LEPROSY 2 Flashcards
- Delayed hypersensitivity reaction associated with sudden alteration of CMI status
- Marked by infiltration of lesion by activated CD4+ T lymphocytes (T helper cells)
- “Reversal reaction” - upgrading of CMI status
- Usually observed in the borderline portion
- Skin lesions: acute swelling and redness
- Nerves: painful and tender of neuritis, consequent nerve damage and disfigurement; severe - nerve abscesses
- “Silent neuritis” - may lead to sensory and motor impairment in the hands, feet and face
- Arthralgia or arthritis sometimes occur, fever and malaise, tenosynovitis, edema of the feet and hands
Type 1 Leprosy Reaction (T1R)
- An immune complex-mediated syndrome, that causes inflammation of the skin, nerves and other organs, as well as general malaise
- Occurs mostly during multidrug therapy, can also develop in untreated patients
- Evanescent, pink-to-red maculopapular, papular, nodular, or plaque lesions accompanied by malaise and fever, with or without painful swelling of the joints
= Present on the outer aspects of the thighs, legs & face
= Painful or tender and warm, blanch with light finger pressure, last for a few days - Erythema nodosum necroticans: vesicular, pustular, bullous, and necrotic and break down to produce ulceration
- Severe: swollen, painful, and tender nerve trunks with sensory and motor deficits
Type 2 Leprosy Reaction (T2R) - ENL (Erythema Nodosum Leprosum)
Example of Type III hypersensitivity reaction or Arthus phenomenon
Type 2 Leprosy Reaction (T2R) - ENL (Erythema Nodosum Leprosum)
- May be a variant of erythema nodosum necroticans
- Marked vasculitis and thrombosis of the superficial and deep vessels - hemorrhage and infarction of the skin
- Begins as slightly indurated, bluish-red, ill-defined, painful, and rarely palpable plaques with an erythematous halo
- After a few days, they become purplish at the center; a central hemorrhagic infarct may develop, and a necrotic eschar that detaches easily and leaves an ulcer of irregular shape
- Remains afebrile throughout
Lucio’s Phenomenon
- Used for the sensory, motor, and/or autonomic nerve deficits that occurs because of the pathologic processes
- Neuritis (nerve inflammation) - subacute, demyelinating and unremitting event involving cutaneous nerves and larger peripheral nerves
- Can occur at any time during leprosy, but more common and severe during leprosy reactions (mainly T1R)
- Can lead to secondary impairments - muscle atrophy, mobile- and fixed-joint contractures, bone absorption of digits, and cracks and wounds
Leprosy Reactions:
Nerve Function Impairment, Neuritis, and Disfigurement
progressive sensory or motor impairment in the
absence of symptoms in Leprosy Reaction
“Silent neuritis” or “Quiet nerve paralysis”
Diagnosed when 2 or these 3 signs are present of leprosy
- Hypopigmented or erythematous skin lesions with definite loss or impairment of sensation
- Involvement of peripheral nerves, as demonstrated by definite thickening with sensory impairment
- A positive result for AFB in slit-skin smears, presence of AFB in a skin smear or biopsy sample, or a positive result in a biopsy PCR
Testing of Skin Sensation
- Light touch sensation
- Pain
- Thermal sensation
Slit-Skin Smear
- Taken from four sites: right earlobe, the forehead above the eyebrows, the chin, and the left buttock in men or left upper thigh in women
- Stained using Ziehl-Neelsen reagent and examined with a light microscope
Skin biopsy
- Done to confirm the diagnosis of leprosy, to classify the disease, to support the diagnosis of reactions, and to determine cure after the completion of multidrug therapy
- Macular lesions: taken from the middle of a lesion
- Plaques: active indurated edge
- Numerous with different morphologies: more than one biopsy
- is a specific lipid on the M. Leprae cell wall
- used for serologic diagnosis of leprosy
=Multibacillary (90-95%), Paucibacillary (25-60%) - ML flow test: developed for detection of antibody to PGL-1
= Multibacillary (92-97%%), paucibacillary (32-40%)
PGL-1 Antibody Test
- Measures cellular immunity against lepromin
-mThe reaction is measured as induration in millimeters
3-4 weeks after intradermal inoculation. - Negative lepromin test: LL or BL leprosy (indicating the
lack of a protective cellular response
Lepromin Test (Mitsuda Skin Test)
Significantly enhances the detection of M. Leprae, especially in bacteriologic indexnegative leprosy and cases that do not fulfill the criteria for cardinal signs of leprosy
