Primary tuberculosis of glans penis after intravesical Bacillus Calmette Guerin immunotherapy.

A 55-year-old male with carcinoma in situ of urinary bladder was treated with weekly intravesical injections of Bacillus Calmette Guerin (BCG) vaccine. Three days after the sixth injection, he developed low grade fever and multiple grouped punched out, 2-3 mm ulcers around meatus and corona glandis. In addition, multiple, firm, indurated, nontender papules and few deeper nodules were present on the proximal part of glans penis, along with bilateral enlarged, matted and nontender inguinal lymph nodes. There was no history suggestive of sexually transmitted diseases and high risk behavior. Chest X-ray was within normal limits, and Mantoux, Venereal Disease Research Laboratory (VDRL) and HIV antibody tests were negative. The biopsy from the penile ulcer revealed epithelioid cell granuloma with Langhans giant cells. Fine needle aspiration cytology from the lymph node also revealed epithelioid cell granuloma and acid fast bacilli on Ziehl Neelsen's stain. The tissue biopsy grew Mycobacterium tuberculosis. The BCG immunotherapy was stopped and patient was treated with four drug antitubercular therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide in standard daily doses along with pyridoxine. The edema resolved and the ulcers started healing within 2 weeks, and at 6 weeks after starting antitubercular therapy almost complete healing occurred. To the best of our knowledge, we describe the first case of an Indian patient with BCG induced primary tuberculosis of penis after immunotherapy for carcinoma urinary bladder and review the previously described cases to increase awareness of this condition in dermatologists and venereologists.

Leprosy and tuberculosis: an insight-review.

A quick glance at this review article provides an insight into the common and different features of M. leprae and M. tuberculosis and the diseases caused by these organisms. Table I provides the popular names, history, stigma, description of the disease, clinical features, classification and the types of disease manifestations, who are affected, Signs and Symptoms, Clinical examination, treatment regimens, reactions, relapses, immunity, infectiousness, risk groups, deformities, sequelae, transmission, prevention, complications, vaccination, laboratory studies, days of importance for both the diseases. Table II provides information regarding the causative organisms, M. leprae and M. tuberculosis, their size, genome, protein coding region, lost genes, pseudogenes, classification, predilection, incubation period, ecology, cell structure, metabolism, resistance, bacterial index, growth in vitro, experimental animals, etc. Table III provides figures of M. leprae and M. tuberculosis, their genome, Lepromin and Tuberculin testing, Global scenario, Indian scenario, colonies of M. leprae and M. tuberculosis, drugs for treatment of tuberculosis and leprosy (MDT blister pack), and so on.

Is Crohn's disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis, and Johne's disease.

Although Crohn's disease is considered to be autoimmune in origin, there is increasing evidence that it may have an infectious cause. The most plausible candidate is Mycobacterium avium subspecies paratuberculosis (MAP). Intriguingly, Koch's postulates may have been fulfilled for MAP and Crohn's disease, even though they still have not been met for Mycobacterium leprae and leprosy. In animals MAP causes Johne's disease, a chronic wasting intestinal diarrhoeal disease evocative of Crohn's disease. Johne's disease occurs in wild and domesticated animals, including dairy herds. Viable MAP is found in human and cow milk, and is not reliably killed by standard pasteurisation. MAP is ubiquitous in the environment including in potable water. Since cell-wall-deficient MAP usually cannot be identified by Ziehl-Neelsen staining, identification of MAP in human beings requires culture or detection of MAP DNA or RNA. If infectious in origin, Crohn's disease should be curable with appropriate antibiotics. Many studies that argue against a causative role for MAP in Crohn's disease have used antibiotics that are inactive against MAP. However, trials that include macrolide antibiotics indicate that a cure for Crohn's disease is possible. The necessary length of therapy remains to be determined. Mycobacterial diseases have protean clinical manifestations, as does Crohn's disease. The necessity of stratifying Crohn's disease into two clinical manifestations (perforating and non-perforating) when interpreting the results of antibiotic therapy is discussed. Rational studies to evaluate appropriate therapies to cure Crohn's disease are proposed.

Doenças granulomatosas da laringe / Granulomatous diseases of the larynx

Realizamos uma revisäo sobre as principais doenças granulomatosas que podem acometer a laringe, devido à grande ocorrência dessas afecçöes no Brasil e em outros países de clima tropical e subtropical. Ressaltamos os aspectos histopatológicos para o seu diagnóstico, assim como o seu tratamento.

Nonspecific resistance to Mycobacteria: the role of the Nramp1 gene.

