leprosy_ Lyme disease - PDF by bvishaal


Discovered in 1873 by Dr G Armauer Hansen. Leprosy is also
called Hansen's disease.

leprosy which affects the nervous system, the skin, the eyes
and the upper respiratory tract of a human.
Leprosy has been recognized since biblical times.

Leprosy affects 12-15 million people worldwide.

In thirteenth century there were about 200 leper hospitals

By fifteenth century it was no longer endemic in England.

Now leprosy is rare in the UK and USA.
 Mainly people who have a weakened immune system get

It can be passed on by coughing, sneezing or by through
open skin to skin contact.

 It usually infects children aged 10-14 and adults aged 35-44.
Causative agent: Mycobacterium leprae
There is no animal reservoir
Mode of transmission: it is directly related to overcrowding and
poor hygiene.

Infection is acquired by prolonged contact with patients with
lepromatous leprosy. The organism is discharged in large
numbers in nasal secretions and from skin lesions.

In United States, leprosy occurs primarily in Texas, Louisiana,
California & Hawaii.
They are Gram positive bacilli.

It can be stained by Ziehl-Neelsen staining, the acid fast bacilli
are arranged singly, in parallel bundles (like rolls of cigarettes).

   M. leprae cannot be grown in artificial culture media.

   Animal models have been used for experimental infection
    with M. leprae –foot pad of mouse,
    Nine – banded armadillos.

   The generation time is found to be 12 -13 days.
The bacillus Mycobacterium leprae, is a slow growing organism
with a preference for cooler temperatures.

Therefore, the skin, the nose, the ear lobes, certain peripheral
nerves and the slightly cooler anterior part of the eye are, in
particular, affected by leprosy.

Incubation time is about 5 years, but may be longer.
The photograph on the right shows nasal discharge
containing many red-stained bacilli.
Multibacillary leprosy patients develop ulcers in the nasal
septum, with heavy loads of M. leprae.
A septum perforation finally causes the collapse of the nose
in such patients.
Virulence properties:

Cell wall of the bacilli is made up of – four layers

The outer most layer is composed of mycosides- a major
component is the phenolic glycolipid – 1 (PGL-1).

This protects the bacilli from host cell enzyme and suppresses
cell mediated immunity.
The organism replicates intracellularly, typically within skin
    histocytes, endothelial cells and the Schwann cells of

There are two distinct forms of leprosy-

1. Tuberculoid leprosy
2. Lepromatous leprosy

There are several intermediate forms between the two extremes
How do we diagnose it?
How the pain is caused-

When a person with leprosy          So he keeps walking until the blister
gets a blister, it does not hurt.   bursts and becomes infected.

Still without pain, the infection      At this time the bone is destroyed
gets deeper and attacks the            and the foot becomes more and
bone.                                  more deformed.
      Clinical disease classification

Based on number of lesions & bacilli in lesions:
   Paucibacillary leprosy- no bacilli in lesion (TT,BT)
   Multibacillary leprosy – bacilli present in lesions (LL, BL)

Ridley Jopling‘s classification based on immune status
(Lepromine test) & histopathology

   Indeterminate, Tuberculoid, BT, BL, Lepromatous
Ridley- Jopling Classification
Clinical presentation:
Indeterminant type: early unstable tissue reaction with mild
transient tissue lesion. Often resembling maculo-anaesthetic
patches. Lesions heal spontaneously or may progress to TT or
LL type.

In tuberculoid leprosy- Disease occurs when the cell mediated
immune response is partially effective

 Lesions are characterized by blotchy red lesions with
 anesthetic areas on face, trunk and extremities.

 Lesions are solitary or few in number.

 Lesions have a raised, erythematous margin and a flat center.
 Nerve damage due to the cell mediated immune response
 causes a loss of sensation to touch, temperature, and pain
 within the lesion

 Granulomas    containing giant cells are formed.

A skin biopsy reveals many lymphocytic and epithelial
 cells, but no AFB.

