23- 159 - LEPROSY Flashcards
Causative agent of lucio leprosy
mycobacterium lepromatosis
What is triple lewis response
Dilation of blood capillaries as a secondary axon reflex erythema, which is dependent on nerve integrity, may be tested using a 1:1000 histamine solution, injected intradermally in normal and lesional skin. Within 5 to 10 seconds, erythema will result from the direct action of histamine on the capillaries, causing vasodilation in both areas, normal and lesional. Two minutes after this a secondary erythema caused by capillary dilation will occur only on normal skin. The last phase of triple Lewis response is exudation of liquid to the dermis, resulting in wheal formation in both areas. Therefore, the triple Lewis response is incomplete only on lesional skin, with the absence of secondary erythema.
hallmarks of Leprosy
- loss of sensation within skin lesions,
- nerve swelling or pain, or
- demonstration of acid-fast bacilli in skin smears or biopsies
infantile nodular leprosy is a type of what leprosy spectrum?
tuberculoid leprosy
A special self-healing type of tuberculoid leprosy that can be found as a single nodular lesion, but also as papules or plaques, usually on the face of the child
infantile nodular leprosy
histoid leprosy is a type of what spectrum of leprosy?
lepromatous leprosy
A special type of lepromatous leprosy that has an even higher bacillary load than the usual lepromatous leprosy, with rafts of bacilli called globi, presenting diffuse shiny nodules and papules, and a variable degree of skin infiltration
histoid leprosy
lucio leprosy is what type of leprosy spectrum?
lepromatous leprosy
main skin manifestation is infiltration
Lucio leprosy
characterized by classical foveolar lesions
borderline-borderline
doubling time of M.leprae
13 days
incubation period of M.leprae
3 - 7 years
The histopathology of the borderline-tuberculoid form can be distinguished from tuberculoid leprosy by the presence of what feature?
subepidermal grenz zone
Identify the spectrum
- there are aggregates of epithelioid cells, scarce dispersed lymphocytes, no Langhans multinucleated giant cells, and increasing numbers of acid-fast bacilli
borderline-borderline
identify the spectrum
- shows an epidermis that is usually normal and the subepidermal clear zone is absent.
- There is a noncaseating dermal granulomatous process composed chiefly of activated macrophages (epithelioid cells) with CD4 + T cells in the center of the epithelioid cells, CD8 + T cells in the mantle surrounding the granuloma, and giant cells of the Langhans type.
- Peripheral nerve involvement, cellular infiltration of sweat glands, and invasion of the arrectores pilorum muscle by a granulomatous infiltrate is common.
- There are no acid-fast bacilli or when they are present are found more frequently within peripheral nerves, arrectores pilorum muscle, or even granulomas
Tuberculoid leprosy
- In general, there is no well-defined granuloma with organized collections of epithelioid cells, and there is a reduction in the frequency of lymphocytes and scarce Langhans cells with rare acid-fast bacilli
- (+) grenz zone
borderline-tuberculoid
- shows a subepidermal grenz zone, aggregates of macrophages, occasional epithelioid cells with abundant cytoplasm, and some foamy cells, with few lymphocytes.
- A great number of** bacilli and some globi** can be found
Borderline lepromatous
- there is a normal to** flattened epidermis**, subepidermal grenz zone, aggregates and sheets of foamy macrophages admixed with predominantly CD8+ lymphocytes and plasma cells throughout the dermis and into the subcutaneous fat.
- Huge numbers of acid-fast bacilli and globi are found **within foamy macrophages (Virchow cells), **nerves, arrectores pilorum muscle, follicular epithelium, and sweat glands
lepromatous leprosy
What do you call the cells with acid-fast bacilli and globi within foamy macrophages
Virchow cells
- characterized by epidermal atrophy, a subepidermal **grenz zone, **and a dermis showing sheets of predominantly spindle-shaped cells with **nuclear pyknosis and foamy cytoplasm, **vacuolated, and arranged in a storiform pattern
- CD68-positive macrophages and spindle cells are present
Histoid leprosy
- The characteristic histologic features are edema and a mixed inflammatory infiltrate in the dermis and in the subcutis, predominantly neutrophils with eosinophils, lymphocytes, aggregates of foamy macrophages, plasma cells, and mast cells.
- Vasculitis and a mixed lobular and septal panniculitis
ENL or Type 2 reaction
The predominant lymphocyte present in ENL
T-helper cell
- The main microscopic features are that of a cutaneous or subcutis necrotizing vasculitis.
- There is **fibrinoid necrosis **of small and medium-sized vessels.
- The other histologic picture reported are necrosis of epidermis and superficial dermis, **micro-abscess **formation, angiogenesis, endothelial swelling, vascular occlusion caused by luminal thrombi, and deposits of fibrin in small blood vessel walls of the dermis and the subcutis
Lucio phenomenon or erythema necrotisans
a refined tool for nerve function assessment at diagnosis, and for patient followup to detect and characterize new lesions, especially **during reversal reaction or ENL, **or to evaluate entrapment syndromes and neuropathic pain
Electroneuromyography
differentiate Type I and type II reactions
Reversal reaction/Type I Reaction
* can occur in up to 30% of patients
* majority occur in borderline forms, mainly borderlinelepromatous and borderline-borderline, followed by lepromatous leprosy
* It starts as a sudden worsening of skin lesions and nerve function impairment,
* no apparent systemic involvement
* previous and newly developing lesions may be bright red, hot, and sensitive to the touch, sometimes ulcerated, frequently associated with peripheral nerve enlargement, and usually accompanied by pain
* requires immediate intervention, because it can result in nerve impairment and permanent disabilities
Erythema Nodosum Leprosum/ Type II Reaction
* aggressive vasculitis with immune complex deposition affecting different organs, resulting in, among other sequelae, neuritis, panniculitis, glomerulonephritis, arthralgia, epididymitis, orchitis, eye inflammation, osteitis and lymphadenitis
* with systemic symptoms such as fever, edema and malaise
Treatment of Type I reaction
Prednisone (1-2 mg/ kg/d with slow taper ~3 months)
- Reversal reaction can be treated with prednisone at doses of 1 to 2 mg/kg/d in a regressive scheme, diminishing 10% to 15% of the dose every 15 days, with a complete cycle of treatment lasting up to 3 months.