The genus Mycobacteria consists of over 50 species that include two of the best-known human pathogens, M. tuberculosis and M. leprae, the causes of tuberculosis (TB) and leprosy, respectively. Whereas the spread of leprosy currently appears to be under control, there are presently about 30 million active cases of TB worldwide, with an alarming increase in the number of multidrug resistant case of M. tuberculosis. As strategies for antibiotic intervention against TB become more limited, it is imperative to develop new therapeutic approaches against this oppressive disease. One promising avenue is to characterize the host genes and gene products which regulate resistance to mycobacterial infections. In the mouse, resistance and susceptibility to intracellular growth of Mycobacteria in macrophages is controlled by the Bcg (Nramp1) gene, which has now been cloned and shown to encode a macrophage transmembrane protein with a putative transporter function. Sequencing of Nramp1 revealed that susceptibility to infection is associates with a single, nonconservative glycine to aspartic acid substitution at position 169 (G169D). Although the intracellular location of the Nramp1 protein in macrophages has not yet been determined, a phagosomal site has been postulated. Consistent with the proposed role of Nramp1 in macrophage activation, recent studies of the Nramp1 promoter region have revealed consensus sequences associated with responsiveness to IFN-gamma and LPS. Finally, a total of 11 polymorphisms have been identified within the human NRAMP1 gene which are being used to test for linkage of NRAMP1 alleles with human susceptibility to TB and leprosy.

[The 69th annual meeting symposium. II: Mechanism of necrotizing granuloma formation and its function].

Histological features of tuberculosis are caseation necrosis and epithelioid cell granuloma formation. Both phenomena are interpreted as expression of cellular immunity. Caseation necrosis is thought to be immunopathology and epithelioid cell granuloma formation is considered to be expression of protective immunity. Recently roles of cytokines for granuloma formation are gradually elucidated. In this symposium, mechanisms and functions of necrosis and granuloma formation Dr. Akagawa reported differentiation of two types of phenotypically different macrophages from human monocytes by GM (granulocyte-macrophage)-CSF or M (macrophage)-CSF. Interestingly such a basic differentiation induced by CSF was affected by IL-4 (interleukin-4). Langerhans-like dendritic cells were generated by cooperation of GM-CSF and IL-4, and multinucleated cells were generated by cooperation of IL-4 and M-CSF. Dr. Fukuda reported human Langerhans cell granulomatosis (LCG) from the pathological and immunohistochemical standpoints. In situ proliferation of LCs in the LCG was demonstrated by immunohistochemistry using antibody to PCNA (proliferating cell nuclear antigen) which is used to detect proliferating cells. In the course of granuloma formation, damage and disruption of lung structure such as alveolar basement membrane and elastic tissue framework, and reactive intraluminar fibrosis was observed. Mechanism of cystic dilation was also reported. Cytokines might play important roles in these events. Dr. Ina demonstrated experimental epithelioid cell granuloma formation. Extract (granuloma inducing factor, GIF) from Schistosoma mansoni Egg-induced granuloma, TNF -alpha, or IL-1 beta were coated, individually on the surface of beads, then these beads were inoculated to rat's skins or cultured with rat's monocytes. Four weeks later, epithelioid cell granuloma was demonstrated histologically and electronmicroscopically around beads in vitro and in vivo. GIF-induced granuloma was more organized than cytokine-induced ones. In vitro using human monocytes, activated macrophages accumulated around beads of which cytokines or GIF were coated. It was suspected that many cytokines or other factors are needed to make epithelioid cell granuloma. Dr. Sakamoto showed the presence of acid fast bacilli and various inflammatory cells including lymphocytes and macrophages in the tuberculous caseous necrosis after exudative reaction (E-necrosis) by immunohistochemistry. But no acid fast bacilli or inflammatory cells were found in the caseous necrosis after productive reaction (P-necrosis). TNF-alpha (tumor necrosis factor-alpha) and IL-4 were stained in the E-necrosis and IL-4 and ICAM-1 (intercellular adhesion molecule-1) were positively stained in the cytoplasm of epithelioid cells by immunohistochemistry. It was suspected that many cells and cytokines were involved in epithelioid cell granuloma formation and caseous necrosis formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Patogenia comparada das cepas de micobactérias BCG e H37Rv em hamster (Mesocrisetus auratus): influência das vias sanguínea e linfática / Comparative pathogenesis of mycobacterial strains BCG and H37Rv in hamster (Mesocrisetus auratus): influence of blood and lymphatic pathways

Some aspects of the pathogeny of tuberculosis was experimentally investigated by inoculating either an attenuated mycobacteria strain BCG, or a virulent strainM. tuberculosis H37Rv into the foot pad or the cheek pouch of hamster. The inoculation of these agents determined different patterns of lesion. The BCG-induced lesionsin the foot pad had a tendency to descrease in size. On the other hand, the lesions induced by H37Rv showed a progressive evolution. The same pattern of evolution was observed with the lesions induced in the cheek pouch. However, the H37Rv disseminated to internal organs and the BCG did not. When BCG or H37Rv were inoculated in the foot pad of animals, the popliteal lymph node showed respectively a 21 fold and 68 fold increase in weight

