Cutaneous nocardiosis with discharging sinus clinically mimicking tuberculosis diagnosed by cytology.

Nocardiosis is primarily a pulmonary infection commonly seen in immunocompromised individuals. However, lymphocutaneous nocardiosis is observed in immunocompetent individuals often after trauma. The clinical and cytomorphological features of lymphocutaneous nocardiosis closely mimic the most common infections in India such as tuberculosis and mycetoma (very common cutaneous infection with discharging sinus). As it is crucial to differentiate nocardiosis from tuberculosis, to avoid unnecessary antitubercular treatment, special stains like modified Ziehl-Neelsen stain and Gram stain can be employed to differentiate the morphology of Nocardia from tuberculosis. Fine-needle cytology from these cutaneous lesions helps in yielding adequate material for rapid and accurate diagnosis of immediate specific antibiotic treatment. We report a rare case that presented with clinical diagnosis of tuberculosis but turned out to be nocardiosis on cytomorphology with simple and most feasible fine-needle aspiration method of tissue diagnosis and scrape cytology.

Expressions of Antimicrobial Peptides LL-37, Human Beta Defensin-2 and -3 in the Lesions of Cutaneous Tuberculosis and Tuberculids.

BACKGROUND: Antimicrobial peptides, including cathelicidin LL-37, human beta defensin (HBD)-2, and HBD-3, are important elements of the innate immune response and involved in modulation of the adaptive immunity, and they also play an important role in cutaneous defense against Mycobacterium tuberculosis. METHODS: The fresh skin tissues and paraffin-embedded biopsy samples from three cutaneous tuberculosis, two tuberculids, and ten healthy individuals were collected. The expressions of LL-37, HBD-2, and HBD-3 mRNA in the lesions of three cutaneous tuberculosis and two tuberculids were detected by quantitative real-time polymerase chain reaction; the protein expressions were detected by immunohistochemistry and Western blotting methods. RESULTS: The expressions of LL-37 mRNA and protein in the lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. The expression of HBD-2 mRNA had an increasing trend in the lesions of cutaneous tuberculosis and tuberculids compared with that of normal skin; however, the expression of HBD-2 protein in the lesions of cutaneous tuberculosis had a decreasing trend compared with that of normal skin, and the expression of HBD-2 protein in the lesions of tuberculids was similar to that of normal skin. The expressions of HBD-3 mRNA and protein in lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. CONCLUSIONS: Our study indicated that the expression of HBD-2 and HBD-3 mRNA and protein in lesions of cutaneous tuberculosis may be not consistent with that of tuberculids. However, an inherent limitation of the present study was that the sample size was small, and the roles and regulation mechanisms of LL-37, HBD-2, and HBD-3 in cutaneous tuberculosis and tuberculids need to be further investigated.

Tuberculosis cutánea y pulmonar en paciente inmunocompetente / No disponible

La tuberculosis continúa siendo, en la actualidad, una enfermedad frecuente en nuestro medio debido principalmente a dos factores, la inmigración y la coinfección con el virus de la inmunodeficiencia humana. La afectación cutánea por Mycobacterium tuberculosis es muy poco habitual y, concretamente, la forma periorificial o ulcerosa, que se asocia a tuberculosis pulmonar extensa, es excepcional. Sin embargo, su incidencia puede aumentar en el futuro debido a los factores anteriormente citados junto a la inmunodepresión asociada al envejecimiento de la población y a los tratamientos inmunosupresores, por lo que se hace imprescindible incluir dicha enfermedad en el diagnóstico diferencial de las lesiones cutáneas en pacientes con tuberculosis pulmonar. Su diagnóstico requiere el aislamiento en el cultivo o la positividad en la técnica de reacción en cadena de la polimerasa de M. tuberculosis, y su tratamiento es el mismo que el de la tuberculosis pulmonar

Tuberculosis remains today a common disease in our daily lives mainly due to two causes, immigration and coinfection with the human immunodeficiency virus. Skin involvement by Mycobacterium tuberculosis is highly unusual, and particularly periorificial or ulcer form, which is associated with extensive pulmonary tuberculosis, is uncommon. However, its appearance may increase in the future due to the causes mentioned above, as well as immunosuppression associated with an aging population, and immunosuppressive treatments. Therefore, it is essential to include this disease in the differential diagnosis of skin lesions in patients with pulmonary tuberculosis. Diagnosis requires culture isolation or positivity of the M. tuberculosis polymerase chain reaction technique. Its treatment is the same as that of the pulmonary tuberculosis

Tetraphenylphosphonium as a novel molecular probe for imaging tumors.