 The   lepromin test is +ve
   In tuberculoid leprosy the organisms are much more sparse
    but characteristic granuloma form in the dermis.
                                   Hypopigmented Macule
Lesions on the face
                                   in Tuberculoid Leprosy

                      Tuberculoid Lesion
2. Lepromatous leprosy: The disease occurs when there is
defective cell mediated immunity against the organism

May involve all areas of the skin and lesions have a waxy,
nodular appearance.

There is destruction of cutaneous nerves.

The skin may thicken and fold.

Foamy histiocytes are seen.
   There is a loss of eyebrows and eyelashes

   There may be destruction of the nasal septum and the
    nasal mucosa is loaded with organisms.

   The skin and mucous membrane lesions contain large
    number of organism.

   The lepromin test is -ve
Lepromatous leprosy:
Loss of Eyebrows/Eyelashes

                             Arm Nodules in
                             Lepromatous Leprosy
symmetrical enlargement of
the peripheral nerves.

              Active, Neglected Nodulous Lepromatous
              Leprosy Lesions on Face
Leprosy-Classic Facial Appearance: Patient with chronic M
Leprae infection that has led to collapse of nasal septum and
subsequent development of classic "Leonine Facies." Patient
has lost digits of hand secondary to leprosy as well.
Damage Due to Secondary Infection:

                             Deformed Foot and Leg
Intermediate forms:

There is a hypopigmented macule

There may or may not be sensory loss within the macule

The macule may completely resolve
      Differences between LL &TL

Feature             LL                  TL
Bacilli in lesion   numerous            Scanty / absent

CMI                 deficient           Adequate
Lepromin test       negative            Positive
Infectivity         Highly infectious   Non infectious

Mycobacterial ab    detected            Not detected

Prognosis           poor                good

   Tuberculoid - epithelioid granulomas with scarce or
    no bacilli.

   Lepromatous hemisphere, granulomas containing
    modified macrophages called lepra cells, with
    numerous bacilli seen.

   In borderline leprosy, both types of granulomas may
    coexist (epithelioid or lepra cells).

   Intradermal delayed type Hypersensitivity test to study
    the CMI in leprosy (Mitsuda in 1919)

Antigens for the test

   Bacillary lepromin – purified bacterial components
    from foot pad of mice or armedillos
   It is not a diagnostic test
   Disease classification
   Prognosis assessment
   Assessment of immune status of individual.
    Lepromin positive indicates resistance to infection.
After the onset of therapy, patients with lepromatous leprosy
often develop a Reactionary state -
Erythema nodosum leprosum (ENL)
This is an antibody mediated reaction in which immune
complexes are formed

It is characterized by painful, erythematous nodules.

It is seen mainly along the extensor surfaces of the tibia and
ulna; neuritis; and uveitis.
   Erythema nodosum leprosum
Laboratory diagnosis:

Specimen collected: skin biopsy or nasal scrapings
Acid fast stain- is done to demonstrate the bacilli.

Lipid laden macrophages called ―foam cells‖ containing acid
fast bacilli are seen.

In tuberculoid form the appearance of typical granuloma is
sufficient for diagnosis.
     Skin smears
Cigar bundle appearance

Animal inoculation

9 banded Armadillo

                     Foot pad of mice
Dapsone (diamino diphenyl sulfone) is given.

Now combination therapy is recommended.
e.g. Dapsone, rifampin and clofazimine for lepromatous leprosy

Dapsone and rifampin for tuberculoid form.

Treatment is given for at least 2 years.

Thalidomide is the treatment of choice for ENL reactions.
Other Mycobacterial skin infections:

Mycobacterium marinum          these prefer cooler tempt.
Mycobacterium ulcerans         & cause skin infections

M. marinum is associated with water and marine organisms.
Human infections follow trauma, often minor such as a graze
acquired while climbing out of swimming pool or while
cleaning acquarium.
Incubation period is 2-8 wks.
Initial lesion appears as small papules, which may enlarge and

The lesions are granulomas hence the name ‗swimming pool
granuloma‘ or ‗fish-tank granuloma‘.

