DERMATOLOGY EXIMIUS

LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

Hansen disease
• Mycobacterium leprae
– acid-fast, rod-shaped
bacillus
– grows extremely slowly
and has not been
successfully cultured in
vitro
• chronic infection
• 2 connected diseases
– skin and peripheral nerves (immunologic
response)
• historical stigma
– highly visible debilities and sequelae

WHO (World Health Organization): LEPROSY

• 1990s
– launched a campaign to eliminate leprosy as a
public health problem by 2000
• Elimination:
– defined as a reduction of patients with leprosy
requiring multidrug therapy to fewer than 1 per
10,000 population.
- This goal was achieved in terms of global
prevalence by 2002.
- As of 2014, none of the 122 countries where
leprosy was endemic in 1985 still have
prevalence rates of greater than 1 per 10,000
population
- Sad truth: 1985: multi drug therapy has cured over 14
million of patients worldwide, however the number of
patients affected by the disease remained unchanged from
1980-2000
- Gradual reduction of the case happened bet 2001-2006
- Goal: 2015
- to reduce the rate of new cases with grade-2 disabilities
worldwide by at least 35%
- 9 September 2019 | Geneva | New Delhi −−Data published
by the World Health Organization (WHO)
- - 208,619 new cases of leprosy were reported in 2018
from 127 countries, including all priority endemic
countries, compared with 211 009 cases (representing a
slight global decrease of 1.2%) in 2017
The number of new cases has decreased overall from 244 796 in
2009 to 208 619 in 2018.
LEPROSY: PHILIPPINES
• 16th century
• 1906 to 1980
• Culion Leper Colony
– Goal: isolation
– Gov. General L. Wood
– 2006: WHO leprosy free
• Chaulmoogra oil
– oil from the seeds of Hydnocarpus wightianus
(Chaulmoogra) has been widely used in Indian
and Chinese traditional medicine for the
treatment of leprosy
• Seven years after the World Health Organization (WHO)
declared a leprosy free vision, the Philippines successfully
eliminated leprosy at the national level
• This means the prevalence was reduced to less than one
case per 10,000 people
• However, recent report by the Department of Health
(DOH) revealed pockets of cases in the country account to
about 1,500 leprosy cases identified mostly from poor
communities each year.
• In the Western Pacific Region, the Philippines has the
highest number of new cases detected. This is an
indication that transmission is still ongoing and new
strategies are needed to eliminate and interrupt the
transmission of the disease.

TRANSCRIBERS GROUP 2 1
 DERMATOLOGY EXIMIUS
LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

Leprosy Alert and Response Network System (LEARNS) app – These countries are mostly in Southeast Asia,
• country’s first mobile phone-based leprosy North and South America, Africa, and the
teleconsultation system eastern seaboard of the Pacific Ocean and the
• a product of partnership between the DOH-Novartis Task Western Mediterranean coast
Force and Philippine Council for Health Research and – India alone accounts for 64 percent of all new
Development (PCHRD) cases in the world.
• mobile health (mHealth) tool that enables health care
practitioners in remote areas to refer suspected leprosy
patients to experts by sending a picture of the skin lesion
and patient details through their mobile phone via either
SMS or the LEARNS application
• LEARNS promotes early case finding and helps reduce
delays in diagnosis and treatment
• Aside from case finding, LEARNS also provides data for
disease surveillance, reaction and treatment outcome
monitoring, message broadcasting, patient education, and
report generation

CLASSIFICATION OF LEPROSY • The current prevalence of leprosy is approximately 0.34