UNLABELLED: Mitochondrial membrane potential (DeltaPsim)-dependent enhanced uptake of phosphonium salts, including (3)H-tetraphenylphosphonium ((3)H-TPP), in tumor cells, suggests the potential use of phosphonium salts as tracers for tumor imaging. In this study, we characterize the tumor accumulation of (3)H-TPP and compare it with (18)F-FDG in cell culture and in xenograft, metastatic, and inflammation models in living animals. METHODS: (3)H-TPP and (3)H-FDG accumulation was compared in cell culture with a variety of cell lines in different glucose concentrations. Normal biodistribution and tumor uptake were assessed using nude mice with or without subcutaneous xenograft tumors (C6). To compare the accumulation of (3)H-TPP and (18)F-FDG in a metastatic tumor, severe combined immunodeficiency mice were tail-vein injected with human melanoma cell lines (A375-FL). To characterize the accumulation of (3)H-TPP and (18)F-FDG in inflammation, an inflammatory reaction was induced by subcutaneous injection of Complete Freund's Adjuvant in the left hind paw of Sprague-Dawley rat. RESULTS: The DeltaPsim data from a separate study and the current (3)H-TPP uptake data showed good correlation (r(2) = 0.82, P < 0.05). (3)H-TPP accumulation was significantly greater than that of (3)H-FDG for glucose >/=100 mg/dL. The biodistribution study of (3)H-TPP showed low uptake in most tissues but high accumulation in the heart and kidneys. (3)H-TPP accumulation in xenograft or metastatic tumors was comparable with that of (18)F-FDG, whereas (3)H-TPP accumulation in inflammatory tissues was markedly lower than that of (18)F-FDG. CONCLUSION: The sensitive tumor accumulation of (3)H-TPP with less propensity for inflammatory regions warrants further investigation of radiolabeled phosphonium analogs for tumor imaging in living subjects.

Increased inflammatory cytokines and new collagen formation in cutaneous tuberculosis and sarcoidosis.

BACKGROUND: Interactions between mononuclear cells, vascular endothelium, fibroblasts, and cytokines during the inflammatory reaction within a granuloma have the potential to contribute to the progression to fibrosis. METHODS: Biopsy specimens of six tuberculous and eight sarcoidosis skin lesions were examined by immunohistochemistry to seek evidence for the presence of inflammatory and fibrotic reactions in human granulomatous disease. Additionally, to understand how a T cell mediated delayed type hypersensitivity reaction--a component of chronic granulomatous inflammation--could progress to fibrosis, the human in vivo model of the cutaneous tuberculin Heaf reaction to purified protein derivative (PPD) was studied in a group of 48 subjects. RESULTS: Granulomas from tuberculous and sarcoidosis skin biopsy specimens were seen to contain cells with marked staining by antibodies to fibronectin, transforming growth factor beta (pan TGF-beta), and type 1 procollagen (PCP-1). Accentuated staining of extracellular matrix was seen both in the granulomas and in the peri-granulomatous regions. Less prominent staining was observed using antibodies against interleukin 1 beta (IL-1 beta) and alpha-smooth muscle actin (alpha-SMA). Biopsies of Heaf reactions revealed cells staining for IL-1 beta, tumour necrosis factor alpha (TNF-alpha), platelet derived growth factor B (PDGF-B), and fibronectin which were detected as early as day 1 and persisted throughout the 14 day study period. Cells staining for PCP-1 increased to greatest abundance at day 14. All these cytokines were present in low abundance in biopsy specimens from sites inoculated with saline only. CONCLUSIONS: Evidence is provided that granulomas in tuberculosis and sarcoidosis behave as active centres of fibrogenesis. Using the Heaf model, the temporal relationship between the early appearance of cytokines and the later increase in the collagen precursor PCP-1 linked the immune mediated chronic inflammatory response with subsequent fibrosis and suggested that the tuberculin Heaf reaction will serve as a model for studying the early events of granuloma formation in patients with tuberculosis and sarcoidosis.

Biometals in skin and sera of leprosy patients and their correlation to trace element contents of M. leprae and histological types of the disease; a comparative study with cutaneous tuberculosis.

The present study has provided information on the biometal contents of killed and dried Mycobacterium leprae as well as dermal granulomas induced by the invading mycobacteria in various histological types of leprosy patients. For comparison, the biometal contents of the contralateral leprosy-unaffected skin of the same patients also were measured. The study also reports changes of serum levels of the biometals in these patients which were compared with those in healthy control subjects and patients with skin tuberculosis. These data show that M. leprae is rich in zinc. During the course of the evolution of the disease there is gross alteration of the dynamics of the inflammatory cell population that infiltrates into leprosy granulomas, resulting in the alterations of trace element contents of the disease-affected skin lesions. Interestingly, the changes of the biometal contents in the granulomas of the patients with skin tuberculosis are similar to those in leprosy patients. It is postulated that the significant decrease of the contents of copper, zinc, iron, calcium and magnesium in the disease-affected skin in comparison to that of the contralateral healthy skin is a local effect, perhaps due to erosion or influx of biometal-deficient inflammatory cells into the affected skin with eventual loss of connective tissue of skin and mobilization of tissue-bound microelements into the vascular compartment. On the contrary, the changes in biometal levels in the sera of leprosy patients appear to be a general effect perhaps due to the release of interleukin-1, a product of inflammatory cells, causing hypercupremic, hypozincemic and hypoferremic responses in the hosts. Moreover, growth and multiplication of M. leprae, especially in polar lepromatous leprosy patients with a high bacillary load, demand essential biometals which may be mobilized into the bacterial bodies from the hosts. This perhaps results in the change in the homeostasis of the essential biometals in the hosts.