M. ulcerans cause chronic painless cutaneous ulcers known as
‗Buruli ulcers‘.
   Fish tank granuloma -
   Borrelia species are loosely coiled, motile spirochetes that
    stain readily with Giemsa and Sliver stain. Observed by
    darkfield microscopy.

   They can be cultured in bacteriologic media containing
    serum or tissue extracts.

   They are transmitted by arhtropods

   They cause two major diseases-
                                 Lyme disease
                                 Relapsing fever
General Considerations

   The syndrome of relapsing fever consists of two clinical

   Epidemic relapsing fever caused by Borrelia recurrentis
    (LBRF) and transmitted by the human body louse and

   Endemic relapsing fever caused by Borrelia hermsii and
    other spp. (TBRF) and transmitted by soft ticks
Essentials of Diagnosis of relapsing fever:
 The most common presentation is fever with rash, headache,
  shaking chills, myalgias, arthralgias, and during the acute phase
 Louse-borne relapsing fever (LBRF) is epidemic, caused by

   B. recurrentis, and characterized by one or two relapses.
 Tick-borne relapsing fever (TBRF) is endemic, caused by Borrelia

  hermsii & several Borrelia species, and characterized by multiple
  clinical relapses.
 Organisms can be visualized in blood smears of febrile patients,

  unlike other spirochetal pathogens, using dark-field microscopy or
  Giemsa or Wright stains.
 Helical (3-10 spirals) spirochetes, motile (flagella).

 Weil-Felix reaction: Proteus OX-K agglutinin titers are elevated

  (this is more common in LBRF).
Essentials of Diagnosis of lyme disease
   Most common in the northeastern, upper midwestern, and western
    parts of the United States.
   Borrelia burgdorferi is the longest (20-30 µm) and narrowest (0.2-0.3
    µm) spirochete member of the Borrelia genus and has the fewest
    flagella (7-11).
   Erythema migrans (EM) is a red expanding lesion with central
    clearing that is commonly seen during the early stage of Lyme
   The most common systems affected are the skin (EM), the joints
    (arthritis), the CNS (facial palsy), and the heart (conduction defects).
   Serology is not standardized; it is insensitive in early infection and
    does not distinguish active from inactive infection.
   Grows in Barbour-Stoenner-Kelly medium from skin biopsy and other
   Polymerase chain reaction (PCR) can be useful in synovial-fluid
    analysis. It has limited value with blood, CSF, and urine.
What is Lyme disease?
 Most common tick/insect-borne disease in the U.S.

 A disease that can cause skin, joint, heart and nervous system

 Lyme disease can affect people of all ages.

 Named after the town of Lyme, Connecticut where it was

  first described in 1976.
 In US the regions primarily affected are- states along the
  North Atlantic seaboard; the northern Midwestern states, and
  the West coast- California.
 80% cases occurred in 4 states have been from- New York,

  Connecticut, Pennsylvania, & New Jersey.
General Considerations
 Lyme disease is a tick-borne illness caused by the spirochete
  B. burgdorferi.
Lyme disease can be divided into
 Stage 1: Early disease (EM)

 Stage 2: Disseminated infection

 Stage 3: Late disease (persistent infection).

   The first stage involves the skin, followed by stages 2 and 3,
    which often affect the skin, joints, CNS, and heart.
 Lyme disease is the most common vector-borne infection in the

  United States.
 It is transmitted by ticks from the genus Ixodes.

 The Ixodes tick goes through a 2-year life cycle that is

  composed of three stages: larva, nymph, and adult.
 Tick larvae acquire the spirochete via a blood meal from an

  infected host. Both the nymph and female adult infect humans.
  A tick must be attached for at least 24 h to transmit the
 Ixodes ticks in the northeastern and midwestern United States

  belong to the Ixodes dammini (scapularis) species
 In the western United States to Ixodes pacificus

 In Europe to Ixodes ricinus

 In Asia to Ixodes persulcatus.
   The main reservoir of the organism consists of small
    mammals, especially the white – footed mouse, upon which
    the nymph feeds.

