LEPRA

REACTIONS
Presented by Dr Aarti Pandey
(JR2 Dermatology)
 INTRODUCTION
• Leprosy reactions are immunologically mediated
episodes of acute or subacute inflammation which
interrupt, the relatively uneventful usual chronic
course of disease affecting the skin, nerves, mucous
membrane and/or other sites.
TYPES OF LEPROSY
REACTIONS
• Three types of reactions recognized are
classified as follows:
Type 1 Reaction
Type 2 Reaction or Erythema Nodosum
Leprosum
The Lucio Phenomenon
TYPE 1 REACTION
The type 1 reaction (T1R) is a delayed
hypersensitivity reaction associated with
sudden alteration of cell-mediated
immunity.
Borderline spectrum
The skin or nerves or both may be
affected
Upgrading or Reversal Reaction
When there is increase in the immunity,
the shift is from borderline spectrum
toward the tuberculoid pole and is called
upgrading or reversal reaction.
Downgrading Reaction
If there is sudden shift toward the
lepromatous pole with reduction of
immunity, it is called as downgrading
reaction.
 TYPE 1 REACTION
(REVERSAL REACTION)
The Risk Factors for Type 1 Reactions:
Borderline group of patients (BT, BB
and BL)
Patients who have one episode of
reaction are more likely to develop a
second episode of reaction.
Female gender carries a higher risk be due to
hormonal fluctuations,Pregnancy and delivery
(highest in the first 6 months after delivery) .
Older age group
Multiple and disseminated patches involving larger
body areas and multiple nerve involvement
Large facial patches and lesions near the eyes are at
risk of developing lagophthalmos due to a reactions
Those with Nerve enlargement, paresthesia and
tenderness
Positive SSS
Starting of treatment may precipitate reaction due to
increased break down and release of bacterial
antigens. Increased bioavailability of antigens
triggers the delayed type hypersensitivity (DTH)
response.
 RRs is observed to be relatively higher when MDT is
administered combined with immunotherapy
Mycobacterium indicus pranii (MIP) as compared to
those under MDT alone
Hepatitis B or C may be risk factors for developing
RRs
IMMUNOPATHOMECHA
NISMS
Increased cell-mediated (Type IV) immune response
to Mycobacterium leprae antigens
Activation of CD4+ lymphocytes (Th1 type) and
increased expression of adhesion molecules on
endothelium, increased IL-2 and IFN-Y
 CLINICAL
MANIFESTATIONS
Symptoms:
Burning, stinging, warmth, rapid color change in
the skin lesions
Aches and pains in the extremities and of loss of
strength and/or sensory perception.
They may suddenly start dropping things from
their hands and/or stumble when walking
Signs:
Increased inflammation of some or all of the pre-
existing skin patches or plaques which become
erythematous, swollen and may be tender
Necrosis and ulceration can occur in severe
cases. Lesions desquamate as they subside
Crops of fresh inflamed skin lesions in the form of
plaques may appear in previously clinically
uninvolved skin
Edema of extremities or face, frequently
accompanied by nerve involvement
 Neuritis: Rapid swelling with severe pain\tenderness
of one or more peripheral nerves is common.
The peripheral nerve affected is usually close to the
inflamed skin lesion or situated over the area
innervated by the corresponding nerve.
In the severe form of T1R nerve abscess
is formed
Sometimes loss of nerve function occurs suddenly
without other signs of inflammation, making it much
less obvious— the so called ‘silent neuritis’, i.e.
without apparent neuritis, producing claw hand, foot
drop and facial palsy.
Tenosynovitis due to synovial inflammation
manifested with a moderately painful swelling over
the dorsum of one or both hands and very rarely over
the dorsum of the feet
Very severe reaction may be characterized by
necrosis and deep ulceration
Systemic manifestations like fever, malaise, vomiting,
epistaxis and joint pain are unusual.
 GRADING OF
REVERSAL REACTIONS
Reversal reactions (RRs) can be graded as mild or
severe in form
Mild
Few skin lesions with features of reaction clinically;
without any nerve pain or loss of function
Severe
Nerve pain or paresthesia
Increasing loss of nerve function
Fever or discomfort
Edema of hands, feet
Mild reaction persisting for more than 6 weeks
Reaction of skin lesion on the face
Ulcerative skin lesion
CRITERIA FOR DIAGNOSIS
OF TYPE 1 REACTION (T1R)
by Naafs and his team
MAJOR
Pre-existing and/or new skin lesions become
inflamed, red and swollen
MINOR
1. One or more nerves become tender and may be
swollen
Crops of new (painless) lesions appear
Sudden edema of face and extremities of the disease
Recent loss of sensation in hands and feet or signs
of recent nerve damage (loss of sweating, sensation,
muscle strength) in an area supplied by a particular
nerve.
