Introduction Lepra 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 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.
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- and 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.
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- 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).
b) Histology ofa) Lesions on buttocks and thighs Lucio’s Phenomenon in Lucio’s Phenomenon