- If there is a worsening of the clinical situation, it may be necessary to go back to the previous higher dose, extending this level of corticosteroid treatment for 30 to 45 days, followed by tapering off again.
- After an equivalence conversion calculation, prednisone may be replaced by other steroids, including its metabolite prednisolone, dexamethasone, or deflazacort.
- Calcium intake of 1200 to 1500 mg/d and vitamin D supplements are recommended for any patient using glucocorticoids, independent of dose and duration of therapy.
Treatment of Type II reaction or ENL
Thalidomide 100-400 mg/d
+
prednisone (1-2 mg/kg/d) OR pentoxifylline 400 mg TID
In cases where the use of thalidomide must be avoided, pentoxifylline 400 mg, 3 times a day, is an alternative drug, quite useful for controlling limb edema and systemic symptoms
main skin manifestation of ENL
erythema nodosum
severe cutaneous necrotizing vasculitis AKA
Lucio phenomenon
Differentiate reactions from relapses
Reactions
* may occur before, during, and a few years after multidrug therapy.
* Usually, they are **acute, with a rapid appearance of new lesions **and infiltration of the old ones, deterioration of neural function, and/or systemic involvement, **responding well to treatment **with antiinflammatory drugs.
Relapses
* slowly progressing, almost always with resurgence of primary lesions followed by the gradual appearance of** new lesions**, together with **nerve involvement, **and, in contrast, there is no response to antiinflammatory drugs.
3 groups of medications used for treating leprosy
- antibiotics: dapsone, rifampicin, clofazimine
- antiinflammatory or immunosuppressants: Prednisone, Thalidomide, Clofazimine
- analgesic drugs.
G6PD-deficient patients using dapsone are at a greater risk of developing what?
severe life-threatening hemolytic anemia
Give examples of possible AE of dapsone
- severe life-threatening hemolytic anemia - for G6PD deficient
- Dapsone hypersensitivity syndrome
- drug rash with eosinophilia and systemic symptoms (DRESS syndrome)
- pigment that, in addition to its unknown antibiotic mechanism, also has antiinflammatory properties
- The main objection as far as patients are concerned is its** affinity to fat tissue and macrophage deposits** leading to skin hyperpigmentation, especially in the lesions.
Clofazimine
Dose of dapsone
100 mg OD/ 1-2mg/kg
Dose of clofazimine
300 mg once a month, and 50 mg per day
Give posible AE of clofazimine
- skin hyperpigmentation
- skin dryness
Dose of Rifampicin
administered once per month with supervision, 450 mg to children and 600 mg to adults
Posible AE of rifampicin
- face and neck redness,
- pruritus and cutaneous rash,
- loss of appetite,
- nausea,
- vomiting, and diarrhea,
- malaise (which may require cessation of the drug),
- purpura,
- epistaxis
- Flulike syndrome, a not well-understood immunologic side effect occurring with the use of intermittent doses of rifampicin, is characterized by fever, asthenia, myalgia, and headache, sometimes accompanied by bone pain
substitute drugs available, either to resistant strains or to patients with side effects on multidrug therapy
ofloxacin, minocycline, or clarithromycin
dose of clarithromycin
500 mg/d
Dose of Minocycline (substitute for dapsone or clofazimine)
100 mg/d
Dose of Ofloxacin
400 mg/d
- hyperinfection of this parasite is a concern in use of long-term oral steroids
- drug regimen used for prevention
- Strongiloydes stercoralis hyperinfection
- Ivermectin 200 µg/ kg/d for 2 days, repeated after 2 weeks
A special self-healing type of tuberculoid leprosy can be found as a single nodular lesion, but also as papules or plaques, usually on the face of the child
infantile nodular leprosy
established by a complete lack of cell-mediated immunity, usually presenting with plentiful nodular lesions disseminated throughout the body, associated with diffuse infiltration
polar lepromatous leprosy
Chronic neuritis/ Neuropathy may happen to all spectrum except what spectrum?
Indeterminate
A special type of lepromatous leprosy that has an even higher bacillary load than the usual lepromatous leprosy, with rafts of bacilli called globi, presenting diffuse shiny nodules and papules, and a variable degree of skin infiltration
histoid leprosy
Mycobacterium species isolated in patients with Lucio leprosy
Mycobacterium lepromatosis,
the main skin manifestation of Lucio leprosy
infiltration
this spectrum presents a **clear infiltrative band **around the periphery of the lesions, changing from a very sharp border in tuberculoid leprosy to a more diffuse infiltrated outer layer
borderline-tuberculoid leprosy
sprectrum that presents with classical foveolar lesions
borderline-borderline
effective cell-mediated immunity decreases, allowing a progressive spread and increase in the number of bacilli, an increase in infiltration of the lesions, with the evolution to form more nodular lesions, often involving the face and ears
borderline-lepromatous leprosy
