Mycobacterium leprae: Difference between revisions
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Mycobacterium leprae
m (Text replacement - "Clinical Presentation" to "Clinical Manifestations") |
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− | == |
+ | ==Background== |
− | === |
+ | ===Microbiology=== |
− | * Slow-growing Stain::Gram-positive]] and Stain::acid-fast]] [[Cellular shape::bacillus]] |
||
+ | *Slow-growing [[Stain::Gram-positive]] and [[Stain::acid-fast]] [[Shape::bacillus]] |
||
− | === Epidemiology === |
||
− | * About 1 million cases worldwide each year, but is rare in North America |
||
− | ** Number may be underestimated due to difficulties with reliable diagnosis |
||
− | * Most commonly occurs in Southeast Asia (especially India) and Brazil |
||
− | * Decreasing incidence over the past several decades, likely due to short-course multidrug therapy starting in 1982 |
||
− | * Humans are thought to be the main reservoir, but it has been found in animals as well (particularly nine-banded armadillos) |
||
− | * Transmitted most likely by respiratory droplets, though can also be transmitted by direct contact, transplacentally, through breast milk, and after animal exposure |
||
− | === |
+ | ===Epidemiology=== |
− | * Age, with peaks in adolescence and ≥30 years |
||
− | * Adult men (compared to adult women) |
||
− | * Duration of contact with an infected patient, and the burden of bacilli in the patient |
||
+ | *About 1 million cases worldwide each year, but is rare in North America |
||
− | === Pathophysiology === |
||
+ | **Number may be underestimated due to difficulties with reliable diagnosis |
||
− | * The clinical spectrum of disease depends on the host immune response to infection |
||
+ | *Most commonly occurs in Southeast Asia (especially India) and Brazil |
||
− | * A robust Th1 CD4 response causes tuberculoid leprosy, which is paucibacillary and well-controlled |
||
+ | *Decreasing incidence over the past several decades, likely due to short-course multidrug therapy starting in 1982 |
||
− | ** Requires interferon-γ |
||
+ | *Humans are thought to be the main reservoir, but it has been found in animals as well (particularly nine-banded armadillos) |
||
− | * A Th2 CD4 response causes lepromatous leprosy, which is multibacillary and more progressive |
||
+ | *Transmitted most likely by respiratory droplets, though can also be transmitted by direct contact, transplacentally, through breast milk, and after animal exposure |
||
+ | ===Risk Factors=== |
||
− | == Clinical Manifestations == |
||
− | * Following exposure, about 95% clear it spontaneously |
||
− | * For those who do not, there is an incubation period of 3-5 years (with wide range) that is usually followed by indeterminate leprosy |
||
− | ** Single, ill-defined, hypopigmented skin lesion |
||
− | ** About 75% spontaneously resolve, with the other 25% progressing |
||
− | * Classic presentation is anaesthetic hypopigmented skin lesion with thickened nerves |
||
− | * Skin lesions can be: annular, asymmetric macules or plaques with central clearing and elevated borders (in tuberculoid) or symmetric, poorly-demarcated nodules and plaques or diffuse infiltration (lepromatous) |
||
− | ** Lepromatous can also have xanthoma-likek or dermatofibroma-like lesions, leonine facies, and eyebrow alopecia |
||
+ | *Age, with peaks in adolescence and ≥30 years |
||
− | === Spectrum of disease === |
||
+ | *Adult men (compared to adult women) |
||
− | * Clinical spectrum can be classified based on the number of lesions and burden of mycobacteria |
||
+ | *Duration of contact with an infected patient, and the burden of bacilli in the patient |
||
− | ** '''Paucibacillary (PB)''' disease has 1 to 5 skin lesions, without bacilli on skin slit smear |
