CNS Infections- Leprosy Flashcards
Mycobacterium leprae (Leprosy, AKA Hansen’s Disease) primarily involves
involves peripheral nerves and skin in cooler regions of the body and mucus membranes and tissues of upper respiratory tract
Leprosy is the most common treatable cause of __________
neuropathy in the world
Mycobacterium leprae description
- 4 strains
- Acid-fast bacillus rod (mycolic acids in cell wall),
- Slow growth rate (estimated generation time is about 12 hours).
- Cannot be cultivated in vitro (Never cultured in vivo for diagnostic purposes)
An obligate intracellular pathogen, which grows in:
- macrophages,
2. histocytes of skin,
3. Schwann cells of nerves.
Incidence in the world most often occurs in
- Southeast Asia: India, Indonesia, Bangladesh, Myanmar (Burma).
- The remaining cases are primarily in Brazil, Nigeria
Transmission is primarily from diseased patients (esp. those with lepromatous form) via:
- aerosol route from persons with the lepromatous form of disease.
- Mucous membranes or broken skin on the one person makes direct contact with skin lesions from persons with the lepromatous form of disease.
Most common form of infection is
asymptomatic form
With respect to Schwann cells (SC) The organism binds laminin-2 to alpha-dystroglycan on Schwann cells (these binding proteins are not found in CNS) to enter Schwann cells. Only infects __________
non-myelinating SC that surrounds bundles of small diameter sensory nerve fibers.
Also causes demyelination of peripheral nerves, which activates myelin-forming SC to ___________ (this is a normal physiological process for myelin-forming SC).
de-differentiate & become non-myelinated
-These de-differentiated SC are now susceptible to infection by M. leprae
Sensory nerve loss in initially confined to
to the skin rash (with losses to temperature greater than losses to pinprick and light touch. Proprioception and vibration modalities are often preserved).
Sensory nerve loss progresses to
multiple mono-neuropathies with large nerve sensory and motor involvement and distal painless injuries.
The nerves affected are primarily the pressure/trauma-dependent nerves, with the ulnar nerve at the elbow involved most often, followed in order by
the superficial radial cutaneous and median nerve at the wrist, sural, radial, Popliteal fossa - Common peroneal nerve, Great auricular nerve in the neck and branches of the facial nerve (facial paralysis/lagophthalmos)
Deep tendon reflexes generally ________
preserved because the muscle spindles and large-fiber nerves are not involved
3 cardinal signs of disease
- Skin lesions.
- Skin anesthesia.
- Peripheral nerve enlargement
Peripheral nerve enlargement causes 3 things:
KNOW!!!
- **Deformities due to weakness and wasting of muscles (eg, claw hand or foot drop secondary to muscle weakness)
- **Sensory symptoms, such as diminished to complete loss of sensation, paresthesias in the distribution of affected nerves, and neuralgic pain when the nerve is struck or stretched.
- **Spontaneous painless blisters, burns, and trophic ulcers on hands and feet, post sensory loss
Disease Classification is based on the immune response of host
Ridley Jopling classification:
- Tuberculoid (TT) form
- Lepromatous (LL) form
- Borderline (3) forms (borderline boarderline, BB, BT, BL)
To classify, World health organization uses:
- Paucibacillary (PB) leprosy is defined as five or fewer skin lesions without detectable bacilli on skin smears = TT form.
- Patients with only a single skin lesion are classified separately as single lesion PB = TT form.
- Multibacillary (MB) leprosy is defined as six or more lesions and may be skin smear positive = LL form
Tuberculoid (TT) form, is it contagious?
NO
Tuberculoid (TT) form description
- Damage to patient’s skin and nerves occur via CMI
- Patients have a positive response to lepromin skin testing
- sensory loss in the skin rash, multiple mono-neuropathies with large nerve sensory and motor involvement
- There is no caseous necrosis observed in skin lesions but it may be present in peripheral nerves
Skin lesion description in Tuberculoid form (TT)
- *skin plaques**
- granulomatous (CMI response to agent)
- large, asymmetric, few in number
- hypopigmented, flattened, dry, scaly center.
- sharply demarcated, raised edge,
- with no sensation in center of lesion or the whole area around the lesion due to invasion of the nerves
- with few acid-fast organisms present.
- lesions tend to destroy the normal skin organs such as sweat glands and hair follicles
Skin lesions with TT are unique because
they have no sensation in center of lesion or the whole area around the lesion due to invasion of the nerves
For TT, Sensory loss as described above with progress to multiple mono-neuropathies occasionally causes ___________
extreme pain beyond endurance
Lepromatous (LL) form - Contagious, yes or no?
YES
During Lepromatous (LL) form damage to patient occurs via __________: Macrophages infiltrate the infection site with histocytes and engulf large numbers of bacilli, fill-up with lipid debris from bacilli, and enlarge, they are then designated as ___________, and cause skin lesions but multiple, __________ lesions throughout the body (nerves, eyes, and internal organs in addition to the skin).