DIFFERENTIAL DIAGNOSIS
Reversal reaction, particularly late RR, must be
differentiated from relapse
And the other skin conditions like acute urticaria,
erysipelas, cellulitis and insect bite reaction.
THE RISK FACTORS FOR
TYPE 2 REACTIONS:
Lepromatous leprosy
Bacterial index (BI) of >4+
Patients with < 40 years of age
Intercurrent infections: Streptococcal, viral, intestinal
parasites, filariasis, malaria
Trauma
Surgical intervention
Physical and mental stress
Vaccination
Pregnancy and parturition, lactation
Ingestion of potassium iodide.
Ted anti - Mleprae Antibodies
 HISTOPATHOLOGY
Dense infiltration of dermal and subcutaneous tissue
by neutrophils (sometimes forming microabcesses),
superimposed on existing lepromatous diffuse
granuloma.
Vasculitis, damage to collagen and elastic fibers are
common features clinically manifesting as skin
necrosis and ulcerations
 CLINICAL
MANIFESTATIONS
Type 2 reaction occurs mostly during the course of
antileprosy treatment.
A few cases present for the first time with features
of reaction before leprosy is diagnosed and
treatment started
There may be appearance of crops of skin lesions in
the form of painful/tender evanescent maculopapular,
papular, nodular or plaque type of lesions with the
appearance of constitutional signs and symptoms.
Rheumatic Onset
In one-third of the cases, pain and swelling in the
joints precede or are a component of other
constitutional symptoms.
Fever, joint pains, other constitutional signs and
symptoms, and skin lesions develop together.
Fever follows the appearance of skin lesions.
SKIN LESIONS - ERYTHEMA
NODOSUM LEPROSUM
There is sudden appearance of crops of evanescent
(lasting for few days) pink (rose) colored tender
papules, nodules or plaques variable in size.
They are painful and tender to touch.
These lesions may be present inside the dermis
and visible clearly or may be deep enough
involving subcutaneous tissue forming
subcutaneous nodule (SCN) where they are
palpable rather than visible. The nodules are
dome-shaped and ill-defined. These skin lesions
are known as ENL
The common sites of appearance of ENL are
outer aspects of thighs, legs and face.
They may appear anywhere on the skin except
the hairy scalp, axillae, groin and perineum
These may be few or multiple, if multiple they
tend to be distributed bilaterally and
symmetrically.
Tender, warmer, and blanch with light finger
pressure.
ENL lesions may not uncommonly become vesicular,
pustular, bullous and necrotic and break down to
produce ulceration called as erythema nodosum
necroticans
The ENL lesions subside with desquamation or there
may be peeling of the superficial skin
There may be edema of the hands, feet or face.
When the inflammatory edema on the dorsum of the
hand is associated with Sub cutaneous nodules and
arthritis of the interphalangeal (IP) joints; it
constitutes the clinical condition known as the
reaction hand
 LEPROMATOUS
EXACERBATION
Characterized by exacerbation of the LL skin lesions;
they are swollen, red, painful and tender.
There may be constitutional symptoms
Lesions may ulcerate involve cartilage of pinna giving
a rat bitten appearance.
Exacerbation may involve the mucosa, leading to
nasal stuffiness and hoarseness of voice.
Rarely, laryngeal edema may require emergency
tracheostomy
Acute exacerbation of the disease is mainly seen in
very advanced lepromatous patients with nodular and
plaque like lesions.
Unusual Pattern of Vesiculobullous Type 2
Reactions:
Atypical bullous lesions in T2Rs arranged in an
annular fashion on the extensor aspects of arms
and lower legs have been described in a
pregnant lady after ingestion of ofloxacin
SYSTEMIC MANIFESTATIONS
In T2R, the systemic manifestations like fever,
malaise, headache, muscle, joint and bone pain,
usually confining to tibia are common, may precede
the appearance of ENL.
The rise of temperature is usually of intermittent type
in the acute stage with the fastigium in the evening.
As the reaction subsides, the temperature comes
down.
 NERVE INVOLVEMENT
Nerve damage may occur in T2R, but not as quickly
as it occurs in T1R.
Due to inflammatory edema and cellular exudates in
the perineurium; the nerve is unable to accommodate
the increase in its bulk contents.
Compression of the vasa nervorum and of the nerve
fibers, results in precipitation of acute symptoms.
Added compression is provided by points of
entrapment of certain sites
In severe T2R there may be swollen, painful, and
tender nerve trunks with loss of function
 ACUTE MYOSITIS
Extension of the process of SCN formation, from the
subcutis to deep into the muscle through deep
fascia.
The entire involved region feels woody hard.
In some cases painful, tender, firm nodular lesions
occur in the muscle fibers per se.
The movement of the muscles is painful
 ARTHRITIS
joint swelling, pain, tenderness, with limitation of
movements.