||
− | ** '''Multibacillary (MB)''' disease has more than 5 skin lesions, with or without nerve involvement or bacilli on slit-skin smear (regardless of number of lesions) |
||
− | * Can also be classified based on general clinical appearance |
||
− | ** '''Tuberculoid leprosy (TT)''' corresponds to paucibacillary |
||
− | ** '''Borderline tuberculoid leprosy (BT)''' |
||
− | ** '''Borderline leprosy (BB)''' |
||
− | ** '''Borerdline lepromatous leprosy (BL)''' |
||
− | ** '''Lepromatous leprosy (LL)''' corresponding to multibacillary disease |
||
− | === |
+ | ===Pathophysiology=== |
− | * A cell-mediated hypersensitivity reaction that can develop in the course of treatment |
||
− | * Also known as a '''reversal reaction''' due to the apparent worsening of the lesion |
||
− | * Occurs most commonly in the borderline cases and may signal progression to the cell-mediated tuberculoid end of the clinical spectrum |
||
+ | *The clinical spectrum of disease depends on the host immune response to infection |
||
− | === Type 2 reaction === |
||
+ | *A robust Th1 CD4 response causes tuberculoid leprosy, which is paucibacillary and well-controlled |
||
− | * A humorally-mediated hypersensitivity reaction that can develop in the course of treatment |
||
+ | **Requires interferon-γ |
||
− | * Also known as '''erythema nodosum leprosum''' |
||
+ | *A Th2 CD4 response causes lepromatous leprosy, which is multibacillary and more progressive |
||
− | * Characterized by systemic illness and immune-complex deposition that appears as groups of tender subcutaneous nodules |
||
− | * May have other signs of vasculitis, including fevers, arthralgias, neuralgia, lymphadenopathy, orchitis, and dactylitis |
||
+ | ==Clinical Manifestations== |
||
− | === Physical examination === |
||
+ | |||
− | ==== Commonly affected nerves ==== |
||
+ | *Following exposure, about 95% clear it spontaneously |
||
+ | *For those who do not, there is an incubation period of [[Usual incubation period::3-5 years]] (with [[Incubation period range::wide range]]) that is usually followed by indeterminate leprosy |
||
+ | **Single, ill-defined, hypopigmented skin lesion |
||
+ | **About 75% spontaneously resolve, with the other 25% progressing |
||
+ | *Classic presentation is '''anaesthetic''' hypopigmented skin lesion with thickened nerves |
||
+ | *Skin lesions can be: annular, asymmetric macules or plaques with central clearing and elevated borders (in tuberculoid) or symmetric, poorly-demarcated nodules and plaques or diffuse infiltration (lepromatous) |
||
+ | **Lepromatous can also have xanthoma-likek or dermatofibroma-like lesions, leonine facies, and eyebrow alopecia |
||
+ | |||
+ | ===Spectrum of Disease=== |
||
+ | |||
+ | *Clinical spectrum can be classified based on the number of lesions and burden of mycobacteria |
||
+ | **'''Paucibacillary (PB)''' disease has 1 to 5 skin lesions, without bacilli on skin slit smear |
||
+ | **'''Multibacillary (MB)''' disease has more than 5 skin lesions, with or without nerve involvement or bacilli on slit-skin smear (regardless of number of lesions) |
||
+ | *Can also be classified based on general clinical appearance |
||
+ | **'''Tuberculoid leprosy (TT)''' corresponds to paucibacillary |
||
+ | **'''Borderline tuberculoid leprosy (BT)''' |
||
+ | **'''Borderline leprosy (BB)''' |
||
+ | **'''Borerdline lepromatous leprosy (BL)''' |
||
+ | **'''Lepromatous leprosy (LL)''' corresponding to multibacillary disease |
||
+ | |||
+ | ===Type I Reaction=== |
||
+ | |||
+ | *A cell-mediated hypersensitivity reaction that can develop in the course of treatment |
||
+ | *Also known as a '''reversal reaction''' due to the apparent worsening of the lesion |
||
