Difference Between Type 1 and Type 2 Lepra Reactions
Type 1 lepra reaction is a delayed-type hypersensitivity (cell-mediated) immune response characterized by acute inflammation of existing leprosy lesions with edema and potential nerve damage, while Type 2 lepra reaction (Erythema Nodosum Leprosum/ENL) is an immune complex-mediated (antibody-mediated) systemic inflammatory response presenting with new tender erythematous nodules and constitutional symptoms.
Immunological Basis
Type 1 Reaction:
- Cell-mediated (Th1) delayed-type hypersensitivity response 1
- Represents a shift in immune response toward the tuberculoid pole (upgrading) or away from it (downgrading) 1
- Occurs as the immune system recognizes and responds to mycobacterial antigens in existing lesions 1
Type 2 Reaction:
- Th2-mediated type III hypersensitivity reaction involving immune complex deposition 2
- Antigen-antibody mediated immune complex reaction with systemic inflammatory response 2
- Associated with high bacterial load and circulating immune complexes 2
Clinical Presentation
Type 1 Reaction:
- Acute inflammation and edema of pre-existing leprosy skin lesions 1
- Lesions become erythematous, swollen, and may ulcerate 3
- Pruritus and pain in affected lesions 3
- Acute neuritis with nerve tenderness and potential nerve function loss 1
- Typically no new lesions appear—existing lesions become inflamed 1
- Constitutional symptoms are usually absent or mild 1
Type 2 Reaction (ENL):
- New tender, erythematous, evanescent nodules appearing mainly on face, arms, and legs 2
- Subcutaneous nodules that are characteristically tender 4
- Lesions may present as vesicles, pustules, bullae, or become necrotic 4
- Systemic constitutional symptoms are prominent (fever, malaise, arthralgia) 2
- Multiple organ involvement possible (eyes, joints, kidneys, nerves, testes) 4
- Lesions heal with scarring that may become inflamed during flare-ups 4
Histopathological Features
Type 1 Reaction:
- Dermal or intragranuloma edema (present in 50% of cases, correlates with severe reactions) 1
- Lymphocytes or macrophages predominate as inflammatory cells 1
- Three patterns: upgrading reactions, downgrading reactions, or reactions without directional change 1
- Preserved grenz zone with papillary dermal edema 3
- Subtle variations in granuloma cell composition help differentiate reaction types 1
Type 2 Reaction:
- Neutrophils are the major inflammatory cells (present in 8/14 cases in one study) 1
- Dermal edema common (seen in 11/14 cases) 1
- Some cases show neutrophilic vasculitis 1
- Notably, 5/14 cases may show no histological neutrophil infiltration, making diagnosis challenging 1
Patient Population at Risk
Type 1 Reaction:
- Occurs across the leprosy spectrum but most common in borderline forms 1
- Can occur before, during, or after treatment 3
- May develop as early as 10 weeks after starting multidrug therapy 3
Type 2 Reaction:
- Over 50% of lepromatous leprosy patients affected (prior to multidrug therapy era) 2
- 25% of borderline lepromatous leprosy patients affected 2
- Rare in histoid leprosy variants 3
Laboratory Monitoring
Type 1 Reaction:
- Alpha-1-antitrypsin (A1A) levels correlate better with disease activity 5
- A1A superior for monitoring course of Type 1 reactions 5
Type 2 Reaction:
- C-reactive protein (CRP) levels correlate well with disease activity 5
- CRP definitely superior to A1A for monitoring Type 2 reactions 5
Treatment Approach
Type 1 Reaction:
- Continue multibacillary multidrug therapy (MBMDT) 3
- Prednisolone 0.75 mg/kg body weight/day for moderate to severe reactions 3
- NSAIDs and antihistamines for mild symptoms 3
- Taper corticosteroids over 20 weeks after symptomatic relief 3
- Monitor for nerve function deterioration requiring urgent intervention 1
Type 2 Reaction:
- Thalidomide is the drug of choice for severe atypical reactions due to anti-TNF-α action 2
- Corticosteroids for patients where thalidomide is contraindicated 2
- Continue anti-leprosy treatment throughout reaction 2
Critical Pitfalls to Avoid
- Misdiagnosis risk: Type 2 reactions without typical ENL nodules can be mistaken for Type 1 reactions—histology showing neutrophil predominance distinguishes them 1
- Delayed diagnosis: Atypical presentations (bullous, necrotic, urticarial variants) may be missed if clinician is unfamiliar with variants 2
- Inadequate monitoring: Histopathological analysis should be integral to evaluation of all lepra reactions, not just clinical assessment 1
- Drug reaction confusion: Rare desquamative rash in Type 2 reactions must be differentiated from drug-related rash 4
- Organ involvement: Type 2 reactions can involve multiple organs; delayed treatment leads to complications and poor prognosis 4