Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy- A comparative study.

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient.

As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Chronic type 2 reaction possibly triggered by an asymptomatic Bartonella henselae infection in a leprosy patient

ABSTRACT As leprosy and leprosy reactions are the most prevalent infectious cause of physical disability, it is important to commit efforts to better understand these chronic reactions. Infections, even when asymptomatic, can trigger leprosy reactions and Bartonella spp. in turn, can cause chronic infections. We presented a case of a 51-year-old man who was admitted presenting with chronic type 2 leprosy reactions. He had a lepromatous form of leprosy that was histologically diagnosed six months after the onset of signs and symptoms compatible with a chronic type 2 reaction. He reported a history of a previous hepatitis B diagnosis. During a 24-month multidrug therapy (MDT), chronic reactions were partially controlled with prednisone and thalidomide. Thirty-three months following the leprosy treatment, he still experienced chronic reactions, and whole bacilli as well as globi were found on a new skin biopsy. Since coinfections can trigger type 2 reactions and the patient had close contact with animals and ticks, we investigated the presence of a Bartonella sp. infection. Bartonella henselae DNA was detected in a skin fragment obtained before the beginning of the leprosy retreatment. However, even after six months of a second leprosy MDT, he continued to experience type 2 chronic reactions. He was admitted to the hospital to undergo an intravenous antibiotic therapy for 14 days and then complete the treatment per os for ten more weeks. Leprosy reactions improved following the treatment for B. henselae. After completing the MDT treatment, he has been accompanied for sixty months with no signs of leprosy or leprosy reactions. The asymptomatic infection by B. henselaein this patient was considered the putative trigger of chronic leprosy reactions and leprosy relapse.

Second-harmonic generation imaging analysis can help distinguish sarcoidosis from tuberculoid leprosy.

Sarcoidosis and tuberculoid leprosy (TL) are prototypes of granulomatous inflammation in dermatology, which embody one of the histopathology limitations in distinguishing some diseases. Recent advances in the use of nonlinear optical microscopy in skin have enabled techniques, such as second-harmonic generation (SHG), to become powerful tools to study the physical and biochemical properties of skin. We use SHG images to analyze the collagen network, to distinguish differences between sarcoidosis and TL granulomas. SHG images obtained from skin biopsies of 33 patients with TL and 24 with sarcoidosis retrospectively were analyzed using first-order statistics (FOS) and second-order statistics, such as gray-level co-occurrence matrix (GLCM). Among the four parameters evaluated (optical density, entropy, contrast, and second angular moment), only contrast demonstrated statistical significance, being higher in sarcoidosis (p = 0.02; 4908.31 versus 2822.17). The results may indicate insufficient differentiating power for most tested FOS and GLCM parameters in classifying sarcoidosis and TL granulomas, when used individually. But in combination with histopathology (H&E and complementary stains, such as silver and fast acid stains), SHG analysis, like contrast, can contribute to distinguishing between these diseases. This study can provide a way to evaluate collagen distribution in granulomatous diseases.

Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy from sarcoidosis.

BACKGROUND: More than 200 000 new cases of leprosy are detected worldwide annually. Physicians commonly have difficulty in differentiating tuberculoid form of leprosy (TL) from sarcoidosis' cutaneous manifestation. METHODS: Skin biopsies of 33 patients with TL and 24 with sarcoidosis were reviewed on hematoxylin and eosin- and Gomori-stained sections, in order to find reliable criteria for distinguishing one disease from another. RESULTS: Nine of the 24 features analyzed presented significant predictive value for diagnosis (P < .05). Predominance of tuberculoid granulomas in adnexal and neural distribution, and granulomas replacing the nerves localized within sweat gland glomeruli were predictive to TL diagnosis. For sarcoidosis, dermal fibrosis, back-to-back distribution of the granulomas, presence of atypical giant cells and plasma cells, greater number of conventional giant cells, and spared nerves beside the granuloma were predictive criteria. The median surface density of reticulin fibers was significantly higher in sarcoidosis (3.44) than in TL (2.99). Nonetheless, using logistic regression, this variable did not discriminate between the diseases (P = .096). CONCLUSIONS: Isolated histological features are not fully predictive to differentiate the 2 diseases. However, those with statistical value can assist this distinction in diagnostic practice. Although the results of the analysis of the reticulin fibers density did not tell apart TL from sarcoidosis, they corroborate the idea of fiber fragmentation within tuberculoid leprosy granulomas, reiterating the importance of morphometry in the histological examination.

Vasculonecrotic reactions in leprosy.

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.

Vasculonecrotic reactions in leprosy

Multibacillary, lepromatous or borderline leprosy patients may present two types of vasculonecrotic reactions: Lucio phenomenon and that associated with erythema nodosum leprosum. Despite they can be distinguished through clinical and histological characteristics; both are often used as synonyms. It is said that leprosy reaction should be properly classified for therapeutic reasons, since it is well known that in Lucio phenomenon there is not a good response to thalidomide. The authors reported two cases of vasculonecrotic phenomena in lepromatous leprosy sharing clinical and histopathological characteristics of both reaction subtypes. The findings may indicate the spectral nature of the reaction phenomena in leprosy and emphasize the importance of the clinic-pathological correlation for proper classification. Our findings may contribute to the understanding of leprosy reactions pathogenesis, broaden the knowledge about their outcome with standard treatment, and provide the scientific background to design better therapeutic strategies for these complications.