+ | *Occurs most commonly in the borderline cases and may signal progression to the cell-mediated tuberculoid end of the clinical spectrum |
||
+ | |||
+ | ===Type 2 Reaction=== |
||
+ | |||
+ | *A humorally-mediated hypersensitivity reaction that can develop in the course of treatment |
||
+ | *Also known as '''erythema nodosum leprosum''' |
||
+ | *Characterized by systemic illness and immune-complex deposition that appears as groups of tender subcutaneous nodules |
||
+ | *May have other signs of vasculitis, including fevers, arthralgias, neuralgia, lymphadenopathy, orchitis, and dactylitis |
||
+ | |||
+ | ===Physical Examination=== |
||
+ | ====Commonly Affected Nerves==== |
||
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Trunk!!Palpation!!Sensation!!Movement!!Deformity |
|- |
|- |
||
− | | |
+ | |Ulnar nerve |
− | | |
+ | |Just superior to medial epicondyle |
− | | |
+ | |Fifth digit and ulnar aspect of hand |
− | | |
+ | |Fifth digit abduction |
− | | |
+ | |Claw deformity of little and ring fingers |
|- |
|- |
||
− | | |
+ | |Median nerve |
− | | |
+ | |Palmar wrist just medial to palmaris longus |
− | | |
+ | |Lateral three fingers and palm |
− | | |
+ | |Thumb abduction |
− | | |
+ | |Claw deformity of first through third digits |
|} |
|} |
||
− | == |
+ | == Differential Diagnosis == |
+ | |||
− | === WHO recommendations === |
||
+ | * '''Hypopigmented patches:''' [[vitiligo]], [[pityriasis alba]], [[post-inflammatory hypopigmentation]] |
||
+ | * '''Erythematous macules and plaques:''' [[psoriasis]], [[tinea corporis]], [[nummular dermatitis]], [[syphilis]], [[mycosis fungoides]], [[sarcoidosis]] |
||
+ | * '''Annular plaques:''' [[granuloma annulare]], [[tinea corporis]], [[psoriasis]] |
||
+ | * '''Nodules:''' [[keloid]], [[dermatofibroma]], [[lymphoma]], [[metastasis]], [[sarcoidosis]], [[non-tuberculous mycobacteria]], [[fungal infection]] |
||
+ | * '''Leonine facies:''' [[Paget disease of bone]], [[mycosis fungoides]], [[polyostatic fibrous dysplasia]], [[amyloidosis]], [[lichen myxedematosus]], [[leishmaniasis]], [[lipoid proteinosis]], [[progressive nodular histiocytosis]], [[mastocytosis]] |
||
+ | * '''Reversal reaction:''' [[cellulitis]], [[drug eruption]], [[lymphoma]], [[tumid lupus]], [[Sweet syndrome]] |
||
+ | * '''Erythema nodosum leprosum:''' [[erythema nodosum]], [[sepsis]], [[panniculitis]], flare of [[connective tissue disease]] |
||
+ | * '''Neurologic findings:''' heritable neuropathies, polyneuropathy, entrapment neuropathy, cervicobrachial and scalenus syndromes, syringomyelia, [[amyloidosis]], [[neurofibroma]] |
||
+ | ** Leprosy never causes upper motor neuron lesions, and spares proximal muscles as well as deep tendon reflexes and proprioception |
||
+ | ** Sensory findings in leprosy are worse distally, though there may be islands of preserved sensation |
||
+ | ** Leprosy never involves CNS |
||
+ | |||
+ | == Diagnosis == |
||
+ | |||
+ | * Worldwide, the diagnosis is made based on clinical findings with or without slit-skin smears or biopsy |
||
+ | ** At least one of: loss of sensation in a hypopigmented or reddish skin patch; thickened or enlarged peripheral nerve with loos of sensation and/or muscle weakness; or presence of acid-fast bacilli in slit-skin smear |
||
+ | ** A positive slit-skin smear is diagnostic of multibacillary disease |
||
+ | * Slit-skin smear is made by scraping with a scalpel blade an opening of small slits made in pinched skin |
||
+ | ** The expressed tissue fluid is smeared on a slide and stained for acid-fast bacilli by Fite’s method |
||
+ | ** The pinching makes the skin relatively avascular, to minimize contamination with blood |
||
+ | ** Initial skin smears are usually taken from the routine sites of both earlobes, elbows, and knees, as well as several typical lesions from the patient |
||
