LEPROSY REACTIONAL

STATES

ASHAR IQBAL LODI080201134

IntroductionLepra reactions comprise several common

immunologically inflammatory states that can cause considerable morbidity.

Some of these reactions precede diagnosis and institution of effective antimicrobial therapy.

Other reactions occur after the initiation of appropriate chemotherapy.

Types

Lepra Reaction are of two types :1. Type 1 Lepra Reactions : (Downgrading and Reversal Reactions)

2. Type 2 Lepra Reactions : Erythema Nodosum Leprosum (ENL)

Type 1 Lepra Reactions :It is delayed type of hypersensitivity.Occur in patients with borderline forms of

leprosy .Classic signs of inflammation within previously

involved macules,papules and plaques,which are markedly erythematous, swollen and oedematous.

Mainly involves the trunk.Occasionally,there is appearance of new skin

lesions,neuritis and fever (low-grade).Associated with large numbers of T cells

bearing / g d receptors – a unique feature of leprosy.

Contd..Cutaneous lesions ,which are markedly

erythematous, swollen and oedematous with sharp margins are common.

Desquamation and ulceration of lesions may occur.Nerve trunk involvement is also common .Ulnar nerve involvement at the elbow (most

common), painful and exquisitely tender, results in clawing of hand.

Wrist drop due to radial nerve involvement.Footdrop occurs when peroneal nerve is involved.Facial palsy may also be associated .Edema is the most characteristic microscopic

feature.

Cutaneous Lesions inType 1 Lepra Reaction

Facial Palsy and claw hand in Type 1 Lepra Reaction

A)Claw Hand with ulceration

of palmar surface.B)Loss of longitudinal arch

with flat/boat shaped foot

Histology of Type 1 Lepra Reaction

Contd..

Downgrading Reactions :When type 1 lepra reactions precede the

initiation of appropriate antimicrobial therapy.Histologically , more lepromatous .

Loss of focalization and tubercle formation. Decrease in number of lymphocytes. Epithelioid cells co-differentiate towards simple

histiocytes and may show intracellular oedema. Bacillary multiplication & rising morphological

index. Extracellular oedema.

Contd.Reversal Reactions :

Occur after the initiation of antimicrobial therapy.Histologically,more tuberculoid.

Oedema and increase in lymphocytic infiltration & volume.

Macrophage differentiation towardsepitheloid cells and giant cells take appearance of Langhan’s cells.

Occasionally,necrosis with in the granuloma. Increased number of bacilli & morphological index falls.

Occur in the first months or years after the initiation of therapy.

Typified by TH 1 cytokine profile,with an influx of CD4+ T helper cells and increased levels of IFN- gand IL-2.

Type 2 Lepra Reactions :Erythema nodosum leprosum (ENL)

occurs exclusively in patients near the lepromatous end of the leprosy spectrum (BL-LL) and is more severe.

It is Type III hypresensitivity reaction.30 % of all lepromatous cases have at least

one attack of ENL.90 % of cases follow the institution of

chemotherapy, generally within 2 years .May precede diagnosis and initiation of

therapy .Dome-shaped lesions with ill-defined margins .

Contd.Associated with elevated levels of circulating tumor

necrosis factor (TNF),TH2 cytokine profile and high levels of IL-6 and IL-8.

Hence,thought to be a cause of immune complex deposition due to the antigen from the dying bacilli.

Histologically,Focus of inflammation is away from the major skin

lesions,deep in the dermis.Polymorph infiltration,oedema & cellular disintegration.Few bacilli at centre of reaction site (More if severe).Vascular necrosis with haemorrhage and ulceration.

Contd.Most common features are :

Crops of painful,swollen,tender,erythematous, shiny papules (resolve in a few days to a week but may recur), sitting on the skin or involving deep dermis mainly on the face and extremities with fever.

Malaise Symptoms of neuritis ,uveitis, orchitis ,

lymphadenitis , glomerulonephritis . Anemia . Leukocytosis . Abnormal liver function tests (increased

aminotransferase levels). Arthiritis and Iridocyclitis.

Cutaneous Lesions inErythema nodosum leprosum

A) Unusual presentation in ENL

B) Histology of ENL

Contd.Patients may have a single bout of ENL or

chronic recurrent manifestations.Bouts may be mild or severe and generalized

& may rarely cause death.Skin biopsy reveals vasculitis or panniculitis

characteristically with polymorphonuclear leukocytes and sometimes with lymphocytes.

Presence of HLA-DR framework antigen of epidermal cells (marker of delayed hypersensitivity).

Higher levels of IL-2 and IFN- g is usually seen in polar lepromatous disease.

Lucio’s Phenomenon :Unusual reaction seen exclusively in

patients from the Caribbean and Mexico having diffuse lepromatous form of lepromatous leprosy,who are left untreated.

Patient develops recurrent crops of large,sharply marginated,ulcerative lesions (lower extremities).

May be generalized and fatal as a result of secondary infection and consequent septic bacteremia.

Contd.

Histologically,Ischemic necrosis of the epidermis and

superficial dermis.Heavy parasitism of endothelial cells with

AFB.Endothelial proliferation and thrombus

formation in large vessels of the deeper dermis.

Probably,mediated by immune complexes (like ENL).

a)Lesions on buttocks and thighs in Lucio’s Phenomenon

b) Histology ofLucio’s Phenomenon