrolide antibiotic is usually used. Which reduces the incidence of fetal infection but it may not modify its severity.
Pyrimethamine plus sulfadiazine can also be used when the fetus is infected.



The usual followed protocol is:
If the pregnant suspected or confirmed of toxoplasmosis during gestation:
-In less than 18 weeks – spiramycin therapy and fetal ultrasound are adviced.
 Amniotic fluid PCR should be done after 18 weeks.
If PCR and ultrasound show negative results the spiramycin therapy(1 g, thrice a day ttill deleivery) can be continued.
Or if PCR and/or ultrasound show positive result combination therapy with pyrimethamin is preferred.
-In more than 18 weeks gestation: combination therapy with pyrimethamin is preferred.
 Ultrasound and amniotic fluid PCR should be done.

Pyrimethamin combination therapy is:
Pyrimethamin - 50mg, twice a day for two days. Followed by 50mg, once a day till delivery.
Sulfadiazine- 75mg/kg body weight, twice a day for 2 days. Followed by 50mg/kg body weight, twice a day till delivery.
Folinic acid- 10 to 20mg/day.



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Monday 25 February 2013

Nipple discharge - 3

Diagnosis:
-          Physical examination.
-          Sample of discharge to examine for the evidence of infection or cancerous cells.
-          X ray of the breast (mammography).
-          Ultrasound.
-          Blood sample to measure hormonal levels.
-          Brain scan.
-          Surgical excision and analysis of one or more ducts in the nipple.


Management :

-          If caused by normal hormonal changes it will be usually harmless and does not       require treatment.
-          Repeated squeezing should be avoided as that can increase the discharge.
-          Galactorrhoea:  drugs like cabergoline (doapamine 2 receptor agonist) which will reduce the production of prolactin from pituitary gland can be used.
       Bromocriptine (all dopamine receptors agonist but very strong D2 agonist) also serves the purpose.
      Pyridoxin (vitamin B6) also helps in treating galactorrhea.
-          Pus discharge can be treated with antibiotics.
-          Blood stained discharge due to non-cancerous tumor can be treated by surgical removal of that particular duct.
-          Malignant tumors need surgery and radiotherapy. Radiation can possibly destroy any remaining cancerous cells after surgery.

Features
Causes
Diagnosis and management 
Self examination of breast



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Nipple discharge - 2

Abnormal nipple discharge:



Causes :
- Galactorrhea: watery or milk discharge in women who are non pregnant or not breast feeding is called galactorrhea.
 Causes: Over production of prolaction from pituitary gland can led to it.
Prolactinoma, the non cancerous tumor of pituitary gland  can cause this.         
Hypothyroidism can lead to increased production of prolaction due to TSH stimulation and can cause galactorrhea.
Drugs like antipsychotic medicines, antacids, some hormones, herbs like anise, fennel and illegal drugs like marijuana etc can cause galactorrhea.
-          Breast infection :  also called as mastitis. The breast will appear sore, red and warm to touch.
Usually seen in breast feeding mothers. When milk ducts get blocked and infected pus discharge from nipples can occur.  
In non breast feeding women, causes like smoking may cause inflammation of the milk ducts and produce pus containing nipple discharge.

-          Fibrocystic breast changes:
Development of fibrous tissue and cysts in breast occurs.
That can cause formation of lumps or thickening.
Causes pain and itching.
Sometimes can lead to clear, white, yellow or green nipple discharge.
          
-          Mammary duct ectasia:
Second most common cause of abnormal nipple discharge.
Usually seen in women who are approaching menopause.  
In duct ectasia inflammation and possible blockage of ducts located underneath the nipple can be seen.
Superadded infection can lead to thick and greenish nipple discharge. 

-          Breast tumors:

-          Intraductal papilloma:
Non cancerous growth in the ducts of the breasts.
Most common cause of abnormal nipple discharge.
When the ducal papillomas get inflamed they may result in nipple discharge that contains blood and sticky fluid.

-          Breast carcinoma:
Sometimes breast carcinoma can cause watery or blood stained nipple discharge when the tumor invades the ducts.
If a patient presents with nipple discharge accompanied by a lump or mass within the breast or with abnormal mammogram.

Intraductal carcinoma: It develops within the ducts of the breast located beneath the nipple and can cause nipple discharge.

Pagets disease: develops in the ducts of the breast and then moves to nipple.
It can cause nipple and surrounding areas to bleed or ooze.
It usually accompanied by another form of breast cancer.


Nipple discharge - 1




Nipple discharge can be of normal and abnormal forms.

Normal nipple discharge:

Features:
-Usually normal discharge occurs from both nipples.
-Discharge releases when the nipples are compressed and squeezed.

Causes:
The conditions in which normal nipple discharge seen are:
-Pregnancy:
In early stages of pregnancy clear breast discharge can be seen.
In later stages of pregnancy discharge can become watery and milky.

-After stopping breast feeding also milk like breast discharge persists for a while.

-Nipples may secrete fluid when they stimulated or squeezed or repeatedly chafed by inner clothing during vigorous exercise etc.
Repeated stimulation of nipple due to skin rash, self breast examination etc also lead to nipple discharge.

-Changes in female sex hormones can cause nipple discharge.
It usually appears just before periods, from both nipples and will be clear and watery in nature.