+ | * Skin biopsy may be more useful in high resource settings |
||
+ | ** Biopsy should be taken from the lesion edge of the most active margin of the most active lesion |
||
+ | ** Ideally full-thickness biopsy including dermis; can be a punch biopsy |
||
+ | ** Stained with Fite staining to maximize sensitivity |
||
+ | |||
+ | ==Management== |
||
+ | ===WHO Recommendations=== |
||
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Disease!!Treatment |
|- |
|- |
||
− | | |
+ | |Paucibacillary||6 months of [[Is treated by::rifampin]], [[Is treated by::dapsone]], and [[Is treated by::clofazimine]] |
|- |
|- |
||
− | | |
+ | |Multibacillary||12 months of [[Is treated by::rifampin]], [[Is treated by::dapsone]], and [[Is treated by::clofazimine]] |
|- |
|- |
||
− | | |
+ | |Rifampin resistance||6 months of at least two second-line drugs (below) with [[clofazimine]], followed by 18 months of one second-line drug with [[clofazimine]] |
|- |
|- |
||
− | | |
+ | |Quinolone resistance||As for rifampin resistance, but without a fluoroquinolone |
|} |
|} |
||
− | === |
+ | ===National Hansens's Disease Program (US)=== |
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Disease!!Treatment |
|- |
|- |
||
− | | |
+ | |Tuberculoid (TT & BT) (i.e. paucibacillary) |
− | | |
+ | |12 months of [[Is treated by::dapsone]] and [[Is treated by::rifampicin]] |
|- |
|- |
||
− | | |
+ | |Lepromatous (LL, BL, and BB) (i.e. multibacillary) |
− | | |
+ | |24 months of [[Is treated by::dapsone]], [[Is treated by::rifampicin]], and [[Is treated by::clofazimine]] |
|} |
|} |
||
− | === |
+ | ===Second-Line Antibiotics=== |
+ | |||
− | * [[Is treated by::Clarithromycin]] |
||
− | * |
+ | *[[Is treated by::Clarithromycin]] |
+ | *[[Is treated by::Minocycline]] |
||
− | * Fluoroquinolones: [[Is treated by::ofloxacin]], [[Is treated by::levofloxacin]], or [[Is treated by::moxifloxacin]] |
||
+ | *Fluoroquinolones: [[Is treated by::ofloxacin]], [[Is treated by::levofloxacin]], or [[Is treated by::moxifloxacin]] |
||
{{DISPLAYTITLE:''Mycobacterium leprae''}} |
{{DISPLAYTITLE:''Mycobacterium leprae''}} |
||
Line 105: | Line 142: | ||
[[Category:Mycobacteria]] |
[[Category:Mycobacteria]] |
||
− | === |
+ | ===Management of Reactions=== |
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Reaction!!Management |
|- |
|- |
||
− | | |
+ | |Reversal reaction limited to skin |
− | | |
+ | |monitor clinically |
|- |
|- |
||
− | | |
+ | |Reversal reaction involving nerves |
− | | |
+ | |corticosteroids with slow taper, and [[rifampin]] changed to monthly from daily |
|- |
|- |
||
− | | |
+ | |Other reversal reaction |
− | | |
+ | |corticosteroids based on clinical judgment |
|- |
|- |
||
− | | |
+ | |Erythema nodosum leprosum with neuritis |
− | | |
+ | |[[prednisone]] 1 mg/kg/day (40 to 60 mg/day), tapered over 2 to 4 weeks, possibly with [[thalidomide]] or [[clofazimine]] as a steroid-sparing agent |
|- |
|- |
||
− | | |
+ | |Mild erythema nodosum leprosum |
− | | |
+ | |[[thalidomide]] 50 to 100 mg nightly |
|} |
|} |
||
+ | |||
+ | == Prevention == |
||
+ | |||
+ | * Unclear whether household contacts require prophylaxis[[CiteRef::boodman2021le]] |
||
+ | ** Some experts recommend prophylaxis, particularly for exposure to multibacillary patients |
||
+ | ** Regimen unclear; most Canadian experts use single-dose [[rifampin]], in accordance with WHO recommendations |
||
+ | ** May instead do annual screening by physical examination for between 2 and 10 years |
Latest revision as of 16:01, 5 November 2021
Background
Microbiology
- Slow-growing Gram-positive and acid-fast bacillus
Epidemiology
- About 1 million cases worldwide each year, but is rare in North America
- Number may be underestimated due to difficulties with reliable diagnosis
- Most commonly occurs in Southeast Asia (especially India) and Brazil
