histopathology of type 1 lepra reaction shows edema within granuloma separating inflammatory cells with density of lymphocytes in the dermis . to distinguish between upgrading and downgrading reaction histopathologicaly , serial examination of biopsies
histopathology of skin lesions of type 2 lepra reaction ( erythema nodosum leprosum , enl ) shows dermal edema , neutrophilic infiltration and vasculitis on a background of macrophage granuloma .
wide variations in clinical presentation of leprosy in reaction , make histopathology an important tool for supporting clinical diagnosis . while leprosy is histopathologicaly relatively easy to diagnose , lepra reactions are not always diagnosable under the microscope .
although our study included clinical features , we decided to focus on histopathologic features and their clinicopathologic co - relation .
a retrospective clinicopathological analysis of 64 skin biopsies of patients with lepra reaction visiting a tertiary care centre during year 20052008 was done .
we included skin biopsy specimens of patients of all ages , diagnosed as lepra reaction ( type 1 and type 2 ) after clinico - pathological correlation .
those with doubtful diagnosis were clinically reviewed and if needed , excluded from the study .
histopathological reevaluation of the skin biopsies stained with hematoxylin and eosin stain was done and findings were recorded .
afb staining was not done routinely , as it was not useful for diagnosis of lepra reactions .
clinical review was not possible for 4 patients ( 1 of type 1 reaction and 3 of type 2 reaction ) for logistic reasons .
the age of the patients included in study ranged from 6 years to 68 years ( mean age 35.55 years ) for type 1 reaction , while it was 11 to 65 years ( mean age 40.10 years ) for type 2 reaction .
the leprosy spectrum ( based on clinicopathologic co - relation ) and type of reaction observed in our patients is mentioned in table 1 , while table 2 details their clinical features .
type of lepra reaction and clinical spectrum of hansen 's disease clinical profile of patients histopathological observations in type 1 reaction are illustrated in table 3 . the most consistent finding in type 1 reaction was higher than expected accumulation of lymphocytes within granuloma which was seen in all specimens , followed by occurrence of edema in papillary dermis , pyknosis of lymphocytes , and edema in the granuloma followed by folliculotropism [ figure 1 ] and lymphocytic panniculitis [ figure 2 ] .
histopathological observations in type 1 reaction lymphocytic infiltratation of follicle ( folliculotropism ) lymphocytic panniculitis histopathological observations in type 2 reaction have been depicted in table 4 .
we observed that , the presence of neutrophils in the granuloma was a uniform feature seen in all lesions of enl [ figure 3 ] .
other common findings were leukocytoclasia and papillary dermal edema ( 81% each ) and lobular [ figure 4 ] and septal neutrophilic panniculitis ( 66% ) .
prior studies on histopathologic features of lepra reactions are prospective clinicopathological evaluations . due to the sheer amount of data
e.g. , vasculitis is mentioned as a finding but individual histopathologic features of vasculitis like fibrin in vessel wall or fibrin thrombi or leukocytoclasia are not described .
dermal edema , loosening of granuloma , and predominance or increase in number of lymphocytes are described as a feature of type 1 reaction in prior studies .
interpretation of pyknosis of lymphocytes can be difficult at times as it can be influenced by inter - observer variations .
we observed that , lymphocytes in granuloma associated with dermal edema and/or edema within the granuloma is highly suggestive type 1 reaction .
epidermotropism has classically been described with mycosis fungoides but here we observed it in few lesions of type 1 lepra reaction .
lazaro - medina et al . have described some new markers for type 1 reaction which include spongiosis of the epidermal and follicular epithelium with exocytosis of mononuclear cells , parakeratosis , focal interface changes with occasional individual cell necrosis of keratinocytes , and follicular mucinosis . some of these findings like epidermal and follicular epithelium spongiosis , interface change were also observed by us .
occurrence of giant cells in the granuloma is one of the finding which helps in classifying histopathologically the features of upgrading and downgrading type1 lepra reactions .
lockwood dn and co - workers in a prospective study compared skin lesions with type 1 reaction with non - reactional controls ; in addition to intra dermal and intra granuloma edema they noted increase in giant cell size and giant cell numbers in type 1 reaction .
as in our study such comparison with non - reactional control was not done , we are unable to make any comments on the findings they described .
neutrophils are not seen in ordinary lesions of leprosy . in type 2 lepra reactions , because of the immune complex deposition , neutrophils are attracted in these lesions .