Papulonecrotic tuberculid. A clinical, histopathological, and immunohistochemical study of 15 patients.

We report 10 women and five men with papulonecrotic tuberculid, an uncommon form of cutaneous tuberculosis (TB). The mean age was 22.6 years (range, 2 1/2-35 years) at presentation. The Mantoux test was strongly positive in 13 patients. Five patients showed presumptive evidence of associated TB; in one case, the presence of TB was proven by culture. Response to anti-TB was dramatic in all cases. Clinical findings were similar to those previously published. We emphasize the simultaneous occurrence of erythema induratum, associated Takayasu's disease, possible associated phlebitic tuberculid, and clinical mimicry of acute bacterial endocarditis. The main histopathological findings obtained from 27 biopsy specimens included dermal necrosis (26 of 27 cases), a poorly formed granulomatous infiltrate (27 of 27 cases), vasculitis (11 of 27 cases), perivascular spongy edema (11 of 27 cases), and follicular necrosis or suppuration (five of 27 cases). A Ziehl-Neelsen stain was negative in all biopsy specimens. Immunohistochemical labeling revealed a preponderance of T-lymphocytes (UCHL-1+), monocytes-macrophages (S-100+), and Langerhans cells (ACT+), indicative of a type IV hypersensitivity reaction. B-lymphocytes (L26+) were sparse. Conditions that may be confused with PNT on clinical or histopathological ground include pityriasis lichenoides et varioliformis acuta, papular urticaria, papulopustular syphilide, miliary TB, septicemia, perforating granuloma annulare, chondrodermatitis nodularis, reactive perforating collagenosis, allergic granulomatosis, suppurative folliculitis, and infectious causes of palisading granulomas. Papulonecrotic tuberculid has distinct clinical, histopathological, and immunohistochemical features. Awareness of this entity is important since an appropriate diagnosis is necessary for the institution of timely curative treatment.

Cutaneous spindle-cell pseudotumors due to Mycobacterium gordonae and Leishmania infantum. An immunophenotypic study.

We report two patients with AIDS who had cutaneous spindle-cell pseudotumors caused by Leishmania infantum in one instance and by an atypical mycobacterium in the other. The lesions mimicked neoplasms with predominantly spindled macrophages, similar to those seen in the histoid variant of leprosy. This histoid reaction is known to be related to mycobacteria. To our knowledge, this is the first case of histoid reaction due to leishmania. In both cases, the histiocytic cells were positive for vimentin and desmin but negative for alpha-smooth muscle. In addition, the immunostaining by lysosyme and alpha 1 antitrypsin was positive in both and in one the S-100 protein was positive. This reaction suggests dual myofibroblast and histiocytic differentiation.

Persistence of protein, carbohydrate and was components of tubercle bacilli in dermal BCG lesions.

Dermal tuberculous lesions were produced in rabbits with Bacille Calmette Guèrin and biopsied on days 4, 14, 21, 35, and 56. Frozen sections prepared from the biopsy specimens were stained by the peroxidase-antiperoxidase immunocytochemical technique with antisera against whole tubercle bacilli and antisera against the protein B, polysaccharide I, and wax D fractions of tubercle bacilli. In the primary lesions, protein B was often undetectable at 21 days, and polysaccharide I was often undetectable at 35 days. Wax D disappeared more slowly than the other bacillary components evaluated, and some wax D was still found at 56 days (if the lesions had not completely healed). Antisera against intact tubercle bacilli produced results similar to those produced by antiserum against wax D. These studies suggest that the chronicity of tuberculous lesions is due, at least in part, to the persistence of the wax D-like component of tubercle bacilli.

Macrophage accumulation, division, maturation, and digestive and microbicidal capacities in tuberculous lesions. I. Studies involving their incorporation of tritiated thymidine and their content of lysosomal enzymes and bacilli.

Dermal and pulmonary tuberculous lesions were produced in rabbits with BCG, biopsied, incubated in vitro with tritiated thymidine ((3)HT) under hyperbaric oxygen, quickly frozen, sectioned in a cryostat, stained for the lysosomal enzyme beta-galactosidase, autoradiographed, stained for acid-fast bacilli and counterstained with hematoxylin. As macrophages developed into epithelioid cells, they could still divide-ie, incorporate (3)HT. However, once they became fully mature epithelioid cells that were 4-plus in beta-galactosidase, they could not do so. Tuberclebacilli did not stimulate macrophage division. On the contrary, macrophages containing bacilli did not divide, except when the lesions began. During the development of tuberculous lesions, macrophages (including those rich in enzymes and those containing bacilli) died, forming caseous centers. Therefore, local cell division did not seem to be the main mechanism by which macrophages reduced their bacillary load. Such division seemed mainly to occur in young macrophages that had recently immigrated into the lesions from the bloodstream and had not yet ingested bacilli.