23- 159 - LEPROSY

Question 1

Causative agent of lucio leprosy

Answer 1

mycobacterium lepromatosis

Question 2

What is triple lewis response

Answer 2

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.

Question 3

hallmarks of Leprosy

Answer 3

• loss of sensation within skin lesions,
• nerve swelling or pain, or
• demonstration of acid-fast bacilli in skin smears or biopsies

Question 4

infantile nodular leprosy is a type of what leprosy spectrum?

Answer 4

tuberculoid leprosy

Question 5

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

Answer 5

infantile nodular leprosy

Question 6

histoid leprosy is a type of what spectrum of leprosy?

Answer 6

lepromatous leprosy

Question 7

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

Answer 7

histoid leprosy

Question 8

lucio leprosy is what type of leprosy spectrum?

Answer 8

lepromatous leprosy

Question 9

main skin manifestation is infiltration

Answer 9

Lucio leprosy

Question 10

characterized by classical foveolar lesions

Answer 10

borderline-borderline

Question 11

doubling time of M.leprae

Answer 11

13 days

Question 12

incubation period of M.leprae

Answer 12

3 - 7 years

Question 13

The histopathology of the borderline-tuberculoid form can be distinguished from tuberculoid leprosy by the presence of what feature?

Answer 13

subepidermal grenz zone

Question 14

Identify the spectrum

• there are aggregates of epithelioid cells, scarce dispersed lymphocytes, no Langhans multinucleated giant cells, and increasing numbers of acid-fast bacilli

Answer 14

borderline-borderline

Question 15

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

Answer 15

Tuberculoid leprosy

Question 16

• 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

Answer 16

borderline-tuberculoid

Question 17

• 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

Answer 17

Borderline lepromatous

Question 18

• 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

Answer 18

lepromatous leprosy

Question 19

What do you call the cells with acid-fast bacilli and globi within foamy macrophages

Answer 19

Virchow cells

Question 20

• 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

Answer 20

Histoid leprosy

Question 21

• 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

Answer 21

ENL or Type 2 reaction

Question 22

The predominant lymphocyte present in ENL

Answer 22

T-helper cell

Question 23

• 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

Answer 23

Lucio phenomenon or erythema necrotisans

Question 24

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

Answer 24

Electroneuromyography

Question 25

differentiate Type I and type II reactions

Answer 25

**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**

Question 26

Treatment of Type I reaction

Answer 26

Prednisone (1-2 mg/ kg/d with slow taper ~3 months) ## Footnote * 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.

Question 27

Treatment of Type II reaction or ENL

Answer 27

**Thalidomide** 100-400 mg/d + **prednisone** (1-2 mg/kg/d) OR **pentoxifylline** 400 mg TID ## Footnote 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

Question 28

main skin manifestation of ENL

Answer 28

erythema nodosum

Question 29

severe cutaneous necrotizing vasculitis AKA

Answer 29

Lucio phenomenon

Question 30

Differentiate reactions from relapses

Answer 30

*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.**

Question 31

3 groups of medications used for treating leprosy

Answer 31

1. antibiotics: dapsone, rifampicin, clofazimine 2. antiinflammatory or immunosuppressants: Prednisone, Thalidomide, Clofazimine 3. analgesic drugs.

Question 32

G6PD-deficient patients using dapsone are at a greater risk of developing what?

Answer 32

severe life-threatening hemolytic anemia

Question 33

Give examples of possible AE of dapsone

Answer 33

* severe life-threatening hemolytic anemia - for G6PD deficient * Dapsone hypersensitivity syndrome * drug rash with eosinophilia and systemic symptoms (DRESS syndrome)

Question 34

* 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.

Answer 34

Clofazimine

Question 35

Dose of dapsone

Answer 35

100 mg OD/ 1-2mg/kg

Question 36

Dose of clofazimine

Answer 36

300 mg once a month, and 50 mg per day

Question 37

Give posible AE of clofazimine

Answer 37

* skin hyperpigmentation * skin dryness

Question 38

Dose of Rifampicin

Answer 38

administered once per month with supervision, **450 mg to children and 600 mg to adults**

Question 39

Posible AE of rifampicin

Answer 39

* 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**

Question 40

substitute drugs available, either to resistant strains or to patients with side effects on multidrug therapy

Answer 40

ofloxacin, minocycline, or clarithromycin

Question 41

dose of clarithromycin

Answer 41

500 mg/d

Question 42

Dose of Minocycline (substitute for dapsone or clofazimine)

Answer 42

100 mg/d

Question 43

Dose of Ofloxacin

Answer 43

400 mg/d

Question 44

1. hyperinfection of this parasite is a concern in use of long-term oral steroids 2. drug regimen used for prevention

Answer 44

1. Strongiloydes stercoralis hyperinfection 2. Ivermectin 200 µg/ kg/d for 2 days, repeated after 2 weeks

Question 45

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

Answer 45

infantile nodular leprosy

Question 46

established by a complete lack of cell-mediated immunity, usually presenting with plentiful nodular lesions disseminated throughout the body, associated with diffuse infiltration

Answer 46

polar lepromatous leprosy

Question 47

Chronic neuritis/ Neuropathy may happen to all spectrum except what spectrum?

Answer 47

Indeterminate

Question 48

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

Answer 48

histoid leprosy

Question 49

Mycobacterium species isolated in patients with Lucio leprosy

Answer 49

Mycobacterium lepromatosis,

Question 50

the main skin manifestation of Lucio leprosy

Answer 50

infiltration

Question 51

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**

Answer 51

borderline-tuberculoid leprosy

Question 52

sprectrum that presents with classical **foveolar** lesions

Answer 52

borderline-borderline

Question 53

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

Answer 53

borderline-lepromatous leprosy