Synovial effusions and bursitis occur
Joints commonly affected are knee,
metacarpophalangeal, IP, wrist and ankle joints
INVOLVEMENT OF NOSE
The infiltration and nodules present in the nasal
septum and inferior turbinate may be swollen with
blocking of the nose leading to difficulty in breathing.
It may be associated with pain and epistaxis
In severe cases the nodules may ulcerate, the
cartilage may be involved resulting in perforation of
the septum
SOFT PALATE INVOLVEMENT
The soft palate, base of the uvula may be hyperemic
and may ulcerate.
Repeated ulceration may lead to complete
destruction.
HARD PALATE INVOLVEMENT
Hard palate may similarly be hyperemic and swollen
Erosion of these reacting lesions involves the bone
with destruction and eventually a perforation of the
palate may result
INVOLVEMENT OF LARYNX
In presulfone era the inflammatory reaction involving
the larynx was a life threatening complication.
The edema of the epiglottis or of the false vocal
cords led to respiratory embarrassment which
sometimes necessitated tracheostomy as a life-
saving procedure
 BONE CHANGES
Osteoperiostitis:
Common over the anterior aspect of the tibia.
There are severe bone pains and soft tender
swelling of the anterior aspect of tibia
Repeated attacks may lead to laying down of new
bone with thickening of the cortex
Besides tibial involvement it may also involve the
phalanges (dactylitis) producing spindle-shaped
swellings with tenderness. This can occur at the
upper end of ulna, the lower end of fibula, and the
calcaneum
Osteoporosis may occur without accompanying
arthritis. The phalanges and metacarpals are
commonest sites
Lymph Node Enlargement:
During ENL episodes, there is often acute and
painful enlargement of inguinal, axillary, cervical
and epitrochlear lymph nodes along with
constitutional signs and symptoms.
Occasionally, large abscesses are formed which
break open through lymph node capsule and skin
producing sinuses with discharge of pus
Involvement of Liver
Hepatic enlargement below the costal margin is
sometimes observed. The liver is soft and tender.
Involvement of Kidneys
Acute glomerulonephritis in leprosy may be
associated with ENL, due to the immune
complex deposition involving antigens of M.
leprae. Routine examination of urine reveals
albuminuria
Suprarenal Involvement
The blood pressure remains low due to
hypofunction of the suprarenal gland during
reactive phases
Acute Epididymo-orchitis
There may be acute pain, tenderness and
swelling in the scrotum during T2R due to acute
inflammation of the testes and epididymis.
 There may be concomitant swelling and
tenderness of the breast
Repeated attacks of reaction result in testicular
atrophy and
Hematological Changes
A hemolytic crisis may be encountered with a
dangerous fall in the RBC count and
hemoglobin.
There is sudden pallor; the patient develops
breathlessness on the slightest exertion
 CRITERIA FOR
DIAGNOSIS OF T2R
MAJOR:
Sudden eruption of tender (red) papules,
nodules or plaques, which may ulcerate
MINOR:
Mild fever,
The patient is unwell
Tender enlarged nerves
Increased loss of sensation or muscle power
MINOR:
Arthritis, Lymphadenitis, Epididymo-orchitis,
Iridocyclitis or episcleritis
Edema of extremities or face
Positive Ryrie or Ellis test
Certain clinical tests are used as a clue for
diagnosis of T2R.
Ryrie Test
Stroking the sole of the foot with the back of a
reflex hammer elicits a burning pain which also
may be noticed when watching the patient walk,
which seems as if he is walking on hot coals.
Ellis Test
Squeezing the wrist during ENL elicits a painful
reaction;
LABORATORY TESTS
Leukocytosis
Elevated ESR
Fall in Hb, RBC count
Rise in serum transaminases
URM
LUCIO PHENOMENON
Seen In Uniformly diffuse shiny infiltrative non-
nodular form of LL leprosy, called as Lucio
leprosy which is chiefly encountered in Mexicans
M. leprae are found unusually in large numbers in
the endothelial cells of superficial blood vessels,
and this finding may be responsible for the
serious vascular complications seen during the
reactive phase
There is marked vasculitis and thrombosis of the
superficial and deep vessels resulting in
hemorrhage and infarction of the skin.
 CLINICAL
MANIFESTATIONS
The reaction begins with slightly indurated red-
bluish plaques on the skin with an erythematous
halo, usually on one of the limbs, but may also
develop on other areas of the body.
The lesions are ill-defined, but painful and rarely
palpable.
The shape of lesions is irregular or triangular
After a few days they become purplish at the
center, a central hemorrhagic infarct may
develop with or without blister formation.
Later, this becomes a necrotic eschar, which
detaches easily, leaving an ulcer of irregular
shape.
The ulcer heals leaving a superficial scar
Specific histopathological features: Ischemic
epidermal necrosis, necrotizing vasculitis of small
blood vessels in the upper dermis, severe focal
endothelial proliferation of mid-dermal vessels,
and by presence of large number of AFB in
endothelial cells
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