LEPROSY

Definition: Chronic granulomatous infectious disease of skin & peripheral nerves, Caused by Mycobacterium Leprae, also known as Hansen’s disease. Skin, muscles, eyes, bones, testes and internal organs can also be involved.
Etiopathogenesis Causative organism Mycobacterium Leprae is a weak acid fast obligate intracellular bacilli. Discovered by Gerhard Heunk Armauer Hansen in 1873 in Norway.
Can be grown in foot pad of mice & nine banded Armadillos.
Very low infectivity even Conjugal partners have 5% risk of transmission of disease.

genetic susceptibility is also seen
Risk of children acquiring infection from infected adults in the family is 60%.

• Transmission: Still uncertain but most likely, spread s via droplet mode, from untreated patients nasal  mucosa, other routes can be skin to skin or may be via GIT.
• Generation time is 12 days, Incubation period is 2—7 yrs. (average 3-5 yrs)
• The optimal temperature for growth for leprae bacilli is 30 - 33 centigrade
• Virulence factor of M. Leprae is phenolic glycolipid I, a surface lipid, specific to this bacillus.
• Common sites which are involved — Skin, Peripheral Nerve, generally involves every organ except CNS & Ovaries and lungs.
• M. Leprae attacks Schwann cells of peripheral nerves, unmyelinated are more affected.
• Tuberculoid leprosy is the one end of spectrum of disease, is seen in high resistance person
• Lepromatous leprosy is the other end of spectrum of disease, seen in low resistance person.
• Transplacental Infection does not occur
• In India, tuberculoid leprosy is more common as compared to Lepromatous Leprosy.

Some general facts about leprosy ace:
• Cell mediated immune response of the host determine the type of leprosy.
• TT and LL patients are stable
• TT leprosy often self heals, most common type of leprosy in India.
• First clinical symptom in leprosy is numbness. .
• LL leprosy remains heavily infected unless given appropriate chemotherapy.
• BR leprosy is the most unstable, with most patients down grading if not treated
• Leprosy can affect all ages and both sexes.
• The limited growth of M. leprae in the mouse foot pad provided a way to screen for therapeutic agents and to identify drug resistance in leprosy.
• The recognition of leprosy in the nine banded armadillo provided a source of large quantities of highly
 purified M leprae for biochemical anti immunologic studies including preparation of vaccine for leprosy

PRENATAL DIAGNOSTIC TESTING PROCEDURES

Ultrasound

This noninvasive imaging modality is used for guidance of invasive prenatal diagnostic procedures. No adverse effects have been identified when using low-energy transducers. Current recommendations are to perform sonography in pregnancy only for obstetric indications. Optimal gestational age for identification of fetal anatomic structural anomalies is 18—20 weeks. Accuracy of gestational dating is ±5 days at less than 12 weeks, and ±7 days between 12 and 18 weeks. Specificity and sensitivity for identification of fetal anomalies is less than perfect.

Chorionic Villous Sampling (CVS)

This refers to aspiration of placental tissue precursors under sonographic guidance for fetal karyotyping. It is performed between 9 and 12 weeks gestation. Follow-up testing with triple marker screening and sonogram is needed to assess for neural tube defects. Placental mosaicism may be rarely present although fetal karyotype is normal. Pregnancy loss rate is 0.7%. Advantages include the early gestational age at which karyotype is available.

Amniocentesis

This refers to trans-abdominal needle withdrawal of amniotic fluid under sonographic guidance. When performed for genetic purposes (fetal karyotyping, alpha-fetoprotein determination, biochemical studies), the gestational age is usually 15—20 weeks. When performed for Rh isoimmunization (bilirubin level), the gestational age is usually after 24 weeks. When performed for fetal maturity studies (lecithin-sphingomyelin ratio, phosphatidyl glycerol, the gestational age is after 34 weeks. Pregnancy loss rate is 0.5%.

Percutaneous Umbilical Blood Sampling (PUBS)

This refers to sonographically guided transabdominal aspiration of fetal blood from the umbilical vein. It is performed after 20 weeks for fetal karyotyping, IgM antibody detection, blood typing, and intrauterine blood transfusion. Pregnancy loss rate is 1-2%.

Fetoscopy

This largely experimental procedure refers to sonographically guided transabdominal placement of a fiberoptic scope for purposes of fetal tissue biopsy and coagulation of placental vessels in twin- twin transfusion syndrome. It is performed between 18 and 20 weeks in suspected congenital ichthyosis. Pregnancy loss rate is 3—5%. 

