Evaluation of key histologic variables in skin biopsies of patients of borderline leprosy with type 1 lepra reaction.

BACKGROUND: Leprosy remains an important health problem mainly in the African and South-East Asia regions. Type 1 reaction is an immune-mediated phenomenon known to complicate at least 30% of patients of leprosy. Diagnosing type 1 reaction correctly is important for timely institution of therapy to prevent and treat neuropathy-associated disability and morbidity. There is paucity of literature on definitive criteria for histologic diagnosis of type 1 reaction. This study was conducted to determine the key histologic variables for diagnosing type 1 reaction. METHODS: This was a prospective study recruiting 104 patients with borderline leprosy. Three pathologists blinded to the clinical diagnosis independently assessed the cases. The agreement between each histological variable and clinical diagnosis was then calculated by using Cohen's kappa (Κ) coefficient. RESULTS: Histological diagnosis of type 1 reaction was given to 27 (67.5%) of 40 clinically diagnosed cases of type 1 reaction cases. Histological variables chosen as key variables for histological diagnosis of type 1 reaction were presence of giant cells, dermal edema, intragranuloma edema, granuloma fraction 31-50%, and presence of medium to large giant cells. CONCLUSION: This study has shown that T1R are still underdiagnosed histologically in comparison with clinical assessments. The key variables for diagnosing type 1 reaction were proposed.

Type I reaction in leprosy--a histopathological analysis.

Even though type 1 lepra reaction (TIR) is a commonly encountered clinical problem, its histology has not yet been clearly delineated. This study attempts to enumerate the most sensitive parameters for the histological diagnosis of TIR. Case records between March 2007 and September 2007 of patients with TIR were reviewed and the biopsies were evaluated by a pathologist blinded to the previous diagnoses. Twenty three patients were included in the study. The most sensitive parameters in our study were dermal edema, intra-granuloma edema and giant cell size. Though clinical findings should remain the mainstay of diagnosis of TIR, the above mentioned parameters should be evaluated in biopsies of leprosy to look for signs of reaction which might otherwise be missed.

The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis.

BACKGROUND: Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity. METHODS: In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared. RESULTS: Reactions were under-diagnosed, with 32-62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34-53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves. CONCLUSIONS: This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.

[Human monocyte-derived multinucleated giant cells].

Multinucleated giant cells (MGC) are characteristic cells in granulomatous disorders such as sarcoidosis and leprosy. There are two types of MGC; foreign body-type and Langhans-type cells. The exact mechanisms of the formation and the functional significance of MGC are not determined, although their morphological features are well understood. MGC are also formed in vitro from peripheral blood mononuclear cells by stimulation with cytokines and lectins. Particularly IFN-gamma is considered to play a pivotal role in monocyte fusion. IL-3, IL-4, IL-13, and GM-CSF are other reported cytokines involved in MGC formation. In addition to such inflammatory mediators, a factor derived from the pathogens of granulomatous disorders may be necessary for MGC formation. Muramyl dipeptide, a peptidoglycan portion of bacterial cell walls, is one of the candidates and can preferentially induce Langhans-type cells in in vitro MGC formation system. Although the exact mechanisms of in vitro MGC formation remains unknown, cell surface molecules such as P2X7 receptor, integrins, CD98, and macrophage fusion protein are considered to be involved in fusion process. Monocytes of sarcoidosis patients expressed higher levels of P2X7 and had a higher ability to induce MGC than those of healthy controls. Effective agents for sarcoidosis such as tranilast, alloprinol, and captopril inhibited in vitro MGC formation, suggesting their therapeutic effects through the direct effects on monocytes. Thus, an in vitro MGC formation model would be a useful tool to understand the relevance of MGC in granulomatous disorders.

Fine needle aspiration cytology of reactions in leprosy.

OBJECTIVE: To define diagnostic cytomorphologic features of reactions in leprosy. STUDY DESIGN: Part-retrospective, part-prospective, single-blind, controlled study of the applicability of fine needle aspiration cytology in the diagnosis of reactions in leprosy. Cytomorphologic features were compared in 42 clinically diagnosed patients with reactions in leprosy with those in a control group of patients with nonreactional leprosy. The study groups included type 1 and type 2 reactions in 35 and 9 patients, respectively. May-Grünwald-Giemsa and Ziehl-Neelsen staining methods were employed. RESULTS: Statistically significant (P < .01) cytomorphologic features of type 1 reaction were the presence of fragments of collagen and elastin; giant cells; giant cells exhibiting elastin phagocytosis; loose, epithelioid cell granulomas; and fibroblasts. Type 2 reaction was characterized in aspirates by the presence of an abundance of neutrophils in a background of lepromatous leprosy (P < .01). CONCLUSION: Criteria that are used in histopathology for the diagnosis of leprosy reactions can be applied satisfactorily to cytologic smears. A good correlation between clinical diagnosis and cytomorphology can be achieved. Multiple-site aspirates from the skin, nerve and lymph nodes are helpful in substantiating the diagnosis.

Giant cell myocarditis and myositis associated with thymoma and leprosy.

Myocarditis is an inflammatory form of heart disease which is usually preceded by a viral infection. Giant cell myocarditis is an uncommon and nonspecific form of this disease. Sporadic reports have linked giant cell myocarditis with thymoma and concomitant myositis. The authors report a patient with leprosy who, six months after initiation of treatment, developed sudden onset of congestive heart failure and cardiac arrhythmias unresponsive to aggressive medical therapy. In addition to confirming leprosy, autopsy showed a mixed cell type thymoma, severe giant cell myocarditis and extensive myositis.