- Decreasing incidence over the past several decades, likely due to short-course multidrug therapy starting in 1982
- Humans are thought to be the main reservoir, but it has been found in animals as well (particularly nine-banded armadillos)
- Transmitted most likely by respiratory droplets, though can also be transmitted by direct contact, transplacentally, through breast milk, and after animal exposure
Risk Factors
- Age, with peaks in adolescence and ≥30 years
- Adult men (compared to adult women)
- Duration of contact with an infected patient, and the burden of bacilli in the patient
Pathophysiology
- The clinical spectrum of disease depends on the host immune response to infection
- A robust Th1 CD4 response causes tuberculoid leprosy, which is paucibacillary and well-controlled
- Requires interferon-γ
- A Th2 CD4 response causes lepromatous leprosy, which is multibacillary and more progressive
Clinical Manifestations
- Following exposure, about 95% clear it spontaneously
- For those who do not, there is an incubation period of 3-5 years (with wide range) that is usually followed by indeterminate leprosy
- Single, ill-defined, hypopigmented skin lesion
- About 75% spontaneously resolve, with the other 25% progressing
- Classic presentation is anaesthetic hypopigmented skin lesion with thickened nerves
- Skin lesions can be: annular, asymmetric macules or plaques with central clearing and elevated borders (in tuberculoid) or symmetric, poorly-demarcated nodules and plaques or diffuse infiltration (lepromatous)
- Lepromatous can also have xanthoma-likek or dermatofibroma-like lesions, leonine facies, and eyebrow alopecia
Spectrum of Disease
- Clinical spectrum can be classified based on the number of lesions and burden of mycobacteria
- Paucibacillary (PB) disease has 1 to 5 skin lesions, without bacilli on skin slit smear
- Multibacillary (MB) disease has more than 5 skin lesions, with or without nerve involvement or bacilli on slit-skin smear (regardless of number of lesions)
- Can also be classified based on general clinical appearance
- Tuberculoid leprosy (TT) corresponds to paucibacillary
- Borderline tuberculoid leprosy (BT)
- Borderline leprosy (BB)
- Borerdline lepromatous leprosy (BL)
- Lepromatous leprosy (LL) corresponding to multibacillary disease
Type I Reaction
- A cell-mediated hypersensitivity reaction that can develop in the course of treatment
- Also known as a reversal reaction due to the apparent worsening of the lesion
- Occurs most commonly in the borderline cases and may signal progression to the cell-mediated tuberculoid end of the clinical spectrum
Type 2 Reaction
- A humorally-mediated hypersensitivity reaction that can develop in the course of treatment
- Also known as erythema nodosum leprosum
- Characterized by systemic illness and immune-complex deposition that appears as groups of tender subcutaneous nodules
- May have other signs of vasculitis, including fevers, arthralgias, neuralgia, lymphadenopathy, orchitis, and dactylitis
Physical Examination
Commonly Affected Nerves
Trunk | Palpation | Sensation | Movement | Deformity |
---|---|---|---|---|
Ulnar nerve | Just superior to medial epicondyle | Fifth digit and ulnar aspect of hand | Fifth digit abduction | Claw deformity of little and ring fingers |
Median nerve | Palmar wrist just medial to palmaris longus | Lateral three fingers and palm | Thumb abduction | Claw deformity of first through third digits |
Differential Diagnosis
- Hypopigmented patches: vitiligo, pityriasis alba, post-inflammatory hypopigmentation
- Erythematous macules and plaques: psoriasis, tinea corporis, nummular dermatitis, syphilis, mycosis fungoides, sarcoidosis
- Annular plaques: granuloma annulare, tinea corporis, psoriasis