• Leprosy has 2 classification schemas:
• the 5-category Ridley-Jopling system
– The axis of classification is the degree of
Lepromin reaction
• Lepromin skin test
– determines what type
of leprosy a person has
– involves the injection of a
standardized extract of the
inactivated "leprosy bacillus"
(M. leprae or "Hansen's
bacillus") under the skin
– not recommended as a
primary mode of diagnosis.
• Positive reaction means:
– A) 10mm or more induration
after 48hrs
– B) 5mm or above nodule
after 21 days
Ridley-Jopling Classification
per 10,000
• Over 200 000 new cases of leprosy have been reported
annually in recent years
– Primary source: lepromatous patients who are
not being treated
– Microbe persists in fomites and other sources
outside the patient’s body when conditions are
right however, most people in endemic areas
have developed resistance to the
mycobacterium
• Mortality/Morbidity
– Rarely fatal
• Primary consequence:
– Nerve impairment
– Debilitating sequelae
• According to one study, 33-56% of newly diagnosed
patients already displayed signs of impaired nerve
function.
• According to estimates, 3 million people who have
completed multidrug therapy for leprosy have sustained
disability due to nerve damage.
• Although both lepromatous leprosy and tuberculoid
leprosy involve the skin and peripheral nerves, tuberculoid
leprosy has more severe manifestations.
• Nerve involvement results in loss of sensory and motor
function, which may lead to frequent trauma and
amputation.
– Ulnar nerve is most commonly involved

• Damage in the following nerves is associated

WHO standard LEPROSY CLASSIFICATION with characteristic impairments in leprosy:
• In an endemic country or area, an individual should be – Ulnar and median - Clawed hand
regarded as having leprosy if he or she shows ONE of the – Posterior tibial - Plantar
following cardinal signs: insensitivity and clawed toes
• Skin lesion consistent with leprosy and with definite – Common peroneal –Foot drop
sensory loss, with or without thickened nerves – Radial cutaneous, facial, and greater
• Positive skin smears auricular nerves
• Race
EPIDEMIOLOGY – no racial predilection
• The highest rates of leprosy are in tropical countries, • Sex
especially in Asia and Africa – male-to-female ratio of 2:1
• Underdeveloped nations are at the greatest risk and, even
today, 105 countries qualify as endemic for the disease

TRANSCRIBERS GROUP 2 2
 DERMATOLOGY EXIMIUS
LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

• Age – Palpation of peripheral nerves for pain or

– occur at any age enlargement, with particular attention paid to
– age-specific incidence of leprosy peaks in the following locations:
children younger than 10 years, who account for • Elbows - Ulnar nerve
20% of leprosy cases. • Wrist - Superficial radial cutaneous and
– Leprosy is very rare in infants; however, they are median nerves
at a relatively high risk of acquiring leprosy from • Popliteal fossa - Common peroneal
the mother, especially in cases of lepromatous nerve
leprosy or midborderline leprosy. • Neck - Great auricular nerve

