LEPROSY, LEPRA REACTION (by syasha@ stellata)

Definition/Also known as: Erythema Nodosum Leprosum Lepromatous Lepra Reaction or Type 2 reaction (Jopling 1971) Type 2 reactions occur in patients with MB disease & cause acute inflammation in any organ or tissue where M. leprae are found In the skin, type 2 reactions cause ENL Reversal Reaction (RR) A delayed hypersensitivity reaction (type IV hypersensitivity reaction) occur in patients with borderline disease (BL, BB, BT) immunological status is unstable. Lucio Phenomenon So-called Latapi lepromalosis (Lucio leprosy) A type 2 condition in leprosy probably mediated by immune complexes associated with severe necrosis of the arterioles whose endothelium is massively invaded by Mycobacterium leprae in patients with non-nodular lepromatous leprosy Most prevalent in Mexico and the Caribbean region Unique feature- seen only in untreated patients The mechanism of pathogenesis is thought to be mediated by immune-complex deposition Histopathology Characterised by ischemic necrosis of the epidermis and superficial dermis, heavy infestation of endothelial cells with acid-fast bacilli, and endothelial proliferation and thrombosis in the larger vessels of the deeper dermis

Incidence

Pathogenesis

Over of LL and of BL patients will experience type 2 reaction. Commonest in patients who have had enough treatment (second and third years treatment), to reduce the morphological index under 5%. Histology The bacilli often shown by carbol fuchsin as fragmented or granular. But if they cannot be shown, their ghosts can be shown by electron microscopy, and antigens by immunofluorescense, bound to macrophages and connective tissue. Mild lesions polymorphs, oedema and cellular disintegration. Severe ENL larger bacillary deposits, polymorph infiltration is intense and extend at the dermis and oedema. May followed with necrosis and ulceration. Immunology Is a classical example of an immune complex disease

Antigen (ML) bacilli reactions with T lymphocytes and a rapid change in CMI in borderline patients. The rx is associated with a rapid increase in specific CMI upgrading reaction. The rx is associated with a reduction in immunity downgrading reaction. Histopathology Edema the acute phase. The inflammatory cells spread out and disorganization of the granuloma. Increase in lymphocytes.

Predilection sites

Release of mycobacterial antigens from the macrophages is required for formation and deposition of the immune complexes which induce the acute tissue damage and the clinical symptoms. Complement change in serum during acute ENL are quite limited. Immune complex formation associated with ENL mainly occurs extravascular. Face Extensor surfaces of the limbs May also be seen elsewhere Lesions tend to recur at a same sites Sign Painful red nodules superficial or deep in the dermis, dome shaped with ill defined margins, shiny and tender ulcerate thick yellow pus contain polymorphs and degenerate acid-fast bacilli, but sterile on culture. They appear in crops, new ones appearing as old ones subside over the course of a few days. If not resolve completely painful panniculitis develops for month or year inflamed skin and subcutaneous tissue become fixed to underlying fascia, muscle and bone immobilize a hand or foot or even the face. This tissue is poorly vascularized and may ulcerate with the slightest trauma Symptoms Generalized illness Temperature rises to 40 C daily, usually in the late afternoon, and remits. Patient becomes exhausted and prostrated by pain, headache, anorexia, insomnia and

Langhansgiant cells may also be seen. AFB in the lesions of bl are considerably reduced or completely disappear, indicating is true upgrading of the lesion and an increase in immunity Extremities Face and trunk are spared

Clinical features

Skin lesions acutely inflamed, edema; erythema, desquamation, may ulcerate tender or painful. Neuritis is the most important part of a type I reaction BT. Nerves rapidly swollen, painful and tender. Paraesthesiae or pain. Loss of motor function develops rapidly. Pure neural leprosy may present in this way.

Diffuse cutaneous infiltration A purplish suffusion of the hands and feet Wide spread sensory loss Telangiectatic mats/eruptive telangiectasias Nasal septum perforation, shiny thickened skin Body hair loss Total alopecia of eyebrows and eyelashes Anaemia Edema Ulceration of both legs No motor palsies Eyes not damaged Painful red patches appear on the skin especially extremities, become purpuric, ulcerate covered with black crust healing & finally develop an eschar which falls off to leave a

depression. Following manifestations may appear: - iridocyclitis (may be the only sign of reaction) - orchitis - dactylitis - tender enlargement of all peripheral nerves & tender lymphadenopathy Less commonly, muscles may be tender and joints may be painful or even swollen, and there may be epistaxis and proteinuria.

superficial atrophic scar Face and trunk are spared Become fatal as a result of secondary bacterial infection and sepsis Laboratorium examination Normocrom mormositer anemia Leucocytosis with neutrofilia absolut Hipergamaglobulinemia Indeks bacterial: 3,7 +

Differential diagnosis

Treatment

Neurofibromatosis Sarcoidosis Drug eruption Dermal leishmaniasis Continue the antileprosy medication (MDT) Mild cases bed rest, symptomatic: aspirin, sedation and nonsteroidal antiinflammatory Severe cases prednisone 40-60 mg daily tapered slowly over months or year Chronic cases: - prednisone 20-30 mg daily + clofazimine 300 mg daily (if no gastrointestinal intervening) dose gradually lowered to 100 mg daily, and increasing it again if reaction exacerbates. - Continue clofazimine until bacterial negativity, since the reaction sometimes recurs if the drug is discontinued sooner. Thalidomide is also the treatment of choice for ENL - Starting dose 100 mg 3-4 times daily reaction controlled tapered if possible discontinued within 3-4 weeks.

Continue the antileprosy medication (MDT) Severe cases prednisone 4060 mg daily tapered slowly over months or year. Indications for prednisone: - Neuritis - Lesions that threaten to ulcerate - Lesions appearing at cosmetically important sites Chronic cases: - prednisone 20-30 mg daily + clofazimine 300 mg daily (if no gastrointestinal intervening) dose gradually lowered to 100 mg daily, and increasing it again if reaction exacerbates.

Consists of polychemotherapy for multibacilli Anti-leprosy therapy (dapsone, rifampin, & clofazimine) Optimal wound care Responds very well to thalidomide Cortikosteroid Treatment for bacteriemia including antibiotics In severe cases, exchange tranfusion is helpful

Prognosis

Other alternatives are chloroquine and Dapson: dosis 50mg antimonials more toxic supressif effect to RR - Chloroquine starting dose 250 mg 3 times Azathioprine: dosis 50daily for a week (reaction controlled) and 100mg to prevent synthesis then lowered to 250 mg twice daily for a nucleat acid week, followed by 250 mg daily. - Potassium antimony tartrate initial dose 30 mg given as 0,5%-1% solution intravenously given every other day gradually increased to 60 mg but total dose do not exceed 500-600 mg. If no response at sixth dose discontinued - Stibophen initial dose 1.5 ml intramuscular. If no adverse reaction 3.0 ml is given 2 days later, followed by 3-5 ml every other day. The total dose should not exceed 30ml. Early diagnosis and treatment and energetic management of reactional states prevent the development of all disabilities

Together we learn, together we make perfection.

RGP 2008