- Sensitive to as few as 1-10 bacilli and yield positive results in 60-7% of smear negative cases
Gene Amplification (PCR) Technique
- Ulnar and median nerves, posterior tibial nerve - usually tested for touch sensation
- Semmes-Weinstein monofilament (SWM) test - most reliable test
- Impairment is <6 months, and/or new nerve function impairment is diagnosed: glucocorticoid should be given
- WHO recommends ballpoint pen be used, if filaments not available
Touch Sensation Testing
Voluntary Muscle Testing
- Facial nerve -
- Ulnar nerve -
- Median nerve -
- Radial nerve -
- Common peroneal nerve -
- Facial nerve - eye closure
- Ulnar nerve - finger abduction;
- Median nerve - thumb opposition;
- Radial nerve - wrist extension;
- Common peroneal nerve - ankle extension
sensitive measure for detection of peripheral autonomic nerve damage in leprosy patients
Laser Doppler measurement of autonomic vasomotor reflexes
Drugs recommended in treatment for leprosy
- Dapsone
- Rifampin
- Cloofazimine
- monthly dose of rifampin together with daily doses of dapsone and daily and monthly doses of clofazimine
- 12 months
Multibacillary leprosy
- treated with 2 drugs, monthly doses of rifampin and daily doses of dapsone
- 6 months
Paucibacillary leprosy
- Hepatotoxicity - mild transient elevation of hepatic aminotransferases (not an indication for discontinuation)
- Urine discoloration occurs - harmless
Rifampin
- Poor safety profile
- Can cause mild hemolysis, may cause anemia, or rarely, psychosis
- DDS Syndrome (Dapsone hypersensitivity syndrome): develops 6 weeks after commencement, manifests as fever, skin rash, eosinophilia, lymphadenopathy, hepatitis and encephalopathy
= 10% fatality rate: liver failure, sepsis, and bone marrow failure
= Require systemic glucocorticoid - Other rare but severe cutaneous adverse reactions: erythema multiforme, Stevens-Johnson syndrome, toxic epidermmal necrolysis, and exfoliative dermatitis
- Agranulocytosis, hepatitis, cholestatic jaundice
Dapsone
- High drug concentration found in the intestinal mucosa, mesenteric lymph nodes, and body fat
- Skin doscoloration - most noticeable adverse event, ranging from red to purple or black, with degree of discoloration depending on the dosage
- Can accumulate in active leprosy skin lesions, making them prominent
=Fades within 6-12 months of discontinuation - Urine, sputum, and sweat may become pink
- Characteristic ichthyosis on the shins and forearms
- Adverse GI events: mild cramps to diarrhea and weight loss (from crystal deposition in the wall of the small bowel)
Clofazimine
Relapse - multiplication of M. Leprae, with an increase of at least 2+ over the previous value in BI at any single site, usually occurs in conjunction with evidence of clinical deterioation
Multibacillary leprosy
- Symptoms may resemble Type 1 Reaction
- Therapeutic trial with glucocorticoids may help distinguish between the two
- Type 1 Reaction - definite improvement within 4 weeks of initiation of glucocorticoid therapy
- Clinical relapse - Lack of response
Multibacillary leprosy
Daily treatment with at least 2 second-line drugs (Clarithromycin, Minocycline, or a Quinolone) plus Clofazimine for 6 months, followed by Clofazimine plus one of the second-line drugs daily for additional 18 months
Rifampin-Resistant leprosy
Treatment of Leprosy Reactions
Short-acting glucocorticoids (Prednisolone)
Type 1 Reactions
Treatment of Leprosy Reactions
- Aspirin and Pentoxifylline
- Thalidomine - if rapid effect is needed
= Teratogenicity - Acute ENL - glucocorticoids
Type 2 Reactions
Treatment and Prognosis of Nerve Function Impairment
High-dose prednisolone - drug of choice
Nerve decompression surgery
Treatment of Neuropathic Pain
- Tricyclic antidepressants
- Phenothiazines
- Anticonvulsants
- Combined with analgesics and anti-inflammatory drugs
Prevention & Control
Vaccination
- The Bacille Calmette-Guerin (BCG) vaccine - provides varying degrees of protection
- 2 promising vaccines: MIP vaccine from India (based on killed Mycobacterium indicus pranii), LepVax vaccine
Prevention & Control
Post exposure Chemoprophylaxis
Single-dose Rifampin
Prevention & Control
“Zero Leprosy”
- Focusing on zero infection and disease, zero disability, and zero stigma and discrimination
- Singled-dose Rifampin - one of the key strategies to achieve these goals