SYMPTOMS PHYSICAL FINDINGS IN SPECIFIC LEPROSY SUBTYPES

• Painless skin patch accompanied by TUBERCULOID LEPROSY
loss of sensation but not itchiness • Initial lesion: (+) sharply demarcated
(Loss of sensation is a feature of hypopigmented macule (ovoid, circular,
tuberculoid leprosy, unlike or serpiginous) elevated with a dry scaly
lepromatous leprosy, in which center and erythematous borders
sensation is preserved.) • Common lesion sites:
• Loss of sensation or – Buttocks
paresthesias where the affected – Face
peripheral nerves are – Extensor surfaces of limbs
distributed – **The perineum, scalp, and
• Wasting and muscle axilla are not normally involved
weakness because of the temperature
• Foot drop or clawed hands differential in these zones, as
• Ulcerations on hands or feet predilection is toward cooler zones.
• Lagophthalmos, iridocyclitis, • As the disease progresses, lesions tend to destroy the
corneal ulceration, and/or normal skin organs such as sweat glands and hair follicles
secondary cataract due to • Superficial nerves that lead from the lesions tend to
nerve damage and direct enlarge and are sometimes palpable
bacillary skin or eye invasion • The patient may experience severe neuropathic pain.
• Symptoms in reactions are as follows: • Nerve involvement can also lead to trauma and muscle
• Type 1 (reversal) - Sudden onset of skin redness atrophy.
and new lesions
• Type 2 (erythema nodosum leprosum [ENL]; LEPROMATOUS LEPROSY
• - Many skin nodules, fever, redness of eyes, • Characterized by: extensive bilaterally
muscle pain, and joint pain symmetric cutaneous involvement, which can
include macules, nodules, plaques, or papules
TRAVEL & EXPOSURE • Lesions : (+) poorly defined borders and raised
• Leprosy should be considered in anyone who has lived in and indurated centers.
the tropics or who has traveled for prolonged periods to • As in all forms of leprosy, lepromatous lesions are worst
endemic areas on cooler parts of the body
• Incubation period: few months to 20-50 years – Face - Ears -Wrists -
• Mean incubation time: Elbows -Buttocks -Knees.
– 10 years for lepromatous leprosy • Hoarseness, loss of eyebrows and eyelashes,
– 4 years for tuberculoid leprosy and nasal collapse secondary to septa
– The organism's slow dividing time (once every 2 wk) perforation may occur in advanced cases of
contributes to the challenge of epidemiologically disease
linking exposures to the development of disease. • Involvement of the eye may include keratitis, glaucoma, or
• Because of immunologic reasons, only around 5-10% of iridocyclitis
the population is estimated to be susceptible to infection. • The leonine facies associated with leprosy
develop as the disease progresses, and the
PHYSICAL EXAMINATION facial skin becomes thickened and
• Cardinal signs: corrugated.
– Hypoesthesia • Axillary and inguinal adenopathy may develop, in addition
– Skin lesions to scarring of the testes and subsequent gynecomastia and
– Peripheral neuropathy sterility.
• First physical signs of leprosy are usually cutaneous • Nerve involvement in lepromatous leprosy is not as severe
• The subtype of leprosy often determines the degree of as in tuberculoid leprosy, since nerves, although visibly
skin involvement thickened and highly infected, still function reasonably
• Physical examination should include the following: well in early stages of the disease.
– Evaluation of skin lesions
– Careful sensory and motor examination

TRANSCRIBERS GROUP 2 3
 DERMATOLOGY EXIMIUS
LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

BORDERLINE TUBERCULOID LEPROSY

• The lesions are few or moderate and asymmetric with DIFFERENTIAL DIAGNOSES
almost complete anesthesia
• Peripheral nerves are often involved and
thickened asymmetrically, and cutaneous
nerves are sometimes enlarged
• is a cutaneous condition similar to tuberculoid Allergic Contact Dermatitis
leprosy except the skin lesions are smaller Dermatologic Manifestations of Pinta
and more numerous. Sarcoidosis
MIDBORDERLINE LEPROSY Pediatric Contact Dermatitis Psoriasis
• The number of skin lesions is Granuloma Annulare Scabies
moderate, and they are asymmetrical Insect Bites Syphilis
and somewhat anesthetic Irritant Contact Dermatitis Tinea Versicolor
• Peripheral nerves may be somewhat Leishmaniasis Vitiligo
symmetrically enlarged, but Onchocerciasis (River Blindness) Drug Eruptions
cutaneous nerves are not
LABORATORY STUDIES
• The WHO case definition of leprosy is M leprae infection
BORDERLINE LEPROMATOUS LEPROSY in an individual who has not completed a course of
• Moderate to numerous slightly asymmetrical skin lesions treatment and has one or more of the following:
appear with minor or no anesthesia. – Hypopigmented or reddish skin lesions with loss
• Peripheral nerves are of sensation
often enlarged – Involvement of the peripheral nerves as
symmetrically, but demonstrated by their thickening and associated
cutaneous nerves are loss of sensation
not. – Skin smear positive for acid-fast bacilli
INDETERMINATE LEPROSY • Laboratory studies include the following:
• Skin lesions are typically either hypopigmented or • Skin biopsy, nasal smears, or both are used to assess for
hyperpigmented macules or plaques acid-fast bacilli using Fite stain. Biopsies should be full
• Patients may note that these lesions are anesthetic or dermal thickness taken from an edge of the lesion that
paresthetic. appears most active.
• Serologic assays can be used to detect phenolic glycolipid-
CAUSES OF LEPROSY 1 (specific for M leprae) and lipoarabinomannan
• Causative agent: M. Leprae (commonly seen in mycobacteria)
• Acid fast, gram-positive bacillus • Molecular probes detect 40-50% of cases missed on prior
• An obligate intracellular organism with a predilection for histologic evaluation. Since probes require a minimum
Schwann cells and macrophages. amount of genetic material (ie, 104 DNA copies), they can
• M leprae has not been successfully grown using artificial fail to identify paucibacillary leprosy.
media • Laboratory tests related to drug treatment follow-up
include the following:
ROUTE OF TRANSMISSION – CBC count
• HAS NOT BEEN DEFINITIVELY ESTABLISHED – Creatinine level
• Human-to-human aerosol spread of nasal secretions – Liver function tests
– most likely mode of transmission in most cases
• Leprosy is not spread by touch, since the mycobacteria are IMMUNOLOGIC TESTS
incapable of crossing intact skin • Polymerase chain reaction (PCR):
• Living near people with leprosy is associated with – PCR and recombinant DNA technology have
increased transmission allowed for the development of gene probes
• Among household contacts, the relative risk for leprosy is with M leprae–specific sequences. This
increased 8- to 10-fold in multibacillary and 2- to 4-fold in technology can be used to identify the
paucibacillary forms mycobacterium in biopsy samples, skin and nasal
• Animal reservoirs do exist (armadillos, certain nonhuman smears, and blood and tissue sections
primates), and cases of suspected zoonotic transmission
have been reported. • Phenolic glycolipid-1:
– This is a specific serologic test based on the
DIAGNOSTIC CONSIDERATIONS detection of antibodies to phenolic glycolipid-1.
• Superficial mycoses (tinea versicolor) This test yields a sensitivity of 95% for the
• Birthmarks and scars detection of lepromatous leprosy but only 30%
• Granuloma multiforme for tuberculoid leprosy
• Lupus erythematosus
• Pityriasis rosacia
• Diabetes mellitus (neuropathy)