   Deer, horses, dogs, and other larger mammals are an
    obligatory host in the tick‘s lifecycle but are not an important
    reservoir of the organism.

   Most cases have their onset during summer and occur in
    association with hiking, camping, and residence in wooded,
    rural, or coastal areas.
Ticks that cause Lyme disease

   Black-legged (or deer) tick: Transmits Lyme disease to
    humans. Found in north-central and northeastern U.S.

   Lone star tick: Found in Texas and has been known to
    transmit Lyme disease.

   Rocky Mountain tick: Can transmit Lyme disease as well as
    Rocky Mountain spotted fever.
Ticks that cause Lyme disease

                                          Lone Star Tick
                                  (Amblyomma americanum)

  Black-legged Tick
  (Ixodes scapularis)

                    Rocky Mountain Tick
                  (Dermacentor andersoni )

   B. burgdorferi is the longest (20-30 µm) and narrowest (0.2-
    0.3 µm), and has the fewest flagella (7-11).
   This organism can be grown from skin biopsy and other
    specimens on an artificial medium called Barbour-
    Stoenner-Kelly at 33°C.
   The B. burgdorferi surface membrane is studded with
    lipoproteins called outer-surface proteins (OSPs) A, B, C,
    D, E, and F.
   Other prominent antigens include
                                flagellar protein
                                heat shock protein
                                protoplasmic cylinder antigen
   B. burgdorferi is capable of altering its surface lipoproteins
    by recombining gene cassettes in a manner that resembles
    the mechanism of antigenic variation among the relapsing
    fever borreliae.
   The antigenic variability seen among different isolates has
    important implications for serologic tests and vaccine
   In the United States, most strains belong to the genomic
    group B. burgdorferi sensu stricto
   In Europe most strains belong to the groups known as
    B. garinii and B. afzelii.
 After inoculation in the skin, B. burgdorferi replicates

  within the dermis producing EM and spreads
  hematogenously to other organs.
 The organism has tropism for the skin, joints, heart and

 A rise in immunoglobulin M (IgM) is detected within 2-3

  weeks after the onset of infection.
 An increase in IgG and IgA is established after 2-3 months

  of infection.
 Host genetic factors may determine the likelihood of tissue

  damage; for example, patients with human leukocyte
  antigens DR4 and DR2 may be more susceptible to chronic
Lyme Disease: Signs and Symptoms
Stages of Lyme disease:
 Stage 1 (Early stage) – 3 to 30 days after bite.

   Flu-like symptoms develop within 7 – 14 days.
   Symptoms include fatigue, headache, fever and chills,
    muscle and joint pain, nausea, vomiting, dizziness and, a
    non-productive cough.
   Skin lesion(s) may appear as a small red circular rash
    around the bite and expand.
   Secondary skin rashes appear in nearly 80% of individuals
    with Lyme disease.
Lyme Disease – Skin Rash

(Skin rash)
Lyme Disease – Skin Rash

(Skin rash)
   Stage II– May occur weeks or months after the onset
    of Lyme disease.

   Cardiac and neurologic involvement predominates.
   Myocarditis with various forms of heart block occurs.
   Acute (aspetic) meningitis and cranial neurophathies
    also occur – like seventh palsy (Bell‘s palsy) are
    prominent during this stage.
   In Stage 3: Arthritis usually of large joints
    e.g. Knees, is characteristic findings.