Innate immune response
“foamy macrophages”
symmetrically distributed
During LL form, damage to patient occurs via Humoral immune response: _____________ is common → joints and kidney inflammation due to deposition of Ag-Ab complexes followed by inflammation – a _______ hypersensitivity response at these sites.
A polyclonal hypergammaglobulinemia
type III
Nerve damage like TT form occurs – Sensory loss, however patients are specifically NON-responsive (anergic) to ____________ but is capable of a normal CMI response to other agents, including other mycobacteria.
lepromin (Ag) and/or the organism,
Skin lesions are a cardinal sign of LL, due to the innate immune response:
- extensive
- raised (papular or nodular lepromas skin lesions)
- irregularly shaped, with poorly defined edges.
- bilaterally symmetrical,
- lesions can coalsces.
- high densities (109 → 1010 cells/g tissue) of M. leprae are present in each lesion.
Other S/S of Lepromatous (LL) form
- extensive tissue destruction (e.g., nasal cartilage [saddle nose], perforated nasal septum, swollen enlarged ear lobes) occurs.
- loss of body hair.
- arthralgias.
- myalgias
- redness of the eyes (cannot close eyelids/ lagophthalmos).
- severe neuropathy & sensory loss →claw hand and foot drop
- bone reabsorption & trauma result in loss of digits.
- Kidney failure (most common cause of death)
Borderline (3) forms (borderline (BB, BT, BL):
- Both types of lesions are present. Disease can go either way depending upon immune status of the patient.
- Most leprosy patients fall within the borderline forms
During diagnosis, Full thickness skin biopsy specimen is taken and histology will show
- if organized epithelioid granulomas are present the patient has TT form.
- if “foamy macrophages” are present then patient has LL form.
- If disorganized epithelioid granulomas are present, the patient has the borderline form LT
Type of staining used? KNOW!
Acid-fast staining by Fite-Farco modification of the acid-fast (carbol fusin) stain of skin biopsy specimen from the advancing margin of an active lesion
Acid Fast Stain will show
TT form- no bacilli are present (rare)
LL form- High densities of acid-fast bacilli
- Numbers of bacilli falling within the range of a. and b. of above are present in a patient with boarderline form
- Slit-skin smear can be used for semiquantitive enumeration of bacilli in skin to assess patients during and after treatment
Lepromin test is observed both 2 or 3 days and then 3 to 4w after injection, results are expressed as size of induration in mm. This test is NOT used for:
- Not diagnostic or prognostic (Not FDA approved, not available in the US)
- Not used to monitor progress in therapy.
- Not used to determine infection or exposure to M. leprae (low sensitivity & specificity).
- Is a DTH response (a measure of lymphocyte/macrophage accumulation/proliferation at injection site).
- Is used to assess disease form, but skin biopsy is preferred means to determine disease form
Positive vs Negative Lepromin test
- A negative response to the test is associated with a person with LL form
- A positive response (actual granuloma formation) is associated with a person with TT form
Multidrug therapy (MDT) is now the norm, due in part, to emerging resistance strains:
- dapsone (sulfanilamide) and either or both of the two below:
- rifampin
- clofazimine – a fat-soluble riminophenazine dye, antibacterial that inhibits DNA replication, anti-inflammatory and immunosuppressive, produces pink to brownish skin pigmentation in nearly all patients within a few weeks, as well as similar discoloration of most bodily fluids and secretions.
Treatment time for TT vs LL
TT form: 6 months and 2 drugs.
LL form: 2 years and 3 drugs.
- Patients are considered noninfectious within 1→2 weeks of treatment (usually after the first dose)
- Monitor drug therapy with microscopic examination of stained skin smears
Erythema nodosum leprosum (ENL) is believed to be due to ____________
massive release of bacterial antigens and can occur in absence of treatment
-Occurs in many patients within 1 y of initiation of effective treatment
Erythema nodosum leprosum (ENL) is characterized by:
- deep, tender, extremely painful, red papules or nodules (lepromas) on face, arms, thighs
- a generalized systemic response including fever, joint pain, edema, proteinuria and malaise, neuritis
NOT the same as
regular erythema nodosum
Treatment for ENL
- Thalidomide (for lepromatous form, specifically to reduce occurrence of ENL; eliminates need for corticosteroid use)
- Clofazimine
Prognosis for TT, LL and BT/BL
TT – good even without treatment, but treat anyway.
LL – poor without treatment
B – depends upon if patient is BT or BL
-high #s of bacilli post treatment= relapse is common
Respiratory isolation is required for
LL and the indeterminate forms until chemotherapy becomes effective.
-No quarantine or hospitalization required for TT.
Chemoprophylaxis is used for
close contacts
vaccine is available/approved in India, Brazil; can be preventative for neonates