Abnormal nipple discharge:



Features:
-          Usually bloody nipple discharge will be abnormal only.
-          Discharge only from one breast.
-          Discharge occurring spontaneously without touch or stimulation or irritation.
-          Usually color is not a better predictor of abnormality. Because sometimes normal discharge can also occur in forms like clear, white, yellow, greenish etc.
Features
Causes
Diagnosis and management
Self examination of breast

Sunday 24 February 2013

Vulval leukoplakia – part 5






Differential diagnosis of leukoplakia cont..:



Vulval vitiligo:
-Depigmented spots with clear boundaries can be seen.
-No keratosis or infiltration or itching.
-Same type of lesions can be on other parts of the body.
-HPE: complete lack of dopamine stained melanocytes in the basal layer.
-Easy to differentiate with leukoplakia.
 



Vulval neurodermatitis:
-Usually distributed on both sides of the outer labia.
-Conscious itching sensation will be present.
-Skin lesions can develop due to continuous scratching.
-HPE: changes of chronic dermatitis, thickening of skin layers can be seen. There will be no spindle shaped cells which will help in differentiating with leukoplakia.
 




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Saturday 23 February 2013

Vulval leukoplakia – part 4




Differential diagnosis of leukoplakia :

Keratosis:
-White skin cells due to hypopigmented keratosis with out heteromorphism.
-Appear as ill-defined white spots with no or mild infiltration.
-If the keratosis prolongs for long term it can turn into leukoplakia etc lesions.


Oral lichen planus in combination with genital lichen planus
-Can appear on genital skin or at mucocutaneous junction.
-Usually appears as polygonal flat purple or dark red papules with glossy surface.
-HPE: colloid bodies, basal liquefaction, degeneration, dermal infiltration of lymphocytes etc.

 



Atrophic lichen sclerosis:
-Often occurs on labia.
-It is atrophic vulvar dystrophy.
-Appear as blue and white papules, integrated pale hypo pigmented spots can be seen.
-Can involve anus and vagina to form a dumble – shaped lesions.
-Itching will be minimal usually.

                                                                                                                                   

                                                                                                                              to be continued..

Friday 22 February 2013

Vulval leukoplakia – part 3



Prevention:

-Pertinacious diet containing vitamins, minerals etc. should  include milk, eggs etc.
-Treating provoking factors like diabetes, endocrine diseases etc.
-Treating EB virus, candidial infections etc.
-Maintaining vulval local health like reducing the moisture, friction, heat production etc.

Treatment:

-With appropriate and early intervention around 96 to 97% cases can be prevented from becoming worse.
-Local treatment – to keep the vulva clean and dry.
-Using mild soaps and avoiding soap over scrub etc.
-For itching local corticosteroids can be used.
-For keratosis proliferative lesions topical 0.025% to 0.05% Vitamin-A acid ointment or 2.5% fluorouracil ointment can be used.


(Fluorouracil helps in blocking the conversion of uracil into thymidine. Thereby it inhibits DNA synthesis, which prevents tumor cell proliferation and differentiation. It can be used in precancerous skin lesions and also in malignant skin lesions.)
 -Leukoplakia with mild dysplasia can be treated with this combination therapy and long term follow-up.
-In case of leukoplakia lesions with atypical cellular features with possibility of development of carcinoma in situ needs surgery.

Thursday 21 February 2013

Vulval leukoplakia – part 2



Pathogenesis:
It is a mucosal or epidermal epithelial proliferative lesion.
In leukoplakia mucosal epithelium becomes keratinized ranging from granular layer thickness.

Histopathological features:
-Significant hyperkeratosis
-Granular layer thickening
-Mucosal or skin epithelial hyperplasia
-Acanthosis thickening
-Epithelial crest
-Infiltration of dermal lymphocytes and plasma cells
-Appearance of prickle cell layer
-Cells with irregular shape and mitotic figures
squamous hyperplasia

Symptoms and signs:

-Patient will usually present with irregular milky white shiny patches or plaques with slightly elevated mucosal surface, well defined borders and state clearly.
These lesions can be seen on genital organs like vaginal mucosa, urethral mucosa, clitoris, labia majora, labia minora etc.

Itching is one more common feature.
Itching can lead scratching, rubbing which can in turn lead to flushing, edema, erosion, ulcers or liquenification.
With progression of time some lesions can become:
-Uplifted, state unclearly
-Surface becomes more keratinized, rough and hard to touch.
-Bleeding from the erosion or ulcers can be seen.

Diagnosis:
Histopathological examination and clinical features collectively help in diagnosis.



Wednesday 20 February 2013

Vulval leukoplakia – part 1




 Definition:

Generally benign keratotic white lesions on the vulva are called as vulval leukoplakia or precancerous disease or white spot disease.

In these more are benign or pre-cancerous lesions. Only 4 to 6% can be cancerous.

Nowadays instead of using the general term leukoplakia, one standard nomenclature has developed based on the histopathological findings of the vulval lesions.

And these lesions are called non-neoplastic epithelial disorders in general. And these are subdivided into:
-Squamous cell hyperplasia.
-Lichen sclerosus.
-And other dermatoses.

Causes of leukoplakia:

Exact etiology is not clear. But the possible factors are:

-Systemic factors like:  
    Diabetes
    Endocrine disorders
    Malnutrition
   Vitamin deficiency
   Pituitary-ovarian dysfunction

-EB virus infection

-Candida albicans infection

-HPV infection seen in around 22% of the patients.

-Can be seen in patients with oral leukoplakia.

-P 53 gene mutation leading to cell proliferation.

-Local factors like:
   Genital partial wetness
   Heat stimulation
   Rubbing
  Age related atrophy

-Previous similar lesions

-The skin graft to vulva can also get the lesions.