   Chronic progressive central nervous system disease also
What are the signs of Lyme disease?
                             Rash
                                May look like a
                                 ―bull‘s eye‖ or a
                             Sore muscles
                             Very tired

                 Swollen joints
                   Sometimes   it can be very
Diagnosing Lyme Disease
 Notify a doctor if you become ill after being bitten by a

 A diagnosis will be made based on clinical signs and

  symptoms and the results of a blood test.
   Diagnosis is done by serological tests by
   ELIZA: detecting IgM or rising titer of IgG antibody
   Indirect Immunofluorescence test.
   IgM is detectable 2 weeks after infection and peaks 3-6
   A positive test result should be confirmed by Western Blot
   Detection of spirochetal DNA by PCR is useful in synovial
    fluid (75-85% of sensitivity). However, the sensitivity of
    PCR in CSF, blood, or urine samples has not been well
Prevent Lyme Disease
  Check for ticks daily
  Avoid tick areas
  Cover up with light colored
 clothing + tuck pants in socks!

                       Make your yard
                        safer—create a dry
                        path between woods
                        and your yard.

                            Use bug spray
Pets can get Lyme Disease, too.
                  Check your pet for ticks
                   after it has been outside.
                  There are collars, sprays,
                   powders, and other
                   treatments to stop ticks
                   from biting your pet.
                  Ask your veterinarian for
                   advice on protecting your
                   pet from tick bites.

   Other facts
   Lyme disease cannot be transmitted person-to-person.
   People being treated with antibiotics for Lyme disease
    should not donate blood. Scientists have found that
    the Lyme disease bacteria can live in blood stored for
   You cannot get Lyme disease from eating venison or
    squirrel meat.
   Differential Diagnosis
   Lyme disease mimics many different diseases.
   The EM lesion may be confused with streptococcal cellulitis,
    erythema multiforme (the latter lesions tend to be smaller,
    urticarial, or vesicular and may occur on mucosal surfaces), and
    erythema marginatum (these lesions are smaller and migrate
    rapidly in minutes to hours).
   Lyme arthritis can be distinguished from other rheumatoid
    diseases, such as acute rheumatic fever, based on the EM lesion
    and the brief episode of synovitis.
   The chronic form of Lyme arthritis may resemble pauciarticular
    juvenile rheumatoid arthritis, psoriatic arthritis, Reiter's syndrome,
    and reactive arthritis caused by members of the Salmonella,
    Shigella, Campylobacter, and Yersinia genera. This form of
    arthritis may also be associated with rubella, hepatitis B, or
    echoviruses. The aseptic meningitis in Lyme disease may
    resemble enteroviral, leptospiral, or early tuberculous meningitis.
Treatment: Antibiotic therapy

   Doxycycline and amoxicillin are used for two to four weeks
    in early cases.
   For more severe forms or late-stage disease, treatment with
    intravenous ceftriaxone or penicillin is more effective.

   A recombinant vaccine containing outer surface protein
    (OspA) of the organism is available.
   It is recommended for people living in endemic area.
     You can prevent Lyme Disease by
       Keeping Ticks off your Body!
2. Each of the following statements concerning
   Mycobacterium leprae is correct EXCEPT:

A) In lepromatous leprosy, large numbers of organisms are
  usually seen in acid fast stained smears.

B) The organism will grow on bacteriologic media in 3-6

C) Prolonged therapy (9 months or longer) is required to
  prevent recurrence.

D) Skin tests for delayed hypersensitivity are useful
4.Which one of the following statement is TRUE about
  lepromatous leprosy

A. neuropathy occurs before skin lesions

B. skin lesions are typically anaesthetic

C. skin lesions are typically symmetrical

D. the lepromin test is positive
5. You observe a 40-year-old man begging on a street in a town
   in India. He has clawing of the fourth and fifth digits with
   loss of distal parts of the digits of both hands, strongly
   suggesting leprosy. The causative agent of this disease

A) is susceptible to isoniazid and rifampin
B) grows in parts of the body that are cooler than 37°C
C) can be cultured in the laboratory using Middlebrook 7H11
D) is seen in high numbers in biopsies of tuberculoid leprosy
E) commonly infects people in Texas, because armadillos are
  hosts of Mycobacterium leprae.
 Mims: 2nd edition- chapter 23
Levinson : 7th edition-chapter 48
Jawetz: 23rd edition-chapter 45.

To top