TRANSCRIBERS GROUP 2 4
 DERMATOLOGY EXIMIUS
LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

• Lymphocyte migration inhibition test (LMIT): • The WHO recently recommended single-dose treatment
– As determined by a lymphocyte transformation with rifampin, minocycline, or ofloxacin in patients with
and LMIT, cell-mediated immunity to M leprae is paucibacillary leprosy who have a single skin lesion.
absent in patients with lepromatous leprosy but • However, the WHO still recommends the use of the long-
present in those with tuberculoid leprosy term multidrug regimens whenever possible because they
• Lepromin skin test (not available in the United States): have been found to be more efficacious.
– Although not diagnostic of exposure to or
infection with M leprae, this test assesses a Multidrug Therapy Plan Recommended by the WHO
patient's ability to mount a granulomatous
Type of Daily, Self- Monthly Months of
response against a skin injection of killed M Leprosy Administered Supervised Treatment
leprae. Patients with tuberculoid leprosy or
borderline lepromatous leprosy typically have a
Dapsone 100 Rifampicin
positive response (>5 mm). Patients with Paucibacillary 6
mg 600 mg
lepromatous leprosy typically have no response
• Contact or family screening for history of leprosy
Rifampicin
600 mg,
PROCEDURES Single-lesion Ofloxacin Single
• Skin biopsy samples stained with hematoxylin-eosin and N/A
paucibacillary 400 mg, dose
Fite-Faraco Minocycline
– Primary basis for laboratory diagnosis and 100 mg
categorization
– A full-thickness skin biopsy sample should be Dapsone 100 Rifampicin
taken from an advancing border of an active mg, 600 mg,
Multibacillary 12
lesion and should include dermis and epidermis Clofazimine Clofazimine
50 mg 300 mg
– Skin smears that demonstrate acid-fast bacilli
strongly suggest a diagnosis of leprosy, but the
bacilli may not be demonstrable in tuberculoid Dapsone 2 Rifampicin
mg/kg, 10 mg/kg, Same as
(paucibacillary) leprosy Pediatric
Clofazimine 1 Clofazimine in adults
• A nerve biopsy mg/kg 6 mg/kg
– Can be beneficial in ruling out diseases such as
hereditary neuropathies or polyarteritis nodosa.
– May help identify abnormalities in patients with
subclinical leprosy and may be the only way to
definitively diagnose completely neuropathic
forms of leprosy
– if needed to confirm diagnosis, a purely sensory
nerve (eg, sural or radial cutaneous nerve)
should be used. This procedure is rarely
necessary