neutrophils were present either within the granulomatous infiltrate or / and in the interstitium with or without leukocytoclasia . in a few sections
more severe and recent onset lesions of lepra reactions showed much denser infiltrate as compared less severe and subsiding lesions .
we noted neutrophilic spongiosis as more common than intraepidermal pustule formation . the dense collection of neutrophils in the epidermis and dermis is probably responsible for the clinical finding of pustules in enl lesions .
infiltration of sweat duct and sweat gland by neutrophils was found in a few cases without any evidence of damage or necrosis of the sweat duct or sweat glands .
the histopathologic spectrum of vasculitis range from endothelial swelling , neutrophilic infiltration of the vessel wall with destruction of the walls and leucocytoclasia .
a variable degree of vascular involvement in type 2 reaction was noted in our study and majority of the lesions with type 2 reaction did not have all classical features of vasculitis .
this finding was in slight disagreement with previous literature where vasculitis affecting arterioles and venules was observed in 50% cases of type 2 reaction by job et al . in 1964 and
fibrin in vessel wall was the commonest sign observed followed by fibrin thrombi and neutrophils in vessel wall in few cases .
the histological features of vasculitis depend upon the stage at which a lesion has been biopsied .
an older lesion will have sparse neutrophilic infiltrate and predominance of mononuclear cells whereas an early lesion show predominantly neutophilic infiltrate with fibrin deposition .
occlusion of the vascular lumina with extensive involvement where vessels in lower part of the dermis and subcutaneous tissue are involved leads to necrosis or ulceration of the lesion .
the vascular changes we noted were more prevalent in the upper and mid dermis than subcutaneous tissue .
necrosis and ulceration is fairly uncommon in enl in contrast to lucio reaction where ulceration and necrosis is almost always seen . in lucio reaction endothelial proliferation along with thrombosis of dermal and subcutaneous vessels leads to ischemic necrosis and ulceration .
as we observed , occlusion of vessel lumen was seen in a few lesions and was limited to upper and mid dermis and that may be the reason why none of the lesion in our study showed ulceration and necrosis .
similar to the observation of lymphocytic involvement of follicle in type 1 reaction , a few cases ( 5% ) of type 2 reaction showed lymphocytic infiltration of sebaceous lobules .
involvement of subcutaneous tissue by granulomatous infiltrate can be seen in cases of lepromatous leprosy though the lesion is not in reaction . but
the presence of neutrophils in subcutaneous tissue is an important clue to the type 2 reaction .
papillary dermal edema and lymphocytic infiltration within granulomas were the most consistent signs of type 1 lepra reaction followed by edema in granuloma and pyknosis of lymphocytes .
infiltration of granulomas by neutrophils was the most reliable sign in cases of type 2 reaction .
a few new findings were folliculotropism , epidermotropism , and lymphocytic panniculitis in type 1 reaction and neutrophils in sweat ducts and lymphocytes in sebaceous lobules in type 2 reaction , which needs validation .
 background : lepra reactions are not always diagnosable under the microscope . 
 we analyzed skin histopathology in 64 cases of lepra reaction.aim:to make detailed observations on histopathologic features of type 1 and type 2 lepra reaction ( erythema nodosum leprosum , enl).materials and methods : in this retrospective study , we included 64 patients diagnosed during a 3-year period as lepra reaction based on clinico - pathological co-relation.results:out of the 64 patients , 22 were of type 1 reaction and 42 of enl . 
 the most consistent finding in type 1 reaction was papillary dermal edema ( 86% ) followed by pyknosis of lymphocytes ( 77% ) and intercellular edema within granuloma ( 73% ) . 
 surprisingly , folliculotropism of lymphocytes was seen in 55% and subcutaneous infiltration in 36% . in enl , 
 the most common finding was presence of neutrophils within the granuloma ( 100% ) , followed by leukocytoclasia ( 81% ) , papillary dermal edema ( 81% ) , and neutrophilic panniculitis ( 69% ) . 
 fibrin in the vessel wall or / and granulomas was noted in only 38% while fibrin thrombi in the vessel walls were seen in only 12% of cases.conclusion:infiltration of macrophage granulomas by neutrophils is a reliable sign of enl . 
 classical signs of vasculitis are not always present in enl . 
 folliculotropism and lymphocytic panniculitis were frequent in type 1 reactions while neutrophilic panniculitis was common with enl . 
Introduction
Materials and Methods
Results
Discussion
Conclusion