Da relação imunobiológica entre tuberculose e lepra

The purpose of the present paper is to answer objections raised by some authors that conversion of Mitsuda negativity after BCG vaccination is caused by the antigenic action of the lepromin test previous to the vaccination. To this end there have been studied the effects upon the Mitsuda reaction of repeated lepromin injections, in comparison with the effects of orally administred BCG without previous lepromin test. Results obtained with 61 children of parents with leprosy are reported (2 children were lost from experiment, one by death and one by removal to another institution). These children, taken from their parents in their first dayof life, ranged in age at the beginning of the experiment from 3 days to 12 months 6 days. They were divided by lot into three groups so as to make the age relationship in each group approximatelythe same. Group A: 21 nonvaccinated children who underwent 4 lepromin test at intervals of about 3 months. After the fourth injection the Mitsuda reaction was positive in 9 cases (43%), only one of them strong enough to be necrotic. The 12 negatives were afterwards given BCG, and then 7 more (58% of the negatives) gave positive Mitsuda reactions. Group B: 20 children BCG-vaccinated orally with three weekly doses of 0.10 or 0.20 gm., according to age. a lepromin test performed nine months after vaccination gave 17 (85%) strongly positive (necrotic) Mitsuda reactions. The other 3 cases (one 1 + and two negative) were given another course of BCG vaccination, after which they were retested with lepromin; 2 of them then gave strongly positive (necrotic) Mitsuda reaction. Group C: 20 control children did not get BCG and were tested with lepromin for the first time 9 months after the study was begun. Al were completely negative. Analysis of the results from groups studied proved then to be statistcally significally significant, with...

Segundo tema: Reciprocidade do comportamento da infecção leprótica em face da tuberculose e vice versa, do ponto de vista epidemiológico, clínico, imuno-alérgico e sorológico / Two theme: \"Reciprocity of the behavior of leprous infection in the face of tuberculosis and vice versa, in terms of epidemiological, clinical, immuno-allergic and serological

The author reports his work and other data about the correlation between tuberculosis and leprosy, considered under the immunoallergic, clinic and epidemiologic point of view. 1. Cosidering the immunoallergic correlation between tuberculosis and leprosy with all the data available, he says that in some materials there is an association between positive tuberculin and the positivity of lepromin. There are other elements that reduce the importance of the above mentioned association and of eventual consensibilization. New experiments should be done, especially out of urban areas and in children, in order to comprove that the paralellism of the tuberculin and lepromin curves depends of a relation of cause and effect and not of an association. 2. The researchs of Fernandez, Melson, Hadler and Ziti, and others, favor the hypothesis of transitory tuberculin sensibilization caused by the "M. leprae" and "m. lepraemurium". However, there are many data that reduce its importance. In case it come to be proved in other experiments it wil be difficult to apreciate correctly the correlation between the tuberculin and the lepromin test. When would the first influence to second of vice-versa? and in what degree? Even proved this cross sensibilization from "M. leprae" to "M. tuberculosis", the A. thinks that it would be of slight importance, without interfering largely in the specificity of the tuberculin test. 3. Tuberculosis influencing the clinical course of leprosy and vice versa: the author believes that the data are not enough to prove that tuberculosissnakes more favorable the clinical course of leprosy and vice versa. 4. Tuberculosis influencing the epidemiology of leprosy and vice versa: the author considers the Chaussinand's hypothesis that the erradication of leprosy in Europe was chiefly determined by presence of tuberculosis among the people. The following itens were...

Da relação imunológica entre tuberculose e lepra. II - Da inter-relação entre as reações tubercul¡nica em filhos de doentes de lepra / Action therapeutic anti-leprosy of the sulfone-parent and complex sulfones

Cento e oitenta e cinco crinaças, sadias, filhos de doentes de lepra, de 2 a 16 anos de idade, internadas no Educandário Santa Terezinha, de Carapicuíba, São Paulo, foram provadas com as reações de Mantoux até 1:10 e a reação lerpom¡nica realizada segundo a técnica de Mitsuda-Hayashi. Cento e quarenta e oito delas foram internadas logo após o nascimento (grupo sem contacto). Outras 37 só foram internadas depois de uma convivência, com seus pais doentes, variável de 1 mês a 6 anos (grupo de contacto). Do total das 185 crianças, 45 revelaram-se positivas ao Mantoux (24,32%) e 129 reagiram à lepromina (69,73%). No grupo sem contacto, a reação de Mantoux foi positiva em 29,94% dos casos e a reação de Mitsuda em 64,19%. No grupo de contacto essas reações foram positivas, respectivamente, em 37,83% e 91,89%. Os casos sensíveis à tuberculina, no grupo sem contacto, são explicáveis pelo contágio tuberculoso contra¡do no decorrer dos anos dentro do Educandário através do pessoal de enfermagem e demais auxiliares que se renovam constantemente. Dessa forma a incidência de alérgicos no grupo de contacto, pode também ser explicada, em parte pelos contágios tuberculosos contra¡dos antes do internamento, e em parte depois dêste. O estudo comparativo da reação de Mantoux e de Mitsuda, mostrou que em tôdas as crianças tuberculino-positivas, também houve resposta positiva à lepromina (45 casos). Por outro lado, a reação de Mitsuda foi positiva somente em 84 casos dos 140 negativos de Mantoux a 1:10. Considerando a positividade do Mitsuda apenas nos insensíveis à tuberculina, nos grupos sem contacto e com contacto, verificou-se que em 117 casos negativos ao Mantoux, no primeiro grupo houve 64 (54,70%) positivos à lepromina, enquanto que de 23 crianças igualmente insensíveis à tuberculina no segundo grupo, 20 (86,95%) responderam à reação de Mitsuda...