HISTOLOGIC FINDINGS
• Lepromatous lesions generally contain numerous acid-fast
bacilli and fat-laden macrophages with a paucity of
lymphocytes
• Histopathology of leprosy: Large numbers of acid-fast
bacilli (in clusters) in histiocytes and within nerves
• Tuberculoid lesions contain few-to-no acid-fast bacilli but
manifest granulomatous changes with epithelial cells and
lymphocytes

STAGING SURGICAL CARE

• Leprosy is staged or graded based on microscopy findings
to classify cases as paucibacillary or multibacillary so that
duration and type of drug therapy can be determined
MEDICAL CARE
• In response to the increased incidence of dapsone
resistance, the WHO introduced a multidrug regimen in
1981 that includes rifampicin, dapsone, and clofazimine.
• Some clinical studies have also shown that certain
quinolones, minocycline, and azithromycin have activity
against M leprae.
TRANSCRIBERS GROUP 2
• The goals of surgical treatment in patients with leprosy are
to prevent further deterioration, to improve motor
function, and, in some cases, to improve sensation
• Neural surgery
• Reconstruction and functional restoration
• Eye procedures
• Cosmetic surgery
COMPLICATIONS
• Careful attention to the development of reversal reactions
during treatment and prompt and proper management
will minimize long-term neurologic sequelae
5
 DERMATOLOGY EXIMIUS
LEPROSY 2021
Heraluz Liquigan-Damo, RPh, MD, PAPSHPI MARCH 2020

TYPE 1 REACTION
– Reversal reaction, or lepra type 1 reaction
– Delayed-type hypersensitivity reaction
– Arises when borderline leprosy shifts toward
borderline lepromatous leprosy with treatment
– These types of reactions reflect the development
of an appropriate immune response and the
local generation of tumor necrosis factor-alpha
and interferon-gamma.
– Characterized by:
• edema and erythema of existing skin
lesions
• formation of new skin lesions
• Neuritis
• additional sensory and motor loss
– The likelihood of a type 1 reaction in patients
with borderline leprosy is 30%.
– Treatment:
• NSAIDs
• High-dose steroids MEDICATION SUMMARY
• Prednisone is given at a dose of 40-60 • The goals of pharmacotherapy are to eliminate the
mg/day with a decreasing taper of 5 infection, to prevent complications, to halt its further
mg every 2-4 weeks after transmission and spread, and to reduce morbidity.
improvement is demonstrated. • The multidrug therapy (MDT) plan recommended by the
WHO can be used to plan therapy based on the type of
TYPE 2 REACTION leprosy (paucibacillary or multibacillary) and whether it is
• Erythema nodosum leprosum (ENL) supervised monthly or self-administered daily
• Lepra type 2 reaction
• A complication of lepromatous leprosy
• Characterized by the development of inflamed
subcutaneous nodules accompanied at times by fever,
lymphadenopathy, and arthralgias.
• High levels of tumor necrosis factor-alpha and immune
complex deposition are associated with ENL.
• Treatment:
– Prednisolone
– Clofazimine
– Thalidomide
– Mild ENL reactions are treated with aspirin 600-
1200 mg/day in 4-6 doses per day
• Severe ENL reactions are treated with prednisone 60-80
mg/day with a slow taper, reducing by 5-10 mg every 2-4
weeks, depending on response and severity, to prevent
residual deformity and nerve damage.
• Alternatively, thalidomide 100 mg PO 4 times per day (if
available and in the absence of contraindications) can be
used in cases that involve large subcutaneous plaques,
arthritis, and temperature that exceeds 38.8°C

LUCIO PHENOMENON
• Severe complication of multibacillary leprosy that is
marked by blue hemorrhagic plaques and necrotic
ulcerations
• The bacilli may extend to the endothelial cells along with
the appearance of necrotic epidermis and vasculitis with
thrombus formation and endothelial proliferation

TRANSCRIBERS GROUP 2 6