Function of the Skin

Function	Structure
Protection from harmful agents of external environment: biological germs, ultraviolet light & chemicals	Epidermis
Preservation of a balanced internal environment	Epidermis
Shock absorber	Subcutaneous fat
Temperature regulation	Blood vessels & eccrine sweat glands
Insulation	Subcutaneous fat
Sensation	Nerve endings
Lubrication	Sebaceous glands
Protection & grip	Nails
Calorie reserve	Subcutaneous fat
Vitamin D synthesis	Epidermis
Body odour	Apocrine sweat glands
Psychosocial	Hair & Nails

                 RHESUS ISOIMMUNIZATION

Rh blood group incompatibility arises when an Rh-negative woman conceives an Rh-positive fetus. RBCs from the fetus can enter the woman’s circulation during pregnancy or, more commonly, during birth. These “foreign” RBCs stimulate the production of maternal anti-bodies against the Rh factor. Spontaneous or induced abortions of an Rh-positive fetus can also result in isoimmunization. In subsequent pregnancies, transplacental transmission of the maternal anti-Rh antibody leads to hemolytic anemia in the fetus or neonate. The resulting disease, called erythroblastosis fetalis, may be fatal. Unless a woman was previously sensitized by transfusion, a first pregnancy rarely leads to erythroblastosis fetalis. Isoimmunization does not have signs or symptoms during pregnancy, although hydrops fetalis and fetal demise may occur in severe cases. In less severe cases, bilirubin levels in the newborncan increase dramatically because of the hemolytic anemia. This can lead to kernicterus, characterized by decreased tone, poor feeding, apnea, seizures, and death. Survivors of kernicterus can be left with mental retardation, choreoathetosis, and hearing loss.

High maternal anti-Rh antibody titers, checked in Rh-negative women at the first prenatal visit and at week 26, suggest sensitization of the mother. Amniocentesis showing high bilirubin levels in theamniotic fluid suggests more severe disease and potential for fetal death.

If bilirubin levels are elevated, intrauterine transfusions to the fetus can be performed at 2-week intervals. Delivery should be minimally traumatic, and the placenta should not be manually removed.

Inthe neonate, hyperbilirubinemia may necessitate phototherapy or an exchange transfusion.
At the first prenatal checkup, all patients should be screened for Rh type. If the patient is Rhnegative, maternal Rh antibody titers should be checked early in the pregnancy and repeated at the twenty-sixth week of gestation. A previously unsensitized mother will not normally produce anti-Rh antibody until after delivery, when mixing of the maternal and fetal blood occurs. Rh isoimmunization can be prevented by injecting the mother with anti-Rh immunoglobulin (RhoGAM) at 28 weeks and within 3 days of delivery. Immunoglobulin C binds the fetal Rh factor and prevents the mother from developing anti-Rh antibodies but is too large to pass though the placenta to the Rh-positive fetus. RhoGAM should be given at the termination of each pregnancy, whether a delivery, ectopic pregnancy, or abortion, as well as any other time when feto-maternal hemorrhage may occur (e.g., amniocentesis or trauma). 

 EPIDERMOLYSIS BULLOSA

 Clinical Features

1 This is extremely rare group of hereditary blistering disorders which are characterized by blisters and erosions resulting from trivial trauma.

2.  Blisters occur soon after birth and mainly concentrate on bony prominence of 4 limbs.

3. An acquired form mimicking Bullous Pemphigoid known as epidermolysis bullosa acquisita (EBA) occurs in adults.

4. Bullae tend to occur at sites of trauma.

5. The IgG in these patients binds to the anchoring fibrils attached to the Lamina densa.

 6. EBA may be associated with underlying systemic diseases like SLE, inflammatory bowel disease, amyloidosis and internal malignancy.

 Investigations

The diagnosis can be confirmed by skin biopsy for histopathology and electronmicroscopy. EBA can be differentiated from bullous pemphigoid by the sodium chloride split skin test and immunofluorescence on the skin specimen. In EBA, the blister occurs below the split, whereas, the blister occurs on the roof of the split in bullous pemphigoid.

Treatment

For the hereditary EB, no effective treatment is available at present. Antenatal diagnosis and genetic counselling can be offered. Systemic steroid can be useful in EBA.