- Nodules: keloid, dermatofibroma, lymphoma, metastasis, sarcoidosis, non-tuberculous mycobacteria, fungal infection
- Leonine facies: Paget disease of bone, mycosis fungoides, polyostatic fibrous dysplasia, amyloidosis, lichen myxedematosus, leishmaniasis, lipoid proteinosis, progressive nodular histiocytosis, mastocytosis
- Reversal reaction: cellulitis, drug eruption, lymphoma, tumid lupus, Sweet syndrome
- Erythema nodosum leprosum: erythema nodosum, sepsis, panniculitis, flare of connective tissue disease
- Neurologic findings: heritable neuropathies, polyneuropathy, entrapment neuropathy, cervicobrachial and scalenus syndromes, syringomyelia, amyloidosis, neurofibroma
- Leprosy never causes upper motor neuron lesions, and spares proximal muscles as well as deep tendon reflexes and proprioception
- Sensory findings in leprosy are worse distally, though there may be islands of preserved sensation
- Leprosy never involves CNS
Diagnosis
- Worldwide, the diagnosis is made based on clinical findings with or without slit-skin smears or biopsy
- At least one of: loss of sensation in a hypopigmented or reddish skin patch; thickened or enlarged peripheral nerve with loos of sensation and/or muscle weakness; or presence of acid-fast bacilli in slit-skin smear
- A positive slit-skin smear is diagnostic of multibacillary disease
- Slit-skin smear is made by scraping with a scalpel blade an opening of small slits made in pinched skin
- The expressed tissue fluid is smeared on a slide and stained for acid-fast bacilli by Fite’s method
- The pinching makes the skin relatively avascular, to minimize contamination with blood
- Initial skin smears are usually taken from the routine sites of both earlobes, elbows, and knees, as well as several typical lesions from the patient
- Skin biopsy may be more useful in high resource settings
- Biopsy should be taken from the lesion edge of the most active margin of the most active lesion
- Ideally full-thickness biopsy including dermis; can be a punch biopsy
- Stained with Fite staining to maximize sensitivity
Management
WHO Recommendations
Disease | Treatment |
---|---|
Paucibacillary | 6 months of rifampin, dapsone, and clofazimine |
Multibacillary | 12 months of rifampin, dapsone, and clofazimine |
Rifampin resistance | 6 months of at least two second-line drugs (below) with clofazimine, followed by 18 months of one second-line drug with clofazimine |
Quinolone resistance | As for rifampin resistance, but without a fluoroquinolone |
National Hansens's Disease Program (US)
Disease | Treatment |
---|---|
Tuberculoid (TT & BT) (i.e. paucibacillary) | 12 months of dapsone and rifampicin |
Lepromatous (LL, BL, and BB) (i.e. multibacillary) | 24 months of dapsone, rifampicin, and clofazimine |
Second-Line Antibiotics
- Clarithromycin
- Minocycline
- Fluoroquinolones: ofloxacin, levofloxacin, or moxifloxacin
Management of Reactions
Reaction | Management |
---|---|
Reversal reaction limited to skin | monitor clinically |
Reversal reaction involving nerves | corticosteroids with slow taper, and rifampin changed to monthly from daily |
Other reversal reaction | corticosteroids based on clinical judgment |
Erythema nodosum leprosum with neuritis | prednisone 1 mg/kg/day (40 to 60 mg/day), tapered over 2 to 4 weeks, possibly with thalidomide or clofazimine as a steroid-sparing agent |
Mild erythema nodosum leprosum | thalidomide 50 to 100 mg nightly |
Prevention
- Unclear whether household contacts require prophylaxis1
- Some experts recommend prophylaxis, particularly for exposure to multibacillary patients
- Regimen unclear; most Canadian experts use single-dose rifampin, in accordance with WHO recommendations
- May instead do annual screening by physical examination for between 2 and 10 years
References
- ^ boodman2021le